[Predictive model based multimetric index of macroinvertebrates for river health assessment].

PubMed

Chen, Kai; Yu, Hai Yan; Zhang, Ji Wei; Wang, Bei Xin; Chen, Qiu Wen

2017-06-18

Improving the stability of integrity of biotic index (IBI; i.e., multi-metric indices, MMI) across temporal and spatial scales is one of the most important issues in water ecosystem integrity bioassessment and water environment management. Using datasets of field-based macroinvertebrate and physicochemical variables and GIS-based natural predictors (e.g., geomorphology and climate) and land use variables collected at 227 river sites from 2004 to 2011 across the Zhejiang Province, China, we used random forests (RF) to adjust the effects of natural variations at temporal and spatial scales on macroinvertebrate metrics. We then developed natural variations adjusted (predictive) and unadjusted (null) MMIs and compared performance between them. The core me-trics selected for predictive and null MMIs were different from each other, and natural variations within core metrics in predictive MMI explained by RF models ranged between 11.4% and 61.2%. The predictive MMI was more precise and accurate, but less responsive and sensitive than null MMI. The multivariate nearest-neighbor test determined that 9 test sites and 1 most degraded site were flagged outside of the environmental space of the reference site network. We found that combination of predictive MMI developed by using predictive model and the nearest-neighbor test performed best and decreased risks of inferring type I (designating a water body as being in poor biological condition, when it was actually in good condition) and type II (designating a water body as being in good biological condition, when it was actually in poor condition) errors. Our results provided an effective method to improve the stability and performance of integrity of biotic index.

Advancedmonitoring Systems for Landslide Risk Reduction in THE'SIQ' of PETRA (jordan)

NASA Astrophysics Data System (ADS)

Delmonaco, G.; Brini, M.; Cesaro, G.

2017-08-01

The UNESCO World Heritage Site of Petra is characterized by a spectacular geo-archaeological landscape that lead to its inscription as World Heritage Site in 1985. Petra is also a fragile site facing a wide diversity of risks, ranging from those posed by environmental factors as well as those attributed to tourism. In recent years, hazardous natural phenomena were registered as increasingly impacting the site, and most specifically the 'Siq', a 1.2 km naturally formed gorge serving as the only tourist entrance to the archaeological park, posing a major threat to cultural heritage and visitors. These recent events have prompted UNESCO Amman Office, in cooperation with the national authorities, to develop a strategy towards prevention and mitigation of instability phenomena at the 'Siq' and, thus, further contribute to the management and conservation of the site through the implementation of the multi-year Italian funded "Siq Stability" project Actions have been primarily focusing on the analysis of the stability conditions of the 'Siq' slopes, the installation of an integrated monitoring system and the definition and implementation of mitigation measures against rock instability. This paper reports a detailed description of the integrated monitoring system installed paying particular attention on the wireless monitoring devices and the EASA applications, which proved to be some of the most successful systems implemented in the framework of the project. Some preliminary results regarding the data retrieved, policies applied and actions taken to ensure long-term sustainability and capacity development of the national authorities are also reported.

3-D Resistivity Tomography for Cliff Stability Study at the D-Day Pointe du Hoc Historic Site in Normandy, France

NASA Astrophysics Data System (ADS)

Udphuay, S.; Everett, M. E.; Guenther, T.; Warden, R. R.

2007-12-01

The D-Day invasion site at Pointe du Hoc in Normandy, France is one of the most important World War II battlefields. The site remains today a valuable historic cultural resource. However the site is vulnerable to cliff collapses that could endanger the observation post building and U.S. Ranger memorial located just landward of the sea stack, and an anti-aircraft gun emplacement, Col. Rudder's command post, located on the cliff edge about 200 m east of the observation post. A 3-D resistivity tomography incorporating extreme topography is used in this study to provide a detailed site stability assessment with special attention to these two buildings. Multi-electrode resistivity measurements were made across the cliff face and along the top of the cliff around the two at-risk buildings to map major subsurface fracture zones and void spaces that could indicate possible accumulations and pathways of groundwater. The ingress of acidic groundwater through the underlying carbonate formations enlarges pre-existing tectonic fractures via limestone dissolution and weakens the overall structural integrity of the cliff. The achieved 3-D resistivity tomograms provide diagnostic subsurface resistivity distributions. Resistive zones associated with subsurface void spaces have been located. These void spaces constitute a stability geohazard as they become significant drainage routes during and after periods of heavy rainfalls.

Contribution of physical modelling to climate-driven landslide hazard mapping: an alpine test site

NASA Astrophysics Data System (ADS)

Vandromme, R.; Desramaut, N.; Baills, A.; Hohmann, A.; Grandjean, G.; Sedan, O.; Mallet, J. P.

2012-04-01

The aim of this work is to develop a methodology for integrating climate change scenarios into quantitative hazard assessment and especially their precipitation component. The effects of climate change will be different depending on both the location of the site and the type of landslide considered. Indeed, mass movements can be triggered by different factors. This paper describes a methodology to address this issue and shows an application on an alpine test site. Mechanical approaches represent a solution for quantitative landslide susceptibility and hazard modeling. However, as the quantity and the quality of data are generally very heterogeneous at a regional scale, it is necessary to take into account the uncertainty in the analysis. In this perspective, a new hazard modeling method is developed and integrated in a program named ALICE. This program integrates mechanical stability analysis through a GIS software taking into account data uncertainty. This method proposes a quantitative classification of landslide hazard and offers a useful tool to gain time and efficiency in hazard mapping. However, an expertise approach is still necessary to finalize the maps. Indeed it is the only way to take into account some influent factors in slope stability such as heterogeneity of the geological formations or effects of anthropic interventions. To go further, the alpine test site (Barcelonnette area, France) is being used to integrate climate change scenarios into ALICE program, and especially their precipitation component with the help of a hydrological model (GARDENIA) and the regional climate model REMO (Jacob, 2001). From a DEM, land-cover map, geology, geotechnical data and so forth the program classifies hazard zones depending on geotechnics and different hydrological contexts varying in time. This communication, realized within the framework of Safeland project, is supported by the European Commission under the 7th Framework Programme for Research and Technological Development, Area "Environment", Activity 1.3.3.1 "Prediction of triggering and risk assessment for landslides".

Design, synthesis and evaluation of photoactivatable derivatives of microtubule (MT)-active [1,2,4]triazolo[1,5-a]pyrimidines.

PubMed

Oukoloff, Killian; Kovalevich, Jane; Cornec, Anne-Sophie; Yao, Yuemang; Owyang, Zachary A; James, Michael; Trojanowski, John Q; Lee, Virginia M-Y; Smith, Amos B; Brunden, Kurt R; Ballatore, Carlo

2018-05-05

The [1,2,4]triazolo[1,5-a]pyrimidines comprise a promising class of non-naturally occurring microtubule (MT)-active compounds. Prior studies revealed that different triazolopyrimidine substitutions can yield molecules that either promote MT stabilization or disrupt MT integrity. These differences can have important ramifications in the therapeutic applications of triazolopyrimidines and suggest that different analogues may exhibit different binding modes within the same site or possibly interact with tubulin/MTs at alternative binding sites. To help discern these possibilities, a series of photoactivatable triazolopyrimidine congeners was designed, synthesized and evaluated in cellular assays with the goal of identifying candidate probes for photoaffinity labeling experiments. These studies led to the identification of different derivatives that incorporate a diazirine ring in the amine substituent at position 7 of the triazolopyrimidine heterocycle, resulting in molecules that either promote stabilization of MTs or disrupt MT integrity. These photoactivatable candidate probes hold promise to investigate the mode of action of MT-active triazolopyrimidines. Copyright © 2018 Elsevier Ltd. All rights reserved.

Drosophila melanogaster muscle LIM protein and alpha-actinin function together to stabilize muscle cytoarchitecture: a potential role for Mlp84B in actin-crosslinking.

PubMed

Clark, Kathleen A; Kadrmas, Julie L

2013-06-01

Stabilization of tissue architecture during development and growth is essential to maintain structural integrity. Because of its contractile nature, muscle is especially susceptible to physiological stresses, and has multiple mechanisms to maintain structural integrity. The Drosophila melanogaster Muscle LIM Protein (MLP), Mlp84B, participates in muscle maintenance, yet its precise mechanism of action is still controversial. Through a candidate approach, we identified α-actinin as a protein that functions with Mlp84B to ensure muscle integrity. α-actinin RNAi animals die primarily as pupae, and Mlp84B RNAi animals are adult viable. RNAi knockdown of Mlp84B and α-actinin together produces synergistic early larval lethality and destabilization of Z-line structures. We recapitulated these phenotypes using combinations of traditional loss-of-function alleles and single-gene RNAi. We observe that Mlp84B induces the formation of actin loops in muscle cell nuclei in the absence of nuclear α-actinin, suggesting Mlp84B has intrinsic actin cross-linking activity, which may complement α-actinin cross-linking activity at sites of actin filament anchorage. These results reveal a molecular mechanism for MLP stabilization of muscle and implicate reduced actin crosslinking as the primary destabilizing defect in MLP-associated cardiomyopathies. Our data support a model in which α-actinin and Mlp84B have important and overlapping functions at sites of actin filament anchorage to preserve muscle structure and function. Copyright © 2013 Wiley Periodicals, Inc.

Structure-Based Network Analysis of Activation Mechanisms in the ErbB Family of Receptor Tyrosine Kinases: The Regulatory Spine Residues Are Global Mediators of Structural Stability and Allosteric Interactions

PubMed Central

James, Kevin A.; Verkhivker, Gennady M.

2014-01-01

The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced “superacceptor” activity in oncogenic EGFR dimers. We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. The results of this study have pointed to a central role of the conserved His-Arg-Asp (HRD) motif in the catalytic loop and the Asp-Phe-Gly (DFG) motif as key mediators of structural stability and allosteric communications in the ErbB kinases. We have determined that residues that are indispensable for kinase regulation and catalysis often corresponded to the high centrality nodes within the protein structure network and could be distinguished by their unique network signatures. The optimal communication pathways are also controlled by these nodes and may ensure efficient allosteric signaling in the functional kinase state. Structure-based network analysis has quantified subtle effects of ATP binding on conformational dynamics and stability of the EGFR structures. Consistent with the NMR studies, we have found that nucleotide-induced modulation of the residue interaction networks is not limited to the ATP site, and may enhance allosteric cooperativity with the substrate binding region by increasing communication capabilities of mediating residues. PMID:25427151

Strongly localized dark modes in binary discrete media with cubic-quintic nonlinearity within the anti-continuum limit

NASA Astrophysics Data System (ADS)

Taib, L. Abdul; Hadi, M. S. Abdul; Umarov, B. A.

2017-12-01

The existence of dark strongly localized modes of binary discrete media with cubic-quintic nonlinearity is numerically demonstrated by solving the relevant discrete nonlinear Schrödinger equations. In the model, the coupling coefficients between adjacent sites are set to be relatively small representing the anti-continuum limit. In addition, approximated analytical solutions for vectorial solitons with various topologies are derived. Stability analysis of the localized states was performed using the standard linearized eigenfrequency problem. The prediction from the stability analysis are furthermore verified by direct numerical integrations.

Methane hydrate formation in turbidite sediments of northern Cascadia, IODP Expedition 311

USGS Publications Warehouse

Torres, M.E.; Trehu, A.M.; Cespedes, N.; Kastner, M.; Wortmann, U.G.; Kim, J.-H.; Long, P.; Malinverno, A.; Pohlman, J.W.; Riedel, M.; Collett, T.

2008-01-01

Expedition 311 of the Integrated Ocean Drilling Program (IODP) to northern Cascadia recovered gas-hydrate bearing sediments along a SW-NE transect from the first ridge of the accretionary margin to the eastward limit of gas-hydrate stability. In this study we contrast the gas gas-hydrate distribution from two sites drilled ~ 8??km apart in different tectonic settings. At Site U1325, drilled on a depositional basin with nearly horizontal sedimentary sequences, the gas-hydrate distribution shows a trend of increasing saturation toward the base of gas-hydrate stability, consistent with several model simulations in the literature. Site U1326 was drilled on an uplifted ridge characterized by faulting, which has likely experienced some mass wasting events. Here the gas hydrate does not show a clear depth-distribution trend, the highest gas-hydrate saturation occurs well within the gas-hydrate stability zone at the shallow depth of ~ 49??mbsf. Sediments at both sites are characterized by abundant coarse-grained (sand) layers up to 23??cm in thickness, and are interspaced within fine-grained (clay and silty clay) detrital sediments. The gas-hydrate distribution is punctuated by localized depth intervals of high gas-hydrate saturation, which preferentially occur in the coarse-grained horizons and occupy up to 60% of the pore space at Site U1325 and > 80% at Site U1326. Detailed analyses of contiguous samples of different lithologies show that when enough methane is present, about 90% of the variance in gas-hydrate saturation can be explained by the sand (> 63????m) content of the sediments. The variability in gas-hydrate occupancy of sandy horizons at Site U1326 reflects an insufficient methane supply to the sediment section between 190 and 245??mbsf. ?? 2008 Elsevier B.V.

Assessing indicators of rangeland health with remote sensing in southeast Arizona

Treesearch

Jared Buono; Philip Heilman; David Williams; Phillip Guertin

2005-01-01

The goal of this study was to scale up ground-based range assessments to ranch and landscape scales in southeast Arizona using remote sensing and minimum amount of field data collection. Remotely sensed metrics of canopy cover, biomass, and mesquite composition were used to assess soil and site stability and biotic integrity. Ground-based assessments were conducted on...

Dimer interface of bovine cytochrome c oxidase is influenced by local posttranslational modifications and lipid binding

PubMed Central

Liko, Idlir; Degiacomi, Matteo T.; Mohammed, Shabaz; Yoshikawa, Shinya; Schmidt, Carla; Robinson, Carol V.

2016-01-01

Bovine cytochrome c oxidase is an integral membrane protein complex comprising 13 protein subunits and associated lipids. Dimerization of the complex has been proposed; however, definitive evidence for the dimer is lacking. We used advanced mass spectrometry methods to investigate the oligomeric state of cytochrome c oxidase and the potential role of lipids and posttranslational modifications in its subunit interfaces. Mass spectrometry of the intact protein complex revealed that both the monomer and the dimer are stabilized by large lipid entities. We identified these lipid species from the purified protein complex, thus implying that they interact specifically with the enzyme. We further identified phosphorylation and acetylation sites of cytochrome c oxidase, located in the peripheral subunits and in the dimer interface, respectively. Comparing our phosphorylation and acetylation sites with those found in previous studies of bovine, mouse, rat, and human cytochrome c oxidase, we found that whereas some acetylation sites within the dimer interface are conserved, suggesting a role for regulation and stabilization of the dimer, phosphorylation sites were less conserved and more transient. Our results therefore provide insights into the locations and interactions of lipids with acetylated residues within the dimer interface of this enzyme, and thereby contribute to a better understanding of its structure in the natural membrane. Moreover dimeric cytochrome c oxidase, comprising 20 transmembrane, six extramembrane subunits, and associated lipids, represents the largest integral membrane protein complex that has been transferred via electrospray intact into the gas phase of a mass spectrometer, representing a significant technological advance. PMID:27364008

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

Jung, Haeryong; Lee, Eunyong; Jeong, YiYeong

Korea Radioactive-waste Management Corporation (KRMC) established in 2009 has started a new project to collect information on long-term stability of deep geological environments on the Korean Peninsula. The information has been built up in the integrated natural barrier database system available on web (www.deepgeodisposal.kr). The database system also includes socially and economically important information, such as land use, mining area, natural conservation area, population density, and industrial complex, because some of this information is used as exclusionary criteria during the site selection process for a deep geological repository for safe and secure containment and isolation of spent nuclear fuel andmore » other long-lived radioactive waste in Korea. Although the official site selection process has not been started yet in Korea, current integrated natural barrier database system and socio-economic database is believed that the database system will be effectively utilized to narrow down the number of sites where future investigation is most promising in the site selection process for a deep geological repository and to enhance public acceptance by providing readily-available relevant scientific information on deep geological environments in Korea. (authors)« less

Importance of geologic characterization of potential low-level radioactive waste disposal sites

USGS Publications Warehouse

Weibel, C.P.; Berg, R.C.

1991-01-01

Using the example of the Geff Alternative Site in Wayne County, Illinois, for the disposal of low-level radioactive waste, this paper demonstrates, from a policy and public opinion perspective, the importance of accurately determining site stratigraphy. Complete and accurate characterization of geologic materials and determination of site stratigraphy at potential low-level waste disposal sites provides the frame-work for subsequent hydrologic and geochemical investigations. Proper geologic characterization is critical to determine the long-term site stability and the extent of interactions of groundwater between the site and its surroundings. Failure to adequately characterize site stratigraphy can lead to the incorrect evaluation of the geology of a site, which in turn may result in a lack of public confidence. A potential problem of lack of public confidence was alleviated as a result of the resolution and proper definition of the Geff Alternative Site stratigraphy. The integrity of the investigation was not questioned and public perception was not compromised. ?? 1991 Springer-Verlag New York Inc.

Modification of quinone electrochemistry by the proteins in the biological electron transfer chains: examples from photosynthetic reaction centers

PubMed Central

Gunner, M. R.; Madeo, Jennifer; Zhu, Zhenyu

2009-01-01

Quinones such as ubiquinone are the lipid soluble electron and proton carriers in the membranes of mitochondria, chloroplasts and oxygenic bacteria. Quinones undergo controlled redox reactions bound to specific sites in integral membrane proteins such as the cytochrome bc1 oxidoreductase. The quinone reactions in bacterial photosynthesis are amongst the best characterized, presenting a model to understand how proteins modulate cofactor chemistry. The free energy of ubiquinone redox reactions in aqueous solution and in the QA and QB sites of the bacterial photosynthetic reaction centers (RCs) are compared. In the primary QA site ubiquinone is reduced only to the anionic semiquinone (Q•−) while in the secondary QB site the product is the doubly reduced, doubly protonated quinol (QH2). The ways in which the protein modifies the relative energy of each reduced and protonated intermediate are described. For example, the protein stabilizes Q•− while destabilizing Q= relative to aqueous solution through electrostatic interactions. In addition, kinetic and thermodynamic mechanisms for stabilizing the intermediate semiquinones are compared. Evidence for the protein sequestering anionic compounds by slowing both on and off rates as well as by binding the anion more tightly is reviewed. PMID:18979192

Tools Developed to Prepare and Stabilize Reactor Spent Fuel for Retrieval from Tile Holes - 12251

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

Horne, Michael; Clough, Malcolm

Spent fuel from the Chalk River Laboratories (CRL) nuclear reactors is stored in the waste management areas on site. This fuel is contained within carbon steel spent fuel cans that are stored inside vertical carbon steel lined concrete pipes in the ground known as tile holes. The fuel cans have been stored in the tile holes for greater than 30 years. Some of the fuel cans have experienced corrosion which may have affected their structural integrity as well as the potential to form hydrogen gas. In addition to these potential hazards, there was a need to clean contaminated surfaces insidemore » of and around the exposed upper surface of the tile holes. As part of the site waste management remediation plan spent fuel will be retrieved from degraded tile holes, dried, and relocated to a new purpose built above ground storage facility. There have been a number of tools that are required to be developed to ensure spent fuel cans are in a safe condition prior to retrieval and re-location. A series of special purpose tools have been designed and constructed to stabilize the contents of the tile holes, to determine the integrity of the fuel containers and to decontaminate inside and around the tile holes. Described herein are the methods and types of tools used. Tools that have been presented here have been used, or will be used in the near future, in the waste management areas of the CRL Site in preparation for storage of spent fuel in a new above ground facility. The stabilization tools have been demonstrated on mock-up facilities prior to successful use in the field to remove hydrogen gas and uranium hydrides from the fuel cans. A lifting tool has been developed and used successfully in the field to confirm the integrity of the fuel cans for future relocation. A tool using a commercial dry ice blaster has been developed and is ready to start mock-up trials and is scheduled to be used in the field during the summer of 2012. (authors)« less

Rock slope stability analysis along the North Carolina section of the Blue Ridge Parkway: Using a geographic information system (GIS) to integrate site data and digital geologic maps

USGS Publications Warehouse

Latham, R.S.; Wooten, R.M.; Cattanach, B.L.; Merschat, C.E.; Bozdog, G.N.

2009-01-01

In 2008, the North Carolina Geological Survey (NCGS) completed a five-year geologic and geohazards inventory of the 406-km long North Carolina segment of the Blue Ridge Parkway (BRP). The ArcGIS??? format deliverables for rock slopes include a slope movement and slope movement deposit database and maps and site-specific rock slope stability assessments at 158 locations. Database entries for known and potential rock slope failures include: location data, failure modes and dimensions, activity dates and levels, structural and lithologic data, the occurrence of sulfide minerals and acid-producing potential test results. Rock slope stability assessments include photographs of the rock cuts and show locations and orientations of rock data, seepage zones, and kinematic stability analyses. Assigned preliminary geologic hazard ratings of low, moderate and high indicate the generalized relative probability of rock fall and/or rock slide activity at a given location. Statistics compiled based on the database indicate some general patterns within the data. This information provides the National Park Service with tools that can aid in emergency preparedness, and in budgeting mitigation, maintenance and repair measures. Copyright 2009 ARMA, American Rock Mechanics Association.

Arabidopsis SYT1 maintains stability of cortical endoplasmic reticulum networks and VAP27-1-enriched endoplasmic reticulum-plasma membrane contact sites.

PubMed

Siao, Wei; Wang, Pengwei; Voigt, Boris; Hussey, Patrick J; Baluska, Frantisek

2016-11-01

Arabidopsis synaptotagmin 1 (SYT1) is localized on the endoplasmic reticulum-plasma membrane (ER-PM) contact sites in leaf and root cells. The ER-PM localization of Arabidopsis SYT1 resembles that of the extended synaptotagmins (E-SYTs) in animal cells. In mammals, E-SYTs have been shown to regulate calcium signaling, lipid transfer, and endocytosis. Arabidopsis SYT1 was reported to be essential for maintaining cell integrity and virus movement. This study provides detailed insight into the subcellular localization of SYT1 and VAP27-1, another ER-PM-tethering protein. SYT1 and VAP27-1 were shown to be localized on distinct ER-PM contact sites. The VAP27-1-enriched ER-PM contact sites (V-EPCSs) were always in contact with the SYT1-enriched ER-PM contact sites (S-EPCSs). The V-EPCSs still existed in the leaf epidermal cells of the SYT1 null mutant; however, they were less stable than those in the wild type. The polygonal networks of cortical ER disassembled and the mobility of VAP27-1 protein on the ER-PM contact sites increased in leaf cells of the SYT1 null mutant. These results suggest that SYT1 is responsible for stabilizing the ER network and V-EPCSs. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

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.

Correlation between Initial BIC and the Insertion Torque/Depth Integral Recorded with an Instantaneous Torque-Measuring Implant Motor: An in vivo Study.

PubMed

Capparé, Paolo; Vinci, Raffaele; Di Stefano, Danilo Alessio; Traini, Tonino; Pantaleo, Giuseppe; Gherlone, Enrico Felice; Gastaldi, Giorgio

2015-10-01

Quantitative intraoperative evaluation of bone quality at implant placement site and postinsertion implant primary stability assessment are two key parameters to perform implant-supported rehabilitation properly. A novel micromotor has been recently introduced allowing to measure bone density at implant placement site and to record implant insertion-related parameters, such as the instantaneous, average and peak insertion torque values, and the insertion torque/depth integral. The aim of this study was to investigate in vivo if any correlation existed between initial bone-to-implant contact (BIC) and bone density and integral values recorded with the instrument. Twenty-five patients seeking for implant-supported rehabilitation of edentulous areas were consecutively treated. Before implant placement, bone density at the insertion site was measured. For each patient, an undersized 3.3 × 8-mm implant was placed, recording the insertion torque/depth integral values. After 15 minutes, the undersized implant was retrieved with a 0.5 mm-thick layer of bone surrounding it. Standard implants were consequently placed. Retrieved implants were analyzed for initial BIC quantification after fixation, dehydration, acrylic resin embedment, sections cutting and grinding, and toluidine-blue and acid fuchsine staining. Correlation between initial BIC values, bone density at the insertion site, and the torque/depth integral values was investigated by linear regression analysis. A significant linear correlation was found to exist between initial BIC and (a) bone density at the insertion site (R = 0.96, explained variance R(2)  = 0.92) and (b) torque/depth integral at placement (R = 0.81, explained variance R(2)  = 0.66). The system provided quantitative, reliable data correlating significantly with immediate postinsertion initial BIC, and could therefore represent a valuable tool both for clinical research and for the oral implantologist in his/her daily clinical practice. © 2015 Wiley Periodicals, Inc.

The chimpanzee nest quantified: morphology and ecology of arboreal sleeping platforms within the dry habitat site of Toro-Semliki Wildlife Reserve, Uganda.

PubMed

Samson, David R

2012-10-01

The nightly construction of a sleeping platform (SP) or "nest" is widely regarded as a universal behavior among great apes, yet SP structural morphology has been incompletely quantified to date. This is in part due to the inherent difficulties of gathering empirical data on arboreally sited SPs. I gathered quantitative structural data on SPs (n = 65) at the Toro-Semliki Wildlife Reserve from May to June 2008 and from August 2010 to January 2011. I measured SP length (semi-major axis length), width (semi-minor axis length), radii (length from the surface center to the rim edge 45° from the axis), depth (width of the concavity from the surface center to the parallel rim), and thickness (ventral center to the dorsal underside of the SP). SP complexity was defined with a scored index. SP complexity was found to be correlated with SP circumference, surface area, mass, proportion of soft leafy material to hard woody material, number of frame support branches used in its construction, and other measures that are argued to index "comfort." In addition, the height of the tree canopy above the SP was negatively correlated with SP complexity. Greater complexity (and therefore stability) is argued to maintain SP integrity, stability and restraint in the face of greater wind speeds, thereby reducing the probability of falls. Given the observation that males site SPs lower than females (Fruth and Hohmann, Ethology 94:113-126, 1994; Brownlow et al., Am J Primatol 55:49-55, 2001), and that SP diameters were greater for SPs sited low in the canopy at Semliki, it is inferred that more massive males benefit from lower climbing expenses and greater stability. These data support Baldwin and colleagues' (Primates 22:474-486, 1981) hypothesis that the principal advantage of SPs over open-branch sleeping sites is the greater stability required by large-bodied great apes.

One- and two-photon states for quantum information

NASA Astrophysics Data System (ADS)

Peters, Nicholas A.

To find expression stability among transgenic lines, the Recombinase Mediated Transgene Integration (RMTI) technology using the Cre/ lox-mediated site-specific gene integration system was used. The objectives were to develop an efficient method of site-specific transgene integration and to test the effectiveness of this method by assaying transgene expression in the RMTI lines. The RMTI technology allows the precise integration of a transgene in a previously placed target genomic location containing a lox site. The efficiency of CRE-mediated site-specific integration in rice by particle bombardment was found to vary from 3 to 28% in nine different experiments. Some hemizygous site-specific integration plants that were derived from homozygous target locus were found to undergo CRE-mediated reversion of the integration locus. No reversion was observed in callus; however, reverting cells may have been excluded due to selection pressure. The expression of the transgene gus was studied in all 40 callus lines, 12 regenerated T0 plants and the T1 and T2 progenies of 5 lines. The isogenic SC lines had an average expression level based on the activity of beta-glucuronidase of 158 +/- 9 units/mg protein (mean +/- SEM; n=3; variance within SC lines are expressed as standard error of the mean SEM) indicating a significantly higher level of expression, as compared to MC lines that had a much lower expression level 44 +/- 8 units/mg protein (mean +/- SEM; n=3) and the imprecise lines that had 22 +/- 8 units/mg protein (mean +/- SEM; n=3). Transgene expression in the callus cells of precise single copy lines varied by ˜3 fold, whereas that in multi-copy lines varied by ˜30 fold. Furthermore, precise single copy lines, on an average, contained ˜3.5 fold higher expression than multi-copy lines. Transgene expression in the plants of precise single-copy lines was highly variable, which was found to be due to the loss of the integration because of CRE-mediated reversion in the locus. (Abstract shortened by UMI.)

Biodiveristy and Stability of Aboriginal Salmon Fisheries in the Fraser River Watershed

NASA Astrophysics Data System (ADS)

Nesbitt, H. K.; Moore, J.

2015-12-01

Natural watersheds are hierarchical networks that may confer stability to ecosystem functions through integration of upstream biodiversity, whereby upstream asset diversification stabilizes the aggregate downstream through the portfolio effect. Here we show that riverine structure and its associated diversity confer stability of salmon catch and lengthened fishing seasons for Aboriginal fisheries on the Fraser River (1370km) in BC, Canada, the second longest dam-free salmon migration route in North America. In Canada, Aboriginal people have rights to fish for food, social, and ceremonial (FSC) purposes. FSC fisheries are located throughout the Fraser watershed and have access to varying levels of salmon diversity based on their location. For instance, fisheries at the mouth of the river have access to all of the salmon that spawn throughout the entire watershed, thus integrating across the complete diversity profile of the entire river. In contrast, fisheries in the headwaters have access to fewer salmon species and populations and thus fish from a much less diverse portfolio. These spatial gradients of diversity within watersheds provide a natural contrast for quantifying the effects of different types of diversity on interannual resource stability and seasonal availability. We acquired weekly and yearly catch totals from 1983 to 2012 (30 years) for Chinook, chum, coho, pink, and sockeye salmon for 21 FSC fishing sites throughout the Fraser River watershed from Fisheries and Oceans Canada. We examined how both population- and species-level diversity affects catch stability and season length at each site by quantifying year-to-year variability and within-year season length respectively. Salmon species diversity made fisheries up to 28% more stable in their catch than predicted with 3.7 more weeks to fish on average. Fisheries with access to high population diversity had up to 3.8 times more stable catch and 3 times longer seasons than less diverse fisheries. We show that both species- and population-level diversity support food security in First Nations fisheries. These data indicate that protecting multiple dimensions of biodiversity, such as through preserving the natural structure of watersheds, will promote food security of Aboriginal people.

Real-time sub-Ångstrom imaging of reversible and irreversible conformations in rhodium catalysts and graphene

NASA Astrophysics Data System (ADS)

Kisielowski, Christian; Wang, Lin-Wang; Specht, Petra; Calderon, Hector A.; Barton, Bastian; Jiang, Bin; Kang, Joo H.; Cieslinski, Robert

2013-07-01

The dynamic responses of a rhodium catalyst and a graphene sheet are investigated upon random excitation with 80 kV electrons. An extraordinary electron microscope stability and resolution allow studying temporary atom displacements from their equilibrium lattice sites into metastable sites across projected distances as short as 60 pm. In the rhodium catalyst, directed and reversible atom displacements emerge from excitations into metastable interstitial sites and surface states that can be explained by single atom trajectories. Calculated energy barriers of 0.13 eV and 1.05 eV allow capturing single atom trapping events at video rates that are stabilized by the Rh [110] surface corrugation. Molecular dynamics simulations reveal that randomly delivered electrons can also reversibly enhance the sp3 and the sp1 characters of the sp2-bonded carbon atoms in graphene. The underlying collective atom motion can dynamically stabilize characteristic atom displacements that are unpredictable by single atom trajectories. We detect three specific displacements and use two of them to propose a path for the irreversible phase transformation of a graphene nanoribbon into carbene. Collectively stabilized atom displacements greatly exceed the thermal vibration amplitudes described by Debye-Waller factors and their measured dose rate dependence is attributed to tunable phonon contributions to the internal energy of the systems. Our experiments suggest operating electron microscopes with beam currents as small as zepto-amperes/nm2 in a weak-excitation approach to improve on sample integrity and allow for time-resolved studies of conformational object changes that probe for functional behavior of catalytic surfaces or molecules.

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.

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.

The insertion torque-depth curve integral as a measure of implant primary stability: An in vitro study on polyurethane foam blocks.

PubMed

Di Stefano, Danilo Alessio; Arosio, Paolo; Gastaldi, Giorgio; Gherlone, Enrico

2017-07-08

Recent research has shown that dynamic parameters correlate with insertion energy-that is, the total work needed to place an implant into its site-might convey more reliable information concerning immediate implant primary stability at insertion than the commonly used insertion torque (IT), the reverse torque (RT), or the implant stability quotient (ISQ). Yet knowledge on these dynamic parameters is still limited. The purpose of this in vitro study was to evaluate whether an energy-related parameter, the torque-depth curve integral (I), could be a reliable measure of primary stability. This was done by assessing if (I) measurement was operator-independent, by investigating its correlation with other known primary stability parameters (IT, RT, or ISQ) by quantifying the (I) average error and correlating (I), IT, RT, and ISQ variations with bone density. Five operators placed 200 implants in polyurethane foam blocks of different densities using a micromotor that calculated the (I) during implant placement. Primary implant stability was assessed by measuring the ISQ, IT, and RT. ANOVA tests were used to evaluate whether measurements were operator independent (P>.05 in all cases). A correlation analysis was performed between (I) and IT, ISQ, and RT. The (I) average error was calculated and compared with that of the other parameters by ANOVA. (I)-density, IT-density, ISQ-density, and RT-density plots were drawn, and their slopes were compared by ANCOVA. The (I) measurements were operator independent and correlated with IT, ISQ, and RT. The average error of these parameters was not significantly different (P>.05 in all cases). The (I)-density, IT-density, ISQ-density, and RT-density curves were linear in the 0.16 to 0.49 g/cm³ range, with the (I)-density curves having a significantly greater slope than those regarding the other parameters (P≤.001 in all cases). The torque-depth curve integral (I) provides a reliable assessment of primary stability and shows a greater sensitivity to density variations than other known primary stability parameters. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Computational design of variants for cephalosporin C acylase from Pseudomonas strain N176 with improved stability and activity.

PubMed

Tian, Ye; Huang, Xiaoqiang; Li, Qing; Zhu, Yushan

2017-01-01

In this report, redesigning cephalosporin C acylase from the Pseudomonas strain N176 revealed that the loss of stability owing to the introduced mutations at the active site can be recovered by repacking the nearby hydrophobic core regions. Starting from a quadruple mutant M31βF/H57βS/V68βA/H70βS, whose decrease in stability is largely owing to the mutation V68βA at the active site, we employed a computational enzyme design strategy that integrated design both at hydrophobic core regions for stability enhancement and at the active site for activity improvement. Single-point mutations L154βF, Y167βF, L180βF and their combinations L154βF/L180βF and L154βF/Y167βF/L180βF were found to display improved stability and activity. The two-point mutant L154βF/L180βF increased the protein melting temperature (T m ) by 11.7 °C and the catalytic efficiency V max /K m by 57 % compared with the values of the starting quadruple mutant. The catalytic efficiency of the resulting sixfold mutant M31βF/H57βS/V68βA/H70βS/L154βF/L180βF is recovered to become comparable to that of the triple mutant M31βF/H57βS/H70βS, but with a higher T m . Further experiments showed that single-point mutations L154βF, L180βF, and their combination contribute no stability enhancement to the triple mutant M31βF/H57βS/H70βS. These results verify that the lost stability because of mutation V68βA at the active site was recovered by introducing mutations L154βF and L180βF at hydrophobic core regions. Importantly, mutation V68βA in the six-residue mutant provides more space to accommodate the bulky side chain of cephalosporin C, which could help in designing cephalosporin C acylase mutants with higher activities and the practical one-step enzymatic route to prepare 7-aminocephalosporanic acid at industrial-scale levels.

A combination of ferric nitrate/EDDS-enhanced washing and sludge-derived biochar stabilization of metal-contaminated soils.

PubMed

Yoo, Jong-Chan; Beiyuan, Jingzi; Wang, Lei; Tsang, Daniel C W; Baek, Kitae; Bolan, Nanthi S; Ok, Yong Sik; Li, Xiang-Dong

2018-03-01

In this study, soil washing and stabilization as a two-step soil remediation strategy was performed to remediate Pb- and Cu-contaminated soils from shooting range and railway sites. Ferric nitrate (Fe(NO 3 ) 3 ) and [S,S]-ethylenediamine disuccinate (EDDS) were used as washing agents, whereas three types of sludge-derived biochars and phosphogypsum were employed as soil stabilizers. While Fe(NO 3 ) 3 extracted larger amounts of metals compared to EDDS (84% Pb and 64% Cu from shooting range soil; 30% Pb and 40% Cu from railway site soil), it caused severe soil acidification. Both Fe(NO 3 ) 3 and EDDS washing enhanced the mobility of residual metals in the two soils, which in most cases could be mitigated by subsequent 2-month stabilization by sludge-derived biochars or phosphogypsum. By contrast, the metal bioaccessibility could only be reduced by soil washing. Nutrient-rich sludge-derived biochar replenished available P and K in both soils, whereas Fe(NO 3 ) 3 washing provided available nitrogen (N). Soil amendment enhanced acid phosphatase activity but marginally improved soil dehydrogenase and urease activity in the treated soils, possibly due to the influence of residual metals. This study supported the integration of soil washing (by Fe(NO 3 ) 3 or EDDS) with soil stabilization (by sludge-derived biochars or phosphogypsum) for accomplishing the reduction of metal mobility and bioaccessibility, while restoring the environmental quality of the treated soils. Copyright © 2017 Elsevier B.V. All rights reserved.

Toward a Flexible Variable Stiffness Endoport for Single-Site Partial Nephrectomy.

PubMed

Amanov, E; Nguyen, T-D; Markmann, S; Imkamp, F; Burgner-Kahrs, J

2018-05-31

Laparoscopic partial nephrectomy for localized renal tumors is an upcoming standard minimally invasive surgical procedure. However, a single-site laparoscopic approach would be even more preferable in terms of invasiveness. While the manual approach offers rigid curved tools, robotic single-site systems provide high degrees of freedom manipulators. However, they either provide only a straight deployment port, lack of instrument integration, or cannot be reconfigured. Therefore, the current main shortcomings of single-site surgery approaches include limited tool dexterity, visualization, and intuitive use by the surgeons. For partial nephrectomy in particular, the accessibility of the tumors remains limited and requires invasive kidney mobilization (separation of the kidney from the surrounding tissue), resulting in patient stress and prolonged surgery. We address these limitations by introducing a flexible, robotic, variable stiffness port with several working channels, which consists of a two-segment tendon-driven continuum robot with integrated granular and layer jamming for stabilizing the pose and shape. We investigate biocompatible granules for granular jamming and demonstrate the stiffening capabilities in terms of pose and shape accuracy with experimental evaluations. Additionally, we conduct in vitro experiments on a phantom and prove that the visualization of tumors at various sites is increased up to 38% in comparison to straight endoscopes.

A human fecal contamination index for ranking impaired ...

EPA Pesticide Factsheets

Human fecal pollution of surface water remains a public health concern worldwide. As a result, there is a growing interest in the application of human-associated fecal source identification quantitative real-time PCR (qPCR) technologies for recreational water quality risk management. The transition from a research subject to a management tool requires the integration of standardized water sampling, laboratory, and data analysis procedures. In this study, a standardized HF183/BacR287 qPCR method was combined with a water sampling strategy and Bayesian data algorithm to establish a human fecal contamination index that can be used to rank impaired recreational water sites polluted with human waste. Stability and bias of index predictions were investigated under various parameters including siteswith different pollution levels, sampling period time range (1-15 weeks), and number of qPCR replicates per sample (2-14 replicates). Sensitivity analyses were conducted with simulated data sets (100 iterations) seeded with HF183/BacR287 qPCR laboratory measurements from water samples collected from three Southern California sites (588 qPCR measurements). Findings suggest that site ranking is feasible and that all parameters tested influence stability and bias in human fecal contamination indexscoring. Trends identified by sensitivity analyses will provide managers with the information needed to design and conduct field studies to rank impaired recreational water sites based

Highly accessible AU-rich regions in 3' untranslated regions are hotspots for binding of regulatory factors.

PubMed

Plass, Mireya; Rasmussen, Simon H; Krogh, Anders

2017-04-01

Post-transcriptional regulation is regarded as one of the major processes involved in the regulation of gene expression. It is mainly performed by RNA binding proteins and microRNAs, which target RNAs and typically affect their stability. Recent efforts from the scientific community have aimed at understanding post-transcriptional regulation at a global scale by using high-throughput sequencing techniques such as cross-linking and immunoprecipitation (CLIP), which facilitates identification of binding sites of these regulatory factors. However, the diversity in the experimental procedures and bioinformatics analyses has hindered the integration of multiple datasets and thus limited the development of an integrated view of post-transcriptional regulation. In this work, we have performed a comprehensive analysis of 107 CLIP datasets from 49 different RBPs in HEK293 cells to shed light on the complex interactions that govern post-transcriptional regulation. By developing a more stringent CLIP analysis pipeline we have discovered the existence of conserved regulatory AU-rich regions in the 3'UTRs where miRNAs and RBPs that regulate several processes such as polyadenylation or mRNA stability bind. Analogous to promoters, many factors have binding sites overlapping or in close proximity in these hotspots and hence the regulation of the mRNA may depend on their relative concentrations. This hypothesis is supported by RBP knockdown experiments that alter the relative concentration of RBPs in the cell. Upon AGO2 knockdown (KD), transcripts containing "free" target sites show increased expression levels compared to those containing target sites in hotspots, which suggests that target sites within hotspots are less available for miRNAs to bind. Interestingly, these hotspots appear enriched in genes with regulatory functions such as DNA binding and RNA binding. Taken together, our results suggest that hotspots are functional regulatory elements that define an extra layer of regulation of post-transcriptional regulatory networks.

Highly accessible AU-rich regions in 3’ untranslated regions are hotspots for binding of regulatory factors

PubMed Central

2017-01-01

Post-transcriptional regulation is regarded as one of the major processes involved in the regulation of gene expression. It is mainly performed by RNA binding proteins and microRNAs, which target RNAs and typically affect their stability. Recent efforts from the scientific community have aimed at understanding post-transcriptional regulation at a global scale by using high-throughput sequencing techniques such as cross-linking and immunoprecipitation (CLIP), which facilitates identification of binding sites of these regulatory factors. However, the diversity in the experimental procedures and bioinformatics analyses has hindered the integration of multiple datasets and thus limited the development of an integrated view of post-transcriptional regulation. In this work, we have performed a comprehensive analysis of 107 CLIP datasets from 49 different RBPs in HEK293 cells to shed light on the complex interactions that govern post-transcriptional regulation. By developing a more stringent CLIP analysis pipeline we have discovered the existence of conserved regulatory AU-rich regions in the 3’UTRs where miRNAs and RBPs that regulate several processes such as polyadenylation or mRNA stability bind. Analogous to promoters, many factors have binding sites overlapping or in close proximity in these hotspots and hence the regulation of the mRNA may depend on their relative concentrations. This hypothesis is supported by RBP knockdown experiments that alter the relative concentration of RBPs in the cell. Upon AGO2 knockdown (KD), transcripts containing “free” target sites show increased expression levels compared to those containing target sites in hotspots, which suggests that target sites within hotspots are less available for miRNAs to bind. Interestingly, these hotspots appear enriched in genes with regulatory functions such as DNA binding and RNA binding. Taken together, our results suggest that hotspots are functional regulatory elements that define an extra layer of regulation of post-transcriptional regulatory networks. PMID:28410363

A novel integrated framework and improved methodology of computer-aided drug design.

PubMed

Chen, Calvin Yu-Chian

2013-01-01

Computer-aided drug design (CADD) is a critical initiating step of drug development, but a single model capable of covering all designing aspects remains to be elucidated. Hence, we developed a drug design modeling framework that integrates multiple approaches, including machine learning based quantitative structure-activity relationship (QSAR) analysis, 3D-QSAR, Bayesian network, pharmacophore modeling, and structure-based docking algorithm. Restrictions for each model were defined for improved individual and overall accuracy. An integration method was applied to join the results from each model to minimize bias and errors. In addition, the integrated model adopts both static and dynamic analysis to validate the intermolecular stabilities of the receptor-ligand conformation. The proposed protocol was applied to identifying HER2 inhibitors from traditional Chinese medicine (TCM) as an example for validating our new protocol. Eight potent leads were identified from six TCM sources. A joint validation system comprised of comparative molecular field analysis, comparative molecular similarity indices analysis, and molecular dynamics simulation further characterized the candidates into three potential binding conformations and validated the binding stability of each protein-ligand complex. The ligand pathway was also performed to predict the ligand "in" and "exit" from the binding site. In summary, we propose a novel systematic CADD methodology for the identification, analysis, and characterization of drug-like candidates.

Integration Profile and Safety of an Adenovirus Hybrid-Vector Utilizing Hyperactive Sleeping Beauty Transposase for Somatic Integration

PubMed Central

Zhang, Wenli; Muck-Hausl, Martin; Wang, Jichang; Sun, Chuanbo; Gebbing, Maren; Miskey, Csaba; Ivics, Zoltan; Izsvak, Zsuzsanna; Ehrhardt, Anja

2013-01-01

We recently developed adenovirus/transposase hybrid-vectors utilizing the previously described hyperactive Sleeping Beauty (SB) transposase HSB5 for somatic integration and we could show stabilized transgene expression in mice and a canine model for hemophilia B. However, the safety profile of these hybrid-vectors with respect to vector dose and genotoxicity remains to be investigated. Herein, we evaluated this hybrid-vector system in C57Bl/6 mice with escalating vector dose settings. We found that in all mice which received the hyperactive SB transposase, transgene expression levels were stabilized in a dose-dependent manner and that the highest vector dose was accompanied by fatalities in mice. To analyze potential genotoxic side-effects due to somatic integration into host chromosomes, we performed a genome-wide integration site analysis using linker-mediated PCR (LM-PCR) and linear amplification-mediated PCR (LAM-PCR). Analysis of genomic DNA samples obtained from HSB5 treated female and male mice revealed a total of 1327 unique transposition events. Overall the chromosomal distribution pattern was close-to-random and we observed a random integration profile with respect to integration into gene and non-gene areas. Notably, when using the LM-PCR protocol, 27 extra-chromosomal integration events were identified, most likely caused by transposon excision and subsequent transposition into the delivered adenoviral vector genome. In total, this study provides a careful evaluation of the safety profile of adenovirus/Sleeping Beauty transposase hybrid-vectors. The obtained information will be useful when designing future preclinical studies utilizing hybrid-vectors in small and large animal models. PMID:24124483

Protein stability and dynamics influenced by ligands in extremophilic complexes - a molecular dynamics investigation.

PubMed

Khan, Sara; Farooq, Umar; Kurnikova, Maria

2017-08-22

In this study, we explore the structural and dynamic adaptations of the Tryptophan synthase α-subunit in a ligand bound state in psychrophilic, mesophilic and hyperthermophilic organisms at different temperatures by MD simulations. We quantify the global and local fluctuations in the 40 ns time scale by analyzing the root mean square deviation/fluctuations. The distinct behavior of the active site and loop 6 is observed with the elevation of temperature. Protein stability relies more on electrostatic interactions, and these interactions might be responsible for the stability of varying temperature evolved proteins. The paper also focuses on the effect of temperature on protein dynamics and stability governed by the distinct behavior of the ligand associated with its retention, binding and dissociation over the course of time. The integration of principle component analysis and a free energy landscape was useful in identifying the conformational space accessible to ligand bound homologues and how the presence of the ligand alters the conformational and dynamic properties of the protein.

Disruption of the Putative Vascular Leak Peptide Sequence in the Stabilized Ricin Vaccine Candidate RTA1-33/44-198

PubMed Central

Janosi, Laszlo; Compton, Jaimee R.; Legler, Patricia M.; Steele, Keith E.; Davis, Jon M.; Matyas, Gary R.; Millard, Charles B.

2013-01-01

Vitetta and colleagues identified and characterized a putative vascular leak peptide (VLP) consensus sequence in recombinant ricin toxin A-chain (RTA) that contributed to dose-limiting human toxicity when RTA was administered intravenously in large quantities during chemotherapy. We disrupted this potentially toxic site within the more stable RTA1-33/44-198 vaccine immunogen and determined the impact of these mutations on protein stability, structure and protective immunogenicity using an experimental intranasal ricin challenge model in BALB/c mice to determine if the mutations were compatible. Single amino acid substitutions at the positions corresponding with RTA D75 (to A, or N) and V76 (to I, or M) had minor effects on the apparent protein melting temperature of RTA1-33/44-198 but all four variants retained greater apparent stability than the parent RTA. Moreover, each VLP(−) variant tested provided protection comparable with that of RTA1-33/44-198 against supralethal intranasal ricin challenge as judged by animal survival and several biomarkers. To understand better how VLP substitutions and mutations near the VLP site impact epitope structure, we introduced a previously described thermal stabilizing disulfide bond (R48C/T77C) along with the D75N or V76I substitutions in RTA1-33/44-198. The D75N mutation was compatible with the adjacent stabilizing R48C/T77C disulfide bond and the Tm was unaffected, whereas the V76I mutation was less compatible with the adjacent disulfide bond involving C77. A crystal structure of the RTA1-33/44-198 R48C/T77C/D75N variant showed that the structural integrity of the immunogen was largely conserved and that a stable immunogen could be produced from E. coli. We conclude that it is feasible to disrupt the VLP site in RTA1-33/44-198 with little or no impact on apparent protein stability or protective efficacy in mice and such variants can be stabilized further by introduction of a disulfide bond. PMID:23364220

DbPTM 3.0: an informative resource for investigating substrate site specificity and functional association of protein post-translational modifications.

PubMed

Lu, Cheng-Tsung; Huang, Kai-Yao; Su, Min-Gang; Lee, Tzong-Yi; Bretaña, Neil Arvin; Chang, Wen-Chi; Chen, Yi-Ju; Chen, Yu-Ju; Huang, Hsien-Da

2013-01-01

Protein modification is an extremely important post-translational regulation that adjusts the physical and chemical properties, conformation, stability and activity of a protein; thus altering protein function. Due to the high throughput of mass spectrometry (MS)-based methods in identifying site-specific post-translational modifications (PTMs), dbPTM (http://dbPTM.mbc.nctu.edu.tw/) is updated to integrate experimental PTMs obtained from public resources as well as manually curated MS/MS peptides associated with PTMs from research articles. Version 3.0 of dbPTM aims to be an informative resource for investigating the substrate specificity of PTM sites and functional association of PTMs between substrates and their interacting proteins. In order to investigate the substrate specificity for modification sites, a newly developed statistical method has been applied to identify the significant substrate motifs for each type of PTMs containing sufficient experimental data. According to the data statistics in dbPTM, >60% of PTM sites are located in the functional domains of proteins. It is known that most PTMs can create binding sites for specific protein-interaction domains that work together for cellular function. Thus, this update integrates protein-protein interaction and domain-domain interaction to determine the functional association of PTM sites located in protein-interacting domains. Additionally, the information of structural topologies on transmembrane (TM) proteins is integrated in dbPTM in order to delineate the structural correlation between the reported PTM sites and TM topologies. To facilitate the investigation of PTMs on TM proteins, the PTM substrate sites and the structural topology are graphically represented. Also, literature information related to PTMs, orthologous conservations and substrate motifs of PTMs are also provided in the resource. Finally, this version features an improved web interface to facilitate convenient access to the resource.

Gram-negative trimeric porins have specific LPS binding sites that are essential for porin biogenesis

PubMed Central

Arunmanee, Wanatchaporn; Pathania, Monisha; Solovyova, Alexandra S.; Le Brun, Anton P.; Ridley, Helen; Baslé, Arnaud; van den Berg, Bert; Lakey, Jeremy H.

2016-01-01

The outer membrane (OM) of gram-negative bacteria is an unusual asymmetric bilayer with an external monolayer of lipopolysaccharide (LPS) and an inner layer of phospholipids. The LPS layer is rigid and stabilized by divalent cation cross-links between phosphate groups on the core oligosaccharide regions. This means that the OM is robust and highly impermeable to toxins and antibiotics. During their biogenesis, OM proteins (OMPs), which function as transporters and receptors, must integrate into this ordered monolayer while preserving its impermeability. Here we reveal the specific interactions between the trimeric porins of Enterobacteriaceae and LPS. Isolated porins form complexes with variable numbers of LPS molecules, which are stabilized by calcium ions. In earlier studies, two high-affinity sites were predicted to contain groups of positively charged side chains. Mutation of these residues led to the loss of LPS binding and, in one site, also prevented trimerization of the porin, explaining the previously observed effect of LPS mutants on porin folding. The high-resolution X-ray crystal structure of a trimeric porin–LPS complex not only helps to explain the mutagenesis results but also reveals more complex, subtle porin–LPS interactions and a bridging calcium ion. PMID:27493217

Multidisciplinary study on anthropogenic landslides in Nepal

NASA Astrophysics Data System (ADS)

Puglia, Christopher; Derron, Marc-Henri; Nicolet, Pierrick; Sudmeier-Rieux, Karen; Jaboyedoff, Michel; Devkota, Sanjay

2013-04-01

Nepal is a country in which shallow landslide is a frequent phenomenon. Monsoon is the main triggering factor but anthropogenic influence is often significant too. Indeed, many infrastructures, such as roads or water pipes, are not built in a rigorous way because of a lack of funds and knowledge. In the present study we examine the technical, social and economic issues of landslide management for two sites in Nepal. The first site is located in Sanusiruwari VDC (Sindhupalchock district, central Nepal) and the second one in Namadi VDC (Ramecchap district, central Nepal). Both sites are affected by landslides induced by the construction of hydropower plants. These landslides may threaten the viability of the hydropower plants. At both sites the problems are quite similar, but the first site project is a private one and the second one is a public one implemented by the United Nations Development Programme (UNDP). For both sites, bioengineering methods using Vetiver (Vetyveria zizanioides) plantations is the main stabilization measure. To follow the progression of both landslides, fieldwork observations were conducted before and after the 2012 rainy season, including photogrammetric and distancemeter acquisitions. Main issues were discussed with communities and stakeholders of the hydropower projects through interviews and participatory risk mapping. Main issues include: lack of communication between the project managers and communities leading to conflict and the lack of maintenance of the bio-engineering sites, leading to less effective Vetiver growth and slope stabilization. Comparing the landslide management (technical, social and economic) of the two projects allows to point out some specific issues within an integrated risk perspective.

Integrated, long term, sustainable, cost effective biosolids management at a large Canadian wastewater treatment facility.

PubMed

Leblanc, R J; Allain, C J; Laughton, P J; Henry, J G

2004-01-01

The Greater Moncton Sewerage Commission's 115,000 m3/d advanced, chemically assisted primary wastewater treatment facility located in New Brunswick, Canada, has developed an integrated, long term, sustainable, cost effective programme for the management and beneficial utilization of biosolids from lime stabilized raw sludge. The paper overviews biosolids production, lime stabilization, conveyance, and odour control followed by an indepth discussion of the wastewater sludge as a resource programme, namely: composting, mine site reclamation, landfill cover, land application for agricultural use, tree farming, sod farm base as a soil enrichment, topsoil manufacturing. The paper also addresses the issues of metals, pathogens, organic compounds, the quality control program along with the regulatory requirements. Biosolids capital and operating costs are presented. Research results on removal of metals from primary sludge using a unique biological process known as BIOSOL as developed by the University of Toronto, Canada to remove metals and destroy pathogens are presented. The paper also discusses an ongoing cooperative research project with the Université de Moncton where various mixtures of plant biosolids are composted with low quality soil. Integration, approach to sustainability and "cumulative effects" as part of the overall biosolids management strategy are also discussed.

Influence of Stepped Osteotomy on Primary Stability of Implants Inserted in Low-Density Bone Sites: An In Vitro Study.

PubMed

Degidi, Marco; Daprile, Giuseppe; Piattelli, Adriano

The aims of this study were to evaluate the ability of a stepped osteotomy to improve dental implant primary stability in low-density bone sites and to investigate possible correlations between primary stability parameters. The study was performed on fresh humid bovine bone classified as type III. The test group consisted of 30 Astra Tech EV implants inserted following the protocol provided by the manufacturer. The first control group consisted of 30 Astra Tech EV implants inserted in sites without the underpreparation of the apical portion. The second control group consisted of 30 Astra Tech TX implants inserted following the protocol provided by the manufacturer. Implant insertion was performed at the predetermined 30 rpm. The insertion torque data were recorded and exported as a curve; using a trapezoidal integration technique, the area underlying the curve was calculated: this area represents the variable torque work (VTW). Peak insertion torque (pIT) and resonance frequency analysis (RFA) were also recorded. A Mann-Whitney test showed that the mean VTW was significantly higher in the test group compared with the first control and second control groups; furthermore, statistical analysis showed that pIT also was significantly higher in the test group compared with the first and second control groups. Analyzing RFA values, only the difference between the test group and second control group showed statistical significance. Pearson correlation analysis showed a very strong positive correlation between pIT and VTW values in all groups; furthermore, it showed a positive correlation between pIT and RFA values and between VTW and RFA values only in the test group. Within the limitations of an in vitro study, the results show that stepped osteotomy can be a viable method to improve implant primary stability in low-density bone sites, and that, when a traditional osteotomy method is performed, RFA presents no correlation with pIT and VTW.

Immunogenicity and thermal stability of a combined vaccine against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases.

PubMed

Saydam, Manolya; Burkin, Karena; Care, Rory; Rigsby, Peter; Bolgiano, Barbara; Mawas, Fatme

2010-08-31

The immunogenicity, structure and stability of a combined conjugate vaccine against Haemophilus influenzae type b and meningococcal serogroup C (Hib/MenC) were investigated. A rat model for immunogenicity showed that antibody responses to Hib and MenC in the combined vaccine were similar to or higher than those of individual conjugates given alone, or concomitantly at separate sites. At elevated temperatures, the combination vaccine was slightly more stable than a monovalent Hib-TT vaccine, with respect to molecular size, which could be attributed to differences in the formulations. Following 5 weeks incubation at 56 degrees C, there was some dissociation of high molecular weight conjugate without significant loss of saccharide integrity; however, this did not significantly affect the vaccine immunogenicity, demonstrating the stability of this lyophilized vaccine. (c) 2010 Elsevier Ltd. All rights reserved.

Applications analysis report: Silicate Technology Corporation's solidification/stabilization technology for organic and inorganic contaminants in soils

NASA Astrophysics Data System (ADS)

Bates, E.

1992-12-01

The STC demonstration was conducted under EPA's Superfund Innovative Technology Evaluation (SITE) Program in November, 1990, at the Selma Pressure Treating (SPT) wood preserving site in Selma, California. The SPT site was contaminated with both organics, predominantly pentachlorophenol (PCP), inorganics, mainly arsenic, chromium, and copper. Extensive sampling and analyses were performed on the waste both before and after treatment to compare physical, chemical, and leaching characteristics of raw and treated wastes. STC's contaminated soil treatment process was evaluated based on contaminant mobility measured by numerous leaching tests, structural integrity of the solidified material, measured by physical and engineering tests and morphological examinations; and economic analysis, using cost information supplied by STC and the results of the SITE demonstration, the vendor's design and test data, and other laboratory and field applications of the technology. It discusses the advantages, disadvantages, and limitations, as well as estimated costs of the technology.

A Copper(II)-Paddlewheel Metal-Organic Framework with Exceptional Hydrolytic Stability and Selective Adsorption and Detection Ability of Aniline in Water.

PubMed

Chen, Ya; Wang, Bin; Wang, Xiaoqing; Xie, Lin-Hua; Li, Jinping; Xie, Yabo; Li, Jian-Rong

2017-08-16

Copper(II)-paddlewheel-based metal-organic frameworks (CP-MOFs) represent a unique subclass of MOFs with highly predictable porous structures, facile syntheses, and functional open metal sites. However, the lack of high hydrolytic stability is an obstacle for CP-MOFs in many practical applications. In this work, we report a new CP-MOF, [Cu 4 (tdhb)] (BUT-155), which is constructed from a judiciously designed carboxylate ligand with high coordination connectivity (octatopic), abundant hydrophobic substituents (six methyl groups), and substituent constrained geometry (tetrahedral backbone), tdhb 8- [H 8 tdhb = 3,3',5,5'-tetrakis(3,5-dicarboxyphenyl)-2,2',4,4',6,6'-hexamethylbiphenyl)]. BUT-155 shows high porosity with a Brunauer-Emmett-Teller surface area of 2070 m 2 /g. Quite interestingly, this CP-MOF retains its structural integrity after being treated in water for 10 days at room temperature or in boiling water for 24 h. To the best of our knowledge, BUT-155 represents the first CP-MOF that is demonstrated to retain its structural integrity in boiling water. The high hydrolytic stability of BUT-155 allowed us to carry out adsorption studies of water vapor and aqueous organic pollutants on it. Water-vapor adsorption reveals a sigmoidal isotherm and a high uptake (46.7 wt %), which is highly reversible and regenerable. In addition, because of the availability of soft-acid-type open Cu(II) sites, BUT-155 shows a high performance for selective adsorption of soft-base-type aniline over water or phenol, and a naked-eye detectable color change for the MOF sample accompanies this. The adsorption selectivity and high adsorption capacity of aniline in BUT-155 are also well-interpreted by single-crystal structures of the water- and aniline-included phases of BUT-155.

DAC-3 Pointing Stability Analysis Results for SAGE 3 and Other Users of the International Space Station (ISS) Payload Attachment Sites (PAS)

NASA Technical Reports Server (NTRS)

Woods-Vedeler, Jessica A.; Rombado, Gabriel

1997-01-01

The purpose of this paper is to provide final results of a pointing stability analysis for external payload attachment sites (PAS) on the International Space Station (ISS). As a specific example, the pointing stability requirement of the SAGE III atmospheric science instrument was examined in this paper. The instrument requires 10 arcsec stability over 2 second periods. SAGE 3 will be mounted on the ISS starboard side at the lower, outboard FIAS. In this engineering analysis, an open-loop DAC-3 finite element model of ISS was used by the Microgravity Group at Johnson Space Flight Center to generate transient responses at PAS to a limited number of disturbances. The model included dynamics up to 50 Hz. Disturbance models considered included operation of the solar array rotary joints, thermal radiator rotary joints, and control moment gyros. Responses were filtered to model the anticipated vibration attenuation effects of active control systems on the solar and thermal radiator rotary joints. A pointing stability analysis was conducted by double integrating acceleration transient over a 2 second period. Results of the analysis are tabulated for ISS X, Y, and Z Axis rotations. These results indicate that the largest excursions in rotation during pointing occurred due to rapid slewing of the thermal radiator. Even without attenuation at the rotary joints, the resulting pointing error was limited to less than 1.6 arcsec. With vibration control at the joints, to a maximum 0.5 arcsec over a 2 second period. Based on this current level of model definition, it was concluded that between 0 - 50 Hz, the pointing stability requirement for SAGE 3 will not be exceeded by the disturbances evaluated in this study.

Using Ground Targets to Validate S-NPP VIIRS Day-Night Band Calibration

NASA Technical Reports Server (NTRS)

Chen, Xuexia; Wu, Aisheng; Xiong, Xiaoxiong; Lei, Ning; Wang, Zhipeng; Chiang, Kwofu

2016-01-01

In this study, the observations from S-NPP VIIRS Day-Night band (DNB) and Moderate resolution bands (M bands) of Libya 4 and Dome C over the first four years of the mission are used to assess the DNB low gain calibration stability. The Sensor Data Records produced by NASA Land Product Evaluation and Algorithm Testing Element (PEATE) are acquired from nearly nadir overpasses for Libya 4 desert and Dome C snow surfaces. A kernel-driven bidirectional reflectance distribution function (BRDF) correction model is used for both Libya 4 and Dome C sites to correct the surface BRDF influence. At both sites, the simulated top-of-atmosphere (TOA) DNB reflectances based on SCIAMACHY spectral data are compared with Land PEATE TOA reflectances based on modulated Relative Spectral Response (RSR). In the Libya 4 site, the results indicate a decrease of 1.03% in Land PEATE TOA reflectance and a decrease of 1.01% in SCIAMACHY derived TOA reflectance over the period from April 2012 to January 2016. In the Dome C site, the decreases are 0.29% and 0.14%, respectively. The consistency between SCIAMACHY and Land PEATE data trends is good. The small difference between SCIAMACHY and Land PEATE derived TOA reflectances could be caused by changes in the surface targets, atmosphere status, and on-orbit calibration. The reflectances and radiances of Land PEATE DNB are also compared with matching M bands and the integral M bands based on M4, M5, and M7. The fitting trends of the DNB to integral M bands ratios indicate a 0.75% decrease at the Libya 4 site and a 1.89% decrease at the Dome C site. Part of the difference is due to an insufficient number of sampled bands available within the DNB wavelength range. The above results indicate that the Land PEATE VIIRS DNB product is accurate and stable. The methods used in this study can be used on other satellite instruments to provide quantitative assessments for calibration stability.

How Mg2+ ion and water network affect the stability and structure of non-Watson-Crick base pairs in E. coli loop E of 5S rRNA: a molecular dynamics and reference interaction site model (RISM) study.

PubMed

Shanker, Sudhanshu; Bandyopadhyay, Pradipta

2017-08-01

The non-Watson-Crick (non-WC) base pairs of Escherichia coli loop E of 5S rRNA are stabilized by Mg 2+ ions through water-mediated interaction. It is important to know the synergic role of Mg 2+ and the water network surrounding Mg 2+ in stabilizing the non-WC base pairs of RNA. For this purpose, free energy change of the system is calculated using molecular dynamics (MD) simulation as Mg 2+ is pulled from RNA, which causes disturbance of the water network. It was found that Mg 2+ remains hexahydrated unless it is close to or far from RNA. In the pentahydrated form, Mg 2+ interacts directly with RNA. Water network has been identified by two complimentary methods; MD followed by a density-based clustering algorithm and three-dimensional-reference interaction site model. These two methods gave similar results. Identification of water network around Mg 2+ and non-WC base pairs gives a clue to the strong effect of water network on the stability of this RNA. Based on sequence analysis of all Eubacteria 5s rRNA, we propose that hexahydrated Mg 2+ is an integral part of this RNA and geometry of base pairs surrounding it adjust to accommodate the [Formula: see text]. Overall the findings from this work can help in understanding the basis of the complex structure and stability of RNA with non-WC base pairs.

Constitutive expression of human gastric lipase in Pichia pastoris and site-directed mutagenesis of key lid-stabilizing residues.

PubMed

Sams, Laura; Amara, Sawsan; Chakroun, Almahdi; Coudre, Sébastien; Paume, Julie; Giallo, Jacqueline; Carrière, Frédéric

2017-10-01

The cDNA encoding human gastric lipase (HGL) was integrated into the genome of Pichia pastoris using the pGAPZα A transfer vector. The HGL signal peptide was replaced by the yeast α-factor to achieve an efficient secretion. Active rHGL was produced by the transformed yeast but its levels and stability were dependent on the pH. The highest activity was obtained upon buffering the culture medium at pH5, a condition that allowed preserving enzyme activity over time. A large fraction (72±2%) of secreted rHGL remained however bound to the yeast cells, and was released by washing the cell pellet with an acid glycine-HCl buffer (pH2.2). This procedure allowed establishing a first step of purification that was completed by size exclusion chromatography. N-terminal sequencing and MALDI-ToF mass spectrometry revealed that rHGL was produced in its mature form, with a global mass of 50,837±32Da corresponding to a N-glycosylated form of HGL polypeptide (43,193Da). rHGL activity was characterized as a function of pH, various substrates and in the presence of bile salts and pepsin, and was found similar to native HGL, except for slight changes in pH optima. We then studied by site-directed mutagenesis the role of three key residues (K4, E225, R229) involved in salt bridges stabilizing the lid domain that controls the access to the active site and is part of the interfacial recognition site. Their substitution has an impact on the pH-dependent activity of rHGL and its relative activities on medium and long chain triglycerides. Copyright © 2017 Elsevier B.V. All rights reserved.

2007 Weather and Aeolian Sand-Transport Data from the Colorado River Corridor, Grand Canyon, Arizona

USGS Publications Warehouse

Draut, Amy E.; Andrews, Timothy; Fairley, Helen C.; Brown, Christopher R.

2009-01-01

Weather data constitute an integral part of ecosystem monitoring in the Colorado River corridor and are particularly valuable for understanding processes of landscape change that contribute to the stability of archeological sites. Data collected in 2007 are reported from nine weather stations in the Colorado River corridor through Grand Canyon, Ariz. The stations were deployed in February and March 2007 to measure wind speed and direction, rainfall, air temperature, relative humidity, and barometric pressure. Sand traps near each weather station collect windblown sand, from which daily aeolian sand-transport rates are calculated. The data reported here were collected as part of an ongoing study to test and evaluate methods for quantifying processes that affect the physical integrity of archeological sites along the river corridor; as such, these data can be used to identify rainfall events capable of causing gully incision and to predict likely transport pathways for aeolian sand, two landscape processes integral to the preservation of archeological sites. Weather data also have widespread applications to other studies of physical, cultural, and biological resources in Grand Canyon. Aeolian sand-transport data reported here, collected in the year before the March 2008 High-Flow Experiment (HFE) at Glen Canyon Dam, represent baseline data against which the effects of the 2008 HFE on windblown sand will be compared in future reports.

Flexibility and Stability Trade-Off in Active Site of Cold-Adapted Pseudomonas mandelii Esterase EstK.

PubMed

Truongvan, Ngoc; Jang, Sei-Heon; Lee, ChangWoo

2016-06-28

Cold-adapted enzymes exhibit enhanced conformational flexibility, especially in their active sites, as compared with their warmer-temperature counterparts. However, the mechanism by which cold-adapted enzymes maintain their active site stability is largely unknown. In this study, we investigated the role of conserved D308-Y309 residues located in the same loop as the catalytic H307 residue in the cold-adapted esterase EstK from Pseudomonas mandelii. Mutation of D308 and/or Y309 to Ala or deletion resulted in increased conformational flexibility. Particularly, the D308A or Y309A mutant showed enhanced substrate affinity and catalytic rate, as compared with wild-type EstK, via enlargement of the active site. However, all mutant EstK enzymes exhibited reduced thermal stability. The effect of mutation was greater for D308 than Y309. These results indicate that D308 is not preferable for substrate selection and catalytic activity, whereas hydrogen bond formation involving D308 is critical for active site stabilization. Taken together, conformation of the EstK active site is constrained via flexibility-stability trade-off for enzyme catalysis and thermal stability. Our study provides further insights into active site stabilization of cold-adapted enzymes.

The Effects of Molecular Crowding on the Structure and Stability of G-Quadruplexes with an Abasic Site

PubMed Central

Fujimoto, Takeshi; Nakano, Shu-ichi; Miyoshi, Daisuke; Sugimoto, Naoki

2011-01-01

Both cellular environmental factors and chemical modifications critically affect the properties of nucleic acids. However, the structure and stability of DNA containing abasic sites under cell-mimicking molecular crowding conditions remain unclear. Here, we investigated the molecular crowding effects on the structure and stability of the G-quadruplexes including a single abasic site. Structural analysis by circular dichroism showed that molecular crowding by PEG200 did not affect the topology of the G-quadruplex structure with or without an abasic site. Thermodynamic analysis further demonstrated that the degree of stabilization of the G-quadruplex by molecular crowding decreased with substitution of an abasic site for a single guanine. Notably, we found that the molecular crowding effects on the enthalpy change for G-quadruplex formation had a linear relationship with the abasic site effects depending on its position. These results are useful for predicting the structure and stability of G-quadruplexes with abasic sites in the cell-mimicking conditions. PMID:21949901

Specific phospholipid binding to Na,K-ATPase at two distinct sites.

PubMed

Habeck, Michael; Kapri-Pardes, Einat; Sharon, Michal; Karlish, Steven J D

2017-03-14

Membrane protein function can be affected by the physical state of the lipid bilayer and specific lipid-protein interactions. For Na,K-ATPase, bilayer properties can modulate pump activity, and, as observed in crystal structures, several lipids are bound within the transmembrane domain. Furthermore, Na,K-ATPase activity depends on phosphatidylserine (PS) and cholesterol, which stabilize the protein, and polyunsaturated phosphatidylcholine (PC) or phosphatidylethanolamine (PE), known to stimulate Na,K-ATPase activity. Based on lipid structural specificity and kinetic mechanisms, specific interactions of both PS and PC/PE have been inferred. Nevertheless, specific binding sites have not been identified definitively. We address this question with native mass spectrometry (MS) and site-directed mutagenesis. Native MS shows directly that one molecule each of 18:0/18:1 PS and 18:0/20:4 PC can bind specifically to purified human Na,K-ATPase (α 1 β 1 ). By replacing lysine residues at proposed phospholipid-binding sites with glutamines, the two sites have been identified. Mutations in the cytoplasmic αL8-9 loop destabilize the protein but do not affect Na,K-ATPase activity, whereas mutations in transmembrane helices (TM), αTM2 and αTM4, abolish the stimulation of activity by 18:0/20:4 PC but do not affect stability. When these data are linked to crystal structures, the underlying mechanism of PS and PC/PE effects emerges. PS (and cholesterol) bind between αTM 8, 9, 10, near the FXYD subunit, and maintain topological integrity of the labile C terminus of the α subunit (site A). PC/PE binds between αTM2, 4, 6, and 9 and accelerates the rate-limiting E 1 P-E 2 P conformational transition (site B). We discuss the potential physiological implications.

Unexpected Effects of K+ and Adenosine Triphosphate on the Thermal Stability of Na+,K+-ATPase.

PubMed

Placenti, M Agueda; Kaufman, Sergio B; González Flecha, F Luis; González Lebrero, Rodolfo M

2017-05-18

Na + ,K + -ATPase is an integral membrane protein which couples ATP hydrolysis to the transport of three Na + out and two K + into the cell. The aim of this work is to characterize the effect of K + , ATP, and Mg 2+ (essential activator) on the Na + ,K + -ATPase thermal stability. Under all conditions tested, thermal inactivation of the enzyme is concomitant with a structural change involving the ATP binding site and membrane-associated regions. Both ligands exert a clear stabilizing effect due to both enthalpic and entropic contributions. Competition experiments between ATP and K + showed that, when ATP is present, the inactivation rate coefficient exhibits a biphasic dependence on K + concentration. At low [K + ], destabilization of the enzyme is observed, while stabilization occurred at larger cation concentrations. This is not expected for a simple competition between the enzyme and two ligands that individually protect the enzyme. A model that includes enzyme species with none, one, or two K + and/or one molecule of ATP bound explains the experimental data. We concluded that, despite both ligands stabilizing the enzyme, the species with one K + and one ATP simultaneously bound is unstable.

Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy.

PubMed

Nandi, Nilay; Tyra, Lauren K; Stenesen, Drew; Krämer, Helmut

2014-10-27

How cellular stresses up-regulate autophagy is not fully understood. One potential regulator is the Drosophila melanogaster protein Acinus (Acn), which is necessary for autophagy induction and triggers excess autophagy when overexpressed. We show that cell type-specific regulation of Acn depends on proteolysis by the caspase Dcp-1. Basal Dcp-1 activity in developing photoreceptors is sufficient for this cleavage without a need for apoptosis to elevate caspase activity. On the other hand, Acn was stabilized by loss of Dcp-1 function or by the presence of a mutation in Acn that eliminates its conserved caspase cleavage site. Acn stability also was regulated by AKT1-mediated phosphorylation. Flies that expressed stabilized forms of Acn, either the phosphomimetic Acn(S641,731D) or the caspase-resistant Acn(D527A), exhibited enhanced basal autophagy. Physiologically, these flies showed improvements in processes known to be autophagy dependent, including increased starvation resistance, reduced Huntingtin-induced neurodegeneration, and prolonged life span. These data indicate that AKT1 and caspase-dependent regulation of Acn stability adjusts basal autophagy levels. © 2014 Nandi et al.

Kinetic analysis of the effects of target structure on siRNA efficiency

NASA Astrophysics Data System (ADS)

Chen, Jiawen; Zhang, Wenbing

2012-12-01

RNAi efficiency for target cleavage and protein expression is related to the target structure. Considering the RNA-induced silencing complex (RISC) as a multiple turnover enzyme, we investigated the effect of target mRNA structure on siRNA efficiency with kinetic analysis. The 4-step model was used to study the target cleavage kinetic process: hybridization nucleation at an accessible target site, RISC-mRNA hybrid elongation along with mRNA target structure melting, target cleavage, and enzyme reactivation. At this model, the terms accounting for the target accessibility, stability, and the seed and the nucleation site effects are all included. The results are in good agreement with that of experiments which show different arguments about the structure effects on siRNA efficiency. It shows that the siRNA efficiency is influenced by the integrated factors of target's accessibility, stability, and the seed effects. To study the off-target effects, a simple model of one siRNA binding to two mRNA targets was designed. By using this model, the possibility for diminishing the off-target effects by the concentration of siRNA was discussed.

10 CFR 61.44 - Stability of the disposal site after closure.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Stability of the disposal site after closure. 61.44 Section 61.44 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Performance Objectives § 61.44 Stability of the disposal site after closure. The disposal...

10 CFR 61.44 - Stability of the disposal site after closure.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Stability of the disposal site after closure. 61.44 Section 61.44 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Performance Objectives § 61.44 Stability of the disposal site after closure. The disposal...

10 CFR 61.44 - Stability of the disposal site after closure.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Stability of the disposal site after closure. 61.44 Section 61.44 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Performance Objectives § 61.44 Stability of the disposal site after closure. The disposal...

10 CFR 61.44 - Stability of the disposal site after closure.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Stability of the disposal site after closure. 61.44 Section 61.44 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Performance Objectives § 61.44 Stability of the disposal site after closure. The disposal...

10 CFR 61.44 - Stability of the disposal site after closure.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Stability of the disposal site after closure. 61.44 Section 61.44 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Performance Objectives § 61.44 Stability of the disposal site after closure. The disposal...

An integrated approach to monitoring the calibration stability of operational dual-polarization radars

DOE PAGES

Vaccarono, Mattia; Bechini, Renzo; Chandrasekar, Chandra V.; ...

2016-11-08

The stability of weather radar calibration is a mandatory aspect for quantitative applications, such as rainfall estimation, short-term weather prediction and initialization of numerical atmospheric and hydrological models. Over the years, calibration monitoring techniques based on external sources have been developed, specifically calibration using the Sun and calibration based on ground clutter returns. In this paper, these two techniques are integrated and complemented with a self-consistency procedure and an intercalibration technique. The aim of the integrated approach is to implement a robust method for online monitoring, able to detect significant changes in the radar calibration. The physical consistency of polarimetricmore » radar observables is exploited using the self-consistency approach, based on the expected correspondence between dual-polarization power and phase measurements in rain. This technique allows a reference absolute value to be provided for the radar calibration, from which eventual deviations may be detected using the other procedures. In particular, the ground clutter calibration is implemented on both polarization channels (horizontal and vertical) for each radar scan, allowing the polarimetric variables to be monitored and hardware failures to promptly be recognized. The Sun calibration allows monitoring the calibration and sensitivity of the radar receiver, in addition to the antenna pointing accuracy. It is applied using observations collected during the standard operational scans but requires long integration times (several days) in order to accumulate a sufficient amount of useful data. Finally, an intercalibration technique is developed and performed to compare colocated measurements collected in rain by two radars in overlapping regions. The integrated approach is performed on the C-band weather radar network in northwestern Italy, during July–October 2014. The set of methods considered appears suitable to establish an online tool to monitor the stability of the radar calibration with an accuracy of about 2 dB. In conclusion, this is considered adequate to automatically detect any unexpected change in the radar system requiring further data analysis or on-site measurements.« less

Engineered catalytic biofilms: Site-specific enzyme immobilization onto E. coli curli nanofibers.

PubMed

Botyanszki, Zsofia; Tay, Pei Kun R; Nguyen, Peter Q; Nussbaumer, Martin G; Joshi, Neel S

2015-10-01

Biocatalytic transformations generally rely on purified enzymes or whole cells to perform complex transformations that are used on industrial scale for chemical, drug, and biofuel synthesis, pesticide decontamination, and water purification. However, both of these systems have inherent disadvantages related to the costs associated with enzyme purification, the long-term stability of immobilized enzymes, catalyst recovery, and compatibility with harsh reaction conditions. We developed a novel strategy for producing rationally designed biocatalytic surfaces based on Biofilm Integrated Nanofiber Display (BIND), which exploits the curli system of E. coli to create a functional nanofiber network capable of covalent immobilization of enzymes. This approach is attractive because it is scalable, represents a modular strategy for site-specific enzyme immobilization, and has the potential to stabilize enzymes under denaturing environmental conditions. We site-specifically immobilized a recombinant α-amylase, fused to the SpyCatcher attachment domain, onto E. coli curli fibers displaying complementary SpyTag capture domains. We characterized the effectiveness of this immobilization technique on the biofilms and tested the stability of immobilized α-amylase in unfavorable conditions. This enzyme-modified biofilm maintained its activity when exposed to a wide range of pH and organic solvent conditions. In contrast to other biofilm-based catalysts, which rely on high cellular metabolism, the modified curli-based biofilm remained active even after cell death due to organic solvent exposure. This work lays the foundation for a new and versatile method of using the extracellular polymeric matrix of E. coli for creating novel biocatalytic surfaces. © 2015 Wiley Periodicals, Inc.

An integrated, structure- and energy-based view of the genetic code.

PubMed

Grosjean, Henri; Westhof, Eric

2016-09-30

The principles of mRNA decoding are conserved among all extant life forms. We present an integrative view of all the interaction networks between mRNA, tRNA and rRNA: the intrinsic stability of codon-anticodon duplex, the conformation of the anticodon hairpin, the presence of modified nucleotides, the occurrence of non-Watson-Crick pairs in the codon-anticodon helix and the interactions with bases of rRNA at the A-site decoding site. We derive a more information-rich, alternative representation of the genetic code, that is circular with an unsymmetrical distribution of codons leading to a clear segregation between GC-rich 4-codon boxes and AU-rich 2:2-codon and 3:1-codon boxes. All tRNA sequence variations can be visualized, within an internal structural and energy framework, for each organism, and each anticodon of the sense codons. The multiplicity and complexity of nucleotide modifications at positions 34 and 37 of the anticodon loop segregate meaningfully, and correlate well with the necessity to stabilize AU-rich codon-anticodon pairs and to avoid miscoding in split codon boxes. The evolution and expansion of the genetic code is viewed as being originally based on GC content with progressive introduction of A/U together with tRNA modifications. The representation we present should help the engineering of the genetic code to include non-natural amino acids. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Memristor-integrated voltage-stabilizing supercapacitor system.

PubMed

Liu, Bin; Liu, Boyang; Wang, Xianfu; Wu, Xinghui; Zhao, Wenning; Xu, Zhimou; Chen, Di; Shen, Guozhen

2014-08-06

Voltage-stabilized supercapacitors: A single supercapacitor formed with PCBM/Pt/IPS nanorod-array electrodes is designed and delivers enhanced areal capacitance, capacitance retention, and excellent electrical stability under bending, while a significant voltage-decrease is observed during the discharging process. Once integrated with the memristor, the memristor-integrated supercapacitor systems deliver an extremely low voltage-drop, indicating greatly enhanced voltage-stabilizing features. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solidification/Stabilization Use at Superfund Sites

EPA Pesticide Factsheets

To provide interested stakeholders such as project managers, technology service providers, consulting engineers, site owners, and the general public with the most recent information about solidification/stabilization applications at Superfund sites...

Physical integrity: the missing link in biological monitoring and TMDLs.

PubMed

Asmus, Brenda; Magner, Joseph A; Vondracek, Bruce; Perry, Jim

2009-12-01

The Clean Water Act mandates that the chemical, physical, and biological integrity of our nation's waters be maintained and restored. Physical integrity has often been defined as physical habitat integrity, and as such, data collected during biological monitoring programs focus primarily on habitat quality. However, we argue that channel stability is a more appropriate measure of physical integrity and that channel stability is a foundational element of physical habitat integrity in low-gradient alluvial streams. We highlight assessment tools that could supplement stream assessments and the Total Maximum Daily Load stressor identification process: field surveys of bankfull cross-sections; longitudinal thalweg profiles; particle size distribution; and regionally calibrated, visual, stream stability assessments. Benefits of measuring channel stability include a more informed selection of reference or best attainable stream condition for an Index of Biotic Integrity, establishment of a baseline for monitoring changes in present and future condition, and indication of channel stability for investigations of chemical and biological impairments associated with sediment discontinuity and loss of habitat quality.

Characterization and Remediation of Contaminated Sites:Modeling, Measurement and Assessment

NASA Astrophysics Data System (ADS)

Basu, N. B.; Rao, P. C.; Poyer, I. C.; Christ, J. A.; Zhang, C. Y.; Jawitz, J. W.; Werth, C. J.; Annable, M. D.; Hatfield, K.

2008-05-01

The complexity of natural systems makes it impossible to estimate parameters at the required level of spatial and temporal detail. Thus, it becomes necessary to transition from spatially distributed parameters to spatially integrated parameters that are capable of adequately capturing the system dynamics, without always accounting for local process behavior. Contaminant flux across the source control plane is proposed as an integrated metric that captures source behavior and links it to plume dynamics. Contaminant fluxes were measured using an innovative technology, the passive flux meter at field sites contaminated with dense non-aqueous phase liquids or DNAPLs in the US and Australia. Flux distributions were observed to be positively or negatively correlated with the conductivity distribution, depending on the source characteristics of the site. The impact of partial source depletion on the mean contaminant flux and flux architecture was investigated in three-dimensional complex heterogeneous settings using the multiphase transport code UTCHEM and the reactive transport code ISCO3D. Source mass depletion reduced the mean contaminant flux approximately linearly, while the contaminant flux standard deviation reduced proportionally with the mean (i.e., coefficient of variation of flux distribution is constant with time). Similar analysis was performed using data from field sites, and the results confirmed the numerical simulations. The linearity of the mass depletion-flux reduction relationship indicates the ability to design remediation systems that deplete mass to achieve target reduction in source strength. Stability of the flux distribution indicates the ability to characterize the distributions in time once the initial distribution is known. Lagrangian techniques were used to predict contaminant flux behavior during source depletion in terms of the statistics of the hydrodynamic and DNAPL distribution. The advantage of the Lagrangian techniques lies in their small computation time and their inclusion of spatially integrated parameters that can be measured in the field using tracer tests. Analytical models that couple source depletion to plume transport were used for optimization of source and plume treatment. These models are being used for the development of decision and management tools (for DNAPL sites) that consider uncertainty assessments as an integral part of the decision-making process for contaminated site remediation.

Structural and Functional Analysis of an mRNP Complex That Mediates the High Stability of Human β-Globin mRNA

PubMed Central

Yu, Jia; Russell, J. Eric

2001-01-01

Human globins are encoded by mRNAs exhibiting high stabilities in transcriptionally silenced erythrocyte progenitors. Unlike α-globin mRNA, whose stability is enhanced by assembly of a specific messenger RNP (mRNP) α complex on its 3′ untranslated region (UTR), neither the structure(s) nor the mechanism(s) that effects the high-level stability of human β-globin mRNA has been identified. The present work describes an mRNP complex assembling on the 3′ UTR of the β-globin mRNA that exhibits many of the properties of the stability-enhancing α complex. The β-globin mRNP complex is shown to contain one or more factors homologous to αCP, a 39-kDa RNA-binding protein that is integral to α-complex assembly. Sequence analysis implicates a specific 14-nucleotide pyrimidine-rich track within its 3′ UTR as the site of β-globin mRNP assembly. The importance of this track to mRNA stability is subsequently verified in vivo using mice expressing human β-globin transgenes that contain informative mutations in this region. In combination, the in vitro and in vivo analyses indicate that the high stabilities of the α- and β-globin mRNAs are maintained through related mRNP complexes that may share a common regulatory pathway. PMID:11486027

Inducible model for β-six-mediated site-specific recombination in mammalian cells

PubMed Central

Servert, Pilar; Garcia-Castro, Javier; Díaz, Vicente; Lucas, Daniel; Gonzalez, Manuel A.; Martínez-A, Carlos; Bernad, Antonio

2006-01-01

The prokaryotic β recombinase catalyzes site-specific recombination between two directly oriented minimal six sites in chromatin-integrated substrates. Here, we demonstrate that an enhanced green fluorescent protein (EGFP)-fused version of β recombinase (β-EGFP) is fully active, retaining most specific activity. It is used to develop a recombination-dependent activatable gene expression (RAGE) system based on the androgen receptor (AR) ligand-binding domain (LBD). Two hybrid molecules, a direct fusion of the LBD-AR to the C-terminus of β recombinase (β-AR) and a triple fusion of β-EGFP to the same ligand-binding domain (β-EGFP-AR), were engineered and their subcellular behavior, stability and catalytic activity were evaluated. Both chimeric β recombinase proteins showed in vivo inducible recombinogenic activity dependent on addition of an androgen receptor agonist, although the β-AR fusion protein demonstrated more accurate ligand-dependent translocation from cytoplasm to nucleus. PMID:16394020

Evaluation of New Repair Methods for Seal Surface Defects on Reusable Solid Rocket Motor (RSRM) Hardware

NASA Technical Reports Server (NTRS)

Stanley, Stephanie; Selvidge, Shawn

2003-01-01

The focus of the evaluation was to develop a back-up method to cell plating for the improvement or repair of seal surface defects within D6-AC steel and 7075-T73 aluminum used in the RSRM program. Several techniques were investigated including thermal and non-thermal based techniques. Ideally the repair would maintain the inherent properties of the substrate without losing integrity at the repair site. The repaired sites were tested for adhesion, corrosion, hardness, microhardness, surface toughness, thermal stability, ability to withstand bending of the repair site, and the ability to endure a high-pressure water blast without compromising the repaired site. The repaired material could not change the inherent properties of the substrate throughout each of the test in order to remain a possible technique to repair the RSRM substrate materials. One repair method, Electro-Spark Alloying, passed all the testing and is considered a candidate for further evaluation.

Evaluation of New Repair Methods for Seal Surface Defects on Reusable Solid Rocket Motor (RSRM) Hardware

NASA Technical Reports Server (NTRS)

Stanley, Stephanie D.; Selvidge, Shawn A.; Cash, Steve (Technical Monitor)

2002-01-01

The focus of the evaluation was to develop a back-up method to cell plating for the improvement or repair of seal surface defects within D6-AC steel and 7075-T73 aluminum used in the RSRM program. Several techniques were investigated including thermal and non-thermal based techniques. Ideally the repair would maintain the inherent properties of the substrate without losing integrity at the repair site. The repaired sites were tested for adhesion, corrosion, hardness, microhardness, surface toughness, thermal stability, ability to withstand bending of the repair site, and the ability to endure a high-pressure water blast without compromising the repaired site. The repaired material could not change the inherent properties of the substrate throughout each of the test in order to remain a possible technique to repair the RSRM substrate materials. One repair method, Electro-Spark Alloying, passed all the testing and is considered a candidate for further evaluation.

Transcription and DNA Damage: Holding Hands or Crossing Swords?

PubMed

D'Alessandro, Giuseppina; d'Adda di Fagagna, Fabrizio

2017-10-27

Transcription has classically been considered a potential threat to genome integrity. Collision between transcription and DNA replication machinery, and retention of DNA:RNA hybrids, may result in genome instability. On the other hand, it has been proposed that active genes repair faster and preferentially via homologous recombination. Moreover, while canonical transcription is inhibited in the proximity of DNA double-strand breaks, a growing body of evidence supports active non-canonical transcription at DNA damage sites. Small non-coding RNAs accumulate at DNA double-strand break sites in mammals and other organisms, and are involved in DNA damage signaling and repair. Furthermore, RNA binding proteins are recruited to DNA damage sites and participate in the DNA damage response. Here, we discuss the impact of transcription on genome stability, the role of RNA binding proteins at DNA damage sites, and the function of small non-coding RNAs generated upon damage in the signaling and repair of DNA lesions. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2009-01-01

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

Integration of Reference Frames Using VLBI

NASA Technical Reports Server (NTRS)

Ma, Chopo; Smith, David E. (Technical Monitor)

2001-01-01

Very Long Baseline Interferometry (VLBI) has the unique potential to integrate the terrestrial and celestial reference frames through simultaneous estimation of positions and velocities of approx. 40 active VLBI stations and a similar number of stations/sites with sufficient historical data, the position and position stability of approx. 150 well-observed extragalactic radio sources and another approx. 500 sources distributed fairly uniformly on the sky, and the time series of the five parameters that specify the relative orientation of the two frames. The full realization of this potential is limited by a number of factors including the temporal and spatial distribution of the stations, uneven distribution of observations over the sources and the sky, variations in source structure, modeling of the solid/fluid Earth and troposphere, logistical restrictions on the daily observing network size, and differing strategies for optimizing analysis for TRF, for CRF and for EOP. The current status of separately optimized and integrated VLBI analysis will be discussed.

Gait ataxia in humans: vestibular and cerebellar control of dynamic stability.

PubMed

Schniepp, Roman; Möhwald, Ken; Wuehr, Max

2017-10-01

During human locomotion, vestibular feedback control is fundamental for maintaining dynamic stability and adapting the gait pattern to external circumstances. Within the supraspinal locomotor network, the cerebellum represents the key site for the integration of vestibular feedback information. The cerebellum is further important for the fine-tuning and coordination of limb movements during walking. The aim of this review article is to highlight the shared structural and functional sensorimotor principles in vestibular and cerebellar locomotion control. Vestibular feedback for the maintenance of dynamic stability is integrated into the locomotor pattern via midline, caudal cerebellar structures (vermis, flocculonodular lobe). Hemispheric regions of the cerebellum facilitate feed-forward control of multi-joint coordination and higher locomotor functions. Characteristic features of the gait disorder in patients with vestibular deficits or cerebellar ataxia are increased levels of spatiotemporal gait variability in the fore-aft and the medio-lateral gait dimension. In the fore-aft dimension, pathologic increases of gait fluctuations critically depend on the locomotion speed and predominantly manifest during slow walking velocities. This feature is associated with an increased risk of falls in both patients with vestibular hypofunction as well as patients with cerebellar ataxia. Pharmacological approaches for the treatment of vestibular or cerebellar gait ataxia are currently not available. However, new promising options are currently tested in randomized, controlled trials (fampridine/FACEG; acetyl-DL-leucine/ALCAT).

Site occupancy, composition and magnetic structure dependencies of martensitic transformation in Mn2Ni1 + x Sn1-x.

PubMed

Kundu, Ashis; Ghosh, Subhradip

2017-11-29

A delicate balance between various factors such as site occupancy, composition and magnetic ordering seems to affect the stability of the martensitic phase in [Formula: see text] [Formula: see text] [Formula: see text]. Using first-principles DFT calculations, we explore the impacts of each one of these factors on the martensitic stability of this system. Our results on total energies, magnetic moments and electronic structures upon changes in the composition, the magnetic configurations and the site occupancies show that the occupancies at the 4d sites in the inverse Heusler crystal structure play the most crucial role. The presence of Mn at the 4d sites originally occupied by Sn and its interaction with the Mn atoms at other sites decide the stability of the martensitic phases. This explains the discrepancy between the experiments and earlier DFT calculations regarding phase stability in [Formula: see text]NiSn. Our results qualitatively explain the trends observed experimentally with regard to martensitic phase stability and the magnetisations in Ni-excess, Sn-deficient [Formula: see text]NiSn system.

Zwitterionic versus canonical amino acids over the various defects in zeolites: A two-layer ONIOM calculation

PubMed Central

Yang, Gang; Zhou, Lijun

2014-01-01

Defects are often considered as the active sites for chemical reactions. Here a variety of defects in zeolites are used to stabilize zwitterionic glycine that is not self-stable in gas phase; in addition, effects of acidic strengths and zeolite channels on zwitterionic stabilization are demonstrated. Glycine zwitterions can be stabilized by all these defects and energetically prefer to canonical structures over Al and Ga Lewis acidic sites rather than Ti Lewis acidic site, silanol and titanol hydroxyls. For titanol (Ti-OH), glycine interacts with framework Ti and hydroxyl sites competitively, and the former with Lewis acidity predominates. The transformations from canonical to zwitterionic glycine are obviously more facile over Al and Ga Lewis acidic sites than over Ti Lewis acidic site, titanol and silanol hydroxyls. Charge transfers that generally increase with adsorption energies are found to largely decide the zwitterionic stabilization effects. Zeolite channels play a significant role during the stabilization process. In absence of zeolite channels, canonical structures predominate for all defects; glycine zwitterions remain stable over Al and Ga Lewis acidic sites and only with synergy of H-bonding interactions can exist over Ti Lewis acidic site, while automatically transform to canonical structures over silanol and titanol hydroxyls. PMID:25307449

Biochemical Characterization of Novel Retroviral Integrase Proteins

PubMed Central

Ballandras-Colas, Allison; Naraharisetty, Hema; Li, Xiang; Serrao, Erik; Engelman, Alan

2013-01-01

Integrase is an essential retroviral enzyme, catalyzing the stable integration of reverse transcribed DNA into cellular DNA. Several aspects of the integration mechanism, including the length of host DNA sequence duplication flanking the integrated provirus, which can be from 4 to 6 bp, and the nucleotide preferences at the site of integration, are thought to cluster among the different retroviral genera. To date only the spumavirus prototype foamy virus integrase has provided diffractable crystals of integrase-DNA complexes, revealing unprecedented details on the molecular mechanisms of DNA integration. Here, we characterize five previously unstudied integrase proteins, including those derived from the alpharetrovirus lymphoproliferative disease virus (LPDV), betaretroviruses Jaagsiekte sheep retrovirus (JSRV), and mouse mammary tumor virus (MMTV), epsilonretrovirus walleye dermal sarcoma virus (WDSV), and gammaretrovirus reticuloendotheliosis virus strain A (Rev-A) to identify potential novel structural biology candidates. Integrase expressed in bacterial cells was analyzed for solubility, stability during purification, and, once purified, 3′ processing and DNA strand transfer activities in vitro. We show that while we were unable to extract or purify accountable amounts of WDSV, JRSV, or LPDV integrase, purified MMTV and Rev-A integrase each preferentially support the concerted integration of two viral DNA ends into target DNA. The sequencing of concerted Rev-A integration products indicates high fidelity cleavage of target DNA strands separated by 5 bp during integration, which contrasts with the 4 bp duplication generated by a separate gammaretrovirus, the Moloney murine leukemia virus (MLV). By comparing Rev-A in vitro integration sites to those generated by MLV in cells, we concordantly conclude that the spacing of target DNA cleavage is more evolutionarily flexible than are the target DNA base contacts made by integrase during integration. Given their desirable concerted DNA integration profiles, Rev-A and MMTV integrase proteins have been earmarked for structural biology studies. PMID:24124581

Integrating Near-Real Time Hydrologic-Response Monitoring and Modeling for Improved Assessments of Slope Stability Along the Coastal Bluffs of the Puget Sound Rail Corridor, Washington State

NASA Astrophysics Data System (ADS)

Mirus, B. B.; Baum, R. L.; Stark, B.; Smith, J. B.; Michel, A.

2015-12-01

Previous USGS research on landslide potential in hillside areas and coastal bluffs around Puget Sound, WA, has identified rainfall thresholds and antecedent moisture conditions that correlate with heightened probability of shallow landslides. However, physically based assessments of temporal and spatial variability in landslide potential require improved quantitative characterization of the hydrologic controls on landslide initiation in heterogeneous geologic materials. Here we present preliminary steps towards integrating monitoring of hydrologic response with physically based numerical modeling to inform the development of a landslide warning system for a railway corridor along the eastern shore of Puget Sound. We instrumented two sites along the steep coastal bluffs - one active landslide and one currently stable slope with the potential for failure - to monitor rainfall, soil-moisture, and pore-pressure dynamics in near-real time. We applied a distributed model of variably saturated subsurface flow for each site, with heterogeneous hydraulic-property distributions based on our detailed site characterization of the surficial colluvium and the underlying glacial-lacustrine deposits that form the bluffs. We calibrated the model with observed volumetric water content and matric potential time series, then used simulated pore pressures from the calibrated model to calculate the suction stress and the corresponding distribution of the factor of safety against landsliding with the infinite slope approximation. Although the utility of the model is limited by uncertainty in the deeper groundwater flow system, the continuous simulation of near-surface hydrologic response can help to quantify the temporal variations in the potential for shallow slope failures at the two sites. Thus the integration of near-real time monitoring and physically based modeling contributes a useful tool towards mitigating hazards along the Puget Sound railway corridor.

Dancing through Life: Molecular Dynamics Simulations and Network-Centric Modeling of Allosteric Mechanisms in Hsp70 and Hsp110 Chaperone Proteins.

PubMed

Stetz, Gabrielle; Verkhivker, Gennady M

2015-01-01

Hsp70 and Hsp110 chaperones play an important role in regulating cellular processes that involve protein folding and stabilization, which are essential for the integrity of signaling networks. Although many aspects of allosteric regulatory mechanisms in Hsp70 and Hsp110 chaperones have been extensively studied and significantly advanced in recent experimental studies, the atomistic picture of signal propagation and energetics of dynamics-based communication still remain unresolved. In this work, we have combined molecular dynamics simulations and protein stability analysis of the chaperone structures with the network modeling of residue interaction networks to characterize molecular determinants of allosteric mechanisms. We have shown that allosteric mechanisms of Hsp70 and Hsp110 chaperones may be primarily determined by nucleotide-induced redistribution of local conformational ensembles in the inter-domain regions and the substrate binding domain. Conformational dynamics and energetics of the peptide substrate binding with the Hsp70 structures has been analyzed using free energy calculations, revealing allosteric hotspots that control negative cooperativity between regulatory sites. The results have indicated that cooperative interactions may promote a population-shift mechanism in Hsp70, in which functional residues are organized in a broad and robust allosteric network that can link the nucleotide-binding site and the substrate-binding regions. A smaller allosteric network in Hsp110 structures may elicit an entropy-driven allostery that occurs in the absence of global structural changes. We have found that global mediating residues with high network centrality may be organized in stable local communities that are indispensable for structural stability and efficient allosteric communications. The network-centric analysis of allosteric interactions has also established that centrality of functional residues could correlate with their sensitivity to mutations across diverse chaperone functions. This study reconciles a wide spectrum of structural and functional experiments by demonstrating how integration of molecular simulations and network-centric modeling may explain thermodynamic and mechanistic aspects of allosteric regulation in chaperones.

Dancing through Life: Molecular Dynamics Simulations and Network-Centric Modeling of Allosteric Mechanisms in Hsp70 and Hsp110 Chaperone Proteins

PubMed Central

Stetz, Gabrielle; Verkhivker, Gennady M.

2015-01-01

Hsp70 and Hsp110 chaperones play an important role in regulating cellular processes that involve protein folding and stabilization, which are essential for the integrity of signaling networks. Although many aspects of allosteric regulatory mechanisms in Hsp70 and Hsp110 chaperones have been extensively studied and significantly advanced in recent experimental studies, the atomistic picture of signal propagation and energetics of dynamics-based communication still remain unresolved. In this work, we have combined molecular dynamics simulations and protein stability analysis of the chaperone structures with the network modeling of residue interaction networks to characterize molecular determinants of allosteric mechanisms. We have shown that allosteric mechanisms of Hsp70 and Hsp110 chaperones may be primarily determined by nucleotide-induced redistribution of local conformational ensembles in the inter-domain regions and the substrate binding domain. Conformational dynamics and energetics of the peptide substrate binding with the Hsp70 structures has been analyzed using free energy calculations, revealing allosteric hotspots that control negative cooperativity between regulatory sites. The results have indicated that cooperative interactions may promote a population-shift mechanism in Hsp70, in which functional residues are organized in a broad and robust allosteric network that can link the nucleotide-binding site and the substrate-binding regions. A smaller allosteric network in Hsp110 structures may elicit an entropy-driven allostery that occurs in the absence of global structural changes. We have found that global mediating residues with high network centrality may be organized in stable local communities that are indispensable for structural stability and efficient allosteric communications. The network-centric analysis of allosteric interactions has also established that centrality of functional residues could correlate with their sensitivity to mutations across diverse chaperone functions. This study reconciles a wide spectrum of structural and functional experiments by demonstrating how integration of molecular simulations and network-centric modeling may explain thermodynamic and mechanistic aspects of allosteric regulation in chaperones. PMID:26619280

An external sodium ion binding site controls allosteric gating in TRPV1 channels

PubMed Central

Jara-Oseguera, Andres; Bae, Chanhyung; Swartz, Kenton J

2016-01-01

TRPV1 channels in sensory neurons are integrators of painful stimuli and heat, yet how they integrate diverse stimuli and sense temperature remains elusive. Here, we show that external sodium ions stabilize the TRPV1 channel in a closed state, such that removing the external ion leads to channel activation. In studying the underlying mechanism, we find that the temperature sensors in TRPV1 activate in two steps to favor opening, and that the binding of sodium to an extracellular site exerts allosteric control over temperature-sensor activation and opening of the pore. The binding of a tarantula toxin to the external pore also exerts control over temperature-sensor activation, whereas binding of vanilloids influences temperature-sensitivity by largely affecting the open/closed equilibrium. Our results reveal a fundamental role of the external pore in the allosteric control of TRPV1 channel gating and provide essential constraints for understanding how these channels can be tuned by diverse stimuli. DOI: http://dx.doi.org/10.7554/eLife.13356.001 PMID:26882503

Structural integration in hypoxia-inducible factors

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

Wu, Dalei; Potluri, Nalini; Lu, Jingping

The hypoxia-inducible factors (HIFs) coordinate cellular adaptations to low oxygen stress by regulating transcriptional programs in erythropoiesis, angiogenesis and metabolism. These programs promote the growth and progression of many tumours, making HIFs attractive anticancer targets. Transcriptionally active HIFs consist of HIF-alpha and ARNT (also called HIF-1 beta) subunits. Here we describe crystal structures for each of mouse HIF-2 alpha-ARNT and HIF-1 alpha-ARNT heterodimers in states that include bound small molecules and their hypoxia response element. A highly integrated quaternary architecture is shared by HIF-2 alpha-ARNT and HIF-1 alpha-ARNT, wherein ARNT spirals around the outside of each HIF-alpha subunit. Five distinctmore » pockets are observed that permit small-molecule binding, including PAS domain encapsulated sites and an interfacial cavity formed through subunit heterodimerization. The DNA-reading head rotates, extends and cooperates with a distal PAS domain to bind hypoxia response elements. HIF-alpha mutations linked to human cancers map to sensitive sites that establish DNA binding and the stability of PAS domains and pockets.« less

Conserved tyrosine 182 residue in hyperthermophilic esterase EstE1 plays a critical role in stabilizing the active site.

PubMed

Truongvan, Ngoc; Chung, Hye-Shin; Jang, Sei-Heon; Lee, ChangWoo

2016-03-01

An aromatic amino acid, Tyr or Trp, located in the esterase active site wall, is highly conserved, with hyperthermophilic esterases showing preference for Tyr and lower temperature esterases showing preference for Trp. In this study, we investigated the role of Tyr(182) in the active site wall of hyperthermophilic esterase EstE1. Mutation of Tyr to Phe or Ala had a moderate effect on EstE1 thermal stability. However, a small-to-large mutation such as Tyr to His or Trp had a devastating effect on thermal stability. All mutant EstE1 enzymes showed reduced catalytic rates and enhanced substrate affinities as compared with wild-type EstE1. Hydrogen bond formation involving Tyr(182) was unimportant for maintaining EstE1 thermal stability, as the EstE1 structure is already adapted to high temperatures via increased intramolecular interactions. However, removal of hydrogen bond from Tyr(182) significantly decreased EstE1 catalytic activity, suggesting its role in stabilization of the active site. These results suggest that Tyr is preferred over a similarly sized Phe residue or bulky His or Trp residue in the active site walls of hyperthermophilic esterases for stabilizing the active site and regulating catalytic activity at high temperatures.

Defect Effects on TiO2 Nanosheets: Stabilizing Single Atomic Site Au and Promoting Catalytic Properties.

PubMed

Wan, Jiawei; Chen, Wenxing; Jia, Chuanyi; Zheng, Lirong; Dong, Juncai; Zheng, Xusheng; Wang, Yu; Yan, Wensheng; Chen, Chen; Peng, Qing; Wang, Dingsheng; Li, Yadong

2018-03-01

Isolated single atomic site catalysts have attracted great interest due to their remarkable catalytic properties. Because of their high surface energy, single atoms are highly mobile and tend to form aggregate during synthetic and catalytic processes. Therefore, it is a significant challenge to fabricate isolated single atomic site catalysts with good stability. Herein, a gentle method to stabilize single atomic site metal by constructing defects on the surface of supports is presented. As a proof of concept, single atomic site Au supported on defective TiO 2 nanosheets is prepared and it is discovered that (1) the surface defects on TiO 2 nanosheets can effectively stabilize Au single atomic sites through forming the Ti-Au-Ti structure; and (2) the Ti-Au-Ti structure can also promote the catalytic properties through reducing the energy barrier and relieving the competitive adsorption on isolated Au atomic sites. It is believed that this work paves a way to design stable and active single atomic site catalysts on oxide supports. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

10 CFR 61.62 - Funding for disposal site closure and stabilization.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Section 61.62 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Financial Assurances § 61.62 Funding for disposal site closure and stabilization. (a) The... and stabilization, including: (1) Decontamination or dismantlement of land disposal facility...

10 CFR 61.62 - Funding for disposal site closure and stabilization.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Section 61.62 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Financial Assurances § 61.62 Funding for disposal site closure and stabilization. (a) The... and stabilization, including: (1) Decontamination or dismantlement of land disposal facility...

10 CFR 61.62 - Funding for disposal site closure and stabilization.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Section 61.62 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Financial Assurances § 61.62 Funding for disposal site closure and stabilization. (a) The... and stabilization, including: (1) Decontamination or dismantlement of land disposal facility...

10 CFR 61.62 - Funding for disposal site closure and stabilization.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 61.62 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Financial Assurances § 61.62 Funding for disposal site closure and stabilization. (a) The... and stabilization, including: (1) Decontamination or dismantlement of land disposal facility...

10 CFR 61.62 - Funding for disposal site closure and stabilization.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Section 61.62 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Financial Assurances § 61.62 Funding for disposal site closure and stabilization. (a) The... and stabilization, including: (1) Decontamination or dismantlement of land disposal facility...

Integrated track stability assessment and monitoring system (ITSAMS).

DOT National Transportation Integrated Search

2006-10-01

The overall objective of project is to continue the development of remote sensing : technologies that can be integrated and deployed in a mobile inspection vehicle i.e. Integrated : Track Stability Assessment and Monitoring System (ITSAMS).

SUMMARY OF SOLIDIFICATION/STABILIZATION SITE DEMONSTRATIONS AT UNCONTROLLED HAZARDOUS WASTE SITES

EPA Science Inventory

Four large-scale solidification/stabilization demonstrations have occurred under EPA's SITE program. In general, physical testing results have been acceptable. Reduction in metal leachability, as determined by the TCLP test, has been observed. Reduction in organic leachability ha...

Wind and turbine characteristics needed for integration of wind turbine arrays into a utility system

NASA Technical Reports Server (NTRS)

Park, G. L.

1982-01-01

Wind data and wind turbine generator (WTG) performance characteristics are often available in a form inconvenient for use by utility planners and engineers. The steps used by utility planners are summarized and the type of wind and WTG data needed for integration of WTG arrays suggested. These included long term yearly velocity averages for preliminary site feasibility, hourly velocities on a 'wind season' basis for more detailed economic analysis and for reliability studies, worst-case velocity profiles for gusts, and various minute-to-hourly velocity profiles for estimating the effect of longer-term wind fluctuations on utility operations. wind turbine data needed includes electrical properties of the generator, startup and shutdown characteristics, protection characteristics, pitch control response and control strategy, and electro-mechanical model for stability analysis.

Site directed mutagenesis of the heme axial ligands of cytochrome b559 affects the stability of the photosystem II complex.

PubMed Central

Pakrasi, H B; De Ciechi, P; Whitmarsh, J

1991-01-01

Cytochrome (cyt) b559, an integral membrane protein, is an essential component of the photosystem II (PSII) complex in the thylakoid membranes of oxygenic photosynthetic organisms. Cyt b559 has two subunits, alpha and beta, each with one predicted membrane spanning alpha-helical domain. The heme cofactor of this cytochrome is coordinated between two histidine residues. Each of the two subunit polypeptides of cyt b559 has one His residue. To investigate the influence of these His residues on the structure of cyt b559 and the PSII complex, we used a site directed mutagenesis approach to replace each His residue with a Leu residue. Introduction of these missense mutations in the transformable unicellular cyanobacterium, Synechocystis 6803, resulted in complete loss of PSII activity. Northern blot analysis showed that these mutations did not affect the stability of the polycistronic mRNA that encompasses both the psbE and the psbF genes, encoding the alpha and the beta subunits, respectively. Moreover, both of the single His mutants showed the presence of the alpha subunit which was 1.5 kd smaller than the same polypeptide in wild type cells. A secondary effect of such a structural change was that D1 and D2, two proteins that form the catalytic core (reaction center) of PSII, were also destabilized. Our results demonstrate that proper axial coordination of the heme cofactor in cyt b559 is important for the structural integrity of the reaction center of PSII. Images PMID:1904816

Adsorption of small molecules on the [Zn-Zn]2+ linkage in zeolite. A DFT study of ferrierite

NASA Astrophysics Data System (ADS)

Benco, Lubomir

2017-02-01

In zeolites monovalent Zn(I) forms a sub-nano particles [Zn-Zn]2+ stabilized in rings of the zeolite framework, which exhibit interesting catalytic properties. This work reports on adsorption properties of [Zn-Zn]2+ particles in zeolite ferrierite investigated for a set of probing diatomic (N2, O2, H2, CO, NO) and triatomic (CO2, N2O, NO2, H2O) molecules using dispersion-corrected DFT. Three [Zn-Zn]2+ sites are compared differing in the location and stability. On all sites molecules form physisorbed clusters with the molecule connected on-top of the Zn-Zn linkage. In physisorbed clusters adsorption induces only slight change of bonding and the geometry of the Zn-Zn linkage. Some molecules can form stable chemisorbed clusters in which the molecule is integrated between two Zn+ cations. The sandwich-like chemisorption causes pronounced changes of bonding and can lead to the transfer of the electron density between two Zn+ cations and to a change of the oxidation state. The knowledge of bonding of small molecules can help understanding of the mechanism of conversion reactions catalyzed by sub-nano [Zn-Zn] particles.

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

NASA Astrophysics Data System (ADS)

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

2015-04-01

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

Application of integral equation theory to analyze stability of electric field in multimode microwave heating cavity

NASA Astrophysics Data System (ADS)

Tang, Zhengming; Hong, Tao; Chen, Fangyuan; Zhu, Huacheng; Huang, Kama

2017-10-01

Microwave heating uniformity is mainly dependent on and affected by electric field. However, little study has paid attention to its stability characteristics in multimode cavity. In this paper, this problem is studied by the theory of Freedholm integral equation. Firstly, Helmholtz equation and the electric dyadic Green's function are used to derive the electric field integral equation. Then, the stability of electric field is demonstrated as the characteristics of solutions to Freedholm integral equation. Finally, the stability characteristics are obtained and verified by finite element calculation. This study not only can provide a comprehensive interpretation of electric field in multimode cavity but also help us make better use of microwave energy.

Fiscal Year 2012 Revegetation Assessment

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

Jenifer Nordstrom

2012-11-01

This report summarizes the Fiscal Year 2012 Revegetation Assessment by Battelle Energy Alliance, LLC. This assessment was conducted to supplement documentation related to the Storm Water Pollution Prevention Plan for Construction Activities and to ensure that disturbed vegetation and soil at various locations are being restored. This report provides the following information for each site being monitored by the Idaho National Laboratory Environmental Support and Services: • Summary of each site • Assessment of vegetation status and site stabilization at each location • Actions and Resolutions for each site. Ten disturbed sites were evaluated for this assessment. Six have achievedmore » final stabilization. The remaining four sites not meeting the criteria for final stabilization will be evaluated again in the next fiscal year.« less

Stability and delay sensitivity of neutral fractional-delay systems.

PubMed

Xu, Qi; Shi, Min; Wang, Zaihua

2016-08-01

This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

SOLIDIFICATION/STABILIZATION FOR REMEDIATON OF WOOD PRESERVING SITES: TREATMENT FOR DIOXINS, PCP, CREOSOTE, AND METALS

EPA Science Inventory

This article discusses the use of solidification/stabilization (S/S) to treat soils contaminated with organic and inorganic chemicals at wood preserving sites. Solidification is defined for this article as making a material into a free standing solid. Stabilization is defined as ...

THE SITE DEMONSTRATION OF CHEMFIX SOLIDIFICATION/ STABILIZATION PROCESS AT THE PORTABLE EQUIPMENT SALVAGE COMPANY SITE

EPA Science Inventory

A demonstration of the GHEMFIX solidification/stabilization process was conducted under the United States Environmental Protection Agency`s (EPA) Superfund Innovative Technology Evaluation (SITE) program. The demonstration was conducted in March 1989, at the Portable Equipment Sa...

Integrated geological-geophysical models of unstable slopes in seismogenic areas in NW and SE Europe

NASA Astrophysics Data System (ADS)

Mreyen, Anne-Sophie; Micu, Mihai; Onaca, Alexandru; Demoulin, Alain; Havenith, Hans-Balder

2017-04-01

We will present a series of new integrated 3D models of landslide sites that were investigated in distinctive seismotectonic and climatic contexts: (1) along the Hockai Fault Zone in Belgium, with the 1692 Verviers Earthquake (M 6 - 6.5) as most prominent earthquake that occurred in that fault zone and (2) in the seismic region of Vrancea, Romania, where four earthquakes with Mw > 7.4 have been recorded during the last two centuries. Both sites present deep-seated failures located in more or less seismically active areas. In such areas, slope stability analyses have to take into account the possible contributions to ground failure. Our investigation methods had to be adapted to capture the deep structure as well as the physico-mechanical characteristics that influence the dynamic behaviour of the landslide body. Field surveys included electrical resistivity tomography profiles, seismic refraction profiles (analysed in terms of both seismic P-wave tomography and surface waves), ambient noise measurements to determine the soil resonance frequencies through H/V analysis, complemented by geological and geomorphic mapping. The H/V method, in particular, is more and more used for landslide investigations or sites marked by topographic relief (in addition to the more classical applications on flat sites). Results of data interpretation were compiled in 3D geological-geophysical models supported by high resolution remote sensing data of the ground surface. Data and results were not only analysed in parallel or successively; to ensure full integration of all inputs-outputs, some data fusion and geostatistical techniques were applied to establish closer links between them. Inside the 3D models, material boundaries were defined in terms of surfaces and volumes. Those models were used as inputs for 2D dynamic numerical simulations completed with the UDEC (Itasca) software. For some sites, a full back-analysis was carried out to assess the possibility of a seismic triggering of the landslides.

Humid site stabilization and closure

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

Cutshall, N.H.

1981-01-01

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

Critical aspects of integrated monitoring systems for landslides risk management: strategies for a reliable approach

NASA Astrophysics Data System (ADS)

Castagnetti, C.; Bertacchini, E.; Capra, A.; Corsini, A.

2012-04-01

The use of advanced technologies for remotely monitor surface processes is a successful way for improving the knowledge of phenomena evolution. In addition, the integration of various techniques is becoming more and more common in order to implement early warning systems that can monitor the evolution of landslides in time and prevent emergencies. The reliability of those systems plays a key role when Public Administrations have to plan actions in case of disasters or for preventing an incoming emergency. To have confidence in the information given by the system is an essential condition for a successful policy aiming to protect the population. The research deals with the major critical aspects to be taken into account when implementing a reliable monitoring system for unstable slopes. The importance of those aspects is often neglected, unlike the effects of a not careful implementation and management of the system can lead to erroneous interpretations of the phenomenon itself. The case study which ruled the research and highlighted the actual need of guidelines for setting up a reliable monitoring system is the Valoria landslide, located in the Northern Italy. The system is based on the integration of an automatic Total Station (TS) measuring 45 reflectors and a master GPS, acting as the reference station for three rovers placed within the landslide. In order to monitor local disturbing effects, a bi-dimensional clinometer has been applied on the TS pillar. Topographic measurements have been also integrated with geotechnical sensors (inclinometers and piezometers) in a GIS for landslide risk management. At the very beginning, periodic measurements were carried out, while the system is now performing continuously since 2008. The system permitted to evaluate movements from few millimeter till some meters per day in most dangerous areas. A more spatially continuous description has been also provided by LiDAR and terrestrial SAR interferometry. Some of the most interesting and critical aspects that will be deeper described and analyzed are: - strategy for planning a successful integrated system for continuous monitoring. - Choice of the reference frame: local coordinate system or georeferenced one. - Stability of the site for the master unit positioning: GPS time series analysis for controlling the effective stability. Thanks to the GPS master station that are operating for over three years, atmospheric disturbances affecting the signal may be removed in order to carefully verify the stability of the area and to establish whether the site is geologically stable, as originally suggested, or not. In the latter case, the magnitude of movements may also be computed for providing corrections to TS observations. - Stability of the monumentation, both for reference points and TS pillar. This is an essential aspect for avoiding misinterpretations when analyzing displacements of prisms placed within the landslide. The results of experiences carried out by Authors over last years about different landslides will be presented in order to propose guidelines for a sort of procedure aiming to increase the reliability of the information provided by the system and the usefulness for local Agencies.

Genetic stability of gene targeted immunoglobulin loci. I. Heavy chain isotype exchange induced by a universal gene replacement vector.

PubMed Central

Kardinal, C; Selmayr, M; Mocikat, R

1996-01-01

Gene targeting at the immunoglobulin loci of B cells is an efficient tool for studying immunoglobulin expression or generating chimeric antibodies. We have shown that vector integration induced by human immunoglobulin G1 (IgG1) insertion vectors results in subsequent vector excision mediated by the duplicated target sequence, whereas replacement events which could be induced by the same constructs remain stable. We could demonstrate that the distribution of the vector homology strongly influences the genetic stability obtained. To this end we developed a novel type of a heavy chain replacement vector making use of the heavy chain class switch recombination sequence. Despite the presence of a two-sided homology this construct is universally applicable irrespective of the constant gene region utilized by the B cell. In comparison to an integration vector the frequency of stable incorporation was strongly increased, but we still observed vector excision, although at a markedly reduced rate. The latter events even occurred with circular constructs. Linearization of the construct at various sites and the comparison with an integration vector that carries the identical homology sequence, but differs in the distribution of homology, revealed the following features of homologous recombination of immunoglobulin genes: (i) the integration frequency is only determined by the length of the homology flank where the cross-over takes place; (ii) a 5' flank that does not meet the minimum requirement of homology length cannot be complemented by a sufficient 3' flank; (iii) free vector ends play a role for integration as well as for replacement targeting; (iv) truncating recombination events are suppressed in the presence of two flanks. Furthermore, we show that the switch region that was used as 3' flank is non-functional in an inverted orientation. Images Figure 2 PMID:8958041

Genetic stability of gene targeted immunoglobulin loci. I. Heavy chain isotype exchange induced by a universal gene replacement vector.

PubMed

Kardinal, C; Selmayr, M; Mocikat, R

1996-11-01

Gene targeting at the immunoglobulin loci of B cells is an efficient tool for studying immunoglobulin expression or generating chimeric antibodies. We have shown that vector integration induced by human immunoglobulin G1 (IgG1) insertion vectors results in subsequent vector excision mediated by the duplicated target sequence, whereas replacement events which could be induced by the same constructs remain stable. We could demonstrate that the distribution of the vector homology strongly influences the genetic stability obtained. To this end we developed a novel type of a heavy chain replacement vector making use of the heavy chain class switch recombination sequence. Despite the presence of a two-sided homology this construct is universally applicable irrespective of the constant gene region utilized by the B cell. In comparison to an integration vector the frequency of stable incorporation was strongly increased, but we still observed vector excision, although at a markedly reduced rate. The latter events even occurred with circular constructs. Linearization of the construct at various sites and the comparison with an integration vector that carries the identical homology sequence, but differs in the distribution of homology, revealed the following features of homologous recombination of immunoglobulin genes: (i) the integration frequency is only determined by the length of the homology flank where the cross-over takes place; (ii) a 5' flank that does not meet the minimum requirement of homology length cannot be complemented by a sufficient 3' flank; (iii) free vector ends play a role for integration as well as for replacement targeting; (iv) truncating recombination events are suppressed in the presence of two flanks. Furthermore, we show that the switch region that was used as 3' flank is non-functional in an inverted orientation.

Rangeland health attributes and indicators for qualitative assessment

USGS Publications Warehouse

Pyke, David A.; Herrick, J.E.; Pellant, Mike

2002-01-01

Panels of experts from the Society for Range Management and the National Research Council proposed that status of rangeland ecosystems could be ascertained by evaluating an ecological site's potential to conserve soil resources and by a series of indicators for ecosystem processes and site stability. Using these recommendations as a starting point, we developed a rapid, qualitative method for assessing a moment-in-time status of rangelands. Evaluators rate 17 indicators to assess 3 ecosystem attributes (soil and site stability, hydrologic function, and biotic integrity) for a given location. Indicators include rills, water flow patterns, pedestals and terracettes, bare ground, gullies, wind scour and depositional areas, litter movement, soil resistance to erosion, soil surface loss or degradation, plant composition relative to infiltration, soil compaction, plant functional/structural groups, plant mortality, litter amount, annual production, invasive plants, and reproductive capability. In this paper, we detail the development and evolution of the technique and introduce a modified ecological reference worksheet that documents the expected presence and amount of each indicator on the ecological site. In addition, we review the intended applications for this technique and clarify the differences between assessment and monitoring that lead us to recommend this technique be used for moment-in-time assessments and not be used for temporal monitoring of rangeland status. Lastly, we propose a mechanism for adapting and modifying this technique to reflect improvements in understanding of ecosystem processes. We support the need for quantitative measures for monitoring rangeland health and propose some measures that we believe may address some of the 17 indicators.

Evaluation of water binding, seed coat permeability and germination characteristics of wheat seeds equilibrated at different relative humidities.

PubMed

Chatterjee, Nabamita; Nagarajan, Shantha

2006-08-01

The relative binding of seed water and seed coat membrane stability were measured in two contrasting wheat (Triticum aestivum L) varieties, HDR 77 (drought-tolerant) and HD 2009 (susceptible) using seed water sorption isotherms, electrical conductivity (EC) of leachates and desorption-absorption isotherms. Analysis of sorption isotherm at 25 degrees C showed that the seeds of HDR 77 had significantly higher number of strong binding sites, with correspondingly greater amount of seed water as strongly bound water, as compared to HD 2009. Total number of binding sites was also higher in HDR 77 than HD 2009, which explained the better desiccation tolerance and higher capacity to bind water in seeds of HDR 77. EC of seed leachate in both varieties did not change with respect to change in equilibrium relative humidity (RII), indicating the general seed coat membrane stability of wheat seeds. However, absolute conductivity values were higher for HD 2009. showing its relatively porous seed coat membrane. Significantly lower area enclosed by the desorption-absorption isotherm loop in HDR 77, as compared to HD 2009 also indicated the greater membrane integrity of HDR 77. Germination and seedling vigour of HD 2009 were reduced when equilibrated over very low and very high RH. In contrast, germination and vigour in HDR 77 were maintained high, except at very high RH, indicating again its desiccation tolerance. Thus, the study demonstrated the relative drought tolerance of HDR 77, on the basis of seed water-binding characteristics and seed membrane stability. Seed membrane stability as measured by seed leachate conductivity or as area under dehydration-rehydration loop may be used as a preliminary screening test for drought tolerance in wheat.

Experimental and computational analysis of the transition state for ribonuclease A-catalyzed RNA 2′-O-transphosphorylation

PubMed Central

Gu, Hong; Zhang, Shuming; Wong, Kin-Yiu; Radak, Brian K.; Dissanayake, Thakshila; Kellerman, Daniel L.; Dai, Qing; Miyagi, Masaru; Anderson, Vernon E.; York, Darrin M.; Piccirilli, Joseph A.; Harris, Michael E.

2013-01-01

Enzymes function by stabilizing reaction transition states; therefore, comparison of the transition states of enzymatic and nonenzymatic model reactions can provide insight into biological catalysis. Catalysis of RNA 2′-O-transphosphorylation by ribonuclease A is proposed to involve electrostatic stabilization and acid/base catalysis, although the structure of the rate-limiting transition state is uncertain. Here, we describe coordinated kinetic isotope effect (KIE) analyses, molecular dynamics simulations, and quantum mechanical calculations to model the transition state and mechanism of RNase A. Comparison of the 18O KIEs on the 2′O nucleophile, 5′O leaving group, and nonbridging phosphoryl oxygens for RNase A to values observed for hydronium- or hydroxide-catalyzed reactions indicate a late anionic transition state. Molecular dynamics simulations using an anionic phosphorane transition state mimic suggest that H-bonding by protonated His12 and Lys41 stabilizes the transition state by neutralizing the negative charge on the nonbridging phosphoryl oxygens. Quantum mechanical calculations consistent with the experimental KIEs indicate that expulsion of the 5′O remains an integral feature of the rate-limiting step both on and off the enzyme. Electrostatic interactions with positively charged amino acid site chains (His12/Lys41), together with proton transfer from His119, render departure of the 5′O less advanced compared with the solution reaction and stabilize charge buildup in the transition state. The ability to obtain a chemically detailed description of 2′-O-transphosphorylation transition states provides an opportunity to advance our understanding of biological catalysis significantly by determining how the catalytic modes and active site environments of phosphoryl transferases influence transition state structure. PMID:23878223

Slope stability and bearing capacity of landfills and simple on-site test methods.

PubMed

Yamawaki, Atsushi; Doi, Yoichi; Omine, Kiyoshi

2017-07-01

This study discusses strength characteristics (slope stability, bearing capacity, etc.) of waste landfills through on-site tests that were carried out at 29 locations in 19 sites in Japan and three other countries, and proposes simple methods to test and assess the mechanical strength of landfills on site. Also, the possibility of using a landfill site was investigated by a full-scale eccentric loading test. As a result of this, landfills containing more than about 10 cm long plastics or other fibrous materials were found to be resilient and hard to yield. An on-site full scale test proved that no differential settlement occurs. The repose angle test proposed as a simple on-site test method has been confirmed to be a good indicator for slope stability assessment. The repose angle test suggested that landfills which have high, near-saturation water content have considerably poorer slope stability. The results of our repose angle test and the impact acceleration test were related to the internal friction angle and the cohesion, respectively. In addition to this, it was found that the air pore volume ratio measured by an on-site air pore volume ratio test is likely to be related to various strength parameters.

A globally efficient means of distributing UTC time and frequency through GPS

NASA Technical Reports Server (NTRS)

Kusters, John A.; Giffard, Robin P.; Cutler, Leonard S.; Allan, David W.; Miranian, Mihran

1995-01-01

Time and frequency outputs comparable in quality to the best laboratories have been demonstrated on an integrated system suitable for field application on a global basis. The system measures the time difference between 1 pulse-per-second (pps) signals derived from local primary frequency standards and from a multi-channel GPS C/A receiver. The measured data is processed through optimal SA Filter algorithms that enhance both the stability and accuracy of GPS timing signals. Experiments were run simultaneously at four different sites. Even with large distances between sites, the overall results show a high degree of cross-correlation of the SA noise. With sufficiently long simultaneous measurement sequences, the data shows that determination of the difference in local frequency from an accepted remote standard to better than 1 x 10(exp -14) is possible. This method yields frequency accuracy, stability, and timing stability comparable to that obtained with more conventional common-view experiments. In addition, this approach provides UTC(USNO MC) in real time to an accuracy better than 20 ns without the problems normally associated with conventional common-view techniques. An experimental tracking loop was also set up to demonstrate the use of enhanced GPS for dissemination of UTC(USNO MC) over a wide geographic area. Properly disciplining a cesium standard with a multi-channel GPS receiver, with additional input from USNO, has been found to permit maintaining a timing precision of better than 10 ns between Palo Alto, CA and Washington, DC.

Floating wind turbine system

NASA Technical Reports Server (NTRS)

Viterna, Larry A. (Inventor)

2009-01-01

A floating wind turbine system with a tower structure that includes at least one stability arm extending therefrom and that is anchored to the sea floor with a rotatable position retention device that facilitates deep water installations. Variable buoyancy for the wind turbine system is provided by buoyancy chambers that are integral to the tower itself as well as the stability arm. Pumps are included for adjusting the buoyancy as an aid in system transport, installation, repair and removal. The wind turbine rotor is located downwind of the tower structure to allow the wind turbine to follow the wind direction without an active yaw drive system. The support tower and stability arm structure is designed to balance tension in the tether with buoyancy, gravity and wind forces in such a way that the top of the support tower leans downwind, providing a large clearance between the support tower and the rotor blade tips. This large clearance facilitates the use of articulated rotor hubs to reduced damaging structural dynamic loads. Major components of the turbine can be assembled at the shore and transported to an offshore installation site.

Noncomparative scaling of aromaticity through electron itinerancy

NASA Astrophysics Data System (ADS)

Paul, Satadal; Goswami, Tamal; Misra, Anirban

2015-10-01

Aromaticity is a multidimensional concept and not a directly observable. These facts have always stood in the way of developing an appropriate theoretical framework for scaling of aromaticity. In the present work, a quantitative account of aromaticity is developed on the basis of cyclic delocalization of π-electrons, which is the phenomenon leading to unique features of aromatic molecules. The stabilization in molecular energy, caused by delocalization of π-electrons is obtained as a second order perturbation energy for archetypal aromatic systems. The final expression parameterizes the aromatic stabilization energy in terms of atom to atom charge transfer integral, onsite repulsion energy and the population of spin orbitals at each site in the delocalized π-electrons. An appropriate computational platform is framed to compute each and individual parameter in the derived equation. The numerical values of aromatic stabilization energies obtained for various aromatic molecules are found to be in close agreement with available theoretical and experimental reports. Thus the reliable estimate of aromaticity through the proposed formalism renders it as a useful tool for the direct assessment of aromaticity, which has been a long standing problem in chemistry.

Processed pseudogenes of human endogenous retroviruses generated by LINEs: their integration, stability, and distribution.

PubMed

Pavlícek, Adam; Paces, Jan; Elleder, Daniel; Hejnar, Jirí

2002-03-01

We report here the presence of numerous processed pseudogenes derived from the W family of endogenous retroviruses in the human genome. These pseudogenes are structurally colinear with the retroviral mRNA followed by a poly(A) tail. Our analysis of insertion sites of HERV-W processed pseudogenes shows a strong preference for the insertion motif of long interspersed nuclear element (LINE) retrotransposons. The genomic distribution, stability during evolution, and frequent truncations at the 5' end resemble those of the pseudogenes generated by LINEs. We therefore suggest that HERV-W processed pseudogenes arose by multiple and independent LINE-mediated retrotransposition of retroviral mRNA. These data document that the majority of HERV-W copies are actually nontranscribed promoterless pseudogenes. The current search for HERV-Ws associated with several human diseases should concentrate on a small subset of transcriptionally competent elements.

Results of tests in the NASA/LARC 31-inch CFHT on an 0.010-scale model (32-OT) of the space shuttle configuration 3 to determine the RCS jet flowfield interaction effects on aerodynamic characteristics (IA60/OA105), volume 1

NASA Technical Reports Server (NTRS)

Thornton, D. E.

1974-01-01

Tests were conducted in the NASA Langley Research Center 31-inch continuous Flow Hypersonic Wind Tunnel to determine RCS jet interaction effect on the hypersonic aerodynamic and stability and control characteristics prior to return to launch site (RTLS) abort separation. The model used was an 0.010-scale replica of the Space Shuttle Vehicle Configuration 3. Hypersonic stability data were obtained from tests at Mach 10.3 and dynamic pressure of 150 psf for the integrated Orbiter and external tank and the Orbiter alone. RCS modes of pitch, yaw, and roll at free flight dynamic pressure simulation of 7, 20, and 50 psf were investigated. The effects of speedbrake, bodyflap, elevon, and aileron deflections were also investigated.

A study of stability effects in forested terrain

NASA Astrophysics Data System (ADS)

Desmond, Cian J.; Watson, Simon

2014-12-01

Data from four well instrumented met masts located in heavily forested European sites in different locations and terrain types are examined. Seven stability metrics are applied to the data sets and a novel method is used to identify the metric which most consistently identifies stability events of importance for wind energy generation. It was found that the Obukhov length, as calculated by fast response sonic anemometer, provides the most reliable results in these highly complex sites. It was also found that non-neutral stabilities can be expected a significant portion of the time for wind speeds of less than 10 m/s at the considered sites.

Agrobacterium tumefaciens-mediated transformation of Mucor circinelloides.

PubMed

Nyilasi, I; Acs, K; Papp, T; Nagy, E; Vágvölgyi, C

2005-01-01

The Agrobacterium tumefaciens-mediated transformation of the zygomycetous fungus Mucor circinelloides is described. A method was also developed for the hygromycin B-based selection of Mucor transformants. Transformation with the hygromycin B phosphotransferase gene of Escherichia coli controlled by the heterologous Aspergillus nidulans trpC promoter resulted in hygromycin B-resistant clones. The presence of the hygromycin resistance gene in the genome of the transformants was verified by polymerase chain reaction and Southern hybridization: the latter analyses revealed integrations in the host genome at different sites in different transformants. The stability of transformants remained questionable during the latter analyses.

A Paradox-based data collection and management system for multi-center randomized clinical trials.

PubMed

Abdellatif, Mazen; Reda, Domenic J

2004-02-01

We have developed a Paradox-based data collection and management system for large-scale multi-site randomized clinical trials. The system runs under Windows operating system and integrates Symantec pcAnywhere32 telecommunications software for data transmission and remote control sessions, PKZIP utility for the compression/decompression of transmitted data, and Stat/Transfer for exporting the centralized Paradox database for analyses. We initially developed this system for VA Cooperative Study #399 'The Effect of Antiarrhythmic Therapy in Maintaining Stability of Sinus Rhythm in Atrial Fibrillation', which collects over 1000 variables on 706 patients at 20 sites. Patient intake for this 5-year study began in March of 1998. We have also developed an enhanced version of this system, which is being used in the NIH-funded 'Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT)' that collects over 1200 variables on 1588 patients at 13 sites. Patient intake for this 4-year study began in October of 2000.

Architecturing hierarchical function layers on self-assembled viral templates as 3D nano-array electrodes for integrated Li-ion microbatteries.

PubMed

Liu, Yihang; Zhang, Wei; Zhu, Yujie; Luo, Yanting; Xu, Yunhua; Brown, Adam; Culver, James N; Lundgren, Cynthia A; Xu, Kang; Wang, Yuan; Wang, Chunsheng

2013-01-09

This work enables an elegant bottom-up solution to engineer 3D microbattery arrays as integral power sources for microelectronics. Thus, multilayers of functional materials were hierarchically architectured over tobacco mosaic virus (TMV) templates that were genetically modified to self-assemble in a vertical manner on current-collectors, so that optimum power and energy densities accompanied with excellent cycle-life could be achieved on a minimum footprint. The resultant microbattery based on self-aligned LiFePO(4) nanoforests of shell-core-shell structure, with precise arrangement of various auxiliary material layers including a central nanometric metal core as direct electronic pathway to current collector, delivers excellent energy density and stable cycling stability only rivaled by the best Li-ion batteries of conventional configurations, while providing rate performance per foot-print and on-site manufacturability unavailable from the latter. This approach could open a new avenue for microelectromechanical systems (MEMS) applications, which would significantly benefit from the concept that electrochemically active components be directly engineered and fabricated as an integral part of the integrated circuit (IC).

Assessing Soil Organic C Stability at the Continental Scale: An Analysis of Soil C and Radiocarbon Profiles Across the NEON Sites

NASA Astrophysics Data System (ADS)

Heckman, K. A.; Gallo, A.; Hatten, J. A.; Swanston, C.; McKnight, D. M.; Strahm, B. D.; Sanclements, M.

2017-12-01

Soil carbon stocks have become recognized as increasingly important in the context of climate change and global C cycle modeling. As modelers seek to identify key parameters affecting the size and stability of belowground C stocks, attention has been drawn to the mineral matrix and the soil physiochemical factors influenced by it. Though clay content has often been utilized as a convenient and key explanatory variable for soil C dynamics, its utility has recently come under scrutiny as new paradigms of soil organic matter stabilization have been developed. We utilized soil cores from a range of National Ecological Observatory Network (NEON) experimental plots to examine the influence of physicochemical parameters on soil C stocks and turnover, and their relative importance in comparison to climatic variables. Soils were cored at NEON sites, sampled by genetic horizon, and density separated into light fractions (particulate organics neither occluded within aggregates nor associated with mineral surfaces), occluded fractions (particulate organics occluded within aggregates), and heavy fractions (organics associated with mineral surfaces). Bulk soils and density fractions were measured for % C and radiocarbon abundance (as a measure of C stability). Carbon and radiocarbon abundances were examined among fractions and in the context of climatic variables (temperature, precipitation, elevation) and soil physiochemical variables (% clay and pH). No direct relationships between temperature and soil C or radiocarbon abundances were found. As a whole, soil radiocarbon abundance in density fractions decreased in the order of light>heavy>occluded, highlighting the importance of both surface sorption and aggregation to the preservation of organics. Radiocarbon abundance was correlated with pH, with variance also grouping by dominate vegetation type. Soil order was also identified as an important proxy variable for C and radiocarbon abundance. Preliminary results suggest that both integrative proxies as well as physicochemical properties may be needed to account for variation in soil C abundance and stability at the continental scale.

WHEAT GERM CELL-FREE TRANSLATION, PURIFICATION, AND ASSEMBLY OF A FUNCTIONAL HUMAN STEAROYL-COA DESATURASE COMPLEX

PubMed Central

Goren, Michael A.; Fox, Brian G.

2008-01-01

A wheat germ cell-free extract was used to perform in vitro translation of human stearoyl-CoA desaturase in the presence of unilamelar liposomes, and near complete transfer of the expressed integral membrane protein into the liposome was observed. Moreover, co-translation of the desaturase along with human cytochrome b5 led to transfer of both membrane proteins into the liposomes. A simple, single step purification via centrifugation in a density gradient yielded proteoliposomes with the desaturase in high purity as judged by capillary electrophoresis. After in vitro reconstitution of the non-heme iron and heme active sites, the function of the reconstituted enzyme complex was demonstrated by conversion of stearoyl-CoA to oleoyl-CoA. This simple translation approach obviates the use of detergents or other lipids to stabilize and isolate a catalytically active integral membrane enzyme. The applicability of cell-free translation to the assembly and purification of other integral membrane protein complexes is discussed. PMID:18765284

Wheat germ cell-free translation, purification, and assembly of a functional human stearoyl-CoA desaturase complex.

PubMed

Goren, Michael A; Fox, Brian G

2008-12-01

A wheat germ cell-free extract was used to perform in vitro translation of human stearoyl-CoA desaturase in the presence of unilamelar liposomes, and near complete transfer of the expressed integral membrane protein into the liposome was observed. Moreover, co-translation of the desaturase along with human cytochrome b(5) led to transfer of both membrane proteins into the liposomes. A simple, single step purification via centrifugation in a density gradient yielded proteoliposomes with the desaturase in high purity as judged by capillary electrophoresis. After in vitro reconstitution of the non-heme iron and heme active sites, the function of the reconstituted enzyme complex was demonstrated by conversion of stearoyl-CoA to oleoyl-CoA. This simple translation approach obviates the use of detergents or other lipids to stabilize and isolate a catalytically active integral membrane enzyme. The applicability of cell-free translation to the assembly and purification of other integral membrane protein complexes is discussed.

A FLINN Station at Pinon Flat Observatory

NASA Technical Reports Server (NTRS)

Agnew, Duncan Carr; Wyatt, Frank

1997-01-01

The main objectives are: (1) To develop Pinon Flat Observatory (PFO) as a prototype 'integrated' FLINN station: one from which many types of data are collected, combined, and made available to the DOSE program to enhance studies of local and regional strains; (2) To develop the theoretical framework and methods to integrate the various types of auxiliary data which are to be collected by NASA at space-geodetic sites of the FLINN network, with the aim of learning as much as possible about the nature of earth deformation; (3) To develop procedures for the efficient and useful storage and retrieval of such auxiliary data so that they may be efficiently utilized by DOSE investigators; (4) To investigate the stability of ground monumentation now used in space-geodetic measurements, including the field testing of existing and new monument designs.

Adaptation of eastern whitepine provenances to planting sites

Treesearch

Maurice E., Jr. Demeritt; Peter W. Garrett

1996-01-01

Eastern white pine provenances from the extreme limits of the natural range of this species are changing from above- and below-average stability to average stability for height growth with increasing age. The regression method is useful for evaluating the stability of provenance to planting sites. The same general conclusions are reached for the performance at...

Enhanced enzyme kinetic stability by increasing rigidity within the active site.

PubMed

Xie, Yuan; An, Jiao; Yang, Guangyu; Wu, Geng; Zhang, Yong; Cui, Li; Feng, Yan

2014-03-14

Enzyme stability is an important issue for protein engineers. Understanding how rigidity in the active site affects protein kinetic stability will provide new insight into enzyme stabilization. In this study, we demonstrated enhanced kinetic stability of Candida antarctica lipase B (CalB) by mutating the structurally flexible residues within the active site. Six residues within 10 Å of the catalytic Ser(105) residue with a high B factor were selected for iterative saturation mutagenesis. After screening 2200 colonies, we obtained the D223G/L278M mutant, which exhibited a 13-fold increase in half-life at 48 °C and a 12 °C higher T50(15), the temperature at which enzyme activity is reduced to 50% after a 15-min heat treatment. Further characterization showed that global unfolding resistance against both thermal and chemical denaturation also improved. Analysis of the crystal structures of wild-type CalB and the D223G/L278M mutant revealed that the latter formed an extra main chain hydrogen bond network with seven structurally coupled residues within the flexible α10 helix that are primarily involved in forming the active site. Further investigation of the relative B factor profile and molecular dynamics simulation confirmed that the enhanced rigidity decreased fluctuation of the active site residues at high temperature. These results indicate that enhancing the rigidity of the flexible segment within the active site may provide an efficient method for improving enzyme kinetic stability.

Aggregate stability, root length and root thickness influenced by a mycorrhizal inoculum? - Results from a three-year eco-engineering field experiment on an alpine slope.

NASA Astrophysics Data System (ADS)

Bast, Alexander; Wilcke, Wolfgang; Lüscher, Peter; Graf, Frank; Gärtner, Holger

2014-05-01

In mountain environments many slopes are covered by coarse grained, glacial-, periglacial- or/and denudation-derived substrate. These slopes show a high geomorphic activity and are susceptible for erosional processes, shallow landslides or debris flows, which can result in a high socio-economic hazard potential. This is especially true for steep slopes, lacking a protecting vegetation cover. Regarding hazard prevention, eco-engineering gained in importance because related techniques provide a sustainable measure to protect erosion-prone hillslopes. The idea of using plants for sustainable erosion control and protection against shallow landslides, demands some essential requirements, as e.g., a stable seedbed providing appropriate water and nutrient supply. However, degraded alpine slopes are often unstable and the coarse-grained material shows a low retention capacity of water and nutrients. Extreme conditions like this hamper a fast and sustainable development of a protecting vegetation cover even if pioneer plants are used to stabilize the slopes. Thus, the question arises what needs to be done to give planted saplings within eco-engineering projects maximum support developing their above- and belowground structures to promote slope stabilization. Laboratory experiments using potted plants have shown a positive impact of mycorrhizal fungi inoculation plant development and soil structure, i.e. the formation of (stable) aggregates within several months. Soil aggregate stability is an integrating parameter, reflecting several aspects of the plant-soil system and for this also an indicator of soil development and soil stability. Because of this and based on the promising laboratory results, we intended to apply this approach in a field-experiment We established (i) mycorrhizal and (ii) non-mycorrhizal treated eco-engineered research plots on a field experimental scale, covering a total area of approx. 1000 m2 on an ENE exposed slope (coarse morainic and denudation-derived substrate; inclination ~40 - 45 °; elevation 1220 - 1360 m a.s.l.) located in the Eastern Swiss Alps, where many environmental parameters can be seen as homogeneous. Soil aggregate stability, the formation of water stable aggregates and the fine-root development was quantified at the end of three consecutively vegetation periods. Our results show, that an impact of the mycorrhizal inoculum on aggregate stability was not traceable after one vegetation period, which contradicts our expectations and former laboratory experiments. At the mycorrhizal inoculated site, fine roots showed indeed a lower root length density compared to the non-mycorrhizal treated site, but the proportion of roots with thicker diameters tended to be higher. At the end of the third vegetation period this pattern changed. Aggregate stability is then highest at the inoculated site and root length density increased showing the highest values as well. The tendency to thicker root diameters at the mycorrhizal treated site can be confirmed. Our findings show that studies on a field experimental scale are inevitable. Laboratory experiments and field studies complement each other, and lead to a better understanding, having regard to a successful application of sustainable eco-engineering measures on erosion-prone slopes in alpine environments.

Evaluation of the Main Ceos Pseudo Calibration Sites Using Modis Brdf/albedo Products

NASA Astrophysics Data System (ADS)

Kharbouche, Said; Muller, Jan-Peter

2016-06-01

This work describes our findings about an evaluation of the stability and the consistency of twenty primary PICSs (Pseudo-Invariant Calibration Sites). We present an analysis of 13 years of 8-daily MODIS products of BRDF parameters and white-sky-albedos (WSA) over the shortwave band. This time series of WSA and BRDFs shows the variation of the "stability" varies significantly from site to site. Using a 10x10 km window size over all the sites, the change in of WSA stability is around 4% but the isotropicity, which is an important element in inter-satellite calibration, can vary from 75% to 98%. Moreover, some PICS, especially, Libya-4 which is one of the PICS which is most employed, has significant and relatively fast changes in wintertime. PICS observations of BRDF/albedo shows that the Libya-4 PICS has the best performance but it is not too far from some sites such as Libya-1 and Mali. This study also reveals that Niger-3 PICS has the longest continuous period of high stability per year, and Sudan has the most isotropic surface. These observations have important implications for the use of these sites.

Towards novel multiferroic and magnetoelectric materials: dipole stability in tetragonal tungsten bronzes

PubMed Central

Rotaru, Andrei; Miller, Andrew J.; Arnold, Donna C.; Morrison, Finlay D.

2014-01-01

We discuss the strategy for development of novel functional materials with the tetragonal tungsten bronze structure. From the starting composition Ba6GaNb9O30, the effect of A- and B-site substitutions on the dielectric properties is used to develop an understanding of the origin and stability of the dipolar response in these compounds. Both tetragonal strain induced by large B-site cations and local strain variations created by isovalent A-site substitutions enhance dipole stability but result in a dilute, weakly correlated dipolar response and canonical relaxor behaviour. Decreasing cation size at the perovskite A2-site increases the dipolar displacements in the surrounding octahedra, but insufficiently to result in dipole ordering. Mechanisms introducing small A-site lanthanide cations and incorporation of A-site vacancies to induce ferroelectricity and magnetism are presented. PMID:24421377

Temporal Characterization of Hydrates System Dynamics beneath Seafloor Mounds. Integrating Time-Lapse Electrical Resistivity Methods and In Situ Observations of Multiple Oceanographic Parameters

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

Lutken, Carol; Macelloni, Leonardo; D'Emidio, Marco

This study was designed to investigate temporal variations in hydrate system dynamics by measuring changes in volumes of hydrate beneath hydrate-bearing mounds on the continental slope of the northern Gulf of Mexico, the landward extreme of hydrate occurrence in this region. Direct Current Resistivity (DCR) measurements were made contemporaneously with measurements of oceanographic parameters at Woolsey Mound, a carbonate-hydrate complex on the mid-continental slope, where formation and dissociation of hydrates are most vulnerable to variations in oceanographic parameters affected by climate change, and where changes in hydrate stability can readily translate to loss of seafloor stability, impacts to benthic ecosystems,more » and venting of greenhouse gases to the water-column, and eventually, the atmosphere. We focused our study on hydrate within seafloor mounds because the structurally-focused methane flux at these sites likely causes hydrate formation and dissociation processes to occur at higher rates than at sites where the methane flux is less concentrated and we wanted to maximize our chances of witnessing association/dissociation of hydrates. We selected a particularly well-studied hydrate-bearing seafloor mound near the landward extent of the hydrate stability zone, Woolsey Mound (MC118). This mid-slope site has been studied extensively and the project was able to leverage considerable resources from the team’s research experience at MC118. The site exhibits seafloor features associated with gas expulsion, hydrates have been documented at the seafloor, and changes in the outcropping hydrates have been documented, photographically, to have occurred over a period of months. We conducted observatory-based, in situ measurements to 1) characterize, geophysically, the sub-bottom distribution of hydrate and its temporal variability, and 2) contemporaneously record relevant environmental parameters (temperature, pressure, salinity, turbidity, bottom currents) to detect short-term changes within the hydrates system, identify relationships/impacts of local oceanographic parameters on the hydrates system, and improve our understanding of how seafloor instability is affected by hydrates-driven changes. A 2009 DCR survey of MC118 demonstrated that we could image resistivity anomalies to a depth of 75m below the seafloor in water depths of 1km. We reconfigured this system to operate autonomously on the seafloor in a pre-programmed mode, for periods of months. We designed and built a novel seafloor lander and deployment capability that would allow us to investigate the seafloor at potential deployment sites and deploy instruments only when conditions met our criteria. This lander held the DCR system, controlling computers, and battery power supply, as well as instruments to record oceanographic parameters. During the first of two cruises to the study site, we conducted resistivity surveying, selected a monitoring site, and deployed the instrumented lander and DCR, centered on what appeared to be the most active locations within the site, programmed to collect a DCR profile, weekly. After a 4.5-month residence on the seafloor, the team recovered all equipment. Unfortunately, several equipment failures occurred prior to recovery of the instrument packages. Prior to the failures, however, two resistivity profiles were collected together with oceanographic data. Results show, unequivocally, that significant changes can occur in both hydrate volume and distribution during time periods as brief as one week. Occurrences appear to be controlled by both deep and near-surface structure. Results have been integrated with seismic data from the area and show correspondence in space of hydrate and structures, including faults and gas chimneys.« less

Using the Sonoran Desert test site to monitor the long-term radiometric stability of the Landsat TM/ETM+ and Terra MODIS sensors

USGS Publications Warehouse

Angal, A.; Xiong, X.; Choi, T.; Chander, G.; Wu, A.

2009-01-01

Pseudo-invariant ground targets have been extensively used to monitor the long-term radiometric calibration stability of remote sensing instruments. The NASA MODIS Characterization Support Team (MCST), in collaboration with members from the U.S. Geological Survey (USGS) Earth Resources Observation and Science (EROS) Center, has previously demonstrated the use of pseudo-invariant ground sites for the long-term stability monitoring of Terra MODIS and Landsat 7 ETM+ sensors. This paper focuses on the results derived from observations made over the Sonoran Desert. Additionally, Landsat 5 TM data over the Sonoran Desert site were used to evaluate the temporal stability of this site. Top-ofatmosphere (TOA) reflectances were computed for the closely matched TM, ETM+, and MODIS spectral bands over selected regions of interest. The impacts due to different viewing geometries, or the effect of test site Bi-directional Reflectance Distribution Function (BRDF), are also presented. ?? 2009 SPIE.

Impact of calcium on N1 influenza neuraminidase dynamics and binding free energy.

PubMed

Lawrenz, Morgan; Wereszczynski, Jeff; Amaro, Rommie; Walker, Ross; Roitberg, Adrian; McCammon, J Andrew

2010-08-15

The highly pathogenic influenza strains H5N1 and H1N1 are currently treated with inhibitors of the viral surface protein neuraminidase (N1). Crystal structures of N1 indicate a conserved, high affinity calcium binding site located near the active site. The specific role of this calcium in the enzyme mechanism is unknown, though it has been shown to be important for enzymatic activity and thermostability. We report molecular dynamics (MD) simulations of calcium-bound and calcium-free N1 complexes with the inhibitor oseltamivir (marketed as the drug Tamiflu), independently using both the AMBER FF99SB and GROMOS96 force fields, to give structural insight into calcium stabilization of key framework residues. Y347, which demonstrates similar sampling patterns in the simulations of both force fields, is implicated as an important N1 residue that can "clamp" the ligand into a favorable binding pose. Free energy perturbation and thermodynamic integration calculations, using two different force fields, support the importance of Y347 and indicate a +3 to +5 kcal/mol change in the binding free energy of oseltamivir in the absence of calcium. With the important role of structure-based drug design for neuraminidase inhibitors and the growing literature on emerging strains and subtypes, inclusion of this calcium for active site stability is particularly crucial for computational efforts such as homology modeling, virtual screening, and free energy methods. 2010 Wiley-Liss, Inc.

A summary of impacts of wind power integration on power system small-signal stability

NASA Astrophysics Data System (ADS)

Yan, Lei; Wang, Kewen

2017-05-01

Wind power has been increasingly integrated into power systems over the last few decades because of the global energy crisis and the pressure on environmental protection, and the stability of the system connected with wind power is becoming more prominent. This paper summaries the research status, achievements as well as deficiencies of the research on the impact of wind power integration on power system small-signal stability. In the end, the further research needed are discussed.

Stabilizing detached Bridgman melt crystal growth: Proportional-integral feedback control

NASA Astrophysics Data System (ADS)

Yeckel, Andrew; Daoutidis, Prodromos; Derby, Jeffrey J.

2012-10-01

The dynamics, operability limits, and tuning of a proportional-integral feedback controller to stabilize detached vertical Bridgman crystal growth are analyzed using a capillary model of shape stability. The manipulated variable is the pressure difference between upper and lower vapor spaces, and the controlled variable is the gap width at the triple-phase line. Open and closed loop dynamics of step changes in these state variables are analyzed under both shape stable and shape unstable growth conditions. Effects of step changes in static contact angle and growth angle are also studied. Proportional and proportional-integral control can stabilize unstable growth, but only within tight operability limits imposed by the narrow range of allowed meniscus shapes. These limits are used to establish safe operating ranges of controller gain. Strong nonlinearity of the capillary model restricts the range of perturbations that can be stabilized, and under some circumstances, stabilizes a spurious operating state far from the set point. Stabilizing detachment at low growth angle proves difficult and becomes impossible at zero growth angle.

Long-term health and germline transmission in transgenic cattle following transposon-mediated gene transfer.

PubMed

Yum, Soo-Young; Lee, Song-Jeon; Park, Sin-Gi; Shin, In-Gang; Hahn, Sang-Eun; Choi, Woo-Jae; Kim, Hee-Soo; Kim, Hyeong-Jong; Bae, Seong-Hun; Lee, Je-Hyeong; Moon, Joo-Yeong; Lee, Woo-Sung; Lee, Ji-Hyun; Lee, Choong-Il; Kim, Seong-Jin; Jang, Goo

2018-05-23

Transposon-mediated, non-viral gene delivery is a powerful tool for generating stable cell lines and transgenic animals. However, as multi-copy insertion is the preferred integration pattern, there is the potential for uncontrolled changes in endogenous gene expression and detrimental effects in cells or animals. Our group has previously reported on the generation of several transgenic cattle by using microinjection of the Sleeping Beauty (SB) and PiggyBac (PB) transposons and seeks to explore the long-term effects of this technology on cattle. Transgenic cattle, one female (SNU-SB-1) and one male (SNU-PB-1), reached over 36 months of age with no significant health issues and normal blood parameters. The detection of transgene integration and fluorescent signal in oocytes and sperm suggested the capacity for germline transmission in both of the founder animals. After natural breeding, the founder transgenic cow delivered a male calf and secreted milk containing fluorescent transgenic proteins. The calf expressed green fluorescent protein in primary cells from ear skin, with no significant change in overall genomic stability and blood parameters. Three sites of transgene integration were identified by next-generation sequencing of the calf's genome. Overall, these data demonstrate that transposon-mediated transgenesis can be applied to cattle without being detrimental to their long-term genomic stability or general health. We further suggest that this technology may be usefully applied in other fields, such as the generation of transgenic animal models.

APPLICATIONS ANALYSIS REPORT: CHEMFIX TECHNOLOGIES, INC. - SOLIDIFICATION/STABILIZATION PROCESS

EPA Science Inventory

In support of the U.S. Environmental Protection Agency's (EPA) Superfund Innovative Technology Evaluation (SITE) Program, this report evaluates the Chemfix Technologies, Inc. (Chemfix), solidification/stabilization technology for on-site treatment of hazardous waste. The Chemfix ...

A case study on the feasibility and performance of an UWB-AoA real time location system for resources management of civil construction projects

NASA Astrophysics Data System (ADS)

Mok, Esmond; Xia, Linyuan; Retscher, Guenther; Tian, Hui

2010-06-01

The application of integrated satellite and modern wireless positioning technologies for ubiquitous real-time resources management in large scale civil engineering projects can greatly optimize the time and cost in the construction process, and is now the trend for modern construction project management. As the outdoor conditions of most civil construction sites are open to sky, satellite positioning with the popularly used Global Positioning System (GPS) has been proved to be very efficient and effective. However, the condition in indoor and underground construction site is very complicated due to the fact that different construction activities would be carried out in different congested areas, involving heavy construction plant, equipment, professionals and technical personnel. Nowadays different emerging technologies such as Wi-Fi and ZigBee can be adopted for position and tracking in indoor environments. Nevertheless, under the very complicated construction site conditions these technologies may fail due to movement of human resources and construction plant, variation of metrological conditions, and serious multipath effects of signals. It is considered that Ultra Wide Band (UWB) technology is more suitable for indoor construction site environments. In this paper, a case study on the attempt of integrating GPS with Ubisense Real-time Location System (RTLS) for resources management in an underground railway construction site is discussed. Laboratory and field tests have shown that the RTLS can provide better resources management capability in terms of positioning accuracy and stability than Wi-Fi and ZigBee technologies under complicated construction environments. The test results show that the system can normally achieve better than 15 cm accuracy, and better than 1 m under adverse geometrical site condition. However, the high instrumental set up cost and the requirement for high quality data transmission cable for high precision time synchronization between sensors may deter wide application of similar system for resources management in construction sites.

Effects of Vegetation Structure on the Location of Lion Kill Sites in African Thicket.

PubMed

Davies, Andrew B; Tambling, Craig J; Kerley, Graham I H; Asner, Gregory P

2016-01-01

Predator-prey relationships are integral to ecosystem stability and functioning. These relationships are, however, difficult to maintain in protected areas where large predators are increasingly being reintroduced and confined. Where predators make kills has a profound influence on their role in ecosystems, but the relative importance of environmental variables in determining kill sites, and how these might vary across ecosystems is poorly known. We investigated kill sites for lions in South Africa's thicket biome, testing the importance of vegetation structure for kill site locations compared to other environmental variables. Kill sites were located over four years using GPS telemetry and compared to non-kill sites that had been occupied by lions, as well as to random sites within lion ranges. Measurements of 3D vegetation structure obtained from Light Detection and Ranging (LiDAR) were used to calculate the visible area (viewshed) around each site and, along with wind and moonlight data, used to compare kill sites between lion sexes, prey species and prey sexes. Viewshed area was the most important predictor of kill sites (sites in dense vegetation were twice as likely to be kill sites compared to open areas), followed by wind speed and, less so, moonlight. Kill sites for different prey species varied with vegetation structure, and male prey were killed when wind speeds were higher compared to female prey of the same species. Our results demonstrate that vegetation structure is an important component of predator-prey interactions, with varying effects across ecosystems. Such differences require consideration in terms of the ecological roles performed by predators, and in predator and prey conservation.

Site occupancy, composition and magnetic structure dependencies of martensitic transformation in Mn₂Ni_1+xSn_1-x.

PubMed

Kundu, Ashis; Ghosh, Subhradip

2017-11-14

A delicate balance between various factors such as site occupancy, composition and magnetic ordering seems to affect the stability of the martensitic phase in Mn₂Ni_1+xSn_1-x. Using first-principles DFT calculations, we explore the impacts of each one of these factors on the martensitic stability of this system. Our results on total energies, magnetic moments and electronic structures upon changes in the composition, the magnetic configurations and the site occupancies show that the occupancies at the 4d sites in the Inverse Heusler crystal structure play the most crucial role. The presence of Mn at the 4d sites originally occupied by Sn and its interaction with the Mn atoms at other sites decide the stability of the martensitic phases. This explains the discrepancy between the experiments and earlier DFT calculations regarding phase stability in Mn₂NiSn. Our results qualitatively explain the trends observed experimentally with regard to martensitic phase stability and the magnetisations in Ni-excess, Sn-deficient Mn₂NiSn system. © 2017 IOP Publishing Ltd.

Bioreduction and immobilization of uranium in situ: a case study at a USA Department of Energy radioactive waste site, Oak Ridge, Tennessee

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

Wu, Weimin; Carley, Jack M; Watson, David B

Bioremediation of uranium contaminated groundwater was tested by delivery of ethanol as an electron donor source to stimulate indigenous microbial bioactivity for reduction and immobilization of uranium in situ, followed by tests of stability of uranium sequestration in the bioreduced area via delivery of dissolved oxygen or nitrate at the US Department of energy's Integrated Field Research Challenge site located at Oak Ridge, Tennessee, USA. After long term treatment that spanned years, uranium in groundwater was reduced from 40-60 mg {center_dot} L{sup -1} to <0.03 mg {center_dot} L{sup -1}, below the USA EPA standard for drinking water. The bioreduced uraniummore » was stable under anaerobic or anoxic conditions, but addition of DO and nitrate to the bioreduced zone caused U remobilization. The change in the microbial community and functional microorganisms related to uranium reduction and oxidation were characterized. The delivery of ethanol as electron donor stimulated the activities of indigenous microorganisms for reduction of U(VI) to U(IV). Results indicated that the immobilized U could be partially remobilized by D0 and nitrate via microbial activity. An anoxic environmental condition without nitrate is essential to maintain the stability of bioreduced uranium.« less

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

PubMed

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

2015-07-07

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

Site-Specific Recombination at XerC/D Sites Mediates the Formation and Resolution of Plasmid Co-integrates Carrying a blaOXA-58- and TnaphA6-Resistance Module in Acinetobacter baumannii

PubMed Central

Cameranesi, María M.; Morán-Barrio, Jorgelina; Limansky, Adriana S.; Repizo, Guillermo D.; Viale, Alejandro M.

2018-01-01

Members of the genus Acinetobacter possess distinct plasmid types which provide effective platforms for the acquisition, evolution, and dissemination of antimicrobial resistance structures. Many plasmid-borne resistance structures are bordered by short DNA sequences providing potential recognition sites for the host XerC and XerD site-specific tyrosine recombinases (XerC/D-like sites). However, whether these sites are active in recombination and how they assist the mobilization of associated resistance structures is still poorly understood. Here we characterized the plasmids carried by Acinetobacter baumannii Ab242, a multidrug-resistant clinical strain belonging to the ST104 (Oxford scheme) which produces an OXA-58 carbapenem-hydrolyzing class-D β-lactamase (CHDL). Plasmid sequencing and characterization of replication, stability, and adaptive modules revealed the presence in Ab242 of three novel plasmids lacking self-transferability functions which were designated pAb242_9, pAb242_12, and pAb242_25, respectively. Among them, only pAb242_25 was found to carry an adaptive module encompassing an ISAba825-blaOXA-58 arrangement accompanied by a TnaphA6 transposon, the whole structure conferring simultaneous resistance to carbapenems and aminoglycosides. Ab242 plasmids harbor several XerC/D-like sites, with most sites found in pAb242_25 located in the vicinity or within the adaptive module described above. Electrotransformation of susceptible A. nosocomialis cells with Ab242 plasmids followed by imipenem selection indicated that the transforming plasmid form was a co-integrate resulting from the fusion of pAb242_25 and pAb242_12. Further characterization by cloning and sequencing studies indicated that a XerC/D site in pAb242_25 and another in pAb242_12 provided the active sister pair for the inter-molecular site-specific recombination reaction mediating the fusion of these two plasmids. Moreover, the resulting co-integrate was found also to undergo intra-molecular resolution at the new pair of XerC/D sites generated during fusion thus regenerating the original pAb242_25 and pAb242_12 plasmids. These observations provide the first evidence indicating that XerC/D-like sites in A. baumannii plasmids can provide active pairs for site-specific recombination mediating inter-molecular fusions and intra-molecular resolutions. The overall results shed light on the evolutionary dynamics of A. baumannii plasmids and the underlying mechanisms of dissemination of genetic structures responsible for carbapenem and other antibiotics resistance among the Acinetobacter clinical population. PMID:29434581

Technology Demonstration Summary, Chemfix Solidification/Stabilization Process, Clackamas, Oregon

EPA Science Inventory

ChemfIx's* patented stabilization/solidification technology was demonstrated at the Portable Equipment Salvage Company (PESC) site in Clackamas, Oregon, as part of the Superfund Innovative Technology Evaluation (SITE) program. The Chemfix process is designed to solidify and sta...

Mesoscale Variation of Mechanisms Contributing to Stability in Rocky Shore Communities

PubMed Central

Valdivia, Nelson; González, Andrés E.; Manzur, Tatiana; Broitman, Bernardo R.

2013-01-01

Environmental fluctuations can generate asynchronous species’ fluctuations and community stability, due to compensatory dynamics of species with different environmental tolerances. We tested this hypothesis in intertidal hard-bottom communities of north-central Chile, where a persistent upwelling centre maintains a mosaic in sea surface temperatures (SST) over 10s of kilometres along the shore. Coastal upwelling implies colder and temporally more stable SST relative to downstream sites. Uni- and multivariate analyses of multiyear timeseries of SST and species abundances showed more asynchronous fluctuations and higher stability in sites characterised by warmer and more variable SST. Nevertheless, these effects were weakened after including data obtained in sites affected by less persistent upwelling centres. Further, dominant species were more stable in sites exposed to high SST variability. The strength of other processes that can influence community stability, chiefly statistical averaging and overyielding, did not vary significantly between SST regimes. Our results provide observational evidence supporting the idea that exogenously driven compensatory dynamics and the stabilising effects of dominant species can determine the stability of ecosystems facing environmental fluctuations. PMID:23326592

Nitrogen-Doped Carbon Nanotubes Supported by Macroporous Carbon as an Efficient Enzymatic Biosensing Platform for Glucose.

PubMed

Song, Yonghai; Lu, Xingping; Li, Yi; Guo, Qiaohui; Chen, Shuiliang; Mao, Lanqun; Hou, Haoqing; Wang, Li

2016-01-19

Effective immobilization of enzymes/proteins on an electrode surface is very essential for biosensor development, but it still remains challenging because enzymes/proteins tend to form close-packed structures on the electrode surface. In this work, nitrogen-doped carbon nanotubes (NCNTs) supported by three-dimensional Kenaf Stem-derived porous carbon (3D-KSC) (denoted as 3D-KSC/NCNTs) nanocomposites were constructed as the supporting matrix to load glucose oxidase (GOD) for preparing integrated glucose biosensors. These NCNTs are vertically arrayed on the channel walls of the 3D-KSC via the chemical vapor deposition method, which could noticeably increase the effective surface area, mechanical stability, and active sites (originating from the doped nitrogen) of the nanocomposites. The integrated glucose biosensor exhibits some advantages over the traditional GOD electrodes in terms of the capability to promote the direct electron transfer of GOD, enhance the mechanical stability of the biosensor attributed to the strong interaction between NCNTs and GOD, and enlarge the specific surface area to efficiently load a large number of GODs. The as-prepared biosensor shows a good performance toward both oxygen reduction and glucose biosensing. This study essentially offers a novel approach for the development of biosensors with excellent analytical properties.

A Framework for Managing Diver Impacts on Historic Shipwrecks

NASA Astrophysics Data System (ADS)

Edney, Joanne

2016-12-01

Shipwrecks are becoming increasingly popular and, therefore important attractions for recreational scuba divers. Divers' usage of these sites has the potential to create a range of adverse impacts on their cultural heritage values. Impacts associated with recreational scuba diving include boat anchor and mooring damage, impairment of site integrity and stability, the effects of intentional and unintentional contact with shipwrecks and artifacts, as well as divers' exhaled air bubbles coming into contact with shipwrecks. While these consequences may not present a major threat in comparison to other human impacts, such as fishing activities, extractive industries or commercial salvage, their cumulative effect can be significant, particularly at sites where visitation levels are high. Unlike natural events such as storms, diver impacts can be controlled and managing these impacts is an important component of a heritage management strategy for any site. Heritage managers face the difficult challenge of, on the one hand, balancing divers' access to important underwater cultural heritage sites, and on the other hand, protecting these sites. This paper outlines the causes and nature of potential recreational diver impacts on shipwrecks, briefly describing a range of management approaches that can mitigate such impacts, and presents a framework for the management of diver impacts on cultural heritage values of historic shipwrecks. The framework is designed to assist managers in deciding on appropriate management actions and priorities for particular sites.

A decade of insights into grassland ecosystem responses to global environmental change

USGS Publications Warehouse

Borer, Elizabeth T.; Grace, James B.; Harpole, W. Stanley; MacDougall, Andrew S.; Seabloom, Eric W.

2017-01-01

Earth’s biodiversity and carbon uptake by plants, or primary productivity, are intricately interlinked, underlie many essential ecosystem processes, and depend on the interplay among environmental factors, many of which are being changed by human activities. While ecological theory generalizes across taxa and environments, most empirical tests of factors controlling diversity and productivity have been observational, single-site experiments, or meta-analyses, limiting our understanding of variation among site-level responses and tests of general mechanisms. A synthesis of results from ten years of a globally distributed, coordinated experiment, the Nutrient Network (NutNet), demonstrates that species diversity promotes ecosystem productivity and stability, and that nutrient supply and herbivory control diversity via changes in composition, including invasions of non-native species and extinction of native species. Distributed experimental networks are a powerful tool for tests and integration of multiple theories and for generating multivariate predictions about the effects of global changes on future ecosystems.

A core hSSB1–INTS complex participates in the DNA damage response

PubMed Central

Zhang, Feng; Ma, Teng; Yu, Xiaochun

2013-01-01

Summary Human single-stranded DNA-binding protein 1 (hSSB1) plays an important role in the DNA damage response and the maintenance of genomic stability. It has been shown that the core hSSB1 complex contains hSSB1, INTS3 and C9orf80. Using protein affinity purification, we have identified integrator complex subunit 6 (INTS6) as a major subunit of the core hSSB1 complex. INTS6 forms a stable complex with INTS3 and hSSB1 both in vitro and in vivo. In this complex, INTS6 directly interacts with INTS3. In response to the DNA damage response, along with INTS3 and hSSB1, INTS6 relocates to the DNA damage sites. Moreover, the hSSB1–INTS complex regulates the accumulation of RAD51 and BRCA1 at DNA damage sites and the correlated homologous recombination. PMID:23986477

Temporal Stability of the Human Skin Microbiome.

PubMed

Oh, Julia; Byrd, Allyson L; Park, Morgan; Kong, Heidi H; Segre, Julia A

2016-05-05

Biogeography and individuality shape the structural and functional composition of the human skin microbiome. To explore these factors' contribution to skin microbial community stability, we generated metagenomic sequence data from longitudinal samples collected over months and years. Analyzing these samples using a multi-kingdom, reference-based approach, we found that despite the skin's exposure to the external environment, its bacterial, fungal, and viral communities were largely stable over time. Site, individuality, and phylogeny were all determinants of stability. Foot sites exhibited the most variability; individuals differed in stability; and transience was a particular characteristic of eukaryotic viruses, which showed little site-specificity in colonization. Strain and single-nucleotide variant-level analysis showed that individuals maintain, rather than reacquire, prevalent microbes from the environment. Longitudinal stability of skin microbial communities generates hypotheses about colonization resistance and empowers clinical studies exploring alterations observed in disease states. Copyright © 2016 Elsevier Inc. All rights reserved.

EO-1 Hyperion reflectance time series at calibration and validation sites: stability and sensitivity to seasonal dynamics

Treesearch

Petya K. Entcheva Campbell; Elizabeth M. Middleton; Kurt J. Thome; Raymond F. Kokaly; Karl Fred Huemmrich; David Lagomasino; Kimberly A. Novick; Nathaniel A. Brunsell

2013-01-01

This study evaluated Earth Observing 1 (EO-1) Hyperion reflectance time series at established calibration sites to assess the instrument stability and suitability for monitoring vegetation functional parameters. Our analysis using three pseudo-invariant calibration sites in North America indicated that the reflectance time series are devoid of apparent spectral trends...

Technical area status report for waste destruction and stabilization

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

Dalton, J.D.; Harris, T.L.; DeWitt, L.M.

1993-08-01

The Office of Environmental Restoration and Waste Management (EM) was established by the Department of Energy (DOE) to direct and coordinate waste management and site remediation programs/activities throughout the DOE complex. In order to successfully achieve the goal of properly managing waste and the cleanup of the DOE sites, the EM was divided into five organizations: the Office of Planning and Resource Management (EM-10); the Office of Environmental Quality Assurance and Resource Management (EM-20); the Office of Waste Operations (EM-30); the Office of Environmental Restoration (EM-40); and the Office of Technology and Development (EM-50). The mission of the Office ofmore » Technology Development (OTD) is to develop treatment technologies for DOE`s operational and environmental restoration wastes where current treatment technologies are inadequate or not available. The Mixed Waste Integrated Program (MWIP) was created by OTD to assist in the development of treatment technologies for the DOE mixed low-level wastes (MLLW). The MWIP has established five Technical Support Groups (TSGs) whose purpose is to identify, evaluate, and develop treatment technologies within five general technical areas representing waste treatment functions from initial waste handling through generation of final waste forms. These TSGs are: (1) Front-End Waste Handling, (2) Physical/Chemical Treatment, (3) Waste Destruction and Stabilization, (4) Second-Stage Destruction and Offgas Treatment, and (5) Final Waste Forms. This report describes the functions of the Waste Destruction and Stabilization (WDS) group. Specifically, the following items are discussed: DOE waste stream identification; summary of previous efforts; summary of WDS treatment technologies; currently funded WDS activities; and recommendations for future activities.« less

Stability Mechanisms of a Thermophilic Laccase Probed by Molecular Dynamics

PubMed Central

Christensen, Niels J.; Kepp, Kasper P.

2013-01-01

Laccases are highly stable, industrially important enzymes capable of oxidizing a large range of substrates. Causes for their stability are, as for other proteins, poorly understood. In this work, multiple-seed molecular dynamics (MD) was applied to a Trametes versicolor laccase in response to variable ionic strengths, temperatures, and glycosylation status. Near-physiological conditions provided excellent agreement with the crystal structure (average RMSD ∼0.92 Å) and residual agreement with experimental B-factors. The persistence of backbone hydrogen bonds was identified as a key descriptor of structural response to environment, whereas solvent-accessibility, radius of gyration, and fluctuations were only locally relevant. Backbone hydrogen bonds decreased systematically with temperature in all simulations (∼9 per 50 K), probing structural changes associated with enthalpy-entropy compensation. Approaching T opt (∼350 K) from 300 K, this change correlated with a beginning “unzipping” of critical β-sheets. 0 M ionic strength triggered partial denucleation of the C-terminal (known experimentally to be sensitive) at 400 K, suggesting a general salt stabilization effect. In contrast, F− (but not Cl−) specifically impaired secondary structure by formation of strong hydrogen bonds with backbone NH, providing a mechanism for experimentally observed small anion destabilization, potentially remedied by site-directed mutagenesis at critical intrusion sites. N-glycosylation was found to support structural integrity by increasing persistent backbone hydrogen bonds by ∼4 across simulations, mainly via prevention of F− intrusion. Hydrogen-bond loss in distinct loop regions and ends of critical β-sheets suggest potential strategies for laboratory optimization of these industrially important enzymes. PMID:23658618

Biomechanical evaluation of oversized drilling technique on primary implant stability measured by insertion torque and resonance frequency analysis

PubMed Central

Santamaría-Arrieta, Gorka; Brizuela-Velasco, Aritza; Fernández-González, Felipe J.; Chávarri-Prado, David; Chento-Valiente, Yelko; Solaberrieta, Eneko; Diéguez-Pereira, Markel; Yurrebaso-Asúa, Jaime

2016-01-01

Background This study evaluated the influence of implant site preparation depth on primary stability measured by insertion torque and resonance frequency analysis (RFA). Material and Methods Thirty-two implant sites were prepared in eight veal rib blocks. Sixteen sites were prepared using the conventional drilling sequence recommended by the manufacturer to a working depth of 10mm. The remaining 16 sites were prepared using an oversize drilling technique (overpreparation) to a working depth of 12mm. Bone density was determined using cone beam computerized tomography (CBCT). The implants were placed and primary stability was measured by two methods: insertion torque (Ncm), and RFA (implant stability quotient [ISQ]). Results The highest torque values were achieved by the conventional drilling technique (10mm). The ANOVA test confirmed that there was a significant correlation between torque and drilling depth (p<0.05). However, no statistically significant differences were obtained between ISQ values at 10 or 12 mm drilling depths (p>0.05) at either measurement direction (cortical and medullar). No statistical relation between torque and ISQ values was identified, or between bone density and primary stability (p >0.05). Conclusions Vertical overpreparation of the implant bed will obtain lower insertion torque values, but does not produce statistically significant differences in ISQ values. Key words:Implant stability quotient, overdrilling, primary stability, resonance frequency analysis, torque. PMID:27398182

Technology Demonstration Summary Site Program Demonstration Test Soliditech Inc Solidification-stabilization Process

EPA Science Inventory

The major objective of the Soliditech, Inc., SITE demonstration was to develop reliable performance and cost information about the Soliditech solidification, stabilization technology. The Soliditech process mixes hazardous waste materials with Portland cement or pozzolanic m...

APPLICATIONS ANALYSIS REPORT: SITE PROGRAM DEMONSTRATION TEST SOLIDITECH, INC. SOLIDIFICATION/ STABILIZATION PROCESS

EPA Science Inventory

This Applications Analysis Report evaluates the Soliditech, Inc., solidification/ stabilization process for the on-site treatment of waste materials. The Soliditech process mixes and chemically treats waste material with Urrichem (a proprietary reagent), additives, pozzolanic mat...

Postoperative Aortic Neck Dilation: Myth or Fact?

PubMed

Ribner, A S; Tassiopoulos, A K

2018-06-01

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

Top-down control in a patchy environment: revisiting the stabilizing role of food-dependent predator dispersal.

PubMed

Morozov, Andrew; Sen, Moitri; Banerjee, Malay

2012-02-01

In this paper, we revisit the stabilizing role that predator dispersal and aggregation have in the top-down regulation of predator-prey systems in a heterogeneous environment. We consider an environment consisting of sites interconnected by dispersal, and propose a novel mechanism of stabilization for the case with a non-sigmoid functional response of predators. We assume that the carrying capacity of the prey is infinitely large in each site, and show that successful top-down regulation of this otherwise globally unstable system is made possible through an interplay between the unevenness of prey fitness across the sites and the rapid food-dependent migration of predators. We argue that this mechanism of stabilization is different from those previously reported in the literature: in particular, it requires a high degree of synchronicity in local oscillations of species densities across the sites. Prey outbreaks take place synchronously, but the unevenness of prey growth rates across the sites results in a pronounced difference in the species densities, and so the predator quickly disperses to the sites with the highest prey abundances. For this reason, the consumption of prey mostly takes place in the sites with high densities of prey, which assures an efficient suppression of outbreaks. Furthermore, when the total size of prey population is low, the distribution of both species among the sites becomes more even, and this prevents overconsumption of the prey by the predator. Finally, we put forward the hypothesis that this mechanism, when considered in a tri-trophic plankton community in the water column, can explain the stability of the nutrient-rich low-chlorophyll open ocean regions. Copyright © 2011 Elsevier Inc. All rights reserved.

Implementation of Biotic Integrity Metrics to Identify the Effects of Land Use on the Diversity of Wetlands

NASA Astrophysics Data System (ADS)

Mills, L. D.; Hamilton, S. W.; Schiller, J. R.

2005-05-01

To identify critical biological measures of wetland health, we studied twelve wetlands in north-central Tennessee and south-central Kentucky, six impacted by row crop agriculture and six unimpacted. Aquatic macroinvertebrate were collected using 10.2 cm clear PVC pipe funnel traps and wire minnow traps. Seven samples were collected from each site between May 19 and August 8, 2004. Qualitative samples (one person-hour) were collected with dip nets from each wetland to correspond with the early July trap samples. Water quality parameters measured included dissolved oxygen, pH, temperature, specific conductance, and turbidity with multiparameter aquatic probe and nephlometer. Macroinvertebrates from three sets of samples for each site were identified, when possible, to genus. The number of organism collected per trap-period per site ranged from 43 to 2224. Fifty-six taxa were identified. Generally, natural areas showed greater species richness, diversity and evenness than agricultural sites. Dipterans, primarily chironomids, were the most dominant assemblages. The three most abundant predatory orders, Coleoptera, Odonata and Hemiptera, showed alternating patterns of dominance. Habitat stability and greater vegetative complexity, which are impacted by surrounding agricultural practices, appear to be strongly related to higher species diversity.

2008 Weather and Aeolian Sand-Transport Data from the Colorado River Corridor, Grand Canyon, Arizona

USGS Publications Warehouse

Draut, Amy E.; Sondossi, Hoda A.; Hazel, Joseph E.; Andrews, Timothy; Fairley, Helen C.; Brown, Christopher R.; Vanaman, Karen M.

2009-01-01

This report presents measurements of weather parameters and aeolian (windblown) sand transport made in 2008 near selected archaeological sites in the Colorado River corridor through Grand Canyon, Ariz. The quantitative methods and data discussed here form a basis for monitoring ecosystem processes that affect archeological-site stability. Combined with forthcoming work to evaluate landscape evolution at nearby archaeological sites, these data can be used to document the relationship between physical processes, including weather and aeolian sand transport, and their effects on the physical integrity of archaeological sites. Data collected in 2008 reveal event- and seasonal-scale variations in rainfall, wind, temperature, humidity, and barometric pressure. Broad seasonal changes in aeolian sediment flux are also apparent at most study sites. The continuation of monitoring that began in 2007, and installation of equipment at several new sites in early 2008, allowed evaluation of the effects of the March 2008 high-flow experiment (HFE) on aeolian sand transport. At two of the nine sites studied, spring and summer winds reworked 2008 HFE sandbars to form new aeolian dunes, at which sand moved inland toward larger, well-established dune fields. At the other seven study sites, neither dune formation nor enhanced sand transport after the HFE were observed. At several of those sites, dominant wind directions in spring 2008 were not oriented such that much HFE sand would have moved inland; at other sites, lack of increased inland sand flux is attributable to lack of sandbar enlargement near the study sites or to inhibition of sand movement by vegetation or local topography.

Genotype-environment interaction and stability in ten-year height growth of Norway spruce Clones (Picea abies Karst.).

Treesearch

J.B. St. Clair; J. Kleinschmit

1986-01-01

Norway spruce cuttings of 40 clones were tested on seven contrasting sites in northern Germany. Analysis of variance for ten-year height growth indicate a highly significant clone x site interaction. This interaction may be reduced by selection of stable clones. Several measures of stability were calculated and discussed. Characterization of sites by the method of...

Stability of GNSS Monumentation: Analysis of Co-Located Monuments in the UNAVCO Plate Boundary Observatory

NASA Astrophysics Data System (ADS)

Blume, F.; Herring, T.; Mattioli, G. S.; Feaux, K.; Walls, C. P.; Austin, K. E.; Dittmann, S. T.

2017-12-01

Geodetic-quality permanent GNSS stations have used a number of different monument styles for the purpose of ensuring that the motions of the GNSS antenna reflect those of the Earth's crust while minimizing non-tectonic motions near the surface. Monuments range from simple masts mounted on buildings or drilled into bedrock, costing a few hundred dollars to machine-drilled-braced monuments in soil costing tens of thousands. The stability of an individual monument will depend on its design, the construction techniques used to install it, and the local surface geology where it is installed. Previous studies have separately investigated pairs of identical monuments at a single site, monument type performance using global statistical analysis, and multiple monument styles at a single site, yet the stability of different monument types in similar geologic conditions has not been adequately determined. To better characterize the stability of various monument styles in diverse geologic conditions UNAVCO constructed two additional monuments at five existing PBO stations in 2013. Deep drilled-braced, short drilled-braced, and single mast type monuments were installed at sites with bedrock at the surface; deep drilled-braced, short driven-braced and pillar type monuments were installed at sites with alluvium or soil at the surface. The sites include a variety of geographic, hydrologic, and geologic conditions. Data collected from the PBO Multi-Monument Experiment have been analyzed using a variety of methods. Each site is characterized using quality-control parameters such as multipath, signal-to-noise and previously determined seasonal variations. High-precision processing by PBO Analysis Centers with GAMIT and GIPSY use regional and global schemes and yield time-series with millimeter-level that determine noise content, overall site stability relative to other PBO sites and differential motions between the individual monuments. Sub-millimeter results from single-frequency short-baseline processing efforts show further details of monument performance. Results show that while local site characteristics may dominate time-series stability, braced monuments outperform pillars in sediments, and an inexpensive mast installed in bedrock can be as stable as an expensive drilled-braced monument.

Magnetism and high magnetic-field-induced stability of alloy carbides in Fe-based materials.

PubMed

Hou, T P; Wu, K M; Liu, W M; Peet, M J; Hulme-Smith, C N; Guo, L; Zhuang, L

2018-02-14

Understanding the nature of the magnetic-field-induced precipitation behaviors represents a major step forward towards unravelling the real nature of interesting phenomena in Fe-based alloys and especially towards solving the key materials problem for the development of fusion energy. Experimental results indicate that the applied high magnetic field effectively promotes the precipitation of M 23 C 6 carbides. We build an integrated method, which breaks through the limitations of zero temperature and zero external field, to concentrate on the dependence of the stability induced by the magnetic effect, excluding the thermal effect. We investigate the intimate relationship between the external field and the origins of various magnetics structural characteristics, which are derived from the interactions among the various Wyckoff sites of iron atoms, antiparallel spin of chromium and Fe-C bond distances. The high-magnetic-field-induced exchange coupling increases with the strength of the external field, which then causes an increase in the parallel magnetic moment. The stability of the alloy carbide M 23 C 6 is more dependent on external field effects than thermal effects, whereas that of M 2 C, M 3 C and M 7 C 3 is mainly determined by thermal effects.

Meshfree Modeling of Munitions Penetration in Soils

DTIC Science & Technology

2017-04-01

discretization ...................... 8 Figure 2. Nodal smoothing domain for the modified stabilized nonconforming nodal integration...projectile ............................................................................................... 36 Figure 17. Discretization for the...List of Acronyms DEM: discrete element methods FEM: finite element methods MSNNI: modified stabilized nonconforming nodal integration RK

Contributions of all 20 amino acids at site 96 to the stability and structure of T4 lysozyme

PubMed Central

Mooers, Blaine H M; Baase, Walter A; Wray, Jonathan W; Matthews, Brian W

2009-01-01

To try to resolve the loss of stability in the temperature-sensitive mutant of T4 lysozyme, Arg 96 → His, all of the remaining 18 naturally occurring amino acids were substituted at site 96. Also, in response to suggestions that the charged residues Lys85 and Asp89, which are 5–8 Å away, may have important effects, each of these amino acids was replaced with alanine. Crystal structures were determined for many of the variants. With the exception of the tryptophan and valine mutants R96W and R96V, the crystallographic analysis shows that the substituted side chain following the path of Arg96 in wildtype (WT). The melting temperatures of the variants decrease by up to ∼16°C with WT being most stable. There are two site 96 replacements, with lysine or glutamine, that leave the stability close to that of WT. The only element that the side chains of these residues have in common with the WT arginine is the set of three carbon atoms at the Cα, Cβ, and Cγ positions. Although each side chain is long and flexible with a polar group at the distal position, the details of the hydrogen bonding to the rest of the protein differ in each case. Also, the glutamine replacement lacks a positive charge. This shows that there is some adaptability in achieving full stabilization at this site. At the other extreme, to be maximally destabilizing a mutation at site 96 must not only eliminate favorable interactions but also introduce an unfavorable element such as steric strain or a hydrogen-bonding group that remains unsatisfied. Overall, the study highlights the essential need for atomic resolution site-specific structural information to understand and to predict the stability of mutant proteins. It can be very misleading to simply assume that conservative amino acid substitutions cause small changes in stability, whereas large stability changes are associated with nonconservative replacements. PMID:19384988

NiCo2O4 nanosheets in-situ grown on three dimensional porous Ni film current collectors as integrated electrodes for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Wang, Tao; Guo, Ying; Zhao, Bo; Yu, Shuhui; Yang, Hai-Peng; Lu, Daniel; Fu, Xian-Zhu; Sun, Rong; Wong, Ching-Ping

2015-07-01

Three dimensional interconnected hierarchical porous Ni films are easily fabricated as effective current collectors through hydrogen bubble template electrochemical deposition. The binder-free integrated electrodes of spinel NiCo2O4 nanosheets directly coated the three dimensional porous Ni films are facilely obtained through successively electrochemical co-deposition of Ni/Co alloy layer then followed by subsequent annealing at 350 °C in air. Compared with NiCo2O4 nanosheets on smooth Ni foil or porous NiO/Ni film electrodes, the porous NiCo2O4/Ni integrated film electrodes for supercapacitors demonstrate remarkably higher area specific capacitance. The porous NiCo2O4/Ni film electrodes also exhibit excellent rate capability and cycling stability. The super electrochemical capacitive performances are attributed to the unique integrated architecture of NiCo2O4 nanosheets in-situ grown on three dimensional continuous hierarchical porous Ni collector collectors, which could provide large electrode-electrolyte interface area, high active sites, low contact resistance between current collector and active materials, fast electron conduction and ion/electrolyte diffusion.

Structural and functional dissection reveals distinct roles of Ca2+-binding sites in the giant adhesin SiiE of Salmonella enterica

PubMed Central

Klingl, Stefan; Sandmann, Achim; Taccardi, Nicola; Sticht, Heinrich; Muller, Yves A.; Hensel, Michael

2017-01-01

The giant non-fimbrial adhesin SiiE of Salmonella enterica mediates the first contact to the apical site of epithelial cells and enables subsequent invasion. SiiE is a 595 kDa protein composed of 53 repetitive bacterial immunoglobulin (BIg) domains and the only known substrate of the SPI4-encoded type 1 secretion system (T1SS). The crystal structure of BIg50-52 of SiiE revealed two distinct Ca2+-binding sites per BIg domain formed by conserved aspartate or glutamate residues. In a mutational analysis Ca2+-binding sites were disrupted by aspartate to serine exchange at various positions in the BIg domains of SiiE. Amounts of secreted SiiE diminish with a decreasing number of intact Ca2+-binding sites. BIg domains of SiiE contain distinct Ca2+-binding sites, with type I sites being similar to other T1SS-secreted proteins and type II sites newly identified in SiiE. We functionally and structurally dissected the roles of type I and type II Ca2+-binding sites in SiiE, as well as the importance of Ca2+-binding sites in various positions of SiiE. Type I Ca2+-binding sites were critical for efficient secretion of SiiE and a decreasing number of type I sites correlated with reduced secretion. Type II sites were less important for secretion, stability and surface expression of SiiE, however integrity of type II sites in the C-terminal portion was required for the function of SiiE in mediating adhesion and invasion. PMID:28558023

Overpressure and consolidation near the seafloor of Brazos-Trinity Basin IV, northwest deepwater Gulf of Mexico

NASA Astrophysics Data System (ADS)

Schneider, Julia; Flemings, Peter B.; Dugan, Brandon; Long, Hui; Germaine, John T.

2009-05-01

Pore water overpressures (u*) within mudstones beneath Brazos-Trinity Basin IV (deepwater Gulf of Mexico, offshore Texas) are greater than 70% of the hydrostatic vertical effective stress (σ'vh) [λ* = 0.7 = (u*/σ'vh)]. These results are compatible with recent observations that suggest sedimentation rates in this region are rapid (6 mm/a). We compare the petrophysical properties and pore pressures within a 127-m-thick package of mudstone penetrated at two locations: Integrated Ocean Drilling Program (IODP) sites U1319 and U1320. Site U1319 is at the margin of Brazos-Trinity Basin IV, whereas Site U1320 lies at its center, beneath 180 m of turbidite fill. Experimentally derived preconsolidation stresses and an in situ pore pressure measurement record overpressure at Site U1319 and Site U1320 (λ* ˜ 0.2 to 0.8 and λ* ˜ 0.8, respectively). We use these data to define an average vertical effective stress gradient. Assuming that void ratio (e) is proportional to the log of vertical effective stress (σ'v), we predict pore pressures (u) throughout the mudstone at both sites using bulk density data. Overpressures are greater at Site U1320 due to rapid deposition of the overlying turbidites. However, a large fraction of the overpressure induced by the turbidite load applied at Site U1320 has dissipated by drainage into the overlying basin fill. High overpressures near the seafloor drive shallow fluid flow, reduce slope stability, and may explain large submarine landslides.

DFT study on stability and H2 adsorption activity of bimetallic Au79-nPdn (n = 1-55) clusters

NASA Astrophysics Data System (ADS)

Liu, Xuejing; Tian, Dongxu; Meng, Changgong

2013-03-01

The stability and H2 adsorption activity of bimetallic Au79-nPdn (n = 1-55) clusters were studied by density functional theory with GGA-PW91 functional. The stability order for four Pd substitution types is face > mid-edge > corner > edge, and the stability is improved with increasing Pd content. In contrast with the stability order, H2 adsorption activity is corner ≈ edge > mid-edge > face. The Au36Pd43 (3) with Au:Pd ≈ 1:1 ratio and twenty-four Pd substitutions at (1 1 1) facets and nineteen Pd substitutions at subshell sites shows high stability and H2 non-activated dissociation activity. The partial density of d-states and d band center revealed that the electronic properties are closely associated with the geometric characteristic and adsorption activity. Correlating the d band center ɛd and the adsorption energies, the ɛd order agrees with the adsorption activity that the Pd substitution at edge and corner sites are more active than at face and mid-edge sites.

Design of electrolyzer for carbon dioxide conversion to fuels and chemicals

NASA Astrophysics Data System (ADS)

Rosen, Jonathan S.

The stabilization of global atmospheric CO2 levels requires a transition towards a renewable energy based economy as well as methods for handling current CO2 output from fossil fuels. Challenges with renewable energy intermittency have thus far limited the use of these alternative energy sources to only a fraction of the current energy portfolio. To enable more widespread use of renewable energy systems, methods of large scale energy storage must be developed to store excess renewable energy when demand is low and allow for combined use of energy storage and renewable systems when demand is high. To date, no one technique has demonstrated energy storage methods on the gigawatt scale needed for integration with renewable sources; therefore the development of suitable energy storage technologies, such as CO2 electrolysis to fuels is needed. In this work, research efforts have focused on two major thrusts related to electrochemical methods of CO 2 conversion to fuels. The first thrust focuses on the synthesis and design of highly efficient anode and cathode catalysts with emphasis on understanding structure-property relationships. A second thrust focuses on the design of novel electrochemical devices for CO2 conversion and integration of synthesized materials into flow cell systems. On the anode side, the synthesis of highly active catalysts using abundant transition metals is crucial to reducing capital costs and enabling widespread use of electrochemical CO2 conversion devices. Highly active mesoporous Co3O4 and metal-substituted Co3O4 water oxidation catalysts were designed to investigate the role of the spinel structure on water oxidation activity. Further analysis of metal substituted samples reveal the importance of the octahedral sites in the spinel structure, which was later used to design an Mg-Co3O4 sample with improved water oxidation activity. The design of efficient cathode materials which can selectivity reduce CO2 to fuels and chemicals is critical to the widespread use of CO2 electrolysis. A nanoporous Ag material was synthesized through a dealloying technique able to operate with less than 0.5 V overpotential and high selectivity towards CO. CO is a valuable intermediate chemical which can used in Fischer-Tropsch or Gas-to-liquids technologies to produce liquids fuels. A detailed investigation of nanostructured Ag catalysts found stepped sites to be responsible for enhanced CO2 reduction activity due to improved stabilization of the COOH intermediate on the catalyst surface. In addition, an low-cost Zn dendrite electrocatalyst was developed using an electroplating technique. Low coordinated sites formed through electrodeposition demonstrated the suppression of hydrogen evolution while maintaining CO activity. The Zn dendrite electrocatalyst was further examined using a newly developed in situ X-ray absorption technique able to probe catalyst stability and crystalline structure under CO2 reduction operating conditions. A final hurdle in the realization of CO2 electrolysis technologies is the integration of catalysts into working flow cell devices. To address this issue and enable testing in a practical system, a highly efficient and robust CO2 electrolysis flow cell was designed including the scale up of the previous nanoporous Ag synthesis procedure. Using the modified porous Ag catalyst, currents in the Amp regime were demonstrated approaching rates needed for energy storage applications. Stability on the order of days was successfully demonstrated due to use of robust system components and conditions suitable for process scale up.

Hydration Changes upon DNA Folding Studied by Osmotic Stress Experiments

PubMed Central

Nakano, Shu-ichi; Yamaguchi, Daisuke; Tateishi-Karimata, Hisae; Miyoshi, Daisuke; Sugimoto, Naoki

2012-01-01

The thermal stability of nucleic acid structures is perturbed under the conditions that mimic the intracellular environment, typically rich in inert components and under osmotic stress. We now describe the thermodynamic stability of DNA oligonucleotide structures in the presence of high background concentrations of neutral cosolutes. Small cosolutes destabilize the basepair structures, and the DNA structures consisting of the same nearest-neighbor composition show similar thermodynamic parameters in the presence of various types of cosolutes. The osmotic stress experiments reveal that water binding to flexible loops, unstable mismatches, and an abasic site upon DNA folding are almost negligible, whereas the binding to stable mismatch pairs is significant. The studies using the basepair-mimic nucleosides and the peptide nucleic acid suggest that the sugar-phosphate backbone and the integrity of the basepair conformation make important contributions to the binding of water molecules to the DNA bases and helical grooves. The study of the DNA hydration provides the basis for understanding and predicting nucleic acid structures in nonaqueous solvent systems. PMID:22735531

A metropolitan airport disaster plan--coordination of a multihospital response to provide on-site resuscitation and stabilization before evacuation.

PubMed

Dove, D B; Del Guercio, L R; Stahl, W M; Star, L D; Abelson, L C

1982-07-01

At the John F. Kennedy International Airport in New York City, disaster planning has been an integral part of the airport operations for the past 20 years. The medical component of this disaster planning has focused around the Medical Office at JFK. Through this office, on-site emergency medical teams have been established and trained from all ranks of airport personnel. Following the crash of a Boeing 727 aircraft in 1975, a new concept was added to disaster planning for JFK, which involves bringing the hospital, its facilities, and its personnel to the scene. A new piece of equipment, known as Emergency Mobile Hospital, was developed with the cooperation of the airlines, the operating authority of the airport, and other interested parties. Two such vehicles are now in constant readiness at the airport, and together provide two operating rooms, 12 monitored ICU beds, a 16-bed burn unit, and 72 other beds to be used for on-site stabilization of critically ill patients, before transfer to a definitive care facility. Under the auspices of a single area medical school (New York Medical College) and its affiliated departments of surgery, trauma teams are made available to be airlifted to the scene within 30 minutes of notification. Additional medical teams from other medical school hospitals serve as backup support. The principle of bringing the hospital to the emergency, and of assembling trauma teams for the initial phase, remains the same for Kennedy Airport as for that of any other metropolitan airport.

Promoting the Adsorption of Metal Ions on Kaolinite by Defect Sites: A Molecular Dynamics Study

PubMed Central

Li, Xiong; Li, Hang; Yang, Gang

2015-01-01

Defect sites exist abundantly in minerals and play a crucial role for a variety of important processes. Here molecular dynamics simulations are used to comprehensively investigate the adsorption behaviors, stabilities and mechanisms of metal ions on defective minerals, considering different ionic concentrations, defect sizes and contents. Outer-sphere adsorbed Pb2+ ions predominate for all models (regular and defective), while inner-sphere Na+ ions, which exist sporadically only at concentrated solutions for regular models, govern the adsorption for all defective models. Adsorption quantities and stabilities of metal ions on kaolinite are fundamentally promoted by defect sites, thus explaining the experimental observations. Defect sites improve the stabilities of both inner- and outer-sphere adsorption, and (quasi) inner-sphere Pb2+ ions emerge only at defect sites that reinforce the interactions. Adsorption configurations are greatly altered by defect sites but respond weakly by changing defect sizes or contents. Both adsorption quantities and stabilities are enhanced by increasing defect sizes or contents, while ionic concentrations mainly affect adsorption quantities. We also find that adsorption of metal ions and anions can be promoted by each other and proceeds in a collaborative mechanism. Results thus obtained are beneficial to comprehend related processes for all types of minerals. PMID:26403873

Bioassessment in nonperennial streams: Hydrologic stability influences assessment validity

NASA Astrophysics Data System (ADS)

Mazor, R. D.; Stein, E. D.; Schiff, K.; Ode, P.; Rehn, A.

2011-12-01

Nonperennial streams pose a challenge for bioassessment, as assessment tools developed in perennial streams may not work in these systems. For example, indices of biotic integrity (IBIs) developed in perennial streams may give improper indications of impairment in nonperennial streams, or may be unstable. We sampled benthic macroinvertebrates from 12 nonperennial streams in southern California. In addition, we deployed loggers to obtain continuous measures of flow. 3 sites were revisited over 2 years. For each site, we calculated several metrics, IBIs, and O/E scores to determine if assessments were consistent and valid throughout the summer. Hydrology varied widely among the streams, with several streams drying between sampling events. IBIs suggested good ecological health at the beginning of the study, but declined sharply at some sites. Multivariate ordination suggested that, despite differences among sites, changes in community structure were similar, with shifts from Ephemeroptera, Plecoptera, and Trichoptera to Coleoptera and more tolerant organisms. Site revisits revealed a surprising level of variability, as 2 of the 3 revisited sites had perennial or near-perennial flow in the second year of sampling. IBI scores were more consistent in streams with stable hydrographs than in those with strongly intermittent hydrographs. These results suggest that nonperennial streams can be monitored successfully, but they may require short index periods and distinct metrics from those used in perennial streams. In addition, better approaches to mapping nonperennial streams are required.

The SKI repository performance assessment project Site-94

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

Andersson, J.; Dverstorp, B.; Sjoeblom, R.

1995-12-01

SITE-94 is a research project conducted as a performance assessment of a hypothetical repository for spent nuclear fuel, but with real pre-excavation data from a real site. The geosphere, the engineered barriers and the processes for radionuclide release and transport comprise an integrated interdependent system, which is described by an influence diagram (PID) that reflects how different Features, Events or Processes (FEPs) inside the system interact. Site evaluation is used to determine information of transport paths in the geosphere and to deliver information on geosphere interaction with the engineered barriers. A three-dimensional geological structure model of the site as wellmore » as alternative conceptual models consistent with the existing hydrological field data, have been analyzed. Groundwater chemistry is evaluated and a model, fairly consistent with the flow model, for the origin of the different waters has been developed. The geological structure model is also used for analyzing the mechanical stability of the site. Several phenomena of relevance for copper corrosion in a repository environment have been investigated. For Reference Case conditions and regardless of flow variability, output is dominated by I-129, which, for a single canister, may give rise to drinking water well doses in the order of 10{sup -6}Sv/yr. Finally, it appears that the procedures involved in the development of influence diagrams may be a promising tool for quality assurance of performance assessments.« less

miREE: miRNA recognition elements ensemble

PubMed Central

2011-01-01

Background Computational methods for microRNA target prediction are a fundamental step to understand the miRNA role in gene regulation, a key process in molecular biology. In this paper we present miREE, a novel microRNA target prediction tool. miREE is an ensemble of two parts entailing complementary but integrated roles in the prediction. The Ab-Initio module leverages upon a genetic algorithmic approach to generate a set of candidate sites on the basis of their microRNA-mRNA duplex stability properties. Then, a Support Vector Machine (SVM) learning module evaluates the impact of microRNA recognition elements on the target gene. As a result the prediction takes into account information regarding both miRNA-target structural stability and accessibility. Results The proposed method significantly improves the state-of-the-art prediction tools in terms of accuracy with a better balance between specificity and sensitivity, as demonstrated by the experiments conducted on several large datasets across different species. miREE achieves this result by tackling two of the main challenges of current prediction tools: (1) The reduced number of false positives for the Ab-Initio part thanks to the integration of a machine learning module (2) the specificity of the machine learning part, obtained through an innovative technique for rich and representative negative records generation. The validation was conducted on experimental datasets where the miRNA:mRNA interactions had been obtained through (1) direct validation where even the binding site is provided, or through (2) indirect validation, based on gene expression variations obtained from high-throughput experiments where the specific interaction is not validated in detail and consequently the specific binding site is not provided. Conclusions The coupling of two parts: a sensitive Ab-Initio module and a selective machine learning part capable of recognizing the false positives, leads to an improved balance between sensitivity and specificity. miREE obtains a reasonable trade-off between filtering false positives and identifying targets. miREE tool is available online at http://didattica-online.polito.it/eda/miREE/ PMID:22115078

TECHNOLOGY EVALUATION REPORT: CHEMFIX TECHNOLOGIES, INC. - SOLIDIFICATION/STABILIZATION PROCESS - CLACKAMAS, OREGON - VOLUME I

EPA Science Inventory

The CHEMFIX solidification/stabilization process was evaluated in the U.S. Environment Protection Agency's SITE program. Waste from an uncontrolled hazardous waste site was treated by the CHEMFIX process and subjected to a variety of physical and chemical test methods. Physical t...

TECHNOLOGY EVALUATION REPORT: CHEMFIX TECHNOLOGIES, INC. - SOLIDIFICATION/STABILIZATION PROCESS - CLACKAMAS, OREGON - VOLUME II

EPA Science Inventory

The CHEMFIX solidification/stabilization process was evaluated in the U.S. Environmental Protection Agency's SITE program. Waste from an uncontrolled hazardous waste site was treated by the CHEMFIX process and subjected to a variety of physical and chemical test methods. Physical...

Solidification/Stabilization Resource Guide

EPA Pesticide Factsheets

This Solidification/Stabilization Resource Guide is intended to inform site cleanup managers of recently-published materials such as field reports and guidance documents that address issues relevant to solidification/stabilization technologies.

Effects of Vegetation Structure on the Location of Lion Kill Sites in African Thicket

PubMed Central

Davies, Andrew B.; Tambling, Craig J.; Kerley, Graham I. H.; Asner, Gregory P.

2016-01-01

Predator-prey relationships are integral to ecosystem stability and functioning. These relationships are, however, difficult to maintain in protected areas where large predators are increasingly being reintroduced and confined. Where predators make kills has a profound influence on their role in ecosystems, but the relative importance of environmental variables in determining kill sites, and how these might vary across ecosystems is poorly known. We investigated kill sites for lions in South Africa’s thicket biome, testing the importance of vegetation structure for kill site locations compared to other environmental variables. Kill sites were located over four years using GPS telemetry and compared to non-kill sites that had been occupied by lions, as well as to random sites within lion ranges. Measurements of 3D vegetation structure obtained from Light Detection and Ranging (LiDAR) were used to calculate the visible area (viewshed) around each site and, along with wind and moonlight data, used to compare kill sites between lion sexes, prey species and prey sexes. Viewshed area was the most important predictor of kill sites (sites in dense vegetation were twice as likely to be kill sites compared to open areas), followed by wind speed and, less so, moonlight. Kill sites for different prey species varied with vegetation structure, and male prey were killed when wind speeds were higher compared to female prey of the same species. Our results demonstrate that vegetation structure is an important component of predator-prey interactions, with varying effects across ecosystems. Such differences require consideration in terms of the ecological roles performed by predators, and in predator and prey conservation. PMID:26910832

DNA transformations of Candida tropicalis with replicating and integrative vectors.

PubMed

Sanglard, D; Fiechter, A

1992-12-01

The alkane-assimilating yeast Candida tropicalis was used as a host for DNA transformations. A stable ade2 mutant (Ha900) obtained by UV-mutagenesis was used as a recipient for different vectors carrying selectable markers. A first vector, pMK16, that was developed for the transformation of C. albicans and carries an ADE2 gene marker and a Candida autonomously replicating sequence (CARS) element promoting autonomous replication, was compatible for transforming Ha900. Two transformant types were observed: (i) pink transformants which easily lose pMK16 under non-selective growth conditions; (ii) white transformants, in which the same plasmid exhibited a higher mitotic stability. In both cases pMK16 could be rescued from these cells in Escherichia coli. A second vector, pADE2, containing the isolated C. tropicalis ADE2, gene, was used to transform Ha900. This vector integrated in the yeast genome at homologous sites of the ade2 locus. Different integration types were observed at one or both ade2 alleles in single or in tandem repeats.

Labeling Biomolecules with Radiorhenium - a Review of the Bifunctional Chelators

PubMed Central

Liu, Guozheng; Hnatowich, Donald J.

2007-01-01

For radiotherapy, biomolecules such as intact antibodies, antibody fragments, peptides, DNAs and other oligomers have all been labeled with radiorhenium (186Re and 188Re). Three different approaches have been employed that may be referred to as direct, indirect and integral labeling. Direct labeling applies to proteins and involves the initial reduction of endogenous disulfide bridges to provide chelation sites. Indirect labeling can apply to most biomolecules and involves the initial attachment of an exogenous chelator. Finally, integral labeling is a special case applying only to small molecules in which the metallic radionuclide serves to link two parts of a biomolecule together in forming the labeled complex. While the number of varieties for the direct and integral radiolabeling approaches is rather limited, a fairly large and diverse number of chelators have been reported in the case of indirect labeling. Our objective herein is to provide an overview of the various chelators that have been used in the indirect labeling of biomolecules with radiorhenium, including details on the labeling procedures, the stability of the radiolabel and, where possible, the influence of the label on biological properties. PMID:17504162

Spatial and temporal analyses for multiscale monitoring of landslides: Examples from Northern Ireland

NASA Astrophysics Data System (ADS)

Bell, Andrew; McKinley, Jennifer; Hughes, David

2013-04-01

Landslides in the form of debris flows, large scale rotational features and composite mudflows impact transport corridors cutting off local communities and in some instances result in loss of life. This study presents landslide monitoring methods used for predicting and characterising landslide activity along transport corridors. A variety of approaches are discussed: desk based risk assessment of slopes using Geographical Information Systems (GIS); Aerial LiDAR surveys and Terrestrial LiDAR monitoring and field instrumentation of selected sites. A GIS based case study is discussed which provides risk assessment for the potential of slope stability issues. Layers incorporated within the system include Digital Elevation Model (DEM), slope, aspect, solid and drift geology and groundwater conditions. Additional datasets include consequence of failure. These are combined within a risk model, presented as likelihoods of failure. This integrated spatial approach for slope risk assessment provides the user with a preliminary risk assessment of sites. An innovative "Flexviewer" web-based server interface allows users to view data without needing advanced GIS techniques to gather information about selected areas. On a macro landscape scale, Aerial LiDAR (ALS) surveys are used for the characterisation of landslides from the surrounding terrain. DEMs are generated along with terrain derivatives: slope, curvature and various measures of terrain roughness. Spatial analysis of terrain morphological parameters allow characterisation of slope stability issues and are used to predict areas of potential failure or recently failure terrain. On a local scale ground monitoring approaches are employed for the monitoring of changes in selected slopes using ALS and risk assessment approaches. Results are shown from on-going bimonthly Terrestrial LiDAR (TLS) monitoring of the slope within a site specific geodectically referenced network. This has allowed a classification of changes in the slopes with DEMs of difference showing areas of recent movement, erosion and deposition. In addition, changes in the structure of the slope characterised by DEM of difference and morphological parameters in the form of roughness, slope and curvature measures are progressively linked to failures indicated from temporal DEM monitoring. Preliminary results are presented for a case site at Straidkilly Point, Glenarm, Co. Antrim, Northern Ireland, illustrating multiple approaches to the spatial and temporal monitoring of landslides. These indicate how spatial morphological approaches and risk assessment frameworks coupled with TLS monitoring and field instrumentation enable characterisation and prediction of potential areas of slope stability issues. On site weather instrumentation and piezometers document changes in pore water pressures resulting in site-specific information with geotechnical observations parameterised within the temporal LiDAR monitoring. This provides a multifaceted approach to the characterisation and analysis of slope stability issues. The presented methodology of multiscale datasets and surveying approaches utilising spatial parameters and risk index mapping enables a more comprehensive and effective prediction of landslides resulting in effective characterisation and remediation strategies.

Design of an unified chassis controller for rollover prevention, manoeuvrability and lateral stability

NASA Astrophysics Data System (ADS)

Yoon, Jangyeol; Yim, Seongjin; Cho, Wanki; Koo, Bongyeong; Yi, Kyongsu

2010-11-01

This paper describes a unified chassis control (UCC) strategy to prevent vehicle rollover and improve both manoeuvrability and lateral stability. Since previous researches on rollover prevention are only focused on the reduction of lateral acceleration, the manoeuvrability and lateral stability cannot be guaranteed. For this reason, it is necessary to design a UCC controller to prevent rollover and improve lateral stability by integrating electronic stability control, active front steering and continuous damping control. This integration is performed through switching among several control modes and a simulation is performed to validate the proposed method. Simulation results indicate that a significant improvement in rollover prevention, manoeuvrability and lateral stability can be expected from the proposed UCC system.

EPA SITE DEMONSTRATION OF THE INTERNATIONAL WASTE TECHNOLOGIES/GEO-CON IN SITU STABILIZATION/ SOLIDIFICATION PROCESS

EPA Science Inventory

This paper presents an EPA evaluation of the first field demonstration of an in situ stabilization/solidification process for contaminated soil under the EPA Superfund Innovative Technology Evaluation (SITE) program. Demonstration of this process was a joint effort of two vendors...

Technology Demonstration Summary: International Waste Technologies In Situ Stabilization/Solidification, Hialeah, Florida

EPA Science Inventory

An evaluation was performed of the International Waste Technologies (IWT) HWT-20 additive and the Geo-Con, Inc. deep-soil-mixing equipment for an in situ stabilization/solidification process and its applicability as an on-site treatment method for waste site cleanup. The analysis...

Metal stabilization of collagen and de novo designed mimetic peptides

PubMed Central

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

2017-01-01

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

Predictability of dune activity in real dune fields under unidirectional wind regimes

NASA Astrophysics Data System (ADS)

Barchyn, Thomas E.; Hugenholtz, Chris H.

2015-02-01

We present an analysis of 10 dune fields to test a model-derived hypothesis of dune field activity. The hypothesis suggests that a quantifiable threshold exists for stabilization in unidirectional wind regimes: active dunes have slipface deposition rates that exceed the vegetation deposition tolerance, and stabilizing dunes have the opposite. We quantified aeolian sand flux, slipface geometry, and vegetation deposition tolerance to directly test the hypothesis at four dune fields (Bigstick, White Sands Stable, White Sands Active, and Cape Cod). We indirectly tested the hypothesis at six additional dune fields with limited vegetation data (Hanford, Año Nuevo, Skagen Odde, Salton Sea, Oceano Stable, and Oceano Active, "inverse calculation sites"). We used digital topographic data and estimates of aeolian sand flux to approximate the slipface deposition rates prior to stabilization. Results revealed a distinct, quantifiable, and consistent pattern despite diverse environmental conditions: the modal peak of prestabilization slipface deposition rates was 80% of the vegetation deposition tolerance at stabilized or stabilizing dune fields. Results from inverse calculation sites indicate deposition rates at stabilized sites were near a hypothesized maximum vegetation deposition tolerance (1 m a-1), and active sites had slipface deposition rates much higher. Overall, these results confirm the hypothesis and provide evidence of a globally applicable, simple, and previously unidentified predictor for the dynamics of vegetation cover in dune fields under unidirectional wind regimes.

Metal Stabilization of Collagen and de Novo Designed Mimetic Peptides.

PubMed

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

2015-08-18

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

Ka-Band Atmospheric Phase Stability Measurements in Goldstone, CA; White Sands, NM; and Guam

NASA Technical Reports Server (NTRS)

Zemba, Michael J.; Morse, Jacquelynne Rose; Nessel, James A.

2014-01-01

As spacecraft communication links are driven to higher frequencies (e.g. Ka-band) both by spectrum congestion and the appeal of higher data rates, the propagation phenomena at these frequencies must be well characterized for effective system design. In particular, the phase stability of a site at a given frequency will govern whether or not the site is a practical location for an antenna array, particularly if uplink capabilities are desired. Propagation studies to characterize such phenomena must be done on a site-by-site basis due to the wide variety of climates and weather conditions at each ground terminal. Accordingly, in order to statistically characterize the atmospheric effects on Ka-Band links, site test interferometers (STIs) have been deployed at three of NASA's operational sites to directly measure each site's tropospheric phase stability. Using three years of results from these experiments, this paper will statistically characterize the simultaneous atmospheric phase noise measurements recorded by the STIs deployed at the following ground station sites: the Goldstone Deep Space Communications Complex near Barstow, CA; the White Sands Ground Terminal near Las Cruces, NM; and the Guam Remote Ground Terminal on the island of Guam.

Market segmentation strategy in internet market

NASA Astrophysics Data System (ADS)

Ren, Yawei; Yang, Deli; Diao, Xinjun

2010-04-01

This paper presents a model to describe the competitive dynamics of web sites on the WWW market and analyze the stability of the model which is composed of one powerful site and two small sites. One of the most important results that emerge from this simple model is that strong competition among websites does not necessarily lead to the demise of the small website on the WWW market. From the stability analysis of the model, we obtain a series of conditions in which small sites can obtain competitive advantages by using the market segmentation strategy.

Design and Testing of a Ground-based System for Phase Stabilized Standard Frequency Transmission

NASA Astrophysics Data System (ADS)

Wang, J. Q.; Jiang, Y. C.; Gou, W.; Yu, L. F.; Liu, Q. H.; Fan, Q. Y.; Lou, F. X.; Lao, B. Q.

2014-09-01

In this paper, a 1.5 GHz phase stabilized frequency transmission system is described. Compatible with the coaxial cable and optical fiber transmission media, the system has both the capabilities of real-time and post phase compensation. The phase stabilizing principle of the equipment is analyzed, and its performance is evaluated. Under the test environment, the results of the prototype system based on a coaxial cable show that the real-time compensation mode can improve the phase stabilities by more than 112 times in comparison with the uncompensated cables. The frequency stabilities are also improved significantly with a 7-second integration time, and one order-of-magnitude improvement is achieved after 60 seconds. The post compensation mode can improve phase fluctuations by 40 times. The frequency stabilities can be improved significantly after 2.5-second integration, while a 10-fold enhancement is achieved after 40 seconds. With longer integration time, both real-time and post compensation modes can improve the frequency stabilities by more than 1.5 orders of magnitude. The proposed equipment can effectively reduce slowly stretching effects due to the factors such as the temperature coefficient variations of the transmission medium and mechanical disturbances.

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

PubMed

Liu, Ying; Lu, Zheming; Xu, Ruiping; Ke, Yang

2016-02-02

Integration of human papillomavirus (HPV) DNA into the host genome can be a driver mutation in cervical carcinoma. Identification of HPV integration at base resolution has been a longstanding technical challenge, largely due to sensitivity masking by HPV in episomes or concatenated forms. The aim was to enhance the understanding of the precise localization of HPV integration sites using an innovative strategy. Using HPV capture technology combined with next generation sequencing, HPV prevalence and the exact integration sites of the HPV DNA in 47 primary cervical cancer samples and 2 cell lines were investigated. A total of 117 unique HPV integration sites were identified, including HPV16 (n = 101), HPV18 (n = 7), and HPV58 (n = 9). We observed that the HPV16 integration sites were broadly located across the whole viral genome. In addition, either single or multiple integration events could occur frequently for HPV16, ranging from 1 to 19 per sample. The viral integration sites were distributed across almost all the chromosomes, except chromosome 22. All the cervical cancer cases harboring more than four HPV16 integration sites showed clinical diagnosis of stage III carcinoma. A significant enrichment of overlapping nucleotides shared between the human genome and HPV genome at integration breakpoints was observed, indicating that it may play an important role in the HPV integration process. The results expand on knowledge from previous findings on HPV16 and HPV18 integration sites and allow a better understanding of the molecular basis of the pathogenesis of cervical carcinoma.

Integration of ambient seismic noise monitoring, displacement and meteorological measurements to infer the temperature-controlled long-term evolution of a complex prone-to-fall cliff

NASA Astrophysics Data System (ADS)

Colombero, C.; Baillet, L.; Comina, C.; Jongmans, D.; Larose, E.; Valentin, J.; Vinciguerra, S.

2018-06-01

Monitoring the temporal evolution of resonance frequencies and velocity changes detected from ambient seismic noise recordings can help in recognizing reversible and irreversible modifications within unstable rock volumes. With this aim, the long-term ambient seismic noise data set acquired at the potentially unstable cliff of Madonna delSasso (NW Italian Alps) was analysed in this study, using both spectral analysis and cross-correlation techniques. Noise results were integrated and compared with direct displacement measurements and meteorological data, to understand the long-term evolution of the cliff. No irreversible modifications in the stability of the site were detected over the monitored period. Conversely, daily and seasonal air temperature fluctuations were found to control resonance frequency values, amplitudes and directivities and to induce reversible velocity changes within the fractured rock mass. The immediate modification in the noise parameters due to temperature fluctuations was interpreted as the result of rock mass thermal expansion and contraction, inducing variations in the contact stiffness along the fractures isolating two unstable compartments. Differences with previous case studies were highlighted in the long-term evolution of noise spectral amplitudes and directivities, due to the complex 3-D fracture setting of the site and to the combined effects of the two unstable compartments.

Planning for district mental health services in South Africa: a situational analysis of a rural district site.

PubMed

Petersen, Inge; Bhana, Arvin; Campbell-Hall, Victoria; Mjadu, Sithembile; Lund, Crick; Kleintjies, Sharon; Hosegood, Victoria; Flisher, Alan J

2009-03-01

The shift in emphasis to universal primary health care in post-apartheid South Africa has been accompanied by a process of decentralization of mental health services to district level, as set out in the new Mental Health Care Act, no. 17, of 2002 and the 1997 White Paper on the Transformation of the Health System. This study sought to assess progress in South Africa with respect to deinstitutionalization and the integration of mental health into primary health care, with a view to understanding the resource implications of these processes at district level. A situational analysis in one district site, typical of rural areas in South Africa, was conducted, based on qualitative interviews with key stakeholders and the World Health Organization's Assessment Instrument for Mental Health Systems (WHO-AIMS). The findings suggest that the decentralization process remains largely limited to emergency management of psychiatric patients and ongoing psychopharmacological care of patients with stabilized chronic conditions. We suggest that, in a similar vein to other low- to middle-income countries, deinstitutionalization and comprehensive integrated mental health care in South Africa is hampered by a lack of resources for mental health care within the primary health care resource package, as well as the inefficient use of existing mental health resources.

Characterization of a Field Spectroradiometer for Unattended Vegetation Monitoring. Key Sensor Models and Impacts on Reflectance

PubMed Central

Pacheco-Labrador, Javier; Martín, M. Pilar

2015-01-01

Field spectroradiometers integrated in automated systems at Eddy Covariance (EC) sites are a powerful tool for monitoring and upscaling vegetation physiology and carbon and water fluxes. However, exposure to varying environmental conditions can affect the functioning of these sensors, especially if these cannot be completely insulated and stabilized. This can cause inaccuracy in the spectral measurements and hinder the comparison between data acquired at different sites. This paper describes the characterization of key sensor models in a double beam spectroradiometer necessary to calculate the Hemispherical-Conical Reflectance Factor (HCRF). Dark current, temperature dependence, non-linearity, spectral calibration and cosine receptor directional responses are modeled in the laboratory as a function of temperature, instrument settings, radiation measured or illumination angle. These models are used to correct the spectral measurements acquired continuously by the same instrument integrated outdoors in an automated system (AMSPEC-MED). Results suggest that part of the instrumental issues cancel out mutually or can be controlled by the instrument configuration, so that changes induced in HCFR reached about 0.05 at maximum. However, these corrections are necessary to ensure the inter-comparison of data with other ground or remote sensors and to discriminate instrumentally induced changes in HCRF from those related with vegetation physiology and directional effects. PMID:25679315

Robust Stabilization of T-S Fuzzy Stochastic Descriptor Systems via Integral Sliding Modes.

PubMed

Li, Jinghao; Zhang, Qingling; Yan, Xing-Gang; Spurgeon, Sarah K

2017-09-19

This paper addresses the robust stabilization problem for T-S fuzzy stochastic descriptor systems using an integral sliding mode control paradigm. A classical integral sliding mode control scheme and a nonparallel distributed compensation (Non-PDC) integral sliding mode control scheme are presented. It is shown that two restrictive assumptions previously adopted developing sliding mode controllers for Takagi-Sugeno (T-S) fuzzy stochastic systems are not required with the proposed framework. A unified framework for sliding mode control of T-S fuzzy systems is formulated. The proposed Non-PDC integral sliding mode control scheme encompasses existing schemes when the previously imposed assumptions hold. Stability of the sliding motion is analyzed and the sliding mode controller is parameterized in terms of the solutions of a set of linear matrix inequalities which facilitates design. The methodology is applied to an inverted pendulum model to validate the effectiveness of the results presented.

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

PubMed

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

2017-06-17

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

Accurate detection for a wide range of mutation and editing sites of microRNAs from small RNA high-throughput sequencing profiles

PubMed Central

Zheng, Yun; Ji, Bo; Song, Renhua; Wang, Shengpeng; Li, Ting; Zhang, Xiaotuo; Chen, Kun; Li, Tianqing; Li, Jinyan

2016-01-01

Various types of mutation and editing (M/E) events in microRNAs (miRNAs) can change the stabilities of pre-miRNAs and/or complementarities between miRNAs and their targets. Small RNA (sRNA) high-throughput sequencing (HTS) profiles can contain many mutated and edited miRNAs. Systematic detection of miRNA mutation and editing sites from the huge volume of sRNA HTS profiles is computationally difficult, as high sensitivity and low false positive rate (FPR) are both required. We propose a novel method (named MiRME) for an accurate and fast detection of miRNA M/E sites using a progressive sequence alignment approach which refines sensitivity and improves FPR step-by-step. From 70 sRNA HTS profiles with over 1.3 billion reads, MiRME has detected thousands of statistically significant M/E sites, including 3′-editing sites, 57 A-to-I editing sites (of which 32 are novel), as well as some putative non-canonical editing sites. We demonstrated that a few non-canonical editing sites were not resulted from mutations in genome by integrating the analysis of genome HTS profiles of two human cell lines, suggesting the existence of new editing types to further diversify the functions of miRNAs. Compared with six existing studies or methods, MiRME has shown much superior performance for the identification and visualization of the M/E sites of miRNAs from the ever-increasing sRNA HTS profiles. PMID:27229138

More than mere numbers: the impact of lethal control on the social stability of a top-order predator.

PubMed

Wallach, Arian D; Ritchie, Euan G; Read, John; O'Neill, Adam J

2009-09-02

Population control of socially complex species may have profound ecological implications that remain largely invisible if only their abundance is considered. Here we discuss the effects of control on a socially complex top-order predator, the dingo (Canis lupus dingo). Since European occupation of Australia, dingoes have been controlled over much of the continent. Our aim was to investigate the effects of control on their abundance and social stability. We hypothesized that dingo abundance and social stability are not linearly related, and proposed a theoretical model in which dingo populations may fluctuate between three main states: (A) below carrying capacity and socially fractured, (B) above carrying capacity and socially fractured, or (C) at carrying capacity and socially stable. We predicted that lethal control would drive dingoes into the unstable states A or B, and that relaxation of control would allow recovery towards C. We tested our predictions by surveying relative abundance (track density) and indicators of social stability (scent-marking and howling) at seven sites in the arid zone subject to differing degrees of control. We also monitored changes in dingo abundance and social stability following relaxation and intensification of control. Sites where dingoes had been controlled within the previous two years were characterized by low scent-marking activity, but abundance was similar at sites with and without control. Signs of social stability steadily increased the longer an area was allowed to recover from control, but change in abundance did not follow a consistent path. Comparison of abundance and stability among all sites and years demonstrated that control severely fractures social groups, but that the effect of control on abundance was neither consistent nor predictable. Management decisions involving large social predators must therefore consider social stability to ensure their conservation and ecological functioning.

Enhancers Are Major Targets for Murine Leukemia Virus Vector Integration

PubMed Central

De Ravin, Suk See; Su, Ling; Theobald, Narda; Choi, Uimook; Macpherson, Janet L.; Poidinger, Michael; Symonds, Geoff; Pond, Susan M.; Ferris, Andrea L.; Hughes, Stephen H.

2014-01-01

ABSTRACT Retroviral vectors have been used in successful gene therapies. However, in some patients, insertional mutagenesis led to leukemia or myelodysplasia. Both the strong promoter/enhancer elements in the long terminal repeats (LTRs) of murine leukemia virus (MLV)-based vectors and the vector-specific integration site preferences played an important role in these adverse clinical events. MLV integration is known to prefer regions in or near transcription start sites (TSS). Recently, BET family proteins were shown to be the major cellular proteins responsible for targeting MLV integration. Although MLV integration sites are significantly enriched at TSS, only a small fraction of the MLV integration sites (<15%) occur in this region. To resolve this apparent discrepancy, we created a high-resolution genome-wide integration map of more than one million integration sites from CD34+ hematopoietic stem cells transduced with a clinically relevant MLV-based vector. The integration sites form ∼60,000 tight clusters. These clusters comprise ∼1.9% of the genome. The vast majority (87%) of the integration sites are located within histone H3K4me1 islands, a hallmark of enhancers. The majority of these clusters also have H3K27ac histone modifications, which mark active enhancers. The enhancers of some oncogenes, including LMO2, are highly preferred targets for integration without in vivo selection. IMPORTANCE We show that active enhancer regions are the major targets for MLV integration; this means that MLV preferentially integrates in regions that are favorable for viral gene expression in a variety of cell types. The results provide insights for MLV integration target site selection and also explain the high risk of insertional mutagenesis that is associated with gene therapy trials using MLV vectors. PMID:24501411

Comprehensive profiling of retroviral integration sites using target enrichment methods from historical koala samples without an assembled reference genome

PubMed Central

Alquezar-Planas, David E.; Ishida, Yasuko; Courtiol, Alexandre; Timms, Peter; Johnson, Rebecca N.; Lenz, Dorina; Helgen, Kristofer M.; Roca, Alfred L.; Hartman, Stefanie

2016-01-01

Background. Retroviral integration into the host germline results in permanent viral colonization of vertebrate genomes. The koala retrovirus (KoRV) is currently invading the germline of the koala (Phascolarctos cinereus) and provides a unique opportunity for studying retroviral endogenization. Previous analysis of KoRV integration patterns in modern koalas demonstrate that they share integration sites primarily if they are related, indicating that the process is currently driven by vertical transmission rather than infection. However, due to methodological challenges, KoRV integrations have not been comprehensively characterized. Results. To overcome these challenges, we applied and compared three target enrichment techniques coupled with next generation sequencing (NGS) and a newly customized sequence-clustering based computational pipeline to determine the integration sites for 10 museum Queensland and New South Wales (NSW) koala samples collected between the 1870s and late 1980s. A secondary aim of this study sought to identify common integration sites across modern and historical specimens by comparing our dataset to previously published studies. Several million sequences were processed, and the KoRV integration sites in each koala were characterized. Conclusions. Although the three enrichment methods each exhibited bias in integration site retrieval, a combination of two methods, Primer Extension Capture and hybridization capture is recommended for future studies on historical samples. Moreover, identification of integration sites shows that the proportion of integration sites shared between any two koalas is quite small. PMID:27069793

Precise Orbital and Geodetic Parameter Estimation using SLR Observations for ILRS AAC

NASA Astrophysics Data System (ADS)

Kim, Young-Rok; Park, Eunseo; Oh, Hyungjik Jay; Park, Sang-Young; Lim, Hyung-Chul; Park, Chandeok

2013-12-01

In this study, we present results of precise orbital geodetic parameter estimation using satellite laser ranging (SLR) observations for the International Laser Ranging Service (ILRS) associate analysis center (AAC). Using normal point observations of LAGEOS-1, LAGEOS-2, ETALON-1, and ETALON-2 in SLR consolidated laser ranging data format, the NASA/ GSFC GEODYN II and SOLVE software programs were utilized for precise orbit determination (POD) and finding solutions of a terrestrial reference frame (TRF) and Earth orientation parameters (EOPs). For POD, a weekly-based orbit determination strategy was employed to process SLR observations taken from 20 weeks in 2013. For solutions of TRF and EOPs, loosely constrained scheme was used to integrate POD results of four geodetic SLR satellites. The coordinates of 11 ILRS core sites were determined and daily polar motion and polar motion rates were estimated. The root mean square (RMS) value of post-fit residuals was used for orbit quality assessment, and both the stability of TRF and the precision of EOPs by external comparison were analyzed for verification of our solutions. Results of post-fit residuals show that the RMS of the orbits of LAGEOS-1 and LAGEOS-2 are 1.20 and 1.12 cm, and those of ETALON-1 and ETALON-2 are 1.02 and 1.11 cm, respectively. The stability analysis of TRF shows that the mean value of 3D stability of the coordinates of 11 ILRS core sites is 7.0 mm. An external comparison, with respect to International Earth rotation and Reference systems Service (IERS) 08 C04 results, shows that standard deviations of polar motion XP and YP are 0.754 milliarcseconds (mas) and 0.576 mas, respectively. Our results of precise orbital and geodetic parameter estimation are reasonable and help advance research at ILRS AAC.

Expression and characterization of a low molecular weight recombinant human gelatin: development of a substitute for animal-derived gelatin with superior features.

PubMed

Olsen, David; Jiang, Jenny; Chang, Robert; Duffy, Robert; Sakaguchi, Masahiro; Leigh, Scott; Lundgard, Robert; Ju, Julia; Buschman, Frank; Truong-Le, Vu; Pham, Binh; Polarek, James W

2005-04-01

Gelatin is used as a stabilizer in several vaccines. Allergic reactions to gelatins have been reported, including anaphylaxis. These gelatins are derived from animal tissues and thus represent a potential source of contaminants that cause transmissible spongiform encephalopathies. We have developed a low molecular weight human sequence gelatin that can substitute for the animal sourced materials. A cDNA fragment encoding 101 amino acids of the human proalpha1 (I) chain was amplified, cloned into plasmid pPICZalpha, integrated into Pichia pastoris strain X-33, and isolates expressing high levels of recombinant gelatin FG-5001 were identified. Purified FG-5001 was able to stabilize a live attenuated viral vaccine as effectively as porcine gelatin. This prototype recombinant gelatin was homogeneous with respect to molecular weight but consisted of several charge isoforms. These isoforms were separated by cation exchange chromatography and found to result from a combination of truncation of the C-terminal arginine and post-translational phosphorylation. Site-directed mutagenesis was used to identify the primary site of phosphorylation as serine residue 546; serine 543 was phosphorylated at a low level. A new construct was designed encoding an engineered gelatin, FG-5009, with point mutations that eliminated the charge heterogeneity. FG-5009 was not recognized by antigelatin IgE antibodies from children with confirmed gelatin allergies, establishing the low allergenic potential of this gelatin. The homogeneity of FG-5009, the ability to produce large quantities in a reproducible manner, and its low allergenic potential make this a superior substitute for the animal gelatin hydrolysates currently used to stabilize many pharmaceuticals.

Mechanical Stability of Fractured Rift Basin Mudstones: from lab to basin scale

NASA Astrophysics Data System (ADS)

Zakharova, N. V.; Goldberg, D.; Collins, D.; Swager, L.; Payne, W. G.

2016-12-01

Understanding petrophysical and mechanical properties of caprock mudstones is essential for ensuring good containment and mechanical formation stability at potential CO2 storage sites. Natural heterogeneity and presence of fractures, however, create challenges for accurate prediction of mudstone behavior under injection conditions and at reservoir scale. In this study, we present a multi-scale geomechanical analysis for Mesozoic mudstones from the Newark Rift basin, integrating petropyshical core and borehole data, in situ stress measurements, and caprock stability modeling. The project funded by the U.S. Department of Energy's National Energy Technology Laboratory (NETL) focuses on the Newark basin as a representative locality for a series of the Mesozoic rift basins in eastern North America considered as potential CO2 storage sites. An extensive core characterization program, which included laboratory CT scans, XRD, SEM, MICP, porosity, permeability, acoustic velocity measurements, and geomechanical testing under a range of confining pressures, revealed large variability and heterogeneity in both petrophysical and mechanical properties. Estimates of unconfined compressive strength for these predominantly lacustrine mudstones range from 5,000 to 50,000 psi, with only a weak correlation to clay content. Thinly bedded intervals exhibit up to 30% strength anisotropy. Mineralized fractures, abundant in most formations, are characterized by compressive strength as low as 10% of matrix strength. Upscaling these observations from core to reservoir scale is challenging. No simple one-to-one correlation between mechanical and petrophyscial properties exists, and therefore, we develop multivariate empirical relationships among these properties. A large suite of geophysical logs, including new measurements of the in situ stress field, is used to extrapolate these relationships to a basin-scale geomechanical model and predict mudstone behavior under injection conditions.

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

PubMed

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

2016-07-04

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

Independent Assessment of ITRF Site Velocities using GPS Imaging

NASA Astrophysics Data System (ADS)

Blewitt, G.; Hammond, W. C.; Kreemer, C.; Altamimi, Z.

2015-12-01

The long-term stability of ITRF is critical to the most challenging scientific applications such as the slow variation of sea level, and of ice sheet loading in Greenland and Antarctica. In 2010, the National Research Council recommended aiming for stability at the level of 1 mm/decade in the ITRF origin and scale. This requires that the ITRF include many globally-distributed sites with motions that are predictable to within a few mm/decade, with a significant number of sites having collocated stations of multiple techniques. Quantifying the stability of ITRF stations can be useful to understand stability of ITRF parameters, and to help the selection and weighting of ITRF stations. Here we apply a new suite of techniques for an independent assessment of ITRF site velocities. Our "GPS Imaging" suite is founded on the principle that, for the case of large numbers of data, the trend can be estimated objectively, automatically, robustly, and accurately by applying non-parametric techniques, which use quantile statistics (e.g., the median). At the foundation of GPS Imaging is the estimator "MIDAS" (Median Interannual Difference Adjusted for Skewness). MIDAS estimates the velocity with a realistic error bar based on sub-sampling the coordinate time series. MIDAS is robust to step discontinuities, outliers, seasonality, and heteroscedasticity. Common-mode noise filters enhance regional- to continental-scale precision in MIDAS estimates, just as they do for standard estimation techniques. Secondly, in regions where there is sufficient spatial sampling, GPS Imaging uses MIDAS velocity estimates to generate a regionally-representative velocity map. For this we apply a median spatial filter to despeckle the maps. We use GPS Imaging to address two questions: (1) How well do the ITRF site velocities derived by parametric estimation agree with non-parametric techniques? (2) Are ITRF site velocities regionally representative? These questions aim to get a handle on (1) the accuracy of ITRF site velocities as a function of characteristics of contributing station data, such as number of step parameters and total time span; and (2) evidence of local processes affecting site velocity, which may impact site stability. Such quantification can be used to rank stations in terms the risk that they may pose to the stability of ITRF.

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

PubMed

Spinozzi, Giulio; Calabria, Andrea; Brasca, Stefano; Beretta, Stefano; Merelli, Ivan; Milanesi, Luciano; Montini, Eugenio

2017-11-25

Bioinformatics tools designed to identify lentiviral or retroviral vector insertion sites in the genome of host cells are used to address the safety and long-term efficacy of hematopoietic stem cell gene therapy applications and to study the clonal dynamics of hematopoietic reconstitution. The increasing number of gene therapy clinical trials combined with the increasing amount of Next Generation Sequencing data, aimed at identifying integration sites, require both highly accurate and efficient computational software able to correctly process "big data" in a reasonable computational time. Here we present VISPA2 (Vector Integration Site Parallel Analysis, version 2), the latest optimized computational pipeline for integration site identification and analysis with the following features: (1) the sequence analysis for the integration site processing is fully compliant with paired-end reads and includes a sequence quality filter before and after the alignment on the target genome; (2) an heuristic algorithm to reduce false positive integration sites at nucleotide level to reduce the impact of Polymerase Chain Reaction or trimming/alignment artifacts; (3) a classification and annotation module for integration sites; (4) a user friendly web interface as researcher front-end to perform integration site analyses without computational skills; (5) the time speedup of all steps through parallelization (Hadoop free). We tested VISPA2 performances using simulated and real datasets of lentiviral vector integration sites, previously obtained from patients enrolled in a hematopoietic stem cell gene therapy clinical trial and compared the results with other preexisting tools for integration site analysis. On the computational side, VISPA2 showed a > 6-fold speedup and improved precision and recall metrics (1 and 0.97 respectively) compared to previously developed computational pipelines. These performances indicate that VISPA2 is a fast, reliable and user-friendly tool for integration site analysis, which allows gene therapy integration data to be handled in a cost and time effective fashion. Moreover, the web access of VISPA2 ( http://openserver.itb.cnr.it/vispa/ ) ensures accessibility and ease of usage to researches of a complex analytical tool. We released the source code of VISPA2 in a public repository ( https://bitbucket.org/andreacalabria/vispa2 ).

Simple locking of infrared and ultraviolet diode lasers to a visible laser using a LabVIEW proportional-integral-derivative controller on a Fabry-Perot signal.

PubMed

Kwolek, J M; Wells, J E; Goodman, D S; Smith, W W

2016-05-01

Simultaneous laser locking of infrared (IR) and ultraviolet lasers to a visible stabilized reference laser is demonstrated via a Fabry-Perot (FP) cavity. LabVIEW is used to analyze the input, and an internal proportional-integral-derivative algorithm converts the FP signal to an analog locking feedback signal. The locking program stabilized both lasers to a long term stability of better than 9 MHz, with a custom-built IR laser undergoing significant improvement in frequency stabilization. The results of this study demonstrate the viability of a simple, computer-controlled, non-temperature-stabilized FP locking scheme for our applications, laser cooling of Ca(+) ions, and its use in other applications with similar modest frequency stabilization requirements.

Co3O4 nanocrystals with exposed low-surface-energy planes anchored on chemically integrated graphitic carbon nitride-modified nitrogen-doped graphene: A high-performance anode material for lithium-ion batteries

NASA Astrophysics Data System (ADS)

Zhang, Wenyao; Fu, Yongsheng; Wang, Xin

2018-05-01

A facile strategy to synthesize a composite composed of cubic Co3O4 nanocrystals anchored on chemically integrated g-C3N4-modified N-graphene (CN-NG) as an advanced anode material for high-performance lithium-ion batteries is reported. It is found that the morphology of the Co3O4 nanocrystals contains blunt-edge nanocubes with well-demarcated boundaries and numerous exposed low-index (1 1 1) crystallographic facets. These planes can be directly involved in the electrochemical reactions, providing rapid Li-ion transport channels for charging and discharging and thus enhancing the round-trip diffusion efficiency. On the other hand, the CN-NG support displays unusual textural features, such as superior structural stability, accessible active sites, and good electrical conductivity. The experimental results reveal that the chemical and electronic coupling of graphitic carbon nitride and nitrogen-doped graphene synergistically facilitate the anchoring of Co3O4 nanocrystals and prevents their migration. The resulting Co3O4/CN-NG composite exhibits a high specific reversible capacity of up to 1096 mAh g-1 with excellent cycling stability and rate capability. We believe that such a hybrid carbon support could open a new path for applications in electrocatalysis, sensors, supercapacitors, etc., in the near future.

Molecular insights into the mechanism of thermal stability of actinomycete mannanase.

PubMed

Kumagai, Yuya; Uraji, Misugi; Wan, Kun; Okuyama, Masayuki; Kimura, Atsuo; Hatanaka, Tadashi

2016-09-01

Streptomyces thermolilacinus mannanase (StMan), which requires Ca(2+) for its enhanced thermal stability and hydrolysis activity, possesses two Ca(2+) -binding sites in loop6 and loop7. We evaluated the function of the Ca(2+) -binding site in loop7 and the hydrogen bond between residues Ser247 in loop6 and Asp279 in loop7. The Ca(2+) -binding in loop7 was involved only in thermal stability. Mutations of Ser247 or Asp279 retained the Ca(2+) -binding ability; however, mutants showed less thermal stability than StMan. Phylogenetic analysis indicated that most glycoside hydrolase family 5 subfamily 8 mannanases could be stabilized by Ca(2+) ; however, the mechanism of StMan thermal stability was found to be quite specific in some actinomycete mannanases. © 2016 Federation of European Biochemical Societies.

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

PubMed

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

2017-01-13

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

Stability of implants placed in fresh sockets versus healed alveolar sites: Early findings.

PubMed

Gehrke, Sergio Alexandre; da Silva Neto, Ulisses Tavares; Rossetti, Paulo Henrique Orlato; Watinaga, Sidney Eiji; Giro, Gabriela; Shibli, Jamil Awad

2016-05-01

The present study measured implant stability quotient (ISQ) values at three different time points after surgical procedures to compare whether the stability values differed between implants placed in fresh extraction sockets versus healed alveolar sites. To measure implant stability, resonance frequency analysis (RFA) was performed in 77 patients (53 women, 24 men) with a total of 120 dental implants. These implants were divided into two groups: Group 1 included 60 implants in healed alveolar sites (22 in the maxilla, 38 in the mandible), and Group 2 included 60 implants in fresh sockets (41 in the maxilla, 19 in the mandible). Implant stability was measured immediately at implant placement (baseline), 90, and 150 days later. Statistical analysis was made using a multivariate regression linear model at implant level (α = 0.05). Overall, the means and standard deviations of the ISQ values were 62.7 ± 7.14 (95% confidence interval [CI], 39-88) at baseline, 70.0 ± 6.22 (95% CI, 46-88) at 90 days, and 73.4 ± 5.84 (95% CI, 58-88) at 150 days. In Group 1, the ISQs ranged between 64.3 ± 6.20 and 75.0 ± 5.69, while in Group 2, presented lower values that ranged between 61.2 ± 8.09 and 71.9 ± 5.99 (P = 0.002). Anatomic location and times periods were the only identified variables with an influence on ISQ values at implant level (P < 0.0001). The stabilities of the implants placed in the fresh sockets and in healed sites exhibited similar evolutions in ISQ values and thus osseointegration; however, the implants in the healed alveolar sites exhibited superior values at all time points. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

Tanouchi, Yu; Covert, Markus W

2017-09-19

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

76 FR 13072 - Airworthiness Directives; Saab AB, Saab Aerosystems Model SAAB 2000 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-10

... important to the structural integrity of the horizontal stabilizer. Corrosion damage in these areas, if not... structural integrity of the horizontal stabilizer. Corrosion damage in these areas, if not detected and... convoluted tubing on the harness, applying corrosion prevention compound to the inspected area, making sure...

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

NASA Astrophysics Data System (ADS)

Lampitt, Richard S.; Larkin, Kate E.; EuroSITES Consortium

2010-05-01

EuroSITES is a 3 year (2008-2011) EU collaborative project (3.5MEuro) with the objective to integrate and enhance the nine existing open ocean fixed point observatories around Europe (www.eurosites.info). These observatories are primarily composed of full depth moorings and make multidisciplinary in situ observations within the water column as the European contribution to the global array OceanSITES (www.oceansites.org). In the first 18 months, all 9 observatories have been active and integration has been significant through the maintenance and enhancement of observatory hardware. Highlights include the enhancement of observatories with sensors to measure O2, pCO2, chlorophyll, and nitrate in near real-time from the upper 1000 m. In addition, some seafloor missions are also actively supported. These include seafloor platforms currently deployed in the Mediterranean, one for tsunami detection and one to monitor fluid flow related to seismic activity and slope stability. Upcoming seafloor science missions in 2010 include monitoring benthic biological communities and associated biogeochemistry as indicators of climate change in both the Northeast Atlantic and Mediterranean. EuroSITES also promotes the development of innovative sensors and samplers in order to progress capability to measure climate-relevant properties of the ocean. These include further developing current technologies for autonomous long-term monitoring of oxygen consumption in the mesopelagic, pH and mesozooplankton abundance. Many of these science missions are directly related to complementary activities in other European projects such as EPOCA, HYPOX and ESONET. In 2010 a direct collaboration including in situ field work will take place between ESONET and EuroSITES. The demonstration mission MODOO (funded by ESONET) will be implemented in 2010 at the EuroSITES PAP observatory. Field work will include deployment of a seafloor lander system with various sensors which will send data to shore in real time via the EuroSITES water column infrastructure. EuroSITES Data management is led by NOCS, UK with CORIOLIS, France as one of the Global Data assembly centre (GDAC) for both EuroSITES and OceanSITES. EuroSITES maintains the OceanSITES and GEO philosophy of open access to data in near real-time. With a common data policy and standardised data formats (OceanSITES NetCDF) EuroSITES is increasing the potential users of in situ ocean datasets and the societal benefit of these data. For instance, CORIOLIS is central to the ever increasing contribution of EuroSITES as an upstream data provider to the GMES project MyOcean (both real-time and delayed-mode data). Outreach and knowledge transfer of EuroSITES activities and results are also a key component to the project with a dedicated outreach website, Fact Sheet, cruise diaries and educational tools being developed in the first 18 months. In 2010 a film will be released to represent the network and this will be distributed to a wide audience through the European network of aquaria and at other outreach events. In addition, the EuroSITES project and it's relevance to global ocean observation initiatives continues to be actively promoted at both scientific and non-specialist meetings and events. By the end of EuroSITES in April 2011, the 9 core ocean observatories will be well integrated. Each observatory will have enhanced infrastructure to include both physical and biogeoechemical sensors. Science missions in the ocean interior and seafloor/subseafloor will have progressed European ocean observational capability significantly. Collaborations will have taken place or will be at an advanced stage of planning with related European and international projects including ESONET FP6 NoE and the NSF funded Ocean Observatories Initiative (OOI) (400M over 5 years). EuroSITES will continue to develop it's contribution to the ocean component of the Group on Earth Observations (GEO) through task AR-09-03c 'Global Ocean Observing Systems' and related societal benefit areas.

Long-lived groupers require structurally stable reefs in the face of repeated climate change disturbances

NASA Astrophysics Data System (ADS)

Karkarey, R.; Kelkar, N.; Lobo, A. Savio; Alcoverro, T.; Arthur, R.

2014-06-01

Benthic recovery from climate-related disturbances does not always warrant a commensurate functional recovery for reef-associated fish communities. Here, we examine the distribution of benthic groupers (family Serranidae) in coral reef communities from the Lakshadweep archipelago (Arabian Sea) in response to structural complexity and long-term habitat stability. These coral reefs that have been subject to two major El Niño Southern Oscillation-related coral bleaching events in the last decades (1998 and 2010). First, we employ a long-term (12-yr) benthic-monitoring dataset to track habitat structural stability at twelve reef sites in the archipelago. Structural stability of reefs was strongly driven by exposure to monsoon storms and depth, which made deeper and more sheltered reefs on the eastern aspect more stable than the more exposed (western) and shallower reefs. We surveyed groupers (species richness, abundance, biomass) in 60 sites across the entire archipelago, representing both exposures and depths. Sites were selected along a gradient of structural complexity from very low to high. Grouper biomass appeared to vary with habitat stability with significant differences between depth and exposure; sheltered deep reefs had a higher grouper biomass than either sheltered shallow or exposed (deep and shallow) reefs. Species richness and abundance showed similar (though not significant) trends. More interestingly, average grouper biomass increased exponentially with structural complexity, but only at the sheltered deep (high stability) sites, despite the availability of recovered structure at exposed deep and shallow sites (lower-stability sites). This trend was especially pronounced for long-lived groupers (life span >10 yrs). These results suggest that long-lived groupers may prefer temporally stable reefs, independent of the local availability of habitat structure. In reefs subject to repeated disturbances, the presence of structurally stable reefs may be critical as refuges for functionally important, long-lived species like groupers.

Improved characterization, monitoring and instability assessment of high rock faces by integrating TLS and GB-InSAR

NASA Astrophysics Data System (ADS)

Bianchetti, Matteo; Agliardi, Federico; Villa, Alberto; Battista Crosta, Giovanni; Rivolta, Carlo

2015-04-01

Rockfall risk analysis require quantifying rockfall onset susceptibility and magnitude scenarios at source areas, and the expected rockfall trajectories and related dynamic quantities. Analysis efforts usually focus on the rockfall runout component, whereas rock mass characterization and block size distribution quantification, monitoring and analysis of unstable rock volumes are usually performed using simplified approaches, due to technological and site-specific issues. Nevertheless, proper quantification of rock slope stability and rockfall magnitude scenarios is key when dealing with high rock walls, where widespread rockfall sources and high variability of release mechanisms and block volumes can result in excessive modelling uncertainties and poorly constrained mitigation measures. We explored the potential of integrating field, remote sensing, structural analysis and stability modelling techniques to improve hazard assessment at the Gallivaggio sanctuary site, a XVI century heritage located along the State Road 36 in the Spluga Valley (Italian Central Alps). The site is impended by a subvertical cliff up to 600 m high, made of granitic orthogneiss of the Truzzo granitic complex (Tambo Nappe, upper Pennidic domain). The rock mass is cut by NNW and NW-trending slope-scale structural lineaments and by 5-6 fracture sets with variable spatial distribution, spacing and persistence, which bound blocks up to tens of cubic meters and control the 3D slope morphology. The area is characterised by widespread rock slope instability from rockfalls to massive failures. Although a 180 m long embankment was built to protect the site from rockfalls, concerns remain about potential large unstable rock volumes or flyrocks projected by the widely observed impact fragmentation of stiff rock blocks. Thus, the authority in charge started a series of periodical GB-InSAR monitoring surveys using LiSALabTM technology (12 surveys in 2011-2014), which outlined the occurrence of unstable spots spread over the cliff, with cm-scale cumulative displacements in the observation period. To support the interpretation and analysis of these data, we carried out multitemporal TLS surveys (5 sessions between September 2012 and October 2014) using a Riegl VZ-1000 long-range laser scanner. We performed rock mass structural analyses on dense TLS point clouds using two different approaches: 1) manual discontinuity orientation and intensity measurement from digital outcrops; 2) automatic feature extraction and intensity evaluation through the development of an original Matlab tool, suited for multi-scale applications and optimized for parallel computing. Results were validated using field discontinuity measurements and compared to evaluate advantages and limitations of different approaches, and allowed: 1) outlining the precise location, geometry and kinematics of unstable blocks and block clusters corresponding to radar moving spots; 2) performing stability analyses; 3) quantifying rockwall changes over the observation period. Our analysis provided a robust spatial characterization of rockfall sources, block size distribution and onset susceptibility as input for 3D runout modelling and quantitative risk analysis.

Stability and maturity of biowaste composts derived by small municipalities: Correlation among physical, chemical and biological indices.

PubMed

Oviedo-Ocaña, E R; Torres-Lozada, P; Marmolejo-Rebellon, L F; Hoyos, L V; Gonzales, S; Barrena, R; Komilis, D; Sanchez, A

2015-10-01

Stability and maturity are important criteria to guarantee the quality of a compost that is applied to agriculture or used as amendment in degraded soils. Although different techniques exist to evaluate stability and maturity, the application of laboratory tests in municipalities in developing countries can be limited due to cost and application complexities. In the composting facilities of such places, some classical low cost on-site tests to monitor the composting process are usually implemented; however, such tests do not necessarily clearly identify conditions of stability and maturity. In this article, we have applied and compared results of stability and maturity tests that can be easily employed on site (i.e. temperature, pH, moisture, electrical conductivity [EC], odor and color), and of tests that require more complex laboratory techniques (volatile solids, C/N ratio, self-heating, respirometric index, germination index [GI]). The evaluation of the above was performed in the field scale using 2 piles of biowaste applied compost. The monitoring period was from day 70 to day 190 of the process. Results showed that the low-cost tests traditionally employed to monitor the composting process on-site, such as temperature, color and moisture, do not provide consistent determinations with the more complex laboratory tests used to assess stability (e.g. respiration index, self-heating, volatile solids). In the case of maturity tests (GI, pH, EC), both the on-site tests (pH, EC) and the laboratory test (GI) provided consistent results. Although, stability was indicated for most of the samples, the maturity tests indicated that products were consistently immature. Thus, a stable product is not necessarily mature. Conclusively, the decision on the quality of the compost in the installations located in developing countries requires the simultaneous use of a combination of tests that are performed both in the laboratory and on-site. Copyright © 2015 Elsevier Ltd. All rights reserved.

Archaeological site stabilization in the Tennessee River Valley: Phase 3, Research Paper No. 7, Tennessee Valley Authority Publications in Anthropology No. 49

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

Fay, P.M.

1987-01-01

Destruction of archaeological properties within the Tennessee River system, particularly along its main stem, has been a problem almost since TVA was established. In an attempt to stop the loss of massive portions of our cultural resources, the TVA contracted in 1983 to establish a program of site stabilization using experimental techniques. This report is the first installation of observations on the site protection measures placed during 1983. This report also contains pertinent observations on preserved sites not within TVA holdings. 20 refs., 25 figs.

Immediate Loading of Tapered Implants Placed in Postextraction Sockets and Healed Sites.

PubMed

Han, Chang-Hun; Mangano, Francesco; Mortellaro, Carmen; Park, Kwang-Bum

2016-07-01

The aim of the present study was to compare the survival, stability, and complications of immediately loaded implants placed in postextraction sockets and healed sites. Over a 2-year period, all patients presenting with partial or complete edentulism of the maxilla and/or mandible (healed site group, at least 4 months of healing after tooth extraction) or in need of replacement of nonrecoverable failing teeth (postextraction group) were considered for inclusion in this study. Tapered implants featuring a nanostructured calcium-incorporated surface were placed and loaded immediately. The prosthetic restorations comprised single crowns, fixed partial dentures, and fixed full arches. Primary outcomes were implant survival, stability, and complications. Implant stability was assessed at placement and at each follow-up evaluation (1 week, 3 months, and 1 year after placement): implants with an insertion torque (IT) <45 N·cm and/or with an implant stability quotient (ISQ) <70 were considered failed for immediate loading. A statistical analysis was performed. Thirty implants were placed in postextraction sockets of 17 patients, and 32 implants were placed in healed sites of 22 patients. There were no statistically significant differences in ISQ values between the 2 groups, at each assessment. In total, 60 implants (96.8%) had an IT ≥45 and an ISQ ≥70 at placement and at each follow-up control: all these implants were successfully loaded. Only 2 implants (1 in a postextraction socket and 1 in a healed site, 3.2%) could not achieve an IT ≥45 N·cm and/or an ISQ ≥70 at placement or over time: accordingly, these were considered failed for stability, as they could not be subjected to immediate loading. One of these 2 implants, in a healed site of a posterior maxilla, had to be removed, yielding an overall 1-year implant survival rate of 98.4%. No complications were reported. No significant differences were reported between the 2 groups with respect to implant failures and complications. Immediately loaded implants placed in postextraction sockets and healed sites had similar high survival and stability, with no reported complications. Further long-term studies on larger samples of patients are needed to confirm these results.

Catalytically active Au-O(OH) x- species stabilized by alkali ions on zeolites and mesoporous oxides

DOE PAGES

Yang, Ming; Li, Sha; Wang, Yuan; ...

2014-11-27

Here we report that the addition of alkali ions (sodium or potassium) to gold on KLTL-zeolite and mesoporous MCM-41 silica stabilizes mononuclear gold in Au-O(OH) x-(Na or K) ensembles. This single-site gold species is active for the low-temperature (<200°C) water-gas shift (WGS) reaction. Unexpectedly, gold is thus similar to platinum in creating –O linkages with more than eight alkali ions and establishing an active site on various supports. The intrinsic activity of the single-site gold species is the same on irreducible supports as on reducible ceria, iron oxide, and titania supports, apparently all sharing a common, similarly structured gold activemore » site. This finding paves the way for using earth-abundant supports to disperse and stabilize precious metal atoms with alkali additives for the WGS and potentially other fuel-processing reactions.« less

Importance of structural stability to success of mourning dove nests

USGS Publications Warehouse

Coon, R.A.; Nichols, J.D.; Percival, H.F.

1981-01-01

Studies of nest-site selection and nesting habitats often involve a "characterization" of nests and of habitats in which nests are found. Our objective in the present work is to identify nest-site characteristics that are associated with variation in components of Mourning Dove (Zenaida macroura) fitness (e.g. the probability of a nest succeeding), as opposed to simply "characterizing" dove nest sites. If certain nest- site characteristics affect the probability that a nest will succeed, then we suspect that these characteristics will be associated with either concealment (the probability of detection by certain predators) or structural stability (the probability of eggs or entire nests falling to the ground as a result of wind, rain storms, parental activity, etc.). Although other workers agree that structural stability is an important determinant of Mourning Dove nesting success (e.g. McClure 1944: 384; Woolfenden and Rohwer 1969: 59), we are aware of no actual tests of this hypothesis.

Influence of sulfhydryl sites on metal binding by bacteria

NASA Astrophysics Data System (ADS)

Nell, Ryan M.; Fein, Jeremy B.

2017-02-01

The role of sulfhydryl sites within bacterial cell envelopes is still unknown, but the sites may control the fate and bioavailability of metals. Organic sulfhydryl compounds are important complexing ligands in aqueous systems and they can influence metal speciation in natural waters. Though representing only approximately 5-10% of the total available binding sites on bacterial surfaces, sulfhydryl sites exhibit high binding affinities for some metals. Due to the potential importance of bacterial sulfhydryl sites in natural systems, metal-bacterial sulfhydryl site binding constants must be determined in order to construct accurate models of the fate and distribution of metals in these systems. To date, only Cd-sulfhydryl binding has been quantified. In this study, the thermodynamic stabilities of Mn-, Co-, Ni-, Zn-, Sr- and Pb-sulfhydryl bacterial cell envelope complexes were determined for the bacterial species Shewanella oneidensis MR-1. Metal adsorption experiments were conducted as a function of both pH, ranging from 5.0 to 7.0, and metal loading, from 0.5 to 40.0 μmol/g (wet weight) bacteria, in batch experiments in order to determine if metal-sulfhydryl binding occurs. Initially, the data were used to calculate the value of the stability constants for the important metal-sulfhydryl bacterial complexes for each metal-loading condition studied, assuming a single binding reaction for the dominant metal-binding site type under the pH conditions of the experiments. For most of the metals that we studied, these calculated stability constant values increased significantly with decreasing metal loading, strongly suggesting that our initial assumption was not valid and that more than one type of binding occurs at the assumed binding site. We then modeled each dataset with two distinct site types with identical acidity constants: one site with a high metal-site stability constant value, which we take to represent metal-sulfhydryl binding and which dominates under low metal loading conditions, and another more abundant site that we term non-sulfhydryl sites that becomes important at high metal loadings. The resulting calculated stability constants do not vary significantly as a function of metal loading and yield reasonable fits to the observed adsorption behaviors as a function of both pH and metal loading. We use the results to calculate the speciation of metals bound by the bacterial envelope in realistic bacteria-bearing, heavy metal contaminated systems in order to demonstrate the potential importance of metal-sulfhydryl binding in the budget of bacterially-adsorbed metals under low metal-loading conditions.

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

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

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

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2006-01-01

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

Application of Two-Parameter Stabilizing Functions in Solving a Convolution-Type Integral Equation by Regularization Method

NASA Astrophysics Data System (ADS)

Maslakov, M. L.

2018-04-01

This paper examines the solution of convolution-type integral equations of the first kind by applying the Tikhonov regularization method with two-parameter stabilizing functions. The class of stabilizing functions is expanded in order to improve the accuracy of the resulting solution. The features of the problem formulation for identification and adaptive signal correction are described. A method for choosing regularization parameters in problems of identification and adaptive signal correction is suggested.

Methyl Transfer by Substrate Signaling from a Knotted Protein Fold

PubMed Central

Christian, Thomas; Sakaguchi, Reiko; Perlinska, Agata P.; Lahoud, Georges; Ito, Takuhiro; Taylor, Erika A.; Yokoyama, Shigeyuki; Sulkowska, Joanna I.; Hou, Ya-Ming

2017-01-01

Proteins with knotted configurations are restricted in conformational space relative to unknotted proteins. Little is known if knotted proteins have sufficient dynamics to communicate between spatially separated substrate-binding sites. In bacteria, TrmD is a methyl transferase that uses a knotted protein fold to catalyze methyl transfer from S-adenosyl methionine (AdoMet) to G37-tRNA. The product m1G37-tRNA is essential for life as a determinant to maintain protein synthesis reading-frame. Using an integrated approach of structure, kinetic, and computational analysis, we show here that the structurally constrained TrmD knot is required for its catalytic activity. Unexpectedly, the TrmD knot has complex internal movements that respond to AdoMet binding and signaling. Most of the signaling propagates the free energy of AdoMet binding to stabilize tRNA binding and to assemble the active site. This work demonstrates new principles of knots as an organized structure that captures the free energies of substrate binding to facilitate catalysis. PMID:27571175

The High-Resolution Structure of Activated Opsin Reveals a Conserved Solvent Network in the Transmembrane Region Essential for Activation.

PubMed

Blankenship, Elise; Vahedi-Faridi, Ardeschir; Lodowski, David T

2015-12-01

Rhodopsin, a light-activated G protein coupled receptor (GPCR), has been the subject of numerous biochemical and structural investigations, serving as a model receptor for GPCRs and their activation. We present the 2.3-Å resolution structure of native source rhodopsin stabilized in a conformation competent for G protein binding. An extensive water-mediated hydrogen bond network linking the chromophore binding site to the site of G protein binding is observed, providing connections to conserved motifs essential for GPCR activation. Comparison of this extensive solvent-mediated hydrogen-bonding network with the positions of ordered solvent in earlier crystallographic structures of rhodopsin photointermediates reveals both static structural and dynamic functional water-protein interactions present during the activation process. When considered along with observations that solvent occupies similar positions in the structures of other GPCRs, these analyses strongly support an integral role for this dynamic ordered water network in both rhodopsin and GPCR activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Single Sublattice Endotaxial Phase Separation Driven by Charge Frustration in a Complex Oxide

PubMed Central

2013-01-01

Complex transition-metal oxides are important functional materials in areas such as energy and information storage. The cubic ABO3 perovskite is an archetypal example of this class, formed by the occupation of small octahedral B-sites within an AO3 network defined by larger A cations. We show that introduction of chemically mismatched octahedral cations into a cubic perovskite oxide parent phase modifies structure and composition beyond the unit cell length scale on the B sublattice alone. This affords an endotaxial nanocomposite of two cubic perovskite phases with distinct properties. These locally B-site cation-ordered and -disordered phases share a single AO3 network and have enhanced stability against the formation of a competing hexagonal structure over the single-phase parent. Synergic integration of the distinct properties of these phases by the coherent interfaces of the composite produces solid oxide fuel cell cathode performance superior to that expected from the component phases in isolation. PMID:23750709

Rational modification of protein stability by targeting surface sites leads to complicated results

PubMed Central

Xiao, Shifeng; Patsalo, Vadim; Shan, Bing; Bi, Yuan; Green, David F.; Raleigh, Daniel P.

2013-01-01

The rational modification of protein stability is an important goal of protein design. Protein surface electrostatic interactions are not evolutionarily optimized for stability and are an attractive target for the rational redesign of proteins. We show that surface charge mutants can exert stabilizing effects in distinct and unanticipated ways, including ones that are not predicted by existing methods, even when only solvent-exposed sites are targeted. Individual mutation of three solvent-exposed lysines in the villin headpiece subdomain significantly stabilizes the protein, but the mechanism of stabilization is very different in each case. One mutation destabilizes native-state electrostatic interactions but has a larger destabilizing effect on the denatured state, a second removes the desolvation penalty paid by the charged residue, whereas the third introduces unanticipated native-state interactions but does not alter electrostatics. Our results show that even seemingly intuitive mutations can exert their effects through unforeseen and complex interactions. PMID:23798426

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

PubMed Central

Urbic, Tomaz

2016-01-01

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

Long term in vitro stability of fully integrated wireless neural interfaces based on Utah slant electrode array

NASA Astrophysics Data System (ADS)

Sharma, Asha; Rieth, Loren; Tathireddy, Prashant; Harrison, Reid; Solzbacher, Florian

2010-02-01

We herein report in vitro functional stability and recording longevity of a fully integrated wireless neural interface (INI). The INI uses biocompatible Parylene-C as an encapsulation layer, and was immersed in phosphate buffered saline (PBS) for a period of over 150 days. The full functionality (wireless radio-frequency power, command, and signal transmission) and the ability of INI to record artificial action potentials even after 150 days of PBS soaking without any change in signal/noise amplitude constitutes a major milestone in long term stability, and evaluate the encapsulation reliability, functional stability, and potential usefulness for future chronic implants.

Biochemical analyses are instrumental in identifying the impact of mutations on holo and/or apo-forms and on the region(s) of alanine:glyoxylate aminotransferase variants associated with Primary Hyperoxaluria Type I☆

PubMed Central

Oppici, Elisa; Montioli, Riccardo; Lorenzetto, Antonio; Bianconi, Silvia; Borri Voltattorni, Carla; Cellini, Barbara

2012-01-01

Primary Hyperoxaluria Type I (PH1) is a disorder of glyoxylate metabolism caused by mutations in the human AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5′-phosphate (PLP) dependent enzyme. Previous investigations highlighted that, although PH1 is characterized by a significant variability in terms of enzymatic phenotype, the majority of the pathogenic variants are believed to share both structural and functional defects, as mainly revealed by data on AGT activity and expression level in crude cellular extracts. However, the knowledge of the defects of the AGT variants at a protein level is still poor. We therefore performed a side-by-side comparison between normal AGT and nine purified recombinant pathogenic variants in terms of catalytic activity, coenzyme binding mode and affinity, spectroscopic features, oligomerization, and thermal stability of both the holo- and apo-forms. Notably, we chose four variants in which the mutated residues are located in the large domain of AGT either within the active site and interacting with the coenzyme or in its proximity, and five variants in which the mutated residues are distant from the active site either in the large or in the small domain. Overall, this integrated analysis of enzymatic activity, spectroscopic and stability information is used to (i) reassess previous data obtained with crude cellular extracts, (ii) establish which form(s) (i.e. holoenzyme and/or apoenzyme) and region(s) (i.e. active site microenvironment, large and/or small domain) of the protein are affected by each mutation, and (iii) suggest the possible therapeutic approach for patients bearing the examined mutations. PMID:22018727

Biochemical analyses are instrumental in identifying the impact of mutations on holo and/or apo-forms and on the region(s) of alanine:glyoxylate aminotransferase variants associated with primary hyperoxaluria type I.

PubMed

Oppici, Elisa; Montioli, Riccardo; Lorenzetto, Antonio; Bianconi, Silvia; Borri Voltattorni, Carla; Cellini, Barbara

2012-01-01

Primary Hyperoxaluria Type I (PH1) is a disorder of glyoxylate metabolism caused by mutations in the human AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate (PLP) dependent enzyme. Previous investigations highlighted that, although PH1 is characterized by a significant variability in terms of enzymatic phenotype, the majority of the pathogenic variants are believed to share both structural and functional defects, as mainly revealed by data on AGT activity and expression level in crude cellular extracts. However, the knowledge of the defects of the AGT variants at a protein level is still poor. We therefore performed a side-by-side comparison between normal AGT and nine purified recombinant pathogenic variants in terms of catalytic activity, coenzyme binding mode and affinity, spectroscopic features, oligomerization, and thermal stability of both the holo- and apo-forms. Notably, we chose four variants in which the mutated residues are located in the large domain of AGT either within the active site and interacting with the coenzyme or in its proximity, and five variants in which the mutated residues are distant from the active site either in the large or in the small domain. Overall, this integrated analysis of enzymatic activity, spectroscopic and stability information is used to (i) reassess previous data obtained with crude cellular extracts, (ii) establish which form(s) (i.e. holoenzyme and/or apoenzyme) and region(s) (i.e. active site microenvironment, large and/or small domain) of the protein are affected by each mutation, and (iii) suggest the possible therapeutic approach for patients bearing the examined mutations. Copyright © 2011 Elsevier Inc. All rights reserved.

Recent slope failures in the Dolomites (Northeastern Italian Alps) in a context of climate change

NASA Astrophysics Data System (ADS)

Chiarle, Marta; Paranunzio, Roberta; Laio, Francesco; Nigrelli, Guido; Guzzetti, Fausto

2014-05-01

Climate change in the Greater Alpine Region is seriously affecting permafrost distribution, with relevant consequences on slope stability. In the Italian Alps, the number of failures from rockwalls at high elevation markedly increased in the last 20-30 years: the consistent temperature increase, which warmed twice than the global average, may have seriously influenced slope stability, in terms of glaciers retreat and permafrost degradation. Moreover, the growing number of tourists and activities in alpine regions (in particular in the Dolomites) made these areas particularly critical in relation to natural hazards. In this light, an integrated short-term geomorphological and climatic analysis was performed, in order to better comprehend the impact of main climate elements (especially temperature and precipitation) on slope failures in high mountain areas. In this contribution, we focus on three recent slope failures occurred at high elevation sites in the Dolomites (Northeastern Italian Alps), declared a UNESCO World Heritage Site in August 2009. We describe here three important rock falls occurred in the autumn 2013: 1) the Sorapiss rock fall, on 30 September 2013; 2) the Monte Civetta rock fall, on 16 November 2013; 3) the Monte Antelao rock fall, on 22 November 2013. The Monte Civetta rock fall damaged some climbing routes, while the other two landslides did not cause any damage or injury. Despite the limited volume involved, these three events represent an important warning sign in the context of ongoing climate change. Geomorphological information about the rock fall sites were combined with the climatic data acquired from the meteorological stations surrounding the slope failure areas. A short-term climatic analysis was performed, with the aim of understanding the role of the main climatic elements in the triggering of natural instability events in this area and in the Alps in general.

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

PubMed

Hong, Yang; Hondalus, Mary K

2008-10-01

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

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

PubMed

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

2017-09-20

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

Retroviral integration: Site matters

PubMed Central

Demeulemeester, Jonas; De Rijck, Jan

2015-01-01

Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is subject to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success. PMID:26293289

Enhancement of oxidative stability of the subtilisin nattokinase by site-directed mutagenesis expressed in Escherichia coli.

PubMed

Weng, MeiZhi; Zheng, ZhongLiang; Bao, Wei; Cai, YongJun; Yin, Yan; Zou, GuoLin; Zou, GouLin

2009-11-01

Nattokinase (subtilisin NAT, NK) is a bacterial serine protease with strong fibrinolytic activity and it is a potent cardiovascular drug. In medical and commercial applications, however, it is susceptible to chemical oxidation, and subsequent inactivation or denaturation. Here we show that the oxidative stability of NK was substantially increased by optimizing the amino acid residues Thr(220) and Met(222), which were in the vicinity of the catalytic residue Ser(221) of the enzyme. Two nonoxidative amino acids (Ser and Ala) were introduced at these sites using site-directed mutagenesis. Active enzymes were successfully expressed in Escherichia coli with periplasmic secretion and enzymes were purified to homogeneity. The purified enzymes were analyzed with respect to oxidative stability, kinetic parameters, fibrinolytic activity and thermal stability. M222A mutant was found to have a greatly increased oxidative stability compared with wild-type enzyme and it was resistant to inactivation by more than 1 M H(2)O(2), whereas the wild-type enzyme was inactivated by 0.1 M H(2)O(2) (t(1/2) approximately 11.6 min). The other mutant (T220S) also showed an obvious increase in antioxidative ability. Molecular dynamic simulations on wild-type and T220S mutant proteins suggested that a hydrogen bond was formed between Ser(220) and Asn(155), and the spatial structure of Met(222) was changed compared with the wild-type. The present study demonstrates the feasibility of improving oxidative stability of NK by site-directed mutagenesis and shows successful protein engineering cases to improve stability of NK as a potent therapeutic agent.

Actomyosin drives cancer cell nuclear dysmorphia and threatens genome stability.

PubMed

Takaki, Tohru; Montagner, Marco; Serres, Murielle P; Le Berre, Maël; Russell, Matt; Collinson, Lucy; Szuhai, Karoly; Howell, Michael; Boulton, Simon J; Sahai, Erik; Petronczki, Mark

2017-07-24

Altered nuclear shape is a defining feature of cancer cells. The mechanisms underlying nuclear dysmorphia in cancer remain poorly understood. Here we identify PPP1R12A and PPP1CB, two subunits of the myosin phosphatase complex that antagonizes actomyosin contractility, as proteins safeguarding nuclear integrity. Loss of PPP1R12A or PPP1CB causes nuclear fragmentation, nuclear envelope rupture, nuclear compartment breakdown and genome instability. Pharmacological or genetic inhibition of actomyosin contractility restores nuclear architecture and genome integrity in cells lacking PPP1R12A or PPP1CB. We detect actin filaments at nuclear envelope rupture sites and define the Rho-ROCK pathway as the driver of nuclear damage. Lamin A protects nuclei from the impact of actomyosin activity. Blocking contractility increases nuclear circularity in cultured cancer cells and suppresses deformations of xenograft nuclei in vivo. We conclude that actomyosin contractility is a major determinant of nuclear shape and that unrestrained contractility causes nuclear dysmorphia, nuclear envelope rupture and genome instability.

Hcm1 integrates signals from Cdk1 and calcineurin to control cell proliferation

PubMed Central

Arsenault, Heather E.; Roy, Jagoree; Mapa, Claudine E.; Cyert, Martha S.; Benanti, Jennifer A.

2015-01-01

Cyclin-dependent kinase (Cdk1) orchestrates progression through the cell cycle by coordinating the activities of cell-cycle regulators. Although phosphatases that oppose Cdk1 are likely to be necessary to establish dynamic phosphorylation, specific phosphatases that target most Cdk1 substrates have not been identified. In budding yeast, the transcription factor Hcm1 activates expression of genes that regulate chromosome segregation and is critical for maintaining genome stability. Previously we found that Hcm1 activity and degradation are stimulated by Cdk1 phosphorylation of distinct clusters of sites. Here we show that, upon exposure to environmental stress, the phosphatase calcineurin inhibits Hcm1 by specifically removing activating phosphorylations and that this regulation is important for cells to delay proliferation when they encounter stress. Our work identifies a mechanism by which proliferative signals from Cdk1 are removed in response to stress and suggests that Hcm1 functions as a rheostat that integrates stimulatory and inhibitory signals to control cell proliferation. PMID:26269584

A multifunctional biphasic water splitting catalyst tailored for integration with high-performance semiconductor photoanodes

NASA Astrophysics Data System (ADS)

Yang, Jinhui; Cooper, Jason K.; Toma, Francesca M.; Walczak, Karl A.; Favaro, Marco; Beeman, Jeffrey W.; Hess, Lucas H.; Wang, Cheng; Zhu, Chenhui; Gul, Sheraz; Yano, Junko; Kisielowski, Christian; Schwartzberg, Adam; Sharp, Ian D.

2017-03-01

Artificial photosystems are advanced by the development of conformal catalytic materials that promote desired chemical transformations, while also maintaining stability and minimizing parasitic light absorption for integration on surfaces of semiconductor light absorbers. Here, we demonstrate that multifunctional, nanoscale catalysts that enable high-performance photoelectrochemical energy conversion can be engineered by plasma-enhanced atomic layer deposition. The collective properties of tailored Co3O4/Co(OH)2 thin films simultaneously provide high activity for water splitting, permit efficient interfacial charge transport from semiconductor substrates, and enhance durability of chemically sensitive interfaces. These films comprise compact and continuous nanocrystalline Co3O4 spinel that is impervious to phase transformation and impermeable to ions, thereby providing effective protection of the underlying substrate. Moreover, a secondary phase of structurally disordered and chemically labile Co(OH)2 is introduced to ensure a high concentration of catalytically active sites. Application of this coating to photovoltaic p+n-Si junctions yields best reported performance characteristics for crystalline Si photoanodes.

Actomyosin drives cancer cell nuclear dysmorphia and threatens genome stability

PubMed Central

Takaki, Tohru; Montagner, Marco; Serres, Murielle P.; Le Berre, Maël; Russell, Matt; Collinson, Lucy; Szuhai, Karoly; Howell, Michael; Boulton, Simon J.; Sahai, Erik; Petronczki, Mark

2017-01-01

Altered nuclear shape is a defining feature of cancer cells. The mechanisms underlying nuclear dysmorphia in cancer remain poorly understood. Here we identify PPP1R12A and PPP1CB, two subunits of the myosin phosphatase complex that antagonizes actomyosin contractility, as proteins safeguarding nuclear integrity. Loss of PPP1R12A or PPP1CB causes nuclear fragmentation, nuclear envelope rupture, nuclear compartment breakdown and genome instability. Pharmacological or genetic inhibition of actomyosin contractility restores nuclear architecture and genome integrity in cells lacking PPP1R12A or PPP1CB. We detect actin filaments at nuclear envelope rupture sites and define the Rho-ROCK pathway as the driver of nuclear damage. Lamin A protects nuclei from the impact of actomyosin activity. Blocking contractility increases nuclear circularity in cultured cancer cells and suppresses deformations of xenograft nuclei in vivo. We conclude that actomyosin contractility is a major determinant of nuclear shape and that unrestrained contractility causes nuclear dysmorphia, nuclear envelope rupture and genome instability. PMID:28737169

Substrate uptake and protein stability relationship in mammalian histidine decarboxylase.

PubMed

Pino-Angeles, A; Morreale, A; Negri, A; Sánchez-Jiménez, F; Moya-García, A A

2010-01-01

There is some evidence linking the substrate entrance in the active site of mammalian histidine decarboxylase and an increased stability against proteolytic degradation. In this work, we study the basis of this relationship by means of protein structure network analysis and molecular dynamics simulations. We find that the substrate binding to the active site influences the conformation of a flexible region sensible to proteolytic degradation and observe how formation of the Michaelis-Menten complex increases stability in the conformation of this region. (c) 2009 Wiley-Liss, Inc.

Algorithms For Integrating Nonlinear Differential Equations

NASA Technical Reports Server (NTRS)

Freed, A. D.; Walker, K. P.

1994-01-01

Improved algorithms developed for use in numerical integration of systems of nonhomogenous, nonlinear, first-order, ordinary differential equations. In comparison with integration algorithms, these algorithms offer greater stability and accuracy. Several asymptotically correct, thereby enabling retention of stability and accuracy when large increments of independent variable used. Accuracies attainable demonstrated by applying them to systems of nonlinear, first-order, differential equations that arise in study of viscoplastic behavior, spread of acquired immune-deficiency syndrome (AIDS) virus and predator/prey populations.

An efficient liquid chromatography-high resolution mass spectrometry approach for the optimization of the metabolic stability of therapeutic peptides.

PubMed

Esposito, Simone; Mele, Riccardo; Ingenito, Raffaele; Bianchi, Elisabetta; Bonelli, Fabio; Monteagudo, Edith; Orsatti, Laura

2017-04-01

In drug discovery, there is increasing interest in peptides as therapeutic agents due to several appealing characteristics that are typical of this class of compounds, including high target affinity, excellent selectivity, and low toxicity. However, peptides usually present also some challenging ADME (absorption, distribution, metabolism, and excretion) issues such as limited metabolic stability, poor oral bioavailability, and short half-lives. In this context, early preclinical in vitro studies such as plasma metabolic stability assays are crucial to improve developability of a peptidic drug. In order to speed up the optimization of peptide metabolic stability, a strategy was developed for the integrated semi-quantitative determination of metabolic stability of peptides and qualitative identification/structural elucidation of their metabolites in preclinical plasma metabolic stability studies using liquid chromatography-high-resolution Orbitrap™ mass spectrometry (LC-HRMS). Sample preparation was based on protein precipitation: experimental conditions were optimized after evaluating and comparing different organic solvents in order to obtain an adequate extraction of the parent peptides and their metabolites and to minimize matrix effect. Peptides and their metabolites were analyzed by reverse-phase liquid chromatography: a template gradient (total run time, 6 min) was created to allow retention and good peak shape for peptides of different polarity and isoelectric points. Three LC columns were selected to be systematically evaluated for each series of peptides. Targeted and untargeted HRMS data were simultaneously acquired in positive full scan + data-dependent MS/MS acquisition mode, and then processed to calculate plasma half-life and to identify the major cleavage sites, this latter by using the software Biopharma Finder™. Finally, as an example of the application of this workflow, a study that shows the plasma stability improvement of a series of antimicrobial peptides is described. This approach was developed for the evaluation of in vitro plasma metabolic stability studies of peptides, but it could also be applied to other in vitro metabolic stability models (e.g., whole blood, hepatocytes). Graphical Abstract Left: trend plot for omiganan and major metabolites. Right: stability plot for five antimicrobial peptidesafter incubation with mouse plasma.

Stormwater Pollution Prevention Plan (SWPPP) for Coal Storage Area Stabilization Project

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

Project and Design Engineering

2011-03-01

The scope of this project is to stabilize the abandoned coal storage area and redirect the storm water runoff from sanitary sewer system to the storm drain system. Currently, the existing storm water runoff is directed to a perimeter concrete drainage swale and collected in a containment basin. The collected water is then pumped to a treatment facility and after treatment, is discharged to the Y-12 sanitary sewer system. The existing drainage swale and collection basin along with silt fencing will be used during aggregate placement and grading to provide erosion and sediment control. Inlet protection will also be installedmore » around existing structures during the storm water diversion construction. This project scope will include the installation of a non-woven geotextile fabric and compacted mineral aggregate base (paving optional) to stabilize the site. The geotextile specifications are provided on the vendor cut sheets in Appendix B. The installation of a storm water collection/retention area will also be installed on the southern side of the site in accordance with EPA Technical Guidance on Implementing the Stormwater Runoff Requirements for federal Projects under Section 438 of the Energy Independence and Security Act. The total area to be disturbed is approximately 2.5 acres. The order of activities for this Stormwater Pollution Prevention Plan (SWPPP) will be: (1) post notice of coverage (NOC) in a prominent display near entrance of the site; (2) install rain gauge on site or contact Y-12 Plant Shift Superintendent daily for Met tower rain gauge readings; (3) install stabilized construction exit on site; (4) install silt fencing along perimeter as indicated on the attached site plan; (5) regrade site; (6) install geotextile fabric and compacted mineral aggregate base; (7) install catch basin inlet protection where required; (8) excavate and lower existing catch basin tops, re-grade and asphalt to drain; and (9) when all disturbed areas are re-stabilized, remove silt fencing and any other temporary erosion control.« less

Characterization and remediation of a mixed waste-contaminated site at Kirtland Air Force Base, New Mexico

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

Johnston, J.W.; Thacker, M.S.; DeWitt, C.B.

In the area of environmental restoration, one of the most challenging problems is the task of remediating mixed waste-contaminated sites. This paper discusses a successful Interim Corrective Measure (ICM) performed at a mixed waste-contaminated site on Kirtland Air Force Base (AFB) in Albuquerque, New Mexico. The site, known as RW-68, Cratering Area and Radium Dump/Slag Piles, was used during the late 1940s and early 1950s for the destruction and incineration of captured World War II aircraft. It contained 19 slag piles totaling approximately 150 tons of slag, ash, refractory brick, and metal debris. The piles were contaminated with radium-226 andmore » RCRA-characteristic levels of heavy metals. Therefore, the piles were considered mixed waste. To eliminate the threat to human health and the environment, an ICM of removal, segregation, stabilization, and disposal was conducted from October through December 1996. Approximately 120 cubic yards (cu yds) of mixed waste, 188 cu yds of low-level radioactive-contaminated soil, 1 cu yd of low-level radioactive-contaminated debris, 5 cu yds of RCRA-characteristic hazardous waste, and 45 tons of nonhazardous debris were stabilized and disposed of during the ICM. To render the RCRA metals and radionuclides insoluble, stabilization was performed on the mixed and RCRA-characteristic waste streams. All stabilized material was subjected to TCLP analysis to verify it no longer exhibited RCRA-characteristic properties. Radiological and geophysical surveys were conducted concurrently with site remediation activities. These surveys provided real-time documentation of site conditions during each phase of the ICM and confirmed successful cleanup of the site. The three radioactive waste streams, stabilized mixed waste, low-level radioactive-contaminated soil, and low-level radioactive-contaminated debris, were disposed of at the Envirocare low-level radioactive disposal facility.« less

46 CFR 179.212 - Watertight bulkheads for subdivision and damage stability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... this chapter, a monohull vessel which undergoes a simplified stability proof test in accordance with... stability. 179.212 Section 179.212 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) SUBDIVISION, DAMAGE STABILITY, AND WATERTIGHT INTEGRITY Subdivision...

46 CFR 179.212 - Watertight bulkheads for subdivision and damage stability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... this chapter, a monohull vessel which undergoes a simplified stability proof test in accordance with... stability. 179.212 Section 179.212 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) SUBDIVISION, DAMAGE STABILITY, AND WATERTIGHT INTEGRITY Subdivision...

46 CFR 179.212 - Watertight bulkheads for subdivision and damage stability.

Code of Federal Regulations, 2013 CFR

2013-10-01

... this chapter, a monohull vessel which undergoes a simplified stability proof test in accordance with... stability. 179.212 Section 179.212 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) SUBDIVISION, DAMAGE STABILITY, AND WATERTIGHT INTEGRITY Subdivision...

46 CFR 179.212 - Watertight bulkheads for subdivision and damage stability.

Code of Federal Regulations, 2014 CFR

2014-10-01

... this chapter, a monohull vessel which undergoes a simplified stability proof test in accordance with... stability. 179.212 Section 179.212 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) SUBDIVISION, DAMAGE STABILITY, AND WATERTIGHT INTEGRITY Subdivision...

Fabrication of Au 25(SG) 18–ZIF-8 Nanocomposites: A Facile Strategy to Position Au 25(SG) 18 Nanoclusters Inside and Outside ZIF-8

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

Luo, Yucheng; Fan, Shiyan; Yu, Wenqian

Multifunctional composite materials are currently highly desired for sustainable energy applications. A general strategy to integrate atomically precise Au 25(SG) 18 with ZIF-8 (Zn(MeIm) 2, MeIm = 2-methylimidazole), is developed in this paper via the typical Zn-carboxylate type of linkage. Au 25(SG) 18 are uniformly encapsulated into a ZIF-8 framework (Au 25(SG) 18@ZIF-8) by coordination-assisted self-assembly. In contrast, Au 25(SG) 18 integrated by simple impregnation is oriented along the outer surface of ZIF-8 (Au 25(SG) 18/ZIF-8). The porous structure and thermal stability of these nanocomposites are characterized by N 2 adsorption–desorption isothermal analysis and thermal gravimetric analysis. The distribution ofmore » Au 25(SG) 18 in the two nanocomposites is confirmed by electron microscopy, and the accessibility of Au 25(SG) 18 is evaluated by the 4-nitrophenol reduction reaction. The as-prepared nanocomposites retain the high porosity and thermal stability of the ZIF-8 matrix, while also exhibiting the desired catalytic and optical properties derived from the integrated Au 25(SG) 18 nanoclusters (NCs). Au 25(SG) 18@ZIF-8 with isolated Au 25 sites is a promising heterogenous catalyst with size selectivity imparted by the ZIF-8 matrix. Finally, the structural distinction between Au 25(SG) 18@ZIF-8 and Au 25(SG) 18/ZIF-8 determines their different emission features, and provides a new strategy to adjust the optical behavior of Au 25(SG) 18 for applications in bioimaging and biotherapy.« less

Fabrication of Au 25(SG) 18–ZIF-8 Nanocomposites: A Facile Strategy to Position Au 25(SG) 18 Nanoclusters Inside and Outside ZIF-8

DOE PAGES

Luo, Yucheng; Fan, Shiyan; Yu, Wenqian; ...

2017-12-22

Multifunctional composite materials are currently highly desired for sustainable energy applications. A general strategy to integrate atomically precise Au 25(SG) 18 with ZIF-8 (Zn(MeIm) 2, MeIm = 2-methylimidazole), is developed in this paper via the typical Zn-carboxylate type of linkage. Au 25(SG) 18 are uniformly encapsulated into a ZIF-8 framework (Au 25(SG) 18@ZIF-8) by coordination-assisted self-assembly. In contrast, Au 25(SG) 18 integrated by simple impregnation is oriented along the outer surface of ZIF-8 (Au 25(SG) 18/ZIF-8). The porous structure and thermal stability of these nanocomposites are characterized by N 2 adsorption–desorption isothermal analysis and thermal gravimetric analysis. The distribution ofmore » Au 25(SG) 18 in the two nanocomposites is confirmed by electron microscopy, and the accessibility of Au 25(SG) 18 is evaluated by the 4-nitrophenol reduction reaction. The as-prepared nanocomposites retain the high porosity and thermal stability of the ZIF-8 matrix, while also exhibiting the desired catalytic and optical properties derived from the integrated Au 25(SG) 18 nanoclusters (NCs). Au 25(SG) 18@ZIF-8 with isolated Au 25 sites is a promising heterogenous catalyst with size selectivity imparted by the ZIF-8 matrix. Finally, the structural distinction between Au 25(SG) 18@ZIF-8 and Au 25(SG) 18/ZIF-8 determines their different emission features, and provides a new strategy to adjust the optical behavior of Au 25(SG) 18 for applications in bioimaging and biotherapy.« less

Fabrication of Au25 (SG)18 -ZIF-8 Nanocomposites: A Facile Strategy to Position Au25 (SG)18 Nanoclusters Inside and Outside ZIF-8.

PubMed

Luo, Yucheng; Fan, Shiyan; Yu, Wenqian; Wu, Zili; Cullen, David A; Liang, Chaolun; Shi, Jianying; Su, Chengyong

2018-02-01

Multifunctional composite materials are currently highly desired for sustainable energy applications. A general strategy to integrate atomically precise Au 25 (SG) 18 with ZIF-8 (Zn(MeIm) 2 , MeIm = 2-methylimidazole), is developed via the typical Zn-carboxylate type of linkage. Au 25 (SG) 18 are uniformly encapsulated into a ZIF-8 framework (Au 25 (SG) 18 @ZIF-8) by coordination-assisted self-assembly. In contrast, Au 25 (SG) 18 integrated by simple impregnation is oriented along the outer surface of ZIF-8 (Au 25 (SG) 18 /ZIF-8). The porous structure and thermal stability of these nanocomposites are characterized by N 2 adsorption-desorption isothermal analysis and thermal gravimetric analysis. The distribution of Au 25 (SG) 18 in the two nanocomposites is confirmed by electron microscopy, and the accessibility of Au 25 (SG) 18 is evaluated by the 4-nitrophenol reduction reaction. The as-prepared nanocomposites retain the high porosity and thermal stability of the ZIF-8 matrix, while also exhibiting the desired catalytic and optical properties derived from the integrated Au 25 (SG) 18 nanoclusters (NCs). Au 25 (SG) 18 @ZIF-8 with isolated Au 25 sites is a promising heterogenous catalyst with size selectivity imparted by the ZIF-8 matrix. The structural distinction between Au 25 (SG) 18 @ZIF-8 and Au 25 (SG) 18 /ZIF-8 determines their different emission features, and provides a new strategy to adjust the optical behavior of Au 25 (SG) 18 for applications in bioimaging and biotherapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis.

PubMed

Nascimbeni, Anna Chiara; Giordano, Francesca; Dupont, Nicolas; Grasso, Daniel; Vaccaro, Maria I; Codogno, Patrice; Morel, Etienne

2017-07-14

The double-membrane-bound autophagosome is formed by the closure of a structure called the phagophore, origin of which is still unclear. The endoplasmic reticulum (ER) is clearly implicated in autophagosome biogenesis due to the presence of the omegasome subdomain positive for DFCP1, a phosphatidyl-inositol-3-phosphate (PI3P) binding protein. Contribution of other membrane sources, like the plasma membrane (PM), is still difficult to integrate in a global picture. Here we show that ER-plasma membrane contact sites are mobilized for autophagosome biogenesis, by direct implication of the tethering extended synaptotagmins (E-Syts) proteins. Imaging data revealed that early autophagic markers are recruited to E-Syt-containing domains during autophagy and that inhibition of E-Syts expression leads to a reduction in autophagosome biogenesis. Furthermore, we demonstrate that E-Syts are essential for autophagy-associated PI3P synthesis at the cortical ER membrane via the recruitment of VMP1, the stabilizing ER partner of the PI3KC3 complex. These results highlight the contribution of ER-plasma membrane tethers to autophagosome biogenesis regulation and support the importance of membrane contact sites in autophagy. © 2017 The Authors.

Choosing indicators of natural resource condition: A case study in Arches National Park, Utah, USA

USGS Publications Warehouse

Belnap, J.

1998-01-01

Heavy visitor use in many areas of the world have necessitated development of ways to assess visitation impacts. Arches National Park recently completed a Visitor Experience and Resource Protection (VERP) plan. Integral to this plan was developing a method to identify biological indicators that would both measure visitor impacts and response to management actions. The process used in Arches for indicator selection is outlined here as a model applicable to many areas facing similar challenges. The steps were: (1) Vegetation types most used by visitors were identified. Impacted and unimpacted areas in these types were sampled, comparing vegetation and soil factors. (2) Variables found to differ significantly between compared sites were used as potential indicators. (3) Site-specific criteria for indicators were developed, and potential indicators evaluated using these criteria. (4) Chosen indicators were further researched for ecological relevancy. (5) Final indicators were chosen, field tested, and monitoring sites designated. In Arches, indicators were chosen for monitoring annually (soil crust index, soil compaction, number of used social trails and soil aggregate stability) and every five years (vegetation cover and frequency; ground cover; soil chemistry; and plant tissue chemistry).

HIV integration sites and implications for maintenance of the reservoir.

PubMed

Symons, Jori; Cameron, Paul U; Lewin, Sharon R

2018-03-01

To provide an overview of recent research of how HIV integration relates to productive and latent infection and implications for cure strategies. How and where HIV integrates provides new insights into how HIV persists on antiretroviral therapy (ART). Clonal expansion of infected cells with the same integration site demonstrates that T-cell proliferation is an important factor in HIV persistence, however, the driver of proliferation remains unclear. Clones with identical integration sites harbouring defective provirus can accumulate in HIV-infected individuals on ART and defective proviruses can express RNA and produce protein. HIV integration sites differ in clonally expanded and nonexpanded cells and in latently and productively infected cells and this influences basal and inducible transcription. There is a growing number of cellular proteins that can alter the pattern of integration to favour latency. Understanding these pathways may identify new interventions to eliminate latently infected cells. Using advances in analysing HIV integration sites, T-cell proliferation of latently infected cells is thought to play a major role in HIV persistence. Clonal expansion has been demonstrated with both defective and intact viruses. Production of viral RNA and protein from defective viruses may play a role in driving chronic immune activation. The site of integration may determine the likelihood of proliferation and the degree of basal and induced transcription. Finally, host factors and gene expression at the time of infection may determine the integration site. Together these new insights may lead to novel approaches to elimination of latently infected cells.

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

PubMed Central

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

1997-01-01

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

Surface chemical effects on colloid stability and transport through natural porous media

USGS Publications Warehouse

Puls, Robert W.; Paul, Cynthia J.; Clark, Donald A.

1993-01-01

Surface chemical effects on colloidal stability and transport through porous media were investigated using laboratory column techniques. Approximately 100 nm diameter, spherical, iron oxide particles were synthesized as the mobile colloidal phase. The column packing material was retrieved from a sand and gravel aquifer on Cape Cod, MA. Previous studies have indicated enhanced stability and transport of iron oxide particles due to specific adsorption of some inorganic anions on the iron oxide surface. This phenomenon was further evaluated with an anionic surfactant, sodium dodecyl sulfate. Surfactants constitute a significant mass of the contaminant loading at the Cape Cod site and their presence may contribute to colloidal transport as a significant transport mechanism at the site. Other studies at the site have previously demonstrated the occurrence of this transport mechanism for iron phosphate particles. Photon correlation spectroscopy, micro-electrophoretic mobility, and scanning electron microscopy were used to evaluate particle stability, mobility and size. Adsorption of negatively charged organic and inorganic species onto the surface of the iron oxide particles was shown to significantly enhance particle stability and transport through alterations of the electrokinetic properties of the particle surface. Particle breakthrough generally occurred simultaneously with tritiated water, a conservative tracer. The extent of particle breakthrough was primarily dependent upon colloidal stability and surface charge.

Enhanced enzyme stability through site-directed covalent immobilization.

PubMed

Wu, Jeffrey Chun Yu; Hutchings, Christopher Hayden; Lindsay, Mark Jeffrey; Werner, Christopher James; Bundy, Bradley Charles

2015-01-10

Breakthroughs in enzyme immobilization have enabled increased enzyme recovery and reusability, leading to significant decreases in the cost of enzyme use and fueling biocatalysis growth. However, current enzyme immobilization techniques suffer from leaching, enzyme stability, and recoverability and reusability issues. Moreover, these techniques lack the ability to control the orientation of the immobilized enzymes. To determine the impact of orientation on covalently immobilized enzyme activity and stability, we apply our PRECISE (Protein Residue-Explicit Covalent Immobilization for Stability Enhancement) system to a model enzyme, T4 lysozyme. The PRECISE system uses non-canonical amino acid incorporation and the Huisgen 1,3-dipolar cycloaddition "click" reaction to enable directed enzyme immobilization at rationally chosen residues throughout an enzyme. Unlike previous site-specific systems, the PRECISE system is a truly covalent immobilization method. Utilizing this system, enzymes immobilized at proximate and distant locations from the active site were tested for activity and stability under denaturing conditions. Our results demonstrate that orientation control of covalently immobilized enzymes can provide activity and stability benefits exceeding that of traditional random covalent immobilization techniques. PRECISE immobilized enzymes were 50 and 73% more active than randomly immobilized enzymes after harsh freeze-thaw and chemical denaturant treatments. Copyright © 2014 Elsevier B.V. All rights reserved.

A fully integrated oven controlled microelectromechanical oscillator – Part II. Characterization and measurement

DOE PAGES

Wojciechowski, Kenneth E.; Olsson, Roy H.

2015-06-24

Our paper reports the measurement and characterization of a fully integrated oven controlled microelectromechanical oscillator (OCMO). The OCMO takes advantage of high thermal isolation and monolithic integration of both aluminum nitride (AlN) micromechanical resonators and electronic circuitry to thermally stabilize or ovenize all the components that comprise an oscillator. Operation at microscale sizes allows implementation of high thermal resistance platform supports that enable thermal stabilization at very low-power levels when compared with the state-of-the-art oven controlled crystal oscillators. A prototype OCMO has been demonstrated with a measured temperature stability of -1.2 ppb/°C, over the commercial temperature range while using tensmore » of milliwatts of supply power and with a volume of 2.3 mm 3 (not including the printed circuit board-based thermal control loop). Additionally, due to its small thermal time constant, the thermal compensation loop can maintain stability during fast thermal transients (>10 °C/min). This new technology has resulted in a new paradigm in terms of power, size, and warm up time for high thermal stability oscillators.« less

Octahedral tilting instabilities in inorganic halide perovskites

NASA Astrophysics Data System (ADS)

Bechtel, Jonathon S.; Van der Ven, Anton

2018-02-01

Dynamic instabilities, stabilized by anharmonic interactions in cubic and tetragonal halide perovskites at high temperature, play a role in the electronic structure and optoelectronic properties of halide perovskites. In particular, inorganic and hybrid perovskite materials undergo structural phase transitions associated with octahedral tilts of the metal-halide octahedra. We investigate the structural instabilities present in inorganic Cs M X3 perovskites with Pb or Sn on the metal site and Br or I on the X site. Defining primary order parameters in terms of symmetry-adapted collective displacement modes and secondary order parameters in terms of symmetrized Hencky strain components, we unravel the coupling between octahedral tilt modes and macroscopic strains as well as the role of A -site displacements in perovskite phase stability. Symmetry-allowed secondary strain order parameters are enumerated for the 14 unique perovskite tilt systems. Using first-principles calculations to explore the Born-Oppenheimer energy surface in terms of symmetrized order parameters, we find coupling between octahedral tilting and A -site displacements is necessary to stabilize P n m a ground states. Additionally, we show that the relative stability of an inorganic halide perovskite tilt system correlates with the volume decrease from the high-symmetry cubic phase to the low-symmetry distorted phase.

The Competitive Interplay between Allosteric HIV-1 Integrase Inhibitor BI/D and LEDGF/p75 during the Early Stage of HIV-1 Replication Adversely Affects Inhibitor Potency.

PubMed

Feng, Lei; Dharmarajan, Venkatasubramanian; Serrao, Erik; Hoyte, Ashley; Larue, Ross C; Slaughter, Alison; Sharma, Amit; Plumb, Matthew R; Kessl, Jacques J; Fuchs, James R; Bushman, Frederic D; Engelman, Alan N; Griffin, Patrick R; Kvaratskhelia, Mamuka

2016-05-20

Allosteric HIV-1 integrase inhibitors (ALLINIs) have recently emerged as a promising class of antiretroviral agents and are currently in clinical trials. In infected cells, ALLINIs potently inhibit viral replication by impairing virus particle maturation but surprisingly exhibit a reduced EC50 for inhibiting HIV-1 integration in target cells. To better understand the reduced antiviral activity of ALLINIs during the early stage of HIV-1 replication, we investigated the competitive interplay between a potent representative ALLINI, BI/D, and LEDGF/p75 with HIV-1 integrase. While the principal binding sites of BI/D and LEDGF/p75 overlap at the integrase catalytic core domain dimer interface, we show that the inhibitor and the cellular cofactor induce markedly different multimerization patterns of full-length integrase. LEDGF/p75 stabilizes an integrase tetramer through the additional interactions with the integrase N-terminal domain, whereas BI/D induces protein-protein interactions in C-terminal segments that lead to aberrant, higher-order integrase multimerization. We demonstrate that LEDGF/p75 binds HIV-1 integrase with significantly higher affinity than BI/D and that the cellular protein is able to reverse the inhibitor induced aberrant, higher-order integrase multimerization in a dose-dependent manner in vitro. Consistent with these observations, alterations of the cellular levels of LEDGF/p75 markedly affected BI/D EC50 values during the early steps of HIV-1 replication. Furthermore, genome-wide sequencing of HIV-1 integration sites in infected cells demonstrate that LEDGF/p75-dependent integration site selection is adversely affected by BI/D treatment. Taken together, our studies elucidate structural and mechanistic details of the interplay between LEDGF/p75 and BI/D during the early stage of HIV-1 replication.

Stabilization of Telomere G-Quadruplexes Interferes with Human Herpesvirus 6A Chromosomal Integration.

PubMed

Gilbert-Girard, Shella; Gravel, Annie; Artusi, Sara; Richter, Sara N; Wallaschek, Nina; Kaufer, Benedikt B; Flamand, Louis

2017-07-15

Human herpesviruses 6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes using a mechanism that remains poorly understood. To achieve a better understanding of the HHV-6A/B integration mechanism, we made use of BRACO-19, a compound that stabilizes G-quadruplex secondary structures and prevents telomere elongation by the telomerase complex. First, we analyzed the folding of telomeric sequences into G-quadruplex structures and their binding to BRACO-19 using G-quadruplex-specific antibodies and surface plasmon resonance. Circular dichroism studies indicate that BRACO-19 modifies the conformation and greatly stabilizes the G-quadruplexes formed in G-rich telomeric DNA. Subsequently we assessed the effects of BRACO-19 on the HHV-6A initial phase of infection. Our results indicate that BRACO-19 does not affect entry of HHV-6A DNA into cells. We next investigated if stabilization of G-quadruplexes by BRACO-19 affected HHV-6A's ability to integrate its genome into host chromosomes. Incubation of telomerase-expressing cells with BRACO-19, such as HeLa and MCF-7, caused a significant reduction in the HHV-6A integration frequency ( P < 0.002); in contrast, BRACO-19 had no effect on HHV-6 integration frequency in U2OS cells that lack telomerase activity and elongate their telomeres through alternative lengthening mechanisms. Our data suggest that the fluidity of telomeres is important for efficient chromosomal integration of HHV-6A and that interference with telomerase activity negatively affects the generation of cellular clones containing integrated HHV-6A. IMPORTANCE HHV-6A/B can integrate their genomes into the telomeres of infected cells. Telomeres consist of repeated hexanucleotides (TTAGGG) of various lengths (up to several kilobases) and end with a single-stranded 3' extension. To avoid recognition and induce a DNA damage response, the single-stranded overhang folds back on itself and forms a telomeric loop (T-loop) or adopts a tertiary structure, referred to as a G-quadruplex. In the current study, we have examined the effects of a G-quadruplex binding and stabilizing agent, BRACO-19, on HHV-6A chromosomal integration. By stabilizing G-quadruplex structures, BRACO-19 affects the ability of the telomerase complex to elongate telomeres. Our results indicate that BRACO-19 reduces the number of clones harboring integrated HHV-6A. This study is the first of its kind and suggests that telomerase activity is essential to restore a functional telomere of adequate length following HHV-6A integration. Copyright © 2017 American Society for Microbiology.

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

Vaccarono, Mattia; Bechini, Renzo; Chandrasekar, Chandra V.

The stability of weather radar calibration is a mandatory aspect for quantitative applications, such as rainfall estimation, short-term weather prediction and initialization of numerical atmospheric and hydrological models. Over the years, calibration monitoring techniques based on external sources have been developed, specifically calibration using the Sun and calibration based on ground clutter returns. In this paper, these two techniques are integrated and complemented with a self-consistency procedure and an intercalibration technique. The aim of the integrated approach is to implement a robust method for online monitoring, able to detect significant changes in the radar calibration. The physical consistency of polarimetricmore » radar observables is exploited using the self-consistency approach, based on the expected correspondence between dual-polarization power and phase measurements in rain. This technique allows a reference absolute value to be provided for the radar calibration, from which eventual deviations may be detected using the other procedures. In particular, the ground clutter calibration is implemented on both polarization channels (horizontal and vertical) for each radar scan, allowing the polarimetric variables to be monitored and hardware failures to promptly be recognized. The Sun calibration allows monitoring the calibration and sensitivity of the radar receiver, in addition to the antenna pointing accuracy. It is applied using observations collected during the standard operational scans but requires long integration times (several days) in order to accumulate a sufficient amount of useful data. Finally, an intercalibration technique is developed and performed to compare colocated measurements collected in rain by two radars in overlapping regions. The integrated approach is performed on the C-band weather radar network in northwestern Italy, during July–October 2014. The set of methods considered appears suitable to establish an online tool to monitor the stability of the radar calibration with an accuracy of about 2 dB. In conclusion, this is considered adequate to automatically detect any unexpected change in the radar system requiring further data analysis or on-site measurements.« less

Stabilization of apoptotic cells: generation of zombie cells.

PubMed

Oropesa-Ávila, M; Andrade-Talavera, Y; Garrido-Maraver, J; Cordero, M D; de la Mata, M; Cotán, D; Paz, M V; Pavón, A D; Alcocer-Gómez, E; de Lavera, I; Lema, R; Zaderenko, A P; Rodríguez-Moreno, A; Sánchez-Alcázar, J A

2014-08-14

Apoptosis is characterized by degradation of cell components but plasma membrane remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis forming a cortical structure beneath plasma membrane that maintains plasma membrane integrity. Apoptotic cells are also characterized by high reactive oxygen species (ROS) production that can be potentially harmful for the cell. The aim of this study was to develop a method that allows stabilizing apoptotic cells for diagnostic and therapeutic applications. By using a cocktail composed of taxol (a microtubule stabilizer), Zn(2+) (a caspase inhibitor) and coenzyme Q10 (a lipid antioxidant), we were able to stabilize H460 apoptotic cells in cell cultures for at least 72 h, preventing secondary necrosis. Stabilized apoptotic cells maintain many apoptotic cell characteristics such as the presence of apoptotic microtubules, plasma membrane integrity, low intracellular calcium levels and mitochondrial polarization. Apoptotic cell stabilization may open new avenues in apoptosis detection and therapy.

Stabilization of apoptotic cells: generation of zombie cells

PubMed Central

Oropesa-Ávila, M; Andrade-Talavera, Y; Garrido-Maraver, J; Cordero, M D; de la Mata, M; Cotán, D; Paz, M V; Pavón, A D; Alcocer-Gómez, E; de Lavera, I; Lema, R; Zaderenko, A P; Rodríguez-Moreno, A; Sánchez-Alcázar, J A

2014-01-01

Apoptosis is characterized by degradation of cell components but plasma membrane remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis forming a cortical structure beneath plasma membrane that maintains plasma membrane integrity. Apoptotic cells are also characterized by high reactive oxygen species (ROS) production that can be potentially harmful for the cell. The aim of this study was to develop a method that allows stabilizing apoptotic cells for diagnostic and therapeutic applications. By using a cocktail composed of taxol (a microtubule stabilizer), Zn2+ (a caspase inhibitor) and coenzyme Q10 (a lipid antioxidant), we were able to stabilize H460 apoptotic cells in cell cultures for at least 72 h, preventing secondary necrosis. Stabilized apoptotic cells maintain many apoptotic cell characteristics such as the presence of apoptotic microtubules, plasma membrane integrity, low intracellular calcium levels and mitochondrial polarization. Apoptotic cell stabilization may open new avenues in apoptosis detection and therapy. PMID:25118929

Stability analysis of neural networks with time-varying delay: Enhanced stability criteria and conservatism comparisons

NASA Astrophysics Data System (ADS)

Lin, Wen-Juan; He, Yong; Zhang, Chuan-Ke; Wu, Min

2018-01-01

This paper is concerned with the stability analysis of neural networks with a time-varying delay. To assess system stability accurately, the conservatism reduction of stability criteria has attracted many efforts, among which estimating integral terms as exact as possible is a key issue. At first, this paper develops a new relaxed integral inequality to reduce the estimation gap of popular Wirtinger-based inequality (WBI). Then, for showing the advantages of the proposed inequality over several existing inequalities that also improve the WBI, four stability criteria are derived through different inequalities and the same Lyapunov-Krasovskii functional (LKF), and the conservatism comparison of them is analyzed theoretically. Moreover, an improved criterion is established by combining the proposed inequality and an augmented LKF with delay-product-type terms. Finally, several numerical examples are used to demonstrate the advantages of the proposed method.

Environmental assessment of remedial action at the Gunnison Uranium Mill Tailings Site, Gunnison, Colorado. [UMTRA Project

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

Bachrach, A.; Hoopes, J.; Morycz, D.

1984-12-01

This document assesses and compares the environmental impacts of various alternatives for remedial action at the Gunnison uranium of mill tailings site located 0.5 miles south of Gunnison, Colorado. The site covers 56 acres and contains 35 acres of tailings, 2 of the original mill buildings and a water tower. The Uranium Mill Tailings Radiation Control of Act of 1978 (UMTRCA), Public Law 95-604, authorizes the US Department of Energy to clean up the site to reduce the potential health impacts associated with the residual radioactive materials remaining at the site and at associated (vicinity) properties off the site. Themore » US Environmental Protection Agency promulgated standards for the remedial actions (40 CFR 192). Remedial actions must be performed in accordance with these standards and with the occurrence of the Nuclear Regulatory Commission. Four alternatives have been addressed in this document. The first alternative is to consolidate the tailings and associated contaminated soils into a recontoured pile on the southern portion of the existing site. A radon barrier of silty clay would be constructed over the pile and various erosion control measures would be taken to assure the long-term integrity of the pile. Two other alternatives which involve moving the tailings to new locations are assessed in this document. These alternatives generally involve greater short-term impacts and are more costly but would result in the tailings being stabilized in a location farther from the city of Gunnison. The no action alternative is also assessed.« less

Streambed stability and scour potential at selected bridge sites in Michigan

USGS Publications Warehouse

Holtschlag, D.J.; Miller, R.L.

1998-01-01

Contraction scour in the main stream channel at a bridge and local scour near piers and abutments can result in bridge failure. Estimates of contraction-scour and local-scour potentials associated with the 100-year flood were computed for 13 bridge sites in Michigan by use of semi-theoretical equations and procedures recommended by the Federal Highway Administration. These potentials were compared with measures of Streambed stability obtained by use of data from 773 historical streamflow measurements, documenting 20,741 individual Streambed soundings between 1959 and 1995. Analysis of these data indicate small, but statistically significant, monotonic trends in Streambed elevation at 10 sites. No consistent patterns in relations between changes in Streambed elevations and streamflow, flow velocity, or flow depth were evident. Also, estimates of contraction-scour potential were not correlated with measures of Streambed stability, and no differences were detected between measures of Streambed stability in the main channel and stability adjacent to piers. Despite the inconsistencies between measures of Streambed stability and scour potential, data from a single, large flood (greater than a 100-year event) provided field evidence that the relation between scour and streamflow is highly nonlinear. This nonlinearity and the limited availability of measurements of extreme flood events may have reduced the utility of the empirical measures for confirming the nonlinear scour-potential equations and procedures. Results of field surveys using ground-penetrating radar and tuned transducers showed limited ability to aid interpretation of historical scour conditions at four bridge sites. Additional research is needed to confirm the applicability of scour-potential equations for hydrogeologic conditions in Michigan.

Changes in implant stability using different site preparation techniques: twist drills versus piezosurgery. A single-blinded, randomized, controlled clinical trial.

PubMed

Stacchi, Claudio; Vercellotti, Tomaso; Torelli, Lucio; Furlan, Fabio; Di Lenarda, Roberto

2013-04-01

The objective of the present investigation was to longitudinally monitor stability changes of implants inserted using traditional rotary instruments or piezoelectric inserts, and to follow their variations during the first 90 days of healing. A randomized, controlled trial was conducted on 20 patients. Each patient received two identical, adjacent implants in the upper premolar area: the test site was prepared with piezosurgery, and the control site was prepared using twist drills. Resonance frequency analysis measurements were taken by a blinded operator on the day of surgery and after 7, 14, 21, 28, 42, 56, and 90 days. At 90 days, 39 out of 40 implants were osseointegrated (one failure in the control group). Both groups showed an initial decrease in mean implant stability quotient (ISQ) values: a shift in implant stability to increasing ISQ values occurred after 14 days in the test group and after 21 days in the control group. The lowest mean ISQ value was recorded at 14 days for test implants (97.3% of the primary stability) and at 21 days for the control implants (90.8% of the primary stability). ISQ variations with respect to primary stability differed significantly between the two groups during the entire period of observation: from day 14 to day 42, in particular, the differences were extremely significant (p < .0001). All 39 implants were in function successfully at the visit scheduled 1 year after insertion. The findings from this study suggest that ultrasonic implant site preparation results in a limited decrease of ISQ values and in an earlier shifting from a decreasing to an increasing stability pattern, when compared with the traditional drilling technique. From a clinical point of view, implants inserted with the piezoelectric technique demonstrated a short-term clinical success similar to those inserted using twist drills. © 2011 Wiley Periodicals, Inc.

Stability and square integrability of derivatives of solutions of nonlinear fourth order differential equations with delay.

PubMed

Korkmaz, Erdal

2017-01-01

In this paper, we give sufficient conditions for the boundedness, uniform asymptotic stability and square integrability of the solutions to a certain fourth order non-autonomous differential equations with delay by using Lyapunov's second method. The results obtained essentially improve, include and complement the results in the literature.

Morgan Materials Site, Town of Tonawanda, New York

EPA Pesticide Factsheets

The Morgan Materials Site is a series of warehouses where hazardous and nonhazardous products were purchased from chemical companies and improperly stored. EPA assumed the responsibility to stabilize the site.

Assessing Atmospheric CO2 Entrapped in Clay Nanotubes using Residual Gas Analyzer.

PubMed

Das, Sankar; Maity, Abhijit; Pradhan, Manik; Jana, Subhra

2016-02-16

A residual gas analyzer (RGA) coupled with a high-vacuum chamber has been explored to measure atmospheric CO2 entrapped in aminosilane-modified clay nanotubes. Ambient CO2 uptake efficacy together with stability of these novel adsorbents composed of both primary and/or secondary amine sites has been demonstrated at standard ambient temperature and pressure. The unprecedented sensitivity and accuracy of the RGA-based mass spectrometry technique toward atmospheric CO2 measurement has been substantiated with a laser-based optical cavity-enhanced integrated cavity output spectroscopy. The adsorption kinetics of atmospheric CO2 on amine-functionalized clay nanotubes followed the fractional-order kinetic model compared to that of the pseudo-first-order or pseudo-second-order rate equations. The efficiency along with stability of these novel adsorbents has also been demonstrated by their repetitive use for CO2 capture in the oxidative environment. Our findings thus point to a fundamental study on the atmospheric CO2 adsorption by amine-loaded adsorbents using an easy handling and low-cost benchtop RGA-based mass spectrometer, opening a new strategy for CO2 capture and sequestering study.

Entry Atmospheric Flight Control Authority Impacts on GN and C and Trajectory Performance for Orion Exploration Flight Test 1

NASA Technical Reports Server (NTRS)

McNamara, Luke W.

2012-01-01

One of the key design objectives of NASA's Orion Exploration Flight Test 1 (EFT-1) is to execute a guided entry trajectory demonstrating GN&C capability. The focus of this paper is the ight control authority of the vehicle throughout the atmospheric entry ight to the target landing site and its impacts on GN&C, parachute deployment, and integrated performance. The vehicle's attitude control authority is obtained from thrusting 12 Re- action Control System (RCS) engines, with four engines to control yaw, four engines to control pitch, and four engines to control roll. The static and dynamic stability derivatives of the vehicle are determined to assess the inherent aerodynamic stability. The aerodynamic moments at various locations in the entry trajectory are calculated and compared to the available torque provided by the RCS system. Interaction between the vehicle's RCS engine plumes and the aerodynamic conditions are considered to assess thruster effectiveness. This document presents an assessment of Orion's ight control authority and its effectiveness in controlling the vehicle during critical events in the atmospheric entry trajectory.

Isotopic equilibria in aqueous clusters at low temperatures: Insights from the MB-pol many-body potential

NASA Astrophysics Data System (ADS)

Videla, Pablo E.; Rossky, Peter J.; Laria, Daniel

2018-02-01

By combining path-integrals molecular dynamics simulations with the accurate MB-pol potential energy surface, we investigate the role of alternative potential models on isotopic fractionation ratios between H and D atoms at dangling positions in water clusters at low temperatures. Our results show clear stabilizations of the lighter isotope at dangling sites, characterized by free energy differences ΔG that become comparable to or larger than kBT for temperatures below ˜75 K. The comparison between these results to those previously reported using the empirical q-TIP4P/F water model [P. E. Videla et al., J. Phys. Chem. Lett. 5, 2375 (2014)] reveals that the latter Hamiltonian overestimates the H stabilization by ˜25%. Moreover, predictions from the MB-pol model are in much better agreement with measured results reported for similar isotope equilibria at ice surfaces. The dissection of the quantum kinetic energies into orthogonal directions shows that the dominant differences between the two models are to be found in the anharmonic characteristics of the potential energy surfaces along OH bond directions involved in hydrogen bonds.

Active-site copper reduction promotes substrate binding of fungal lytic polysaccharide monooxygenase and reduces stability.

PubMed

Kracher, Daniel; Andlar, Martina; Furtmüller, Paul G; Ludwig, Roland

2018-02-02

Lytic polysaccharide monooxygenases (LPMOs) are a class of copper-containing enzymes that oxidatively degrade insoluble plant polysaccharides and soluble oligosaccharides. Upon reductive activation, they cleave the substrate and promote biomass degradation by hydrolytic enzymes. In this study, we employed LPMO9C from Neurospora crassa , which is active toward cellulose and soluble β-glucans, to study the enzyme-substrate interaction and thermal stability. Binding studies showed that the reduction of the mononuclear active-site copper by ascorbic acid increased the affinity and the maximum binding capacity of LPMO for cellulose. The reduced redox state of the active-site copper and not the subsequent formation of the activated oxygen species increased the affinity toward cellulose. The lower affinity of oxidized LPMO could support its desorption after catalysis and allow hydrolases to access the cleavage site. It also suggests that the copper reduction is not necessarily performed in the substrate-bound state of LPMO. Differential scanning fluorimetry showed a stabilizing effect of the substrates cellulose and xyloglucan on the apparent transition midpoint temperature of the reduced, catalytically active enzyme. Oxidative auto-inactivation and destabilization were observed in the absence of a suitable substrate. Our data reveal the determinants of LPMO stability under turnover and non-turnover conditions and indicate that the reduction of the active-site copper initiates substrate binding. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Chelonia: A self-healing, replicated storage system

NASA Astrophysics Data System (ADS)

Kerr Nilsen, Jon; Toor, Salman; Nagy, Zsombor; Read, Alex

2011-12-01

Chelonia is a novel grid storage system designed to fill the requirements gap between those of large, sophisticated scientific collaborations which have adopted the grid paradigm for their distributed storage needs, and of corporate business communities gravitating towards the cloud paradigm. Chelonia is an integrated system of heterogeneous, geographically dispersed storage sites which is easily and dynamically expandable and optimized for high availability and scalability. The architecture and implementation in term of web-services running inside the Advanced Resource Connector Hosting Environment Dameon (ARC HED) are described and results of tests in both local -area and wide-area networks that demonstrate the fault tolerance, stability and scalability of Chelonia will be presented. In addition, example setups for production deployments for small and medium-sized VO's are described.

Cryogen-free dilution refrigerator for ACTPOL polarization- sensitive receiver

NASA Astrophysics Data System (ADS)

Shvarts, V.; Zhao, Z.; Devlin, M. J.; Klein, J.; Lungu, M.; Schmitt, B.; Thornton, R.

2014-12-01

We present a new cryogenic receiver for the Atacama Cosmology Telescope (ACT), a six-meter diameter off-axis Gregorian telescope located at an altitude of 5,200 meters (17,000 ft.) on Cerro Toco, in Northern Chile. The focal plane contains 3000 polarization-sensitive transition edge sensor (TES) bolometers, and is cooled to below 100 mK with a removable pulse-tube based customised JDry-100 dilution refrigerator insert. The optical tubes and the rest of the receiver are cooled with a dedicated pulse tube to below 3 K. Details of the receiver- to-telescope integration and first season on-site operation are described, including detector base temperature stability in vertical and tilted position as well as remote operation via Ethernet link.

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

PubMed Central

Serrao, Erik; Engelman, Alan N.

2016-01-01

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

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.

Floral trait variation and integration as a function of sexual deception in Gorteria diffusa

PubMed Central

Ellis, Allan G.; Brockington, Samuel F.; de Jager, Marinus L.; Mellers, Gregory; Walker, Rachel H.; Glover, Beverley J.

2014-01-01

Phenotypic integration, the coordinated covariance of suites of morphological traits, is critical for proper functioning of organisms. Angiosperm flowers are complex structures comprising suites of traits that function together to achieve effective pollen transfer. Floral integration could reflect shared genetic and developmental control of these traits, or could arise through pollinator-imposed stabilizing correlational selection on traits. We sought to expose mechanisms underlying floral trait integration in the sexually deceptive daisy, Gorteria diffusa, by testing the hypothesis that stabilizing selection imposed by male pollinators on floral traits involved in mimicry has resulted in tighter integration. To do this, we quantified patterns of floral trait variance and covariance in morphologically divergent G. diffusa floral forms representing a continuum in the levels of sexual deception. We show that integration of traits functioning in visual attraction of male pollinators increases with pollinator deception, and is stronger than integration of non-mimicry trait modules. Consistent patterns of within-population trait variance and covariance across floral forms suggest that integration has not been built by stabilizing correlational selection on genetically independent traits. Instead pollinator specialization has selected for tightened integration within modules of linked traits. Despite potentially strong constraint on morphological evolution imposed by developmental genetic linkages between traits, we demonstrate substantial divergence in traits across G. diffusa floral forms and show that divergence has often occurred without altering within-population patterns of trait correlations. PMID:25002705

Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics

PubMed Central

Doolittle-Hall, Janet M.; Cunningham Glasspoole, Danielle L.; Seaman, William T.; Webster-Cyriaque, Jennifer

2015-01-01

Oncoviruses cause tremendous global cancer burden. For several DNA tumor viruses, human genome integration is consistently associated with cancer development. However, genomic features associated with tumor viral integration are poorly understood. We sought to define genomic determinants for 1897 loci prone to hosting human papillomavirus (HPV), hepatitis B virus (HBV) or Merkel cell polyomavirus (MCPyV). These were compared to HIV, whose enzyme-mediated integration is well understood. A comprehensive catalog of integration sites was constructed from the literature and experimentally-determined HPV integration sites. Features were scored in eight categories (genes, expression, open chromatin, histone modifications, methylation, protein binding, chromatin segmentation and repeats) and compared to random loci. Random forest models determined loci classification and feature selection. HPV and HBV integrants were not fragile site associated. MCPyV preferred integration near sensory perception genes. Unique signatures of integration-associated predictive genomic features were detected. Importantly, repeats, actively-transcribed regions and histone modifications were common tumor viral integration signatures. PMID:26569308

Characterization of genetic elements required for site-specific integration of Lactobacillus delbrueckii subsp. bulgaricus bacteriophage mv4 and construction of an integration-proficient vector for Lactobacillus plantarum.

PubMed Central

Dupont, L; Boizet-Bonhoure, B; Coddeville, M; Auvray, F; Ritzenthaler, P

1995-01-01

Temperate phage mv4 integrates its DNA into the chromosome of Lactobacillus delbrueckii subsp. bulgaricus strains via site-specific recombination. Nucleotide sequencing of a 2.2-kb attP-containing phage fragment revealed the presence of four open reading frames. The larger open reading frame, close to the attP site, encoded a 427-amino-acid polypeptide with similarity in its C-terminal domain to site-specific recombinases of the integrase family. Comparison of the sequences of attP, bacterial attachment site attB, and host-phage junctions attL and attR identified a 17-bp common core sequence, where strand exchange occurs during recombination. Analysis of the attB sequence indicated that the core region overlaps the 3' end of a tRNA(Ser) gene. Phage mv4 DNA integration into the tRNA(Ser) gene preserved an intact tRNA(Ser) gene at the attL site. An integration vector based on the mv4 attP site and int gene was constructed. This vector transforms a heterologous host, L. plantarum, through site-specific integration into the tRNA(Ser) gene of the genome and will be useful for development of an efficient integration system for a number of additional bacterial species in which an identical tRNA gene is present. PMID:7836291

The effects of surgical preparation techniques and implant macro-geometry on primary stability: An in vitro study

PubMed Central

Severino, Marco; Rastelli, Claudio; Bernardi, Sara; Caruso, Silvia; Galli, Massimo; Lamazza, Luca; Di Paolo, Carlo

2017-01-01

Background The attainment of a good primary stability is a necessary condition to ensure the success of osseointegration in implantology. In type IV cancellous bone, however, it is possible that a reduced primary stability can lead to an increased rate of failure. The aim of this study was therefore to determine, with the help of the resonance frequency (Osstell mentor), which technique of implant site preparation (piezo surgery, conventional, under-preparation, bone compaction, osteodistraction) and macro-geometry is able to improve implant stability in type IV cancellous bone. Material and Methods 10 pig ribs were prepared with a surgical pre-drilled guide, calibrated for a correct implant positioning. On each rib, 5 implant sites (one for each technique) were prepared. Successively, 50 conical implants (Tekka Global D) were inserted and measured with the resonance frequency to evaluate the primary stability. Data collected were analyzed by analysis of variance (ANOVA) to test whether the Implant Stability Quotient (ISQ) values of the five techniques were significantly different. Results The results showed that no significant differences among the ISQ values of the five techniques used were found. Also, no significant differences in the macro-geometry of the two types of compared implants were observed. However, the macro-geometry of Tekka implants, characterized by a double condensing thread, seems to provide greater ISQ values than those of single thread implants when using the same technique. Conclusions In light of these preliminary data, it is conceivable that in cases of reduced stability, such as those occurring with a type IV bone, all means ameliorating the primary stability and accelerating the osseointegration can be utilized. Key words:Implant primary stability, resonance frequency analysis, implant site preparation. PMID:28160577

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

NASA Technical Reports Server (NTRS)

Jaynes, R. A.

1983-01-01

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

Zinc cobalt sulfide nanosheets array derived from 2D bimetallic metal-organic frameworks for high-performance supercapacitor.

PubMed

Tao, Kai; Han, Xue; Cheng, Qiuhui; Yang, Yujing; Yang, Zheng; Ma, Qingxiang; Han, Lei

2018-04-19

Porous ternary metal sulfide integrated electrode materials with abundant electroactive sites and redox reactions are very promising for supercapacitors. Here, porous zinc cobalt sulfide nanosheets array on Ni foam (Zn-Co-S/NF) has been successfully constructed by a facile growth of 2D bimetallic zinc/cobalt-based metal-organic frameworks (Zn/Co-MOF) nanosheets with leaf-like morphology on Ni foam, followed by additional sulfurization. The Zn-Co-S/NF nanosheets array is directly acted as an electrode for supercapacitor, showing much better electrochemical performance (2354.3 F g-1 and 88.6% retention over 1000 cycles) when compared with zinc cobalt sulfide powder (355.3 F g-1 and 75.8% retention over 1000 cycles), which is originated from good electric conductivity and mechanical stability, abundant electroactive sites, and facilitated transportation of electron and electrolyte ion endowed by the unique nanosheets array structure. The asymmetric supercapacitor (ASC) device assembled from Zn-Co-S/NF and activated carbon electrodes can deliver the highest energy density of 31.9 Wh kg-1 and the maximum power density of 8.5 kW kg-1. Most importantly, this ASC also presents good cycling stability (97% retention over 1000 cycles). Furthermore, a red light-emitting diode (LED) can be illuminated by two connected ASCs, indicating that as-synthesized Zn-Co-S/NF hold great potential for practical applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interrelations of secondary structure stability and DNA-binding affinity in the bacteriophage SPO1-encoded type II DNA-binding protein TF1.

PubMed

Andera, L; Spangler, C J; Galeone, A; Mayol, L; Geiduschek, E P

1994-02-11

TF1, a homodimeric DNA-binding and -bending protein with a preference for hydroxymethyluracil-containing DNA is the Bacillus subtilis-encoded homolog of the bacterial HU proteins and of the E. coli integration host factor. A temperature-sensitive mutation at amino acid 25 of TF1 (L25-->A) and two intragenic second site revertants at amino acids 15 (E15-->G) and 32 (L32-->I) were previously identified and their effects on virus development were examined. The DNA-binding properties of these proteins and the thermal stability of their secondary structures have now been analyzed. Amino acids 15 and 32 are far removed from the putative DNA-binding domains of TF1 but changes there exert striking effects on DNA affinity that correlate with effects on structure. The double mutant protein TF1-G15I32 binds to a preferred site in hydroxymethyluracil-containing DNA 40 times more tightly, denatures at higher temperature (delta tm = 21 degrees C), and also exchanges subunits much more slowly than does the wild-type protein. The L25-->A mutation makes TF1 secondary structure and DNA-binding highly salt concentration-dependent. The E15-->G mutation partly suppresses this effect: secondary structure of TF1-A25G15 is restored at 21 degrees C by 1 M NaCl or, at low NaCl concentration, by binding to DNA.

Mapping the Fluid Pathways and Permeability Barriers of a Large Gas Hydrate Reservoir

NASA Astrophysics Data System (ADS)

Campbell, A.; Zhang, Y. L.; Sun, L. F.; Saleh, R.; Pun, W.; Bellefleur, G.; Milkereit, B.

2012-12-01

An understanding of the relationship between the physical properties of gas hydrate saturated sedimentary basins aids in the detection, exploration and monitoring one of the world's upcoming energy resources. A large gas hydrate reservoir is located in the MacKenzie Delta of the Canadian Arctic and geophysical logs from the Mallik test site are available for the gas hydrate stability zone (GHSZ) between depths of approximately 850 m to 1100 m. The geophysical data sets from two neighboring boreholes at the Mallik test site are analyzed. Commonly used porosity logs, as well as nuclear magnetic resonance, compressional and Stoneley wave velocity dispersion logs are used to map zones of elevated and severely reduced porosity and permeability respectively. The lateral continuity of horizontal permeability barriers can be further understood with the aid of surface seismic modeling studies. In this integrated study, the behavior of compressional and Stoneley wave velocity dispersion and surface seismic modeling studies are used to identify the fluid pathways and permeability barriers of the gas hydrate reservoir. The results are compared with known nuclear magnetic resonance-derived permeability values. The aim of investigating this heterogeneous medium is to map the fluid pathways and the associated permeability barriers throughout the gas hydrate stability zone. This provides a framework for an understanding of the long-term dissociation of gas hydrates along vertical and horizontal pathways, and will improve the knowledge pertaining to the production of such a promising energy source.

High-Performance Flexible Organic Nano-Floating Gate Memory Devices Functionalized with Cobalt Ferrite Nanoparticles.

PubMed

Jung, Ji Hyung; Kim, Sunghwan; Kim, Hyeonjung; Park, Jongnam; Oh, Joon Hak

2015-10-07

Nano-floating gate memory (NFGM) devices are transistor-type memory devices that use nanostructured materials as charge trap sites. They have recently attracted a great deal of attention due to their excellent performance, capability for multilevel programming, and suitability as platforms for integrated circuits. Herein, novel NFGM devices have been fabricated using semiconducting cobalt ferrite (CoFe2O4) nanoparticles (NPs) as charge trap sites and pentacene as a p-type semiconductor. Monodisperse CoFe2O4 NPs with different diameters have been synthesized by thermal decomposition and embedded in NFGM devices. The particle size effects on the memory performance have been investigated in terms of energy levels and particle-particle interactions. CoFe2O4 NP-based memory devices exhibit a large memory window (≈73.84 V), a high read current on/off ratio (read I(on)/I(off)) of ≈2.98 × 10(3), and excellent data retention. Fast switching behaviors are observed due to the exceptional charge trapping/release capability of CoFe2O4 NPs surrounded by the oleate layer, which acts as an alternative tunneling dielectric layer and simplifies the device fabrication process. Furthermore, the NFGM devices show excellent thermal stability, and flexible memory devices fabricated on plastic substrates exhibit remarkable mechanical and electrical stability. This study demonstrates a viable means of fabricating highly flexible, high-performance organic memory devices. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A fully integrated oven controlled microelectromechanical oscillator -- Part I. Design and fabrication

DOE PAGES

Wojciechowski, Kenneth E.; Baker, Michael S.; Clews, Peggy J.; ...

2015-06-24

Our paper reports the design and fabrication of a fully integrated oven controlled microelectromechanical oscillator (OCMO). This paper begins by describing the limits on oscillator frequency stability imposed by the thermal drift and electronic properties (Q, resistance) of both the resonant tank circuit and feedback electronics required to form an electronic oscillator. An OCMO is presented that takes advantage of high thermal isolation and monolithic integration of both micromechanical resonators and electronic circuitry to thermally stabilize or ovenize all the components that comprise an oscillator. This was achieved by developing a processing technique where both silicon-on-insulator complementary metal-oxide-semiconductor (CMOS) circuitrymore » and piezoelectric aluminum nitride, AlN, micromechanical resonators are placed on a suspended platform within a standard CMOS integrated circuit. Operation at microscale sizes achieves high thermal resistances (~10 °C/mW), and hence thermal stabilization of the oscillators at very low-power levels when compared with the state-of-the-art ovenized crystal oscillators, OCXO. This constant resistance feedback circuit is presented that incorporates on platform resistive heaters and temperature sensors to both measure and stabilize the platform temperature. Moreover, the limits on temperature stability of the OCMO platform and oscillator frequency imposed by the gain of the constant resistance feedback loop, placement of the heater and temperature sensing resistors, as well as platform radiative and convective heat losses are investigated.« less

Site-to-site interdomain communication may mediate different loss-of-function mechanisms in a cancer-associated NQO1 polymorphism

NASA Astrophysics Data System (ADS)

Medina-Carmona, Encarnación; Neira, Jose L.; Salido, Eduardo; Fuchs, Julian E.; Palomino-Morales, Rogelio; Timson, David J.; Pey, Angel L.

2017-03-01

Disease associated genetic variations often cause intracellular enzyme inactivation, dysregulation and instability. However, allosteric communication of mutational effects to distant functional sites leading to loss-of-function remains poorly understood. We characterize here interdomain site-to-site communication by which a common cancer-associated single nucleotide polymorphism (c.C609T/p.P187S) reduces the activity and stability in vivo of NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a FAD-dependent, two-domain multifunctional stress protein acting as a Phase II enzyme, activating cancer pro-drugs and stabilizing p53 and p73α oncosuppressors. We show that p.P187S causes structural and dynamic changes communicated to functional sites far from the mutated site, affecting the FAD binding site located at the N-terminal domain (NTD) and accelerating proteasomal degradation through dynamic effects on the C-terminal domain (CTD). Structural protein:protein interaction studies reveal that the cancer-associated polymorphism does not abolish the interaction with p73α, indicating that oncosuppressor destabilization largely mirrors the low intracellular stability of p.P187S. In conclusion, we show how a single disease associated amino acid change may allosterically perturb several functional sites in an oligomeric and multidomain protein. These results have important implications for the understanding of loss-of-function genetic diseases and the identification of novel structural hot spots as targets for pharmacological intervention.

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

PubMed

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

2016-04-07

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

Ultra-long-term cycling stability of an integrated carbon-sulfur membrane with dual shuttle-inhibiting layers of graphene "nets" and a porous carbon skin.

PubMed

Liu, Mingkai; Meng, Qinghua; Yang, Zhiyuan; Zhao, Xinsheng; Liu, Tianxi

2018-05-15

An integrated carbon-sulfur (CSG/PC) membrane with dual shuttle-inhibiting layers was prepared by inserting graphene "nets" and a porous carbon (PC) skin, and the membrane achieved an extraordinary cycling stability up to 1000 cycles with an average Coulombic efficiency of ∼100%.

Test of the Hill Stability Criterion against Chaos Indicators

NASA Astrophysics Data System (ADS)

Satyal, Suman; Quarles, Billy; Hinse, Tobias

2012-10-01

The efficacy of Hill Stability (HS) criterion is tested against other known chaos indicators such as Maximum Lyapunov Exponents (MLE) and Mean Exponential Growth of Nearby Orbits (MEGNO) maps. First, orbits of four observationally verified binary star systems: γ Cephei, Gliese-86, HD41004, and HD196885 are integrated using standard integration packages (MERCURY, SWIFTER, NBI, C/C++). The HS which measures orbital perturbation of a planet around the primary star due to the secondary star is calculated for each system. The LEs spectra are generated to measure the divergence/convergence rate of stable manifolds and the MEGNO maps are generated by using the variational equations of the system during the integration process. These maps allow to accurately differentiate between stable and unstable dynamical systems. Then the results obtained from the analysis of HS, MLE, and MEGNO maps are checked for their dynamical variations and resemblance. The HS of most of the planets seems to be stable, quasi-periodic for at least ten million years. The MLE and the MEGNO maps also indicate the local quasi-periodicity and global stability in relatively short integration period. The HS criterion is found to be a comparably efficient tool to measure the stability of planetary orbits.

Stabilization of enzymes in ionic liquids via modification of enzyme charge.

PubMed

Nordwald, Erik M; Kaar, Joel L

2013-09-01

Due to the propensity of ionic liquids (ILs) to inactivate enzymes, the development of strategies to improve enzyme utility in these solvents is critical to fully exploit ILs for biocatalysis. We have developed a strategy to broadly improve enzyme utility in ILs based on elucidating the effect of charge modifications on the function of enzymes in IL environments. Results of stability studies in aqueous-IL mixtures indicated a clear connection between the ratio of enzyme-containing positive-to-negative sites and enzyme stability in ILs. Stability studies of the effect of [BMIM][Cl] and [EMIM][EtSO4 ] on chymotrypsin specifically found an optimum ratio of positively-charged amine-to-negatively-charged acid groups (0.39). At this ratio, the half-life of chymotrypsin was increased 1.6- and 4.3-fold relative to wild-type chymotrypsin in [BMIM][Cl] and [EMIM][EtSO4 ], respectively. The half-lives of lipase and papain were similarly increased as much as 4.0 and 2.4-fold, respectively, in [BMIM][Cl] by modifying the ratio of positive-to-negative sites of each enzyme. More generally, the results of stability studies found that modifications that reduce the ratio of enzyme-containing positive-to-negative sites improve enzyme stability in ILs. Understanding the impact of charge modification on enzyme stability in ILs may ultimately be exploited to rationally engineer enzymes for improved function in IL environments. Copyright © 2013 Wiley Periodicals, Inc.

Indium phosphide-based monolithically integrated PIN waveguide photodiode readout for resonant cantilever sensors

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

Siwak, N. P.; Laboratory for the Physical Sciences, 8050 Greenmead Drive, College Park, Maryland 20740; Fan, X. Z.

2014-10-06

An integrated photodiode displacement readout scheme for a microelectromechanical cantilever waveguide resonator sensing platform is presented. III-V semiconductors are used to enable the monolithic integration of passive waveguides with active optical components. This work builds upon previously demonstrated results by measuring the displacement of cantilever waveguide resonators with on-chip waveguide PIN photodiodes. The on-chip integration of the readout provides an additional 70% improvement in mass sensitivity compared to off-chip photodetector designs due to measurement stability and minimized coupling loss. In addition to increased measurement stability, reduced packaging complexity is achieved due to the simplicity of the readout design. We havemore » fabricated cantilever waveguides with integrated photodetectors and experimentally characterized these cantilever sensors with monolithically integrated PIN photodiodes.« less

TECHNOLOGY EVALUATION REPORT: SILICATE TECHNOLOGY CORPORATION - SOLIDIFICATION/STABILIZATION OF PCP AND INORGANIC CONTAMINANTS IN SOILS - SELMA, CA

EPA Science Inventory

This Technolgy Evaluation Report evaluates the solidification/stabilization process of Silicate Technology Corporation (STC) for the on-site treatment of contaminated soil The STC immobilization technology uses a proprietary product (FMS Silicate) to chemically stabilize and ...

Land use imperils plant and animal community stability through changes in asynchrony rather than diversity

PubMed Central

Blüthgen, Nico; Simons, Nadja K.; Jung, Kirsten; Prati, Daniel; Renner, Swen C.; Boch, Steffen; Fischer, Markus; Hölzel, Norbert; Klaus, Valentin H.; Kleinebecker, Till; Tschapka, Marco; Weisser, Wolfgang W.; Gossner, Martin M.

2016-01-01

Human land use may detrimentally affect biodiversity, yet long-term stability of species communities is vital for maintaining ecosystem functioning. Community stability can be achieved by higher species diversity (portfolio effect), higher asynchrony across species (insurance hypothesis) and higher abundance of populations. However, the relative importance of these stabilizing pathways and whether they interact with land use in real-world ecosystems is unknown. We monitored inter-annual fluctuations of 2,671 plant, arthropod, bird and bat species in 300 sites from three regions. Arthropods show 2.0-fold and birds 3.7-fold higher community fluctuations in grasslands than in forests, suggesting a negative impact of forest conversion. Land-use intensity in forests has a negative net impact on stability of bats and in grasslands on birds. Our findings demonstrate that asynchrony across species—much more than species diversity alone—is the main driver of variation in stability across sites and requires more attention in sustainable management. PMID:26869180

Land use imperils plant and animal community stability through changes in asynchrony rather than diversity.

PubMed

Blüthgen, Nico; Simons, Nadja K; Jung, Kirsten; Prati, Daniel; Renner, Swen C; Boch, Steffen; Fischer, Markus; Hölzel, Norbert; Klaus, Valentin H; Kleinebecker, Till; Tschapka, Marco; Weisser, Wolfgang W; Gossner, Martin M

2016-02-12

Human land use may detrimentally affect biodiversity, yet long-term stability of species communities is vital for maintaining ecosystem functioning. Community stability can be achieved by higher species diversity (portfolio effect), higher asynchrony across species (insurance hypothesis) and higher abundance of populations. However, the relative importance of these stabilizing pathways and whether they interact with land use in real-world ecosystems is unknown. We monitored inter-annual fluctuations of 2,671 plant, arthropod, bird and bat species in 300 sites from three regions. Arthropods show 2.0-fold and birds 3.7-fold higher community fluctuations in grasslands than in forests, suggesting a negative impact of forest conversion. Land-use intensity in forests has a negative net impact on stability of bats and in grasslands on birds. Our findings demonstrate that asynchrony across species--much more than species diversity alone--is the main driver of variation in stability across sites and requires more attention in sustainable management.

Stability and Interaction of Coherent Structure in Supersonic Reactive Wakes

NASA Technical Reports Server (NTRS)

Menon, Suresh

1983-01-01

A theoretical formulation and analysis is presented for a study of the stability and interaction of coherent structure in reacting free shear layers. The physical problem under investigation is a premixed hydrogen-oxygen reacting shear layer in the wake of a thin flat plate. The coherent structure is modeled as a periodic disturbance and its stability is determined by the application of linearized hydrodynamic stability theory which results in a generalized eigenvalue problem for reactive flows. Detailed stability analysis of the reactive wake for neutral, symmetrical and antisymmetrical disturbance is presented. Reactive stability criteria is shown to be quite different from classical non-reactive stability. The interaction between the mean flow, coherent structure and fine-scale turbulence is theoretically formulated using the von-Kaman integral technique. Both time-averaging and conditional phase averaging are necessary to separate the three types of motion. The resulting integro-differential equations can then be solved subject to initial conditions with appropriate shape functions. In the laminar flow transition region of interest, the spatial interaction between the mean motion and coherent structure is calculated for both non-reactive and reactive conditions and compared with experimental data wherever available. The fine-scale turbulent motion determined by the application of integral analysis to the fluctuation equations. Since at present this turbulence model is still untested, turbulence is modeled in the interaction problem by a simple algebraic eddy viscosity model. The applicability of the integral turbulence model formulated here is studied parametrically by integrating these equations for the simple case of self-similar mean motion with assumed shape functions. The effect of the motion of the coherent structure is studied and very good agreement is obtained with previous experimental and theoretical works for non-reactive flow. For the reactive case, lack of experimental data made direct comparison difficult. It was determined that the growth rate of the disturbance amplitude is lower for reactive case. The results indicate that the reactive flow stability is in qualitative agreement with experimental observation.

Stability of the Influenza Virus Hemagglutinin Protein Correlates with Evolutionary Dynamics.

PubMed

Klein, Eili Y; Blumenkrantz, Deena; Serohijos, Adrian; Shakhnovich, Eugene; Choi, Jeong-Mo; Rodrigues, João V; Smith, Brendan D; Lane, Andrew P; Feldman, Andrew; Pekosz, Andrew

2018-01-01

Protein thermodynamics are an integral determinant of viral fitness and one of the major drivers of protein evolution. Mutations in the influenza A virus (IAV) hemagglutinin (HA) protein can eliminate neutralizing antibody binding to mediate escape from preexisting antiviral immunity. Prior research on the IAV nucleoprotein suggests that protein stability may constrain seasonal IAV evolution; however, the role of stability in shaping the evolutionary dynamics of the HA protein has not been explored. We used the full coding sequence of 9,797 H1N1pdm09 HA sequences and 16,716 human seasonal H3N2 HA sequences to computationally estimate relative changes in the thermal stability of the HA protein between 2009 and 2016. Phylogenetic methods were used to characterize how stability differences impacted the evolutionary dynamics of the virus. We found that pandemic H1N1 IAV strains split into two lineages that had different relative HA protein stabilities and that later variants were descended from the higher-stability lineage. Analysis of the mutations associated with the selective sweep of the higher-stability lineage found that they were characterized by the early appearance of highly stabilizing mutations, the earliest of which was not located in a known antigenic site. Experimental evidence further suggested that H1N1 HA stability may be correlated with in vitro virus production and infection. A similar analysis of H3N2 strains found that surviving lineages were also largely descended from viruses predicted to encode more-stable HA proteins. Our results suggest that HA protein stability likely plays a significant role in the persistence of different IAV lineages. IMPORTANCE One of the constraints on fast-evolving viruses, such as influenza virus, is protein stability, or how strongly the folded protein holds together. Despite the importance of this protein property, there has been limited investigation of the impact of the stability of the influenza virus hemagglutinin protein-the primary antibody target of the immune system-on its evolution. Using a combination of computational estimates of stability and experiments, our analysis found that viruses with more-stable hemagglutinin proteins were associated with long-term persistence in the population. There are two potential reasons for the observed persistence. One is that more-stable proteins tolerate destabilizing mutations that less-stable proteins could not, thus increasing opportunities for immune escape. The second is that greater stability increases the fitness of the virus through increased production of infectious particles. Further research on the relative importance of these mechanisms could help inform the annual influenza vaccine composition decision process.

Periotest values of implants placed in sockets augmented with calcium phosphosilicate putty graft: a comparative analysis against implants placed in naturally healed sockets.

PubMed

Mahesh, Lanka; Narayan, Tv; Kostakis, Georgios; Shukla, Sagrika

2014-03-01

To measure implant stability using periotest values of implants placed in sockets augmented with calcium phospho-silicate putty (CPS Putty) as compared with implant stability in naturally healed sockets. Twenty two sockets were implanted with CPS Putty immediately after extraction. The sockets were re-entered after a healing period at 5 to 6 months (average 5.3 months) for implant placement. Periotest values were recorded during implant insertion to assess primary stability. These were compared with the Periotest values of 26 implants placed in 22 patients, with naturally healed sockets. Periotest values were significantly lower in the grafted group, indicating better implant stability in sites grafted with CPS putty. Implant stability seems to be significantly higher in sockets augmented using CPS putty when compared to nongrafted sites. This suggests that socket grafting with CPS putty may enhance the quality of available bone for implantation.

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

PubMed

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

2017-01-01

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

Direct Measurement of the Nanomechanical Stability of a Redox Protein Active Site and Its Dependence upon Metal Binding.

PubMed

Giannotti, Marina I; Cabeza de Vaca, Israel; Artés, Juan M; Sanz, Fausto; Guallar, Victor; Gorostiza, Pau

2015-09-10

The structural basis of the low reorganization energy of cupredoxins has long been debated. These proteins reconcile a conformationally heterogeneous and exposed metal-chelating site with the highly rigid copper center required for efficient electron transfer. Here we combine single-molecule mechanical unfolding experiments with statistical analysis and computer simulations to show that the metal-binding region of apo-azurin is mechanically flexible and that high mechanical stability is imparted by copper binding. The unfolding pathway of the metal site depends on the pulling residue and suggests that partial unfolding of the metal-binding site could be facilitated by the physical interaction with certain regions of the redox protein.

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

PubMed

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

2015-07-22

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

WatAA: Atlas of Protein Hydration. Exploring synergies between data mining and ab initio calculations.

PubMed

Černý, Jiří; Schneider, Bohdan; Biedermannová, Lada

2017-07-14

Water molecules represent an integral part of proteins and a key determinant of protein structure, dynamics and function. WatAA is a newly developed, web-based atlas of amino-acid hydration in proteins. The atlas provides information about the ordered first hydration shell of the most populated amino-acid conformers in proteins. The data presented in the atlas are drawn from two sources: experimental data and ab initio quantum-mechanics calculations. The experimental part is based on a data-mining study of a large set of high-resolution protein crystal structures. The crystal-derived data include 3D maps of water distribution around amino-acids and probability of occurrence of each of the identified hydration sites. The quantum mechanics calculations validate and extend this primary description by optimizing the water position for each hydration site, by providing hydrogen atom positions and by quantifying the interaction energy that stabilizes the water molecule at the particular hydration site position. The calculations show that the majority of experimentally derived hydration sites are positioned near local energy minima for water, and the calculated interaction energies help to assess the preference of water for the individual hydration sites. We propose that the atlas can be used to validate water placement in electron density maps in crystallographic refinement, to locate water molecules mediating protein-ligand interactions in drug design, and to prepare and evaluate molecular dynamics simulations. WatAA: Atlas of Protein Hydration is freely available without login at .

SOLIDIFICATION/STABILIZATION CASE STUDIES AT USEPA SUPERFUND SITES

EPA Science Inventory

Oral presentation dicumenting several completed Superfund remediations using solidification/stabilization, both in situ and ex-situ, to treat soils containing metals and organics.
65 slide presentation.

Prediction of the solvent affecting site and the computational design of stable Candida antarctica lipase B in a hydrophilic organic solvent.

PubMed

Park, Hyun June; Joo, Jeong Chan; Park, Kyungmoon; Kim, Yong Hwan; Yoo, Young Je

2013-02-10

Enzyme reactions in organic solvent such as for organic synthesis have great industrial potential. However, enzymes lose their stability in hydrophilic organic solvents due to the deformation of the enzyme by the solvent. It is thus important to enhance the stability of enzymes in hydrophilic organic solvents. Previous approaches have not considered on the interaction between enzymes and solvents due to the lack of information. In this study, the structural motions of the enzyme in methanol cosolvent and the interaction between the enzyme surface and the solvent molecule were investigated using molecular dynamics simulation (MD). By analyzing the MD simulation results, the surface residues of Candida antarctica lipase B (CalB) with higher root mean square deviation (RMSD) in a methanol solvent were considered as methanol affecting site and selected for site-directed mutagenesis. The methanol affecting site was computationally redesigned by lowering the RMSD. Among the candidate mutants, the A8T, A92E, N97Q and T245S mutants showed higher organic solvent stability at various methanol concentrations. The rational approach developed in this study could be applied to the stabilization of other industrial enzymes used in organic solvents. Copyright © 2012 Elsevier B.V. All rights reserved.

The structure of non-hierarchical triple system stability regions

NASA Astrophysics Data System (ADS)

Martynova, A. I.; Orlov, V. V.; Rubinov, A. V.

2009-08-01

A detailed study of the two-dimensional initial conditions region section in the planar three-body problem is performed. The initial conditions for the three well-known stable periodic orbits (the Schubart’s orbit, the Broucke’s orbit and the eight-like orbit) belong to this section. Continuous stability regions (for the fixed integration interval) generated by these periodic orbits are found. Zones of the quick stability violation are outlined. The analysis of some concrete trajectories coming from various stability regions is performed. In particular, trajectories possessing varying number of “eights” formed by moving triple system components are discovered. Orbits with librations are also found. The new periodic orbit originated from the zone siding with the Schubart’s orbit region is discovered. This orbit has reversibility points (each of the outer bodies possess a reversibility point) and two points of close double approach of the central body to each of the outer bodies. The influence of the numerical integration accuracy on the results is studied. The stability regions structure is preserved during calculations with different values of the precision parameter, numerical integration methods and regularization algorithms of the equations of motion.

High Stability Engine Control (HISTEC) Flight Test Results

NASA Technical Reports Server (NTRS)

Southwick, Robert D.; Gallops, George W.; Kerr, Laura J.; Kielb, Robert P.; Welsh, Mark G.; DeLaat, John C.; Orme, John S.

1998-01-01

The High Stability Engine Control (HISTEC) Program, managed and funded by the NASA Lewis Research Center, is a cooperative effort between NASA and Pratt & Whitney (P&W). The program objective is to develop and flight demonstrate an advanced high stability integrated engine control system that uses real-time, measurement-based estimation of inlet pressure distortion to enhance engine stability. Flight testing was performed using the NASA Advanced Controls Technologies for Integrated Vehicles (ACTIVE) F-15 aircraft at the NASA Dryden Flight Research Center. The flight test configuration, details of the research objectives, and the flight test matrix to achieve those objectives are presented. Flight test results are discussed that show the design approach can accurately estimate distortion and perform real-time control actions for engine accommodation.

Characterization of the Sonoran desert as a radiometric calibration target for Earth observing sensors

USGS Publications Warehouse

Angal, Amit; Chander, Gyanesh; Xiong, Xiaoxiong; Choi, Tae-young; Wu, Aisheng

2011-01-01

To provide highly accurate quantitative measurements of the Earth's surface, a comprehensive calibration and validation of the satellite sensors is required. The NASA Moderate Resolution Imaging Spectroradiometer (MODIS) Characterization Support Team, in collaboration with United States Geological Survey, Earth Resources Observation and Science Center, has previously demonstrated the use of African desert sites to monitor the long-term calibration stability of Terra MODIS and Landsat 7 (L7) Enhanced Thematic Mapper plus (ETM+). The current study focuses on evaluating the suitability of the Sonoran Desert test site for post-launch long-term radiometric calibration as well as cross-calibration purposes. Due to the lack of historical and on-going in situ ground measurements, the Sonoran Desert is not usually used for absolute calibration. An in-depth evaluation (spatial, temporal, and spectral stability) of this site using well calibrated L7 ETM+ measurements and local climatology data has been performed. The Sonoran Desert site produced spatial variability of about 3 to 5% in the reflective solar regions, and the temporal variations of the site after correction for view-geometry impacts were generally around 3%. The results demonstrate that, barring the impacts due to occasional precipitation, the Sonoran Desert site can be effectively used for cross-calibration and long-term stability monitoring of satellite sensors, thus, providing a good test site in the western hemisphere.

APE1 incision activity at abasic sites in tandem repeat sequences.

PubMed

Li, Mengxia; Völker, Jens; Breslauer, Kenneth J; Wilson, David M

2014-05-29

Repetitive DNA sequences, such as those present in microsatellites and minisatellites, telomeres, and trinucleotide repeats (linked to fragile X syndrome, Huntington disease, etc.), account for nearly 30% of the human genome. These domains exhibit enhanced susceptibility to oxidative attack to yield base modifications, strand breaks, and abasic sites; have a propensity to adopt non-canonical DNA forms modulated by the positions of the lesions; and, when not properly processed, can contribute to genome instability that underlies aging and disease development. Knowledge on the repair efficiencies of DNA damage within such repetitive sequences is therefore crucial for understanding the impact of such domains on genomic integrity. In the present study, using strategically designed oligonucleotide substrates, we determined the ability of human apurinic/apyrimidinic endonuclease 1 (APE1) to cleave at apurinic/apyrimidinic (AP) sites in a collection of tandem DNA repeat landscapes involving telomeric and CAG/CTG repeat sequences. Our studies reveal the differential influence of domain sequence, conformation, and AP site location/relative positioning on the efficiency of APE1 binding and strand incision. Intriguingly, our data demonstrate that APE1 endonuclease efficiency correlates with the thermodynamic stability of the DNA substrate. We discuss how these results have both predictive and mechanistic consequences for understanding the success and failure of repair protein activity associated with such oxidatively sensitive, conformationally plastic/dynamic repetitive DNA domains. Published by Elsevier Ltd.

Anomalous porosity preservation and preferential accumulation of gas hydrate in the Andaman accretionary wedge, NGHP-01 site 17A

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

Rose, Kelly K.; Johnson, Joel E.; Torres, Marta E.

In addition to well established properties that control the presence or absence of the hydrate stability zone, such as pressure, temperature, and salinity, additional parameters appear to influence the concentration of gas hydrate in host sediments. The stratigraphic record at Site 17A in the Andaman Sea, eastern Indian Ocean, illustrates the need to better understand the role pore-scale phenomena play in the distribution and presence of marine gas hydrates in a variety of subsurface settings. In this paper we integrate field-generated datasets with newly acquired sedimentology, physical property, imaging and geochemical data with mineral saturation and ion activity products ofmore » key mineral phases such as amorphous silica and calcite, to document the presence and nature of secondary precipitates that contributed to anomalous porosity preservation at Site 17A in the Andaman Sea. This study demonstrates the importance of grain-scale subsurface heterogeneities in controlling the occurrence and distribution of concentrated gas hydrate accumulations in marine sediments, and document the importance that increased permeability and enhanced porosity play in supporting gas concentrations sufficient to support gas hydrate formation. The grain scale relationships between porosity, permeability, and gas hydrate saturation documented at Site 17A likely offer insights into what may control the occurrence and distribution of gas hydrate in other sedimentary settings.« less

Site response variation due to the existence of near-field cracks based on strong motion records in the Shi-Wen river valley, southern Taiwan

NASA Astrophysics Data System (ADS)

Wu, Chi-Shin; Yu, Teng-To; Peng, Wen-Fei; Yeh, Yeoin-Tein; Lin, Sih-Siao

2014-10-01

Site effect analysis has been applied to investigate soil classification, alluvium depth, and fracture detection, although the majority of previous studies have typically focused only on the response of large-scale single structures. In contrast, we investigated the site effect for small-scale cracks using a case study in southern Taiwan to provide a means of monitoring slope stability or foundation integrity in situ using only an accelerometer. We adopted both the reference site and horizontal-to-vertical spectral ratio methods. We obtained seismographs associated with the typhoon-related development of a crack set (52 m long, 5 m deep) in a steep slope and compared the resonance frequency between two conditions (with and without cracks). Moreover, we divided the seismic waves into P, S, and coda waves and examined the seismic source effect. Our results demonstrate that frequencies of 14.5-17.5 Hz are most sensitive to these cracks, particularly for the E-W component of the P-waves, which coincides with the crack’s strike. Peak ground acceleration, which is controlled by seismic moment and attenuated distance, is another important factor determining the resonance results. Our results demonstrate that the ratio of temporal seismic waves can be used to detect the existence of nearby subsurface cracks.

Dynamic stability analysis of fractional order leaky integrator echo state neural networks

NASA Astrophysics Data System (ADS)

Pahnehkolaei, Seyed Mehdi Abedi; Alfi, Alireza; Tenreiro Machado, J. A.

2017-06-01

The Leaky integrator echo state neural network (Leaky-ESN) is an improved model of the recurrent neural network (RNN) and adopts an interconnected recurrent grid of processing neurons. This paper presents a new proof for the convergence of a Lyapunov candidate function to zero when time tends to infinity by means of the Caputo fractional derivative with order lying in the range (0, 1). The stability of Fractional-Order Leaky-ESN (FO Leaky-ESN) is then analyzed, and the existence, uniqueness and stability of the equilibrium point are provided. A numerical example demonstrates the feasibility of the proposed method.

Investigation of ODE integrators using interactive graphics. [Ordinary Differential Equations

NASA Technical Reports Server (NTRS)

Brown, R. L.

1978-01-01

Two FORTRAN programs using an interactive graphic terminal to generate accuracy and stability plots for given multistep ordinary differential equation (ODE) integrators are described. The first treats the fixed stepsize linear case with complex variable solutions, and generates plots to show accuracy and error response to step driving function of a numerical solution, as well as the linear stability region. The second generates an analog to the stability region for classes of non-linear ODE's as well as accuracy plots. Both systems can compute method coefficients from a simple specification of the method. Example plots are given.

Microbial Diversity and Metal Speciation Changes in Mine Tailings Following Compost-Assisted Direct Planting: A Four-Year Superfund Site Field Study

NASA Astrophysics Data System (ADS)

Maier, R. M.; Gil-Loaiza, J.; Honeker, L. K.; Hottenstein, J. D.; Valentin-Vargas, A.; Jennings, L. L.; Hammond, C.; Neilson, J. W.; Root, R. A.; Chorover, J.

2014-12-01

EPA estimates that future mine tailings remediation costs will exceed US $50 billion using present technologies based on constructing an inert or biological cap on the tailings. Both approaches require large amounts of capping materials that can be difficult and expensive to obtain especially for sites several thousand hectares in size. An alternative technology is direct planting into tailings. However, direct planting alone is not feasible for many legacy sites due to extreme acidity and high metal content which prevent plant germination and growth. Therefore the process must be "assisted" through the addition of amendments such as compost. Here we present results from the first four years of a field study at the Iron King Mine and Humboldt Smelter Superfund site demonstrating the feasibility of compost-assisted direct planting. Parameters measured during the field study included: canopy cover, pH, nutrient content, plant metal uptake, metal(loid) speciation, mineral analysis, microbiome analysis, and plant root-metal-microbe interactions. Integrated analysis of these parameters suggests that even in this "worst-case scenario" mine tailings site (pH 2.5; As and Pb each exceeding 2 g kg-1), we have created a sustainable system. In this system, phyto-catalyzed stabilization of inorganic contaminants in the root zone is driven by plant root exudates and the associated rhizosphere microbial community. The results of this research will be put into context of a larger topic- that of ecological engineering of mine tailings sites - a technique being proposed to prevent creation of acidic conditions and metal(loid) mobilization in the first place.

Microbial Diversity and Metal Speciation Changes in Mine Tailings Following Compost-Assisted Direct Planting: A Four-Year Superfund Site Field Study

NASA Astrophysics Data System (ADS)

Maier, R. M.; Gil-Loaiza, J.; Honeker, L. K.; Hottenstein, J. D.; Valentin-Vargas, A.; Jennings, L. L.; Hammond, C.; Neilson, J. W.; Root, R. A.; Chorover, J.

2015-12-01

EPA estimates that future mine tailings remediation costs will exceed US $50 billion using present technologies based on constructing an inert or biological cap on the tailings. Both approaches require large amounts of capping materials that can be difficult and expensive to obtain especially for sites several thousand hectares in size. An alternative technology is direct planting into tailings. However, direct planting alone is not feasible for many legacy sites due to extreme acidity and high metal content which prevent plant germination and growth. Therefore the process must be "assisted" through the addition of amendments such as compost. Here we present results from the first four years of a field study at the Iron King Mine and Humboldt Smelter Superfund site demonstrating the feasibility of compost-assisted direct planting. Parameters measured during the field study included: canopy cover, pH, nutrient content, plant metal uptake, metal(loid) speciation, mineral analysis, microbiome analysis, and plant root-metal-microbe interactions. Integrated analysis of these parameters suggests that even in this "worst-case scenario" mine tailings site (pH 2.5; As and Pb each exceeding 2 g kg-1), we have created a sustainable system. In this system, phyto-catalyzed stabilization of inorganic contaminants in the root zone is driven by plant root exudates and the associated rhizosphere microbial community. The results of this research will be put into context of a larger topic- that of ecological engineering of mine tailings sites - a technique being proposed to prevent creation of acidic conditions and metal(loid) mobilization in the first place.

Stabilization Operations Through Military Capacity Building-Integration Between Danish Conventional Forces and Special Operations Forces

DTIC Science & Technology

2016-12-01

Svendsen 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate School Monterey, CA 93943-5000 8. PERFORMING ORGANIZATION REPORT...operations forces should be fully integrated across doctrine, organization , and technology, and predominantly advise, mentor, and train local forces. With...stability operations. This capstone makes additional recommendations related to doctrine, organization , and technology, as well as education and

Taking Stock: Interagency Integration in Stability Operations

DTIC Science & Technology

2012-03-01

implementation of 3000.05. In May 2009, a report to Congress highlighted the biggest challenge to integration as the lack of civilian department and agency...ORHA) and later subsumed by the Coalition Provisional Authority (CPA). On May 11, 2004, NSPD 36, United States Government Operations in Iraq...military audience, although introductory presentations have been given at the U.S. Army Peacekeeping and Stability Operations Institute and Marine

An Integrated Miniature Pulse Tube Cryocooler at 80K

NASA Astrophysics Data System (ADS)

Chen, H. L.; Yang, L. W.; Cai, J. H.; Liang, J. T.; Zhang, L.; Zhou, Y.

2008-03-01

Two integrated models of coaxial miniature pulse tube coolers based on an experimental model are manufactured. Performance of the integrated models is compared to that of the experimental model. Reliability and stability of an integrated model are tested and improved.

Influence of a Confined Methanol Solvent on the Reactivity of Active Sites in UiO-66.

PubMed

Caratelli, Chiara; Hajek, Julianna; Rogge, Sven M J; Vandenbrande, Steven; Meijer, Evert Jan; Waroquier, Michel; Van Speybroeck, Veronique

2018-02-19

UiO-66, composed of Zr-oxide bricks and terephthalate linkers, is currently one of the most studied metal-organic frameworks due to its exceptional stability. Defects can be introduced in the structure, creating undercoordinated Zr atoms which are Lewis acid sites. Here, additional Brønsted sites can be generated by coordinated protic species from the solvent. In this Article, a multilevel modeling approach was applied to unravel the effect of a confined methanol solvent on the active sites in UiO-66. First, active sites were explored with static periodic density functional theory calculations to investigate adsorption of water and methanol. Solvent was then introduced in the pores with grand canonical Monte Carlo simulations, followed by a series of molecular dynamics simulations at operating conditions. A hydrogen-bonded network of methanol molecules is formed, allowing the protons to shuttle between solvent methanol, adsorbed water, and the inorganic brick. Upon deprotonation of an active site, the methanol solvent aids the transfer of protons and stabilizes charged configurations via hydrogen bonding, which could be crucial in stabilizing reactive intermediates. The multilevel modeling approach adopted here sheds light on the important role of a confined solvent on the active sites in the UiO-66 material, introducing dynamic acidity in the system at finite temperatures by which protons may be easily shuttled from various positions at the active sites. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Adaptive integral backstepping sliding mode control for opto-electronic tracking system based on modified LuGre friction model

NASA Astrophysics Data System (ADS)

Yue, Fengfa; Li, Xingfei; Chen, Cheng; Tan, Wenbin

2017-12-01

In order to improve the control accuracy and stability of opto-electronic tracking system fixed on reef or airport under friction and external disturbance conditions, adaptive integral backstepping sliding mode control approach with friction compensation is developed to achieve accurate and stable tracking for fast moving target. The nonlinear observer and slide mode controller based on modified LuGre model with friction compensation can effectively reduce the influence of nonlinear friction and disturbance of this servo system. The stability of the closed-loop system is guaranteed by Lyapunov theory. The steady-state error of the system is eliminated by integral action. The adaptive integral backstepping sliding mode controller and its performance are validated by a nonlinear modified LuGre dynamic model of the opto-electronic tracking system in simulation and practical experiments. The experiment results demonstrate that the proposed controller can effectively realise the accuracy and stability control of opto-electronic tracking system.

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

Kim, Hyun You; Liu, Ping

Mixed metal oxides have attracted considerable attention in heterogeneous catalysis due to the unique stability, reactivity, and selectivity. Here, the activity and stability of the CuTiO x monolayer film supported on Cu(111), CuTiO x/Cu(111), during CO oxidation was explored using density functional theory (DFT). The unique structural frame of CuTiO x is able to stabilize and isolate a single Cu + site on the terrace, which is previously proposed active for CO oxidation. Furthermore, it is not the case, where the reaction via both the Langmuir–Hinshelwood (LH) and the Mars-van Krevelen (M-vK) mechanisms are hindered on such single Cu +more » site. Upon the formation of step-edges, the synergy among Cu δ+ sites, TiO x matrix, and Cu(111) is able to catalyze the reaction well. Depending on temperatures and partial pressure of CO and O 2, the surface structure varies, which determines the dominant mechanism. In accordance with our results, the Cu δ+ ion alone does not work well for CO oxidation in the form of single sites, while the synergy among multiple active sites is necessary to facilitate the reaction.« less

Complex catalytic behaviors of CuTiO x mixed-oxide during CO oxidation

DOE PAGES

Kim, Hyun You; Liu, Ping

2015-09-21

Mixed metal oxides have attracted considerable attention in heterogeneous catalysis due to the unique stability, reactivity, and selectivity. Here, the activity and stability of the CuTiO x monolayer film supported on Cu(111), CuTiO x/Cu(111), during CO oxidation was explored using density functional theory (DFT). The unique structural frame of CuTiO x is able to stabilize and isolate a single Cu + site on the terrace, which is previously proposed active for CO oxidation. Furthermore, it is not the case, where the reaction via both the Langmuir–Hinshelwood (LH) and the Mars-van Krevelen (M-vK) mechanisms are hindered on such single Cu +more » site. Upon the formation of step-edges, the synergy among Cu δ+ sites, TiO x matrix, and Cu(111) is able to catalyze the reaction well. Depending on temperatures and partial pressure of CO and O 2, the surface structure varies, which determines the dominant mechanism. In accordance with our results, the Cu δ+ ion alone does not work well for CO oxidation in the form of single sites, while the synergy among multiple active sites is necessary to facilitate the reaction.« less

Monitoring and evaluation of fly ash stabilization stabilized subgrade constructed by the Wisconsin Department of Transportation.

DOT National Transportation Integrated Search

2010-06-30

This report describes the monitoring and evaluation of a field site where Class C fly ash was used to stabilize the : subgrade during construction of a rigid pavement in a portion of USH 12 near Fort Atkinson, Wisconsin. : Additionally, information f...

Survival of Implants in Immediate Extraction Sockets of Anterior Teeth: Early Clinical Results.

PubMed

Sabir, Mohammad; Alam, Mohammad Nazish

2015-06-01

The aims and objectives of this study were placement of implants in freshly extracted sockets of anterior teeth and to evaluate the implant stability, peri-implant radiolucency and gingival inflammation around implant over a short period of 30 months. A total of 12 patients (8 male and 4 female), ranging in the age from 20 to 50 years, from March 2007 to June 2007, were evaluated for immediate implant placement into 22 fresh extraction sockets. Only maxillary and mandibular anterior teeth/roots (central incisors, lateral incisors and canines) were considered for replacement with implants. One piece implant with integrated abutment and integrated surface, non-submerged, threaded and tapered at apical 5 mm, sand-blasted and acid etched surfaced implants (HI-TEC TRX-OP Implants of Life Care Company) were used. The mobility was not present in any of the implants at all the follow up visits. There were 2 implants at 6 month, 1 implant at 12 month, 1 implant at 18 month visits, showing peri-implant radiolucency at some sites at bone to implant contact site. Severe gingival inflammation was not observed in any of the implant site. At every follow-up visit, every implant met the criteria of success and none was found to be failed over a 30 months duration i.e. 100% success rate was achieved by implants in immediate extraction socket. The success rate of implant survival in this study was found 100%. These implants have fulfilled all the criteria of implant success and based on the defined criteria, the success rate of implants placed in immediate extraction sockets of anterior teeth compared favorably with the conventional implants. The early results of the present study showed that high survival rates with the implants in immediate extraction sockets can be achieved.

Canthaxanthin production with modified Mucor circinelloides strains.

PubMed

Papp, Tamás; Csernetics, Arpád; Nagy, Gábor; Bencsik, Ottó; Iturriaga, Enrique A; Eslava, Arturo P; Vágvölgyi, Csaba

2013-06-01

Canthaxanthin is a natural diketo derivative of β-carotene primarily used by the food and feed industries. Mucor circinelloides is a β-carotene-accumulating zygomycete fungus and one of the model organisms to study the carotenoid biosynthesis in fungi. In this study, the β-carotene ketolase gene (crtW) of the marine bacterium Paracoccus sp. N81106 fused with fungal promoter and terminator regions was integrated into the M. circinelloides genome to construct stable canthaxanthin-producing strains. Different transformation methods including polyethylene glycol-mediated transformation with linear DNA fragments, restriction enzyme-mediated integration and Agrobacterium tumefaciens-mediated transformation were tested to integrate the crtW gene into the Mucor genome. Mitotic stability, site of integration and copy number of the transferred genes were analysed in the transformants, and several stable strains containing the crtW gene in high copy number were isolated. Carotenoid composition of selected transformants and effect of culturing conditions, such as temperature, carbon sources and application of certain additives in the culturing media, on their carotenoid content were analysed. Canthaxanthin-producing transformants were able to survive at higher growth temperature than the untransformed strain, maybe due to the effect of canthaxanthin on the membrane fluidity and integrity. With the application of glucose, trehalose, dihydroxyacetone and L-aspartic acid as sole carbon sources in minimal medium, the crtW-expressing M. circinelloides strain, MS12+pCA8lf/1, produced more than 200 μg/g (dry mass) of canthaxanthin.

Floral trait variation and integration as a function of sexual deception in Gorteria diffusa.

PubMed

Ellis, Allan G; Brockington, Samuel F; de Jager, Marinus L; Mellers, Gregory; Walker, Rachel H; Glover, Beverley J

2014-08-19

Phenotypic integration, the coordinated covariance of suites of morphological traits, is critical for proper functioning of organisms. Angiosperm flowers are complex structures comprising suites of traits that function together to achieve effective pollen transfer. Floral integration could reflect shared genetic and developmental control of these traits, or could arise through pollinator-imposed stabilizing correlational selection on traits. We sought to expose mechanisms underlying floral trait integration in the sexually deceptive daisy, Gorteria diffusa, by testing the hypothesis that stabilizing selection imposed by male pollinators on floral traits involved in mimicry has resulted in tighter integration. To do this, we quantified patterns of floral trait variance and covariance in morphologically divergent G. diffusa floral forms representing a continuum in the levels of sexual deception. We show that integration of traits functioning in visual attraction of male pollinators increases with pollinator deception, and is stronger than integration of non-mimicry trait modules. Consistent patterns of within-population trait variance and covariance across floral forms suggest that integration has not been built by stabilizing correlational selection on genetically independent traits. Instead pollinator specialization has selected for tightened integration within modules of linked traits. Despite potentially strong constraint on morphological evolution imposed by developmental genetic linkages between traits, we demonstrate substantial divergence in traits across G. diffusa floral forms and show that divergence has often occurred without altering within-population patterns of trait correlations. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Gas hydrate drilling transect across northern Cascadia margin - IODP Expedition 311

USGS Publications Warehouse

Riedel, M.; Collett, T.; Malone, M.J.; Collett, T.S.; Mitchell, M.; Guerin, G.; Akiba, F.; Blanc-Valleron, M.; Ellis, M.; Hashimoto, Y.; Heuer, V.; Higashi, Y.; Holland, M.; Jackson, P.D.; Kaneko, M.; Kastner, M.; Kim, J.-H.; Kitajima, H.; Long, P.E.; Malinverno, A.; Myers, Gwen E.; Palekar, L.D.; Pohlman, J.; Schultheiss, P.; Teichert, B.; Torres, M.E.; Trehu, A.M.; Wang, Jingyuan; Worthmann, U.G.; Yoshioka, H.

2009-01-01

A transect of four sites (U1325, U1326, U1327 and U1329) across the northern Cascadia margin was established during Integrated Ocean Drilling Program Expedition 311 to study the occurrence and formation of gas hydrate in accretionary complexes. In addition to the transect sites, a fifth site (U1328) was established at a cold vent with active fluid flow. The four transect sites represent different typical geological environments of gas hydrate occurrence across the northern Cascadia margin from the earliest occurrence on the westernmost first accreted ridge (Site U1326) to the eastward limit of the gas hydrate occurrence in shallower water (Site U1329). Expedition 311 complements previous gas hydrate studies along the Cascadia accretionary complex, especially ODP Leg 146 and Leg 204 by extending the aperture of the transect sampled and introducing new tools to systematically quantify the gas hydrate content of the sediments. Among the most significant findings of the expedition was the occurrence of up to 20 m thick sand-rich turbidite intervals with gas hydrate concentrations locally exceeding 50% of the pore space at Sites U1326 and U1327. Moreover, these anomalous gas hydrate intervals occur at unexpectedly shallow depths of 50-120 metres below seafloor, which is the opposite of what was expected from previous models of gas hydrate formation in accretionary complexes, where gas hydrate was predicted to be more concentrated near the base of the gas hydrate stability zone just above the bottom-simulating reflector. Gas hydrate appears to be mainly concentrated in turbidite sand layers. During Expedition 311, the visual correlation of gas hydrate with sand layers was clearly and repeatedly documented, strongly supporting the importance of grain size in controlling gas hydrate occurrence. The results from the transect sites provide evidence for a structurally complex, lithology-controlled gas hydrate environment on the northern Cascadia margin. Local shallow occurrences of high gas hydrate concentrations contradict the previous model of gas hydrate formation at an accretionary prism. However, long-lived fluid flow (part of the old model) is still required to explain the shallow high gas hydrate concentrations, although it is most likely not pervasive throughout the entire accretionary prism, but rather localized and focused by the tectonic processes. Differences in the fluid flow regime across all of the transect drill sites indicate site-specific and probably disconnected (compartmented) deeper fluid sources in the various parts of the accretionary prism. The data and future analyses will yield a better understanding of the geologic controls, evolution and ultimate fate of gas hydrate in an accretionary prism as an important contribution to the role of gas hydrate methane gas in slope stability and possibly in climate change. ?? The Geological Society of London 2009.

Modification of Nafion membrane with biofunctional SiO2 nanofiber for proton exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Wang, Hang; Li, Xiaojie; Zhuang, Xupin; Cheng, Bowen; Wang, Wei; Kang, Weimin; Shi, Lei; Li, Hongjun

2017-02-01

Proton currents are an integral part of the most important energy-converting structures in biology. We prepared a new type of bioinspired Nafion (Bio-Nafion) membrane composited of biofunctional SiO2 (Bio-SiO2) nanofiber and Nafion matrix. SiO2 nanofibers were prepared by electrospinning silica sol prepared from tetraethyl orthosilicate. Meanwhile, Bio-SiO2 nanofibers were synthesized by immobilizing amino acids (cysteine, serine, lysine, and glycine) on SiO2 nanofibers, which acted as efficient proton-conducting pathways that involved numerous H+ transport sites. In our study, the SiO2 nanofibers biofunctionalized with cysteine were further oxidized, and the composite membranes were designated as Nafion-Cys, Nafion-Lys, Nafion-Ser, and Nafion-Gly, respectively. We then investigated the different polar groups (sbnd SO3H, sbnd OH, and sbnd NH2) of the amino acids that contributed to membrane properties of thermal stability, water uptake (WU), dimensional stability, proton conductivity, and methanol permeability. Nafion-Cys exhibited the highest proton conductivity of 0.2424 S/cm (80 °C). Nafion-Gly showed the lowest proton conductivity and WU because glycine contains the least number of hydrophilic groups among the amino acids. Overall, the introduction of Bio-SiO2 nanofiber to composite membranes significantly improved proton conductivity, dimensional stability, and methanol permeability.

Qcritical as a Geomorphically and Biologically Relevant Flow Threshold for Stormwater Management and Catchment-scale Stream Restoration

NASA Astrophysics Data System (ADS)

Hawley, R. J.; Vietz, G. J.; Wooten, M. S.

2016-12-01

The threshold discharge that initiates streambed mobilization (Qcritical) is one of the most mechanistically-important flows for geomorphic function and biological integrity in stream ecosystems. Increased frequency and duration of flows that exceed Qcritical are a dominant driver of geomorphic instability and excess benthic disturbance in urban/suburban streams (i.e. the urban disturbance regime). Qcritical frequency also corresponds to measures of stream integrity in reference streams, with both geomorphic stability and biological indices significantly correlated to time since a Qcritical event in one 7-y study. Indeed, reference site macroinvertebrate communities during years with atypically frequent Qcritical events were more similar to sites draining watersheds with 30% imperviousness than to reference site communities of more typical rainfall years. Despite its biophysical relevance to stream ecosystems, Qcritical is one of the most overlooked and misunderstood flows in the stormwater management and stream restoration fields. Regional stormwater policies and stream restoration design guidance are often based on the misplaced assumption that streambed erosion does not occur at sub-bankfull events (often assumed to correspond to the 1-y recurrence discharge). Using an international database of nearly 200 sites we show that Qcritical varies by several orders of magnitude as a function of streambed particle size. Qcritical in sand-dominated streams is likely to be orders of magnitude less than the 1-yr discharge, whereas Qcritical in cobble/boulder dominated streams could be much larger than the 1-yr discharge, implying that stormwater/restoration policies focused on the 1-yr event could lack efficacy in many stream settings. Qcritical is a geomorphically- and biologically-relevant discharge threshold when developing stormwater management policies intended to protect streams from excess erosion, designing watershed-scale restoration efforts to restore a more natural disturbance regime, or reconstructing stream reaches designed to restore sediment continuity. Incorporation of Qcritical into such restoration and management efforts ensures that designs are actually tailored to the mechanisms that drive channel erosion and disturbance to the benthos.

SF Box--a tool for evaluating the effects on soil functions in remediation projects.

PubMed

Volchko, Yevheniya; Norrman, Jenny; Rosén, Lars; Norberg, Tommy

2014-10-01

Although remediation is usually aimed at reducing the risks posed by contaminants to human health and the environment, it is also desirable that the remediated soil within future green spaces is capable of providing relevant ecological functions, e.g., basis for primary production. Yet while addressing a contamination problem by reducing contaminant concentration and/or amounts in the soil, the remedial action itself can lead to soil structure disturbances, decline in organic matter and nutrient deficiencies, and in turn affect a soil's capacity to carry out its ecological soil functions. This article presents the Soil Function Box (SF Box) tool that is aimed to facilitate integration of information from suggested soil quality indicators (SQIs) into a management process in remediation using a scoring method. The scored SQIs are integrated into a soil quality index corresponding to 1 of 5 classes. SF Box is applied to 2 cases from Sweden (Kvillebäcken and Hexion), explicitly taking into consideration uncertainties in the results by means of Monte Carlo simulations. At both sites the generated soil quality indices corresponded to a medium soil performance (soil class 3) with a high certainty. The main soil constraints at both Kvillebäcken and Hexion were associated with biological activity in the soil, as soil organisms were unable to supply plant-available N. At the Kvillebäcken site the top layer had a content of coarse fragment (ø > 2 mm) higher than 35%, indicating plant rooting limitations. At the Hexion site, the soil had limited amount of organic matter, thus poor aggregate stability and nutrient cycling potential. In contrast, the soil at Kvillebäcken was rich in organic matter. The soils at both sites were capable of storing a sufficient amount of water for soil organisms between precipitation events. © 2014 SETAC.

Between Site Reliability of Startle Prepulse Inhibition Across Two Early Psychosis Consortia

PubMed Central

Addington, Jean; Cannon, Tyrone D.; Cornblatt, Barbara A.; de la Fuente-Sandoval, Camilo; Mathalon, Dan H.; Perkins, Diana O.; Seidman, Larry J.; Tsuang, Ming; Walker, Elaine F.; Woods, Scott W.; Bachman, Peter; Belger, Ayse; Carrión, Ricardo E.; Donkers, Franc C.L.; Duncan, Erica; Johannesen, Jason; León-Ortiz, Pablo; Light, Gregory; Mondragón, Alejandra; Niznikiewicz, Margaret; Nunag, Jason; Roach, Brian J.; Solís-Vivanco, Rodolfo

2014-01-01

Prepulse inhibition (PPI) and reactivity of the acoustic startle response are widely used biobehavioral markers in psychopathology research. Previous studies have demonstrated that PPI and startle reactivity exhibit substantial within-site stability; between-site stability, however, has not been established. In two separate consortia investigating biomarkers of early psychosis, traveling subjects studies were performed as part of quality assurance procedures in order to assess the fidelity of data across sites. In the North American Prodromal Longitudinal Studies (NAPLS) Consortium, 8 normal subjects traveled to each of the 8 NAPLS sites and were tested twice at each site on the startle PPI paradigm. In preparation for a binational study, 10 healthy subjects were assessed twice in both San Diego and Mexico City. Intraclass correlations between and within sites were significant for PPI and startle response parameters, confirming the reliability of startle measures across sites in both consortia. There were between site differences in startle magnitude in the NAPLS study that did not appear to be related to methods or equipment. In planning multi-site studies, it is essential to institute quality assurance procedures early and establish between site reliability to assure comparable data across sites. PMID:23799460

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

PubMed Central

Justice, James F.; Morgan, Robin W.

2015-01-01

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

Role of Disulfide Bridges in the Activity and Stability of a Cold-Active α-Amylase

PubMed Central

Siddiqui, Khawar Sohail; Poljak, Anne; Guilhaus, Michael; Feller, Georges; D'Amico, Salvino; Gerday, Charles; Cavicchioli, Ricardo

2005-01-01

The cold-adapted α-amylase from Pseudoalteromonas haloplanktis unfolds reversibly and cooperatively according to a two-state mechanism at 30°C and unfolds reversibly and sequentially with two transitions at temperatures below 12°C. To examine the role of the four disulfide bridges in activity and conformational stability of the enzyme, the eight cysteine residues were reduced with β-mercaptoethanol or chemically modified using iodoacetamide or iodoacetic acid. Matrix-assisted laser desorption-time of flight mass spectrometry analysis confirmed that all of the cysteines were modified. The iodoacetamide-modified enzyme reversibly folded/unfolded and retained approximately one-third of its activity. Removal of all disulfide bonds resulted in stabilization of the least stable region of the enzyme (including the active site), with a concomitant decrease in activity (increase in activation enthalpy). Disulfide bond removal had a greater impact on enzyme activity than on stability (particularly the active-site region). The functional role of the disulfide bridges appears to be to prevent the active site from developing ionic interactions. Overall, the study demonstrated that none of the four disulfide bonds are important in stabilizing the native structure of enzyme, and instead, they appear to promote a localized destabilization to preserve activity. PMID:16109962

In vivo study of the effectiveness of quantitative percussion diagnostics as an indicator of the level of structural pathology of teeth after restoration.

PubMed

Sheets, Cherilyn G; Wu, Jean C; Rashad, Samer; Phelan, Michael; Earthman, James C

2017-02-01

Conventional diagnostic aids based upon imagery and patient symptoms do not indicate whether restorative treatments have eliminated structural pathology. The purpose of this clinical study was to evaluate quantitative percussion diagnostics (QPD), a mechanics-based methodology that tests the structural integrity of teeth noninvasively. The study hypothesis was that QPD would provide knowledge of the structural instability of teeth after restorative work. Eight participants with 60 sites needing restoration were enrolled in an IRB-approved clinical study. Each participant was examined comprehensively, including QPD testing. Each site was disassembled and microscopically video documented, and the results were recorded on a defect assessment sheet. A predictive model was developed for the pathology rating based on normalized fit error (NFE) values using data from the before treatment phase of the study published previously. Each restored site was then tested using QPD. The mean change in NFE values after restoration was evaluated by the pathology rating before treatment. The model was then used to predictively classify the rating after restoration based on the NFE values after treatment. The diagnostic potential of the rating was explored as a marker for risk of pathology after restoration. After restoration, 51 of the 60 sites fell below an NFE of 0.04, representing a greatly stabilized tooth site sample group. Several sites remained in the high-risk category and some increased in pathologic micromovement. Two models were used to determine severity with indicative cutoff points to group sites with similar values. The data support the hypothesis that QPD can indicate a revised level of structural instability of teeth after restoration. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Primary healthcare-based integrated care with opioid agonist treatment: First experience from Ukraine.

PubMed

Morozova, Olga; Dvoriak, Sergey; Pykalo, Iryna; Altice, Frederick L

2017-04-01

Ukraine's HIV epidemic is concentrated among people who inject drugs (PWID), however, coverage with opioid agonist therapies (OATs) available mostly at specialty addiction clinics is extremely low. OAT integrated into primary healthcare clinics (PHCs) provides an opportunity for integrating comprehensive healthcare services and scaling up OAT. A pilot study of PHC-based integrated care for drug users conducted in two Ukrainian cities between 2014 and 2016 included three sub-studies: 1) cross-sectional treatment site preference assessment among current OAT patients (N=755); 2) observational cohort of 107 PWID who continued the standard of care versus transition of stabilized and newly enrolled PWID into PHC-based integrated care; and 3) pre/post analysis of attitudes toward PWID and HIV patients by PHC staff (N=26). Among 755 OAT patients, 53.5% preferred receiving OAT at PHCs, which was independently correlated with convenience, trust in physician, and treatment with methadone (vs. buprenorphine). In 107 PWID observed over 6 months, retention in treatment was high: 89% in PWID continuing OAT in specialty addiction treatment settings (standard of care) vs 94% in PWID transitioning to PHCs; and 80% among PWID newly initiating OAT in PHCs. Overall, satisfaction with treatment, subjective self-perception of well-being, and trust in physician significantly increased in patients prescribed OAT in PHCs. Among PHC staff, attitudes towards PWID and HIV patients significantly improved over time. OAT can be successfully integrated into primary care in low and middle-income countries and improves outcomes in both patients and clinicians while potentially scaling-up OAT for PWID. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2012-01-01

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

Integral backstepping sliding mode control for underactuated systems: swing-up and stabilization of the Cart-Pendulum System.

PubMed

Adhikary, Nabanita; Mahanta, Chitralekha

2013-11-01

In this paper an integral backstepping sliding mode controller is proposed for controlling underactuated systems. A feedback control law is designed based on backstepping algorithm and a sliding surface is introduced in the final stage of the algorithm. The backstepping algorithm makes the controller immune to matched and mismatched uncertainties and the sliding mode control provides robustness. The proposed controller ensures asymptotic stability. The effectiveness of the proposed controller is compared against a coupled sliding mode controller for swing-up and stabilization of the Cart-Pendulum System. Simulation results show that the proposed integral backstepping sliding mode controller is able to reject both matched and mismatched uncertainties with a chattering free control law, while utilizing less control effort than the sliding mode controller. Copyright © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

Security region-based small signal stability analysis of power systems with FSIG based wind farm

NASA Astrophysics Data System (ADS)

Qin, Chao; Zeng, Yuan; Yang, Yang; Cui, Xiaodan; Xu, Xialing; Li, Yong

2018-02-01

Based on the Security Region approach, the impact of fixed-speed induction generator based wind farm on the small signal stability of power systems is analyzed. Firstly, the key factors of wind farm on the small signal stability of power systems are analyzed and the parameter space for small signal stability region is formed. Secondly, the small signal stability region of power systems with wind power is established. Thirdly, the corresponding relation between the boundary of SSSR and the dominant oscillation mode is further studied. Results show that the integration of fixed-speed induction generator based wind farm will cause the low frequency oscillation stability of the power system deteriorate. When the output of wind power is high, the oscillation stability of the power system is mainly concerned with the inter-area oscillation mode caused by the integration of the wind farm. Both the active power output and the capacity of reactive power compensation of the wind farm have a significant influence on the SSSR. To improve the oscillation stability of power systems with wind power, it is suggested to reasonably set the reactive power compensation capacity for the wind farm through SSSR.

Direct Epoxidation of Propylene over Stabilized Cu + Surface Sites on Ti Modified Cu 2O

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

Yang, X.; Kattel, S.; Xiong, K.

2015-07-17

Direct propylene epoxidation by O 2 is a challenging reaction because of the strong tendency for complete combustion. Results from the current study demonstrate the feasibility to tune the epoxidation selectivity by generating highly dispersed and stabilized Cu + active sites in a TiCuO x mixed oxide. The TiCuO x surface anchors the key surface intermediate, oxametallacycle, leading to higher selectivity for epoxidation of propylene.

Time-interval for integration of stabilizing haptic and visual information in subjects balancing under static and dynamic conditions

PubMed Central

Honeine, Jean-Louis; Schieppati, Marco

2014-01-01

Maintaining equilibrium is basically a sensorimotor integration task. The central nervous system (CNS) continually and selectively weights and rapidly integrates sensory inputs from multiple sources, and coordinates multiple outputs. The weighting process is based on the availability and accuracy of afferent signals at a given instant, on the time-period required to process each input, and possibly on the plasticity of the relevant pathways. The likelihood that sensory inflow changes while balancing under static or dynamic conditions is high, because subjects can pass from a dark to a well-lit environment or from a tactile-guided stabilization to loss of haptic inflow. This review article presents recent data on the temporal events accompanying sensory transition, on which basic information is fragmentary. The processing time from sensory shift to reaching a new steady state includes the time to (a) subtract or integrate sensory inputs; (b) move from allocentric to egocentric reference or vice versa; and (c) adjust the calibration of motor activity in time and amplitude to the new sensory set. We present examples of processes of integration of posture-stabilizing information, and of the respective sensorimotor time-intervals while allowing or occluding vision or adding or subtracting tactile information. These intervals are short, in the order of 1–2 s for different postural conditions, modalities and deliberate or passive shift. They are just longer for haptic than visual shift, just shorter on withdrawal than on addition of stabilizing input, and on deliberate than unexpected mode. The delays are the shortest (for haptic shift) in blind subjects. Since automatic balance stabilization may be vulnerable to sensory-integration delays and to interference from concurrent cognitive tasks in patients with sensorimotor problems, insight into the processing time for balance control represents a critical step in the design of new balance- and locomotion training devices. PMID:25339872

Integrating plant litter quality, soil organic matter stabilization, and the carbon saturation concept

USDA-ARS?s Scientific Manuscript database

Recent research suggests labile plant litters promote the stabilization of soil organic matter (SOM) in physico-chemically protected fractions with relatively slow turnover. However, the effect of litter quality on SOM stabilization is inconsistent. Labile, ‘high quality’ litters characterized by hi...

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

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

Not Available

1991-12-01

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

Parallel multiphase microflows: fundamental physics, stabilization methods and applications.

PubMed

Aota, Arata; Mawatari, Kazuma; Kitamori, Takehiko

2009-09-07

Parallel multiphase microflows, which can integrate unit operations in a microchip under continuous flow conditions, are discussed. Fundamental physics, stabilization methods and some applications are shown.

Using the Sonoran and Libyan Desert test sites to monitor the temporal stability of reflective solar bands for Landsat 7 enhanced thematic mapper plus and Terra moderate resolution imaging spectroradiometer sensors

USGS Publications Warehouse

Angal, Amit; Xiong, Xiaoxiong; Choi, Tae-young; Chander, Gyanesh; Wu, Aisheng

2010-01-01

Remote sensing imagery is effective for monitoring environmental and climatic changes because of the extent of the global coverage and long time scale of the observations. Radiometric calibration of remote sensing sensors is essential for quantitative & qualitative science and applications. Pseudo-invariant ground targets have been extensively used to monitor the long-term radiometric calibration stability of remote sensing sensors. This paper focuses on the use of the Sonoran Desert site to monitor the radiometric stability of the Landsat 7 (L7) Enhanced Thematic Mapper Plus (ETM+) and Terra Moderate Resolution Imaging Spectroradiometer (MODIS) sensors. The results are compared with the widely used Libya 4 Desert site in an attempt to evaluate the suitability of the Sonoran Desert site for sensor inter-comparison and calibration stability monitoring. Since the overpass times of ETM+ and MODIS differ by about 30 minutes, the impacts due to different view geometries or test site Bi-directional Reflectance Distribution Function (BRDF) are also presented. In general, the long-term drifts in the visible bands are relatively large compared to the drift in the near-infrared bands of both sensors. The lifetime Top-of-Atmosphere (TOA) reflectance trends from both sensors over 10 years are extremely stable, changing by no more than 0.1% per year (except ETM+ Band 1 and MODIS Band 3) over the two sites used for the study. The use of a semi-empirical BRDF model can reduce the impacts due to view geometries, thus enabling a better estimate of sensor temporal drifts.

Use of phytoproductivity data in the choice of native plant species to restore a degraded coal mining site amended with a stabilized industrial organic sludge.

PubMed

Chiochetta, Claudete G; Toumi, Hela; Böhm, Renata F S; Engel, Fernanda; Poyer-Radetski, Gabriel; Rörig, Leonardo R; Adani, Fabrizio; Radetski, Claudemir M

2017-11-01

Coal mining-related activities result in a degraded landscape and sites associated with large amounts of dumped waste material. The arid soil resulting from acid mine drainage affects terrestrial and aquatic ecosystems, and thus, site remediation programs must be implemented to mitigate this sequential deleterious processes. A low-cost alternative material to counterbalance the affected physico-chemical-microbiological aspects of the degraded soil is the amendment with low contaminated and stabilized industrial organic sludge. The content of nutrients P and N, together with stabilized organic matter, makes this material an excellent fertilizer and soil conditioner, fostering biota colonization and succession in the degraded site. However, choice of native plant species to restore a degraded site must be guided by some minimal criteria, such as plant survival/adaptation and plant biomass productivity. Thus, in this 3-month study under environmental conditions, phytoproductivity tests with five native plant species (Surinam cherry Eugenia uniflora L., C. myrianthum-Citharexylum myrianthum, Inga-Inga spp., Brazilian peppertree Schinus terebinthifolius, and Sour cherry Prunus cerasus) were performed to assess these criteria, and additional biochemical parameters were measured in plant tissues (i.e., protein content and peroxidase activity) exposed to different soil/sludge mixture proportions. The results show that three native plants were more adequate to restore vegetation on degraded sites: Surinam cherry, C. myrianthum, and Brazilian peppertree. Thus, this study demonstrates that phytoproductivity tests associated with biochemical endpoint measurements can help in the choice of native plant species, as well as aiding in the choice of the most appropriate soil/stabilized sludge proportion in order to optimize biomass production.

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

PubMed Central

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

2008-01-01

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

Specific insertions of zinc finger domains into Gag-Pol yield engineered retroviral vectors with selective integration properties

PubMed Central

Lim, Kwang-il; Klimczak, Ryan; Yu, Julie H.; Schaffer, David V.

2010-01-01

Retroviral vectors offer benefits of efficient delivery and stable gene expression; however, their clinical use raises the concerns of insertional mutagenesis and potential oncogenesis due to genomic integration preferences in transcriptional start sites (TSS). We have shifted the integration preferences of retroviral vectors by generating a library of viral variants with a DNA-binding domain inserted at random positions throughout murine leukemia virus Gag-Pol, then selecting for variants that are viable and exhibit altered integration properties. We found seven permissive zinc finger domain (ZFD) insertion sites throughout Gag-Pol, including within p12, reverse transcriptase, and integrase. Comprehensive genome integration analysis showed that several ZFD insertions yielded retroviral vector variants with shifted integration patterns that did not favor TSS. Furthermore, integration site analysis revealed selective integration for numerous mutants. For example, two retroviral variants with a given ZFD at appropriate positions in Gag-Pol strikingly integrated primarily into four common sites out of 3.1 × 109 possible human genome locations (P = 4.6 × 10-29). Our findings demonstrate that insertion of DNA-binding motifs into multiple locations in Gag-Pol can make considerable progress toward engineering safer retroviral vectors that integrate into a significantly narrowed pool of sites on human genome and overcome the preference for TSS. PMID:20616052

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

PubMed Central

McAllister, Robert G; Liu, Jiahui; Woods, Matthew W; Tom, Sean K; Rupar, C Anthony; Barr, Stephen D

2014-01-01

The blood–brain barrier controls the passage of molecules from the blood into the central nervous system (CNS) and is a major challenge for treatment of neurological diseases. Metachromatic leukodystrophy is a neurodegenerative lysosomal storage disease caused by loss of arylsulfatase A (ARSA) activity. Gene therapy via intraventricular injection of a lentiviral vector is a potential approach to rapidly and permanently deliver therapeutic levels of ARSA to the CNS. We present the distribution of integration sites of a lentiviral vector encoding human ARSA (LV-ARSA) in murine brain choroid plexus and ependymal cells, administered via a single intracranial injection into the CNS. LV-ARSA did not exhibit a strong preference for integration in or near actively transcribed genes, but exhibited a strong preference for integration in or near satellite DNA. We identified several genomic hotspots for LV-ARSA integration and identified a consensus target site sequence characterized by two G-quadruplex-forming motifs flanking the integration site. In addition, our analysis identified several other non-B DNA motifs as new factors that potentially influence lentivirus integration, including human immunodeficiency virus type-1 in human cells. Together, our data demonstrate a clinically favorable integration site profile in the murine brain and identify non-B DNA as a potential new host factor that influences lentiviral integration in murine and human cells. PMID:25158091

The use of gum Arabic as "Green" stabilizer of poly(aniline) nanocomposites: a comprehensive study of spectroscopic, morphological and electrochemical properties.

PubMed

Quintanilha, Ronaldo C; Orth, Elisa S; Grein-Iankovski, Aline; Riegel-Vidotti, Izabel C; Vidotti, Marcio

2014-11-15

Herein we show the synthesis and characterization of water dispersible composites formed by poly(aniline) and the natural polymer gum Arabic (GA), used as stabilizer. The materials were synthesized via a rapid and straightforward method and were fully characterized by different techniques such as UV-Vis, Raman, FTIR, TEM, SEM and cyclic voltammetry. TEM and SEM images revealed that the proportion of stabilizer highly influences the growth mechanism of the nanostructures. It was found spherical particles, elongated structures and large agglomerates at the lower, intermediate and at the higher GA amount, respectively. Accordingly to fluorescence spectra, different hydrophobic structures are formed depending on the GA amount in aqueous solutions, possibly acting as hosting sites for the PANI growth. In order to further study the PANI polymerization in the presence of GA, kinetics experiments were performed and showed that nucleation is the limiting step for the composite growth and a model is proposed. Spectroscopic experiments showed that the presence of GA affects the PANI conformation, avoiding the formation of phenazine structures which highly impairs the electroactivity of PANI. The material integrity is achieved by strong hydrogen bond interactions between PANI and GA as evidenced by the study of specific NH bands in FTIR and Raman analyses. The intensity of the hydrogen bonds decreased upon higher amounts of GA, probably due to steric impediment around the NH sites. Cyclic voltammograms showed a good electroactivity behavior of the modified electrodes presenting distinguishable diffusional processes through the adsorbed composites. By this way, we have thoroughly investigated the formation and properties of new conducting polymer composite materials. Taken into account the low toxicity of GA and the excellent dispersity in water, the materials can successfully be applied in bioelectrochemical applications or as green corrosion inhibitors. Copyright © 2014 Elsevier Inc. All rights reserved.

Internally bridging water molecule in transmembrane alpha-helical kink.

PubMed

Miyano, Masashi; Ago, Hideo; Saino, Hiromichi; Hori, Tetsuya; Ida, Koh

2010-08-01

There are hundreds of membrane protein atomic coordinates in the Protein Data Bank (PDB), and high-resolution structures of better than 2.5 A enable the visualization of a sizable number of amphiphiles (lipid and/or detergent) and bound water molecules as essential parts of the structure. Upon scrutinizing these high-resolution structures, water molecules were found to 'wedge' and stabilize large kink angle (30-40 degrees) in a simple cylindrical model at the transmembrane helical kinks so as to form an inter-helical cavity to accommodate a ligand binding or active site as a crucial structural feature in alpha-helical integral membrane proteins. Furthermore, some of these water molecules are proposed to play a pivotal role of their conformational change to exert their functional regulation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Design and calibration of field deployable ground-viewing radiometers.

PubMed

Anderson, Nikolaus; Czapla-Myers, Jeffrey; Leisso, Nathan; Biggar, Stuart; Burkhart, Charles; Kingston, Rob; Thome, Kurtis

2013-01-10

Three improved ground-viewing radiometers were built to support the Radiometric Calibration Test Site (RadCaTS) developed by the Remote Sensing Group (RSG) at the University of Arizona. Improved over previous light-emitting diode based versions, these filter-based radiometers employ seven silicon detectors and one InGaAs detector covering a wavelength range of 400-1550 nm. They are temperature controlled and designed for greater stability and lower noise. The radiometer systems show signal-to-noise ratios of greater than 1000 for all eight channels at typical field calibration signal levels. Predeployment laboratory radiance calibrations using a 1 m spherical integrating source compare well with in situ field calibrations using the solar radiation based calibration method; all bands are within ±2.7% for the case tested.

Assessment of stability of the response versus scan angle for the S-NPP VIIRS reflective solar bands using pseudo-invariant desert and Dome C sites

NASA Astrophysics Data System (ADS)

Wu, Aisheng; Xiong, Xiaoxiong J.; Cao, Changyong

2017-09-01

The Visible Infrared Imaging Radiometer Suite (VIIRS) on the Suomi NPP (National Polar-orbiting Partnership) satellite has been in operation for over five years. VIIRS has 22 bands with a spectral range from 0.4 μm to 2.2 μm for the reflective solar bands (RSB). The Earth view swath covers a distance of 3000 km over scan angles of +/- 56.0° off nadir. The on-board calibration of the RSB relies on a solar diffuser (SD) located at a fixed scan angle and a solar diffuser stability monitor (SDSM). The response versus scan angle (RVS) was characterized prelaunch in ambient conditions and is currently used to determine the on-orbit response for all scan angles relative to the SD scan angle. Since the RVS is vitally important to the quality of calibrated level 1B products, it is important to monitor its on-orbit stability, particularly at the short wavelengths (blue) where the most degradation occurs. In this study, the RVS stability is examined based on reflectance trends collected at various scan angles over the selected pseudo-invariant desert sites in Northern Africa and the Dome C snow site in Antarctica. These trends are corrected by the site dependent BRDF (bi-directional reflectance function) model to reduce seasonally related fluctuations. The BRDF corrected trends are examined so any systematic drifts in the scan angle direction would indicate a potential change in RVS. The results of this study provide useful information on VIIRS RVS on-orbit stability performance.

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

Code of Federal Regulations, 2012 CFR

2012-10-01

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

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

Code of Federal Regulations, 2011 CFR

2011-10-01

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

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

Code of Federal Regulations, 2014 CFR

2014-10-01

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

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

Code of Federal Regulations, 2013 CFR

2013-10-01

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

The Function of Neuroendocrine Cells in Prostate Cancer

DTIC Science & Technology

2013-04-01

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

Constitutional Reform for Conflict Management

DTIC Science & Technology

2014-04-01

conflict. Empirical studies reveal that both accommodative and integrative constitutional design can produce political stability , if properly...reform, and the ability of various constitutional designs to promote democracy and political stability .

Integrating Crystallography into Early Metabolism Studies

NASA Astrophysics Data System (ADS)

Cruciani, Gabriele; Aristei, Yasmin; Goracci, Laura; Carosati, Emanuele

Since bioavailability, activity, toxicity, distribution, and final elimination all depend on metabolic biotransformations, it would be extremely advantageous if this information to be produced early in the discovery phase. Once obtained, researchers can judge whether or not a potential candidate should be eliminated from the pipeline, or modified to improve chemical stability or safety. The use of in silico methods to predict the site of metabolism in Phase I cytochrome-mediated reactions is a starting point in any metabolic pathway prediction. This paper presents a new method, which provides the site of metabolism for any CYP-mediated reaction acting on unknown substrates. The methodology can be applied automatically to all the cytochromes whose Xray 3D structure is known, but can be also applied to homology model 3D structures. The fully automated procedure can be used to detect positions that should be protected in order to avoid metabolic degradation, or to check the suitability of a new scaffold or pro-drug. Therefore the procedure is also a valuable new tool in early ADME-Tox, where drug-safety and metabolic profile patterns must be evaluated as soon, and as early, as possible.

Structural mechanism of ligand activation in human calcium-sensing receptor

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

Geng, Yong; Mosyak, Lidia; Kurinov, Igor

2016-07-19

Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that maintains extracellular Ca 2+homeostasis through the regulation of parathyroid hormone secretion. It functions as a disulfide-tethered homodimer composed of three main domains, the Venus Flytrap module, cysteine-rich domain, and seven-helix transmembrane region. Here, we present the crystal structures of the entire extracellular domain of CaSR in the resting and active conformations. We provide direct evidence that L-amino acids are agonists of the receptor. In the active structure, L-Trp occupies the orthosteric agonist-binding site at the interdomain cleft and is primarily responsible for inducing extracellular domain closure to initiate receptor activation.more » Our structures reveal multiple binding sites for Ca 2+and PO 4 3-ions. Both ions are crucial for structural integrity of the receptor. While Ca 2+ions stabilize the active state, PO 4 3-ions reinforce the inactive conformation. The activation mechanism of CaSR involves the formation of a novel dimer interface between subunits.« less

Compositional stability of boreal understorey vegetation after overstorey harvesting across a riparian ecotone

Treesearch

Rebecca L. MacDonald; Han Y.H. Chen; Samuel F. Bartels; Brian J. Palik; Ellie E. Prepas; Frank Gilliam

2015-01-01

Questions: Understanding factors that contribute to the stability of an ecosystem following harvesting is central to predicting responses of boreal ecosystems to increasing human disturbances.While the response of understorey vegetation to harvesting is well understood for upland sites, little is known about compositional stability of riparian understorey vegetation....

Integrated Management of all Historical, Operational and Future Decomissioning Solid ILW at Dounreay

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

Graham, D.

This paper describes major components of the Dounreay Site Restoration Plan, DSRP to deal with the site's solid intermediate level waste, ILW legacy. Historic solid ILW exists in the Shaft (disposals between 1959 and 1977), the Wet Silo (operated between 1973 and 1998), and in operating engineered drummed storage. Significant further arisings are expected from future operations, post-operations clean out and decommissioning through to the completion of site restoration, expected to be complete by about 2060. The raw waste is in many solid forms and also incorporates sludge, some fissile material and hazardous chemical components. The aim of the Solidmore » ILW Project is to treat and condition all this waste to make it passively safe and in a form which can be stored for a substantial period, and then transported to the planned U.K. national deep repository for ILW disposal. The Solid ILW Project involves the construction of head works for waste retrieval operations at the Shaft and Wet Silo, a Waste Treatment Plant and a Conditioned Waste Store to hold the conditioned waste until the disposal facilities become available. In addition, there are infrastructure activities to enable the new construction: contaminated ground remediation, existing building demolition, underground and overground services diversion, sea cliff stabilization, and groundwater isolation at the Shaft.« less

Stabilization of time domain acoustic boundary element method for the exterior problem avoiding the nonuniqueness.

PubMed

Jang, Hae-Won; Ih, Jeong-Guon

2013-03-01

The time domain boundary element method (TBEM) to calculate the exterior sound field using the Kirchhoff integral has difficulties in non-uniqueness and exponential divergence. In this work, a method to stabilize TBEM calculation for the exterior problem is suggested. The time domain CHIEF (Combined Helmholtz Integral Equation Formulation) method is newly formulated to suppress low order fictitious internal modes. This method constrains the surface Kirchhoff integral by forcing the pressures at the additional interior points to be zero when the shortest retarded time between boundary nodes and an interior point elapses. However, even after using the CHIEF method, the TBEM calculation suffers the exponential divergence due to the remaining unstable high order fictitious modes at frequencies higher than the frequency limit of the boundary element model. For complete stabilization, such troublesome modes are selectively adjusted by projecting the time response onto the eigenspace. In a test example for a transiently pulsating sphere, the final average error norm of the stabilized response compared to the analytic solution is 2.5%.

Molecular Characterization of Transgenic Events Using Next Generation Sequencing Approach.

PubMed

Guttikonda, Satish K; Marri, Pradeep; Mammadov, Jafar; Ye, Liang; Soe, Khaing; Richey, Kimberly; Cruse, James; Zhuang, Meibao; Gao, Zhifang; Evans, Clive; Rounsley, Steve; Kumpatla, Siva P

2016-01-01

Demand for the commercial use of genetically modified (GM) crops has been increasing in light of the projected growth of world population to nine billion by 2050. A prerequisite of paramount importance for regulatory submissions is the rigorous safety assessment of GM crops. One of the components of safety assessment is molecular characterization at DNA level which helps to determine the copy number, integrity and stability of a transgene; characterize the integration site within a host genome; and confirm the absence of vector DNA. Historically, molecular characterization has been carried out using Southern blot analysis coupled with Sanger sequencing. While this is a robust approach to characterize the transgenic crops, it is both time- and resource-consuming. The emergence of next-generation sequencing (NGS) technologies has provided highly sensitive and cost- and labor-effective alternative for molecular characterization compared to traditional Southern blot analysis. Herein, we have demonstrated the successful application of both whole genome sequencing and target capture sequencing approaches for the characterization of single and stacked transgenic events and compared the results and inferences with traditional method with respect to key criteria required for regulatory submissions.

A multifunctional biphasic water splitting catalyst tailored for integration with high-performance semiconductor photoanodes

DOE PAGES

Yang, Jinhui; Cooper, Jason K.; Toma, Francesca M.; ...

2016-11-07

Artificial photosystems are advanced by the development of conformal catalytic materials that promote desired chemical transformations, while also maintaining stability and minimizing parasitic light absorption for integration on surfaces of semiconductor light absorbers. We demonstrate that multifunctional, nanoscale catalysts that enable high-performance photoelectrochemical energy conversion can be engineered by plasma-enhanced atomic layer deposition. The collective properties of tailored Co 3 O 4 /Co(OH) 2 thin films simultaneously provide high activity for water splitting, permit efficient interfacial charge transport from semiconductor substrates, and enhance durability of chemically sensitive interfaces. Furthermore, these films comprise compact and continuous nanocrystalline Co 3 O 4more » spinel that is impervious to phase transformation and impermeable to ions, thereby providing effective protection of the underlying substrate. Moreover, a secondary phase of structurally disordered and chemically labile Co(OH) 2 is introduced to ensure a high concentration of catalytically active sites. Application of this coating to photovoltaic p + n-Si junctions yields best reported performance characteristics for crystalline Si photoanodes.« less

Characterization of optical frequency transfer over 154  km of aerial fiber.

PubMed

Gozzard, David R; Schediwy, Sascha W; Wallace, Bruce; Gamatham, Romeo; Grainge, Keith

2017-06-01

We present measurements of the frequency transfer stability and analysis of the noise characteristics of an optical signal propagating over aerial suspended fiber links up to 153.6 km in length. The measured frequency transfer stability over these links is on the order of 10^-11 at an integration time of 1 s dropping to 10^-12 for integration times longer than 100 s. We show that wind-loading of the cable spans is the dominant source of short-timescale noise on the fiber links. We also report an attempt to stabilize the optical frequency transfer over these aerial links.

Gas Hydrate Research Site Selection and Operational Research Plans

NASA Astrophysics Data System (ADS)

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

2009-12-01

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

Eddy-covariance methane flux measurements over a European beech forest

NASA Astrophysics Data System (ADS)

Gentsch, Lydia; Siebicke, Lukas; Knohl, Alexander

2015-04-01

The role of forests in global methane (CH4) turnover is currently not well constrained, partially because of the lack of spatially integrative forest-scale measurements of CH4 fluxes. Soil chamber measurements imply that temperate forests generally act as CH4 sinks. Upscaling of chamber observations to the forest scale is however problematic, if the upscaling is not constrained by concurrent 'top-down' measurements, such as of the eddy-covariance type, which provide sufficient integration of spatial variations and of further potential CH4 flux components within forest ecosystems. Ongoing development of laser absorption-based optical instruments, resulting in enhanced measurement stability, precision and sampling speed, has recently improved the prospects for meaningful eddy-covariance measurements at sites with presumably low CH4 fluxes, hence prone to reach the flux detection limit. At present, we are launching eddy-covariance CH4 measurements at a long-running ICOS flux tower site (Hainich National Park, Germany), located in a semi natural, unmanaged, beech dominated forest. Eddy-covariance measurements will be conducted with a laser spectrometer for parallel CH4, H2Ov and CO2 measurements (FGGA, Los Gatos Research, USA). Independent observations of the CO2 flux by the FGGA and a standard Infrared Gas Analyser (LI-7200, LI-COR, USA) will allow to evaluate data quality of measured CH4 fluxes. Here, we want to present first results with a focus on uncertainties of the calculated CH4 fluxes with regard to instrument precision, data processing and site conditions. In future, we plan to compare eddy-covariance flux estimates to side-by-side turbulent flux observations from a novel eddy accumulation system. Furthermore, soil CH4 fluxes will be measured with four automated chambers situated within the tower footprint. Based on a previous soil chamber study at the same site, we expect the Hainich forest site to act as a CH4 sink. However, we hypothesize that our measurements might also reveal short CH4 emission periods when soils become water-saturated. Nonetheless, CH4 emissions by plants could also result in a close to neutral net CH4 flux.

Site directed recombination

DOEpatents

Jurka, Jerzy W.

1997-01-01

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

Molecular cloning and expression of a gene for a factor which stabilizes formation of inhibitor-mitochondrial ATPase complex from Saccharomyces cerevisiae.

PubMed

Akashi, A; Yoshida, Y; Nakagoshi, H; Kuroki, K; Hashimoto, T; Tagawa, K; Imamoto, F

1988-10-01

Stabilizing factor, a 9 kDa protein, stabilizes and facilitates formation of the complex between mitochondrial ATP synthase and its intrinsic inhibitor protein. A clone containing the gene encoding the 9 kDa protein was selected from a yeast genomic library to determine the structure of its precursor protein. As deduced from the nucleotide sequence, the precursor of the yeast 9 kDa stabilizing factor contains 86 amino acid residues and has a molecular weight of 10,062. From the predicted sequence we infer that the stabilizing factor precursor contains a presequence of 23 amino acid residues at its amino terminus. We also used S1 mapping to determine the initiation site of transcription under glucose-repressed or derepressed conditions. These experiments suggest that transcription of this gene starts at three different sites and that only one of them is not affected by the presence of glucose.

Removal of the Side Chain at the Active-Site Serine by a Glycine Substitution Increases the Stability of a Wide Range of Serine β-Lactamases by Relieving Steric Strain

DOE PAGES

Stojanoski, Vlatko; Adamski, Carolyn J.; Hu, Liya; ...

2016-04-12

Serine β-lactamases are bacterial enzymes that hydrolyze β- lactam antibiotics. They utilize an active-site serine residue as a nucleophile, forming an acyl-enzyme intermediate during hydrolysis. Here, thermal denaturation experiments as well as X-ray crystallography were performed to test the effect of substitution of the catalytic serine with glycine on protein stability in serine β-lactamases. Six different enzymes comprising representatives from each of the three classes of serine β-lactamases were examined, including TEM-1, CTX-M- 14, and KPC-2 of class A, P99 of class C, and OXA-48 and OXA-163 of class D. For each enzyme, the wild type and a serine-to-glycine mutantmore » were evaluated for stability. The glycine mutants all exhibited enhanced thermostability compared to that of the wild type. In contrast, alanine substitutions of the catalytic serine in TEM-1, OXA-48, and OXA-163 did not alter stability, suggesting removal of the Cβ atom is key to the stability increase associated with the glycine mutants. The X-ray crystal structures of P99 S64G, OXA-48 S70G and S70A, and OXA-163 S70G suggest that removal of the side chain of the catalytic serine releases steric strain to improve enzyme stability. In addition, analysis of the torsion angles at the nucleophile position indicates that the glycine mutants exhibit improved distance and angular parameters of the intrahelical hydrogen bond network compared to those of the wild-type enzymes, which is also consistent with increased stability. The increased stability of the mutants indicates that the enzyme pays a price in stability for the presence of a side chain at the catalytic serine position but that the cost is necessary in that removal of the serine drastically impairs function. Our findings support the stability-function hypothesis, which states that active-site residues are optimized for substrate binding and catalysis but that the requirements for catalysis are often not consistent with the requirements for optimal stability.« less

Removal of the Side Chain at the Active-Site Serine by a Glycine Substitution Increases the Stability of a Wide Range of Serine β-Lactamases by Relieving Steric Strain

PubMed Central

Stojanoski, Vlatko; Adamski, Carolyn J.; Hu, Liya; Mehta, Shrenik C.; Sankaran, Banumathi; Zwart, Peter; Prasad, B.V. Venkataram; Palzkill, Timothy

2016-01-01

Serine β-lactamases are bacterial enzymes that hydrolyze β-lactam antibiotics. They utilize an active-site serine residue as a nucleophile, forming an acyl-enzyme intermediate during hydrolysis. In this study, thermal denaturation experiments as well as X-ray crystallography were performed to test the effect of substitution of the catalytic serine by glycine on protein stability in serine β-lactamases. Six different enzymes comprising representatives from each of the three classes of serine β-lactamases were examined including TEM-1, CTX-M-14, and KPC-2 of class A, P99 of class C, and OXA-48 and OXA-163 of class D. For each enzyme, the wild type and a serine-to-glycine mutant were evaluated for stability. The glycine mutants all exhibited enhanced thermostability compared to the wild type. In contrast, alanine substitutions of the catalytic serine in TEM-1, OXA-48 and OXA-163 did not alter stability, suggesting removal of the Cβ atom is key to the stability increase associated with the glycine mutants. The X-ray crystal structures of P99 S64G, OXA-48 S70G and S70A, and OXA-163 S70G suggest that removal of the side chain of the catalytic serine releases steric strain to improve enzyme stability. Additionally, analysis of the torsion angles at the nucleophile position indicates that the glycine mutants exhibit improved distance and angular parameters of the intra-helical hydrogen bond network compared to the wild-type enzymes, which is also consistent with increased stability. The increased stability of the mutants indicates that the enzyme pays a price in stability for the presence of a side chain at the catalytic serine position but that the cost is necessary in that removal of the serine drastically impairs function. These findings support the stability-function hypothesis, which states that active-site residues are optimized for substrate binding and catalysis but that the requirements for catalysis are often not consistent with the requirements for optimal stability. PMID:27073009

Removal of the Side Chain at the Active-Site Serine by a Glycine Substitution Increases the Stability of a Wide Range of Serine β-Lactamases by Relieving Steric Strain

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

Stojanoski, Vlatko; Adamski, Carolyn J.; Hu, Liya

Serine β-lactamases are bacterial enzymes that hydrolyze β- lactam antibiotics. They utilize an active-site serine residue as a nucleophile, forming an acyl-enzyme intermediate during hydrolysis. Here, thermal denaturation experiments as well as X-ray crystallography were performed to test the effect of substitution of the catalytic serine with glycine on protein stability in serine β-lactamases. Six different enzymes comprising representatives from each of the three classes of serine β-lactamases were examined, including TEM-1, CTX-M- 14, and KPC-2 of class A, P99 of class C, and OXA-48 and OXA-163 of class D. For each enzyme, the wild type and a serine-to-glycine mutantmore » were evaluated for stability. The glycine mutants all exhibited enhanced thermostability compared to that of the wild type. In contrast, alanine substitutions of the catalytic serine in TEM-1, OXA-48, and OXA-163 did not alter stability, suggesting removal of the Cβ atom is key to the stability increase associated with the glycine mutants. The X-ray crystal structures of P99 S64G, OXA-48 S70G and S70A, and OXA-163 S70G suggest that removal of the side chain of the catalytic serine releases steric strain to improve enzyme stability. In addition, analysis of the torsion angles at the nucleophile position indicates that the glycine mutants exhibit improved distance and angular parameters of the intrahelical hydrogen bond network compared to those of the wild-type enzymes, which is also consistent with increased stability. The increased stability of the mutants indicates that the enzyme pays a price in stability for the presence of a side chain at the catalytic serine position but that the cost is necessary in that removal of the serine drastically impairs function. Our findings support the stability-function hypothesis, which states that active-site residues are optimized for substrate binding and catalysis but that the requirements for catalysis are often not consistent with the requirements for optimal stability.« less

Stability of Beriplast P fibrin sealant: storage and reconstitution.

PubMed

Eberhard, Ulrich; Broder, Martin; Witzke, Günther

2006-04-26

This study was performed to investigate the stability of Beriplast P fibrin sealant (FS) across a range of storage conditions, both pre- and post-reconstitution. Storage stability of the FS was evaluated during long-term refrigeration (24 months) with or without interim storage at elevated temperatures (40 degrees C for 1 week and 25 degrees C for 1 and 3 months). Stability of individual FS components was assessed by measuring: fibrinogen content, Factor XIII activity (FXIII), thrombin activity and aprotinin potency. The package integrity of each component was also checked (sterility testing, moisture content and pH). Storage stability was also evaluated by testing the reconstituted product for adhesion (tearing force testing after mixing the solutions) and sterility. Reconstitution stability was evaluated following 3-months' storage, for up to 50 h post-reconstitution using the same tests as for the storage stability investigations. Pre-defined specifications were met for fibrinogen content, Factor XIII activity, and thrombin activity, demonstrating storage stability. Package integrity and the functionality and sterility of the reconstituted product were confirmed throughout. Reconstitution stability was demonstrated for up to 50 h following reconstitution, in terms of both tearing force and sterility tests. In conclusion, the storage stability of Beriplast P was demonstrated over a range of 24-month storage schedules including interim exposure to elevated temperature, and the reconstituted product was stable for up to 50 h.

Tibial anatomy in normal small breed dogs including anisometry of various extracapsular stabilizing suture attachment sites.

PubMed

Witte, P G

2015-01-01

To investigate proximal tibial anatomy and its influence on anisometry of extracapsular stabilizing sutures in small dog breeds. Mediolateral radiographs of the femora, stifles, and tibiae of 12 small breed dogs were acquired with the stifles positioned at various angles. Measurements taken included tibial plateau angle (TPA), diaphyseal: proximal tibial angle (DPA), patellar tendon angle (PTA), Z-angle, relative tibial tuberosity width (rTTW), and the distance between six combinations of two femoral and three tibial extra-capsular stabilizing suture (ECS) attachment sites. Theoretical strain through stifle range-of-motion was recorded. The TPA (32° ± 5.8°), DPA (10.2° ± 7.3°), PTA (103.7° ± 6.2°), and Z-angle (70.4° ± 9.0°) were positively correlated with one another (R >0.7), but none were correlated with rTTW (0.93 ± 0.10). The F2-T1 combination of ECS attachment sites had lowest strain for nine stifles. The shortest attachment site separation was at a stifle flexion of 50° for nine stifles. Proximal tibial anatomy measurements could not predict optimal attachment site combination, optimal stifle angle for suture placement, or ECS strain. There is individual variation in the optimal attachment site combination and stifle angle for suture placement, which may influence consistency of outcomes with ECS.

Silica-supported isolated gallium sites as highly active, selective and stable propane dehydrogenation catalysts† †Electronic supplementary information (ESI) available: Experimental details, material characterization data, catalytic measurement details and crystallographic details. CCDC 1499756. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6sc05178b Click here for additional data file. Click here for additional data file.

PubMed Central

Searles, Keith; Siddiqi, Georges; Safonova, Olga V.

2017-01-01

Single-site gallium centers on the surface of silica are prepared via grafting of [Ga(OSi(OtBu)3)3(THF)] on SiO2–700 followed by a thermolysis step. The resulting surface species corresponds to well-defined tetra-coordinate gallium single-sites, [( 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 SiO)3Ga(XOSi)] (X = –H or Si) according to IR, X-ray absorption near-edge structure and extended X-ray absorption fine structure analysis. These gallium sites show high activity, selectivity and stability for propane dehydrogenation with an initial turnover frequency of 20 per h per gallium center, propylene selectivity of ≥93% and remarkable stability over 20 h. The stability of the catalyst probably results from site-isolation of the active site on a non-reducible support such as silica, diminishing facile reduction typical of Ga2O3-based catalysts. PMID:28553501

SWiFT site atmospheric characterization

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

Kelley, Christopher Lee; Ennis, Brandon Lee

2016-01-01

Historical meteorological tall tower data are analyzed from the Texas Tech University 200 m tower to characterize the atmospheric trends of the Scaled Wind Farm Technologies (SWiFT) site. In this report the data are analyzed to reveal bulk atmospheric trends, temporal trends and correlations of atmospheric variables. Through this analysis for the SWiFT turbines the site International Electrotechnical Commission (IEC) classification is determined to be class III-C. Averages and distributions of atmospheric variables are shown, revealing large fluctuations and the importance of understanding the actual site trends as opposed to simply using averages. The site is significantly directional with themore » average wind speed from the south, and particularly so in summer and fall. Site temporal trends are analyzed from both seasonal (time of the year) to daily (hour of the day) perspectives. Atmospheric stability is seen to vary most with time of day and less with time of year. Turbulence intensity is highly correlated with stability, and typical daytime unstable conditions see double the level of turbulence intensity versus that experienced during the average stable night. Shear, veer and atmospheric stability correlations are shown, where shear and veer are both highest for stable atmospheric conditions. An analysis of the Texas Tech University tower anemometer measurements is performed which reveals the extent of the tower shadow effects and sonic tilt misalignment.« less

Base substitutions at scissile bond sites are sufficient to alter RNA-binding and cleavage activity of RNase III.

PubMed

Kim, Kyungsub; Sim, Se-Hoon; Jeon, Che Ok; Lee, Younghoon; Lee, Kangseok

2011-02-01

RNase III, a double-stranded RNA-specific endoribonuclease, degrades bdm mRNA via cleavage at specific sites. To better understand the mechanism of cleavage site selection by RNase III, we performed a genetic screen for sequences containing mutations at the bdm RNA cleavage sites that resulted in altered mRNA stability using a transcriptional bdm'-'cat fusion construct. While most of the isolated mutants showed the increased bdm'-'cat mRNA stability that resulted from the inability of RNase III to cleave the mutated sequences, one mutant sequence (wt-L) displayed in vivo RNA stability similar to that of the wild-type sequence. In vivo and in vitro analyses of the wt-L RNA substrate showed that it was cut only once on the RNA strand to the 5'-terminus by RNase III, while the binding constant of RNase III to this mutant substrate was moderately increased. A base substitution at the uncleaved RNase III cleavage site in wt-L mutant RNA found in another mutant lowered the RNA-binding affinity by 11-fold and abolished the hydrolysis of scissile bonds by RNase III. Our results show that base substitutions at sites forming the scissile bonds are sufficient to alter RNA cleavage as well as the binding activity of RNase III. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

High stability of electro-transport and magnetism against the A-site cation disorder in SrRuO3

PubMed Central

Wang, Y. L.; Liu, M. F.; Liu, R.; Xie, Y. L.; Li, X.; Yan, Z. B.; Liu, J.-M.

2016-01-01

It is known that the electro-transport and magnetism of perovskite alkaline-earth ruthenate oxides are sensitive to the lattice distortion associated with the A-site cation size. Orthorhombic CaRuO3 and cubic BaRuO3 exhibit distinctly different electro-transport and magnetic properties from orthorhombic SrRuO3. It has been suggested that SrRuO3 can be robust against some intrinsic/external perturbations but fragile against some others in terms of electro-transport and magnetism, and it is our motivation to explore such stability against the local site cation disorder. In this work, we prepare a set of SrRuO3-based samples with identical averaged A-site size but different A-site cation disorder (size mismatch) by Ca and Ba co-substitution of Sr. It is revealed that the electro-transport and magnetism of SrRuO3 demonstrate relatively high stability against this A-site cation disorder, characterized by the relatively invariable electrical and magnetic properties in comparison with those of SrRuO3 itself. A simple electro-transport network model is proposed to explain quantitatively the measured behaviors. The present work suggests that SrRuO3 as an itinerant electron ferromagnetic metal possesses relatively high robustness against local lattice distortion and cation occupation disorder. PMID:27297396

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

PubMed Central

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

2017-01-01

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

Vision-based stabilization of nonholonomic mobile robots by integrating sliding-mode control and adaptive approach

NASA Astrophysics Data System (ADS)

Cao, Zhengcai; Yin, Longjie; Fu, Yili

2013-01-01

Vision-based pose stabilization of nonholonomic mobile robots has received extensive attention. At present, most of the solutions of the problem do not take the robot dynamics into account in the controller design, so that these controllers are difficult to realize satisfactory control in practical application. Besides, many of the approaches suffer from the initial speed and torque jump which are not practical in the real world. Considering the kinematics and dynamics, a two-stage visual controller for solving the stabilization problem of a mobile robot is presented, applying the integration of adaptive control, sliding-mode control, and neural dynamics. In the first stage, an adaptive kinematic stabilization controller utilized to generate the command of velocity is developed based on Lyapunov theory. In the second stage, adopting the sliding-mode control approach, a dynamic controller with a variable speed function used to reduce the chattering is designed, which is utilized to generate the command of torque to make the actual velocity of the mobile robot asymptotically reach the desired velocity. Furthermore, to handle the speed and torque jump problems, the neural dynamics model is integrated into the above mentioned controllers. The stability of the proposed control system is analyzed by using Lyapunov theory. Finally, the simulation of the control law is implemented in perturbed case, and the results show that the control scheme can solve the stabilization problem effectively. The proposed control law can solve the speed and torque jump problems, overcome external disturbances, and provide a new solution for the vision-based stabilization of the mobile robot.

Integrated electromagnetic methods for archaeological prospection and stability assessment of anthropogenic mounds: insights into the English Cemetery in Florence

NASA Astrophysics Data System (ADS)

Cappuccini, Luca; Pazzi, Veronica; Tapete, Deodato

2013-04-01

The archaeological interest in anthropogenic mounds as historical products of human occupation generally concerns the understanding of their stratigraphic sequence and the discovery of buried structures. Nevertheless, a further key element relies on the assessment of their stability. This is particularly crucial when the conservation history induced relevant alteration of the former configuration, and a potential collapse might cause damages to heritage and actual risk for public safety. To respond to such dual diagnostic need, we propose an integration approach based on Very Low Frequency Electromagnetic (VLF-EM) qualitative method and 2D-Electrical Resistivity Tomography (2D-ERT), to make the best out of these two techniques in light of their frequencies/bandwidth and methods of soil investigation (15-30 kHz and DC, respectively). We present here the results from the experiments performed on one of the test sites selected to validate the proposed methodology, i.e. the Protestant Cemetery (the so-called "English Cemetery") in Florence, Italy, which is a demonstrative example of a huge sample of anthropogenic mounds within urban and rural environments. Located on a topographic relief, the cemetery testifies a long history since Roman times, as proved by historical documentation and the ceramic findings still now discovered on the (sub-)surface. Converted into a cemetery in 1827, the mound appeared as an anomalous outcrop adjacent to the town walls, prior to the final arrangement and reshaping due to the urban renewal of Florence in 1877, which definitely transformed it into a raised graveyard surrounded by boulevards. A campaign of VLF-EM and ERT measurements was performed to ascertain the presence of a buried part of the ancient eastern wall and identify the key areas of concern for the stability. High values of resistivity were clearly detected and mapped by means of 2D-ERT along the AA' array intercepting the hypothesized location of the buried wall. This measure was cross-validated with the corresponding VLF-EM anomaly profiles, thereby retrieving reliable geophysical evidences suggesting the presence of buried remains. To correlate the effects of inner structures and soil properties with the stability condition of the mound, crack pattern survey was carried out over the wall containing the mound, jointly to an inspection of the cavities and the interspaces between the exterior masonry surfaces and the rear terrain. The spatial distribution of the opened cracks allowed the actual threat for the stability of the mound to be assessed also in relation to the current positions of the cypresses, periodically replanted for landscape reasons. Interesting insights were obtained by mapping the inclination and tilt direction of the gravestones and funerary monuments, as superficial indicators of ground subsidence and soil compaction/collapse at the top of the mound. The benefits achieved for site management and tombstones maintenance have encouraged the exportation of this approach (highly adaptable to include also GPR and seismic methods) to other case studies, and open to a sustainable implementation for the investigation of funerary mounds, such as the Etruscan burial mounds.

EVALUATION OF WASTE STABILIZED BY THE SOLIDITECH SITE TECHNOLOGY

EPA Science Inventory

The Soliditech technology demonstration was conducted at the Imperial Oil Company/Champion Chemicals Superfund Site in Monmouth County, New Jersey. ontamination at this site includes PCBs, lead (with various other metals) and oil and grease. his process mixes the waste material w...

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

PubMed Central

2012-01-01

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

Integration of textile fabric and coconut shell in particleboard

NASA Astrophysics Data System (ADS)

Misnon, M. I.; Bahari, S. A.; Islam, M. M.; Epaarachchi, J. A.

2013-08-01

In this study, cotton fabric and coconut shell were integrated in particleboard to reduce the use of wood. Particleboards containing mixed rubberwood and coconut shell with an equal weight ratio have been integrated with various layers of cotton fabric. These materials were bonded by urea formaldehyde with a content level of 12% by weight. Flexural and water absorption tests were conducted to analyze its mechanical properties and dimensional stability. Results of flexural test showed an increment at least double strength values in fabricated materials as compared to control sample. The existence of fabric in the particleboard system also improved the dimensional stability of the produced material. Enhancement of at least 39% of water absorption could help the dimensional stability of the produced material. Overall, these new particleboards showed better results with the incorporation of cotton fabric layers and this study provided better understanding on mechanical and physical properties of the fabricated particleboard.

Efficient Meshfree Large Deformation Simulation of Rainfall Induced Soil Slope Failure

NASA Astrophysics Data System (ADS)

Wang, Dongdong; Li, Ling

2010-05-01

An efficient Lagrangian Galerkin meshfree framework is presented for large deformation simulation of rainfall-induced soil slope failure. Detailed coupled soil-rainfall seepage equations are given for the proposed formulation. This nonlinear meshfree formulation is featured by the Lagrangian stabilized conforming nodal integration method where the low cost nature of nodal integration approach is kept and at the same time the numerical stability is maintained. The initiation and evolution of progressive failure in the soil slope is modeled by the coupled constitutive equations of isotropic damage and Drucker-Prager pressure-dependent plasticity. The gradient smoothing in the stabilized conforming integration also serves as a non-local regularization of material instability and consequently the present method is capable of effectively capture the shear band failure. The efficacy of the present method is demonstrated by simulating the rainfall-induced failure of two typical soil slopes.

Native backfill materials for mechanically stabilized earth walls.

DOT National Transportation Integrated Search

2005-01-01

Mechanically stabilized earth walls are an attractive alternative to conventional reinforced concrete retaining walls. The economy of these walls for non-critical applications might be improved by using alternative backfills consisting of on-site soi...

Electrical resistivity measurement of mechanically stabilized Earth wall backfill : technical summary.

DOT National Transportation Integrated Search

2016-06-01

In Kansas, mechanically stabilized earth (MSE) retaining walls are typically : backfilled with coarse aggregate. Current backfill material testing procedures used : by the Kansas Department of Transportation (KDOT) utilize on-site observations for : ...

Use of Electronic Hand-held Devices for Collection of Savannah River Site Environmental Data - 13329

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

Marberry, Hugh; Moore, Winston

2013-07-01

Savannah River Nuclear Solutions has begun using Xplore Tablet PC's to collect data in the field for soil samples, groundwater samples, air samples and round sheets at the Savannah River Site (SRS). EPA guidelines for groundwater sampling are incorporated into the application to ensure the sample technician follows the proper protocol. The sample technician is guided through the process for sampling and round sheet data collection by a series of menus and input boxes. Field measurements and well stabilization information are entered into the tablet for uploading into Environmental Restoration Data Management System (ERDMS). The process helps to eliminate inputmore » errors and provides data integrity. A soil sample technician has the ability to collect information about location of sample, field parameter, describe the soil sample, print bottle labels, and print chain of custody for the sample that they have collected. An air sample technician has the ability to provide flow, pressure, hours of operation, print bottle labels and chain of custody for samples they collect. Round sheets are collected using the information provided in the various procedures. The data are collected and uploaded into ERDMS. The equipment used is weather proof and hardened for the field use. Global Positioning System (GPS) capabilities are integrated into the applications to provide the location where samples were collected and to help sample technicians locate wells that are not visited often. (authors)« less

Comparative Characterization of CTX-M-64 and CTX-M-14 Provides Insights into the Structure and Catalytic Activity of the CTX-M Class of Enzymes.

PubMed

He, Dandan; Chiou, Jiachi; Zeng, Zhenling; Chan, Edward Wai-Chi; Liu, Jian-Hua; Chen, Sheng

2016-10-01

Clinical isolates producing hybrid CTX-M β-lactamases, presumably due to recombination between the blaCTX-M-15 and blaCTX-M-14 elements, have emerged in recent years. Among the hybrid enzymes, CTX-M-64 and CTX-M-14 display the most significant difference in catalytic activity. This study aims to investigate the mechanisms underlying such differential enzymatic activities in order to provide insight into the structure/function relationship of this class of enzymes. Sequence alignment analysis showed that the major differences between the amino acid composition of CTX-M-64 and CTX-M-14 lie at both the N and C termini of the enzymes. Single or multiple amino acid substitutions introduced into CTX-M-64 and CTX-M-14 were found to produce only minor effects on hydrolytic functions; such a finding is consistent with the notion that the discrepancy between the functional activities of the two enzymes is not the result of only a few amino acid changes but is attributable to interactions between a unique set of amino acid residues in each enzyme. This theory is supported by the results of the thermal stability assay, which confirmed that CTX-M-64 is significantly more stable than CTX-M-14. Our data confirmed that, in addition to the important residues located in the active site, residues distal to the active site also contribute to the catalytic activity of the enzyme through stabilizing its structural integrity. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Comparative Characterization of CTX-M-64 and CTX-M-14 Provides Insights into the Structure and Catalytic Activity of the CTX-M Class of Enzymes

PubMed Central

He, Dandan; Chiou, Jiachi; Zeng, Zhenling; Chan, Edward Wai-Chi

2016-01-01

Clinical isolates producing hybrid CTX-M β-lactamases, presumably due to recombination between the blaCTX-M-15 and blaCTX-M-14 elements, have emerged in recent years. Among the hybrid enzymes, CTX-M-64 and CTX-M-14 display the most significant difference in catalytic activity. This study aims to investigate the mechanisms underlying such differential enzymatic activities in order to provide insight into the structure/function relationship of this class of enzymes. Sequence alignment analysis showed that the major differences between the amino acid composition of CTX-M-64 and CTX-M-14 lie at both the N and C termini of the enzymes. Single or multiple amino acid substitutions introduced into CTX-M-64 and CTX-M-14 were found to produce only minor effects on hydrolytic functions; such a finding is consistent with the notion that the discrepancy between the functional activities of the two enzymes is not the result of only a few amino acid changes but is attributable to interactions between a unique set of amino acid residues in each enzyme. This theory is supported by the results of the thermal stability assay, which confirmed that CTX-M-64 is significantly more stable than CTX-M-14. Our data confirmed that, in addition to the important residues located in the active site, residues distal to the active site also contribute to the catalytic activity of the enzyme through stabilizing its structural integrity. PMID:27480856

Hot-Fire Test Results of Liquid Oxygen/RP-2 Multi-Element Oxidizer-Rich Preburners

NASA Technical Reports Server (NTRS)

Protz, C. S.; Garcia, C. P.; Casiano, M. J.; Parton, J. A.; Hulka, J. R.

2016-01-01

As part of the Combustion Stability Tool Development project funded by the Air Force Space and Missile Systems Center, the NASA Marshall Space Flight Center was contracted to assemble and hot-fire test a multi-element integrated test article demonstrating combustion characteristics of an oxygen/hydrocarbon propellant oxidizer-rich staged-combustion engine thrust chamber. Such a test article simulates flow through the main injectors of oxygen/kerosene oxidizer-rich staged combustion engines such as the Russian RD-180 or NK-33 engines, or future U.S.-built engine systems such as the Aerojet-Rocketdyne AR-1 engine or the Hydrocarbon Boost program demonstration engine. To supply the oxidizer-rich combustion products to the main injector of the integrated test article, existing subscale preburner injectors from a previous NASA-funded oxidizer-rich staged combustion engine development program were utilized. For the integrated test article, existing and newly designed and fabricated inter-connecting hot gas duct hardware were used to supply the oxidizer-rich combustion products to the oxidizer circuit of the main injector of the thrust chamber. However, before one of the preburners was used in the integrated test article, it was first hot-fire tested at length to prove it could provide the hot exhaust gas mean temperature, thermal uniformity and combustion stability necessary to perform in the integrated test article experiment. This paper presents results from hot-fire testing of several preburner injectors in a representative combustion chamber with a sonic throat. Hydraulic, combustion performance, exhaust gas thermal uniformity, and combustion stability data are presented. Results from combustion stability modeling of these test results are described in a companion paper at this JANNAF conference, while hot-fire test results of the preburner injector in the integrated test article are described in another companion paper.

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

PubMed

Hara, H; Kaji, H

1987-02-01

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

Selection for avian leukosis virus integration sites determines the clonal progression of B-cell lymphomas

PubMed Central

Malhotra, Sanandan; Justice, James; Morgan, Robin

2017-01-01

Avian leukosis virus (ALV) is a simple retrovirus that causes a wide range of tumors in chickens, the most common of which are B-cell lymphomas. The viral genome integrates into the host genome and uses its strong promoter and enhancer sequences to alter the expression of nearby genes, frequently inducing tumors. In this study, we compare the preferences for ALV integration sites in cultured cells and in tumors, by analysis of over 87,000 unique integration sites. In tissue culture we observed integration was relatively random with slight preferences for genes, transcription start sites and CpG islands. We also observed a preference for integrations in or near expressed and spliced genes. The integration pattern in cultured cells changed over the course of selection for oncogenic characteristics in tumors. In comparison to tissue culture, ALV integrations are more highly selected for proximity to transcription start sites in tumors. There is also a significant selection of ALV integrations away from CpG islands in the highly clonally expanded cells in tumors. Additionally, we utilized a high throughput method to quantify the magnitude of clonality in different stages of tumorigenesis. An ALV-induced tumor carries between 700 and 3000 unique integrations, with an average of 2.3 to 4 copies of proviral DNA per infected cell. We observed increasing tumor clonality during progression of B-cell lymphomas and identified gene players (especially TERT and MYB) and biological processes involved in tumor progression. PMID:29099869

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

PubMed Central

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

2015-01-01

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

Impact of flight systems integration on future aircraft design

NASA Technical Reports Server (NTRS)

Hood, R. V.; Dollyhigh, S. M.; Newsom, J. R.

1984-01-01

Integrations trends in aircraft are discussed with an eye to manifestations in future aircraft designs through interdisciplinary technology integration. Current practices use software changes or small hardware fixes to solve problems late in the design process, e.g., low static stability to upgrade fuel efficiency. A total energy control system has been devised to integrate autopilot and autothrottle functions, thereby eliminating hardware, reducing the software, pilot workload, and cost, and improving flight efficiency and performance. Integrated active controls offer reduced weight and larger payloads for transport aircraft. The introduction of vectored thrust may eliminate horizontal and vertical stabilizers, and location of the thrust at the vehicle center of gravity can provide vertical takeoff and landing capabilities. It is suggested that further efforts will open a new discipline, aeroservoelasticity, and tests will become multidisciplinary, involving controls, aerodynamics, propulsion and structures.

Deletion of loop fragment adjacent to active site diminishes the stability and activity of exo-inulinase.

PubMed

Arjomand, Maryam Rezaei; Habibi-Rezaei, Mehran; Ahmadian, Gholamreza; Hassanzadeh, Malihe; Karkhane, Ali Asghar; Asadifar, Mandana; Amanlou, Massoud

2016-11-01

Inulinases are classified as hydrolases and widely used in the food and medical industries. Here, we report the deletion of a six-membered adjacent active site loop fragment ( 74 YGSDVT 79 sequence) from third Ω-loop of the exo-inulinase containing aspartate residue from Aspergillus niger to study its structural and functional importance. Site-directed mutagenesis was used to create the mutant of the exo-inulinase (Δ6SL). To investigate the stability of the region spanning this loop, MD simulations were performed 80ns for 20-85 residues. Molecular docking was performed to compare the interactions in the active sites of enzymes with fructose as a ligand. Accordingly, the functional thermostability of the exo-inulinase was significantly decreased upon loop fragment deletion. Evaluation of the kinetics parameters (V max , K m , k cat and, k cat /K m ) and activation energy (E a ) of the catalysis of enzymes indicated the importance of the deleted sequence on the catalytic performance of the enzyme. In conclusion, six-membered adjacent active site loop fragment not only plays a crucial role in the stability of the enzyme, but also it involves in the enzyme catalysis through lowering the activation energy of the catalysis and effective improving the catalytic performance. Copyright © 2016. Published by Elsevier B.V.

Post-translational modification and stability of low molecular weight cyclin E.

PubMed

Mull, B B; Cox, J; Bui, T; Keyomarsi, K

2009-09-03

Our laboratory has previously described the presence of five tumor-specific low molecular weight isoforms of cyclin E in both tumor cell lines and breast cancer patient biopsies. We have also shown that one of these low forms arises from an alternate start site, whereas the other four appear as two sets of doublets following cleavage through an elastase-like enzyme. However, the origin of both sets of doublets was unknown. Here, we demonstrate that the larger isoform of each doublet is the result of phosphorylation at a key degradation site. Through site-directed mutagenesis of different phosphorylation sites within the cyclin E protein, we discovered that phosphorylation of threonine 395 is responsible for generating the larger isoform of each doublet. Because phosphorylation of threonine 395 has been linked to the proteasome-mediated degradation of full length cyclin E, we examined the stability of T395A phospho-mutants in both non-tumorigenic mammary epithelial cells and tumor cells. The results revealed that the low molecular weight isoforms appear to be stable in both a tumor cell line and a non-tumor forming cell line regardless of the presence of this critical phosphorylation site. The stability of low molecular weight cyclin E may have implications for both tumorigenesis and treatment of tumors expressing them.

Orchestration of Structural, Stereoelectronic, and Hydrogen-Bonding Effects in Stabilizing Triplexes from Engineered Chimeric Collagen Peptides (Pro(X)-Pro(Y)-Gly)6 Incorporating 4(R/S)-Aminoproline.

PubMed

Umashankara, Muddegowda; Sonar, Mahesh V; Bansode, Nitin D; Ganesh, Krishna N

2015-09-04

Collagens are an important family of structural proteins found in the extracellular matrix with triple helix as the characteristic structural motif. The collagen triplex is made of three left-handed polyproline II (PPII) helices with each PPII strand consisting of repetitive units of the tripeptide motif X-Y-Gly, where the amino acids X and Y are most commonly proline (Pro) and 4R-hydroxyproline (Hyp), respectively. A C4-endo pucker at X-site and C4-exo pucker at Y-site have been proposed to be the key for formation of triplex, and the nature of pucker is dependent on both the electronegativity and stereochemistry of the substituent. The present manuscript describes a new class of collagen analogues-chimeric cationic collagens-wherein both X- and Y-sites in collagen triad are simultaneously substituted by a combination of 4(R/S)-(OH/NH2/NH3(+)/NHCHO)-prolyl units and triplex stabilities measured at different pHs and in EG:H2O. Based on the results a model has been proposed with the premise that any factors which specifically favor the ring puckers of C4-endo at X-site and C4-exo at Y-site stabilize the PPII conformation and hence the derived triplexes. The pH-dependent triplex stability uniquely observed with ionizable 4-amino substituent on proline enables one to define the critical combination of factors C4-(exo/endo), intraresidue H-bonding, stereoelectronic (R/S) and n → π* interactions in dictating the triplex strength. The ionizable NH2 substituent at C4 in R/S configuration is thus a versatile probe for delineating the triplex stabilizing factors and the results have potential for designing of collagen analogues with customized properties for material and biological applications.

AAVS1-Targeted Plasmid Integration in AAV Producer Cell Lines.

PubMed

Luo, Yuxia; Frederick, Amy; Martin, John M; Scaria, Abraham; Cheng, Seng H; Armentano, Donna; Wadsworth, Samuel C; Vincent, Karen A

2017-06-01

Adeno-associated virus (AAV) producer cell lines are created via transfection of HeLaS3 cells with a single plasmid containing three components (the vector sequence, the AAV rep and cap genes, and a selectable marker gene). As this plasmid contains both the cis (Rep binding sites) and trans (Rep protein encoded by the rep gene) elements required for site-specific integration, it was predicted that plasmid integration might occur within the AAVS1 locus on human chromosome 19 (chr19). The objective of this study was to investigate whether integration in AAVS1 might be correlated with vector yield. Plasmid integration sites within several independent cell lines were assessed via Southern, fluorescence in situ hybridization (FISH) and PCR analyses. In the Southern analyses, the presence of fragments detected by both rep- and AAVS1-specific probes suggested that for several mid- and high-producing lines, plasmid DNA had integrated into the AAVS1 locus. Analysis with puroR and AAVS1-specific probes suggested that integration in AAVS1 was a more widespread phenomenon. High-producing AAV2-secreted alkaline phosphatase (SEAP) lines (masterwell 82 [MW82] and MW278) were evaluated via FISH using probes specific for the plasmid, AAVS1, and a chr19 marker. FISH analysis detected two plasmid integration sites in MW278 (neither in AAVS1), while a total of three sites were identified in MW82 (two in AAVS1). An inverse PCR assay confirmed integration within AAVS1 for several mid- and high-producing lines. In summary, the FISH, Southern, and PCR data provide evidence of site-specific integration of the plasmid within AAVS1 in several AAV producer cell lines. The data also suggest that integration in AAVS1 is a general phenomenon that is not necessarily restricted to high producers. The results also suggest that plasmid integration within the AAVS1 locus is not an absolute requirement for a high vector yield.

Soil-landscape development and late Quaternary environmental change in coastal Estremadura, Portugal

NASA Astrophysics Data System (ADS)

Daniels, Michael; Haws, Jonathan; Benedetti, Michael; Bicho, Nuno

2015-04-01

This poster integrates soil-landscape analysis with archaeological survey and paleoenvironmental reconstruction. Soils in surface and buried contexts in Estremadura, Portugal, provide evidence of landscape stability and instability, relative age relationships between landforms, and general paleoenvironmental conditions during the late Quaternary. These factors provide insight into the distribution and condition of Paleolithic archaeological sites and help understand the record of human settlement in the region. Late Pleistocene and Holocene dunes extend inland approximately 10 km from coastal source regions. Surface soils in Holocene dunes under maritime pine (Pinus pinaster) forest exhibit A, E, C/Bh and A, C horizon sequences and classify as Quartzipsamments. Surface soils in late Pleistocene dunes exhibit A, E, Bh, Bhs, Bs horizon sequences and classify as Haplorthods. Both Pleistocene and Holocene dunes commonly bury a heavily weathered soil formed in calcareous sandstone. The boundary between underlying buried soils and overlying surface soils is characterized by a lag deposit of medium to coarse, moderately-rounded gravels, underlain immediately by subsurface Bt and Bss horizons. The lag deposit and absence of buried A horizons both indicate intense and/or prolonged surface erosion prior to burial by late Quaternary dunes. Soil-geomorphic relationships therefore suggest at least two distinct episodes of dune emplacement and subsequent landscape stability following an extensive episode late Pleistocene landscape instability and soil erosion. A conceptual model of soil-landscape evolution through the late Quaternary and Holocene results from the integration of soil profile data, proxy paleoenvironmental data, and the partial record of human settled as revealed in the archaeological record.

Hierarchical Type Stability Criteria for Delayed Neural Networks via Canonical Bessel-Legendre Inequalities.

PubMed

Zhang, Xian-Ming; Han, Qing-Long; Zeng, Zhigang

2018-05-01

This paper is concerned with global asymptotic stability of delayed neural networks. Notice that a Bessel-Legendre inequality plays a key role in deriving less conservative stability criteria for delayed neural networks. However, this inequality is in the form of Legendre polynomials and the integral interval is fixed on . As a result, the application scope of the Bessel-Legendre inequality is limited. This paper aims to develop the Bessel-Legendre inequality method so that less conservative stability criteria are expected. First, by introducing a canonical orthogonal polynomial sequel, a canonical Bessel-Legendre inequality and its affine version are established, which are not explicitly in the form of Legendre polynomials. Moreover, the integral interval is shifted to a general one . Second, by introducing a proper augmented Lyapunov-Krasovskii functional, which is tailored for the canonical Bessel-Legendre inequality, some sufficient conditions on global asymptotic stability are formulated for neural networks with constant delays and neural networks with time-varying delays, respectively. These conditions are proven to have a hierarchical feature: the higher level of hierarchy, the less conservatism of the stability criterion. Finally, three numerical examples are given to illustrate the efficiency of the proposed stability criteria.

Integrated Remote Sensing Modalities for Classification at a Legacy Test Site

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

Closed-Loop Control of Chemical Injection Rate for a Direct Nozzle Injection System.

PubMed

Cai, Xiang; Walgenbach, Martin; Doerpmond, Malte; Schulze Lammers, Peter; Sun, Yurui

2016-01-20

To realize site-specific and variable-rate application of agricultural pesticides, accurately metering and controlling the chemical injection rate is necessary. This study presents a prototype of a direct nozzle injection system (DNIS) by which chemical concentration transport lag was greatly reduced. In this system, a rapid-reacting solenoid valve (RRV) was utilized for injecting chemicals, driven by a pulse-width modulation (PWM) signal at 100 Hz, so with varying pulse width the chemical injection rate could be adjusted. Meanwhile, a closed-loop control strategy, proportional-integral-derivative (PID) method, was applied for metering and stabilizing the chemical injection rate. In order to measure chemical flow rates and input them into the controller as a feedback in real-time, a thermodynamic flowmeter that was independent of chemical viscosity was used. Laboratory tests were conducted to assess the performance of DNIS and PID control strategy. Due to the nonlinear input-output characteristics of the RRV, a two-phase PID control process obtained better effects as compared with single PID control strategy. Test results also indicated that the set-point chemical flow rate could be achieved within less than 4 s, and the output stability was improved compared to the case without control strategy.

Asp133 Residue in NhaA Na+/H+ Antiporter Is Required for Stability Cation Binding and Transport.

PubMed

Rimon, Abraham; Dwivedi, Manish; Friedler, Assaf; Padan, Etana

2018-03-16

Na + /H + antiporters have a crucial role in pH and Na + homeostasis in cells. The crystal structure of NhaA, the main antiporter of Escherichia coli, has provided general insights into antiporter mechanisms and revealed a previously unknown structural fold, which has since been identified in several secondary active transporters. This unique structural fold is very delicately electrostatically balanced. Asp133 and Lys 300 have been ascribed essential roles in this balance and, more generally, in the structure and function of the antiporter. In this work, we show the multiple roles of Asp133 in NhaA: (i) The residue's negative charge is critical for the stability of the NhaA structure. (ii) Its main chain is part of the active site. (iii) Its side chain functions as an alkaline-pH-dependent gate, changing the protein's conformation from an inward-facing conformation at acidic pH to an outward-open conformation at alkaline pH, opening the periplasm funnel. On the basis of the experimental data, we propose a tentative mechanism integrating the structural and functional roles of Asp133. Copyright © 2018 Elsevier Ltd. All rights reserved.

Permit application modifications

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

NONE

1995-11-01

This document contains the Permit Application Modifications for the Y-12 Industrial Landfill V site on the Oak Ridge Reservation. These modifications include the assessment of stability of the proposed Landfill V under static and loading conditions. Analyses performed include the general slope stability, veneer stability of the bottom liner and cover system, and a liquefaction potential assessment of the foundation soils.

Carbon Sequestration on Surface Mine Lands

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

Donald Graves; Christopher Barton; Richard Sweigard

2006-03-31

Since the implementation of the federal Surface Mining Control and Reclamation Act of 1977 (SMCRA) in May of 1978, many opportunities have been lost for the reforestation of surface mines in the eastern United States. Research has shown that excessive compaction of spoil material in the backfilling and grading process is the biggest impediment to the establishment of productive forests as a post-mining land use (Ashby, 1998, Burger et al., 1994, Graves et al., 2000). Stability of mine sites was a prominent concern among regulators and mine operators in the years immediately following the implementation of SMCRA. These concerns resultedmore » in the highly compacted, flatly graded, and consequently unproductive spoils of the early post-SMCRA era. However, there is nothing in the regulations that requires mine sites to be overly compacted as long as stability is achieved. It has been cultural barriers and not regulatory barriers that have contributed to the failure of reforestation efforts under the federal law over the past 27 years. Efforts to change the perception that the federal law and regulations impede effective reforestation techniques and interfere with bond release must be implemented. Demonstration of techniques that lead to the successful reforestation of surface mines is one such method that can be used to change perceptions and protect the forest ecosystems that were indigenous to these areas prior to mining. The University of Kentucky initiated a large-scale reforestation effort to address regulatory and cultural impediments to forest reclamation in 2003. During the three years of this project 383,000 trees were planted on over 556 acres in different physiographic areas of Kentucky (Table 1, Figure 1). Species used for the project were similar to those that existed on the sites before mining was initiated (Table 2). A monitoring program was undertaken to evaluate growth and survival of the planted species as a function of spoil characteristics and reclamation practice. In addition, experiments were integrated within the reforestation effort to address specific questions pertaining to sequestration of carbon (C) on these sites.« less

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

PubMed Central

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

2013-01-01

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

Engineered disulfide bonds increase active-site local stability and reduce catalytic activity of a cold-adapted alkaline phosphatase.

PubMed

Asgeirsson, Bjarni; Adalbjörnsson, Björn Vidar; Gylfason, Gudjón Andri

2007-06-01

Alkaline phosphatase is an extracellular enzyme that is membrane-bound in eukaryotes but resides in the periplasmic space of bacteria. It normally carries four cysteine residues that form two disulfide bonds, for instance in the APs of Escherichia coli and vertebrates. An AP variant from a Vibrio sp. has only one cysteine residue. This cysteine is second next to the nucleophilic serine in the active site. We have individually modified seven residues to cysteine that are on two loops predicted to be within a 5 A radius. Four of them formed a disulfide bond to the endogenous cysteine. Thermal stability was monitored by circular dichroism and activity measurements. Global stability was similar to the wild-type enzyme. However, a significant increase in heat-stability was observed for the disulfide-containing variants using activity as a measure, together with a large reduction in catalytic rates (k(cat)) and a general decrease in Km values. The results suggest that a high degree of mobility near the active site and in the helix carrying the endogenous cysteine is essential for full catalytic efficiency in the cold-adapted AP.

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

EPA Science Inventory

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

Economic Assessment: Stability, Security, Transition and Reconstruction Operations

DTIC Science & Technology

2007-03-13

strategy has incorporated economic stability as a central part of post-combat operations and nation building. A viable, growing economy has also been a...and prosperity. Economic stability served as a tool for reconstruction as well as the catalyst for integration as outlined in the Marshall Plan...for future SSTR operations as it relates to economic stability is “Privatization can be a prerequisite for economic growth, especially where

Leaving Group Ability Observably Affects Transition State Structure in a Single Enzyme Active Site.

PubMed

Roston, Daniel; Demapan, Darren; Cui, Qiang

2016-06-15

A reaction's transition state (TS) structure plays a critical role in determining reactivity and has important implications for the design of catalysts, drugs, and other applications. Here, we explore TS structure in the enzyme alkaline phosphatase using hybrid Quantum Mechanics/Molecular Mechanics simulations. We find that minor perturbations to the substrate have major effects on TS structure and the way the enzyme stabilizes the TS. Substrates with good leaving groups (LGs) have little cleavage of the phosphorus-LG bond at the TS, while substrates with poor LGs have substantial cleavage of that bond. The results predict nonlinear free energy relationships for a single rate-determining step, and substantial differences in kinetic isotope effects for different substrates; both trends were observed in previous experimental studies, although the original interpretations differed from the present model. Moreover, due to different degrees of phosphorus-LG bond cleavage at the TS for different substrates, the LG is stabilized by different interactions at the TS: while a poor LG is directly stabilized by an active site zinc ion, a good LG is mainly stabilized by active site water molecules. Our results demonstrate the considerable plasticity of TS structure and stabilization in enzymes. Furthermore, perturbations to reactivity that probe TS structure experimentally (i.e., substituent effects) may substantially perturb the TS they aim to probe, and thus classical experimental approaches such as free energy relations should be interpreted with care.

Molecular Dynamics Simulation of the Crystallizable Fragment of IgG1—Insights for the Design of Fcabs

PubMed Central

Lai, Balder; Hasenhindl, Christoph; Obinger, Christian; Oostenbrink, Chris

2014-01-01

An interesting format in the development of therapeutic monoclonal antibodies uses the crystallizable fragment of IgG1 as starting scaffold. Engineering of its structural loops allows generation of an antigen binding site. However, this might impair the molecule’s conformational stability, which can be overcome by introducing stabilizing point mutations in the CH3 domains. These point mutations often affect the stability and unfolding behavior of both the CH2 and CH3 domains. In order to understand this cross-talk, molecular dynamics simulations of the domains of the Fc fragment of human IgG1 are reported. The structure of human IgG1-Fc obtained from X-ray crystallography is used as a starting point for simulations of the wild-type protein at two different pH values. The stabilizing effect of a single point mutation in the CH3 domain as well as the impact of the hinge region and the glycan tree structure connected to the CH2 domains is investigated. Regions of high local flexibility were identified as potential sites for engineering antigen binding sites. Obtained data are discussed with respect to the available X-ray structure of IgG1-Fc, directed evolution approaches that screen for stability and use of the scaffold IgG1-Fc in the design of antigen binding Fc proteins. PMID:24451126

Analysis of cavern and well stability at the West Hackberry SPR site using a full-dome model.

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

Sobolik, Steven R.

2015-08-01

This report presents computational analyses that simulate the structural response of caverns at the Strategic Petroleum Reserve (SPR) West Hackberry site. The cavern field comprises 22 caverns. Five caverns (6, 7, 8, 9, 11) were acquired from industry and have unusual shapes and a history dating back to 1946. The other 17 caverns (101-117) were leached according to SPR standards in the mid-1980s and have tall cylindrical shapes. The history of the caverns and their shapes are simulated in a three-dimensional geomechanics model of the site that predicts deformations, strains, and stresses. Future leaching scenarios corresponding to oil drawdowns usingmore » fresh water are also simulated by increasing the volume of the caverns. Cavern pressures are varied in the model to capture operational practices in the field. The results of the finite element model are interpreted to provide information on the current and future status of subsidence, well integrity, and cavern stability. The most significant results in this report are relevant to Cavern 6. The cavern is shaped like a bowl with a large ceiling span and is in close proximity to Cavern 9. The analyses predict tensile stresses at the edge of the ceiling during repressurization of Cavern 6 following workover conditions. During a workover the cavern is at low pressure to service a well. The wellhead pressures are atmospheric. When the workover is complete, the cavern is repressurized. The resulting elastic stresses are sufficient to cause tension around the edge of the large ceiling span. With time, these stresses relax to a compressive state because of salt creep. However, the potential for salt fracture and propagation exists, particularly towards Cavern 9. With only 200 feet of salt between the caverns, the operational consequences must be examined if the two caverns become connected. A critical time may be during a workover of Cavern 9 in part because of the operational vulnerabilities, but also because dilatant damage is predicted under the ledge that forms the lower lobe in the cavern. The remaining caverns have no significant issues regarding cavern stability and may be safely enlarged during subsequent oil drawdowns. Predicted well strains and subsidence are significant and consequently future remedial actions may be necessary. These predicted well strains certainly suggest appropriate monitoring through a well-logging program. Subsidence is currently being monitored.« less

Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection

PubMed Central

Maciag, Joseph J.; Mackenzie, Sarah H.; Tucker, Matthew B.; Schipper, Joshua L.; Swartz, Paul; Clark, A. Clay

2016-01-01

The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 Å) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the conserved waters also correspond to sites of posttranslational modifications, suggesting that the conserved waters are an integral part of allosteric mechanisms. To test this hypothesis, we created a library of 19 caspase-3 variants through saturation mutagenesis in a single position of the allosteric site of the dimer interface, and we show that the enzyme activity varies by more than four orders of magnitude. Altogether, our database consists of 37 high-resolution structures of caspase-3 variants, and we demonstrate that the decrease in activity correlates with a loss of conserved water molecules. The data show that the activity of caspase-3 can be fine-tuned through globally desolvating the active conformation within the native ensemble, providing a mechanism for cells to repartition the ensemble and thus fine-tune activity through conformational selection. PMID:27681633

Geochemical analyses reveal the importance of environmental history for blue carbon sequestration

NASA Astrophysics Data System (ADS)

Kelleway, J. J.; Saintilan, N.; Macreadie, P. I.; Baldock, J. A.; Heijnis, H.; Zawadzki, A.; Gadd, P.; Jacobsen, G.; Ralph, P. J.

2017-07-01

Coastal habitats including saltmarshes and mangrove forests can accumulate and store significant blue carbon stocks, which may persist for millennia. Despite this implied stability, the distribution and structure of intertidal-supratidal wetlands are known to respond to changes imposed by geomorphic evolution, climatic, sea level, and anthropogenic influences. In this study, we reconstruct environmental histories and biogeochemical conditions in four wetlands of similar contemporary vegetation in SE Australia. The objective is to assess the importance of historic factors to contemporary organic carbon (C) stocks and accumulation rates. Results from the four cores—two collected from marine-influenced saltmarshes (Wapengo marine site (WAP-M) and Port Stephens marine site (POR-M)) and two from fluvial influenced saltmarshes (Wapengo fluvial site (WAP-F) and Port Stephens fluvial site (POR-F))—highlight different environmental histories and preservation conditions. High C stocks are associated with the presence of a mangrove phase below the contemporary saltmarsh sediments in the POR-M and POR-F cores. 13C nuclear magnetic resonance analyses show this historic mangrove root C to be remarkably stable in its molecular composition despite its age, consistent with its position in deep sediments. WAP-M and WAP-F cores did not contain mangrove root C; however, significant preservation of char C (up to 46% of C in some depths) in WAP-F reveals the importance of historic catchment processes to this site. Together, these results highlight the importance of integrating historic ecosystem and catchment factors into attempts to upscale C accounting to broader spatial scales.

Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection.

PubMed

Maciag, Joseph J; Mackenzie, Sarah H; Tucker, Matthew B; Schipper, Joshua L; Swartz, Paul; Clark, A Clay

2016-10-11

The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 Å) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the conserved waters also correspond to sites of posttranslational modifications, suggesting that the conserved waters are an integral part of allosteric mechanisms. To test this hypothesis, we created a library of 19 caspase-3 variants through saturation mutagenesis in a single position of the allosteric site of the dimer interface, and we show that the enzyme activity varies by more than four orders of magnitude. Altogether, our database consists of 37 high-resolution structures of caspase-3 variants, and we demonstrate that the decrease in activity correlates with a loss of conserved water molecules. The data show that the activity of caspase-3 can be fine-tuned through globally desolvating the active conformation within the native ensemble, providing a mechanism for cells to repartition the ensemble and thus fine-tune activity through conformational selection.

Geological and Geochemical Analysis of Seabed Stability at the Norfolk Ocean Disposal Site. Part 1: Geological Analysis.

DTIC Science & Technology

1983-05-31

ANALYSIS OF SEABED STABILITY AT THE NORFOLK OCEAN DISPOSAL SITE PART 1: GEOLOGICAL ANALYSIS U LU D George F. Oertel, Principal Investigator i- Final Report...eC.it ,ie _. _ r. .. .... All e d !t-o i’~$ ~- - - • ° . .. • : " . o . . . , . . ... - . • , .. . . . . . kkN 4. 18. parameters, diver reconnaissance of...For the period ending September 30, 1982 Prepared for the Department of the Army Norfolk District, Corps of Engineers 803 Front Street D I *Norfolk

Electrical resistivity measurement of mechanically stabilized Earth wall backfill : final report.

DOT National Transportation Integrated Search

2016-06-01

In Kansas, mechanically stabilized earth (MSE) retaining walls are typically backfilled with coarse aggregate. : Current backfill material testing procedures used by the Kansas Department of Transportation (KDOT) utilize on-site : observations for co...

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

Moran, James J.; Kreuzer, Helen W.; Carman, April J.

Acid scavengers are frequently used as stabilizer compounds in a variety of applications. When used to stabilize volatile compounds such as nerve agents, the lower volatility and higher stability of acid scavengers make them more persistent in a post-event forensic setting. We are employing compound-specific stable isotope analysis of the carbon, nitrogen, and hydrogen components of three acid scavenging compounds (N,N-diethylaniline, tributylamine, and triethylamine) as a tool for distinguishing between different samples of the stabilizers. Combined analysis of three stable isotopes in these samples improves the technique’s resolving potential, enhancing sample matching capabilities. The compound specific methods developed here canmore » be applied to instances where these compounds are not pure, such as when mixed with an agent or when found as a residue at an event site. Effective sample matching can be crucial for linking compounds at multiple event sites or linking a supply inventory to an event.« less

Effect of Stability on Mixing in Open Canopies. Chapter 4

NASA Technical Reports Server (NTRS)

Lee, Young-Hee; Mahrt, L.

2005-01-01

In open canopies, the within-canopy flux from the ground surface and understory can account for a significant fraction of the total flux above the canopy. This study incorporates the important influence of within-canopy stability on turbulent mixing and subcanopy fluxes into a first-order closure scheme. Toward this goal, we analyze within-canopy eddy-correlation data from the old aspen site in the Boreal Ecosystem - Atmosphere Study (BOREAS) and a mature ponderosa pine site in Central Oregon, USA. A formulation of within-canopy transport is framed in terms of a stability- dependent mixing length, which approaches Monin-Obukhov similarity theory above the canopy roughness sublayer. The new simple formulation is an improvement upon the usual neglect of the influence of within-canopy stability in simple models. However, frequent well-defined cold air drainage within the pine subcanopy inversion reduces the utility of simple models for nocturnal transport. Other shortcomings of the formulation are discussed.

First results of geodetic deformation monitoring after commencement of CO2 injection at the Aquistore underground CO2 storage site

NASA Astrophysics Data System (ADS)

Craymer, M.; White, D.; Piraszewski, M.; Zhao, Y.; Henton, J.; Silliker, J.; Samsonov, S.

2015-12-01

Aquistore is a demonstration project for the underground storage of CO2 at a depth of ~3350 m near Estevan, Saskatchewan, Canada. An objective of the project is to design, adapt, and test non-seismic monitoring methods that have not been systematically utilized to date for monitoring CO2 storage projects, and to integrate the data from these various monitoring tools to obtain quantitative estimates of the change in subsurface fluid distributions, pressure changes and associated surface deformation. Monitoring methods being applied include satellite-, surface- and wellbore-based monitoring systems and comprise natural- and controlled-source electromagnetic methods, gravity monitoring, continuous GPS, synthetic aperture radar interferometry (InSAR), tiltmeter array analysis, and chemical tracer studies. Here we focus on the GPS, InSAR and gravity monitoring. Five monitoring sites were installed in 2012 and another six in 2013, each including GPS and InSAR corner reflector monuments (some collocated on the same monument). The continuous GPS data from these stations have been processed on a daily basis in both baseline processing mode using the Bernese GPS Software and precise point positioning mode using CSRS-PPP. Gravity measurements at each site have also been performed in fall 2013, spring 2014 and fall 2015, and at two sites in fall 2014. InSAR measurements of deformation have been obtained for a 5 m footprint at each site as well as at the corner reflector point sources. Here we present the first results of this geodetic deformation monitoring after commencement of CO2 injection on April 14, 2015. The time series of these sites are examined, compared and analyzed with respect to monument stability, seasonal signals, longer term trends, and any changes in motion and mass since CO2 injection.

Toward Rational Design of Cu/SSZ-13 Selective Catalytic Reduction Catalysts: Implications from Atomic-Level Understanding of Hydrothermal Stability

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

Song, James; Wang, Yilin; Walter, Eric D.

The hydrothermal stability of Cu/SSZ-13 SCR catalysts has been extensively studied, yet atomic level understanding of changes to the zeolite support and the Cu active sites during hydrothermal aging are still lacking. In this work, via the utilization of spectroscopic methods including solid-state 27Al and 29Si NMR, EPR, DRIFTS, and XPS, together with imaging and elemental mapping using STEM, detailed kinetic analyses, and theoretical calculations with DFT, various Cu species, including two types of isolated active sites and CuOx clusters, were precisely quantified for samples hydrothermally aged under varying conditions. This quantification convincingly confirms the exceptional hydrothermal stability of isolatedmore » Cu2+-2Z sites, and the gradual conversion of [Cu(OH)]+-Z to CuOx clusters with increasing aging severity. This stability difference is rationalized from the hydrolysis activation barrier difference between the two isolated sites via DFT. Discussions are provided on the nature of the CuOx clusters, and their possible detrimental roles on catalyst stability. Finally, a few rational design principles for Cu/SSZ-13 are derived rigorously from the atomic-level understanding of this catalyst obtained here. The authors gratefully acknowledge the US Department of Energy (DOE), Energy Efficiency and Renewable Energy, Vehicle Technologies Office for the support of this work. Computing time was granted by a user proposal at the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL) and by the National Energy Research Scientific Computing Center (NERSC). The experimental studies described in this paper were performed in the EMSL, a national scientific user facility sponsored by the DOE’s Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory (PNNL). PNNL is operated for the US DOE by Battelle.« less

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2017-12-01

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

Evaluating the Contribution of Soil Carbon to Global Climate Change Mitigation in an Integrated Assessment

NASA Astrophysics Data System (ADS)

Thomson, A. M.; Izaurralde, R. C.; Clarke, L. E.

2006-12-01

Assessing the contribution of terrestrial carbon sequestration to national and international climate change mitigation requires integration across scientific and disciplinary boundaries. In a study for the US Climate Change Technology Program, site based measurements and geographic data were used to develop a three- pool, first-order kinetic model of global agricultural soil carbon (C) stock changes over 14 continental scale regions. This model was then used together with land use scenarios from the MiniCAM integrated assessment model in a global analysis of climate change mitigation options. MiniCAM evaluated mitigation strategies within a set of policy environments aimed at achieving atmospheric CO2 stabilization by 2100 under a suite of technology and development scenarios. Adoption of terrestrial sequestration practices is based on competition for land and economic markets for carbon. In the reference case with no climate policy, conversion of agricultural land from conventional cultivation to no tillage over the next century in the United States results in C sequestration of 7.6 to 59.8 Tg C yr-1, which doubles to 19.0 to 143.4 Tg C yr-1 under the most aggressive climate policy. Globally, with no carbon policy, agricultural C sequestration rates range from 75.2 to 18.2 Tg C yr-1 over the century, with the highest rates occurring in the first fifty years. Under the most aggressive global climate change policy, sequestration in agricultural soils reaches up to 190 Tg C yr-1 in the first 15 years. The contribution of agricultural soil C sequestration is a small fraction of the total global carbon offsets necessary to reach the stabilization targets (9 to 20 Gt C yr-1) by the end of the century. This integrated assessment provides decision makers with science-based estimates of the potential magnitude of terrestrial C sequestration relative to other greenhouse gas mitigation strategies in all sectors of the global economy. It also provides insight into the behavior of terrestrial C mitigation options in the presence and absence of climate change mitigation policies.

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

PubMed

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

2014-01-01

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

A stability study of asteroid families near the 3:1 and 5:2 resonance with Jupiter

NASA Astrophysics Data System (ADS)

Hahn, G.; Lagerkvist, C.-I.; Lindblad, B. A.

1993-06-01

The stability and homogeneity of three asteroid families from Lindblad's list (1992) are studied using numerical integration techniques. These families include the Maria family, which lies close to the 3:1 mean motion resonance with Jupiter, the Oppavia-Gefion, and Dora families which are close to the 5:2 resonance. The study is based on a simplified solar system model, which takes into account the perturbations only by Jupiter and Saturn, and Everhart's variable stepsize integrator RA15. Preliminary results indicate that the stability of the orbits of all family members are not affected by the proximity to the 3:1 and 5:2 mean motion resonance with Jupiter.

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

PubMed Central

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

2013-01-01

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

ENGINEERING BULLETIN: SOLIDIFICATION/STABILIZATION OF ORGANICS AND INORGANICS

EPA Science Inventory

Solidification refers to techniques that encapsulate hazardous waste into a solid material of high structural integrity. Encapsulation involves either fine waste particles (microencapsulation) or a large block or container of wastes (macroencapsulation). Stabilization refe...

Processing time of addition or withdrawal of single or combined balance-stabilizing haptic and visual information

PubMed Central

Honeine, Jean-Louis; Crisafulli, Oscar; Sozzi, Stefania

2015-01-01

We investigated the integration time of haptic and visual input and their interaction during stance stabilization. Eleven subjects performed four tandem-stance conditions (60 trials each). Vision, touch, and both vision and touch were added and withdrawn. Furthermore, vision was replaced with touch and vice versa. Body sway, tibialis anterior, and peroneus longus activity were measured. Following addition or withdrawal of vision or touch, an integration time period elapsed before the earliest changes in sway were observed. Thereafter, sway varied exponentially to a new steady-state while reweighting occurred. Latencies of sway changes on sensory addition ranged from 0.6 to 1.5 s across subjects, consistently longer for touch than vision, and were regularly preceded by changes in muscle activity. Addition of vision and touch simultaneously shortened the latencies with respect to vision or touch separately, suggesting cooperation between sensory modalities. Latencies following withdrawal of vision or touch or both simultaneously were shorter than following addition. When vision was replaced with touch or vice versa, adding one modality did not interfere with the effect of withdrawal of the other, suggesting that integration of withdrawal and addition were performed in parallel. The time course of the reweighting process to reach the new steady-state was also shorter on withdrawal than addition. The effects of different sensory inputs on posture stabilization illustrate the operation of a time-consuming, possibly supraspinal process that integrates and fuses modalities for accurate balance control. This study also shows the facilitatory interaction of visual and haptic inputs in integration and reweighting of stance-stabilizing inputs. PMID:26334013

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

PubMed

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

2017-05-05

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

Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

PubMed Central

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

2016-01-01

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

High-Throughput Ligand Discovery Reveals a Sitewise Gradient of Diversity in Broadly Evolved Hydrophilic Fibronectin Domains

PubMed Central

Woldring, Daniel R.; Holec, Patrick V.; Zhou, Hong; Hackel, Benjamin J.

2015-01-01

Discovering new binding function via a combinatorial library in small protein scaffolds requires balance between appropriate mutations to introduce favorable intermolecular interactions while maintaining intramolecular integrity. Sitewise constraints exist in a non-spatial gradient from diverse to conserved in evolved antibody repertoires; yet non-antibody scaffolds generally do not implement this strategy in combinatorial libraries. Despite the fact that biased amino acid distributions, typically elevated in tyrosine, serine, and glycine, have gained wider use in synthetic scaffolds, these distributions are still predominantly applied uniformly to diversified sites. While select sites in fibronectin domains and DARPins have shown benefit from sitewise designs, they have not been deeply evaluated. Inspired by this disparity between diversity distributions in natural libraries and synthetic scaffold libraries, we hypothesized that binders resulting from discovery and evolution would exhibit a non-spatial, sitewise gradient of amino acid diversity. To identify sitewise diversities consistent with efficient evolution in the context of a hydrophilic fibronectin domain, >105 binders to six targets were evolved and sequenced. Evolutionarily favorable amino acid distributions at 25 sites reveal Shannon entropies (range: 0.3–3.9; median: 2.1; standard deviation: 1.1) supporting the diversity gradient hypothesis. Sitewise constraints in evolved sequences are consistent with complementarity, stability, and consensus biases. Implementation of sitewise constrained diversity enables direct selection of nanomolar affinity binders validating an efficient strategy to balance inter- and intra-molecular interaction demands at each site. PMID:26383268

High-beta steady-state research with integrated modeling in the JT-60 Upgrade

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

Ozeki, T.

2007-05-15

Improvement of high-beta performance and its long sustainment was obtained with ferritic steel tiles in the JT-60 Upgrade (JT-60U) [T. Fujita et al., Phys. Plasmas 50, 104 (2005)], which were installed inside the vacuum vessel to reduce fast ion loss by decreasing the toroidal field ripple. When a separation between the plasma surface and the wall was small, high-beta plasmas reached the ideal wall stability limit, i.e., the ideal magnetohydrodynamics stability limit with the wall stabilization. A small rotation velocity of 0.3% of the Alfven velocity was found to be effective for suppressing the resistive wall mode. Sustainment of themore » high normalized beta value of {beta}{sub N}=2.3 has been extended to 28.6 s ({approx}15 times the current diffusion time) by improvement of the confinement and increase in the net heating power. Based on the research in JT-60U experiments and first-principle simulations, integrated models of core, edge-pedestal, and scrape-off-layer (SOL) divertors were developed, and they clarified complex features of reactor-relevant plasmas. The integrated core plasma model indicated that the small amount of electron cyclotron (EC) current density of about half the bootstrap current density could effectively stabilize the neoclassical tearing mode by the localized EC current accurately aligned to the magnetic island center. The integrated edge-pedestal model clarified that the collisionality dependence of energy loss due to the edge-localized mode was caused by the change in the width of the unstable mode and the SOL transport. The integrated SOL-divertor model clarified the effect of the exhaust slot on the pumping efficiency and the cause of enhanced radiation near the X-point multifaceted asymmetric radiation from edge. Success in these consistent analyses using the integrated code indicates that it is an effective means to investigate complex plasmas and to control the integrated performance.« less

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

PubMed

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

2012-12-01

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

Influence of phosphorylation of THR-3, SER-11, and SER-15 on deoxycytidine kinase activity and stability.

PubMed

Smal, C; Ntamashimikiro, S; Arts, A; Van Den Neste, E; Bontemps, F

2010-06-01

Deoxycytidine kinase (dCK) is a key enzyme in the salvage of deoxyribonucleosides and in the activation of several anticancer and antiviral nucleoside analogues. We have recently shown that dCK is a phosphoprotein. Four in vivo phosphorylation sites were identified: Thr-3, Ser-11, Ser-15, and Ser-74. Site-directed mutagenesis demonstrated that phosphorylation of Ser-74, the major phosphorylated residue, strongly influences dCK activity in eucaryotic cells. Here, we show that phosphorylation of the three other sites, located in the N-terminal extremity of the protein, does not significantly modify dCK activity, but phosphorylation of Thr-3 could promote dCK stability.

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

PubMed

Behrens, R; Hayles, J; Nurse, P

2000-12-01

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

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

PubMed Central

Behrens, Ralf; Hayles, Jacky; Nurse, Paul

2000-01-01

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

Soil stabilization mat for lunar launch/landing site

NASA Technical Reports Server (NTRS)

Acord, Amy L.; Cohenour, Mark W.; Ephraim, Daniel; Gochoel, Dennis; Roberts, Jefferson G.

1990-01-01

Facilities which are capable of handling frequent arrivals and departures of spaceships between Earth and a lunar colony are necessary. The facility must be able to provide these services with minimal interruption of operational activity within the colony. The major concerns associated with the space traffic are the dust and rock particles that will be kicked up by the rocket exhaust. As a result of the reduced gravitation of the Moon, these particles scatter over large horizontal distances. This flying debris will not only seriously interrupt the routine operations of the colony, but could cause damage to the equipment and facilities surrounding the launch site. An approach to overcome this problem is presented. A proposed design for a lunar take-off/landing mat is presented. This proposal goes beyond dealing with the usual problems of heat and load resistances associated with take-off and landing, by solving the problem of soil stabilization at the site. Through adequate stabilization, the problem of flying debris is eliminated.

Performance assessment of FY-3C/MERSI on early orbit

NASA Astrophysics Data System (ADS)

Hu, Xiuqing; Xu, Na; Wu, Ronghua; Chen, Lin; Min, Min; Wang, Ling; Xu, Hanlie; Sun, Ling; Yang, Zhongdong; Zhang, Peng

2014-11-01

FY-3C/MERSI has some remarkable improvements compared to the previous MERSIs including better spectral response function (SRF) consistency of different detectors within one band, increasing the capability of lunar observation by space view (SV) and the improvement of radiometric response stability of solar bands. During the In-orbit verification (IOV) commissioning phase, early results that indicate the MERSI representative performance were derived, including the signal noise ratio (SNR), dynamic range, MTF, B2B registration, calibration bias and instrument stability. The SNRs at the solar bands (Bands 1-4 and 6-20) was largely beyond the specifications except for two NIR bands. The in-flight calibration and verification for these bands are also heavily relied on the vicarious techniques such as China radiometric calibration sites(CRCS), cross-calibration, lunar calibration, DCC calibration, stability monitoring using Pseudo Invariant Calibration Sites (PICS) and multi-site radiance simulation. This paper will give the results of the above several calibration methods and monitoring the instrument degradation in early on-orbit time.

PoPMuSiC 2.1: a web server for the estimation of protein stability changes upon mutation and sequence optimality.

PubMed

Dehouck, Yves; Kwasigroch, Jean Marc; Gilis, Dimitri; Rooman, Marianne

2011-05-13

The rational design of modified proteins with controlled stability is of extreme importance in a whole range of applications, notably in the biotechnological and environmental areas, where proteins are used for their catalytic or other functional activities. Future breakthroughs in medical research may also be expected from an improved understanding of the effect of naturally occurring disease-causing mutations on the molecular level. PoPMuSiC-2.1 is a web server that predicts the thermodynamic stability changes caused by single site mutations in proteins, using a linear combination of statistical potentials whose coefficients depend on the solvent accessibility of the mutated residue. PoPMuSiC presents good prediction performances (correlation coefficient of 0.8 between predicted and measured stability changes, in cross validation, after exclusion of 10% outliers). It is moreover very fast, allowing the prediction of the stability changes resulting from all possible mutations in a medium size protein in less than a minute. This unique functionality is user-friendly implemented in PoPMuSiC and is particularly easy to exploit. Another new functionality of our server concerns the estimation of the optimality of each amino acid in the sequence, with respect to the stability of the structure. It may be used to detect structural weaknesses, i.e. clusters of non-optimal residues, which represent particularly interesting sites for introducing targeted mutations. This sequence optimality data is also expected to have significant implications in the prediction and the analysis of particular structural or functional protein regions. To illustrate the interest of this new functionality, we apply it to a dataset of known catalytic sites, and show that a much larger than average concentration of structural weaknesses is detected, quantifying how these sites have been optimized for function rather than stability. The freely available PoPMuSiC-2.1 web server is highly useful for identifying very rapidly a list of possibly relevant mutations with the desired stability properties, on which subsequent experimental studies can be focused. It can also be used to detect sequence regions corresponding to structural weaknesses, which could be functionally important or structurally delicate regions, with obvious applications in rational protein design.

Anatomy of terminal moraine segments and implied lake stability on Ngozumpa Glacier, Nepal, from electrical resistivity tomography (ERT).

PubMed

Thompson, Sarah S; Kulessa, Bernd; Benn, Douglas I; Mertes, Jordan R

2017-04-20

Moraine-dammed lakes at debris-covered glaciers are becoming increasingly common and pose significant outburst flood hazards if the dam is breached. While moraine subsurface structure and internal processes are likely to influence dam stability, only few sites have so far been investigated. We conducted electrical resistivity tomography (ERT) surveys at two sites on the terminal moraine complex of the Ngozumpa Glacier, Nepal, to aid assessment of future terminus stability. The resistivity signature of glacier ice at the site (100-15 kΩ m) is more consistent with values measured from cold glacier ice and while this may be feasible, uncertainties in the data inversion introduce ambiguity to this thermal interpretation. However, the ERT data does provide a significant improvement to our knowledge of the subsurface characteristics at these sites, clearly showing the presence (or absence) of glacier ice. Our interpretation is that of a highly complex latero-terminal moraine, resulting from interaction between previous glacier advance, recession and outburst flooding. If the base-level Spillway Lake continues to expand to a fully formed moraine-dammed glacial lake, the degradation of the ice core could have implications for glacial lake outburst risk.

Anatomy of terminal moraine segments and implied lake stability on Ngozumpa Glacier, Nepal, from electrical resistivity tomography (ERT)

NASA Astrophysics Data System (ADS)

Thompson, Sarah S.; Kulessa, Bernd; Benn, Douglas I.; Mertes, Jordan R.

2017-04-01

Moraine-dammed lakes at debris-covered glaciers are becoming increasingly common and pose significant outburst flood hazards if the dam is breached. While moraine subsurface structure and internal processes are likely to influence dam stability, only few sites have so far been investigated. We conducted electrical resistivity tomography (ERT) surveys at two sites on the terminal moraine complex of the Ngozumpa Glacier, Nepal, to aid assessment of future terminus stability. The resistivity signature of glacier ice at the site (100-15 kΩ m) is more consistent with values measured from cold glacier ice and while this may be feasible, uncertainties in the data inversion introduce ambiguity to this thermal interpretation. However, the ERT data does provide a significant improvement to our knowledge of the subsurface characteristics at these sites, clearly showing the presence (or absence) of glacier ice. Our interpretation is that of a highly complex latero-terminal moraine, resulting from interaction between previous glacier advance, recession and outburst flooding. If the base-level Spillway Lake continues to expand to a fully formed moraine-dammed glacial lake, the degradation of the ice core could have implications for glacial lake outburst risk.

Anatomy of terminal moraine segments and implied lake stability on Ngozumpa Glacier, Nepal, from electrical resistivity tomography (ERT)

PubMed Central

Thompson, Sarah S.; Kulessa, Bernd; Benn, Douglas I.; Mertes, Jordan R.

2017-01-01

Moraine-dammed lakes at debris-covered glaciers are becoming increasingly common and pose significant outburst flood hazards if the dam is breached. While moraine subsurface structure and internal processes are likely to influence dam stability, only few sites have so far been investigated. We conducted electrical resistivity tomography (ERT) surveys at two sites on the terminal moraine complex of the Ngozumpa Glacier, Nepal, to aid assessment of future terminus stability. The resistivity signature of glacier ice at the site (100–15 kΩ m) is more consistent with values measured from cold glacier ice and while this may be feasible, uncertainties in the data inversion introduce ambiguity to this thermal interpretation. However, the ERT data does provide a significant improvement to our knowledge of the subsurface characteristics at these sites, clearly showing the presence (or absence) of glacier ice. Our interpretation is that of a highly complex latero-terminal moraine, resulting from interaction between previous glacier advance, recession and outburst flooding. If the base-level Spillway Lake continues to expand to a fully formed moraine-dammed glacial lake, the degradation of the ice core could have implications for glacial lake outburst risk. PMID:28425458

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

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

GRYGIEL, M.L.

1998-10-08

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

Thermodynamics-hydration relationships within loops that affect G-quadruplexes under molecular crowding conditions.

PubMed

Fujimoto, Takeshi; Nakano, Shu-ichi; Sugimoto, Naoki; Miyoshi, Daisuke

2013-01-31

We systematically investigated the effects of loop length on the conformation, thermodynamic stability, and hydration of DNA G-quadruplexes under dilute and molecular crowding conditions in the presence of Na(+). Structural analysis showed that molecular crowding induced conformational switches of oligonucleotides with the longer guanine stretch and the shorter thymine loop. Thermodynamic parameters further demonstrated that the thermodynamic stability of G-quadruplexes increased by increasing the loop length from two to four, whereas it decreased by increasing the loop length from four to six. Interestingly, we found by osmotic pressure analysis that the number of water molecules released from the G-quadruplex decreased with increasing thermodynamic stability. We assumed that base-stacking interactions within the loops not only stabilized the whole G-quadruplex structure but also created hydration sites by accumulating nucleotide functional groups. The molecular crowding effects on the stability of G-quadruplexes composed of abasic sites, which reduce the stacking interactions at the loops, further demonstrated that G-quadruplexes with fewer stacking interactions within the loops released a larger number of water molecules upon folding. These results showed that the stacking interactions within the loops determined the thermodynamic stability and hydration of the whole G-quadruplex.

Recombinase-mediated cassette exchange (RMCE) for monoclonal antibody expression in the commercially relevant CHOK1SV cell line.

PubMed

Zhang, Lin; Inniss, Mara C; Han, Shu; Moffat, Mark; Jones, Heather; Zhang, Baohong; Cox, Wendy L; Rance, James R; Young, Robert J

2015-01-01

To meet product quality and cost parameters for therapeutic monoclonal antibody (mAb) production, cell lines are required to have excellent growth, stability, and productivity characteristics. In particular, cell line generation stability is critical to the success of a program, especially where high cell line generation numbers are required for large in-market supply. However, a typical process for developing such cell lines is laborious, lengthy, and costly. In this study, we applied a FLP/FRT recombinase-mediated cassette exchange (RMCE) system to build a site-specific integration (SSI) system for mAb expression in the commercially relevant CHOK1SV cell line. Using a vector with a FRT-flanked mAb expression cassette, we generated a clonal cell line with good productivity, long-term production stability, and low mAb gene-copy number indicating the vector was located in a 'hot-spot.' A SSI host cell line was made by removing the mAb genes from the 'hot-spot' by RMCE, creating a 'landing pad' containing two recombination cassettes that allow targeting of one or two copies of recombinant genes. Cell lines made from this host exhibited excellent growth and productivity profiles, and stability for at least 100 generations in the absence of selection agents. Importantly, while clones containing two copies had higher productivity than single copy clones, both were stable over many generations. Taken together, this study suggests the use of FLP-based RMCE to develop SSI host cells for mAb production in CHOK1SV offers significant savings in both resources and overall cell line development time, leading to a shortened 'time-to-clinic' for therapeutic mAbs. © 2015 American Institute of Chemical Engineers.

Uncovering the role of Nb modification in improving the structure stability and electrochemical performance of LiNi0.6Co0.2Mn0.2O2 cathode charged at higher voltage of 4.5 V

NASA Astrophysics Data System (ADS)

Liu, Siyang; Chen, Xiang; Zhao, Jiayue; Su, Junming; Zhang, Congcong; Huang, Tao; Wu, Jianhua; Yu, Aishui

2018-01-01

Ni-rich cathode materials attract ongoing interest due to their high specific capacity (∼200 mAh g-1). However, these materials suffer rapid capacity fading when charged to a high voltage and cycled at elevated temperature. In this study, we propose a facile method to reconstruct the surface structure of LiNi0.6Co0.2Mn0.2O2 via Nb modification, which integrates the merits of partial Nb5+ doping in the pristine structure and surface Li3NbO4 coating. The obtained results from Rietveld refinement and high resolution transmission electron microscopy confirm that Nb5+ is partially doped into Li+ sites within the surface lattice. Further ex-situ powder X-ray diffraction and kinetic analysis using electrochemical impedance spectroscopy reveal that Nb modification stabilizes the layered structure and facilitates the charge transfer process. Owing to the robust surface structure, 1 mol% Nb modified LiNi0.6Co0.2Mn0.2O2 delivers a discharge capacity of 160.9 mAh g-1 with 91% capacity retention after 100 cycles at 3.0-4.5 V, whereas the discharge capacity of the pristine sample drops to 139.6 mAh g-1, corresponding to 78% of its initial value. The presence of Nb5+ in the Li layer exhibits positive effects on stability of layered structure, and the surface Li3NbO4 coating layer increases interfacial stability, which results in superior electrochemical performance.

Geospatial Data Integration for Assessing Landslide Hazard on Engineered Slopes

NASA Astrophysics Data System (ADS)

Miller, P. E.; Mills, J. P.; Barr, S. L.; Birkinshaw, S. J.

2012-07-01

Road and rail networks are essential components of national infrastructures, underpinning the economy, and facilitating the mobility of goods and the human workforce. Earthwork slopes such as cuttings and embankments are primary components, and their reliability is of fundamental importance. However, instability and failure can occur, through processes such as landslides. Monitoring the condition of earthworks is a costly and continuous process for network operators, and currently, geospatial data is largely underutilised. The research presented here addresses this by combining airborne laser scanning and multispectral aerial imagery to develop a methodology for assessing landslide hazard. This is based on the extraction of key slope stability variables from the remotely sensed data. The methodology is implemented through numerical modelling, which is parameterised with the slope stability information, simulated climate conditions, and geotechnical properties. This allows determination of slope stability (expressed through the factor of safety) for a range of simulated scenarios. Regression analysis is then performed in order to develop a functional model relating slope stability to the input variables. The remotely sensed raster datasets are robustly re-sampled to two-dimensional cross-sections to facilitate meaningful interpretation of slope behaviour and mapping of landslide hazard. Results are stored in a geodatabase for spatial analysis within a GIS environment. For a test site located in England, UK, results have shown the utility of the approach in deriving practical hazard assessment information. Outcomes were compared to the network operator's hazard grading data, and show general agreement. The utility of the slope information was also assessed with respect to auto-population of slope geometry, and found to deliver significant improvements over the network operator's existing field-based approaches.

Channel stability of Turkey Creek, Nebraska

USGS Publications Warehouse

Rus, David L.; Soenksen, Philip J.

1998-01-01

Channelization on Turkey Creek and its receiving stream, the South Fork Big Nemaha River, has disturbed the equilibrium of Turkey Creek and has led to channel-stability problems, such as degradation and channel widening, which pose a threat to bridges and land adjacent to the stream. As part of a multiagency study, the U.S. Geological Survey assessed channel stability at two bridge sites on upper and middle portions of Turkey Creek by analyzing streambed-elevation data for gradation changes, comparing recent cross-section surveys and historic accounts, identifying bank-failure blocks, and analyzing tree-ring samples. These results were compared to gradation data and trend results for a U.S. Geological Survey streamflow-gaging station near the mouth of Turkey Creek from a previous study. Examination of data on streambed elevations reveals that degradation has occurred. The streambed elevation declined 0.5 m at the upper site from 1967-97. The streambed elevation declined by 3.2 m at the middle site from 1948-97 and exposed 2 m of the pilings of the Nebraska Highway 8 bridge. Channel widening could not be verified at the two sites from 1967-97, but a historic account indicates widening at the middle site to be two to three times that of the 1949 channel width. Small bank failures were evident at the upper site and a 4-m-wide bank failure occurred at the middle site in 1987 according to tree ring analyses. Examination of streambed-elevation data from a previous study at the lower site reveals a statistically significant aggrading trend from 1958-93. Further examination of these data suggests minor degradation occurred until 1975, followed by aggradation.

The effects of clam fishing on the properties of surface sediments in the lagoon of Venice, Italy

NASA Astrophysics Data System (ADS)

Aspen, R. J.; Vardy, S.; Perkins, R. G.; Davidson, I. R.; Bates, R.; Paterson, D. M.

Harvesting of clams(Tapes philippinarum) has important socio-economic and environmental implications for the Venice lagoon area, Italy. Clam harvesting disrupts the structure of benthic communities but the effects upon sediment stability and surface structure remain unclear. The effect of clam fishing on the sediment properties of the lagoon bed was investigated at two different sites, a heavily fished site (San Angelo) and an infrequently fished site (San Giaccomo). Both sites were assessed for immediate impacts of fishing, using indicators of biogenic sediment stabilisation. Samples were taken at three points along three 100 m linear transects at each site prior to and post fishing. Paired samples were also taken parallel to each transect at a distance of 5m, to allow for temporal variation. Sediment stability, measured with a cohesive strength meter (CSM), was significantly higher at the less impacted site (F1,34 = 6.23, p < 0.018), was correlated with indicators of biogenic sediment stabilisation and decreased by approximately 50% following the trawling event. Concomitant decreases in chlorophyll a (chl a), colloidal-S carbohydrate and dry bulk density were observed on the transect after fishing but not adjacent to the fishing path. At the heavily impacted site, clam fishing by trawling had, in general, no significant effect on the biological and physical properties (although chl a did decrease significantly after fishing). The lack of a significant impact from fishing at the impacted site was attributed to the higher frequency of fishing occurring in this area. Hence, frequent fishing of the lagoon prevents establishment of biotic communities, preventing biostabilisation and thus reduces the stability of the surface sediment.

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

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

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

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

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

DOE PAGES

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

2017-02-24

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

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

PubMed

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

2017-03-15

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

Propulsion System Airframe Integration Issues and Aerodynamic Database Development for the Hyper-X Flight Research Vehicle

NASA Technical Reports Server (NTRS)

Engelund, Walter C.; Holland, Scott D.; Cockrell, Charles E., Jr.; Bittner, Robert D.

1999-01-01

NASA's Hyper-X Research Vehicle will provide a unique opportunity to obtain data on an operational airframe integrated scramjet propulsion system at true flight conditions. The airframe integrated nature of the scramjet engine with the Hyper-X vehicle results in a strong coupling effect between the propulsion system operation and the airframe s basic aerodynamic characteristics. Comments on general airframe integrated scramjet propulsion system effects on vehicle aerodynamic performance, stability, and control are provided, followed by examples specific to the Hyper-X research vehicle. An overview is provided of the current activities associated with the development of the Hyper-X aerodynamic database, including wind tunnel test activities and parallel CFD analysis efforts. A brief summary of the Hyper-X aerodynamic characteristics is provided, including the direct and indirect effects of the airframe integrated scramjet propulsion system operation on the basic airframe stability and control characteristics.

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

PubMed Central

Hüser, Daniela; Weger, Stefan; Heilbronn, Regine

2003-01-01

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

EO-1 Hyperion Reflectance Time Series at Calibration and Validation Sites: Stability and Sensitivity to Seasonal Dynamics

NASA Technical Reports Server (NTRS)

Campbell, Petya K. Entcheva; Middleton, Elizabeth M.; Thome, Kurt J.; Kokaly, Raymond F.; Huemmrich, Karl Fred; Lagomasino, David; Novick, Kimberly A.; Brunsell, Nathaniel A.

2013-01-01

This study evaluated Earth Observing 1 (EO-1) Hyperion reflectance time series at established calibration sites to assess the instrument stability and suitability for monitoring vegetation functional parameters. Our analysis using three pseudo-invariant calibration sites in North America indicated that the reflectance time series are devoid of apparent spectral trends and their stability consistently is within 2.5-5 percent throughout most of the spectral range spanning the 12-plus year data record. Using three vegetated sites instrumented with eddy covariance towers, the Hyperion reflectance time series were evaluated for their ability to determine important variables of ecosystem function. A number of narrowband and derivative vegetation indices (VI) closely described the seasonal profiles in vegetation function and ecosystem carbon exchange (e.g., net and gross ecosystem productivity) in three very different ecosystems, including a hardwood forest and tallgrass prairie in North America, and a Miombo woodland in Africa. Our results demonstrate the potential for scaling the carbon flux tower measurements to local and regional landscape levels. The VIs with stronger relationships to the CO2 parameters were derived using continuous reflectance spectra and included wavelengths associated with chlorophyll content and/or chlorophyll fluorescence. Since these indices cannot be calculated from broadband multispectral instrument data, the opportunity to exploit these spectrometer-based VIs in the future will depend on the launch of satellites such as EnMAP and HyspIRI. This study highlights the practical utility of space-borne spectrometers for characterization of the spectral stability and uniformity of the calibration sites in support of sensor cross-comparisons, and demonstrates the potential of narrowband VIs to track and spatially extend ecosystem functional status as well as carbon processes measured at flux towers.

EO-1 Hyperion reflectance time series at calibration and validation sites: stability and sensitivity to seasonal dynamics

USGS Publications Warehouse

Campbell, P.K.E.; Middleton, E.M.; Thome, K.J.; Kokaly, Raymond F.; Huemmrich, K.F.; Novick, K.A.; Brunsell, N.A.

2013-01-01

This study evaluated Earth Observing 1 (EO-1) Hyperion reflectance time series at established calibration sites to assess the instrument stability and suitability for monitoring vegetation functional parameters. Our analysis using three pseudo-invariant calibration sites in North America indicated that the reflectance time series are devoid of apparent spectral trends and their stability consistently is within 2.5-5 percent throughout most of the spectral range spanning the 12+ year data record. Using three vegetated sites instrumented with eddy covariance towers, the Hyperion reflectance time series were evaluated for their ability to determine important variables of ecosystem function. A number of narrowband and derivative vegetation indices (VI) closely described the seasonal profiles in vegetation function and ecosystem carbon exchange (e.g., net and gross ecosystem productivity) in three very different ecosystems, including a hardwood forest and tallgrass prairie in North America, and a Miombo woodland in Africa. Our results demonstrate the potential for scaling the carbon flux tower measurements to local and regional landscape levels. The VIs with stronger relationships to the CO2 parameters were derived using continuous reflectance spectra and included wavelengths associated with chlorophyll content and/or chlorophyll fluorescence. Since these indices cannot be calculated from broadband multispectral instrument data, the opportunity to exploit these spectrometer-based VIs in the future will depend on the launch of satellites such as EnMAP and HyspIRI. This study highlights the practical utility of space-borne spectrometers for characterization of the spectral stability and uniformity of the calibration sites in support of sensor cross-comparisons, and demonstrates the potential of narrowband VIs to track and spatially extend ecosystem functional status as well as carbon processes measured at flux towers.

Signal Processing Methods for Liquid Rocket Engine Combustion Spontaneous Stability and Rough Combustion Assessments

NASA Technical Reports Server (NTRS)

Kenny, R. Jeremy; Casiano, Matthew; Fischbach, Sean; Hulka, James R.

2012-01-01

Liquid rocket engine combustion stability assessments are traditionally broken into three categories: dynamic stability, spontaneous stability, and rough combustion. This work focuses on comparing the spontaneous stability and rough combustion assessments for several liquid engine programs. The techniques used are those developed at Marshall Space Flight Center (MSFC) for the J-2X Workhorse Gas Generator program. Stability assessment data from the Integrated Powerhead Demonstrator (IPD), FASTRAC, and Common Extensible Cryogenic Engine (CECE) programs are compared against previously processed J-2X Gas Generator data. Prior metrics for spontaneous stability assessments are updated based on the compilation of all data sets.

Design and optimization of integrated gas/condensate plants

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

Root, C.R.; Wilson, J.L.

1995-11-01

An optimized design is demonstrated for combining gas processing and condensate stabilization plants into a single integrated process facility. This integrated design economically provides improved condensate recovery versus use of a simple stabilizer design. A selection matrix showing likely application of this integrated process is presented for use on future designs. Several methods for developing the fluid characterization and for using a process simulator to predict future design compositions are described, which could be useful in other designs. Optimization of flowsheet equipment choices and of design operating pressures and temperatures is demonstrated including the effect of both continuous and discretemore » process equipment size changes. Several similar designs using a turboexpander to provide refrigeration for liquids recovery and stabilizer reflux are described. Operating overthrust and from the P/15-D platform in the Dutch sector of the North Sea has proven these integrated designs are effective. Concerns do remain around operation near or above the critical pressure that should be addressed in future work including providing conservative separator designs, providing sufficient process design safety margin to meet dew point specifications, selecting the most conservative design values of predicted gas dew point and equipment size calculated with different Equations-of-State, and possibly improving the accuracy of PVT calculations in the near critical area.« less

The relation between circadian asynchrony, functional redundancy, and trophic performance in tropical ant communities.

PubMed

Houadria, Mickal; Blüthgen, Nico; Salas-Lopez, Alex; Schmitt, Mona-Isabel; Arndt, Johanna; Schneider, Eric; Orivel, Jérôme; Menzel, Florian

2016-01-01

The diversity-stability relationship has been under intense scrutiny for the past decades, and temporal asynchrony is recognized as an important aspect of ecosystem stability. In contrast to relatively well-studied interannual and seasonal asynchrony, few studies investigate the role of circadian cycles for ecosystem stability. Here, we studied multifunctional redundancy of diurnal and nocturnal ant communities in four tropical rain forest sites. We analyzed how it was influenced by species richness, functional performance, and circadian asynchrony. In two neotropical sites, species richness and functional redundancy were lower at night. In contrast, these parameters did not differ in the two paleotropical sites we studied. Circadian asynchrony between species was pronounced in the neotropical sites, and increased circadian functional redundancy. In general, species richness positively affected functional redundancy, but the effect size depended on the temporal and spatial breadth of the species with highest functional performance. Our analysis shows that high levels of trophic performance were only reached through the presence of such high-performing species, but not by even contributions of multiple, less-efficient species. Thus, these species can increase current functional performance, but reduce overall functional redundancy. Our study highlights that diurnal and nocturnal ecosystem properties of the very same habitat can markedly differ in terms of species richness and functional redundancy. Consequently, like the need to study multiple ecosystem functions, multiple periods of the circadian cycle need to be assessed in order to fully understand the diversity-stability relationship in an ecosystem.

Quadruplexes of human telomere dG{sub 3}(TTAG{sub 3}){sub 3} sequences containing guanine abasic sites

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

Skolakova, Petra; Bednarova, Klara; Vorlickova, Michaela

Research highlights: {yields} Loss of a guanine base does not hinder the formation of G-quadruplex of human telomere sequence. {yields} Each depurination strongly destabilizes the quadruplex of dG{sub 3}(TTAG{sub 3}){sub 3} in NaCl and KCl. {yields} Conformational change of the abasic analogs of dG{sub 3}(TTAG{sub 3}){sub 3} is inhibited in KCl. {yields} The effects abasic sites may affect telomere-end structures in vivo. -- Abstract: This study was performed to evaluate how the loss of a guanine base affects the structure and stability of the three-tetrad G-quadruplex of 5'-dG{sub 3}(TTAG{sub 3}){sub 3}, the basic quadruplex-forming unit of the human telomere DNA.more » None of the 12 possible abasic sites hindered the formation of quadruplexes, but all reduced the thermodynamic stability of the parent quadruplex in both NaCl and KCl. The base loss did not change the Na{sup +}-stabilized intramolecular antiparallel architecture, based on CD spectra, but held up the conformational change induced in dG{sub 3}(TTAG{sub 3}){sub 3} in physiological concentration of KCl. The reduced stability and the inhibited conformational transitions observed here in vitro for the first time may predict that unrepaired abasic sites in G-quadruplexes could lead to changes in the chromosome's terminal protection in vivo.« less

Conformation-selective inhibitors reveal differences in the activation and phosphate-binding loops of the tyrosine kinases Abl and Src

PubMed Central

Hari, Sanjay B.; Perera, B. Gayani K.; Ranjitkar, Pratistha; Seeliger, Markus A.; Maly, Dustin J.

2013-01-01

Over the last decade, an increasingly diverse array of potent and selective inhibitors that target the ATP-binding sites of protein kinases have been developed. Many of these inhibitors, like the clinically approved drug imatinib (Gleevec), stabilize a specific catalytically inactive ATP-binding site conformation of their kinases targets. Imatinib is notable in that it is highly selective for its kinase target, Abl, over other closely-related tyrosine kinases, like Src. In addition, imatinib is highly sensitive to the phosphorylation state of Abl's activation loop, which is believed to be a general characteristic of all inhibitors that stabilize a similar inactive ATP-binding site conformation. In this report, we perform a systematic analysis of a diverse series of ATP-competitive inhibitors that stabilize a similar inactive ATP-binding site conformation as imatinib with the tyrosine kinases Src and Abl. In contrast to imatinib, many of these inhibitors have very similar potencies against Src and Abl. Furthermore, only a subset of this class of inhibitors is sensitive to the phosphorylation state of the activation loop of these kinases. In attempting to explain this observation, we have uncovered an unexpected correlation between Abl's activation loop and another flexible active site feature, called the phosphate-binding loop (p-loop). These studies shed light on how imatinib is able to obtain its high target selectivity and reveal how the conformational preference of flexible active site regions can vary between closely related kinases. PMID:24106839

Environmental Assessment of remedial action at the Ambrosia Lake uranium mill tailings site, Ambrosia Lake, New Mexico

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

Not Available

1987-06-01

This document assesses and compares the environmental impacts of various alternatives for remedial action at the Ambrosia Lake uranium mill tailings site located near Ambrosia Lake, New Mexico. The designated site covers 196 acres and contains 111 acres of tailings and some of the original mill structures. The Uranium Mill Tailings Radiation Control Act (UMTRCA), Public Law 95-604, authorizes the US Department of Energy to clean up the site to reduce the potential health impacts associated with the residual radioactive materials remaining at the site and at associated properties off the site. The US Environmental Protection Agency promulgated standards formore » th remedial action (40 CFR Part 192). Remedial action must be performed in accordance with these standards and with the concurrence of the Nuclear Regulatory Commission. The proposed action is to stabilize the tailings at their present location by consolidating the tailings and associated contaminated materials into a recontoured pile. A radon barrier would be constructed over the pile and various erosion protection measures would be taken to assure the long-term stability of the pile. Another alternative which would involve moving the tailings to a new location is also assessed in this document. This alternative would generally involve greater short-term impacts and costs but would result in stabilization of the tailings at an undeveloped location. The no action alternative is also assessed in this document.« less

Energetic Coupling between Ligand Binding and Dimerization in E. coli Phosphoglycerate Mutase

PubMed Central

Gardner, Nathan W.; Monroe, Lyman K.; Kihara, Daisuke; Park, Chiwook

2016-01-01

Energetic coupling of two molecular events in a protein molecule is ubiquitous in biochemical reactions mediated by proteins, such as catalysis and signal transduction. Here, we investigate energetic coupling between ligand binding and folding of a dimer using a model system that shows three-state equilibrium unfolding in an exceptional quality. The homodimeric E. coli cofactor-dependent phosphoglycerate mutase (dPGM) was found to be stabilized by ATP in a proteome-wide screen, although dPGM does not require or utilize ATP for enzymatic function. We investigated the effect of ATP on the thermodynamic stability of dPGM using equilibrium unfolding. In the absence of ATP, dPGM populates a partially unfolded, monomeric intermediate during equilibrium unfolding. However, addition of 1.0 mM ATP drastically reduces the population of the intermediate by selectively stabilizing the native dimer. Using a computational ligand docking method, we predicted ATP binds to the active site of the enzyme using the triphosphate group. By performing equilibrium unfolding and isothermal titration calorimetry with active-site variants of dPGM, we confirmed that active-site residues are involved in ATP binding. Our findings show that ATP promotes dimerization of the protein by binding to the active site, which is distal from the dimer interface. This cooperativity suggests an energetic coupling between the active-site and the dimer interface. We also propose a structural link to explain how ligand binding to the active site is energetically coupled with dimerization. PMID:26919584

WGM Temperature Tracker

NASA Technical Reports Server (NTRS)

Strekalov, Dmitry V.

2012-01-01

This software implements digital control of a WGM (whispering-gallerymode) resonator temperature based on the dual-mode approach. It comprises one acquisition (dual-channel) and three control modules. The interaction of the proportional-integral loops is designed in the original way, preventing the loops from fighting. The data processing is organized in parallel with the acquisition, which allows the computational overhead time to be suppressed or often completely avoided. WGM resonators potentially provide excellent optical references for metrology, clocks, spectroscopy, and other applications. However, extremely accurate (below micro-Kelvin) temperature stabilization is required. This software allows one specifically advantageous method of such stabilization to be implemented, which is immune to a variety of effects that mask the temperature variation. WGM Temperature Tracker 2.3 (see figure) is a LabVIEW code developed for dual-mode temperature stabilization of WGM resonators. It has allowed for the temperature stabilization at the level of 200 nK with one-second integration time, and 6 nK with 10,000-second integration time, with the above room-temperature set point. This software, in conjunction with the appropriate hardware, can be used as a noncryogenic temperature sensor/ controller with sub-micro-Kelvin sensitivity, which at the time of this reporting considerably outperforms the state of the art.

Engineering Proteins for Thermostability with iRDP Web Server

PubMed Central

Ghanate, Avinash; Ramasamy, Sureshkumar; Suresh, C. G.

2015-01-01

Engineering protein molecules with desired structure and biological functions has been an elusive goal. Development of industrially viable proteins with improved properties such as stability, catalytic activity and altered specificity by modifying the structure of an existing protein has widely been targeted through rational protein engineering. Although a range of factors contributing to thermal stability have been identified and widely researched, the in silico implementation of these as strategies directed towards enhancement of protein stability has not yet been explored extensively. A wide range of structural analysis tools is currently available for in silico protein engineering. However these tools concentrate on only a limited number of factors or individual protein structures, resulting in cumbersome and time-consuming analysis. The iRDP web server presented here provides a unified platform comprising of iCAPS, iStability and iMutants modules. Each module addresses different facets of effective rational engineering of proteins aiming towards enhanced stability. While iCAPS aids in selection of target protein based on factors contributing to structural stability, iStability uniquely offers in silico implementation of known thermostabilization strategies in proteins for identification and stability prediction of potential stabilizing mutation sites. iMutants aims to assess mutants based on changes in local interaction network and degree of residue conservation at the mutation sites. Each module was validated using an extensively diverse dataset. The server is freely accessible at http://irdp.ncl.res.in and has no login requirements. PMID:26436543

Engineering Proteins for Thermostability with iRDP Web Server.

PubMed

Panigrahi, Priyabrata; Sule, Manas; Ghanate, Avinash; Ramasamy, Sureshkumar; Suresh, C G

2015-01-01

Engineering protein molecules with desired structure and biological functions has been an elusive goal. Development of industrially viable proteins with improved properties such as stability, catalytic activity and altered specificity by modifying the structure of an existing protein has widely been targeted through rational protein engineering. Although a range of factors contributing to thermal stability have been identified and widely researched, the in silico implementation of these as strategies directed towards enhancement of protein stability has not yet been explored extensively. A wide range of structural analysis tools is currently available for in silico protein engineering. However these tools concentrate on only a limited number of factors or individual protein structures, resulting in cumbersome and time-consuming analysis. The iRDP web server presented here provides a unified platform comprising of iCAPS, iStability and iMutants modules. Each module addresses different facets of effective rational engineering of proteins aiming towards enhanced stability. While iCAPS aids in selection of target protein based on factors contributing to structural stability, iStability uniquely offers in silico implementation of known thermostabilization strategies in proteins for identification and stability prediction of potential stabilizing mutation sites. iMutants aims to assess mutants based on changes in local interaction network and degree of residue conservation at the mutation sites. Each module was validated using an extensively diverse dataset. The server is freely accessible at http://irdp.ncl.res.in and has no login requirements.

Refining the Genetic Alphabet: A Late-Period Selection Pressure?

PubMed Central

Tor, Yitzhak

2012-01-01

Abstract The transition from genomic ribonucleic acid (RNA) to deoxyribonucleic acid (DNA) in primitive cells may have created a selection pressure that refined the genetic alphabet, resulting from the global weakening of the N-glycosyl bonds. Hydrolytic rupture of these bonds, termed deglycosylation, leaves an abasic site that is the single greatest threat to the stability and integrity of genomic DNA. The rates of deglycosylation are highly dependent on the identity of the nucleobases. Modifications made to the bases, such as deamination, oxidation, and alkylation, can further increase deglycosylation reaction rates, suggesting that the native bases provide optimum N-glycosyl bond stability. To protect their genomes, cells have evolved highly specific enzymes called glycosylases, associated with DNA repair, that detect and remove these damaged bases. In RNA, however, the occurrence of many of these modified bases is deliberate. The dichotomous behavior that cells exhibit toward base modifications may have originated in the RNA world. Modified bases would have been advantageous for the functional and structural repertoire of catalytic RNAs. Yet in an early DNA world, the utility of these heterocycles was greatly diminished, and their presence posed a distinct liability to the stability of cells' genomes. A natural selection for bases exhibiting the greatest resistance to deglycosylation would have ensured the viability of early DNA life, along with the recruitment of DNA repair. Key Words: DNA—Nucleic acids—RNA world—Asteroid—Chemical evolution—Ribozymes. Astrobiology 12, 884–891. PMID:22984873

Dried blood spot on-card derivatization: an alternative form of sample handling to overcome the instability of thiorphan in biological matrix.

PubMed

Mess, Jean-Nicholas; Taillon, Marie-Pierre; Côté, Cynthia; Garofolo, Fabio

2012-12-01

Thiorphan, the active metabolite of racecadotril, can undergo oxidation in biological matrices such as blood and plasma. In bioanalysis, a general approach for the stabilization of such a molecule is to derivatize the thiol group to a more stable thioether, often requiring complex handling procedures at the clinical site. In this research, the concept of dried blood spot (DBS) on-card derivatization was evaluated to stabilize thiorphan. DBS cards were in-house pre-treated with 2-bromo-3'-methoxyacetophenone and left to dry prior to blood spotting. Thiorphan was shown to be effectively derivatized to thiorphan-methoxyacetophenone once applied on the in-house pre-treated cards. Thiorphan-methoxyacetophenone was extracted by soaking a 6 mm DBS punch in methanol containing the internal standard (thiorphan-methoxyacetophenone-D₅). Chromatographic separation was achieved on a Waters XBridge C₁₈ column with a gradient elution of 5 mM NH₄HCO₃ and methanol in 2.5 min and detection by ESI(+)/MS/MS. A linear (weighted 1/x²) relationship was obtained over a concentration range of 5.00-600.00 ng/mL. The assay met regulatory guidelines acceptance criteria for sensitivity, selectivity, precision and accuracy, matrix effect, recovery, dilution integrity and multiple stability evaluations. The DBS on-card derivatization has shown to be an easy and reliable alternative form of sample collection for the quantification of thiorphan. Copyright © 2012 John Wiley & Sons, Ltd.

Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Rifle, Colorado

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

Not Available

1990-02-01

This volume contains appendices D6 through D8 containing laboratory test data: from MK-F investigation, 1987, Old Rifle and New Rifle sites; on bentonite amended radon barrier material; and from MK-F investigation, 1987, riprap tests.

Functional role of the extracellular N-terminal domain of neuropeptide Y subfamily receptors in membrane integration and agonist-stimulated internalization.

PubMed

Lindner, Diana; Walther, Cornelia; Tennemann, Anja; Beck-Sickinger, Annette G

2009-01-01

The N terminus is the most variable element in G protein-coupled receptors (GPCRs), ranging from seven residues up to approximately 5900 residues. For family B and C GPCRs it is described that at least part of the ligand binding site is located within the N terminus. Here we investigated the role of the N terminus in the neuropeptide Y receptor family, which belongs to the class A of GPCRs. We cloned differentially truncated Y receptor mutants, in which the N terminus was partially or completely deleted. We found, that eight amino acids are sufficient for full ligand binding and signal transduction activity. Interestingly, we could show that no specific amino acids but rather the extension of the first transmembrane helix by any residues is sufficient for receptor activity but also for membrane integration in case of the hY(1) and the hY(4) receptors. In contrast, the complete deletion of the N terminus in the hY(2) receptors resulted in a mutant that is fully integrated in the membrane but does not bind the ligand very well and internalizes much slower compared to the wild type receptor. Interestingly, also these effects could be reverted by any N-terminal extension. Accordingly, the most important function of the N termini seems to be the stabilization of the first transmembrane helix to ensure the correct receptor structure, which obviously is essential for ligand binding, integration into the cell membrane and receptor internalization.

Double closed-loop control of integrated optical resonance gyroscope with mean-square exponential stability.

PubMed

Li, Hui; Liu, Liying; Lin, Zhili; Wang, Qiwei; Wang, Xiao; Feng, Lishuang

2018-01-22

A new double closed-loop control system with mean-square exponential stability is firstly proposed to optimize the detection accuracy and dynamic response characteristic of the integrated optical resonance gyroscope (IORG). The influence mechanism of optical nonlinear effects on system detection sensitivity is investigated to optimize the demodulation gain, the maximum sensitivity and the linear work region of a gyro system. Especially, we analyze the effect of optical parameter fluctuation on the parameter uncertainty of system, and investigate the influence principle of laser locking-frequency noise on the closed-loop detection accuracy of angular velocity. The stochastic disturbance model of double closed-loop IORG is established that takes the unfavorable factors such as optical effect nonlinearity, disturbed disturbance, optical parameter fluctuation and unavoidable system noise into consideration. A robust control algorithm is also designed to guarantee the mean-square exponential stability of system with a prescribed H ∞ performance in order to improve the detection accuracy and dynamic performance of IORG. The conducted experiment results demonstrate that the IORG has a dynamic response time less than 76us, a long-term bias stability 7.04°/h with an integration time of 10s over one-hour test, and the corresponding bias stability 1.841°/h based on Allan deviation, which validate the effectiveness and usefulness of the proposed detection scheme.