Review: A Position Paper on Selenium in Ecotoxicology: A Procedure for Deriving Site-Specific Water Quality Criteria

Treesearch

A. Dennis Lemly

1997-01-01

This paper describes a method for deriving site-specific water quality criteria for selenium using a two-step process: (1) gather information on selenium residues and biological effects at the site and in down-gradient systems and (2) examine criteria based on the degree of bioaccumulation, the relationship between mea-sured residues and threshold concentrations for...

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

PubMed Central

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

2014-01-01

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

Transcript Isoform Variation Associated with Cytosine Modification in Human Lymphoblastoid Cell Lines.

PubMed

Zhang, Xu; Zhang, Wei

2016-06-01

Cytosine modification on DNA is variable among individuals, which could correlate with gene expression variation. The effect of cytosine modification on interindividual transcript isoform variation (TIV), however, remains unclear. In this study, we assessed the extent of cytosine modification-specific TIV in lymphoblastoid cell lines (LCLs) derived from unrelated individuals of European and African descent. Our study detected cytosine modification-specific TIVs for 17% of the analyzed genes at a 5% false discovery rate. Forty-five percent of the TIV-associated cytosine modifications correlated with the overall gene expression levels as well, with the corresponding CpG sites overrepresented in transcript initiation sites, transcription factor binding sites, and distinct histone modification peaks, suggesting that alternative isoform transcription underlies the TIVs. Our analysis also revealed 33% of the TIV-associated cytosine modifications that affected specific exons, with the corresponding CpG sites overrepresented in exon/intron junctions, splicing branching points, and transcript termination sites, implying that the TIVs are attributable to alternative splicing or transcription termination. Genetic and epigenetic regulation of TIV shared target preference but exerted independent effects on 61% of the common exon targets. Cytosine modification-specific TIVs detected from LCLs were differentially enriched in those detected from various tissues in The Cancer Genome Atlas, indicating their developmental dependency. Genes containing cytosine modification-specific TIVs were enriched in pathways of cancers and metabolic disorders. Our study demonstrated a prominent effect of cytosine modification variation on the transcript isoform spectrum over gross transcript abundance and revealed epigenetic contributions to diseases that were mediated through cytosine modification-specific TIV. Copyright © 2016 by the Genetics Society of America.

Differentiating Impacts of Watershed Development from Superfund Sites on Stream Macroinvertebrates

EPA Science Inventory

Urbanization effect models were developed and verified at whole watershed scales to predict and differentiate between effects on aquatic life from diffuse, non-point source (NPS) urbanization in the watershed and effects of known local, site-specific origin point sources, contami...

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

ERIC Educational Resources Information Center

Wassom, Julie

2002-01-01

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

The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis.

PubMed

Wu, San-Gang; Li, Hui; Tang, Li-Ying; Sun, Jia-Yuan; Zhang, Wen-Wen; Li, Feng-Yan; Chen, Yong-Xiong; He, Zhen-Yu

2017-06-01

To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer-specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2- and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor-/human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2- subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer-specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor-/human epidermal growth factor receptor 2- subtype conferred a significantly poorer outcome in terms of breast cancer-specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer-specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer-specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and liver metastases might be effective in improving breast cancer-specific survival and overall survival.

Brain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity

PubMed Central

Miller, Megan B.; Yan, Yan; Machida, Kazuya; Kiraly, Drew D.; Levy, Aaron D.; Wu, Yi I.; Lam, TuKiet T.; Abbott, Thomas; Koleske, Anthony J.; Eipper, Betty A.; Mains, Richard E.

2017-01-01

Kalirin7 (Kal7), a postsynaptic Rho GDP/GTP exchange factor (RhoGEF), plays a crucial role in long term potentiation and in the effects of cocaine on behavior and spine morphology. The KALRN gene has been linked to schizophrenia and other disorders of synaptic function. Mass spectrometry was used to quantify phosphorylation at 26 sites in Kal7 from individual adult rat nucleus accumbens and prefrontal cortex before and after exposure to acute or chronic cocaine. Region- and isoform-specific phosphorylation was observed along with region-specific effects of cocaine on Kal7 phosphorylation. Evaluation of the functional significance of multi-site phosphorylation in a complex protein like Kalirin is difficult. With the identification of five tyrosine phosphorylation (pY) sites, a panel of 71 SH2 domains was screened, identifying subsets that interacted with multiple pY sites in Kal7. In addition to this type of reversible interaction, endoproteolytic cleavage by calpain plays an essential role in long-term potentiation. Calpain cleaved Kal7 at two sites, separating the N-terminal domain, which affects spine length, and the PDZ binding motif from the GEF domain. Mutations preventing phosphorylation did not affect calpain sensitivity or GEF activity; phosphomimetic mutations at specific sites altered protein stability, increased calpain sensitivity and reduced GEF activity. PMID:28418645

Site-specific management of cotton root rot using airborne and satellite imagery

USDA-ARS?s Scientific Manuscript database

Cotton root rot is a serious cotton disease that can now be effectively controlled with Topguard Terra Fungicide. The objectives of this research were to demonstrate how site-specific fungicide application could be implemented based on historical remote sensing imagery and variable rate technology. ...

Integration of aerial imaging and variable-rate technology for site-specific aerial herbicide application

USDA-ARS?s Scientific Manuscript database

As remote sensing and variable rate technology are becoming more available for aerial applicators, practical methodologies on effective integration of these technologies are needed for site-specific aerial applications of crop production and protection materials. The objectives of this study were to...

Plant Trait Variation along an Altitudinal Gradient in Mediterranean High Mountain Grasslands: Controlling the Species Turnover Effect

PubMed Central

Pescador, David S.; de Bello, Francesco; Valladares, Fernando; Escudero, Adrián

2015-01-01

Assessing changes in plant functional traits along gradients is useful for understanding the assembly of communities and their response to global and local environmental drivers. However, these changes may reflect the effects of species composition (i.e. composition turnover), species abundance (i.e. species interaction), and intra-specific trait variability (i.e. species plasticity). In order to determine the relevance of the latter, trait variation can be assessed under minimal effects of composition turnover. Nine sampling sites were established along an altitudinal gradient in a Mediterranean high mountain grassland community with low composition turnover (Madrid, Spain; 1940 m–2419 m). Nine functional traits were also measured for ten individuals of around ten plant species at each site, for a total of eleven species across all sites. The relative importance of different sources of variability (within/between site and intra-/inter-specific functional diversity) and trait variation at species and community level along the considered gradients were explored. We found a weak individual species response to altitude and other environmental variables although in some cases, individuals were smaller and leaves were thicker at higher elevations. This lack of species response was most likely due to greater within- than between-site species variation. At the community level, inter-specific functional diversity was generally greater than the intra-specific component except for traits linked to leaf element content (leaf carbon content, leaf nitrogen content, δ13C and δ15N). Inter-specific functional diversity decreased with lower altitude for four leaf traits (specific leaf area, leaf dry matter content, δ13C and δ15N), suggesting trait convergence between species at lower elevations, where water shortage may have a stronger environmental filtering effect than colder temperatures at higher altitudes. Our results suggest that, within a vegetation type encompassing various environmental gradients, both, changes in species abundance and intra-specific trait variability adjust for the community functional response to environmental changes. PMID:25774532

Plant trait variation along an altitudinal gradient in mediterranean high mountain grasslands: controlling the species turnover effect.

PubMed

Pescador, David S; de Bello, Francesco; Valladares, Fernando; Escudero, Adrián

2015-01-01

Assessing changes in plant functional traits along gradients is useful for understanding the assembly of communities and their response to global and local environmental drivers. However, these changes may reflect the effects of species composition (i.e. composition turnover), species abundance (i.e. species interaction), and intra-specific trait variability (i.e. species plasticity). In order to determine the relevance of the latter, trait variation can be assessed under minimal effects of composition turnover. Nine sampling sites were established along an altitudinal gradient in a Mediterranean high mountain grassland community with low composition turnover (Madrid, Spain; 1940 m-2419 m). Nine functional traits were also measured for ten individuals of around ten plant species at each site, for a total of eleven species across all sites. The relative importance of different sources of variability (within/between site and intra-/inter-specific functional diversity) and trait variation at species and community level along the considered gradients were explored. We found a weak individual species response to altitude and other environmental variables although in some cases, individuals were smaller and leaves were thicker at higher elevations. This lack of species response was most likely due to greater within- than between-site species variation. At the community level, inter-specific functional diversity was generally greater than the intra-specific component except for traits linked to leaf element content (leaf carbon content, leaf nitrogen content, δ13C and δ15N). Inter-specific functional diversity decreased with lower altitude for four leaf traits (specific leaf area, leaf dry matter content, δ13C and δ15N), suggesting trait convergence between species at lower elevations, where water shortage may have a stronger environmental filtering effect than colder temperatures at higher altitudes. Our results suggest that, within a vegetation type encompassing various environmental gradients, both, changes in species abundance and intra-specific trait variability adjust for the community functional response to environmental changes.

[The influence of piracetam on behavior and brain receptors in C57BL/6 and BALB/c mice: nootropic and anxiolytic effects].

PubMed

Kovalev, G I; Kondrakhin, E A; Salimov, R M; Neznamov, G G

2013-01-01

The influence of acute and long-term piracetam administration on the dynamics of rapid (non-specific, anxiolytic) and slow (specific, nootropic) behavioral drug effects, as well as on their interrelation with NMDA- and BDZ-receptors was studied in inbred mice strains differing in cognitive and emotional status--C57BL/6 and BALB/c. The BALB/c strain contained 17% less [3H]-flunitrazepam binding sites in frontal cortex and 22% less [3H]-MK801 binding sites in hippocampus as compared to those in C57BL/6 mice. Based on these data, BALB/c strain was used as a model of psychopathology, combining increased anxiety and cognitive deficit. Under the action of single, 7-fold, and 14-fold piracetam i.p. injections (200 mg/kg body weight, daily), a fast increase in NMDA-receptor density and slow escalation of the specific nootropic effect was observed in BALB/c mice. Non-specific anxiolytic effects in these mice increased for the first 1 - 7 days without any changes in BDZ-binding and then decreased to initial values accompanied by decrement of brain receptor concentration. Thus, in BALB/c mice, a slowly manifested specific nootropic action of piracetam develops, following an increase in NMDA receptor density, whereas the non-specific anxiolytic effect precedes the fast-paced changes in BDZ-binding site density.

Demonstration of an Integrated Compliance Model for Predicting Copper Fate and Effects in DoD Harbors

DTIC Science & Technology

2008-11-01

seawater that does not include the natural ingredients that buffer the toxic effects of contaminants. As such, federal WQC could be overprotective ...regulation was overprotective (Earley et al., 2007). Implementation of a site-specific WQS in both cases could reduce the likelihood of TMDL actions...for site-specific factors that regulate bioavailability and toxicity, and thus are often overprotective (Seligman and Zirino, 1998; Zirino and

Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors

PubMed Central

Chorny, Michael; Fishbein, Ilia; Tengood, Jillian E.; Adamo, Richard F.; Alferiev, Ivan S.; Levy, Robert J.

2013-01-01

Gene therapeutic strategies have shown promise in treating vascular disease. However, their translation into clinical use requires pharmaceutical carriers enabling effective, site-specific delivery as well as providing sustained transgene expression in blood vessels. While replication-deficient adenovirus (Ad) offers several important advantages as a vector for vascular gene therapy, its clinical applicability is limited by rapid inactivation, suboptimal transduction efficiency in vascular cells, and serious systemic adverse effects. We hypothesized that novel zinc oleate-based magnetic nanoparticles (MNPs) loaded with Ad would enable effective arterial cell transduction by shifting vector processing to an alternative pathway, protect Ad from inactivation by neutralizing factors, and allow site-specific gene transfer to arteries treated with stent angioplasty using a 2-source magnetic guidance strategy. Ad-loaded MNPs effectively transduced cultured endothelial and smooth muscle cells under magnetic conditions compared to controls and retained capacity for gene transfer after exposure to neutralizing antibodies and lithium iodide, a lytic agent causing disruption of free Ad. Localized arterial gene expression significantly stronger than in control animal groups was demonstrated after magnetically guided MNP delivery in a rat stenting model 2 and 9 d post-treatment, confirming feasibility of using Ad-loaded MNPs to achieve site-specific transduction in stented blood vessels. In conclusion, Ad-loaded MNPs formed by controlled precipitation of zinc oleate represent a novel delivery system, well-suited for efficient, magnetically targeted vascular gene transfer.—Chorny, M., Fishbein, I., Tengood, J. E., Adamo, R. F., Alferiev, I. S., Levy, R. J. Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors. PMID:23407712

Stereoselective L-(3H)quinuclidinyl benzilate-binding sites in nervous tissue of Aplysia californica: evidence for muscarinic receptors

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

Murray, T.F.; Mpitsos, G.J.; Siebenaller, J.F.

The muscarinic antagonist L-(/sup 3/H)quinuclidinyl benzilate (L-(/sup 3/H)QNB) binds with a high affinity (Kd = 0.77 nM) to a single population of specific sites (Bmax = 47 fmol/mg of protein) in nervous tissue of the gastropod mollusc, Aplysia. The specific L-(/sup 3/H)QNB binding is displaced stereoselectively by the enantiomers of benzetimide, dexetimide, and levetimide. The pharmacologically active enantiomer, dexetimide, is more potent than levetimide as an inhibitor of L-(/sup 3/H)QNB binding. Moreover, the muscarinic cholinergic ligands, scopolamine, atropine, oxotremorine, and pilocarpine are effective inhibitors of the specific L-(/sup 3/H)QNB binding, whereas nicotinic receptor antagonists, decamethonium and d-tubocurarine, are considerably lessmore » effective. These pharmacological characteristics of the L-(/sup 3/H)QNB-binding site provide evidence for classical muscarinic receptors in Aplysia nervous tissue. The physiological relevance of the dexetimide-displaceable L-(/sup 3/H)QNB-binding site was supported by the demonstration of the sensitivity of the specific binding to thermal denaturation. Specific binding of L-(/sup 3/H)QNB was also detected in nervous tissue of another marine gastropod, Pleurobranchaea californica. The characteristics of the Aplysia L-(/sup 3/H)QNB-binding site are in accordance with studies of numerous vertebrate and invertebrate tissues indicating that the muscarinic cholinergic receptor site has been highly conserved through evolution.« less

A temporal and spatial assessment of TBT concentrations at dredged material disposal sites around the coast of England and Wales.

PubMed

Bolam, Thi; Barry, Jon; Law, Robin J; James, David; Thomas, Boby; Bolam, Stefan G

2014-02-15

Despite legislative interventions since the 1980s, contemporary concentrations of organotin compounds in marine sediments still impose restrictions on the disposal of dredged material in the UK. Here, we analyse temporal and spatial data to assess the effectiveness of the ban on the use of TBT paints in reducing concentrations at disposal sites. At a national scale, there was a statistically significant increase in the proportion of samples in which the concentration was below the limit of detection (LOD) from 1998 to 2010. This was observed for sediments both inside and outside the disposal sites. However, this temporal decline in organotin concentration is disposal site-specific. Of the four sites studied in detail, two displayed significant increases in proportion of samples below LOD over time. We argue that site-specificity in the effectiveness of the TBT ban results from variations in historical practices at source and unique environmental characteristics of each site. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Site-specific management of cotton root rot using historical remote sensing imagery

USDA-ARS?s Scientific Manuscript database

Cotton root rot can now be effectively controlled with Topguard Terra Fungicide, but site-specific application of the fungicide can greatly reduce treatment cost as only portions of the field are infested with the disease. The overall goal of this three-year project was to demonstrate how to use his...

Integrating soil information into canopy sensor algorithms for improved corn nitrogen rate recommendation

USDA-ARS?s Scientific Manuscript database

Crop canopy sensors have proven effective at determining site-specific nitrogen (N) needs, but several Midwest states use different algorithms to predict site-specific N need. The objective of this research was to determine if soil information can be used to improve the Missouri canopy sensor algori...

Lens-Specific Gene Recruitment of ζ-Crystallin through Pax6, Nrl-Maf, and Brain Suppressor Sites

PubMed Central

Sharon-Friling, Ronit; Richardson, Jill; Sperbeck, Sally; Lee, Douglas; Rauchman, Michael; Maas, Richard; Swaroop, Anand; Wistow, Graeme

1998-01-01

ζ-Crystallin is a taxon-specific crystallin, an enzyme which has undergone direct gene recruitment as a structural component of the guinea pig lens through a Pax6-dependent mechanism. Tissue specificity arises through a combination of effects involving three sites in the lens promoter. The Pax6 site (ZPE) itself shows specificity for an isoform of Pax6 preferentially expressed in lens cells. High-level expression of the promoter requires a second site, identical to an αCE2 site or half Maf response element (MARE), adjacent to the Pax6 site. A promoter fragment containing Pax6 and MARE sites gives lens-preferred induction of a heterologous promoter. Complexes binding the MARE in lens nuclear extracts are antigenically related to Nrl, and cotransfection with Nrl elevates ζ-crystallin promoter activity in lens cells. A truncated ζ promoter containing Nrl-MARE and Pax6 sites has a high level of expression in lens cells in transgenic mice but is also active in the brain. Suppression of the promoter in the brain requires sequences between −498 and −385, and a site in this region forms specific complexes in brain extract. A three-level model for lens-specific Pax6-dependent expression and gene recruitment is suggested: (i) binding of a specific isoform of Pax6; (ii) augmentation of expression through binding of Nrl or a related factor; and (iii) suppression of promoter activity in the central nervous system by an upstream negative element in the brain but not in the lens. PMID:9528779

Identification of cation-binding sites on actin that drive polymerization and modulate bending stiffness

PubMed Central

Kang, Hyeran; Bradley, Michael J.; McCullough, Brannon R.; Pierre, Anaëlle; Grintsevich, Elena E.; Reisler, Emil; De La Cruz, Enrique M.

2012-01-01

The assembly of actin monomers into filaments and networks plays vital roles throughout eukaryotic biology, including intracellular transport, cell motility, cell division, determining cellular shape, and providing cells with mechanical strength. The regulation of actin assembly and modulation of filament mechanical properties are critical for proper actin function. It is well established that physiological salt concentrations promote actin assembly and alter the overall bending mechanics of assembled filaments and networks. However, the molecular origins of these salt-dependent effects, particularly if they involve nonspecific ionic strength effects or specific ion-binding interactions, are unknown. Here, we demonstrate that specific cation binding at two discrete sites situated between adjacent subunits along the long-pitch helix drive actin polymerization and determine the filament bending rigidity. We classify the two sites as “polymerization” and “stiffness” sites based on the effects that mutations at the sites have on salt-dependent filament assembly and bending mechanics, respectively. These results establish the existence and location of the cation-binding sites that confer salt dependence to the assembly and mechanics of actin filaments. PMID:23027950

Probe pressure effects on human skin diffuse reflectance and fluorescence spectroscopy measurements

PubMed Central

Lim, Liang; Nichols, Brandon; Rajaram, Narasimhan; Tunnell, James W.

2011-01-01

Diffuse reflectance and fluorescence spectroscopy are popular research techniques for noninvasive disease diagnostics. Most systems include an optical fiber probe that transmits and collects optical spectra in contact with the suspected lesion. The purpose of this study is to investigate probe pressure effects on human skin spectroscopic measurements. We conduct an in-vivo experiment on human skin tissue to study the short-term (<2 s) and long-term (>30 s) effects of probe pressure on diffuse reflectance and fluorescence measurements. Short-term light probe pressure (P0 < 9 mN∕mm2) effects are within 0 ± 10% on all physiological properties extracted from diffuse reflectance and fluorescence measurements, and less than 0 ± 5% for diagnostically significant physiological properties. Absorption decreases with site-specific variations due to blood being compressed out of the sampled volume. Reduced scattering coefficient variation is site specific. Intrinsic fluorescence shows a large standard error, although no specific pressure-related trend is observed. Differences in tissue structure and morphology contribute to site-specific probe pressure effects. Therefore, the effects of pressure can be minimized when the pressure is small and applied for a short amount of time; however, long-term and large pressures induce significant distortions in measured spectra. PMID:21280899

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

USGS Publications Warehouse

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

1999-01-01

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

Event-based total suspended sediment particle size distribution model

NASA Astrophysics Data System (ADS)

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

2016-05-01

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

Finalizing the Libby Action Plan Research Program | Science ...

EPA Pesticide Factsheets

Libby, Montana is the location of a former vermiculite mine that operated from 1923 to 1990. The vermiculite ore from the mine co-existed with amphibole asbestos, referred to as Libby Amphibole Asbestos (LAA). Combined with the cessation of the asbestos mining and processing operations, there has been significant progress in reducing the exposure to LAA in Libby, Montana. In 2009, the U.S Environmental Protection Agency (EPA) jointly with the Department of Health and Human Services (DHHS) declared a public health emergency in Libby due to observed asbestos-related health effects in the region. As part of this effort, the EPA led a cross-agency research program that conducted analytical, toxicological, and epidemiological research on the health effects of asbestos at the Libby Asbestos Superfund Site (Libby Site) in Libby, Montana. The Libby Action Plan (LAP) was initiated in 2007 to support the site-specific risk assessment for the Libby Site. The goal of the LAP research program was to explore the health effects of LAA, and determine toxicity information specific to LAA in order to accurately inform a human health risk assessment at the Libby Site. LAP research informed data gaps related to the health effects of exposure to LAA, particularly related to specific mechanisms of fiber dosimetry and toxicity (e.g., inflammatory responses), as well as investigated disease progression in exposed populations and advanced asbestos analytical techniques. This work incl

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

ERIC Educational Resources Information Center

Qin, Xu; Hong, Guanglei

2017-01-01

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

Non-site-specific allosteric effect of oxygen on human hemoglobin under high oxygen partial pressure

PubMed Central

Takayanagi, Masayoshi; Kurisaki, Ikuo; Nagaoka, Masataka

2014-01-01

Protein allostery is essential for vital activities. Allosteric regulation of human hemoglobin (HbA) with two quaternary states T and R has been a paradigm of allosteric structural regulation of proteins. It is widely accepted that oxygen molecules (O2) act as a “site-specific” homotropic effector, or the successive O2 binding to the heme brings about the quaternary regulation. However, here we show that the site-specific allosteric effect is not necessarily only a unique mechanism of O2 allostery. Our simulation results revealed that the solution environment of high O2 partial pressure enhances the quaternary change from T to R without binding to the heme, suggesting an additional “non-site-specific” allosteric effect of O2. The latter effect should play a complementary role in the quaternary change by affecting the intersubunit contacts. This analysis must become a milestone in comprehensive understanding of the allosteric regulation of HbA from the molecular point of view. PMID:24710521

Site-specific effects of the nonsteroidal anti-inflammatory drug lysine clonixinate on rat brain opioid receptors.

PubMed

Ortí, E; Coirini, H; Pico, J C

1999-04-01

In addition to effects in the periphery through inhibition of prostaglandin synthesis, several lines of evidence suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) act in the central nervous system. The possibility that the central action of NSAIDs involves regulation of opioid receptors was investigated by quantitative autoradiography of mu, delta, and kappa sites in rat brain slices. Increased (p < 0.05) labeling of mu receptors was observed in thalamic nuclei, gyrus dentate, and layers of the parietal cortex of rats treated for 10 days with lysine clonixinate. Labeling of delta receptors was lower in the lateral septum, and kappa sites decreased in thalamic nuclei. These effects were not mediated through direct interaction with opioid-binding sites, since receptor-binding assays using rat brain membranes confirmed that clonixinate up to 1 x 10(-4) mol/l does not inhibit mu, delta, and kappa receptor specific binding. Central effects of NSAIDs might, therefore, involve interaction with the opioid receptor system through indirect mechanisms.

Quantifying site-specific physical heterogeneity within an estuarine seascape

USGS Publications Warehouse

Kennedy, Cristina G.; Mather, Martha E.; Smith, Joseph M.

2017-01-01

Quantifying physical heterogeneity is essential for meaningful ecological research and effective resource management. Spatial patterns of multiple, co-occurring physical features are rarely quantified across a seascape because of methodological challenges. Here, we identified approaches that measured total site-specific heterogeneity, an often overlooked aspect of estuarine ecosystems. Specifically, we examined 23 metrics that quantified four types of common physical features: (1) river and creek confluences, (2) bathymetric variation including underwater drop-offs, (3) land features such as islands/sandbars, and (4) major underwater channel networks. Our research at 40 sites throughout Plum Island Estuary (PIE) provided solutions to two problems. The first problem was that individual metrics that measured heterogeneity of a single physical feature showed different regional patterns. We solved this first problem by combining multiple metrics for a single feature using a within-physical feature cluster analysis. With this approach, we identified sites with four different types of confluences and three different types of underwater drop-offs. The second problem was that when multiple physical features co-occurred, new patterns of total site-specific heterogeneity were created across the seascape. This pattern of total heterogeneity has potential ecological relevance to structure-oriented predators. To address this second problem, we identified sites with similar types of total physical heterogeneity using an across-physical feature cluster analysis. Then, we calculated an additive heterogeneity index, which integrated all physical features at a site. Finally, we tested if site-specific additive heterogeneity index values differed for across-physical feature clusters. In PIE, the sites with the highest additive heterogeneity index values were clustered together and corresponded to sites where a fish predator, adult striped bass (Morone saxatilis), aggregated in a related acoustic tracking study. In summary, we have shown general approaches to quantifying site-specific heterogeneity.

An unconventional origin of metal-ion rescue and inhibition in the Tetrahymena group I ribozyme reaction.

PubMed Central

Shan, S O; Herschlag, D

2000-01-01

The presence of catalytic metal ions in RNA active sites has often been inferred from metal-ion rescue of modified substrates and sometimes from inhibitory effects of alternative metal ions. Herein we report that, in the Tetrahymena group I ribozyme reaction, the deleterious effect of a thio substitution at the pro-Sp position of the reactive phosphoryl group is rescued by Mn2+. However, analysis of the reaction of this thio substrate and of substrates with other modifications strongly suggest that this rescue does not stem from a direct Mn2+ interaction with the Sp sulfur. Instead, the apparent rescue arises from a Mn2+ ion interacting with the residue immediately 3' of the cleavage site, A(+1), that stabilizes the tertiary interactions between the oligonucleotide substrate (S) and the active site. This metal site is referred to as site D herein. We also present evidence that a previously observed Ca2+ ion that inhibits the chemical step binds to metal site D. These and other observations suggest that, whereas the interactions of Mn2+ at site D are favorable for the chemical reaction, the Ca2+ at site D exerts its inhibitory effect by disrupting the alignment of the substrates within the active site. These results emphasize the vigilance necessary in the design and interpretation of metal-ion rescue and inhibition experiments. Conversely, in-depth mechanistic analysis of the effects of site-specific substrate modifications can allow the effects of specific metal ion-RNA interactions to be revealed and the properties of individual metal-ion sites to be probed, even within the sea of metal ions bound to RNA. PMID:10864040

50 CFR 18.124 - How do I obtain a Letter of Authorization?

Code of Federal Regulations, 2012 CFR

2012-10-01

... polar bears or Pacific walruses in execution of those activities and you want nonlethal incidental take... operation. (2) A site-specific plan to monitor the effects of the activity on the behavior of polar bears... depending on the activity, the location, and the time of year. (3) A site-specific polar bear and/or walrus...

50 CFR 18.124 - How do I obtain a Letter of Authorization?

Code of Federal Regulations, 2011 CFR

2011-10-01

... polar bears or Pacific walruses in execution of those activities and you want nonlethal incidental take... operation. (2) A site-specific plan to monitor the effects of the activity on the behavior of polar bears... depending on the activity, the location, and the time of year. (3) A site-specific polar bear and/or walrus...

50 CFR 18.124 - How do I obtain a Letter of Authorization?

Code of Federal Regulations, 2014 CFR

2014-10-01

... polar bears or Pacific walruses in execution of those activities and you want nonlethal incidental take... operation. (2) A site-specific plan to monitor the effects of the activity on the behavior of polar bears... depending on the activity, the location, and the time of year. (3) A site-specific polar bear and/or walrus...

50 CFR 18.124 - How do I obtain a Letter of Authorization?

Code of Federal Regulations, 2013 CFR

2013-10-01

... polar bears or Pacific walruses in execution of those activities and you want nonlethal incidental take... operation. (2) A site-specific plan to monitor the effects of the activity on the behavior of polar bears... depending on the activity, the location, and the time of year. (3) A site-specific polar bear and/or walrus...

Creating prescription maps from satellite imagery for site-specific management of cotton root rot

USDA-ARS?s Scientific Manuscript database

Cotton root rot is a century-old cotton disease that can now be controlled with Topguard Terra Fungicide. However, as this disease tends to occur in the same general areas within fields year after year, site-specific treatment can be more effective and economical. The objective of this study was to ...

Depth-of-processing effects as college students use academic advising Web sites.

PubMed

Boatright-Horowitz, Su L; Langley, Michelle; Gunnip, Matthew

2009-06-01

This research examined students' cognitive and affective responses to an academic advising Web site. Specifically, we investigated whether exposure to our Web site increased student reports that they would access university Web sites to obtain various types of advising information. A depth-of-processing (DOP) manipulation revealed this effect as students engaged in semantic processing of Web content but not when they engaged in superficial examination of the physical appearance of the same Web site. Students appeared to scan online academic advising materials for information of immediate importance without noticing other information or hyperlinks (e.g., regarding internships and careers). Suggestions are presented for increasing the effectiveness of academic advising Web sites.

Modeling the Embrace of a Mutator: APOBEC Selection of Nucleic Acid Ligands.

PubMed

Salter, Jason D; Smith, Harold C

2018-05-23

The 11-member APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family of zinc-dependent cytidine deaminases bind to RNA and single-stranded DNA (ssDNA) and, in specific contexts, modify select (deoxy)cytidines to (deoxy)uridines. In this review, we describe advances made through high-resolution co-crystal structures of APOBECs bound to mono- or oligonucleotides that reveal potential substrate-specific binding sites at the active site and non-sequence-specific nucleic acid binding sites distal to the active site. We also discuss the effect of APOBEC oligomerization on functionality. Future structural studies will need to address how ssDNA binding away from the active site may enhance catalysis and the mechanism by which RNA binding may modulate catalytic activity on ssDNA. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Site- and species-specific hydrolysis rates of heroin.

PubMed

Szöcs, Levente; Orgován, Gábor; Tóth, Gergő; Kraszni, Márta; Gergó, Lajos; Hosztafi, Sándor; Noszál, Béla

2016-06-30

The hydroxide-catalyzed non-enzymatic, simultaneous and consecutive hydrolyses of diacetylmorphine (DAM, heroin) are quantified in terms of 10 site- and species-specific rate constants in connection with also 10 site- and species-specific acid-base equilibrium constants, comprising all the 12 coexisting species in solution. This characterization involves the major and minor decomposition pathways via 6-acetylmorphine and 3-acetylmorphine, respectively, and morphine, the final product. Hydrolysis has been found to be 18-120 times faster at site 3 than at site 6, depending on the status of the amino group and the rest of the molecule. Nitrogen protonation accelerates the hydrolysis 5-6 times at site 3 and slightly less at site 6. Hydrolysis rate constants are interpreted in terms of intramolecular inductive effects and the concomitant local electron densities. Hydrolysis fraction, a new physico-chemical parameter is introduced and determined to quantify the contribution of the individual microspecies to the overall hydrolysis. Hydrolysis fractions are depicted as a function of pH. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of capillarity and microtopography on wetland specific yield

USGS Publications Warehouse

Sumner, D.M.

2007-01-01

Hydrologic models aid in describing water flows and levels in wetlands. Frequently, these models use a specific yield conceptualization to relate water flows to water level changes. Traditionally, a simple conceptualization of specific yield is used, composed of two constant values for above- and below-surface water levels and neglecting the effects of soil capillarity and land surface microtopography. The effects of capiltarity and microtopography on specific yield were evaluated at three wetland sites in the Florida Everglades. The effect of capillarity on specific yield was incorporated based on the fillable pore space within a soil moisture profile at hydrostatic equilibrium with the water table. The effect of microtopography was based on areal averaging of topographically varying values of specific yield. The results indicate that a more physically-based conceptualization of specific yield incorporating capillary and microtopographic considerations can be substantially different from the traditional two-part conceptualization, and from simpler conceptualizations incorporating only capillarity or only microtopography. For the sites considered, traditional estimates of specific yield could under- or overestimate the more physically based estimates by a factor of two or more. The results suggest that consideration of both capillarity and microtopography is important to the formulation of specific yield in physically based hydrologic models of wetlands. ?? 2007, The Society of Wetland Scientists.

EFFECTS OF A HIGHLY-CONTAMINATED URBAN HARBOR ON AN ESTUARINE FISH SPECIES: ADAPTIVE CHANGES AT SPECIFIC LOCI

EPA Science Inventory

Fundulus heteroclitus populations indigenous to certain highly contaminated sites demonstrate an inherited tolerance to the toxic effects of local chemical contaminants. Our initial studies examining populations of F. heterclitus indigenous to a PCB-contaminated Superfund site at...

Site-specific mouth rinsing can improve oral odor by altering bacterial counts. Blind crossover clinical study.

PubMed

Alqumber, Mohammed A; Arafa, Khaled A

2014-11-01

To determine whether site-specific mouth rinsing with oral disinfectants can improve oral odor beyond the traditional panoral mouth disinfection with mouth rinses by targeting specifically oral malodor implicated anaerobic bacteria. Twenty healthy fasting subjects volunteered for a blinded prospective, descriptive correlational crossover cross-section clinical trial conducted during the month of Ramadan between July and August 2013 in Albaha province in Saudi Arabia involving the application of Listerine Cool Mint mouth rinse by either the traditional panoral rinsing method, or a site-specific disinfection method targeting the subgingival and supragingival plaque and the posterior third of the tongue dorsum, while avoiding the remaining locations within the oral cavity. The viable anaerobic and aerobic bacterial counts, volatile sulfur compounds (VSCs) levels, organoleptic assessment of oral odor, and the tongue-coating index were compared at baseline, one, 5, and 9 hours after the treatment. The site-specific disinfection method reduced the VSCs and anaerobic bacterial loads while keeping the aerobic bacterial numbers higher than the traditional panoral rinsing method. Site-specific disinfection can more effectively maintain a healthy oral cavity by predominantly disinfecting the niches of anaerobic bacteria within the oral cavity.

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

PubMed

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

2016-10-01

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

Conversion of transuranic waste to low level waste by decontamination: a site specific update

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

Allen, R.P.; Hazelton, R.F.

1985-09-01

As a followup to an FY-1984 cost/benefit study, a program was conducted in FY-1985 to transfer to the relevant DOE sites the information and technology for the direct conversion of transuranic (TRU) waste to low-level waste (LLW) by decontamination. As part of this work, the economic evaluation of the various TRUW volume reduction and conversion options was updated and expanded to include site-specific factors. The results show, for the assumptions used, that size reduction, size reduction followed by decontamination, or in situ decontamination are cost effective compared with the no-processing option. The technology transfer activities included site presentations and discussionsmore » with operations and waste management personnel to identify application opportunities and site-specific considerations and constraints that could affect the implementation of TRU waste conversion principles. These discussions disclosed definite potential for the beneficial application of these principles at most of the sites, but also confirmed the existence of site-specific factors ranging from space limitations to LLW disposal restrictions that could preclude particular applications or diminish expected benefits. 8 refs., 2 figs., 4 tabs.« less

Is site-specific APEX calibration necessary for field scale BMP assessment?

USDA-ARS?s Scientific Manuscript database

The possibility of extending parameter sets obtained at one site to sites with similar characteristics is appealing. This study was undertaken to test model performance and compare the effectiveness of best management practices (BMPs) using three parameters sets obtained from three watersheds when a...

Site Transfer Functions of Three-Component Ground Motion in Western Turkey

NASA Astrophysics Data System (ADS)

Ozgur Kurtulmus, Tevfik; Akyol, Nihal; Camyildiz, Murat; Gungor, Talip

2015-04-01

Because of high seismicity accommodating crustal deformation and deep graben structures, on which have, urbanized and industrialized large cities in western Turkey, the importance of site-specific seismic hazard assessments becomes more crucial. Characterizing source, site and path effects is important for both assessing the seismic hazard in a specific region and generation of the building codes/or renewing previous ones. In this study, we evaluated three-component recordings for micro- and moderate-size earthquakes with local magnitudes ranging between 2.0 and 5.6. This dataset is used for site transfer function estimations, utilizing two different spectral ratio approaches 'Standard Spectral Ratio-(SSR)' and 'Horizontal to Vertical Spectral Ratio-(HVSR)' and a 'Generalized Inversion Technique-(GIT)' to highlight site-specific seismic hazard potential of deep basin structures of the region. Obtained transfer functions revealed that the sites located near the basin edges are characterized by broader HVSR curves. Broad HVSR peaks could be attributed to the complexity of wave propagation related to significant 2D/3D velocity variations at the sediment-bedrock interface near the basin edges. Comparison of HVSR and SSR estimates for the sites located on the grabens showed that SSR estimates give larger values at lower frequencies which could be attributed to lateral variations in regional velocity and attenuation values caused by basin geometry and edge effects. However, large amplitude values of vertical component GIT site transfer functions were observed at varying frequency ranges for some of the stations. These results imply that vertical component of ground motion is not amplification free. Contamination of HVSR site transfer function estimates at different frequency bands could be related to complexities in the wave field caused by deep or shallow heterogeneities in the region such as differences in the basin geometries, fracturing and fluid saturation along different propagation paths. The results also show that, even if the site is located on a horst, the presence of weathered zones near the surface could cause moderate frequency dependent site effects.

Targeted modulation of reactive oxygen species in the vascular endothelium.

PubMed

Shuvaev, Vladimir V; Muzykantov, Vladimir R

2011-07-15

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

Autoradiographic localization of endothelin-1 binding sites in porcine skin

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

Zhao, Y.D.; Springall, D.R.; Wharton, J.

Autoradiographic techniques and {sup 125}I-labeled endothelin-1 were used to study the distribution of endothelin-1 binding sites in porcine skin. Specific endothelin-1 binding sites were localized to blood vessels (capillaries, deep cutaneous vascular plexus, arteries, and arterioles), the deep dermal and connective tissue sheath of hair follicles, sebaceous and sweat glands, and arrector pili muscle. Specific binding was inhibited by endothelin-2 and endothelin-3 as well as endothelin-1. Non-specific binding was found in the epidermis and the medulla of hair follicles. No binding was found in connective tissue or fat. These vascular binding sites may represent endothelin receptors, in keeping with themore » known cutaneous vasoconstrictor actions of the peptide. If all binding sites are receptors, the results suggest that endothelin could also regulate the function of sweat glands and may have trophic effects in the skin.« less

Using network screening methods to determine locations with specific safety issues: A design consistency case study.

PubMed

Butsick, Andrew J; Wood, Jonathan S; Jovanis, Paul P

2017-09-01

The Highway Safety Manual provides multiple methods that can be used to identify sites with promise (SWiPs) for safety improvement. However, most of these methods cannot be used to identify sites with specific problems. Furthermore, given that infrastructure funding is often specified for use related to specific problems/programs, a method for identifying SWiPs related to those programs would be very useful. This research establishes a method for Identifying SWiPs with specific issues. This is accomplished using two safety performance functions (SPFs). This method is applied to identifying SWiPs with geometric design consistency issues. Mixed effects negative binomial regression was used to develop two SPFs using 5 years of crash data and over 8754km of two-lane rural roadway. The first SPF contained typical roadway elements while the second contained additional geometric design consistency parameters. After empirical Bayes adjustments, sites with promise (SWiPs) were identified. The disparity between SWiPs identified by the two SPFs was evident; 40 unique sites were identified by each model out of the top 220 segments. By comparing sites across the two models, candidate road segments can be identified where a lack design consistency may be contributing to an increase in expected crashes. Practitioners can use this method to more effectively identify roadway segments suffering from reduced safety performance due to geometric design inconsistency, with detailed engineering studies of identified sites required to confirm the initial assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety performance functions for intersections : final report, December 2009.

DOT National Transportation Integrated Search

2009-12-01

Road safety management activities include screening the network for sites with a potential for safety improvement (Network : Screening), diagnosing safety problems at specific sites, and evaluating the safety effectiveness of implemented : countermea...

Climate and sex ratio variation in a viviparous lizard.

PubMed

Cunningham, George D; While, Geoffrey M; Wapstra, Erik

2017-05-01

The extent to which key biological processes, such as sex determination, respond to environmental fluctuations is fundamental for assessing species' susceptibility to ongoing climate change. Few studies, however, address how climate affects offspring sex in the wild. We monitored two climatically distinct populations of the viviparous skink Niveoscincus ocellatus for 16 years, recording environmental temperatures, offspring sex and date of birth. We found strong population-specific effects of temperature on offspring sex, with female offspring more common in warm years at the lowland site but no effect at the highland site. In contrast, date of birth advanced similarly in response to temperature at both sites. These results suggest strong population-specific effects of temperature on offspring sex that are independent of climatic effects on other physiological processes. These results have significant implications for our understanding of the ecological and evolutionary consequences of variation in sex ratios under climate change. © 2017 The Author(s).

The influence of sex and trauma impact on the rupture site of the ulnar collateral ligament of the thumb.

PubMed

Boesmueller, Sandra; Huf, Wolfgang; Rettl, Gregor; Dahm, Falko; Meznik, Alexander; Muschitz, Gabriela; Kitzinger, Hugo; Bukaty, Adam; Fialka, Christian; Vierhapper, Martin

2017-01-01

Although sex- and gender-specific analyses have been gaining more attention during the last years they have rarely been performed in orthopaedic literature. The primary purpose of this study was to investigate whether for injuries of the UCL the specific location of the rupture is influenced by sex. A secondary study question addressed the sex-independent effect of trauma intensity on the rupture site of the UCL. This study is a retrospective analysis of all patients with either a proximal or distal bony avulsion or with a mid-substance tear or ligament avulsion of the UCL treated surgically between 1992 and 2015 at two level-I trauma centres. Trauma mechanisms leading to the UCL injury were classified into the following categories: (1) blunt trauma (i.e., strains), (2) low-velocity injuries (e.g., fall from standing height, assaults), and (3) high-velocity injuries (e.g., sports injuries, motor vehicle accidents). After reviewing the surgical records, patients were divided into three groups, depending upon the ligament rupture site: (1) mid-substance tears, (2) proximal ligament or bony avulsions and (3) distal ligament or bony avulsions. Dependencies between the specific rupture site and the explanatory variables (sex, age, and trauma intensity) were evaluated using χ2 test and logistic regression analysis. In total, 1582 patients (1094 males, 488 females) met the inclusion criteria. Mean age was 41 years (range: 9-90 years). Taking into account the effects of sex on trauma intensity (p<0.001) and of trauma intensity on rupture site (p<0.001), mid-substance tears occurred more frequently in women, whereas men were more prone to distal ligament or bony avulsions (p<0.001). In other words, sex and rupture site correlated due to the effects of sex on trauma intensity and of trauma intensity on rupture site, but taking into account those effects there still was a significant effect of sex on rupture site. The results of this study demonstrate that with regression analysis both sex and trauma intensity allow to predict rupture site in UCL injuries.

The influence of sex and trauma impact on the rupture site of the ulnar collateral ligament of the thumb

PubMed Central

Huf, Wolfgang; Rettl, Gregor; Dahm, Falko; Meznik, Alexander; Muschitz, Gabriela; Kitzinger, Hugo; Bukaty, Adam; Fialka, Christian; Vierhapper, Martin

2017-01-01

Purpose and hypothesis Although sex- and gender-specific analyses have been gaining more attention during the last years they have rarely been performed in orthopaedic literature. The primary purpose of this study was to investigate whether for injuries of the UCL the specific location of the rupture is influenced by sex. A secondary study question addressed the sex-independent effect of trauma intensity on the rupture site of the UCL. Methods This study is a retrospective analysis of all patients with either a proximal or distal bony avulsion or with a mid-substance tear or ligament avulsion of the UCL treated surgically between 1992 and 2015 at two level-I trauma centres. Trauma mechanisms leading to the UCL injury were classified into the following categories: (1) blunt trauma (i.e., strains), (2) low-velocity injuries (e.g., fall from standing height, assaults), and (3) high-velocity injuries (e.g., sports injuries, motor vehicle accidents). After reviewing the surgical records, patients were divided into three groups, depending upon the ligament rupture site: (1) mid-substance tears, (2) proximal ligament or bony avulsions and (3) distal ligament or bony avulsions. Dependencies between the specific rupture site and the explanatory variables (sex, age, and trauma intensity) were evaluated using χ2 test and logistic regression analysis. Results In total, 1582 patients (1094 males, 488 females) met the inclusion criteria. Mean age was 41 years (range: 9–90 years). Taking into account the effects of sex on trauma intensity (p<0.001) and of trauma intensity on rupture site (p<0.001), mid-substance tears occurred more frequently in women, whereas men were more prone to distal ligament or bony avulsions (p<0.001). In other words, sex and rupture site correlated due to the effects of sex on trauma intensity and of trauma intensity on rupture site, but taking into account those effects there still was a significant effect of sex on rupture site. Conclusions The results of this study demonstrate that with regression analysis both sex and trauma intensity allow to predict rupture site in UCL injuries. PMID:28738083

Relative abundance, site fidelity, and survival of adult lake trout in Lake Michigan from 1999 to 2001: Implications for future restoration strategies

USGS Publications Warehouse

Bronte, C.R.; Holey, M.E.; Madenjian, C.P.; Jonas, J.L.; Claramunt, R.M.; McKee, P.C.; Toneys, M.L.; Ebener, M.P.; Breidert, B.; Fleischer, G.W.; Hess, R.; Martell, A.W.; Olsen, E.J.

2007-01-01

We compared the relative abundance of lake trout Salvelinus namaycush spawners in gill nets during fall 1999–2001 in Lake Michigan at 19 stocked spawning sites with that at 25 unstocked sites to evaluate how effective site-specific stocking was in recolonizing historically important spawning reefs. The abundance of adult fish was higher at stocked onshore and offshore sites than at unstocked sites. This suggests that site-specific stocking is more effective at establishing spawning aggregations than relying on the ability of hatchery-reared lake trout to find spawning reefs, especially those offshore. Spawner densities were generally too low and too young at most sites to expect significant natural reproduction. However, densities were sufficiently high at some sites for reproduction to occur and therefore the lack of recruitment was attributable to other factors. Less than 3% of all spawners could have been wild fish, which indicates that little natural reproduction occurred in past years. Wounding by sea lamprey Petromyzon marinus was generally lower for Seneca Lake strain fish and highest for strains from Lake Superior. Fish captured at offshore sites in southern Lake Michigan had the lowest probability of wounding, while fish at onshore sites in northern Lake Michigan had the highest probability. The relative survival of the Seneca Lake strain was higher than that of the Lewis Lake or the Marquette strains for the older year-classes examined. Survival differences among strains were less evident for younger year-classes. Recaptures of coded-wire-tagged fish of five strains indicated that most fish returned to their stocking site or to a nearby site and that dispersal from stocking sites during spawning was about 100 km. Restoration strategies should rely on site-specific stocking of lake trout strains with good survival at selected historically important offshore spawning sites to increase egg deposition and the probability of natural reproduction in Lake Michigan.

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

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

Sloan, J.W.

1984-01-01

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

n-Dodecyl β-D-maltoside specifically competes with general anesthetics for anesthetic binding sites.

PubMed

Xu, Longhe; Matsunaga, Felipe; Xi, Jin; Li, Min; Ma, Jingyuan; Liu, Renyu

2014-01-01

We recently demonstrated that the anionic detergent sodium dodecyl sulfate (SDS) specifically interacts with the anesthetic binding site in horse spleen apoferritin, a soluble protein which models anesthetic binding sites in receptors. This raises the possibility of other detergents similarly interacting with and occluding such sites from anesthetics, thereby preventing the proper identification of novel anesthetic binding sites. n-Dodecyl β-D-maltoside (DDM) is a non-ionic detergent commonly used during protein-anesthetic studies because of its mild and non-denaturing properties. In this study, we demonstrate that SDS and DDM occupy anesthetic binding sites in the model proteins human serum albumin (HSA) and horse spleen apoferritin and thereby inhibit the binding of the general anesthetics propofol and isoflurane. DDM specifically interacts with HSA (Kd = 40 μM) with a lower affinity than SDS (Kd = 2 μM). DDM exerts all these effects while not perturbing the native structures of either model protein. Computational calculations corroborated the experimental results by demonstrating that the binding sites for DDM and both anesthetics on the model proteins overlapped. Collectively, our results indicate that DDM and SDS specifically interact with anesthetic binding sites and may thus prevent the identification of novel anesthetic sites. Special precaution should be taken when undertaking and interpreting results from protein-anesthetic investigations utilizing detergents like SDS and DDM.

Critical Amino Acids in the Active Site of Meprin Metalloproteinases for Substrate and Peptide Bond Specificity*

PubMed Central

Villa, James P.; Bertenshaw, Greg P.; Bond, Judith S.

2008-01-01

SUMMARY The protease domains of the evolutionarily-related α and ß subunits of meprin metalloproteases are approximately 55% identical at the amino acid level, however, their substrate and peptide bond specificities differ markedly. The meprin ß subunit favors acidic residues proximal to the scissile bond, while the α subunit prefers small or aromatic amino acids flanking the scissile bond. Thus gastrin, a peptide that contains a string of five Glu residues, is an excellent substrate for meprin ß while it is not hydrolyzed by meprin α. Work herein aimed to identify critical amino acids in the meprin active sites that determine the substrate specificity differences. Sequence alignments and homology models, based on the crystal structure of the crayfish astacin, showed electrostatic differences within the meprin active sites. Site-directed mutagenesis of active site residues demonstrated that replacement of a hydrophobic residue by a basic amino acid enabled the meprin α protease to cleave gastrin. The meprin αY199K mutant was most effective; the corresponding mutation of meprin ßK185Y resulted in decreased activity toward gastrin. Peptide cleavage site determinations and kinetic analyses using a variety of peptides extended evidence that meprin αTyr199/ßLys185 are substrate specificity determinants in meprin active sites. These studies shed light on the molecular basis for the substrate specificity differences of astacin metalloproteinases. PMID:12888571

Identification of S-glutathionylation sites in species-specific proteins by incorporating five sequence-derived features into the general pseudo-amino acid composition.

PubMed

Zhao, Xiaowei; Ning, Qiao; Ai, Meiyue; Chai, Haiting; Yang, Guifu

2016-06-07

As a selective and reversible protein post-translational modification, S-glutathionylation generates mixed disulfides between glutathione (GSH) and cysteine residues, and plays an important role in regulating protein activity, stability, and redox regulation. To fully understand S-glutathionylation mechanisms, identification of substrates and specific S-Glutathionylated sites is crucial. Experimental identification of S-glutathionylated sites is labor-intensive and time consuming, so establishing an effective computational method is much desirable due to their convenient and fast speed. Therefore, in this study, a new bioinformatics tool named SSGlu (Species-Specific identification of Protein S-glutathionylation Sites) was developed to identify species-specific protein S-glutathionylated sites, utilizing support vector machines that combine multiple sequence-derived features with a two-step feature selection. By 5-fold cross validation, the performance of SSGlu was measured with an AUC of 0.8105 and 0.8041 for Homo sapiens and Mus musculus, respectively. Additionally, SSGlu was compared with the existing methods, and the higher MCC and AUC of SSGlu demonstrated that SSGlu was very promising to predict S-glutathionylated sites. Furthermore, a site-specific analysis showed that S-glutathionylation intimately correlated with the features derived from its surrounding sites. The conclusions derived from this study might help to understand more of the S-glutathionylation mechanism and guide the related experimental validation. For public access, SSGlu is freely accessible at http://59.73.198.144:8080/SSGlu/. Copyright © 2016 Elsevier Ltd. All rights reserved.

Binding Isotope Effects for para-Aminobenzoic Acid with Dihydropteroate Synthase from Staphylococcus aureus and Plasmodium falciparum.

PubMed

Stratton, Christopher F; Namanja-Magliano, Hilda A; Cameron, Scott A; Schramm, Vern L

2015-10-16

Dihydropteroate synthase is a key enzyme in folate biosynthesis and is the target of the sulfonamide class of antimicrobials. Equilibrium binding isotope effects and density functional theory calculations indicate that the substrate binding sites for para-aminobenzoic acid on the dihydropteroate synthase enzymes from Staphylococcus aureus and Plasmodium falciparum present distinct chemical environments. Specifically, we show that para-aminobenzoic acid occupies a more sterically constrained vibrational environment when bound to dihydropteroate synthase from P. falciparum relative to that of S. aureus. Deletion of a nonhomologous, parasite-specific insert from the plasmodial dihydropteroate synthase abrogated the binding of para-aminobenzoic acid. The loop specific to P. falciparum is important for effective substrate binding and therefore plays a role in modulating the chemical environment at the substrate binding site.

A general way for quantitative magnetic measurement by transmitted electrons

NASA Astrophysics Data System (ADS)

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

2016-01-01

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

Site-specific identification of heparan and chondroitin sulfate glycosaminoglycans in hybrid proteoglycans.

PubMed

Noborn, Fredrik; Gomez Toledo, Alejandro; Green, Anders; Nasir, Waqas; Sihlbom, Carina; Nilsson, Jonas; Larson, Göran

2016-10-03

Heparan sulfate (HS) and chondroitin sulfate (CS) are complex polysaccharides that regulate important biological pathways in virtually all metazoan organisms. The polysaccharides often display opposite effects on cell functions with HS and CS structural motifs presenting unique binding sites for specific ligands. Still, the mechanisms by which glycan biosynthesis generates complex HS and CS polysaccharides required for the regulation of mammalian physiology remain elusive. Here we present a glycoproteomic approach that identifies and differentiates between HS and CS attachment sites and provides identity to the core proteins. Glycopeptides were prepared from perlecan, a complex proteoglycan known to be substituted with both HS and CS chains, further digested with heparinase or chondroitinase ABC to reduce the HS and CS chain lengths respectively, and thereafter analyzed by nLC-MS/MS. This protocol enabled the identification of three consensus HS sites and one hybrid site, carrying either a HS or a CS chain. Inspection of the amino acid sequence at the hybrid attachment locus indicates that certain peptide motifs may encode for the chain type selection process. This analytical approach will become useful when addressing fundamental questions in basic biology specifically in elucidating the functional roles of site-specific glycosylations of proteoglycans.

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

PubMed Central

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

2016-01-01

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

Effects of Social Networking on Adolescent Education

ERIC Educational Resources Information Center

Miah, Muhammed; Omar, Adnan; Allison-Golding, Monique

2013-01-01

In recent years, the use of social networking sites has grown tremendously especially among the teens and high school students. However, very little is known about the scale of use, the purpose, how students use these sites and, more specifically, whether these sites help or hurt their academic progress. This study investigates how high school…

Enhanced magnetoelectric effect in M-type hexaferrites by Co substitution into trigonal bi-pyramidal sites

NASA Astrophysics Data System (ADS)

Beevers, J. E.; Love, C. J.; Lazarov, V. K.; Cavill, S. A.; Izadkhah, H.; Vittoria, C.; Fan, R.; van der Laan, G.; Dhesi, S. S.

2018-02-01

The magnetoelectric effect in M-type Ti-Co doped strontium hexaferrite has been studied using a combination of magnetometry and element specific soft X-ray spectroscopies. A large increase (>×30) in the magnetoelectric coefficient is found when Co2+ enters the trigonal bi-pyramidal site. The 5-fold trigonal bi-pyramidal site has been shown to provide an unusual mechanism for electric polarization based on the displacement of magnetic transition metal (TM) ions. For Co entering this site, an off-centre displacement of the cation may induce a large local electric dipole as well as providing an increased magnetostriction enhancing the magnetoelectric effect.

Identification of 50- and 23-/25-kDa HeLa cell membrane glycoproteins involved in poliovirus infection: occurrence of poliovirus specific binding sites on susceptible and nonsusceptible cells.

PubMed

Barnert, R H; Zeichhardt, H; Habermehl, K O

1992-02-01

Glycoproteins in the range 50 and 23/25 kDa were identified as poliovirus specific binding sites on HeLa cells with the monoclonal antibody mAb 122. mAb 122 is characterized by its partial inhibiting effect on poliovirus reproduction and adsorption when prebound to HeLa cells. The binding sites are endocytosed in native cells and specific for poliovirus as mAb 122 did not interfere with the adsorption of human rhinovirus type 14 (HRV 14). The poliovirus binding sites are present also on nonprimate so called nonsusceptible cells, e.g., mouse L-cells, as could be shown with sensitive ELISA based binding assays and performance of binding studies with fixed cells at 37 degrees.

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

PubMed

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

2008-02-22

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

Genome-wide detection of conservative site-specific recombination in bacteria

PubMed Central

Mathias Garrett, Elizabeth; Camilli, Andrew

2018-01-01

The ability of clonal bacterial populations to generate genomic and phenotypic heterogeneity is thought to be of great importance for many commensal and pathogenic bacteria. One common mechanism contributing to diversity formation relies on the inversion of small genomic DNA segments in a process commonly referred to as conservative site-specific recombination. This phenomenon is known to occur in several bacterial lineages, however it remains notoriously difficult to identify due to the lack of conserved features. Here, we report an easy-to-implement method based on high-throughput paired-end sequencing for genome-wide detection of conservative site-specific recombination on a single-nucleotide level. We demonstrate the effectiveness of the method by successfully detecting several novel inversion sites in an epidemic isolate of the enteric pathogen Clostridium difficile. Using an experimental approach, we validate the inversion potential of all detected sites in C. difficile and quantify their prevalence during exponential and stationary growth in vitro. In addition, we demonstrate that the master recombinase RecV is responsible for the inversion of some but not all invertible sites. Using a fluorescent gene-reporter system, we show that at least one gene from a two-component system located next to an invertible site is expressed in an on-off mode reminiscent of phase variation. We further demonstrate the applicability of our method by mining 209 publicly available sequencing datasets and show that conservative site-specific recombination is common in the bacterial realm but appears to be absent in some lineages. Finally, we show that the gene content associated with the inversion sites is diverse and goes beyond traditionally described surface components. Overall, our method provides a robust platform for detection of conservative site-specific recombination in bacteria and opens a new avenue for global exploration of this important phenomenon. PMID:29621238

Physical activity and cancer risk: dose-response and cancer, all sites and site-specific.

PubMed

Thune, I; Furberg, A S

2001-06-01

The association between physical activity and overall and site-specific cancer risk is elaborated in relation to whether any observed dose-response association between physical activity and cancer can be interpreted in terms of how much physical activity (type, intensity, duration, frequency) is needed to influence site- and gender-specific cancer risk. Observational studies were reviewed that have examined the independent effect of the volume of occupational physical activity (OPA) and/or leisure time physical activity (LPA) on overall and site-specific cancer risk. The evidence of cohort and case-control studies suggests that both leisure time and occupational physical activity protect against overall cancer risk, with a graded dose-response association suggested in both sexes. Confounding effects such as diet, body weight, and parity are often included as a covariate in the analyses, with little influence on the observed associations. A crude graded inverse dose-response association was observed between physical activity and colon cancer in 48 studies including 40,674 colon/colorectal cancer cases for both sexes. A dose-response effect of physical activity on colon cancer risk was especially observed, when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed as MET-hours per week. An observed inverse association with a dose-response relationship between physical activity and breast cancer was also identified in the majority of the 41 studies including 108,031 breast cancer cases. The dose-response relationship was in particular observed in case-control studies and supported by observations in cohort studies when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed by MET-hours per week. This association between physical activity and breast cancer risk is possibly dependent on age at exposure, age at diagnosis, menopausal status and other effect modifiers, e.g., body mass index. Furthermore, data concerning carcinoma of other cancers (prostate, lung, endometrium, ovary, and testicular cancers) are required. A protective effect of physical activity on site-specific cancer risk with a dose-response association between physical activity and colon and pre- and postmenopausal breast cancer supported by identified biological mechanisms has been observed. The optimal permutation of type, intensity, duration, and frequency of physical activity across the lifespan is unclear, but it is gender, age, and site specific and supports moderate activity (>4.5 MET) more than light activities (<4.5 MET). The complicated nature of the physical activity variable, combined with lack of knowledge regarding possible biological mechanisms operating between physical activity and cancer, warrants further studies including controlled clinical randomized trials.

Prediction of equilibrium distributions of isotopologues for methane, ethane and propane using density functional theory

NASA Astrophysics Data System (ADS)

Piasecki, Alison; Sessions, Alex; Peterson, Brian; Eiler, John

2016-10-01

Many previous studies have examined abundances of deuterium (D) and 13C within small organic molecules. Recent advances in analytical instrumentation add the abilities to measure site-specific and multiply substituted isotopologues of natural organics. Here we perform first-principles calculations of the equilibrium distributions of 13C and D in the volatile alkanes (including both single and multiple substitutions), as a guide to the interpretation of current measurements and as a basis for anticipating isotope effects that might be examined with future analytical techniques. The models we present illustrate several common themes of the isotopic structures of the small alkanes, including; temperature dependent enrichment of clumped isotope species, with amplitudes in the order D-D > 13C-D > 13C-13C; similarity in strength of such clumped isotope effects between different molecules (e.g., 13C-D clumping is ∼5‰ enriched at 300 K in methane, ethane and propane); a ∼10× contrast between the amplitudes of stronger adjacent substitution of two heavy isotopes vs. weaker non-adjacent substitution; temperature-dependent site-specific fractionation of D and 13C into interior positions of molecules relative to terminal methyl groups; and a relatively simple additive effect to the overall amplitude of enrichment when clumped and site specific effects combine in the same isotopologue. We suggest that the most promising tools suggested by our results are isotopic thermometers based on site-specific distribution of deuterium, which exhibits strong (∼100‰), highly temperature dependent fractionation between methyl groups and methylene carbon positions in propane (and likely other larger n-alkanes).

Validation of ozone response functions for annual Mediterranean pasture species using close-to-field-conditions experiments.

PubMed

González-Fernández, Ignacio; Sanz, Javier; Calvete-Sogo, Héctor; Elvira, Susana; Alonso, Rocío; Bermejo-Bermejo, Victoria

2017-12-01

Ozone (O 3 ) critical levels have been established under the Long-Range Transboundary Air Pollution Convention to assess the risk of O 3 effects in European vegetation. A recent review study has led to the development of O 3 critical levels for annual Mediterranean pasture species using plants growing in well-watered pots at a coastal site and under low levels of competition. However, uncertainties remain in the extrapolation of the O 3 sensitivity of these species under natural conditions. The response of two O 3 -sensitive annual Mediterranean pasture Trifolium species at the coastal site was compared with the response of the same species growing at a continental site, in natural soil and subject to water-stress and inter-specific competition, representing more closely their natural habitat. The slopes of exposure- and dose-response relationships derived for the two sites showed differences in the response to O 3 between sites attributed to differences in environmental growing conditions, growing medium and the level of inter-specific competition, but the effect of the individual factors could not be assessed separately. Dose-based O 3 indices partially explained differences due to environmental growing conditions between sites. The slopes showed that plants were more sensitive to O 3 at the continental site, but homogeneity of slopes tests revealed that results from both experimental sites may be combined. Although more experimental data considering complex inter-specific competition situations and the effect of important interactive factors such as nitrogen would be needed, these results confirm the validity of applying the current flux-based O 3 critical level under close to natural growing conditions. The AOT40-based O 3 critical level derived at the coastal site was also considered a suitable risk indicator in close to natural growing conditions in the absence of soil moisture limitations on plant growth.

Site specific passive acoustic detection and densities of humpback whale calls off the coast of California

NASA Astrophysics Data System (ADS)

Helble, Tyler Adam

Passive acoustic monitoring of marine mammal calls is an increasingly important method for assessing population numbers, distribution, and behavior. Automated methods are needed to aid in the analyses of the recorded data. When a mammal vocalizes in the marine environment, the received signal is a filtered version of the original waveform emitted by the marine mammal. The waveform is reduced in amplitude and distorted due to propagation effects that are influenced by the bathymetry and environment. It is important to account for these effects to determine a site-specific probability of detection for marine mammal calls in a given study area. A knowledge of that probability function over a range of environmental and ocean noise conditions allows vocalization statistics from recordings of single, fixed, omnidirectional sensors to be compared across sensors and at the same sensor over time with less bias and uncertainty in the results than direct comparison of the raw statistics. This dissertation focuses on both the development of new tools needed to automatically detect humpback whale vocalizations from single-fixed omnidirectional sensors as well as the determination of the site-specific probability of detection for monitoring sites off the coast of California. Using these tools, detected humpback calls are "calibrated" for environmental properties using the site-specific probability of detection values, and presented as call densities (calls per square kilometer per time). A two-year monitoring effort using these calibrated call densities reveals important biological and ecological information on migrating humpback whales off the coast of California. Call density trends are compared between the monitoring sites and at the same monitoring site over time. Call densities also are compared to several natural and human-influenced variables including season, time of day, lunar illumination, and ocean noise. The results reveal substantial differences in call densities between the two sites which were not noticeable using uncorrected (raw) call counts. Additionally, a Lombard effect was observed for humpback whale vocalizations in response to increasing ocean noise. The results presented in this thesis develop techniques to accurately measure marine mammal abundances from passive acoustic sensors.

Open-field test site

NASA Astrophysics Data System (ADS)

Gyoda, Koichi; Shinozuka, Takashi

1995-06-01

An open-field test site with measurement equipment, a turn table, antenna positioners, and measurement auxiliary equipment was remodelled at the CRL north-site. This paper introduces the configuration, specifications and characteristics of this new open-field test site. Measured 3-m and 10-m site attenuations are in good agreement with theoretical values, and this means that this site is suitable for using 3-m and 10-m method EMI/EMC measurements. The site is expected to be effective for antenna measurement, antenna calibration, and studies on EMI/EMC measurement methods.

Cell specific radiation dosimetry in skeleton from life-span carcinogenesis studies. Final report

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

Webster, S.S.J.

1993-04-05

The osteogenic sarcoma is the dominant life-threatening pathology in lifespan studies of beagles exposed to alpha-emitting bone-seeking radionuclides. It was deduced from these studies that certain skeletal sites are more prone to develop tumors. This project sought to determine the bone cells at risk and their cell-specific radiation dose. The cell-specific radiation dose values are related to loss and high Ra-226 and Pu-239 induced osteogenic sarcoma sites, to test different dose response hypothesis and predict the extent of effects in humans.

Cell specific radiation dosimetry in skeleton from life-span carcinogenesis studies

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

Webster, S.S.J.

1993-04-05

The osteogenic sarcoma is the dominant life-threatening pathology in lifespan studies of beagles exposed to alpha-emitting bone-seeking radionuclides. It was deduced from these studies that certain skeletal sites are more prone to develop tumors. This project sought to determine the bone cells at risk and their cell-specific radiation dose. The cell-specific radiation dose values are related to loss and high Ra-226 and Pu-239 induced osteogenic sarcoma sites, to test different dose response hypothesis and predict the extent of effects in humans.

EFFECTS OF CHLORAMINATION AND SITE SPECIFIC ISSUES ON NANOFILTRATION FLUX LOSS AND FOULANT CHARACTERISTICS

EPA Science Inventory

The presence of chloramines or free ammonium ion was found to have little effect on the final specific flux and fouling cake-layer characteristics of nanofiltration membrances fed pretreated Little Miami Aquifer water. The system fed chloraminated water had the greatest amount o...

Characterising variation in wheat traits under hostile soil conditions in India

PubMed Central

Khokhar, Jaswant S.; Sareen, Sindhu; Tyagi, Bhudeva S.; Singh, Gyanendra; Chowdhury, Apurba K.; Dhar, Tapamay; Singh, Vinod; King, Ian P.; Young, Scott D.

2017-01-01

Intensive crop breeding has increased wheat yields and production in India. Wheat improvement in India typically involves selecting yield and component traits under non-hostile soil conditions at regional scales. The aim of this study is to quantify G*E interactions on yield and component traits to further explore site-specific trait selection for hostile soils. Field experiments were conducted at six sites (pH range 4.5–9.5) in 2013–14 and 2014–15, in three agro-climatic regions of India. At each site, yield and component traits were measured on 36 genotypes, representing elite varieties from a wide genetic background developed for different regions. Mean grain yields ranged from 1.0 to 5.5 t ha-1 at hostile and non-hostile sites, respectively. Site (E) had the largest effect on yield and component traits, however, interactions between genotype and site (G*E) affected most traits to a greater extent than genotype alone. Within each agro-climatic region, yield and component traits correlated positively between hostile and non-hostile sites. However, some genotypes performed better under hostile soils, with site-specific relationships between yield and component traits, which supports the value of ongoing site-specific selection activities. PMID:28604800

GREAT I Study of the Upper Mississippi River. Technical Appendixes. Volume 2. Floodplain Management, Dredged Material Uses, Dredging Requirements.

DTIC Science & Technology

1980-09-01

placement of dredged material is proposed, a quantitative analysis of the effects on the 1-percent chance flood be made. The analysis must include a...FPMWG will accept the site. b. Until a quantitative analysis is conducted, place- ment sites be selected following these guidelines. (1) Dredge4 material... Analysis of site-specific encroachments would continue to be made without considering the opposite bank impacts or the long-term cumulative effects. 5

Using a site-specific technical error to establish training responsiveness: a preliminary explorative study.

PubMed

Weatherwax, Ryan M; Harris, Nigel K; Kilding, Andrew E; Dalleck, Lance C

2018-01-01

Even though cardiorespiratory fitness (CRF) training elicits numerous health benefits, not all individuals have positive training responses following a structured CRF intervention. It has been suggested that the technical error (TE), a combination of biological variability and measurement error, should be used to establish specific training responsiveness criteria to gain further insight on the effectiveness of the training program. To date, most training interventions use an absolute change or a TE from previous findings, which do not take into consideration the training site and equipment used to establish training outcomes or the specific cohort being evaluated. The purpose of this investigation was to retrospectively analyze training responsiveness of two CRF training interventions using two common criteria and a site-specific TE. Sixteen men and women completed two maximal graded exercise tests and verification bouts to identify maximal oxygen consumption (VO 2 max) and establish a site-specific TE. The TE was then used to retrospectively analyze training responsiveness in comparison to commonly used criteria: percent change of >0% and >+5.6% in VO 2 max. The TE was found to be 7.7% for relative VO 2 max. χ 2 testing showed significant differences in all training criteria for each intervention and pooled data from both interventions, except between %Δ >0 and %Δ >+7.7% in one of the investigations. Training nonresponsiveness ranged from 11.5% to 34.6%. Findings from the present study support the utility of site-specific TE criterion to quantify training responsiveness. A similar methodology of establishing a site-specific and even cohort specific TE should be considered to establish when true cardiorespiratory training adaptations occur.

Exploitation of the Ornithine Effect Enhances Characterization of Stapled and Cyclic Peptides

NASA Astrophysics Data System (ADS)

Crittenden, Christopher M.; Parker, W. Ryan; Jenner, Zachary B.; Bruns, Kerry A.; Akin, Lucas D.; McGee, William M.; Ciccimaro, Eugene; Brodbelt, Jennifer S.

2016-05-01

A method to facilitate the characterization of stapled or cyclic peptides is reported via an arginine-selective derivatization strategy coupled with MS/MS analysis. Arginine residues are converted to ornithine residues through a deguanidination reaction that installs a highly selectively cleavable site in peptides. Upon activation by CID or UVPD, the ornithine residue cyclizes to promote cleavage of the adjacent amide bond. This Arg-specific process offers a unique strategy for site-selective ring opening of stapled and cyclic peptides. Upon activation of each derivatized peptide, site-specific backbone cleavage at the ornithine residue results in two complementary products: the lactam ring-containing portion of the peptide and the amine-containing portion. The deguanidination process not only provides a specific marker site that initiates fragmentation of the peptide but also offers a means to unlock the staple and differentiate isobaric stapled peptides.

Human disturbance and stage-specific habitat requirements influence snowy plover site occupancy during the breeding season

PubMed Central

Webber, Alyson F; Heath, Julie A; Fischer, Richard A

2013-01-01

Habitat use has important consequences for avian reproductive success and survival. In coastal areas with recreational activity, human disturbance may limit use of otherwise suitable habitat. Snowy plovers Charadrius nivosus have a patchy breeding distribution along the coastal areas on the Florida Panhandle, USA. Our goal was to determine the relative effects of seasonal human disturbance and habitat requirements on snowy plover habitat use. We surveyed 303 sites for snowy plovers, human disturbance, and habitat features between January and July 2009 and 2010. We made multiple visits during three different sampling periods that corresponded to snowy plover breeding: pre-breeding, incubation, and brood-rearing and used multi-season occupancy models to examine whether human disturbance, habitat features, or both influenced site occupancy, colonization (probability of transition from an unoccupied site to an occupied site), and extinction (probability of transition from an occupied site to an unoccupied site). Snowy plover site occupancy and colonization was negatively associated with human disturbance and site extinction was positively associated with human disturbance. Interdune vegetation had a negative effect on occupancy and colonization, indicating that plovers were less likely to use areas with uniform, dense vegetation among dunes. Also, dune shape, beach debris, and access to low-energy foraging areas influenced site occupancy, colonization, and extinction. Plovers used habitat based on beach characteristics that provided stage-specific resource needs; however, human disturbance was the strongest predictor of site occupancy. In addition, vegetation plantings used to enhance dune rehabilitation may negatively impact plover site occupancy. Management actions that decrease human disturbance, such as symbolic fencing and signage, may increase the amount of breeding habitat available to snowy plovers on the Florida Panhandle and in other areas with high human activity. The specific areas that require this protection may vary across snowy plover life history stages. PMID:23610630

Constructing a framework for risk analyses of climate change effects on the water budget of differently sloped vineyards with a numeric simulation using the Monte Carlo method coupled to a water balance model

PubMed Central

Hofmann, Marco; Lux, Robert; Schultz, Hans R.

2014-01-01

Grapes for wine production are a highly climate sensitive crop and vineyard water budget is a decisive factor in quality formation. In order to conduct risk assessments for climate change effects in viticulture models are needed which can be applied to complete growing regions. We first modified an existing simplified geometric vineyard model of radiation interception and resulting water use to incorporate numerical Monte Carlo simulations and the physical aspects of radiation interactions between canopy and vineyard slope and azimuth. We then used four regional climate models to assess for possible effects on the water budget of selected vineyard sites up 2100. The model was developed to describe the partitioning of short-wave radiation between grapevine canopy and soil surface, respectively, green cover, necessary to calculate vineyard evapotranspiration. Soil water storage was allocated to two sub reservoirs. The model was adopted for steep slope vineyards based on coordinate transformation and validated against measurements of grapevine sap flow and soil water content determined down to 1.6 m depth at three different sites over 2 years. The results showed good agreement of modeled and observed soil water dynamics of vineyards with large variations in site specific soil water holding capacity (SWC) and viticultural management. Simulated sap flow was in overall good agreement with measured sap flow but site-specific responses of sap flow to potential evapotranspiration were observed. The analyses of climate change impacts on vineyard water budget demonstrated the importance of site-specific assessment due to natural variations in SWC. The improved model was capable of describing seasonal and site-specific dynamics in soil water content and could be used in an amended version to estimate changes in the water budget of entire grape growing areas due to evolving climatic changes. PMID:25540646

Repeatable source, site, and path effects on the standard deviation for empirical ground-motion prediction models

USGS Publications Warehouse

Lin, P.-S.; Chiou, B.; Abrahamson, N.; Walling, M.; Lee, C.-T.; Cheng, C.-T.

2011-01-01

In this study, we quantify the reduction in the standard deviation for empirical ground-motion prediction models by removing ergodic assumption.We partition the modeling error (residual) into five components, three of which represent the repeatable source-location-specific, site-specific, and path-specific deviations from the population mean. A variance estimation procedure of these error components is developed for use with a set of recordings from earthquakes not heavily clustered in space.With most source locations and propagation paths sampled only once, we opt to exploit the spatial correlation of residuals to estimate the variances associated with the path-specific and the source-location-specific deviations. The estimation procedure is applied to ground-motion amplitudes from 64 shallow earthquakes in Taiwan recorded at 285 sites with at least 10 recordings per site. The estimated variance components are used to quantify the reduction in aleatory variability that can be used in hazard analysis for a single site and for a single path. For peak ground acceleration and spectral accelerations at periods of 0.1, 0.3, 0.5, 1.0, and 3.0 s, we find that the singlesite standard deviations are 9%-14% smaller than the total standard deviation, whereas the single-path standard deviations are 39%-47% smaller.

Local nutrient regimes determine site-specific environmental triggers of cyanobacterial and microcystin variability in urban lakes

NASA Astrophysics Data System (ADS)

Sinang, S. C.; Reichwaldt, E. S.; Ghadouani, A.

2014-10-01

Toxic cyanobacterial blooms in urban lakes present serious health hazards to humans and animals and require effective management strategies. In the management of toxic cyanobacteria blooms, understanding the roles of environmental factors is crucial. To date, a range of environmental factors have been proposed as potential triggers for the spatiotemporal variability of cyanobacterial biomass and microcystins in freshwater systems. However, the environmental triggers of cyanobacteria and microcystin variability remain a subject of debate due to contrasting findings. This issue has raised the question if the environmental triggers are site-specific and unique between water bodies. In this study, we investigated the site-specificity of environmental triggers for cyanobacterial bloom and cyanotoxins dynamics. Our study suggests that cyanobacterial dominance and cyanobacterial microcystin content variability were significantly correlated to phosphorus and iron concentrations. However, the correlations between phosphorus and iron with cyanobacterial biomass and microcystin variability were not consistent between lakes, thus suggesting a site specificity of these environmental factors. The discrepancies in the correlations could be explained by differences in local nutrient concentration and the cyanobacterial community in the systems. The findings of this study suggest that identification of site-specific environmental factors under unique local conditions is an important strategy to enhance positive outcomes in cyanobacterial bloom control measures.

Accounting for regional variation in both natural environment and human disturbance to improve performance of multimetric indices of lotic benthic diatoms.

PubMed

Tang, Tao; Stevenson, R Jan; Infante, Dana M

2016-10-15

Regional variation in both natural environment and human disturbance can influence performance of ecological assessments. In this study we calculated 5 types of benthic diatom multimetric indices (MMIs) with 3 different approaches to account for variation in ecological assessments. We used: site groups defined by ecoregions or diatom typologies; the same or different sets of metrics among site groups; and unmodeled or modeled MMIs, where models accounted for natural variation in metrics within site groups by calculating an expected reference condition for each metric and each site. We used data from the USEPA's National Rivers and Streams Assessment to calculate the MMIs and evaluate changes in MMI performance. MMI performance was evaluated with indices of precision, bias, responsiveness, sensitivity and relevancy which were respectively measured as MMI variation among reference sites, effects of natural variables on MMIs, difference between MMIs at reference and highly disturbed sites, percent of highly disturbed sites properly classified, and relation of MMIs to human disturbance and stressors. All 5 types of MMIs showed considerable discrimination ability. Using different metrics among ecoregions sometimes reduced precision, but it consistently increased responsiveness, sensitivity, and relevancy. Site specific metric modeling reduced bias and increased responsiveness. Combined use of different metrics among site groups and site specific modeling significantly improved MMI performance irrespective of site grouping approach. Compared to ecoregion site classification, grouping sites based on diatom typologies improved precision, but did not improve overall performance of MMIs if we accounted for natural variation in metrics with site specific models. We conclude that using different metrics among ecoregions and site specific metric modeling improve MMI performance, particularly when used together. Applications of these MMI approaches in ecological assessments introduced a tradeoff with assessment consistency when metrics differed across site groups, but they justified the convenient and consistent use of ecoregions. Copyright © 2016 Elsevier B.V. All rights reserved.

Strong metal-support interactions

NASA Technical Reports Server (NTRS)

Vannice, M. Albert

1987-01-01

It has been demonstrated that synergistic metal-support effects can occur which markedly enhance specific activity and alter selectivity in certain reactions. Because of the presence of such effects in certain reactions conducted under reducing conditions (that is, under H2 pressure), but not others, the creation of unique sites at the metal-support interface seems to be the best model at the present time to explain this behavior. The postulation of these sites, which are specific for a certain reactant such as CO, provides an effective explanation for the higher methanation rates that have been reported over some catalysts. The creation of these sites in the adlineation zone is facilitated by hydrogen spillover from the metal surface, and this same process can also enhance the reduction of many oxide supports. Although oxygen spillover is much less probable due to its higher heat of adsorption, it is much less well understood and the possibility of rate enhancements in CO oxidation caused by special interface sites cannot be discounted at the present time. Consequently, this seems to be an important area of future research.

Can camera traps monitor Komodo dragons a large ectothermic predator?

PubMed

Ariefiandy, Achmad; Purwandana, Deni; Seno, Aganto; Ciofi, Claudio; Jessop, Tim S

2013-01-01

Camera trapping has greatly enhanced population monitoring of often cryptic and low abundance apex carnivores. Effectiveness of passive infrared camera trapping, and ultimately population monitoring, relies on temperature mediated differences between the animal and its ambient environment to ensure good camera detection. In ectothermic predators such as large varanid lizards, this criterion is presumed less certain. Here we evaluated the effectiveness of camera trapping to potentially monitor the population status of the Komodo dragon (Varanus komodoensis), an apex predator, using site occupancy approaches. We compared site-specific estimates of site occupancy and detection derived using camera traps and cage traps at 181 trapping locations established across six sites on four islands within Komodo National Park, Eastern Indonesia. Detection and site occupancy at each site were estimated using eight competing models that considered site-specific variation in occupancy (ψ)and varied detection probabilities (p) according to detection method, site and survey number using a single season site occupancy modelling approach. The most parsimonious model [ψ (site), p (site survey); ω = 0.74] suggested that site occupancy estimates differed among sites. Detection probability varied as an interaction between site and survey number. Our results indicate that overall camera traps produced similar estimates of detection and site occupancy to cage traps, irrespective of being paired, or unpaired, with cage traps. Whilst one site showed some evidence detection was affected by trapping method detection was too low to produce an accurate occupancy estimate. Overall, as camera trapping is logistically more feasible it may provide, with further validation, an alternative method for evaluating long-term site occupancy patterns in Komodo dragons, and potentially other large reptiles, aiding conservation of this species.

Can Camera Traps Monitor Komodo Dragons a Large Ectothermic Predator?

PubMed Central

Ariefiandy, Achmad; Purwandana, Deni; Seno, Aganto; Ciofi, Claudio; Jessop, Tim S.

2013-01-01

Camera trapping has greatly enhanced population monitoring of often cryptic and low abundance apex carnivores. Effectiveness of passive infrared camera trapping, and ultimately population monitoring, relies on temperature mediated differences between the animal and its ambient environment to ensure good camera detection. In ectothermic predators such as large varanid lizards, this criterion is presumed less certain. Here we evaluated the effectiveness of camera trapping to potentially monitor the population status of the Komodo dragon (Varanus komodoensis), an apex predator, using site occupancy approaches. We compared site-specific estimates of site occupancy and detection derived using camera traps and cage traps at 181 trapping locations established across six sites on four islands within Komodo National Park, Eastern Indonesia. Detection and site occupancy at each site were estimated using eight competing models that considered site-specific variation in occupancy (ψ)and varied detection probabilities (p) according to detection method, site and survey number using a single season site occupancy modelling approach. The most parsimonious model [ψ (site), p (site*survey); ω = 0.74] suggested that site occupancy estimates differed among sites. Detection probability varied as an interaction between site and survey number. Our results indicate that overall camera traps produced similar estimates of detection and site occupancy to cage traps, irrespective of being paired, or unpaired, with cage traps. Whilst one site showed some evidence detection was affected by trapping method detection was too low to produce an accurate occupancy estimate. Overall, as camera trapping is logistically more feasible it may provide, with further validation, an alternative method for evaluating long-term site occupancy patterns in Komodo dragons, and potentially other large reptiles, aiding conservation of this species. PMID:23527027

Efficient Site-Specific Labeling of Proteins via Cysteines

PubMed Central

Kim, Younggyu; Ho, Sam O.; Gassman, Natalie R.; Korlann, You; Landorf, Elizabeth V.; Collart, Frank R.; Weiss, Shimon

2011-01-01

Methods for chemical modifications of proteins have been crucial for the advancement of proteomics. In particular, site-specific covalent labeling of proteins with fluorophores and other moieties has permitted the development of a multitude of assays for proteome analysis. A common approach for such a modification is solvent-accessible cysteine labeling using thiol-reactive dyes. Cysteine is very attractive for site-specific conjugation due to its relative rarity throughout the proteome and the ease of its introduction into a specific site along the protein's amino acid chain. This is achieved by site-directed mutagenesis, most often without perturbing the protein's function. Bottlenecks in this reaction, however, include the maintenance of reactive thiol groups without oxidation before the reaction, and the effective removal of unreacted molecules prior to fluorescence studies. Here, we describe an efficient, specific, and rapid procedure for cysteine labeling starting from well-reduced proteins in the solid state. The efficacy and specificity of the improved procedure are estimated using a variety of single-cysteine proteins and thiol-reactive dyes. Based on UV/vis absorbance spectra, coupling efficiencies are typically in the range 70–90%, and specificities are better than ~95%. The labeled proteins are evaluated using fluorescence assays, proving that the covalent modification does not alter their function. In addition to maleimide-based conjugation, this improved procedure may be used for other thiol-reactive conjugations such as haloacetyl, alkyl halide, and disulfide interchange derivatives. This facile and rapid procedure is well suited for high throughput proteome analysis. PMID:18275130

Efficient site-specific labeling of proteins via cysteines.

PubMed

Kim, Younggyu; Ho, Sam O; Gassman, Natalie R; Korlann, You; Landorf, Elizabeth V; Collart, Frank R; Weiss, Shimon

2008-03-01

Methods for chemical modifications of proteins have been crucial for the advancement of proteomics. In particular, site-specific covalent labeling of proteins with fluorophores and other moieties has permitted the development of a multitude of assays for proteome analysis. A common approach for such a modification is solvent-accessible cysteine labeling using thiol-reactive dyes. Cysteine is very attractive for site-specific conjugation due to its relative rarity throughout the proteome and the ease of its introduction into a specific site along the protein's amino acid chain. This is achieved by site-directed mutagenesis, most often without perturbing the protein's function. Bottlenecks in this reaction, however, include the maintenance of reactive thiol groups without oxidation before the reaction, and the effective removal of unreacted molecules prior to fluorescence studies. Here, we describe an efficient, specific, and rapid procedure for cysteine labeling starting from well-reduced proteins in the solid state. The efficacy and specificity of the improved procedure are estimated using a variety of single-cysteine proteins and thiol-reactive dyes. Based on UV/vis absorbance spectra, coupling efficiencies are typically in the range 70-90%, and specificities are better than approximately 95%. The labeled proteins are evaluated using fluorescence assays, proving that the covalent modification does not alter their function. In addition to maleimide-based conjugation, this improved procedure may be used for other thiol-reactive conjugations such as haloacetyl, alkyl halide, and disulfide interchange derivatives. This facile and rapid procedure is well suited for high throughput proteome analysis.

Characterization and identification of ubiquitin conjugation sites with E3 ligase recognition specificities.

PubMed

Nguyen, Van-Nui; Huang, Kai-Yao; Huang, Chien-Hsun; Chang, Tzu-Hao; Bretaña, Neil; Lai, K; Weng, Julia; Lee, Tzong-Yi

2015-01-01

In eukaryotes, ubiquitin-conjugation is an important mechanism underlying proteasome-mediated degradation of proteins, and as such, plays an essential role in the regulation of many cellular processes. In the ubiquitin-proteasome pathway, E3 ligases play important roles by recognizing a specific protein substrate and catalyzing the attachment of ubiquitin to a lysine (K) residue. As more and more experimental data on ubiquitin conjugation sites become available, it becomes possible to develop prediction models that can be scaled to big data. However, no development that focuses on the investigation of ubiquitinated substrate specificities has existed. Herein, we present an approach that exploits an iteratively statistical method to identify ubiquitin conjugation sites with substrate site specificities. In this investigation, totally 6259 experimentally validated ubiquitinated proteins were obtained from dbPTM. After having filtered out homologous fragments with 40% sequence identity, the training data set contained 2658 ubiquitination sites (positive data) and 5532 non-ubiquitinated sites (negative data). Due to the difficulty in characterizing the substrate site specificities of E3 ligases by conventional sequence logo analysis, a recursively statistical method has been applied to obtain significant conserved motifs. The profile hidden Markov model (profile HMM) was adopted to construct the predictive models learned from the identified substrate motifs. A five-fold cross validation was then used to evaluate the predictive model, achieving sensitivity, specificity, and accuracy of 73.07%, 65.46%, and 67.93%, respectively. Additionally, an independent testing set, completely blind to the training data of the predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (76.13%) and outperform other ubiquitination site prediction tool. A case study demonstrated the effectiveness of the characterized substrate motifs for identifying ubiquitination sites. The proposed method presents a practical means of preliminary analysis and greatly diminishes the total number of potential targets required for further experimental confirmation. This method may help unravel their mechanisms and roles in E3 recognition and ubiquitin-mediated protein degradation.

Evaluation and implementation of an improved methodology for earthquake ground response analysis : uniform treatment source, path and site effects.

DOT National Transportation Integrated Search

2008-12-01

Shortly after the 1994 Northridge Earthquake, Caltrans geotechnical engineers charged with developing site-specific : response spectra for high priority California bridges initiated a research project aimed at broadening their perspective : from simp...

Are there specific benefits of amoxicillin plus metronidazole in Aggregatibacter actinomycetemcomitans-associated periodontitis? Double-masked, randomized clinical trial of efficacy and safety.

PubMed

Mombelli, Andrea; Cionca, Norbert; Almaghlouth, Adnan; Décaillet, Fabien; Courvoisier, Delphine S; Giannopoulou, Catherine

2013-06-01

It has been suggested that prescription of amoxicillin plus metronidazole in the context of periodontal therapy should be limited to patients with specific microbiologic profiles, especially those testing positive for Aggregatibacter actinomycetemcomitans. The main purpose of this analysis is to determine if patients positive for A. actinomycetemcomitans with moderate to advanced periodontitis benefit specifically from amoxicillin plus metronidazole given as an adjunct to full-mouth scaling and root planing. This is a double-masked, placebo-controlled, randomized longitudinal study including 41 participants who were positive for A. actinomycetemcomitans and 41 participants who were negative for A. actinomycetemcomitans. All 82 patients received full-mouth periodontal debridement performed within 48 hours. Patients then received either systemic antibiotics (375 mg amoxicillin and 500 mg metronidazole, three times daily) or placebo for 7 days. The primary outcome variable was persistence of sites with a probing depth (PD) >4 mm and bleeding on probing (BOP) at the 3-month reevaluation. Using multilevel logistic regression, the effect of the antibiotics was analyzed according to the following factors (interaction effect): A. actinomycetemcomitans-positive or -negative at baseline, sex, age, smoking, tooth being a molar, and interdental location. At reevaluation, participants in the test group had significantly fewer sites with a persisting PD >4 mm and BOP than control patients (P <0.01). Being A. actinomycetemcomitans-positive or -negative did not change the effect of the antibiotics. Patients benefited from the antibiotics irrespective of sex, age, or smoking status. Molars benefited significantly more from the antibiotics than non-molars (P for interaction effect = 0.03). Patients who were positive for A. actinomycetemcomitans had no specific benefit from amoxicillin plus metronidazole. Sites on molars benefited significantly more from the antibiotics than non-molar sites.

Effects of folic acid on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals

PubMed Central

Vollset, Stein Emil; Clarke, Robert; Lewington, Sarah; Ebbing, Marta; Halsey, Jim; Lonn, Eva; Armitage, Jane; Manson, JoAnn E; Hankey, Graeme J; Spence, J David; Galan, Pilar; Bønaa, Kaare H; Jamison, Rex; Gaziano, J Michael; Guarino, Peter; Baron, John A; Logan, Richard FA; Giovannucci, Edward L; den Heijer, Martin; Ueland, Per M; Bennett, Derrick; Collins, Rory; Peto, Richard

2013-01-01

Summary Background Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about cancer risks. We aimed to assess the effects of folic acid supplementation on site-specific cancer rates in the randomised trials. Methods Meta-analyses of data on each individual in all placebo-controlled trials of folic acid for prevention of cardiovascular disease (10 trials, n=46,969) or colorectal adenoma (3 trials, n=2652) that recorded cancer incidence and recruited >500 participants. All trials were evenly randomised. Risk ratios (RRs) compare those allocated folic acid vs those allocated placebo, giving cancer incidence rate ratios (among those still free of cancer) during, but not after the scheduled treatment period. Findings During a weighted mean follow-up duration of 5.5 years, allocation to folic acid quadrupled plasma folate, but had no statistically significant effect on overall cancer incidence (1904 vs 1809 cancers, RR=1.06 [95%CI 0.99–1.13], p=0.10; trend with duration of treatment p=0.46). There was no significant heterogeneity between the results of individual trials (p=0.23), or between the cadiovascular prevention trials and the adenoma prevention trials (p=0.13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast or any other specific site. Interpretation Folic acid supplementation does not substantially increase or decrease site-specific cancer incidence during the first 5 years of treatment. Funding British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency. PMID:23352552

Pretargeted PET Imaging Using a Site-Specifically Labeled Immunoconjugate.

PubMed

Cook, Brendon E; Adumeau, Pierre; Membreno, Rosemery; Carnazza, Kathryn E; Brand, Christian; Reiner, Thomas; Agnew, Brian J; Lewis, Jason S; Zeglis, Brian M

2016-08-17

In recent years, both site-specific bioconjugation techniques and bioorthogonal pretargeting strategies have emerged as exciting technologies with the potential to improve the safety and efficacy of antibody-based nuclear imaging. In the work at hand, we have combined these two approaches to create a pretargeted PET imaging strategy based on the rapid and bioorthogonal inverse electron demand Diels-Alder reaction between a (64)Cu-labeled tetrazine radioligand ((64)Cu-Tz-SarAr) and a site-specifically modified huA33-trans-cyclooctene immunoconjugate ((ss)huA33-PEG12-TCO). A bioconjugation strategy that harnesses enzymatic transformations and strain-promoted azide-alkyne click chemistry was used to site-specifically append PEGylated TCO moieties to the heavy chain glycans of the colorectal cancer-targeting huA33 antibody. Preclinical in vivo validation studies were performed in athymic nude mice bearing A33 antigen-expressing SW1222 human colorectal carcinoma xenografts. To this end, mice were administered (ss)huA33-PEG12-TCO via tail vein injection and-following accumulation intervals of 24 or 48 h-(64)Cu-Tz-SarAr. PET imaging and biodistribution studies reveal that this strategy clearly delineates tumor tissue as early as 1 h post-injection (6.7 ± 1.7%ID/g at 1 h p.i.), producing images with excellent contrast and high tumor-to-background activity concentration ratios (tumor:muscle = 21.5 ± 5.6 at 24 h p.i.). Furthermore, dosimetric calculations illustrate that this pretargeting approach produces only a fraction of the overall effective dose (0.0214 mSv/MBq; 0.079 rem/mCi) of directly labeled radioimmunoconjugates. Ultimately, this method effectively facilitates the high contrast pretargeted PET imaging of colorectal carcinoma using a site-specifically modified immunoconjugate.

Path spectra derived from inversion of source and site spectra for earthquakes in Southern California

NASA Astrophysics Data System (ADS)

Klimasewski, A.; Sahakian, V. J.; Baltay, A.; Boatwright, J.; Fletcher, J. B.; Baker, L. M.

2017-12-01

A large source of epistemic uncertainty in Ground Motion Prediction Equations (GMPEs) is derived from the path term, currently represented as a simple geometric spreading and intrinsic attenuation term. Including additional physical relationships between the path properties and predicted ground motions would produce more accurate and precise, region-specific GMPEs by reclassifying some of the random, aleatory uncertainty as epistemic. This study focuses on regions of Southern California, using data from the Anza network and Southern California Seismic network to create a catalog of events magnitude 2.5 and larger from 1998 to 2016. The catalog encompasses regions of varying geology and therefore varying path and site attenuation. Within this catalog of events, we investigate several collections of event region-to-station pairs, each of which share similar origin locations and stations so that all events have similar paths. Compared with a simple regional GMPE, these paths consistently have high or low residuals. By working with events that have the same path, we can isolate source and site effects, and focus on the remaining residual as path effects. We decompose the recordings into source and site spectra for each unique event and site in our greater Southern California regional database using the inversion method of Andrews (1986). This model represents each natural log record spectra as the sum of its natural log event and site spectra, while constraining each record to a reference site or Brune source spectrum. We estimate a regional, path-specific anelastic attenuation (Q) and site attenuation (t*) from the inversion site spectra and corner frequency from the inversion event spectra. We then compute the residuals between the observed record data, and the inversion model prediction (event*site spectra). This residual is representative of path effects, likely anelastic attenuation along the path that varies from the regional median attenuation. We examine the residuals for our different sets independently to see how path terms differ between event-to-station collections. The path-specific information gained from this can inform development of terms for regional GMPEs, through understanding of these seismological phenomena.

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.

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

NASA Technical Reports Server (NTRS)

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

1984-01-01

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

An electrostatic potassium channel opener targeting the final voltage sensor transition

PubMed Central

Börjesson, Sara I.

2011-01-01

Free polyunsaturated fatty acids (PUFAs) modulate the voltage dependence of voltage-gated ion channels. As an important consequence thereof, PUFAs can suppress epileptic seizures and cardiac arrhythmia. However, molecular details for the interaction between PUFA and ion channels are not well understood. In this study, we have localized the site of action for PUFAs on the voltage-gated Shaker K channel by introducing positive charges on the channel surface, which potentiated the PUFA effect. Furthermore, we found that PUFA mainly affects the final voltage sensor movement, which is closely linked to channel opening, and that specific charges at the extracellular end of the voltage sensor are critical for the PUFA effect. Because different voltage-gated K channels have different charge profiles, this implies channel-specific PUFA effects. The identified site and the pharmacological mechanism will potentially be very useful in future drug design of small-molecule compounds specifically targeting neuronal and cardiac excitability. PMID:21624947

Intein-mediated site-specific synthesis of tumor-targeting protein delivery system: Turning PEG dilemma into prodrug-like feature

PubMed Central

Chen, Yingzhi; Zhang, Meng; Jin, Hongyue; Tang, Yisi; Wang, Huiyuan; Xu, Qin; Li, Yaping; Li, Feng; Huang, Yongzhuo

2017-01-01

Poor tumor-targeted and cytoplasmic delivery is a bottleneck for protein toxin-based cancer therapy. Ideally, a protein toxin drug should remain stealthy in circulation for prolonged half-life and reduced side toxicity, but turn activated at tumor. PEGylation is a solution to achieve the first goal, but creates a hurdle for the second because PEG rejects interaction between the drugs and tumor cells therein. Such PEG dilemma is an unsolved problem in protein delivery. Herein proposed is a concept of turning PEG dilemma into prodrug-like feature. A site-selectively PEGylated, gelatinase-triggered cell-penetrating trichosanthin protein delivery system is developed with three specific aims. The first is to develop an intein-based ligation method for achieving site-specific modification of protein toxins. The second is to develop a prodrug feature that renders protein toxins remaining stealthy in blood for reduced side toxicity and improved EPR effect. The third is to develop a gelatinase activatable cell-penetration strategy for enhanced tumor targeting and cytoplasmic delivery. Of note, site-specific modification is a big challenge in protein drug research, especially for such a complicated, multifunctional protein delivery system. We successfully develop a protocol for constructing a macromolecular prodrug system with intein-mediated ligation synthesis. With an on-column process of purification and intein-mediated cleavage, the site-specific PEGylation then can be readily achieved by conjugation with the activated C-terminus, thus constructing a PEG-capped, cell-penetrating trichosanthin system with a gelatinase-cleavable linker that enables tumor-specific activation of cytoplasmic delivery. It provides a promising method to address the PEG dilemma for enhanced protein drug delivery, and importantly, a facile protocol for site-specific modification of such a class of protein drugs for improving their druggability and industrial translation. PMID:27914267

The effectiveness of small changes for pressure redistribution; using the air mattress for small changes.

PubMed

Tsuchiya, Sayumi; Sato, Aya; Azuma, Eri; Urushidani, Hiroko; Osawa, Masako; Kadoya, Kanaho; Takamura, Mana; Nunomi, Makiko; Mitsuoka, Akimi; Nishizawa Yokono, Tomoe; Sugama, Junko

2016-05-01

Observing small changes (SCs) at specific sites is a new form of managing changes in position. We investigated SCs at specific sites considering interface pressure, contact area, body alignment and physical sensation in nine healthy female adults and evaluated SCs using the air mattress that was divided into six cells (A-F). Thirty-three SC combinations at one or several sites were evaluated. Pressure in the sacral region significantly decreased in 28 SC combinations compared with the supine position (p < 0.05), and the effect of pressure redistribution was greater when SCs were applied at several instead of a single site. The contact area at 17 of the 28 SC combinations significantly increased (p < 0.05). Among sites ranked based on interface pressure, body alignment and physical sensation, SCs at sites BCE, AE and BD were the most favorable. The common feature among these three combinations was that they involved tilting the buttock region and one other site. The findings suggested that SCs at the buttock region could reduce disruptions in alignment as well as the impact on physical sensation caused by the body sinking into the mattress and improve interface pressure redistribution via increased contact area with the mattress. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Zebrafish embryos as a screen for DNA methylation modifications after compound exposure

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

Bouwmeester, Manon C.; Ruiter, Sander; Lommelaars, Tobias

Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin,more » arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis. - Highlights: • Compound induced effects on DNA methylation in zebrafish embryos • Global methylation not an informative biomarker • Minimal genome wide site specific changes as detected with DREAM • Compound/class specific effects suggested by pyrosequence of specific targets • Zebrafish embryo may be a screening model for epigenetic effects.« less

Genetic Encoding of bicyclononynes and trans-cyclooctenes for site-specific protein labeling in vitro and in live mammalian cells via rapid fluorogenic Diels-Alder reactions.

PubMed

Lang, Kathrin; Davis, Lloyd; Wallace, Stephen; Mahesh, Mohan; Cox, Daniel J; Blackman, Melissa L; Fox, Joseph M; Chin, Jason W

2012-06-27

Rapid, site-specific labeling of proteins with diverse probes remains an outstanding challenge for chemical biologists. Enzyme-mediated labeling approaches may be rapid but use protein or peptide fusions that introduce perturbations into the protein under study and may limit the sites that can be labeled, while many "bioorthogonal" reactions for which a component can be genetically encoded are too slow to effect quantitative site-specific labeling of proteins on a time scale that is useful for studying many biological processes. We report a fluorogenic reaction between bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN) and tetrazines that is 3-7 orders of magnitude faster than many bioorthogonal reactions. Unlike the reactions of strained alkenes, including trans-cyclooctenes and norbornenes, with tetrazines, the BCN-tetrazine reaction gives a single product of defined stereochemistry. We have discovered aminoacyl-tRNA synthetase/tRNA pairs for the efficient site-specific incorporation of a BCN-containing amino acid, 1, and a trans-cyclooctene-containing amino acid 2 (which also reacts extremely rapidly with tetrazines) into proteins expressed in Escherichia coli and mammalian cells. We demonstrate the rapid fluorogenic labeling of proteins containing 1 and 2 in vitro, in E. coli , and in live mammalian cells. These approaches may be extended to site-specific protein labeling in animals, and we anticipate that they will have a broad impact on labeling and imaging studies.

Siting Issues for Solar Thermal Power Plants with Small Community Applications

NASA Technical Reports Server (NTRS)

Holbeck, J. J.; Ireland, S. J.

1978-01-01

Technologies for solar thermal plants are being developed to provide energy alternatives for the future. Implementation of these plants requires consideration of siting issues as well as power system technology. While many conventional siting considerations are applicable, there is also a set of unique siting issues for solar thermal plants. Early experimental plants will have special siting considerations. The siting issues associated with small, dispersed solar thermal power plants in the 1 to 10 MWe power range for utility/small community applications are considered. Some specific requirements refer to the first 1 MWe engineering experiment for the Small Power Systems Applications (SPSA) Project. The siting issues themselves are discussed in three categories: (1) system resource requirements, (2) environmental effects on the system, and (3) potential impact of the plant on the environment. Within these categories, specific issues are discussed in a qualitative manner. Examples of limiting factors for some issues are taken from studies of other solar systems.

Developing and applying a site-specific multimedia fate model to address ecological risk of oxytetracycline discharged with aquaculture effluent in coastal waters off Jangheung, Korea.

PubMed

Kim, Woojung; Lee, Yunho; Kim, Sang Don

2017-11-01

The overuse of oxytetracycline (OTC) in aquaculture has become a problem because of its chronic toxic effects on marine ecosystems. The present study assessed the ecological risk of OTC in the coastal waters near the Jangheung Flatfish Farm using a site-specific multimedia fate model to analyze exposure. Before the model was applied, its performance was validated by comparing it with field data. The coastal waters in the testbed were sampled and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by solid-phase extraction (SPE). The concentrations of OTC measured varied from 7.05 to 95.39ng/L. The results of validating the models showed that the site-specific multimedia fate model performed better (root mean square error (RMSE): 24.217, index of agreement (IOA): 0.739) than conventional fugacity approaches. This result demonstrated the utility of this model in supporting effective future management of aquaculture effluent. The results of probabilistic risk assessment indicated that OTC from aquaculture effluent did not cause adverse effects, even in a maximum-use scenario. Copyright © 2017 Elsevier Inc. All rights reserved.

Site specific atomic polarizabilities in endohedral fullerenes and carbon onions

NASA Astrophysics Data System (ADS)

Zope, Rajendra R.; Bhusal, Shusil; Basurto, Luis; Baruah, Tunna; Jackson, Koblar

2015-08-01

We investigate the polarizability of trimetallic nitride endohedral fullerenes by partitioning the total polarizability into site specific components. This analysis indicates that the polarizability of the endohedral fullerene is essentially due to the outer fullerene cage and has insignificant contribution from the encapsulated unit. Thus, the outer fullerene cages effectively shield the encapsulated clusters and behave like Faraday cages. The polarizability of endohedral fullerenes is slightly smaller than the polarizability of the corresponding bare carbon fullerenes. The application of the site specific polarizabilities to C60@C240 and C60@C180 onions shows that, compared to the polarizability of isolated C60 fullerene, the encapsulation of the C60 in C240 and C180 fullerenes reduces its polarizability by 75% and 83%, respectively. The differences in the polarizability of C60 in the two onions is a result of differences in the bonding (intershell electron transfer), fullerene shell relaxations, and intershell separations. The site specific analysis further shows that the outer atoms in a fullerene shell contribute most to the fullerene polarizability.

Site specific atomic polarizabilities in endohedral fullerenes and carbon onions.

PubMed

Zope, Rajendra R; Bhusal, Shusil; Basurto, Luis; Baruah, Tunna; Jackson, Koblar

2015-08-28

We investigate the polarizability of trimetallic nitride endohedral fullerenes by partitioning the total polarizability into site specific components. This analysis indicates that the polarizability of the endohedral fullerene is essentially due to the outer fullerene cage and has insignificant contribution from the encapsulated unit. Thus, the outer fullerene cages effectively shield the encapsulated clusters and behave like Faraday cages. The polarizability of endohedral fullerenes is slightly smaller than the polarizability of the corresponding bare carbon fullerenes. The application of the site specific polarizabilities to C60@C240 and C60@C180 onions shows that, compared to the polarizability of isolated C60 fullerene, the encapsulation of the C60 in C240 and C180 fullerenes reduces its polarizability by 75% and 83%, respectively. The differences in the polarizability of C60 in the two onions is a result of differences in the bonding (intershell electron transfer), fullerene shell relaxations, and intershell separations. The site specific analysis further shows that the outer atoms in a fullerene shell contribute most to the fullerene polarizability.

Site specific atomic polarizabilities in endohedral fullerenes and carbon onions

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

Zope, Rajendra R., E-mail: rzope@utep.edu; Baruah, Tunna; Computational Science Program, The University of Texas at El Paso, El Paso, Texas 79958

2015-08-28

We investigate the polarizability of trimetallic nitride endohedral fullerenes by partitioning the total polarizability into site specific components. This analysis indicates that the polarizability of the endohedral fullerene is essentially due to the outer fullerene cage and has insignificant contribution from the encapsulated unit. Thus, the outer fullerene cages effectively shield the encapsulated clusters and behave like Faraday cages. The polarizability of endohedral fullerenes is slightly smaller than the polarizability of the corresponding bare carbon fullerenes. The application of the site specific polarizabilities to C{sub 60}@C{sub 240} and C{sub 60}@C{sub 180} onions shows that, compared to the polarizability of isolatedmore » C{sub 60} fullerene, the encapsulation of the C{sub 60} in C{sub 240} and C{sub 180} fullerenes reduces its polarizability by 75% and 83%, respectively. The differences in the polarizability of C{sub 60} in the two onions is a result of differences in the bonding (intershell electron transfer), fullerene shell relaxations, and intershell separations. The site specific analysis further shows that the outer atoms in a fullerene shell contribute most to the fullerene polarizability.« less

Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer

PubMed Central

Carvalho, S; Catarino, TA; Dias, AM; Kato, M; Almeida, A; Hessling, B; Figueiredo, J; Gärtner, F; Sanches, JM; Ruppert, T; Miyoshi, E; Pierce, M; Carneiro, F; Kolarich, D; Seruca, R; Yamaguchi, Y; Taniguchi, N; Reis, CA; Pinho, SS

2016-01-01

E-cadherin is a central molecule in the process of gastric carcinogenesis and its posttranslational modifications by N-glycosylation have been described to induce a deleterious effect on cell adhesion associated with tumor cell invasion. However, the role that site-specific glycosylation of E-cadherin has in its defective function in gastric cancer cells needs to be determined. Using transgenic mice models and human clinical samples, we demonstrated that N-acetylglucosaminyltransferase V (GnT-V)-mediated glycosylation causes an abnormal pattern of E-cadherin expression in the gastric mucosa. In vitro models further indicated that, among the four potential N-glycosylation sites of E-cadherin, Asn-554 is the key site that is selectively modified with β1,6 GlcNAc-branched N-glycans catalyzed by GnT-V. This aberrant glycan modification on this specific asparagine site of E-cadherin was demonstrated to affect its critical functions in gastric cancer cells by affecting E-cadherin cellular localization, cis-dimer formation, molecular assembly and stability of the adherens junctions and cell–cell aggregation, which was further observed in human gastric carcinomas. Interestingly, manipulating this site-specific glycosylation, by preventing Asn-554 from receiving the deleterious branched structures, either by a mutation or by silencing GnT-V, resulted in a protective effect on E-cadherin, precluding its functional dysregulation and contributing to tumor suppression. PMID:26189796

Biological role of site-specific O-glycosylation in cell adhesion activity and phosphorylation of osteopontin.

PubMed

Oyama, Midori; Kariya, Yoshinobu; Kariya, Yukiko; Matsumoto, Kana; Kanno, Mayumi; Yamaguchi, Yoshiki; Hashimoto, Yasuhiro

2018-05-09

Osteopontin (OPN) is an extracellular glycosylated phosphoprotein that promotes cell adhesion by interacting with several integrin receptors. We previously reported that an OPN mutant lacking five O-glycosylation sites (Thr 134 /Thr 138 /Thr 143 /Thr 147 /Thr 152 ) in the threonine/proline-rich region increased cell adhesion activity and phosphorylation compared with the wild type. However, the role of O-glycosylation in cell adhesion activity and phosphorylation of OPN remains to be clarified. Here, we show that site-specific O-glycosylation in the threonine/proline-rich region of OPN affects its cell adhesion activity and phosphorylation independently and/or synergistically. Using site-directed mutagenesis, we found that OPN mutants with substitution sets of Thr 134 /Thr 138 or Thr 143 /Thr 147 /Thr 152 had decreased and increased cell adhesion activity, respectively. In contrast, the introduction of a single mutation into the O-glycosylation sites had no effect on OPN cell adhesion activity. An adhesion assay using function-blocking antibodies against αvβ3 and β1 integrins, as well as αvβ3 integrin-overexpressing A549 cells, revealed that site-specific O-glycosylation affected the association of OPN with the two integrins. Phosphorylation analyses using phos-tag and LC-MS/MS indicated that phosphorylation levels and sites were influenced by the O-glycosylation status, although the number of O-glycosylation sites was not correlated with the phosphorylation level in OPN. Furthermore, a correlation analysis between phosphorylation level and cell adhesion activity in OPN mutants with the site-specific O-glycosylation showed that they were not always correlated. These results provide conclusive evidence of a novel regulatory mechanism of cell adhesion activity and phosphorylation of OPN by site-specific O-glycosylation. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

The moderating role of attachment anxiety on social network site use intensity and social capital.

PubMed

Liu, Haihua; Shi, Junqi; Liu, Yihao; Sheng, Zitong

2013-02-01

This study examined the moderating role of attachment anxiety on the relationship between intensity of social network site use and bridging, bonding, and maintained social capital. Data from 322 undergraduate Chinese students were collected. Hierarchical regression analyses showed positive relationships between online intensity of social network site use and the three types of social capital. Moreover, attachment anxiety moderated the effect of intensity of social network site use on social capital. Specifically, for students with lower attachment anxiety, the relationships between intensity of social network site use and bonding and bridging social capital were stronger than those with higher attachment anxiety. The result suggested that social network sites cannot improve highly anxiously attached individuals' social capital effectively; they may need more face-to-face communications.

Statistical and Economic Techniques for Site-specific Nematode Management.

PubMed

Liu, Zheng; Griffin, Terry; Kirkpatrick, Terrence L

2014-03-01

Recent advances in precision agriculture technologies and spatial statistics allow realistic, site-specific estimation of nematode damage to field crops and provide a platform for the site-specific delivery of nematicides within individual fields. This paper reviews the spatial statistical techniques that model correlations among neighboring observations and develop a spatial economic analysis to determine the potential of site-specific nematicide application. The spatial econometric methodology applied in the context of site-specific crop yield response contributes to closing the gap between data analysis and realistic site-specific nematicide recommendations and helps to provide a practical method of site-specifically controlling nematodes.

Effects of organizational complexity and resources on construction site risk.

PubMed

Forteza, Francisco J; Carretero-Gómez, Jose M; Sesé, Albert

2017-09-01

Our research is aimed at studying the relationship between risk level and organizational complexity and resources on constructions sites. Our general hypothesis is that site complexity increases risk, whereas more resources of the structure decrease risk. A Structural Equation Model (SEM) approach was adopted to validate our theoretical model. To develop our study, 957 building sites in Spain were visited and assessed in 2003-2009. All needed data were obtained using a specific tool developed by the authors to assess site risk, structure and resources (Construction Sites Risk Assessment Tool, or CONSRAT). This tool operationalizes the variables to fit our model, specifically, via a site risk index (SRI) and 10 organizational variables. Our random sample is composed largely of small building sites with general high levels of risk, moderate complexity, and low resources on site. The model obtained adequate fit, and results showed empirical evidence that the factors of complexity and resources can be considered predictors of site risk level. Consequently, these results can help companies, managers of construction and regulators to identify which organizational aspects should be improved to prevent risks on sites and consequently accidents. Copyright © 2017 National Safety Council and Elsevier Ltd. All rights reserved.

Efficacy of generic allometric equations for estimating biomass: a test in Japanese natural forests.

PubMed

Ishihara, Masae I; Utsugi, Hajime; Tanouchi, Hiroyuki; Aiba, Masahiro; Kurokawa, Hiroko; Onoda, Yusuke; Nagano, Masahiro; Umehara, Toru; Ando, Makoto; Miyata, Rie; Hiura, Tsutom

2015-07-01

Accurate estimation of tree and forest biomass is key to evaluating forest ecosystem functions and the global carbon cycle. Allometric equations that estimate tree biomass from a set of predictors, such as stem diameter and tree height, are commonly used. Most allometric equations are site specific, usually developed from a small number of trees harvested in a small area, and are either species specific or ignore interspecific differences in allometry. Due to lack of site-specific allometries, local equations are often applied to sites for which they were not originally developed (foreign sites), sometimes leading to large errors in biomass estimates. In this study, we developed generic allometric equations for aboveground biomass and component (stem, branch, leaf, and root) biomass using large, compiled data sets of 1203 harvested trees belonging to 102 species (60 deciduous angiosperm, 32 evergreen angiosperm, and 10 evergreen gymnosperm species) from 70 boreal, temperate, and subtropical natural forests in Japan. The best generic equations provided better biomass estimates than did local equations that were applied to foreign sites. The best generic equations included explanatory variables that represent interspecific differences in allometry in addition to stem diameter, reducing error by 4-12% compared to the generic equations that did not include the interspecific difference. Different explanatory variables were selected for different components. For aboveground and stem biomass, the best generic equations had species-specific wood specific gravity as an explanatory variable. For branch, leaf, and root biomass, the best equations had functional types (deciduous angiosperm, evergreen angiosperm, and evergreen gymnosperm) instead of functional traits (wood specific gravity or leaf mass per area), suggesting importance of other traits in addition to these traits, such as canopy and root architecture. Inclusion of tree height in addition to stem diameter improved the performance of the generic equation only for stem biomass and had no apparent effect on aboveground, branch, leaf, and root biomass at the site level. The development of a generic allometric equation taking account of interspecific differences is an effective approach for accurately estimating aboveground and component biomass in boreal, temperate, and subtropical natural forests.

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

PubMed Central

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

2018-01-01

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

Site-Specific Carbon Isotopes in Organics

NASA Astrophysics Data System (ADS)

Piasecki, A.; Eiler, J. M.

2012-12-01

Natural organic molecules exhibit a wide range of internal site-specific isotope variation (i.e., molecules with same isotopic substitution type but different site). Such variations are generally unconstrained by bulk isotopic measurements. If known, site-specific variations might constrain temperatures of equilibrium, mechanisms of formation or consumption reactions, and possibly other details. For example, lipids can exhibit carbon isotope differences of up to 30‰ between adjacent carbon sites as a result of fractionations arising during decarboxylation of pyruvate and other steps in lipid biosynthesis(1). We present a method for site-specific carbon isotope analysis of propane, based on high-resolution, multi-collector gas source mass spectrometry, using a novel prototype instrument - the Thermo MAT 253 Ultra. This machine has an inlet system and electron bombardment ion source resembling those in conventional stable isotope gas source mass spectrometers, and the energy filter, magnet, and detector array resembling those in multi-collector ICPMS and TIMS. The detector array has 7 detector positions, 6 of which are movable, and each of which can collect ions with either a faraday cup (read through amplifiers ranging from 107-1012 ohms) or an SEM. High mass resolving power (up to 27,000, MRP = M/dM definition) is achieved through a narrow entrance slit, adjustable from 250 to 5 μm. Such resolution can cleanly separate isobaric interferences between isotopologues of organic molecules having the same cardinal mass (e.g., 13CH3 and 12CH2D). We use this technology to analyze the isotopologues and fragments of propane, and use such data to solve for the site-specific carbon isotope fractionation. By measuring isotopologues of both the one-carbon (13CH3) and the two-carbon (13C12CH4) fragment ion, we can solve for both bulk δ13C and the difference in δ13C between the terminal and central carbon position. We tested this method by analyzing mixtures between natural propane and labeled propane (13CH3-12CH2-12CH3). Results are consistent with the expected relative fractionations between the two fragments, indicating limited 'scrambling' of carbon positions of less than 2% in the source. The limits of precision of this method are currently ~0.5 ‰, sufficient to resolve known or suspected position-specific isotope effects in propane. We have explored the expected temperature-dependent equilibrium isotopic distributions of propane using density functional theory and quantum mechanical models of vibrational isotope effects. These models predict the homogeneous isotope exchange equilibria among the various isotopologues of propane, which include several of a wide range of effects that should be measurable by our methods. At 300 K we predict that the central carbon site is 15‰ higher in δ13C and 95 ‰ higher in δD than the terminal carbon site; similarly the molecule containing both a 13C and D in the central site is enriched by ~120 ‰ relative to a random isotopic distribution at 300 K. These predictions present targets for future experimental and empirical studies of the temperature dependence of isotopic ordering in propane. More generally, the methods we are developing for the study of intramolecular isotopic distributions in propane will serve as a model for future study of similar effects in other organic compounds. [1]DeNiro, Epstein (1977) Science Volume 197, 261-263.

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

PubMed

Huang, Wenkang; Nussinov, Ruth; Zhang, Jian

2017-01-01

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

Information on infantile colic on the World Wide Web.

PubMed

Bailey, Shana D; D'Auria, Jennifer P; Haushalter, Jamie P

2013-01-01

The purpose of this study was to explore and describe the type and quality of information on infantile colic that a parent might access on the World Wide Web. Two checklists were used to evaluate the quality indicators of 24 Web sites and the colic-specific content. Fifteen health information Web sites met more of the quality parameters than the nine commercial sites. Eight Web sites included information about colic and infant abuse, with six being health information sites. The colic-specific content on 24 Web sites reflected current issues and controversies; however, the completeness of the information in light of current evidence varied among the Web sites. Strategies to avoid complications of parental stress or infant abuse were not commonly found on the Web sites. Pediatric professionals must guide parents to reliable colic resources that also include emotional support and understanding of infant crying. A best evidence guideline for the United States would eliminate confusion and uncertainty about which colic therapies are safe and effective for parents and professionals. Copyright © 2013 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

The Human Splicing Factor ASF/SF2 can Specifically Recognize Pre-mRNA 5' Splice Sites

NASA Astrophysics Data System (ADS)

Zuo, Ping; Manley, James L.

1994-04-01

ASF/SF2 is a human protein previously shown to function in in vitro pre-mRNA splicing as an essential factor necessary for all splices and also as an alternative splicing factor, capable of switching selection of 5' splice sites. To begin to study the protein's mechanism of action, we have investigated the RNA binding properties of purified recombinant ASF/SF2. Using UV crosslinking and gel shift assays, we demonstrate that the RNA binding region of ASF/SF2 can interact with RNA in a sequence-specific manner, recognizing the 5' splice site in each of two different pre-mRNAs. Point mutations in the 5' splice site consensus can reduce binding by as much as a factor of 100, with the largest effects observed in competition assays. These findings support a model in which ASF/SF2 aids in the recognition of pre-mRNA 5' splice sites.

Acquisition of background and technical information and class trip planning

NASA Technical Reports Server (NTRS)

Mackinnon, R. M.; Wake, W. H.

1981-01-01

Instructors who are very familiar with a study area, as well as those who are not, find the field trip information acquisition and planning process speeded and made more effective by organizing it in stages. The stage follow a deductive progression: from the associated context region, to the study area, to the specific sample window sites, and from generalized background information on the study region to specific technical data on the environmental and human use systems to be interpreted at each site. On the class trip and in the follow up laboratory, the learning/interpretive process are at first deductive in applying previously learned information and skills to analysis of the study site, then inductive in reading and interpreting the landscape, imagery, and maps of the site, correlating them with information of other samples sites and building valid generalizations about the larger study area, its context region, and other (similar and/or contrasting) regions.

Benefit transfer with limited data: An application to recreational fishing losses from surface mining

EPA Science Inventory

The challenges of applying benefit transfer models to policy sites are often underestimated. Analysts commonly need to estimate site-specific effects for areas that lack data on the number of people who use the resource, intensity of use, and other relevant variables. Yet, the be...

Insight to drug delivery aspects for colorectal cancer.

PubMed

Gulbake, Arvind; Jain, Aviral; Jain, Ashish; Jain, Ankit; Jain, Sanjay K

2016-01-14

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide in human beings. Surgery, chemotherapy, radiotherapy and targeted therapies are the conventional four approaches which are currently used for the treatment of CRC. The site specific delivery of chemotherapeutics to their site of action would increase effectiveness with reducing side effects. Targeted oral drug delivery systems based on polysaccharides are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific drug delivery to colon increases its concentration at the target site, and thus requires a lower dose and hence abridged side effects. Some novel therapies are also briefly discussed in article such as receptor (epidermal growth factor receptor, folate receptor, wheat germ agglutinin, VEGF receptor, hyaluronic acid receptor) based targeting therapy; colon targeted proapoptotic anticancer drug delivery system, gene therapy. Even though good treatment options are available for CRC, the ultimate therapeutic approach is to avert the incidence of CRC. It was also found that CRCs could be prevented by diet and nutrition such as calcium, vitamin D, curcumin, quercetin and fish oil supplements. Immunotherapy and vaccination are used nowadays which are showing better results against CRC.

Evaluation of anesthetic technique on surgical site infections (SSIs) at a single institution.

PubMed

Curry, Craig S; Smith, Kahsi A; Allyn, John W

2014-12-01

To determine whether the previously published relationship between anesthetic technique and rate of surgical site infections (SSIs) was influenced by institution specific effects. Retrospective Review of Quality Assurance and Hospital Epidemiology databases. Metropolitan medical center. The records of 7,751 patients who underwent knee or hip joint replacement from 2004 to 2010 were analyzed. Data regarding anesthetic technique, age, ASA status, gender, postoperative temperature, duration of anesthesia and type of surgery were from the department of anesthesiology quality assurance database and SSI cases were identified from the department of epidemiology database. The impact of anesthetic technique and other variables was assessed using bivariate and multivariate techniques. There was no association of anesthetic technique on the rate of SSI. Duration of anesthesia and ASA status were associated with effects on the rate of SSI. The impact of anesthetic technique on SSI following hip and knee replacement surgery may be site specific and using locally gathered quality data may assist in assessing specific institutional impact. Copyright © 2014 Elsevier Inc. All rights reserved.

Toxicity risk assessment of mercury, DDT and arsenic legacy pollution in sediments: A triad approach under low concentration conditions.

PubMed

Marziali, L; Rosignoli, F; Drago, A; Pascariello, S; Valsecchi, L; Rossaro, B; Guzzella, L

2017-09-01

The determination of sediment toxicity is challenging due to site-specific factors affecting pollutants distribution and bioavailability, especially when contamination levels are close to expected non-effect concentrations. Different lines of evidence and sensitive tools are necessary for a proper toxicity risk assessment. We examined the case study of the Toce River (Northern Italy), where past industrial activities determined Hg, DDT and As enrichment in sediments. A triad approach comprising chemical, ecotoxicological and ecological analyses (benthic invertebrates) was carried out for risk assessment of residual contamination in river sediments. A "blank" site upstream from the industrial site was selected to compare the other sites downstream. Sediment, water and benthic invertebrate samplings were carried out following standard protocols. Results emphasized that despite the emissions of the industrial site ceased about 20years ago, sediments in the downstream section of the river remain contaminated by Hg, DDT and As with concentrations exceeding Threshold Effect Concentrations. A chronic whole-sediment test with Chironomus riparius showed decreased development rate and a lower number of eggs per mass in the contaminated sediments. Benthic community was analyzed with the calculation of integrated (STAR_ICMi) and stressor-specific metrics (SPEAR pesticide and mean sensitivity to Hg), but no significant differences were found between upstream and downstream sites. On the other hand, multivariate analysis (partial Redundancy Analysis and variation partitioning) emphasized a slight impact on invertebrate community, accounting for 5% variation in taxa composition. Results show that legacy contaminants in sediments, even at low concentrations, may be bioavailable and possibly toxic for benthic invertebrates. At low concentration levels, sensitive and site-specific tools need to be developed for a proper risk analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Radioimmunoassays and 2-site immunoradiometric "sandwich" assays: basic principles.

PubMed

Rodbard, D

1988-10-01

The "sandwich" or noncompetitive reagent-excess, 2-site immunoradiometric assay (2-site IRMA), ELISA, USERIA, and related techniques, have several advantages compared with the traditional or competitive radioimmunoassays. IRMAs can provide improved sensitivity and specificity. However, IRMAs present some practical problems with nonspecific binding, increased consumption of antibody, biphasic dose response curve, (high dose hook effect), and may require special techniques for dose response curve analysis. We anticipate considerable growth in the popularity and importance of 2-site IRMA.

Psychotomimetic opiate receptors labeled and visualized with (+)-(/sup 3/H)3-(3-hydroxyphenyl)-N-(1-propyl)piperidine

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

Largent, B.L.; Gundlach, A.L.; Snyder, S.H.

1984-08-01

3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP) has been proposed as a selective dopamine autoreceptor agonist in the central nervous system. This report describes the pharmacology and localization of specific high-affinity binding sites for (+)-(/sup 3/H)3-PPP in brain. The drug specificity of (+)-(/sup 3/H)3-PPP binding is identical to that of sigma receptors, which may mediate psychotomimetic effects of some opiates. Haloperidol and the opioid derivatives, pentazocine, cyclazocine, and SKF 10,047 are potent inhibitors of (+)-(/sup 3/H)3-PPP binding. Stereoselectivity is exhibited for the (+) isomers of cyclazocine and SKF 10.047 at the sigma site, opposite to the stereoselectivity seen at ..mu.., sigma, and k opiate receptors.more » (+)-(/sup 3/H)3-PPP does not label dopamine receptors, as potent dopamine agonists and antagonists are weak inhibitors of binding and the localization of specific (+)-(/sup 3/H)3-PPP binding sites does not parallel that of dopamine neurons. Discrete localizations of (+)-(/sup 3/H)3-PPP binding sites in many brain areas including limbic, midbrain, brainstem, and cerebellar regions may explain psychotomimetic actions of opiates and behavior effects of 3-PPP. 41 references, 2 figures, 1 table.« less

Impairments in Site-Specific AS160 Phosphorylation and Effects of Exercise Training

PubMed Central

Consitt, Leslie A.; Van Meter, Jessica; Newton, Christopher A.; Collier, David N.; Dar, Moahad S.; Wojtaszewski, Jørgen F.P.; Treebak, Jonas T.; Tanner, Charles J.; Houmard, Joseph A.

2013-01-01

The purpose of this study was to determine if site-specific phosphorylation at the level of Akt substrate of 160 kDa (AS160) is altered in skeletal muscle from sedentary humans across a wide range of the adult life span (18–84 years of age) and if endurance- and/or strength-oriented exercise training could rescue decrements in insulin action and skeletal muscle AS160 phosphorylation. A euglycemic-hyperinsulinemic clamp and skeletal muscle biopsies were performed in 73 individuals encompassing a wide age range (18–84 years of age), and insulin-stimulated AS160 phosphorylation was determined. Decrements in whole-body insulin action were associated with impairments in insulin-induced phosphorylation of skeletal muscle AS160 on sites Ser-588, Thr-642, Ser-666, and phospho-Akt substrate, but not Ser-318 or Ser-751. Twelve weeks of endurance- or strength-oriented exercise training increased whole-body insulin action and reversed impairments in AS160 phosphorylation evident in insulin-resistant aged individuals. These findings suggest that a dampening of insulin-induced phosphorylation of AS160 on specific sites in skeletal muscle contributes to the insulin resistance evident in a sedentary aging population and that exercise training is an effective intervention for treating these impairments. PMID:23801578

Repeated cycles of electrical stimulation decrease vasoconstriction and axon-reflex vasodilation to noradrenaline in the human forearm

PubMed Central

Drummond, Peter D

2007-01-01

What is already known about this subject Repeated cycles of electrical stimulation inhibit cutaneous vasoconstriction to noradrenaline, but the mechanism is unknown. Investigating this is important because peripheral electrical stimulation is useful for pain modulation and appears to assist cutaneous wound healing. What this study adds Intermittent, brief electrical stimulation of the forearm over a 10-day period inhibited vasoconstriction and axon-reflex vasodilation to noradrenaline, but did not affect vasoconstriction to vasopressin or axon-reflex vasodilation to histamine. Thus, electrical stimulation may evoke a specific reduction in responsiveness to noradrenaline. Aim To investigate whether desensitization to the vasomotor effects of noradrenaline is a specific effect of electrical stimulation. Methods Three sites on the forearm of 10 healthy volunteers were stimulated with 0.2 mA direct current for 2 min twice daily for 10 days. Noradrenaline and histamine were then displaced from ring-shaped iontophoresis chambers into two of the pretreated sites and two untreated sites on the contralateral forearm. Axon-reflex vasodilation was measured from the centre of the ring described by the iontophoresis chamber with a laser Doppler flowmeter. One or two days later, noradrenaline and vasopressin were introduced into pretreated and untreated sites by iontophoresis, and vasoconstriction at sites of administration was measured in the heated forearm. Results The pretreatment blocked vasoconstriction to noradrenaline [median increase in flow 1%, interquartile range (IR) −41 to 52%; median decrease at the untreated site 53%, IR. −70 to −10%; P < 0.05], but did not block vasoconstriction to vasopressin (median decrease 42% at the untreated site and 45% at the pretreated site). Axon-reflex vasodilation to noradrenaline was diminished at the pretreated site (median increase in flow 33%, IR 2–321%; untreated site 247%, IR 31–1087%; P < 0.05). However, axon-reflex vasodilation to histamine did not differ significantly between the pretreated site (median increase 1085%) and the untreated site (median increase 1345%). Conclusions The conditioning pretreatment appears to evoke a specific decrease in responsiveness to noradrenaline. Repeated cycles of electrical stimulation may downregulate neural and vascular responses to noradrenaline by repetitively activating cutaneous sympathetic nerve fibres. PMID:17441931

Time vs. Money: A Quantitative Evaluation of Monitoring Frequency vs. Monitoring Duration.

PubMed

McHugh, Thomas E; Kulkarni, Poonam R; Newell, Charles J

2016-09-01

The National Research Council has estimated that over 126,000 contaminated groundwater sites are unlikely to achieve low ug/L clean-up goals in the foreseeable future. At these sites, cost-effective, long-term monitoring schemes are needed in order to understand the long-term changes in contaminant concentrations. Current monitoring optimization schemes rely on site-specific evaluations to optimize groundwater monitoring frequency. However, when using linear regression to estimate the long-term zero-order or first-order contaminant attenuation rate, the effect of monitoring frequency and monitoring duration on the accuracy and confidence for the estimated attenuation rate is not site-specific. For a fixed number of monitoring events, doubling the time between monitoring events (e.g., changing from quarterly monitoring to semi-annual monitoring) will double the accuracy of estimated attenuation rate. For a fixed monitoring frequency (e.g., semi-annual monitoring), increasing the number of monitoring events by 60% will double the accuracy of the estimated attenuation rate. Combining these two factors, doubling the time between monitoring events (e.g., quarterly monitoring to semi-annual monitoring) while decreasing the total number of monitoring events by 38% will result in no change in the accuracy of the estimated attenuation rate. However, the time required to collect this dataset will increase by 25%. Understanding that the trade-off between monitoring frequency and monitoring duration is not site-specific should simplify the process of optimizing groundwater monitoring frequency at contaminated groundwater sites. © 2016 The Authors. Groundwater published by Wiley Periodicals, Inc. on behalf of National Ground Water Association.

Quantifying Construction Site Sediment Discharge Risk and Treatment Potential

NASA Astrophysics Data System (ADS)

Ferrell, L.; Beighley, R. E.

2006-12-01

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

Intragenic DNA methylation and BORIS-mediated cancer-specific splicing contribute to the Warburg effect

PubMed Central

Singh, Smriti; Narayanan, Sathiya Pandi; Biswas, Kajal; Gupta, Amit; Ahuja, Neha; Yadav, Sandhya; Panday, Rajendra Kumar; Samaiya, Atul; Sharan, Shyam K.

2017-01-01

Aberrant alternative splicing and epigenetic changes are both associated with various cancers, but epigenetic regulation of alternative splicing in cancer is largely unknown. Here we report that the intragenic DNA methylation-mediated binding of Brother of Regulator of Imprinted Sites (BORIS) at the alternative exon of Pyruvate Kinase (PKM) is associated with cancer-specific splicing that promotes the Warburg effect and breast cancer progression. Interestingly, the inhibition of DNA methylation, BORIS depletion, or CRISPR/Cas9-mediated deletion of the BORIS binding site leads to a splicing switch from cancer-specific PKM2 to normal PKM1 isoform. This results in the reversal of the Warburg effect and the inhibition of breast cancer cell growth, which may serve as a useful approach to inhibit the growth of breast cancer cells. Importantly, our results show that in addition to PKM splicing, BORIS also regulates the alternative splicing of several genes in a DNA methylation-dependent manner. Our findings highlight the role of intragenic DNA methylation and DNA binding protein BORIS in cancer-specific splicing and its role in tumorigenesis. PMID:29073069

Oxidative phosphorylation. The relation between the specific binding of trimethlytin and triethyltin to mitochondria and their effects on various mitochondrial functions

PubMed Central

Aldridge, W. N.; Street, B. W.

1971-01-01

1. A binding site (site 1) is present in mitochondria with affinity for trimethyltin and triethyltin adequate for a site to which they could be attached when the processes of energy conservation are inhibited. 2. The quantitative relationships between the binding of trimethyltin and triethyltin to site 1 and their effects on various mitochondrial functions have been examined. 3. ATP synthesis linked to the oxidation of pyruvate, succinate and intramitochondrial substrate, ATP synthesis and oxygen uptake (succinate or pyruvate as substrate) stimulated by uncoupling agents are all inhibited by trimethyltin and triethyltin; when inhibition is less than 50% the ratio (percentage inhibition)/(percentage of binding site 1 complexed) is approx. 10:1. 4. ATP synthesis linked to the oxidation of reduced cytochrome c (ascorbate+NNN′N′-tetramethyl-p-phenylenediamine), ATP hydrolysis and oxygen uptake in the presence of low concentrations of trimethyltin and triethyltin approach zero activity as the proportion of binding site 1 complexed approaches 100%. 5. Possible interpretations of these findings are discussed with reference to published arrangements for coupling of electron transport to ATP synthesis and also to our present knowledge of the chemical and biological specificity of trialkyltin compounds. PMID:5126473

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

PubMed

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

2018-06-01

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

Quantum mechanical calculation of electric fields and vibrational Stark shifts at active site of human aldose reductase

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

Wang, Xianwei; State Key Laboratory of Precision Spectroscopy, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062; Zhang, John Z. H.

2015-11-14

Recent advance in biophysics has made it possible to directly measure site-specific electric field at internal sites of proteins using molecular probes with C = O or C≡N groups in the context of vibrational Stark effect. These measurements directly probe changes of electric field at specific protein sites due to, e.g., mutation and are very useful in protein design. Computational simulation of the Stark effect based on force fields such as AMBER and OPLS, while providing good insight, shows large errors in comparison to experimental measurement due to inherent difficulties associated with point charge based representation of force fields. Inmore » this study, quantum mechanical calculation of protein’s internal electrostatic properties and vibrational Stark shifts was carried out by using electrostatically embedded generalized molecular fractionation with conjugate caps method. Quantum calculated change of mutation-induced electric field and vibrational Stark shift is reported at the internal probing site of enzyme human aldose reductase. The quantum result is in much better agreement with experimental data than those predicted by force fields, underscoring the deficiency of traditional point charge models describing intra-protein electrostatic properties.« less

SU-E-T-420: Failure Effects Mode Analysis for Trigeminal Neuralgia Frameless Radiosurgery

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

Howe, J

2015-06-15

Purpose: Functional radiosurgery has been used successfully in the treatment of trigeminal neuralgia but presents significant challenges to ensuring the high prescription dose is delivered accurately. A review of existing practice should help direct the focus of quality improvement for this treatment regime. Method: Failure modes and effects analysis was used to identify the processes in preparing radiosurgery treatment for TN. The map was developed by a multidisciplinary team including: neurosurgeon, radiation oncology, physicist and therapist. Potential failure modes were identified for each step in the process map as well as potential causes and end effect. A risk priority numbermore » was assigned to each cause. Results: The process map identified 66 individual steps (see attached supporting document). Corrective actions were developed for areas of high risk priority number. Wrong site treatment is at higher risk for trigeminal neuralgia treatment due to the lack of site specific pathologic imaging on MR and CT – additional site specific checks were implemented to minimize the risk of wrong site treatment. Failed collision checks resulted from an insufficient collision model in the treatment planning system and a plan template was developed to address this problem. Conclusion: Failure modes and effects analysis is an effective tool for developing quality improvement in high risk radiotherapy procedures such as functional radiosurgery.« less

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

NASA Astrophysics Data System (ADS)

El Hussain, I. W.

2017-12-01

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

The active site architecture in peroxiredoxins: a case study on Mycobacterium tuberculosis AhpE.

PubMed

Pedre, Brandán; van Bergen, Laura A H; Palló, Anna; Rosado, Leonardo A; Dufe, Veronica Tamu; Molle, Inge Van; Wahni, Khadija; Erdogan, Huriye; Alonso, Mercedes; Proft, Frank De; Messens, Joris

2016-08-11

Peroxiredoxins catalyze the reduction of peroxides, a process of vital importance to survive oxidative stress. A nucleophilic cysteine, also known as the peroxidatic cysteine, is responsible for this catalytic process. We used the Mycobacterium tuberculosis alkyl hydroperoxide reductase E (MtAhpE) as a model to investigate the effect of the chemical environment on the specificity of the reaction. Using an integrative structural (R116A - PDB ; F37H - PDB ), kinetic and computational approach, we explain the mutational effects of key residues in its environment. This study shows that the active site residues are specifically oriented to create an environment which selectively favours a reaction with peroxides.

Impact of wildfires on regional air pollution | Science Inventory ...

EPA Pesticide Factsheets

We examine the impact of wildfires and agricultural/prescribed burning on regional air pollution and Air Quality Index (AQI) between 2006 and 2013. We define daily regional air pollution using monitoring sites for ozone (n=1595), PM2.5 collected by Federal Reference Method (n=1058), and constituents of PM2.5 from the Interagency Monitoring of PROtected Visual Environment (IMPROVE) network (n=264) and use satellite image analysis from the NOAA Hazard Mapping System (HMS) to determine days on which visible smoke plumes are detected in the vertical column of the monitoring site. To examine the impact of smoke from these fires on regional air pollution we use a two stage approach, accounting for within site (1st stage) and between site (2nd stage) variations. At the first stage we estimate a monitor-specific plume day effect describing the relative change in pollutant concentrations on the days impacted by smoke plume while accounting for confounding effects of season and temperature_. At the second stage we combine monitor-specific plume day effects with a Bayesian hierarchical model and estimate a pooled nationally-averaged effect. HMS visible smoke plumes were detected on 6% of ozone, 8% of PM2.5 and 6% of IMPROVE network monitoring days. Our preliminary results indicate that the long range transport of air pollutants from wildfires and prescribed burns increase ozone concentration by 11% and PM2.5 mass by 34%. On all of the days where monitoring sites were AQI

The U.S. Department of Energy's Regulatory and Evaluation Framework for Demonstrating Radiation Protection of the Environment: Implementation at the Hanford Site

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

Antonio, Ernest J.; Tiller, Brett L.; Domotor, S. L.

2005-08-01

Abstract. In 2001, a multi-agency study was conducted to characterize potential environmental effects from radiological and chemical contaminants on the near-shore environment of the Columbia River at the 300 Area of the U.S. Department of Energy’s Hanford Site. Historically, the 300 Area was the location of nuclear fuel fabrication and was the main location for research and development activities from the 1940s until the late 1980s. During past waste handling practices uranium, copper, and other heavy metals were routed to liquid waste streams and ponds near the Columbia River shoreline. The Washington State Department of Health and the Pacific Northwestmore » National Laboratory’s Surface Environmental Surveillance Project sampled various environmental components including river water, riverbank spring water, sediment, fishes, crustaceans, bivalve mollusks, aquatic insects, riparian vegetation, small mammals, and terrestrial invertebrates for analyses of radiological and chemical constituents. The radiological analysis results for water and sediment were used as initial input into the RESRAD BIOTA. The RESRAD BIOTA code showed that maximum radionuclide concentrations measured in water and sediment were lower than the initial screening criteria for concentrations to produce dose rates at existing or proposed limits. Radionuclide concentrations measured in biota samples were used to calculate site-specific bioaccumulation coefficients (Biv) to test the utility of the RESRAD BIOTA’s site-specific screening phase. To further evaluate site-specific effects, the default Relative Biological Effect (RBE) for internal alpha particle emissions was reduced by half and the program’s kinetic/allometric calculation approach was initiated. The subsequent calculations showed the initial RESRAD BIOTA results to be conservative, which is appropriate for screening purposes.« less

Improving vaccine-related pain, distress or fear in healthy children and adolescents - a systematic search of patient-focused interventions.

PubMed

Lee, Vivian Y; Caillaud, Corinne; Fong, Jacqueline; Edwards, Kate M

2018-05-24

The WHO recently highlighted the need for research into potential interventions that can be used to mitigate pain during mass vaccinations, in addition to interventions specific for adolescents. The current review examines the literature on potential interventions that can be used during mass vaccination settings in healthy individuals between the ages of 4 and 15 years old. Criteria for inclusion were: 1)participants between the ages of 4-15 years, 2)interventions that were patient-focused, 3)vaccinations in healthy individuals, 4)outcome measures to include self-reported pain, fear or distress. Twenty-seven articles were identified with a total of 31 interventions. Eleven interventions used injection-site specific interventions, 17 used patient-led interventions and three used a combination of both site-specific and patient-led interventions. Interventions using coolant and vibration together, as well as a combination of site-specific and patient-led interventions, showed the most consistent effects in reducing self-reported pain, fear or distress.

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

PubMed Central

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

2015-01-01

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

Site-Specifically Labeled Immunoconjugates for Molecular Imaging--Part 2: Peptide Tags and Unnatural Amino Acids.

PubMed

Adumeau, Pierre; Sharma, Sai Kiran; Brent, Colleen; Zeglis, Brian M

2016-04-01

Molecular imaging using radioisotope- or fluorophore-labeled antibodies is increasingly becoming a critical component of modern precision medicine. Yet despite this promise, the vast majority of these immunoconjugates are synthesized via the random coupling of amine-reactive bifunctional probes to lysines within the antibody, a process that can result in heterogeneous and poorly defined constructs with suboptimal pharmacological properties. In an effort to circumvent these issues, the last 5 years have played witness to a great deal of research focused on the creation of effective strategies for the site-specific attachment of payloads to antibodies. These chemoselective modification methods yield immunoconjugates that are more homogenous and better defined than constructs created using traditional synthetic approaches. Moreover, site-specifically labeled immunoconjugates have also been shown to exhibit superior in vivo behavior compared to their randomly modified cousins. The over-arching goal of this two-part review is to provide a broad yet detailed account of the various site-specific bioconjugation approaches that have been used to create immunoconjugates for positron emission tomography (PET), single photon emission computed tomography (SPECT), and fluorescence imaging. In Part 1, we covered site-specific bioconjugation techniques based on the modification of cysteine residues and the chemoenzymatic manipulation of glycans. In Part 2, we will detail two families of bioconjugation approaches that leverage biochemical tools to achieve site-specificity. First, we will discuss modification methods that employ peptide tags either as sites for enzyme-catalyzed ligations or as radiometal coordination architectures. And second, we will examine bioconjugation strategies predicated on the incorporation of unnatural or non-canonical amino acids into antibodies via genetic engineering. Finally, we will compare the advantages and disadvantages of the modification strategies covered in both parts of the review and offer a brief discussion of the overall direction of the field.

Development, Evaluation and Implementation of Chief Complaint Groupings to Activate Data Collection: A Multi-Center Study of Clinical Decision Support for Children with Head Trauma.

PubMed

Deakyne, S J; Bajaj, L; Hoffman, J; Alessandrini, E; Ballard, D W; Norris, R; Tzimenatos, L; Swietlik, M; Tham, E; Grundmeier, R W; Kuppermann, N; Dayan, P S

2015-01-01

Overuse of cranial computed tomography scans in children with blunt head trauma unnecessarily exposes them to radiation. The Pediatric Emergency Care Applied Research Network (PECARN) blunt head trauma prediction rules identify children who do not require a computed tomography scan. Electronic health record (EHR) based clinical decision support (CDS) may effectively implement these rules but must only be provided for appropriate patients in order to minimize excessive alerts. To develop, implement and evaluate site-specific groupings of chief complaints (CC) that accurately identify children with head trauma, in order to activate data collection in an EHR. As part of a 13 site clinical trial comparing cranial computed tomography use before and after implementation of CDS, four PECARN sites centrally developed and locally implemented CC groupings to trigger a clinical trial alert (CTA) to facilitate the completion of an emergency department head trauma data collection template. We tested and chose CC groupings to attain high sensitivity while maintaining at least moderate specificity. Due to variability in CCs available, identical groupings across sites were not possible. We noted substantial variability in the sensitivity and specificity of seemingly similar CC groupings between sites. The implemented CC groupings had sensitivities greater than 90% with specificities between 75-89%. During the trial, formal testing and provider feedback led to tailoring of the CC groupings at some sites. CC groupings can be successfully developed and implemented across multiple sites to accurately identify patients who should have a CTA triggered to facilitate EHR data collection. However, CC groupings will necessarily vary in order to attain high sensitivity and moderate-to-high specificity. In future trials, the balance between sensitivity and specificity should be considered based on the nature of the clinical condition, including prevalence and morbidity, in addition to the goals of the intervention being considered.

A fractured rock geophysical toolbox method selection tool

USGS Publications Warehouse

Day-Lewis, F. D.; Johnson, C.D.; Slater, L.D.; Robinson, J.L.; Williams, J.H.; Boyden, C.L.; Werkema, D.D.; Lane, J.W.

2016-01-01

Geophysical technologies have the potential to improve site characterization and monitoring in fractured rock, but the appropriate and effective application of geophysics at a particular site strongly depends on project goals (e.g., identifying discrete fractures) and site characteristics (e.g., lithology). No method works at every site or for every goal. New approaches are needed to identify a set of geophysical methods appropriate to specific project goals and site conditions while considering budget constraints. To this end, we present the Excel-based Fractured-Rock Geophysical Toolbox Method Selection Tool (FRGT-MST). We envision the FRGT-MST (1) equipping remediation professionals with a tool to understand what is likely to be realistic and cost-effective when contracting geophysical services, and (2) reducing applications of geophysics with unrealistic objectives or where methods are likely to fail.

Analysis of illegitimate genomic integration mediated by zinc-finger nucleases: implications for specificity of targeted gene correction

PubMed Central

2010-01-01

Background Formation of site specific genomic double strand breaks (DSBs), induced by the expression of a pair of engineered zinc-finger nucleases (ZFNs), dramatically increases the rates of homologous recombination (HR) between a specific genomic target and a donor plasmid. However, for the safe use of ZFN induced HR in practical applications, possible adverse effects of the technology such as cytotoxicity and genotoxicity need to be well understood. In this work, off-target activity of a pair of ZFNs has been examined by measuring the ratio between HR and illegitimate genomic integration in cells that are growing exponentially, and in cells that have been arrested in the G2/M phase. Results A reporter cell line that contained consensus ZFN binding sites in an enhanced green fluorescent protein (EGFP) reporter gene was used to measure ratios between HR and non-homologous integration of a plasmid template. Both in human cells (HEK 293) containing the consensus ZFN binding sites and in cells lacking the ZFN binding sites, a 3.5 fold increase in the level of illegitimate integration was observed upon ZFN expression. Since the reporter gene containing the consensus ZFN target sites was found to be intact in cells where illegitimate integration had occurred, increased rates of illegitimate integration most likely resulted from the formation of off-target genomic DSBs. Additionally, in a fraction of the ZFN treated cells the co-occurrence of both specific HR and illegitimate integration was observed. As a mean to minimize unspecific effects, cell cycle manipulation of the target cells by induction of a transient G2/M cell cycle arrest was shown to stimulate the activity of HR while having little effect on the levels of illegitimate integration, thus resulting in a nearly eight fold increase in the ratio between the two processes. Conclusions The demonstration that ZFN expression, in addition to stimulating specific gene targeting by HR, leads to increased rates of illegitimate integration emphasizes the importance of careful characterization of ZFN treated cells. In order to reduce off-target events, reversible cell cycle arrest of the target cells in the G2/M phase is an efficient way for increasing the ratio between specific HR and illegitimate integration. PMID:20459736

Mapping mutational effects along the evolutionary landscape of HIV envelope

PubMed Central

Hilton, Sarah K; Overbaugh, Julie

2018-01-01

The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at >100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains. PMID:29590010

Generalized theory on the mechanism of site-specific DNA-protein interactions

NASA Astrophysics Data System (ADS)

Niranjani, G.; Murugan, R.

2016-05-01

We develop a generalized theoretical framework on the binding of transcription factor proteins (TFs) with specific sites on DNA that takes into account the interplay of various factors regarding overall electrostatic potential at the DNA-protein interface, occurrence of kinetic traps along the DNA sequence, presence of other roadblock protein molecules along DNA and crowded environment, conformational fluctuations in the DNA binding domains (DBDs) of TFs, and the conformational state of the DNA. Starting from a Smolochowski type theoretical framework on site-specific binding of TFs we logically build our model by adding the effects of these factors one by one. Our generalized two-step model suggests that the electrostatic attractive forces present inbetween the positively charged DBDs of TFs and the negatively charged phosphate backbone of DNA, along with the counteracting shielding effects of solvent ions, is the core factor that creates a fluidic type environment at the DNA-protein interface. This in turn facilitates various one-dimensional diffusion (1Dd) processes such as sliding, hopping and intersegmental transfers. These facilitating processes as well as flipping dynamics of conformational states of DBDs of TFs between stationary and mobile states can enhance the 1Dd coefficient on a par with three-dimensional diffusion (3Dd). The random coil conformation of DNA also plays critical roles in enhancing the site-specific association rate. The extent of enhancement over the 3Dd controlled rate seems to be directly proportional to the maximum possible 1Dd length. We show that the overall site-specific binding rate scales with the length of DNA in an asymptotic way. For relaxed DNA, the specific binding rate will be independent of the length of DNA as length increases towards infinity. For condensed DNA as in in vivo conditions, the specific binding rate depends on the length of DNA in a turnover way with a maximum. This maximum rate seems to scale with the maximum possible 1Dd length of TFs in a square root manner. Results suggest that 1Dd processes contribute much less to the enhancement of specific binding rate under in vivo conditions for condensed DNA. There exists a critical length of binding stretch of TFs beyond which the probability associated with the random occurrence of similar specific binding sites will be close to zero. TFs in natural systems from prokaryotes to eukaryotes seem to handle sequence-mediated kinetic traps via increasing the length of their recognition stretch or combinatorial binding. TFs overcome the hurdles of roadblocks via switching efficiently between sliding, hopping and intersegmental transfer modes. The site-specific binding rate as well as the maximum possible 1Dd length seem to be directly proportional to the square root of the probability (p R) of finding a nonspecific binding site to be free from dynamic roadblocks. Here p R seems to be a function of the number of nsbs available per DNA binding protein (ϕ) inside the living cell. It seems that p R  >  0.8 when ϕ  >  10 which is true for the Escherichia coli cell system.

Estrogen receptor alpha phosphorylation and its functional impact in human breast cancer.

PubMed

Anbalagan, Muralidharan; Rowan, Brian G

2015-12-15

Estrogen receptor α (ERα) is a member of the nuclear receptor superfamily of transcription factors that regulates cell proliferation, differentiation and homeostasis in various tissues. Sustained exposure to estrogen/estradiol (E2) increases the risk of breast, endometrial and ovarian cancers. ERα function is also regulated by phosphorylation through various kinase signaling pathways that will impact various ERα functions including chromatin interaction, coregulator recruitment and gene expression, as well impact breast tumor growth/morphology and breast cancer patient response to endocrine therapy. However, many of the previously characterized ERα phosphorylation sites do not fully explain the impact of receptor phosphorylation on ERα function. This review discusses work from our laboratory toward understanding a role of ERα site-specific phosphorylation in ERα function and breast cancer. The key findings discussed in this review are: (1) the effect of site specific ERα phosphorylation on temporal recruitment of ERα and unique coactivator complexes to specific genes; (2) the impact of stable disruption of ERα S118 and S167 phosphorylation in breast cancer cells on eliciting unique gene expression profiles that culminate in significant effects on breast cancer growth/morphology/migration/invasion; (3) the Src kinase signaling pathway that impacts ERα phosphorylation to alter ERα function; and (4) circadian disruption by light exposure at night leading to elevated ERK1/2 and Src kinase and phosphorylation of ERα, concomitant with tamoxifen resistance in breast tumor models. Results from these studies demonstrate that even changes to single ERα phosphorylation sites can have a profound impact on ERα function in breast cancer. Future work will extend beyond single site phosphorylation analysis toward identification of specific patterns/profiles of ERα phosphorylation under different physiological/pharmacological conditions to understand how common phosphorylation profiles in breast cancer program specific physiological endpoints such as growth, apoptosis, migration/invasion, and endocrine therapy response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cre/lox-Recombinase-Mediated Cassette Exchange for Reversible Site-Specific Genomic Targeting of the Disease Vector, Aedes aegypti.

PubMed

Häcker, Irina; Harrell Ii, Robert A; Eichner, Gerrit; Pilitt, Kristina L; O'Brochta, David A; Handler, Alfred M; Schetelig, Marc F

2017-03-07

Site-specific genome modification (SSM) is an important tool for mosquito functional genomics and comparative gene expression studies, which contribute to a better understanding of mosquito biology and are thus a key to finding new strategies to eliminate vector-borne diseases. Moreover, it allows for the creation of advanced transgenic strains for vector control programs. SSM circumvents the drawbacks of transposon-mediated transgenesis, where random transgene integration into the host genome results in insertional mutagenesis and variable position effects. We applied the Cre/lox recombinase-mediated cassette exchange (RMCE) system to Aedes aegypti, the vector of dengue, chikungunya, and Zika viruses. In this context we created four target site lines for RMCE and evaluated their fitness costs. Cre-RMCE is functional in a two-step mechanism and with good efficiency in Ae. aegypti. The advantages of Cre-RMCE over existing site-specific modification systems for Ae. aegypti, phiC31-RMCE and CRISPR, originate in the preservation of the recombination sites, which 1) allows successive modifications and rapid expansion or adaptation of existing systems by repeated targeting of the same site; and 2) provides reversibility, thus allowing the excision of undesired sequences. Thereby, Cre-RMCE complements existing genomic modification tools, adding flexibility and versatility to vector genome targeting.

Perimeter intrusion detection and assessment system

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

Eaton, M.J.; Jacobs, J.; McGovern, D.E.

1977-11-01

To obtain an effective perimeter intrusion detection system requires careful sensor selection, procurement, and installation. The selection process involves a thorough understanding of the unique site features and how these features affect the performance of each type of sensor. It is necessary to develop procurement specifications to establish acceptable sensor performance limits. Careful explanation and inspection of critical installation dimensions is required during on-site construction. The implementation of these activities at a particular site is discussed.

Modulating the activity of protein conjugated to gold nanoparticles by site-directed orientation and surface density of bound protein.

PubMed

Liu, Feng; Wang, Lei; Wang, Hongwei; Yuan, Lin; Li, Jingwen; Brash, John Law; Chen, Hong

2015-02-18

The key property of protein-nanoparticle conjugates is the bioactivity of the protein. The ability to accurately modulate the activity of protein on the nanoparticles at the interfaces is important in many applications. In the work reported here, modulation of the activity of protein-gold nanoparticle (AuNP) conjugates by specifically orienting the protein and by varying the surface density of the protein was investigated. Different orientations were achieved by introducing cysteine (Cys) residues at specific sites for binding to gold. We chose Escherichia coli inorganic pyrophosphatase (PPase) as a model protein and used site-directed mutagenesis to generate two mutant types (MTs) with a single Cys residue on the surface: MT1 with Cys near the active center and MT2 with Cys far from the active center. The relative activities of AuNP conjugates with wild type (WT), MT1, and MT2 were found to be 44.8%, 68.8%, and 91.2% of native PPase in aqueous solution. Site-directed orientation with the binding site far from the active center thus allowed almost complete preservation of the protein activity. The relative activity of WT and MT2 conjugates did not change with the surface density of the protein, while that of MT1 increased significantly with increasing surface density. These results demonstrate that site-directed orientation and surface density can both modulate the activity of proteins conjugated to AuNP and that orientation has a greater effect than density. Furthermore, increasing the surface density of the specifically oriented protein MT2, while having no significant effect on the specific activity of the protein, still allowed increased protein loading on the AuNP and thus increased the total protein activity. This is of great importance in the study on the interface of protein and nanoparticle and the applications for enzyme immobilization, drug delivery, and biocatalysis.

Soil respiration response to climate change in Pacific Northwest prairies is mediated by a regional Mediterranean climate gradient.

PubMed

Reynolds, Lorien L; Johnson, Bart R; Pfeifer-Meister, Laurel; Bridgham, Scott D

2015-01-01

Soil respiration is expected to increase with rising global temperatures but the degree of response may depend on soil moisture and other local factors. Experimental climate change studies from single sites cannot discern whether an observed response is site-dependent or generalizable. To deconvolve site-specific vs. regional climatic controls, we examined soil respiration for 18 months along a 520 km climate gradient in three Pacific Northwest, USA prairies that represents increasingly severe Mediterranean conditions from north to south. At each site we implemented a fully factorial combination of 2.5-3 °C warming and 20% added precipitation intensity. The response of soil respiration to warming was driven primarily by the latitudinal climate gradient and not site-specific factors. Warming increased respiration at all sites during months when soil moisture was not limiting. However, these gains were offset by reductions in respiration during seasonal transitions and summer drought due to lengthened periods of soil moisture limitation. The degree of this offset varied along the north-south climate gradient such that in 2011 warming increased cumulative annual soil respiration 28.6% in the northern site, 13.5% in the central site, and not at all in the southern site. Precipitation also stimulated soil respiration more frequently in the south, consistent with an increased duration of moisture limitation. The best predictors of soil respiration in nonlinear models were the Normalized Difference Vegetation Index (NDVI), antecedent soil moisture, and temperature but these models provided biased results at high and low soil respiration. NDVI was an effective integrator of climate and site differences in plant productivity in terms of their combined effects on soil respiration. Our results suggest that soil moisture limitation can offset the effect of warming on soil respiration, and that greater growing-season moisture limitation would constrain cumulative annual responses to warming. © 2014 John Wiley & Sons Ltd.

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

PubMed

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

2012-01-01

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

Computational Prediction of Protein Epsilon Lysine Acetylation Sites Based on a Feature Selection Method.

PubMed

Gao, JianZhao; Tao, Xue-Wen; Zhao, Jia; Feng, Yuan-Ming; Cai, Yu-Dong; Zhang, Ning

2017-01-01

Lysine acetylation, as one type of post-translational modifications (PTM), plays key roles in cellular regulations and can be involved in a variety of human diseases. However, it is often high-cost and time-consuming to use traditional experimental approaches to identify the lysine acetylation sites. Therefore, effective computational methods should be developed to predict the acetylation sites. In this study, we developed a position-specific method for epsilon lysine acetylation site prediction. Sequences of acetylated proteins were retrieved from the UniProt database. Various kinds of features such as position specific scoring matrix (PSSM), amino acid factors (AAF), and disorders were incorporated. A feature selection method based on mRMR (Maximum Relevance Minimum Redundancy) and IFS (Incremental Feature Selection) was employed. Finally, 319 optimal features were selected from total 541 features. Using the 319 optimal features to encode peptides, a predictor was constructed based on dagging. As a result, an accuracy of 69.56% with MCC of 0.2792 was achieved. We analyzed the optimal features, which suggested some important factors determining the lysine acetylation sites. We developed a position-specific method for epsilon lysine acetylation site prediction. A set of optimal features was selected. Analysis of the optimal features provided insights into the mechanism of lysine acetylation sites, providing guidance of experimental validation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Modulation of Cardiac Ryanodine Receptor Channels by Alkaline Earth Cations

PubMed Central

Diaz-Sylvester, Paula L.; Porta, Maura; Copello, Julio A.

2011-01-01

Cardiac ryanodine receptor (RyR2) function is modulated by Ca2+ and Mg2+. To better characterize Ca2+ and Mg2+ binding sites involved in RyR2 regulation, the effects of cytosolic and luminal earth alkaline divalent cations (M2+: Mg2+, Ca2+, Sr2+, Ba2+) were studied on RyR2 from pig ventricle reconstituted in bilayers. RyR2 were activated by M2+ binding to high affinity activating sites at the cytosolic channel surface, specific for Ca2+ or Sr2+. This activation was interfered by Mg2+ and Ba2+ acting at low affinity M2+-unspecific binding sites. When testing the effects of luminal M2+ as current carriers, all M2+ increased maximal RyR2 open probability (compared to Cs+), suggesting the existence of low affinity activating M2+-unspecific sites at the luminal surface. Responses to M2+ vary from channel to channel (heterogeneity). However, with luminal Ba2+or Mg2+, RyR2 were less sensitive to cytosolic Ca2+ and caffeine-mediated activation, openings were shorter and voltage-dependence was more marked (compared to RyR2 with luminal Ca2+or Sr2+). Kinetics of RyR2 with mixtures of luminal Ba2+/Ca2+ and additive action of luminal plus cytosolic Ba2+ or Mg2+ suggest luminal M2+ differentially act on luminal sites rather than accessing cytosolic sites through the pore. This suggests the presence of additional luminal activating Ca2+/Sr2+-specific sites, which stabilize high Po mode (less voltage-dependent) and increase RyR2 sensitivity to cytosolic Ca2+ activation. In summary, RyR2 luminal and cytosolic surfaces have at least two sets of M2+ binding sites (specific for Ca2+ and unspecific for Ca2+/Mg2+) that dynamically modulate channel activity and gating status, depending on SR voltage. PMID:22039534

Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling.

PubMed

Brand, Martin D

2016-11-01

This review examines the generation of reactive oxygen species by mammalian mitochondria, and the status of different sites of production in redox signaling and pathology. Eleven distinct mitochondrial sites associated with substrate oxidation and oxidative phosphorylation leak electrons to oxygen to produce superoxide or hydrogen peroxide: oxoacid dehydrogenase complexes that feed electrons to NAD + ; respiratory complexes I and III, and dehydrogenases, including complex II, that use ubiquinone as acceptor. The topologies, capacities, and substrate dependences of each site have recently clarified. Complex III and mitochondrial glycerol 3-phosphate dehydrogenase generate superoxide to the external side of the mitochondrial inner membrane as well as the matrix, the other sites generate superoxide and/or hydrogen peroxide exclusively in the matrix. These different site-specific topologies are important for redox signaling. The net rate of superoxide or hydrogen peroxide generation depends on the substrates present and the antioxidant systems active in the matrix and cytosol. The rate at each site can now be measured in complex substrate mixtures. In skeletal muscle mitochondria in media mimicking muscle cytosol at rest, four sites dominate, two in complex I and one each in complexes II and III. Specific suppressors of two sites have been identified, the outer ubiquinone-binding site in complex III (site III Qo ) and the site in complex I active during reverse electron transport (site I Q ). These suppressors prevent superoxide/hydrogen peroxide production from a specific site without affecting oxidative phosphorylation, making them excellent tools to investigate the status of the sites in redox signaling, and to suppress the sites to prevent pathologies. They allow the cellular roles of mitochondrial superoxide/hydrogen peroxide production to be investigated without catastrophic confounding bioenergetic effects. They show that sites III Qo and I Q are active in cells and have important roles in redox signaling (e.g. hypoxic signaling and ER-stress) and in causing oxidative damage in a variety of biological contexts. Copyright © 2016 Elsevier Inc. All rights reserved.

Color-specific conditioning effects due to both orange and blue stimuli are observed in a Halobacterium salinarum strain devoid of putative methylatable sites on HtrI.

PubMed

Lucia, S; Cercignani, G; Frediani, A; Petracchi, D

2003-01-01

Behavioral responses of Halobacterium salinarum appear as changes in the frequency of motion reversals. Turning on orange light decreases the reversal frequency, whereas blue light induces reversals. Light pulses normally induce the same response as step-up stimuli. However, anomalous behavioral reactions, including inverse responses, are seen when stimuli are applied in sequence. The occurrence of a prior stimulus is conditioning for successive stimulation on a time scale of the same order of adaptational processes. These prolonged conditioning effects are color-specific. The only adaptation process identified so far is methylation of the transducers, and this could be somehow color-specific. Therefore we tested for the behavioral anomalies in a mutant in which all methylation sites on the transducer have been eliminated. The results show that behavioral anomalies are unaffected by the absence of methylation processes on the transducer.

HIV-1 protease cleavage site prediction based on two-stage feature selection method.

PubMed

Niu, Bing; Yuan, Xiao-Cheng; Roeper, Preston; Su, Qiang; Peng, Chun-Rong; Yin, Jing-Yuan; Ding, Juan; Li, HaiPeng; Lu, Wen-Cong

2013-03-01

Knowledge of the mechanism of HIV protease cleavage specificity is critical to the design of specific and effective HIV inhibitors. Searching for an accurate, robust, and rapid method to correctly predict the cleavage sites in proteins is crucial when searching for possible HIV inhibitors. In this article, HIV-1 protease specificity was studied using the correlation-based feature subset (CfsSubset) selection method combined with Genetic Algorithms method. Thirty important biochemical features were found based on a jackknife test from the original data set containing 4,248 features. By using the AdaBoost method with the thirty selected features the prediction model yields an accuracy of 96.7% for the jackknife test and 92.1% for an independent set test, with increased accuracy over the original dataset by 6.7% and 77.4%, respectively. Our feature selection scheme could be a useful technique for finding effective competitive inhibitors of HIV protease.

Influence of quasi-specific sites on kinetics of target DNA search by a sequence-specific DNA-binding protein.

PubMed

Kemme, Catherine A; Esadze, Alexandre; Iwahara, Junji

2015-11-10

Functions of transcription factors require formation of specific complexes at particular sites in cis-regulatory elements of genes. However, chromosomal DNA contains numerous sites that are similar to the target sequences recognized by transcription factors. The influence of such "quasi-specific" sites on functions of the transcription factors is not well understood at present by experimental means. In this work, using fluorescence methods, we have investigated the influence of quasi-specific DNA sites on the efficiency of target location by the zinc finger DNA-binding domain of the inducible transcription factor Egr-1, which recognizes a 9 bp sequence. By stopped-flow assays, we measured the kinetics of Egr-1's association with a target site on 143 bp DNA in the presence of various competitor DNAs, including nonspecific and quasi-specific sites. The presence of quasi-specific sites on competitor DNA significantly decelerated the target association by the Egr-1 protein. The impact of the quasi-specific sites depended strongly on their affinity, their concentration, and the degree of their binding to the protein. To quantitatively describe the kinetic impact of the quasi-specific sites, we derived an analytical form of the apparent kinetic rate constant for the target association and used it for fitting to the experimental data. Our kinetic data with calf thymus DNA as a competitor suggested that there are millions of high-affinity quasi-specific sites for Egr-1 among the 3 billion bp of genomic DNA. This study quantitatively demonstrates that naturally abundant quasi-specific sites on DNA can considerably impede the target search processes of sequence-specific DNA-binding proteins.

Expanding the Scope of Site-Specific Recombinases for Genetic and Metabolic Engineering

PubMed Central

Gaj, Thomas; Sirk, Shannon J.; Barbas, Carlos F.

2014-01-01

Site-specific recombinases are tremendously valuable tools for basic research and genetic engineering. By promoting high-fidelity DNA modifications, site-specific recombination systems have empowered researchers with unprecedented control over diverse biological functions, enabling countless insights into cellular structure and function. The rigid target specificities of many sites-specific recombinases, however, have limited their adoption in fields that require highly flexible recognition abilities. As a result, intense effort has been directed toward altering the properties of site-specific recombination systems by protein engineering. Here, we review key developments in the rational design and directed molecular evolution of site-specific recombinases, highlighting the numerous applications of these enzymes across diverse fields of study. PMID:23982993

Site specific modification of the human plasma proteome by methylglyoxal

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

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

Increasing evidence identifies dicarbonyl stress from reactive glucose metabolites, such as methylglyoxal (MG), as a major pathogenic link between hyperglycemia and complications of diabetes. MG covalently modifies arginine residues, yet the site specificity of this modification has not been thoroughly investigated. Sites of MG adduction in the plasma proteome were identified using LC–MS/MS analysis in vitro following incubation of plasma proteins with MG. Treatment of plasma proteins with MG yielded 14 putative MG hotspots from five plasma proteins (albumin [nine hotspots], serotransferrin, haptoglobin [2 hotspots], hemopexin, and Ig lambda-2 chain C regions). The search results revealed two versions of MG-argininemore » modification, dihydroxyimidazolidine (R + 72) and hydroimidazolone (R + 54) adducts. One of the sites identified was R257 in human serum albumin, which is a critical residue located in drug binding site I. This site was validated as a target for MG modification by a fluorescent probe displacement assay, which revealed significant drug dissociation at 300 μM MG from a prodan–HSA complex (75 μM). Moreover, twelve human plasma samples (six male, six female, with two type 2 diabetic subjects from both genders) were analyzed using multiple reaction monitoring (MRM) tandem mass spectrometry and revealed the presence of the MG-modified albumin R257 peptide. These data provide insights into the nature of the site-specificity of MG modification of arginine, which may be useful for therapeutic treatments that aim to prevent MG-mediated adverse responses in patients. - Highlights: • Methylglyoxal (MG) selectively modifies arginine sites in human plasma proteome. • Dihydroxyimidazolidine and hydroimidazolone adducts on serum albumin identified • MG modification on albumin R257 associated with loss of drug site I binding capacity • MRM-tandem mass spectrometry enables sensitive detection of albumin MG-R257. • Site-specific MG modification may represent a useful monitor of effective therapy of T2DM.« less

Position specific variation in the rate of evolution in transcription factor binding sites

PubMed Central

Moses, Alan M; Chiang, Derek Y; Kellis, Manolis; Lander, Eric S; Eisen, Michael B

2003-01-01

Background The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they remain difficult to identify. Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution. Results Here we analyse the genome sequences of the budding yeasts Saccharomyces cerevisiae, S. bayanus, S. paradoxus and S. mikatae to study the evolution of transcription factor binding sites. As expected, we find that both experimentally characterized and computationally predicted binding sites evolve slower than surrounding sequence, consistent with the hypothesis that they are under purifying selection. We also observe position-specific variation in the rate of evolution within binding sites. We find that the position-specific rate of evolution is positively correlated with degeneracy among binding sites within S. cerevisiae. We test theoretical predictions for the rate of evolution at positions where the base frequencies deviate from background due to purifying selection and find reasonable agreement with the observed rates of evolution. Finally, we show how the evolutionary characteristics of real binding motifs can be used to distinguish them from artefacts of computational motif finding algorithms. Conclusion As has been observed for protein sequences, the rate of evolution in transcription factor binding sites varies with position, suggesting that some regions are under stronger functional constraint than others. This variation likely reflects the varying importance of different positions in the formation of the protein-DNA complex. The characterization of the pattern of evolution in known binding sites will likely contribute to the effective use of comparative sequence data in the identification of transcription factor binding sites and is an important step toward understanding the evolution of functional non-coding DNA. PMID:12946282

Toxicity of ammonia, cadmium, and nitrobenzene to four local fishes in the Liao River, China and the derivation of site-specific water quality criteria.

PubMed

Liu, Zhihong; Li, Xiaojun; Tai, Peidong; Sun, Lizong; Yuan, Honghong; Yang, Xiaonan

2018-01-01

Water quality criteria (WQC) are considered to be an effective management tool for protecting aquatic environments. To derive site-specific WQC for an area, local data based on local species are essential to improve the applicability of WQC derived. Due to the paucity of local fish data available for the development of site-specific WQC for the Liao River, China, four local and widespread fishes (Pseudorasbora parva， Abbottina liaoningensis, Ctenogobius giurinus, and Misgurnus anguillicaudatus) were chosen to test their sensitivities to ammonia, cadmium and nitrobenzene. These compounds are common and regularly-measured pollutants in Chinese rivers. In addition to the published data for species resident in the Liao River, site-specific WQC for the three chemicals were derived using both a log-logistic species sensitivity distribution (SSD) and the method recommended by the USEPA, in line with current best practice, which were then compared with Chinese national WQC. It was found that A. liaoningensis was the most sensitive, followed, in order, by P. parva, C. giurinus and M. anguillicaudatus was the least sensitive, and this trend was the same to all three chemicals tested. When comparing the SSD derived solely from previously-published data with that including our data on local fish, there were significant differences identified among parameters describing the SSD curves for ammonia and nitrobenzene and significant differences were detected for site-specific WQC derived for all of the three chemicals. Based on the dataset with local fish data taxa, site-specific WQC of Liao River for ammonia, cadmium, and nitrobenzene were derived to be 20.53mg/L (at a pH of 7.0 and temperature of 20°C), 3.76μg/L (at a hardness of 100mg/L CaCO 3 ), and 0.49mg/L, respectively. Using the same deriving method for each chemical, the national Chinese WQC were higher than site-specific WQC derived in this study for ammonia (national WQC of 25.16mg/L) and nitrobenzene (national WQC of 0.57mg/L), while the national WQC for cadmium was lower (national WQC of 1.81μg/L). These results indicated that published data can be helpful for use when deriving site-specific WQC but that there were differences between site-specific and national WQC which may lead to either over- or under-protection depending on the pollutant if national WQC were used as the basis for the water management of specific river systems, like the Liao River. Copyright © 2017. Published by Elsevier Inc.

Association between site-specific bone mineral density and glucose homeostasis and anthropometric traits in healthy men and women.

PubMed

Kim, Se-Min; Cui, Jinrui; Rhyu, Jane; Guo, Xiuqing; Chen, Yii-Der I; Hsueh, Willa A; Rotter, Jerome I; Goodarzi, Mark O

2018-06-01

Patients with type 2 diabetes mellitus have an increased risk of fracture despite normal or increased bone mineral density (BMD). Studies on the relationship of glucose homeostasis with BMD phenotypes have been inconclusive because distinguishing the roles of insulin resistance and hyperglycaemia in bone remodelling is challenging. In this study, we sought to define the relationship of site-specific BMD with glucose homeostasis traits and anthropometric traits. In a cross-sectional study, we examined 787 subjects from the Mexican-American Coronary Artery Disease (MACAD) cohort who had undergone euglycaemic-hyperinsulinaemic clamps, oral glucose tolerance testing and dual X-ray absorptiometry. Glucose homeostasis traits included insulinogenic index (IGI30), insulin sensitivity (M value), insulin clearance (MCRI), fasting insulin, fasting glucose and 2-hour glucose. Univariate and multivariate analyses were performed to assess the association of glucose homeostasis and anthropometric traits with site-specific BMD. Two-hour glucose was negatively associated with arm BMD in women, which remained significant in multivariate analysis (β = -.15, P = .0015). Positive correlations between fasting insulin and BMD at weight-bearing sites, including pelvis (β = .22, P < .0001) and legs (β = .17, P = .001) in women and pelvis (β = .33, P < .0001) in men, lost significance after multivariate adjustment. Lean mass exhibited strong independent positive associations with BMD at multiple sites in both sexes. Our findings suggest that (i) anabolic effects of insulin might work via mechanical loading from lean mass; (ii) a direct negative effect of increasing glucose might be more prominent at cortical-bone-rich sites in women; and (iii) lean mass is a strong positive predictor of bone mass. © 2018 John Wiley & Sons Ltd.

Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles.

PubMed

Aiba, Toshiki; Saito, Toshiyuki; Hayashi, Akiko; Sato, Shinji; Yunokawa, Harunobu; Maruyama, Toru; Fujibuchi, Wataru; Kurita, Hisaka; Tohyama, Chiharu; Ohsako, Seiichiroh

2017-03-09

It has been pointed out that environmental factors or chemicals can cause diseases that are developmental in origin. To detect abnormal epigenetic alterations in DNA methylation, convenient and cost-effective methods are required for such research, in which multiple samples are processed simultaneously. We here present methylated site display (MSD), a unique technique for the preparation of DNA libraries. By combining it with amplified fragment length polymorphism (AFLP) analysis, we developed a new method, MSD-AFLP. Methylated site display libraries consist of only DNAs derived from DNA fragments that are CpG methylated at the 5' end in the original genomic DNA sample. To test the effectiveness of this method, CpG methylation levels in liver, kidney, and hippocampal tissues of mice were compared to examine if MSD-AFLP can detect subtle differences in the levels of tissue-specific differentially methylated CpGs. As a result, many CpG sites suspected to be tissue-specific differentially methylated were detected. Nucleotide sequences adjacent to these methyl-CpG sites were identified and we determined the methylation level by methylation-sensitive restriction endonuclease (MSRE)-PCR analysis to confirm the accuracy of AFLP analysis. The differences of the methylation level among tissues were almost identical among these methods. By MSD-AFLP analysis, we detected many CpGs showing less than 5% statistically significant tissue-specific difference and less than 10% degree of variability. Additionally, MSD-AFLP analysis could be used to identify CpG methylation sites in other organisms including humans. MSD-AFLP analysis can potentially be used to measure slight changes in CpG methylation level. Regarding the remarkable precision, sensitivity, and throughput of MSD-AFLP analysis studies, this method will be advantageous in a variety of epigenetics-based research.

Immunomodulatory Nature and Site Specific Affinity of Mesenchymal Stem Cells: a Hope in Cell Therapy

PubMed Central

Lotfinegad, Parisa; Shamsasenjan, karim; Movassaghpour, Aliakbar; Majidi, Jafar; Baradaran, Behzad

2014-01-01

Immunosuppressive ability of mesenchymal stem cells (MSCs), their differentiation properties to various specialized tissue types, ease of in vitro and in vivo expansion and specific migration capacity, make them to be tested in different clinical trials for the treatment of various diseases. The immunomodulatory effects of MSCs are less identified which probably has high clinically significance. The clinical trials based on primary research will cause better understanding the ability of MSCs in immunomodulatory applications and site specific migration in the optimization of therapy. So, this review focus on MSCs functional role in modulating immune responses, their ability in homing to tumor, their potency as delivery vehicle and their medical importance. PMID:24409403

BEHAVIOR OF PERSISTENT BIOACCUMULATIVE TOXICANTS IN FISH EARLY LIFE STAGES

EPA Science Inventory

Whether through environmental criteria or site-specific risk assessments, many EPA programs rely on linking environmental exposures to levels of adverse effect (or no effect) in fish and wildlife. While empirical relationships of exposure to effect can be used for such assessmen...

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

PubMed

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

2018-03-07

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

Regulation of Alternative Splicing in Vivo by Overexpression of Antagonistic Splicing Factors

NASA Astrophysics Data System (ADS)

Caceres, Javier F.; Stamm, Stefan; Helfman, David M.; Krainer, Adrian R.

1994-09-01

The opposing effects of SF2/ASF and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 influence alternative splicing in vitro. SF2/ASF or hnRNP A1 complementary DNAs were transiently overexpressed in HeLa cells, and the effect on alternative splicing of several cotransfected reporter genes was measured. Increased expression of SF2/ASF activated proximal 5' splice sites, promoted inclusion of a neuron-specific exon, and prevented abnormal exon skipping. Increased expression of hnRNP A1 activated distal 5' splice sites. Therefore, variations in the intracellular levels of antagonistic splicing factors influence different modes of alternative splicing in vivo and may be a natural mechanism for tissue-specific or developmental regulation of gene expression.

Site-specific recoil-induced effects on inner-shell photoionization of linear triatomic molecules: N 1 s photoelectron spectra of N2 O

NASA Astrophysics Data System (ADS)

Krivosenko, Yu. S.; Pavlychev, A. A.

2016-11-01

We investigate hard X-ray ionization of linear triatomic molecules accenting recoil-induced effects on the dynamics of molecular frame. This dynamics is studied within the two-springs and harmonic approximations. The mode-channel relationship connecting the excitations of vibrational, rotational and translational degrees of freedom with the Σ → Σ and Σ → Π photoionization channels is applied to compute the N 1s-1 photoelectron spectra of molecular N2 O for various photon energies. The distinct ionized-site- and molecular-orientation-specific changes in the vibration structure of the 1 s photoelectron lines of terminal and central nitrogen atoms are revealed and discussed.

Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

NASA Astrophysics Data System (ADS)

Viswanathan, Kavitha; Dhabhar, Firdaus S.

2005-04-01

Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

75 FR 65310 - Environmental Management Site-Specific Advisory Board, Nevada

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-22

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Nevada AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Nevada Test Site. The Federal Advisory... Board is to make recommendations to DOE-EM and site management in the areas of environmental restoration...

The allosteric site regulates the voltage sensitivity of muscarinic receptors.

PubMed

Hoppe, Anika; Marti-Solano, Maria; Drabek, Matthäus; Bünemann, Moritz; Kolb, Peter; Rinne, Andreas

2018-01-01

Muscarinic receptors (M-Rs) for acetylcholine (ACh) belong to the class A of G protein-coupled receptors. M-Rs are activated by orthosteric agonists that bind to a specific site buried in the M-R transmembrane helix bundle. In the active conformation, receptor function can be modulated either by allosteric modulators, which bind to the extracellular receptor surface or by the membrane potential via an unknown mechanism. Here, we compared the modulation of M 1 -Rs and M 3 -Rs induced by changes in voltage to their allosteric modulation by chemical compounds. We quantified changes in receptor signaling in single HEK 293 cells with a FRET biosensor for the G q protein cycle. In the presence of ACh, M 1 -R signaling was potentiated by voltage, similarly to positive allosteric modulation by benzyl quinolone carboxylic acid. Conversely, signaling of M 3 -R was attenuated by voltage or the negative allosteric modulator gallamine. Because the orthosteric site is highly conserved among M-Rs, but allosteric sites vary, we constructed "allosteric site" M 3 /M 1 -R chimeras and analyzed their voltage dependencies. Exchanging the entire allosteric sites eliminated the voltage sensitivity of ACh responses for both receptors, but did not affect their modulation by allosteric compounds. Furthermore, a point mutation in M 3 -Rs caused functional uncoupling of the allosteric and orthosteric sites and abolished voltage dependence. Molecular dynamics simulations of the receptor variants indicated a subtype-specific crosstalk between both sites, involving the conserved tyrosine lid structure of the orthosteric site. This molecular crosstalk leads to receptor subtype-specific voltage effects. Copyright © 2017 Elsevier Inc. All rights reserved.

A survey of Canadian websites providing information about female urinary incontinence.

PubMed

Farrell, Karen D; Robinson, Lynne M; Baydock, Sandra A; Farrell, Scott A; Irving, Linda E; O'Connell, Colleen M

2006-08-01

Urinary incontinence (UI) is a prevalent health issue that has significant detrimental effects on quality of life. The Internet offers a unique vehicle for incontinent women to access information that could facilitate conservative self-help therapy. An evaluation of Canadian websites offering female UI information was conducted to determine their quality and readability. We evaluated websites using published general quality criteria for health sites and a quality assessment tool compiled by the authors for specific UI information derived from published, peer-reviewed clinical practice guidelines. Three health care professionals reviewed sites for quality, Canadian content, and interactivity. The readability of health information was also evaluated. Fifty-six Canadian sites (18 professional, 22 organizational, 16 commercial) were evaluated. Significant agreement was found among the raters' evaluations on all measures. For all sites, the mean scores were general quality, 9/14; specific UI quality, 30/122; reading ease, 37/100; grade level, 10.9. The median score for Canadian content was high, but for interactivity it was low. The only significant difference between site types was for general quality (F [2,165]=3.38, P=0.036). Post hoc Tukey's tests showed a significant difference between organizational and commercial sites, with organizational sites having higher general quality. Canadian websites providing female UI information have moderately high general quality, low specific UI information quality, minimal interactivity, and more than minimal Canadian content. The reading level of most sites is too high for average consumers. A webliography of the best sites has been developed to guide patients.

Relative importance of top-down and bottom-up forces in food webs of Sarracenia pitcher communities at a northern and a southern site.

PubMed

Hoekman, David

2011-04-01

The relative importance of resources (bottom-up forces) and natural enemies (top-down forces) for regulating food web dynamics has been debated, and both forces have been found to be critical for determining food web structure. How the relative importance of top-down and bottom-up forces varies between sites with different abiotic conditions is not well understood. Using the pitcher plant inquiline community as a model system, I examine how the relative importance of top-down and bottom-up effects differs between two disparate sites. Resources (ant carcasses) and top predators (mosquito larvae) were manipulated in two identical 4 × 4 factorial press experiments, conducted at two geographically distant sites (Michigan and Florida) within the range of the purple pitcher plant, Sarracenia purpurea, and the aquatic community that resides in its leaves. Overall, top predators reduced the density of prey populations while additional resources bolstered them, and the relative importance of top-down and bottom-up forces varied between sites and for different trophic levels. Specifically, top-down effects on protozoa were stronger in Florida than in Michigan, while the opposite pattern was found for rotifers. These findings experimentally demonstrate that the strength of predator-prey interactions, even those involving the same species, vary across space. While only two sites are compared in this study, I hypothesize that site differences in temperature, which influences metabolic rate, may be responsible for variation in consumer-resource interactions. These findings warrant further investigation into the specific factors that modify the relative importance of top-down and bottom-up effects.

Influence of Quasi-Specific Sites on Kinetics of Target DNA Search by a Sequence-Specific DNA-Binding Protein

PubMed Central

2015-01-01

Functions of transcription factors require formation of specific complexes at particular sites in cis-regulatory elements of genes. However, chromosomal DNA contains numerous sites that are similar to the target sequences recognized by transcription factors. The influence of such “quasi-specific” sites on functions of the transcription factors is not well understood at present by experimental means. In this work, using fluorescence methods, we have investigated the influence of quasi-specific DNA sites on the efficiency of target location by the zinc finger DNA-binding domain of the inducible transcription factor Egr-1, which recognizes a 9 bp sequence. By stopped-flow assays, we measured the kinetics of Egr-1’s association with a target site on 143 bp DNA in the presence of various competitor DNAs, including nonspecific and quasi-specific sites. The presence of quasi-specific sites on competitor DNA significantly decelerated the target association by the Egr-1 protein. The impact of the quasi-specific sites depended strongly on their affinity, their concentration, and the degree of their binding to the protein. To quantitatively describe the kinetic impact of the quasi-specific sites, we derived an analytical form of the apparent kinetic rate constant for the target association and used it for fitting to the experimental data. Our kinetic data with calf thymus DNA as a competitor suggested that there are millions of high-affinity quasi-specific sites for Egr-1 among the 3 billion bp of genomic DNA. This study quantitatively demonstrates that naturally abundant quasi-specific sites on DNA can considerably impede the target search processes of sequence-specific DNA-binding proteins. PMID:26502071

Identification of genomic sites for CRISPR/Cas9-based genome editing in the Vitis vinifera genome

USDA-ARS?s Scientific Manuscript database

CRISPR/Cas9 has been recently demonstrated as an effective and popular genome editing tool for modifying genomes of human, animals, microorganisms, and plants. Success of such genome editing is highly dependent on the availability of suitable target sites in the genomes to be edited. Many specific t...

75 FR 33875 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

... membership in the Exchange. The text of the proposed rule change is available at the Exchange's Web site at http://www.batstrading.com , on the Commission's Web site at http://www.sec.gov , at the principal... for its equity securities market with respect to Modified Destination Specific Orders routed to a dark...

Combined Analyses of Bacterial, Fungal and Nematode Communities in Andosolic Agricultural Soils in Japan

PubMed Central

Bao, Zhihua; Ikunaga, Yoko; Matsushita, Yuko; Morimoto, Sho; Takada-Hoshino, Yuko; Okada, Hiroaki; Oba, Hirosuke; Takemoto, Shuhei; Niwa, Shigeru; Ohigashi, Kentaro; Suzuki, Chika; Nagaoka, Kazunari; Takenaka, Makoto; Urashima, Yasufumi; Sekiguchi, Hiroyuki; Kushida, Atsuhiko; Toyota, Koki; Saito, Masanori; Tsushima, Seiya

2012-01-01

We simultaneously examined the bacteria, fungi and nematode communities in Andosols from four agro-geographical sites in Japan using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and statistical analyses to test the effects of environmental factors including soil properties on these communities depending on geographical sites. Statistical analyses such as Principal component analysis (PCA) and Redundancy analysis (RDA) revealed that the compositions of the three soil biota communities were strongly affected by geographical sites, which were in turn strongly associated with soil characteristics such as total C (TC), total N (TN), C/N ratio and annual mean soil temperature (ST). In particular, the TC, TN and C/N ratio had stronger effects on bacterial and fungal communities than on the nematode community. Additionally, two-way cluster analysis using the combined DGGE profile also indicated that all soil samples were classified into four clusters corresponding to the four sites, showing high site specificity of soil samples, and all DNA bands were classified into four clusters, showing the coexistence of specific DGGE bands of bacteria, fungi and nematodes in Andosol fields. The results of this study suggest that geography relative to soil properties has a simultaneous impact on soil microbial and nematode community compositions. This is the first combined profile analysis of bacteria, fungi and nematodes at different sites with agricultural Andosols. PMID:22223474

Combined analyses of bacterial, fungal and nematode communities in andosolic agricultural soils in Japan.

PubMed

Bao, Zhihua; Ikunaga, Yoko; Matsushita, Yuko; Morimoto, Sho; Takada-Hoshino, Yuko; Okada, Hiroaki; Oba, Hirosuke; Takemoto, Shuhei; Niwa, Shigeru; Ohigashi, Kentaro; Suzuki, Chika; Nagaoka, Kazunari; Takenaka, Makoto; Urashima, Yasufumi; Sekiguchi, Hiroyuki; Kushida, Atsuhiko; Toyota, Koki; Saito, Masanori; Tsushima, Seiya

2012-01-01

We simultaneously examined the bacteria, fungi and nematode communities in Andosols from four agro-geographical sites in Japan using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and statistical analyses to test the effects of environmental factors including soil properties on these communities depending on geographical sites. Statistical analyses such as Principal component analysis (PCA) and Redundancy analysis (RDA) revealed that the compositions of the three soil biota communities were strongly affected by geographical sites, which were in turn strongly associated with soil characteristics such as total C (TC), total N (TN), C/N ratio and annual mean soil temperature (ST). In particular, the TC, TN and C/N ratio had stronger effects on bacterial and fungal communities than on the nematode community. Additionally, two-way cluster analysis using the combined DGGE profile also indicated that all soil samples were classified into four clusters corresponding to the four sites, showing high site specificity of soil samples, and all DNA bands were classified into four clusters, showing the coexistence of specific DGGE bands of bacteria, fungi and nematodes in Andosol fields. The results of this study suggest that geography relative to soil properties has a simultaneous impact on soil microbial and nematode community compositions. This is the first combined profile analysis of bacteria, fungi and nematodes at different sites with agricultural Andosols.

Discovery and validation of information theory-based transcription factor and cofactor binding site motifs.

PubMed

Lu, Ruipeng; Mucaki, Eliseos J; Rogan, Peter K

2017-03-17

Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE ChIP-seq peak datasets of 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating the need to compensate for skewed nucleotide composition, distinguishes true binding motifs from noise, quantifies the strengths of individual binding sites based on computed affinity and detects adjacent cofactor binding sites that coordinate with the targets of primary, immunoprecipitated TFs. We obtained contiguous and bipartite information theory-based position weight matrices (iPWMs) for 93 sequence-specific TFs, discovered 23 cofactor motifs for 127 TFs and revealed six high-confidence novel motifs. The reliability and accuracy of these iPWMs were determined via four independent validation methods, including the detection of experimentally proven binding sites, explanation of effects of characterized SNPs, comparison with previously published motifs and statistical analyses. We also predict previously unreported TF coregulatory interactions (e.g. TF complexes). These iPWMs constitute a powerful tool for predicting the effects of sequence variants in known binding sites, performing mutation analysis on regulatory SNPs and predicting previously unrecognized binding sites and target genes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Expanding the scope of site-specific recombinases for genetic and metabolic engineering.

PubMed

Gaj, Thomas; Sirk, Shannon J; Barbas, Carlos F

2014-01-01

Site-specific recombinases are tremendously valuable tools for basic research and genetic engineering. By promoting high-fidelity DNA modifications, site-specific recombination systems have empowered researchers with unprecedented control over diverse biological functions, enabling countless insights into cellular structure and function. The rigid target specificities of many sites-specific recombinases, however, have limited their adoption in fields that require highly flexible recognition abilities. As a result, intense effort has been directed toward altering the properties of site-specific recombination systems by protein engineering. Here, we review key developments in the rational design and directed molecular evolution of site-specific recombinases, highlighting the numerous applications of these enzymes across diverse fields of study. © 2013 Wiley Periodicals, Inc.

Epizootiology of cranial abscess disease in white-tailed deer (Odocoileus virginianus) of Georgia, USA

USGS Publications Warehouse

Cohen, Bradley S.; Belser, Emily H.; Killmaster, Charlie H.; Bowers, John W.; Irwin, Brian J.; Yabsley, Michael J.; Miller, Karl V.

2015-01-01

Intracranial abscess disease is a cause of natural mortality for mature male white-tailed deer (Odocoileus virginianus). Most cases of abscesses are associated with bacterial infection byTrueperella (Arcanobacterium) pyogenes, but a complete understanding of the epidemiology of this disease is lacking. We quantified the effects of individual characteristics, site-specific herd demographics, land cover, and soil variables in estimating the probability of this disease. We examined 7,545 white-tailed deer from 60 sites throughout Georgia US for signs of cranial abscesses, the predecessor of intracranial abscesses, and recorded the presence or absence of cranial abscesses for each individual examined. We detected no cranial abscesses in 2,562 female deer but 91 abscesses in 4,983 male deer examined (1.8%). A generalized linear mixed model, treating site as a random effect, was used to examine several potential explanatory risk factors including site-level landscape and soil characteristics (soil and forest type), demographic factors (deer density and male to female ratio), and individual host factors (deer sex and age). Model results indicated that the probability of a male having a cranial abscess increased with age and that adult sex ratio (male:female) was positively associated with this disease. Site-specific variables for land cover and soil types were not strongly associated with observations of the disease at the scale measured and a large amount of among-site variability remained. Given the demonstrated effect of age, gender, and local sex ratios but the remaining unexplained spatial variability, additional investigation into spatiotemporal variation of the presumed bacterial causative agent of cranial abscesses appears warranted.

Uncertainty analysis of the simulations of effects of discharging treated wastewater to the Red River of the North at Fargo, North Dakota, and Moorhead, Minnesota

USGS Publications Warehouse

Wesolowski, Edwin A.

1996-01-01

Two separate studies to simulate the effects of discharging treated wastewater to the Red River of the North at Fargo, North Dakota, and Moorhead, Minnesota, have been completed. In the first study, the Red River at Fargo Water-Quality Model was calibrated and verified for icefree conditions. In the second study, the Red River at Fargo Ice-Cover Water-Quality Model was verified for ice-cover conditions.To better understand and apply the Red River at Fargo Water-Quality Model and the Red River at Fargo Ice-Cover Water-Quality Model, the uncertainty associated with simulated constituent concentrations and property values was analyzed and quantified using the Enhanced Stream Water Quality Model-Uncertainty Analysis. The Monte Carlo simulation and first-order error analysis methods were used to analyze the uncertainty in simulated values for six constituents and properties at sites 5, 10, and 14 (upstream to downstream order). The constituents and properties analyzed for uncertainty are specific conductance, total organic nitrogen (reported as nitrogen), total ammonia (reported as nitrogen), total nitrite plus nitrate (reported as nitrogen), 5-day carbonaceous biochemical oxygen demand for ice-cover conditions and ultimate carbonaceous biochemical oxygen demand for ice-free conditions, and dissolved oxygen. Results are given in detail for both the ice-cover and ice-free conditions for specific conductance, total ammonia, and dissolved oxygen.The sensitivity and uncertainty of the simulated constituent concentrations and property values to input variables differ substantially between ice-cover and ice-free conditions. During ice-cover conditions, simulated specific-conductance values are most sensitive to the headwatersource specific-conductance values upstream of site 10 and the point-source specific-conductance values downstream of site 10. These headwater-source and point-source specific-conductance values also are the key sources of uncertainty. Simulated total ammonia concentrations are most sensitive to the point-source total ammonia concentrations at all three sites. Other input variables that contribute substantially to the variability of simulated total ammonia concentrations are the headwater-source total ammonia and the instream reaction coefficient for biological decay of total ammonia to total nitrite. Simulated dissolved-oxygen concentrations at all three sites are most sensitive to headwater-source dissolved-oxygen concentration. This input variable is the key source of variability for simulated dissolved-oxygen concentrations at sites 5 and 10. Headwatersource and point-source dissolved-oxygen concentrations are the key sources of variability for simulated dissolved-oxygen concentrations at site 14.During ice-free conditions, simulated specific-conductance values at all three sites are most sensitive to the headwater-source specific-conductance values. Headwater-source specificconductance values also are the key source of uncertainty. The input variables to which total ammonia and dissolved oxygen are most sensitive vary from site to site and may or may not correspond to the input variables that contribute the most to the variability. The input variables that contribute the most to the variability of simulated total ammonia concentrations are pointsource total ammonia, instream reaction coefficient for biological decay of total ammonia to total nitrite, and Manning's roughness coefficient. The input variables that contribute the most to the variability of simulated dissolved-oxygen concentrations are reaeration rate, sediment oxygen demand rate, and headwater-source algae as chlorophyll a.

In Vivo Investigation of Escitalopram’s Allosteric Site on the Serotonin Transporter

PubMed Central

Murray, Karen E.; Ressler, Kerry J.; Owens, Michael J.

2015-01-01

Escitalopram is a commonly prescribed antidepressant of the selective serotonin reuptake inhibitor class. Clinical evidence and mapping of the serotonin transporter (SERT) identified that escitalopram, in addition to its binding to a primary uptake-blocking site, is capable of binding to the SERT via an allosteric site that is hypothesized to alter escitalopram’s kinetics at the SERT. The studies reported here examined the in vivo role of the SERT allosteric site in escitalopram action. A knockin mouse model that possesses an allosteric-null SERT was developed. Autoradiographic studies indicated that the knockin protein was expressed at a lower density than endogenous mouse SERT (approximately 10–30% of endogenous mouse SERT), but the knockin mice are a viable tool to study the allosteric site. Microdialysis studies in the ventral hippocampus found no measurable decrease in extracellular serotonin response after local escitalopram challenge in mice without the allosteric site compared to mice with the site (p = 0.297). In marble burying assays there was a modest effect of the absence of the allosteric site, with a larger systemic dose of escitalopram (10-fold) necessary for the same effect as in mice with intact SERT (p = 0.023). However, there was no effect of the allosteric site in the tail suspension test. Together these data suggest that there may be a regional specificity in the role of the allosteric site. The lack of a robust effect overall suggests that the role of the allosteric site for escitalopram on the SERT may not produce meaningful in vivo effects. PMID:26621784

Water-quality characteristics and trend analyses for the Tongue, Powder, Cheyenne, and Belle Fourche River drainage basins, Wyoming and Montana, for selected periods, water years 1991 through 2010

USGS Publications Warehouse

Clark, Melanie L.

2012-01-01

The Powder River structural basin in northeastern Wyoming and southeastern Montana is an area of ongoing coalbed natural gas (CBNG) development. Waters produced during CBNG development are managed with a variety of techniques, including surface impoundments and discharges into stream drainages. The interaction of CBNG-produced waters with the atmosphere and the semiarid soils of the Powder River structural basin can affect water chemistry in several ways. Specific conductance and sodium adsorption ratios (SAR) of CBNG-produced waters that are discharged to streams have been of particular concern because they have the potential to affect the use of the water for irrigation. Water-quality monitoring has been conducted since 2001 at main-stem and tributary sites in the Tongue, Powder, Cheyenne, and Belle Fourche River drainage basins in response to concerns about CBNG effects. A study was conducted to summarize characteristics of stream-water quality for water years 2001–10 (October 1, 2000, to September 30, 2010) and examine trends in specific conductance, SAR, and primary constituents that contribute to specific conductance and SAR for changes through time (water years 1991–2010) that may have occurred as a result of CBNG development. Specific conductance and SAR are the focus characteristics of this report. Dissolved calcium, magnesium, and sodium, which are primary contributors to specific conductance and SAR, as well as dissolved alkalinity, chloride, and sulfate, which are other primary contributors to specific conductance, also are described. Stream-water quality in the Tongue, Powder, Cheyenne, and Belle Fourche River drainage basins was variable during water years 2001–10, in part because of variations in streamflow. In general, annual runoff was less than average during water years 2001–06 and near or above average during water years 2007–10. Stream water of the Tongue River had the smallest specific conductance values, sodium adsorption ratios, and major ion concentrations of the main-stem streams. Sites in the Tongue River drainage basin typically had the smallest range of specific conductance and SAR values. The water chemistry of sites in the Powder River drainage basin generally was the most variable as a result of diverse characteristics of that basin. Plains tributaries in the Powder River drainage basin had the largest range of specific conductance and SAR values, in part due to the many tributaries that receive CBNG-produced waters. Trends were analyzed using the seasonal Kendall test with flow-adjusted concentrations to determine changes to water quality through time at sites in the Tongue, Powder, Cheyenne, and Belle Fourche River drainage basins. Trends were evaluated for water years 2001–10 for 17 sites, which generally were on the main-stem streams and primary tributaries. Trends were evaluated for water years 2005–10 for 26 sites to increase the spatial coverage of sites. Trends were evaluated for water years 1991–2010 for eight sites to include water-quality data collected prior to widespread CBNG development and expand the temporal context of trends. Consistent patterns were not observed in trend results for water years 2001–10 for flow-adjusted specific conductance and SAR values in the Tongue, Powder, and Belle Fourche River drainage basins. Significant (p-values less than 0.05) upward trends in flow-adjusted specific conductance values were determined for 3 sites, a downward trend was determined for 1 site, and no significant (p-value greater than 0.05) trends were determined for 13 sites. One of the sites with a significant upward trend was the Tongue River at the Wyoming-Montana State line. No trend in flow-adjusted specific conductance values was determined for the Powder River at Moorhead, Mont. Significant upward trends in flow-adjusted SAR values were determined for 2 sites and no significant trends were determined for 15 sites. No trends in flow-adjusted SAR values were determined for the Tongue River at the Wyoming-Montana State line or for the Powder River at Moorhead, Mont. One of the sites with a significant upward trend in flow-adjusted SAR values was the Powder River at Arvada, Wyo. For water years 2005–10, significant upward trends in flow-adjusted specific conductance values were determined no significant trends were determined for 13 sites. A significant upward trend was determined for flow-adjusted specific conductance values for the Tongue River at the Wyoming-Montana State line. No trend in flow-adjusted specific conductance values was determined for the Powder River at Moorhead, Mont. Significant upward trends in flow-adjusted SAR values were determined for 4 sites, downward trends were determined for 5 sites, and no significant trend was determined for 17 sites. No trends in flow-adjusted SAR values were determined for the Tongue River at the Wyoming-Montana State line or for the Powder River at Moorhead, Mont. Results of the seasonal Kendall test applied to flow-adjusted specific conductance values for water years 1991–2010 indicated no significant trend for eight sites in the Tongue, Powder, and Belle Fourche River drainage basins. No significant trend in flow-adjusted specific conductance was determined for the Tongue River at the Wyoming-Montana State line or the Powder River at Moorhead, Mont. Results of the seasonal Kendall test applied to flow-adjusted SAR values for water years 1991–2010 indicated an upward trend for one site and no significant trend for four sites in the Powder and Belle Fourche River drainage basins. The significant upward trend in flow-adjusted SAR values was determined for the Powder River at Arvada, Wyo., for water years 1991–2010. Results indicate that CBNG development in the Powder River structural basin may have contributed to some trends, such as the upward trend in flow-adjusted SAR for the Powder River at Arvada, Wyo., for water years 1991–2010. An upward trend in flow-adjusted alkalinity concentrations for water years 2001–10 also was determined for the Powder River at Arvada, Wyo. Trend results are consistent with changes that can occur from the addition of sodium and bicarbonate associated with CBNG-produced waters to the Powder River. Upward trends in constituents at other sites, including the Belle Fourche River, may be the result of declining CBNG development, indicating that CBNG-produced waters may have had a dilution effect on some streams. The factors affecting other trends could not be determined because multiple factors could have been affecting the stream-water quality or because trends were observed at sites upstream from CBNG development that may have affected water-quality trends at sites downstream.

40 CFR 148.14 - Waste specific prohibitions-first third wastes.

Code of Federal Regulations, 2013 CFR

2013-07-01

... underground injection at off-site injection facilities. (e) Effective August 8, 1990, the wastes specified in... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Waste specific prohibitions-first third wastes. 148.14 Section 148.14 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

40 CFR 148.14 - Waste specific prohibitions-first third wastes.

Code of Federal Regulations, 2012 CFR

2012-07-01

... underground injection at off-site injection facilities. (e) Effective August 8, 1990, the wastes specified in... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Waste specific prohibitions-first third wastes. 148.14 Section 148.14 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

40 CFR 148.14 - Waste specific prohibitions-first third wastes.

Code of Federal Regulations, 2014 CFR

2014-07-01

... underground injection at off-site injection facilities. (e) Effective August 8, 1990, the wastes specified in... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Waste specific prohibitions-first third wastes. 148.14 Section 148.14 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

Meditation programs for veterans with posttraumatic stress disorder: Aggregate findings from a multi-site evaluation.

PubMed

Heffner, Kathi L; Crean, Hugh F; Kemp, Jan E

2016-05-01

Interest in meditation to manage posttraumatic stress disorder (PTSD) symptoms is increasing. Few studies have examined the effectiveness of meditation programs offered to Veterans within Department of Veterans Affairs (VA) mental health services. The current study addresses this gap using data from a multisite VA demonstration project. Evaluation data collected at 6 VA sites (N = 391 Veterans) before and after a meditation program, and a treatment-as-usual (TAU) program, were examined here using random effects meta-analyses. Site-specific and aggregate between group effect sizes comparing meditation programs to TAU were determined for PTSD severity measured by clinical interview and self-report. Additional outcomes included experiential avoidance and mindfulness. In aggregate, analyses showed medium effect sizes for meditation programs compared to TAU for PTSD severity (clinical interview: effect size (ES) = -0.32; self-report: ES = -0.39). Similarly sized effects of meditation programs were found for overall mindfulness (ES = 0.41) and 1 specific aspect of mindfulness, nonreactivity to inner experience (ES = .37). Additional findings suggested meditation type and program completion differences each moderated program effects. VA-sponsored meditation programs show promise for reducing PTSD severity in Veterans receiving mental health services. Where meditation training fits within mental health services, and for whom programs will be of interest and effective, require further clarification. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

LASIC: Light Activated Site-Specific Conjugation of Native IgGs.

PubMed

Hui, James Z; Tamsen, Shereen; Song, Yang; Tsourkas, Andrew

2015-08-19

Numerous biological applications, from diagnostic assays to immunotherapies, rely on the use of antibody-conjugates. The efficacy of these conjugates can be significantly influenced by the site at which Immunoglobulin G (IgG) is modified. Current methods that provide control over the conjugation site, however, suffer from a number of shortfalls and often require large investments of time and cost. We have developed a novel adapter protein that, when activated by long wavelength UV light, can covalently and site-specifically label the Fc region of nearly any native, full-length IgG, including all human IgG subclasses. Labeling occurs with unprecedented efficiency and speed (>90% after 30 min), with no effect on IgG affinity. The adapter domain can be bacterially expressed and customized to contain a variety of moieties (e.g., biotin, azide, fluorophores), making reliable and efficient conjugation of antibodies widely accessible to researchers at large.

Site classification of Indian strong motion network using response spectra ratios

NASA Astrophysics Data System (ADS)

Chopra, Sumer; Kumar, Vikas; Choudhury, Pallabee; Yadav, R. B. S.

2018-03-01

In the present study, we tried to classify the Indian strong motion sites spread all over Himalaya and adjoining region, located on varied geological formations, based on response spectral ratio. A total of 90 sites were classified based on 395 strong motion records from 94 earthquakes recorded at these sites. The magnitude of these earthquakes are between 2.3 and 7.7 and the hypocentral distance for most of the cases is less than 50 km. The predominant period obtained from response spectral ratios is used to classify these sites. It was found that the shape and predominant peaks of the spectra at these sites match with those in Japan, Italy, Iran, and at some of the sites in Europe and the same classification scheme can be applied to Indian strong motion network. We found that the earlier schemes based on description of near-surface geology, geomorphology, and topography were not able to capture the effect of sediment thickness. The sites are classified into seven classes (CL-I to CL-VII) with varying predominant periods and ranges as proposed by Alessandro et al. (Bull Seismol Soc Am 102:680-695 2012). The effect of magnitudes and hypocentral distances on the shape and predominant peaks were also studied and found to be very small. The classification scheme is robust and cost-effective and can be used in region-specific attenuation relationships for accounting local site effect.

Surface Diversity in Mycoplasma agalactiae Is Driven by Site-Specific DNA Inversions within the vpma Multigene Locus

PubMed Central

Glew, Michelle D.; Marenda, Marc; Rosengarten, Renate; Citti, Christine

2002-01-01

The ruminant pathogen Mycoplasma agalactiae possesses a family of abundantly expressed variable surface lipoproteins called Vpmas. Phenotypic switches between Vpma members have previously been correlated with DNA rearrangements within a locus of vpma genes and are proposed to play an important role in disease pathogenesis. In this study, six vpma genes were characterized in the M. agalactiae type strain PG2. All vpma genes clustered within an 8-kb region and shared highly conserved 5′ untranslated regions, lipoprotein signal sequences, and short N-terminal sequences. Analyses of the vpma loci from consecutive clonal isolates showed that vpma DNA rearrangements were site specific and that cleavage and strand exchange occurred within a minimal region of 21 bp located within the 5′ untranslated region of all vpma genes. This process controlled expression of vpma genes by effectively linking the open reading frame (ORF) of a silent gene to a unique active promoter sequence within the locus. An ORF (xer1) immediately adjacent to one end of the vpma locus did not undergo rearrangement and had significant homology to a distinct subset of genes belonging to the λ integrase family of site-specific xer recombinases. It is proposed that xer1 codes for a site-specific recombinase that is not involved in chromosome dimer resolution but rather is responsible for the observed vpma-specific recombination in M. agalactiae. PMID:12374833

TPA can overcome the requirement for EIa and together act synergistically in stimulating expression of the adenovirus EIII promoter.

PubMed Central

Buckbinder, L; Miralles, V J; Reinberg, D

1989-01-01

We have examined the control of gene expression from the adenovirus early region III (Ad-EIII) promoter, which contains two previously defined elements, the AP1 and ATF sites. We found that the AP1 element is capable of mediating activation by the adenovirus immediate early (EIa) gene products. Consistent with studies demonstrating that the AP1 site mediates signal transduction in response to 12-O-tetradecanoylphorbol 13-acetate (TPA) we have shown that TPA can activate Ad-EIII expression and overcome the requirement for EIa. Together TPA and EIa elicited a synergistic response in expression from the Ad-EIII promoter during both transient expression assays and viral infections. This synergistic effect required the AP1 element. An EIII promoter construct, in which sequences upstream of the TATA box had been replaced with four AP1 sites, was responsive to TPA and EIa and in combination promoted the synergistic effect. The analysis of specific factors involved in transcription from the Ad-EIII indicated that proteins recognizing the ATF and AP1 sites were important in expression from this promoter in vitro. Purification of protein factors that specifically stimulated EIII expression resulted in the isolation of a set of factors of the AP1 family. Affinity purified AP1 recognized and activated transcription through both the AP1 and ATF elements. In addition, a protein fraction was identified with DNA binding activity specific for the ATF element. This fraction was dependent on the ATF site for transcriptional activity. Images PMID:2531661

Ground Motion Uncertainty and Variability (single-station sigma): Insights from Euroseistest, Greece

NASA Astrophysics Data System (ADS)

Ktenidou, O. J.; Roumelioti, Z.; Abrahamson, N. A.; Cotton, F.; Pitilakis, K.

2014-12-01

Despite recent improvements in networks and data, the global aleatory uncertainty (sigma) in GMPEs is still large. One reason is the ergodic approach, where we combine data in space to make up for lack of data in time. By estimating the systematic site response, we can make site-specific GMPEs and use a lower, site-specific uncertainty: single-station sigma. In this study we use the EUROSEISTEST database (http://euroseisdb.civil.auth.gr), which has two distinct advantages: good existing knowledge of site conditions at all stations, and careful relocation of the recorded events. Constraining the site and source parameters as best we can, we minimise the within- and between-events components of the global, ergodic sigma. Following that, knowledge of the site response from empirical and theoretical approaches permits us to move on to single-station sigma. The variability per site is not clearly correlated to the site class. We show that in some cases knowledge of Vs30 is not sufficient, and that site-specific data are needed to capture the response, possibly due to 2D/3D effects from complex geometry. Our values of single-station sigma are low compared to the literature. This may be due to the good ray coverage we have in all directions for small, nearby records. Indeed, our single-station sigma values are similar to published single-path values, which means that they may correspond to a fully -rather than partially- non-ergodic approach. We find larger ground motion variability for short distances and small magnitudes. This may be related to the uncertainty in the depth affecting nearby records more, or to stress drop and causing trade-offs between the source and site terms for small magnitudes.

Effects of high salinity wastewater discharges on unionid mussels in the Allegheny River, Pennsylvania

USGS Publications Warehouse

Kathleen Patnode,; Hittle, Elizabeth A.; Robert Anderson,; Lora Zimmerman,; Fulton, John W.

2015-01-01

We examined the effect of high salinity wastewater (brine) from oil and natural gas drilling on freshwater mussels in the Allegheny River, Pennsylvania, during 2012. Mussel cages (N = 5 per site) were deployed at two sites upstream and four sites downstream of a brine treatment facility on the Allegheny River. Each cage contained 20 juvenile northern riffleshell mussels Epioblasma torulosa rangiana). Continuous specific conductance and temperature data were recorded by water quality probes deployed at each site. To measure the amount of mixing throughout the entire study area, specific conductance surveys were completed two times during low-flow conditions along transects from bank to bank that targeted upstream (reference) reaches, a municipal wastewater treatment plant discharge upstream of the brine-facility discharge, the brine facility, and downstream reaches. Specific conductance data indicated that high specific conductance water from the brine facility (4,000–12,000 µS/cm; mean 7,846) compared to the reference reach (103–188 µS/cm; mean 151) is carried along the left descending bank of the river and that dilution of the discharge via mixing does not occur until 0.5 mi (805 m) downstream. Juvenile northern riffleshell mussel survival was severely impaired within the high specific conductance zone (2 and 34% at and downstream of the brine facility, respectively) and at the municipal wastewater treatment plant (21%) compared to background (84%). We surveyed native mussels (family Unionidae) at 10 transects: 3 upstream, 3 within, and 4 downstream of the high specific conductance zone. Unionid mussel abundance and diversity were lower for all transects within and downstream of the high conductivity zone compared to upstream. The results of this study clearly demonstrate in situ toxicity to juvenile northern riffleshell mussels, a federally endangered species, and to the native unionid mussel assemblage located downstream of a brine discharge to the Allegheny River.

All hazardous waste politics is local: Grass-roots advocacy and public participation in siting and cleanup decisions

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

Lowry, R.C.

1998-12-31

The combined effects of federalism and interest group pluralism pose particularly difficult problems for hazardous waste siting and cleanup decisions. Most national environmental groups have only limited involvement in local hazardous waste politics, while local grass-roots advocates have very different interests and sometimes are pitted against one another. Both the Environmental protection Agency and the Department of energy recently have begun to use site-specific citizen advisory boards at cleanup sites. This approach appears to improve communications at some sites, but does not address the issues of ``not in my back yard`` politics and alleged inequitable exposure to hazardous wastes.

A novel restriction endonuclease GlaI for rapid and highly sensitive detection of DNA methylation coupled with isothermal exponential amplification reaction.

PubMed

Sun, Yueying; Sun, Yuanyuan; Tian, Weimin; Liu, Chenghui; Gao, Kejian; Li, Zhengping

2018-02-07

Sensitive and accurate detection of site-specific DNA methylation is of critical significance for early diagnosis of human diseases, especially cancers. Herein, for the first time we employ a novel methylation-dependent restriction endonuclease GlaI to detect site-specific DNA methylation in a highly specific and sensitive way by coupling with isothermal exponential amplification reaction (EXPAR). GlaI can only cut the methylated target site with excellent selectivity but leave the unmethylated DNA intact. Then the newly exposed end fragments of methylated DNA can trigger EXPAR for highly efficient signal amplification while the intact unmethylated DNA will not initiate EXPAR at all. As such, only the methylated DNA is quantitatively and faithfully reflected by the real-time fluorescence signal of the GlaI-EXPAR system, and the potential false positive interference from unmethylated DNA can be effectively eliminated. Therefore, by integrating the unique features of GlaI for highly specific methylation discrimination and EXPAR for rapid and powerful signal amplification, the elegant GlaI-EXPAR assay allows the direct quantification of methylated DNA with ultrahigh sensitivity and accuracy. The detection limit of methylated DNA target has been pushed down to the aM level and the whole detection process of GlaI-EXPAR can be accomplished within a short time of 2 h. More importantly, ultrahigh specificity is achieved and as low as 0.01% methylated DNA can be clearly identified in the presence of a large excess of unmethylated DNA. This GlaI-EXPAR is also demonstrated to be capable of determining site-specific DNA methylations in real genomic DNA samples. Sharing the distinct advantages of ultrahigh sensitivity, outstanding specificity and facile operation, this new GlaI-EXPAR strategy may provide a robust and reliable platform for the detection of site-specific DNA methylations with low abundances.

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

PubMed

Resnick, Marc L; Sanchez, Julian

2004-01-01

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

Fabrication of nanometer- and micrometer-scale protein structures by site-specific immobilization of histidine-tagged proteins to aminosiloxane films with photoremovable protein-resistant protecting groups

DOE PAGES

Xia, Sijing; Cartron, Michael; Morby, James; ...

2016-01-28

The site-specific immobilization of histidine-tagged proteins to patterns formed by far-field and near-field exposure of films of aminosilanes with protein-resistant photolabile protecting groups is demonstrated. After deprotection of the aminosilane, either through a mask or using a scanning near-field optical microscope, the amine terminal groups are derivatized first with glutaraldehyde and then with N-(5-amino-1-carboxypentyl)iminodiacetic acid to yield a nitrilo-triacetic-acid-terminated surface. After complexation with Ni 2+, this surface binds histidine-tagged GFP and CpcA-PEB in a site-specific fashion. The chemistry is simple and reliable and leads to extensive surface functionalization. Bright fluorescence is observed in fluorescence microscopy images of micrometer- and nanometer-scalemore » patterns. X-ray photoelectron spectroscopy is used to study quantitatively the efficiency of photodeprotection and the reactivity of the modified surfaces. The efficiency of the protein binding process is investigated quantitatively by ellipsometry and by fluorescence microscopy. We find that regions of the surface not exposed to UV light bind negligible amounts of His-tagged proteins, indicating that the oligo(ethylene glycol) adduct on the nitrophenyl protecting group confers excellent protein resistance; in contrast, exposed regions bind His-GFP very effectively, yielding strong fluorescence that is almost completely removed on treatment of the surface with imidazole, confirming a degree of site-specific binding in excess of 90%. As a result, this simple strategy offers a versatile generic route to the spatially selective site-specific immobilization of proteins at surfaces.« less

Net Mineralization Response to Fertilizer Application and Site-Specific Setting in a No-Till Dryland Wheat Agroecosystem in the Pacific Northwest (USA)

NASA Astrophysics Data System (ADS)

Bruner, Emily A.; Brown, David J.; Carpenter-Boggs, Lynn

2015-04-01

Application of nitrogen (N) fertilizers is pivotal to maintaining agricultural productivity. Nutrient management is typically guided by a combined assessment of crop yield requirements, residual soil inorganic N concentration, and predicted N supply from organic matter. However, laboratory assays employed to forecast mineralization potential do not reflect in situ processes occurring in soils, processes that can vary spatially within a field. Furthermore, fertilizer application alters biogeochemical cycles through a variety of mechanisms including priming effects and microbial community alterations. This study investigates in-situ ammonification/nitrification rates utilizing mineralization cores as part of a five-year Site-Specific Climate-Friendly Farming (SCF) project. In-depth accounting of nitrate and ammonium production and flux was possible via a six bag mixed-bed ion exchange resin system. Soil cores (7.5 cm diameter by 15 cm deep) were isolated from the surrounding soil by three resin bags sealed in the top and bottom of individual plastic cylinders. Fifteen locations were selected across a commercial direct-seed wheat field based on statistical clustering of primary and secondary topographic variables. In each location surface soil-resin cores were installed in fertilized and unfertilized plots immediately after spring planting and removed before harvest. In situ ammonification/nitrification rates will be analyzed as a function of both fertilizer application and site-specific environmental characteristics as determined from soil moisture monitoring, soil characterization, and crop analysis at each measurement location. This site-specific information on N transformations and availability can then be used to guide site-specific crop management.

Evaluating Variability and Uncertainty of Geological Strength Index at a Specific Site

NASA Astrophysics Data System (ADS)

Wang, Yu; Aladejare, Adeyemi Emman

2016-09-01

Geological Strength Index (GSI) is an important parameter for estimating rock mass properties. GSI can be estimated from quantitative GSI chart, as an alternative to the direct observational method which requires vast geological experience of rock. GSI chart was developed from past observations and engineering experience, with either empiricism or some theoretical simplifications. The GSI chart thereby contains model uncertainty which arises from its development. The presence of such model uncertainty affects the GSI estimated from GSI chart at a specific site; it is, therefore, imperative to quantify and incorporate the model uncertainty during GSI estimation from the GSI chart. A major challenge for quantifying the GSI chart model uncertainty is a lack of the original datasets that have been used to develop the GSI chart, since the GSI chart was developed from past experience without referring to specific datasets. This paper intends to tackle this problem by developing a Bayesian approach for quantifying the model uncertainty in GSI chart when using it to estimate GSI at a specific site. The model uncertainty in the GSI chart and the inherent spatial variability in GSI are modeled explicitly in the Bayesian approach. The Bayesian approach generates equivalent samples of GSI from the integrated knowledge of GSI chart, prior knowledge and observation data available from site investigation. Equations are derived for the Bayesian approach, and the proposed approach is illustrated using data from a drill and blast tunnel project. The proposed approach effectively tackles the problem of how to quantify the model uncertainty that arises from using GSI chart for characterization of site-specific GSI in a transparent manner.

Fabrication of Nanometer- and Micrometer-Scale Protein Structures by Site-Specific Immobilization of Histidine-Tagged Proteins to Aminosiloxane Films with Photoremovable Protein-Resistant Protecting Groups

PubMed Central

2016-01-01

The site-specific immobilization of histidine-tagged proteins to patterns formed by far-field and near-field exposure of films of aminosilanes with protein-resistant photolabile protecting groups is demonstrated. After deprotection of the aminosilane, either through a mask or using a scanning near-field optical microscope, the amine terminal groups are derivatized first with glutaraldehyde and then with N-(5-amino-1-carboxypentyl)iminodiacetic acid to yield a nitrilo-triacetic-acid-terminated surface. After complexation with Ni2+, this surface binds histidine-tagged GFP and CpcA-PEB in a site-specific fashion. The chemistry is simple and reliable and leads to extensive surface functionalization. Bright fluorescence is observed in fluorescence microscopy images of micrometer- and nanometer-scale patterns. X-ray photoelectron spectroscopy is used to study quantitatively the efficiency of photodeprotection and the reactivity of the modified surfaces. The efficiency of the protein binding process is investigated quantitatively by ellipsometry and by fluorescence microscopy. We find that regions of the surface not exposed to UV light bind negligible amounts of His-tagged proteins, indicating that the oligo(ethylene glycol) adduct on the nitrophenyl protecting group confers excellent protein resistance; in contrast, exposed regions bind His-GFP very effectively, yielding strong fluorescence that is almost completely removed on treatment of the surface with imidazole, confirming a degree of site-specific binding in excess of 90%. This simple strategy offers a versatile generic route to the spatially selective site-specific immobilization of proteins at surfaces. PMID:26820378

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

PubMed

Desai, Kashappa Goud H

2018-04-01

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

Cyclosporine a inhibits apoptosis of rat gingival epithelium.

PubMed

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

2014-08-01

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

10 CFR 52.110 - Termination of license.

Code of Federal Regulations, 2010 CFR

2010-01-01

... NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS... final legally effective order to permanently cease operations has come into effect, the 10 CFR part 52... reasons for concluding that the environmental impacts associated with site-specific decommissioning...

Electrophoretic and field-effect graphene for all-electrical DNA array technology.

PubMed

Xu, Guangyu; Abbott, Jeffrey; Qin, Ling; Yeung, Kitty Y M; Song, Yi; Yoon, Hosang; Kong, Jing; Ham, Donhee

2014-09-05

Field-effect transistor biomolecular sensors based on low-dimensional nanomaterials boast sensitivity, label-free operation and chip-scale construction. Chemical vapour deposition graphene is especially well suited for multiplexed electronic DNA array applications, since its large two-dimensional morphology readily lends itself to top-down fabrication of transistor arrays. Nonetheless, graphene field-effect transistor DNA sensors have been studied mainly at single-device level. Here we create, from chemical vapour deposition graphene, field-effect transistor arrays with two features representing steps towards multiplexed DNA arrays. First, a robust array yield--seven out of eight transistors--is achieved with a 100-fM sensitivity, on par with optical DNA microarrays and at least 10 times higher than prior chemical vapour deposition graphene transistor DNA sensors. Second, each graphene acts as an electrophoretic electrode for site-specific probe DNA immobilization, and performs subsequent site-specific detection of target DNA as a field-effect transistor. The use of graphene as both electrode and transistor suggests a path towards all-electrical multiplexed graphene DNA arrays.

Effects of Site-Specific Guanine C8-Modifications on an Intramolecular DNA G-Quadruplex

PubMed Central

Lech, Christopher Jacques; Cheow Lim, Joefina Kim; Wen Lim, Jocelyn Mei; Amrane, Samir; Heddi, Brahim; Phan, Anh Tuân

2011-01-01

Understanding the fundamentals of G-quadruplex formation is important both for targeting G-quadruplexes formed by natural sequences and for engineering new G-quadruplexes with desired properties. Using a combination of experimental and computational techniques, we have investigated the effects of site-specific substitution of a guanine with C8-modified guanine derivatives, including 8-bromo-guanine, 8-O-methyl-guanine, 8-amino-guanine, and 8-oxo-guanine, within a well-defined (3 + 1) human telomeric G-quadruplex platform. The effects of substitutions on the stability of the G-quadruplex were found to depend on the type and position of the modification among different guanines in the structure. An interesting modification-dependent NMR chemical-shift effect was observed across basepairing within a guanine tetrad. This effect was reproduced by ab initio quantum mechanical computations, which showed that the observed variation in imino proton chemical shift is largely influenced by changes in hydrogen-bond geometry within the guanine tetrad. PMID:22004753

Comparison of screening-level and Monte Carlo approaches for wildlife food web exposure modeling

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

Pastorok, R.; Butcher, M.; LaTier, A.

1995-12-31

The implications of using quantitative uncertainty analysis (e.g., Monte Carlo) and site-specific tissue residue data for wildlife exposure modeling were examined with data on trace elements at the Clark Fork River Superfund Site. Exposure of white-tailed deer, red fox, and American kestrel was evaluated using three approaches. First, a screening-level exposure model was based on conservative estimates of exposure parameters, including estimates of dietary residues derived from bioconcentration factors (BCFs) and soil chemistry. A second model without Monte Carlo was based on site-specific data for tissue residues of trace elements (As, Cd, Cu, Pb, Zn) in key dietary species andmore » plausible assumptions for habitat spatial segmentation and other exposure parameters. Dietary species sampled included dominant grasses (tufted hairgrass and redtop), willows, alfalfa, barley, invertebrates (grasshoppers, spiders, and beetles), and deer mice. Third, the Monte Carlo analysis was based on the site-specific residue data and assumed or estimated distributions for exposure parameters. Substantial uncertainties are associated with several exposure parameters, especially BCFS, such that exposure and risk may be greatly overestimated in screening-level approaches. The results of the three approaches are compared with respect to realism, practicality, and data gaps. Collection of site-specific data on trace elements concentrations in plants and animals eaten by the target wildlife receptors is a cost-effective way to obtain realistic estimates of exposure. Implications of the results for exposure and risk estimates are discussed relative to use of wildlife exposure modeling and evaluation of remedial actions at Superfund sites.« less

Spatial effect of new municipal solid waste landfill siting using different guidelines.

PubMed

Ahmad, Siti Zubaidah; Ahamad, Mohd Sanusi S; Yusoff, Mohd Suffian

2014-01-01

Proper implementation of landfill siting with the right regulations and constraints can prevent undesirable long-term effects. Different countries have respective guidelines on criteria for new landfill sites. In this article, we perform a comparative study of municipal solid waste landfill siting criteria stated in the policies and guidelines of eight different constitutional bodies from Malaysia, Australia, India, U.S.A., Europe, China and the Middle East, and the World Bank. Subsequently, a geographic information system (GIS) multi-criteria evaluation model was applied to determine new suitable landfill sites using different criterion parameters using a constraint mapping technique and weighted linear combination. Application of Macro Modeler provided in the GIS-IDRISI Andes software helps in building and executing multi-step models. In addition, the analytic hierarchy process technique was included to determine the criterion weight of the decision maker's preferences as part of the weighted linear combination procedure. The differences in spatial results of suitable sites obtained signifies that dissimilarity in guideline specifications and requirements will have an effect on the decision-making process.

The effect of interferon on the receptor sites to rabies virus on mouse neuroblastoma cells

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

Briggs, D.J.

1989-01-01

The binding of rabies virus to mouse neuroblastoma cells (MNA) primed with alpha interferon (IFN-{alpha}), beta interferon (IFN-{beta}), or alpha bungarotoxin (BTX) was examined. A saturable number of receptor sites to rabies virus was calculated by increasing the amount of {sup 3}H-CVS added to a constant number of untreated MNA cells. MNA cells were then exposed to 20 I.U. of IFN-{alpha}, IFN-{beta}, or 1 {mu}g of BTX and assayed to determine if these treatments had an effect on the number of receptor sites to rabies virus. Total amount of {sup 3}H-CVS bound to MNA cells was determined during a threemore » hour incubation period. Cold competition assays using 1,000 fold excess unlabeled CVS were used to determine non-specific binding for each treatment. Specific binding was then calculated by subtracting non-specific binding from the total amount of CVS bound to MNA cells. A similar amount of total viral protein bound to untreated and IFN-{beta}, and BTX treated cells after 180 minutes of incubation. The bound protein varied by only 0.07 {mu}g. However, the amount of specific and non-specific binding varied a great deal between treatments. BTX caused an increase in non-specific and a decrease in specific binding of rabies virus. IFN-{beta} produced variable results in non-specific and specific binding while IFN-{alpha} caused mainly specific binding to occur. The most significant change brought about by IFN-{alpha} was an increase in the rate of viral attachment. At 30 minutes post-infection, IFN-{alpha} treated cells had bound 90% of the total amount of virus bound to untreated cells after 180 minutes. The increased binding rate did not cause a productive infection of rabies virus. No viral production was evident after an incubation period of 48 hours in either IFN-{alpha} or IFN-{beta} treated cells.« less

Stereoscopically Observing Manipulative Actions

PubMed Central

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

2016-01-01

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

Stereoscopically Observing Manipulative Actions.

PubMed

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

2016-08-01

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

Specific gravity of hybrid poplars in the north-central region, USA: within-tree variability and site × genotype effects

Treesearch

William L. Headlee; Ronald S. Jr. Zalesny; Richard B. Hall; Edmund O. Bauer; Bradford Bender; Bruce A. Birr; Raymond O. Miller; Jesse A. Randall; Adam H. Wiese

2013-01-01

Specific gravity is an important consideration for traditional uses of hybrid poplars for pulp and solid wood products, as well as for biofuels and bioenergy production. While specific gravity has been shown to be under strong genetic control and subject to within-tree variability, the role of genotype × environment interactions is poorly understood. Most...

Teaching without Faculty: Policy Interactions and Their Effects on the Network of Teaching in German Higher Education

ERIC Educational Resources Information Center

Mitterle, Alexander; Würmann, Carsten; Bloch, Roland

2015-01-01

The impact of higher education reforms on teaching at faculty level in Germany has seldom been explored. Research on teaching at university so far centres on how to teach. Yet, before any (best) practice can take place, teaching requires a specific site where a specific teacher meets a specific number of students. To bring about teaching, teaching…

Infant teething information on the world wide web: taking a byte out of the search.

PubMed

Kozuch, Mary; Peacock, Erica; D'Auria, Jennifer P

2015-01-01

The purpose of this study was to describe and evaluate the quality of infant teething information on selected popular parenting Web sites. Two checklists were used to evaluate the quality of the 16 parenting sites and infant teething-specific content included on each site. Three of the 16 parenting sites did not contain teething-specific articles. Teething-specific content found on 13 of the 16 sites supported a connection between the process of teething and nonspecific symptoms with a perception that management is required. Popular management strategies included chewing on chilled objects, gingival massage, and the use of over-the-counter medications. Information about possible adverse effects of administering medications for infant teething was not found on the majority of sites. Eleven of the 16 sites advised parents to contact their primary care provider if they were uncertain about management for infant teething or whether the symptoms were related to illness. Although infant teething has an evidence base from which parents and professionals can make safe decisions about symptoms and treatment, translating the evidence into professional practice and health-related information on the Internet remains a challenge. Parents and pediatric health providers would benefit greatly from the development of clinical practice guidelines summarizing our present-day understanding of teething symptoms and the limited evidence supporting the use of over-the-counter medications. Copyright © 2015 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

Distinct oxidative cleavage and modification of bovine [Cu-Zn]-SOD by an ascorbic acid/Cu(II) system: Identification of novel copper binding site on SOD molecule

PubMed Central

Uehara, Hiroshi; Luo, Shen; Aryal, Baikuntha; Levine, Rodney L.; Rao, V. Ashutosh

2016-01-01

We investigated the combined effect of ascorbate and copper [Asc/Cu(II)] on the integrity of bovine [Cu-Zn]-superoxide dismutase (bSOD1) as a model system to study the metal catalyzed oxidation (MCO) and fragmentation of proteins. We found Asc/Cu(II) mediates specific cleavage of bSOD1 and generates 12.5 and 3.2 kDa fragments in addition to oxidation/carbonylation of the protein. The effect of other tested transition metals, a metal chelator, and hydrogen peroxide on the cleavage and oxidation indicated that binding of copper to a previously unknown site on SOD1 is responsible for the Asc/Cu(II) specific cleavage and oxidation. We utilized tandem mass spectrometry to identify the specific cleavage sites of Asc/Cu(II)-treated bSOD1. Analyses of tryptic- and AspN-peptides have demonstrated the cleavage to occur at Gly31 with peptide bond breakage with Thr30 and Ser32 through diamide and α-amidation pathways, respectively. The three-dimensional structure of bSOD1 reveals the imidazole ring of His19 localized within 5 Angstrom from the α-carbon of Gly31 providing a structural basis that copper ion, most likely coordinated by His19, catalyzes the specific cleavage reaction. PMID:26872685

Distinct oxidative cleavage and modification of bovine [Cu- Zn]-SOD by an ascorbic acid/Cu(II) system: Identification of novel copper binding site on SOD molecule.

PubMed

Uehara, Hiroshi; Luo, Shen; Aryal, Baikuntha; Levine, Rodney L; Rao, V Ashutosh

2016-05-01

We investigated the combined effect of ascorbate and copper [Asc/Cu(II)] on the integrity of bovine [Cu-Zn]-superoxide dismutase (bSOD1) as a model system to study the metal catalyzed oxidation (MCO) and fragmentation of proteins. We found Asc/Cu(II) mediates specific cleavage of bSOD1 and generates 12.5 and 3.2kDa fragments in addition to oxidation/carbonylation of the protein. The effect of other tested transition metals, a metal chelator, and hydrogen peroxide on the cleavage and oxidation indicated that binding of copper to a previously unknown site on SOD1 is responsible for the Asc/Cu(II) specific cleavage and oxidation. We utilized tandem mass spectrometry to identify the specific cleavage sites of Asc/Cu(II)-treated bSOD1. Analyses of tryptic- and AspN-peptides have demonstrated the cleavage to occur at Gly31 with peptide bond breakage with Thr30 and Ser32 through diamide and α-amidation pathways, respectively. The three-dimensional structure of bSOD1 reveals the imidazole ring of His19 localized within 5Å from the α-carbon of Gly31 providing a structural basis that copper ion, most likely coordinated by His19, catalyzes the specific cleavage reaction. Published by Elsevier Inc.

Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate.

PubMed

Lim, Reyna K V; Yu, Shan; Cheng, Bo; Li, Sijia; Kim, Nam-Jung; Cao, Yu; Chi, Victor; Kim, Ji Young; Chatterjee, Arnab K; Schultz, Peter G; Tremblay, Matthew S; Kazane, Stephanie A

2015-11-18

Liver X receptor (LXR) agonists have been explored as potential treatments for atherosclerosis and other diseases based on their ability to induce reverse cholesterol transport and suppress inflammation. However, this therapeutic potential has been hindered by on-target adverse effects in the liver mediated by excessive lipogenesis. Herein, we report a novel site-specific antibody-drug conjugate (ADC) that selectively delivers a LXR agonist to monocytes/macrophages while sparing hepatocytes. The unnatural amino acid para-acetylphenylalanine (pAcF) was site-specifically incorporated into anti-CD11a IgG, which binds the α-chain component of the lymphocyte function-associated antigen 1 (LFA-1) expressed on nearly all monocytes and macrophages. An aminooxy-modified LXR agonist was conjugated to anti-CD11a IgG through a stable, cathepsin B cleavable oxime linkage to afford a chemically defined ADC. The anti-CD11a IgG-LXR agonist ADC induced LXR activation specifically in human THP-1 monocyte/macrophage cells in vitro (EC50-27 nM), but had no significant effect in hepatocytes, indicating that payload delivery is CD11a-mediated. Moreover, the ADC exhibited higher-fold activation compared to a conventional synthetic LXR agonist T0901317 (Tularik) (3-fold). This novel ADC represents a fundamentally different strategy that uses tissue targeting to overcome the limitations of LXR agonists for potential use in treating atherosclerosis.

Site specific ligand substitution in cubane-type Mo3FeS(4)(4+) clusters: kinetics and mechanism of reaction and isolation of mixed ligand Cl/SPh complexes.

PubMed

Algarra, Andrés G; Basallote, Manuel G; Fernandez-Trujillo, M J; Llusar, Rosa; Pino-Chamorro, Jose A; Sorribes, Ivan; Vicent, Cristian

2010-04-21

The synthesis, crystal structure and solution characterization of the cubane-type [Mo(3)(FeCl)S(4)(dmpe)(3)Cl(3)] (1) (dmpe = 1,2-bis(dimethylphophane-ethane)) cluster are reported and the ligand substitution processes of chloride by thiophenolate investigated. The kinetics and the intimate mechanism of these substitutions reveal that compound 1 undergoes a number of Fe and Mo site specific ligand substitution reactions in acetonitrile solutions. In particular, PhS(-) coordination at the tetrahedral Fe site proceeds in a single resolved kinetic step whereas such substitutions at the Mo sites proceed more slowly. The effect of the presence of acids in the reaction media is also investigated and reveals that an acid excess hinders substitution reactions both at the Fe and Mo sites; however, an acid-promoted solvolysis of the Fe-Cl bonds is observed. Electrospray ionization (ESI) and tandem (ESI-MS/MS) mass spectrometry allow the identification of all the reaction intermediates proposed on the basis of stopped-flow measurements. The distinctive site specific reactivity made it possible to isolate two new clusters of the Mo(3)FeS(4)(4+) family featuring mixed chlorine/thiophenolate ligands, namely Mo(3)S(4)(FeSPh)(dmpe)(3)Cl(3) (2) and [Mo(3)S(4)(FeSPh)(dmpe)(3)(SPh)(3)] (3). A detailed computational study has also been carried out to understand the details of the mechanism of substitution at the M-Cl (M = Mo and Fe) bonds as well as the solvolysis at the Fe-Cl sites, with particular emphasis on the role of acids on the substitution process. The results of the calculations are in agreement with the experimental observations, thus justifying the non-existence of an accelerating effect of acids on the thiophenolate substitution reaction, which differs from previous proposals for the Fe(4)S(4) and MoFe(3)S(4) clusters and some related compounds.

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

NASA Technical Reports Server (NTRS)

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

1985-01-01

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

High-Tc superconductivity: The t-J-V model and its applications

NASA Astrophysics Data System (ADS)

Roy, K.; Pal, P.; Nath, S.; Ghosh, N. K.

2017-05-01

We present numerical results of the t-J-V model in an 8-site tilted square cluster using exact diagonalization (ED) method with periodic boundary conditions. Effective hopping amplitude initially increases with inter-site Coulomb repulsion (V), but decreases at larger V's. The hole-hole correlation decreases with inter-site distances at smaller V. With the increase of Coulomb repulsion, the system becomes ordered. The specific heat curves confirm the non-Fermi liquid behavior of the system under t-J-V model.

78 FR 59012 - Environmental Management Site-Specific Advisory Board Chairs

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-25

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board Chairs AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB) Chairs. The Federal Advisory Committee Act (Pub... and site management in the areas of environmental restoration, waste management, and related...

76 FR 30027 - Land Disposal Restrictions: Site-Specific Treatment Variance for Hazardous Selenium-Bearing Waste...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... Restrictions: Site-Specific Treatment Variance for Hazardous Selenium-Bearing Waste Treated by U.S. Ecology.... Ecology Nevada in Beatty, Nevada and withdrew an existing site- specific treatment variance issued to... 268.44(o)) by granting a site-specific treatment variance to U.S. Ecology Nevada in Beatty, Nevada and...

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Properties of flakeboards from hardwoods growing on southern pine sites

Treesearch

C. -Y. Hse

1975-01-01

Boards 0.5 inch thick were made from 3-inch-long flakes of 9 species of southern hardwoods commonly found on pine sites. The main effects of species were due to variation in wood density; low-density species compacted readily when pressed, and the resulting good flake contact improved bonding and gave boards of high strength. With species having specific gravities...

Properties of flakeboards from hardwoods growing on southern pine sites

Treesearch

Chung-Yun Hse

1975-01-01

Boards 0.5 inch thick were made from 3-inch-long flakes of 9 species of southern hardwoods commonly found on pine sites. The main effects of species were doe to variation in wood density; low-density species compacted readily when pressed, and the resulting good flake contact improved bonding and gave boards of high strength. With species having specific gravities...

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

ERIC Educational Resources Information Center

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

2016-01-01

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

Recognition of DNA abasic site nanocavity by fluorophore-switched probe: Suitable for all sequence environments

NASA Astrophysics Data System (ADS)

Wang, Ying; Hu, Yuehua; Wu, Tao; Zhang, Lihua; Liu, Hua; Zhou, Xiaoshun; Shao, Yong

2016-01-01

Removal of a damaged base in DNA produces an abasic site (AP site) nanocavity. If left un-repaired in vivo by the specific enzyme, this nanocavity will result in nucleotide mutation in the following DNA replication. Therefore, selective recognition of AP site nanocavity by small molecules is important for identification of such DNA damage and development of genetic drugs. In this work, we investigate the fluorescence behavior of isoquinoline alkaloids including palmatine (PAL), berberine (BER), epiberberine (EPI), jatrorrhizine (JAT), coptisine (COP), coralyne (COR), worenine (WOR), berberrubine (BEU), sanguinarine (SAN), chelerythrine (CHE), and nitidine (NIT) upon binding with the AP nanocavity. PAL is screened out as the most efficient fluorophore-switched probe to recognize the AP nanocavity over the fully matched DNA. Its fluorescence enhancement occurs for all of the AP nanocavity sequence environments, which has not been achieved by the previously used probes. The bridged π conjugation effect should partially contribute to the AP nanocavity-specific fluorescence, as opposed to the solvent effect. Due to the strong binding with the AP nanocavity, PAL will find wide applications in the DNA damage recognition and sensor development.

Site-Specific Immunosuppression in Vascularized Composite Allotransplantation: Prospects and Potential

PubMed Central

Schnider, Jonas T.; Weinstock, Matthias; Plock, Jan A.; Solari, Mario G.; Venkataramanan, Raman; Zheng, Xin Xiao; Gorantla, Vijay S.

2013-01-01

Skin is the most immunogenic component of a vascularized composite allograft (VCA) and is the primary trigger and target of rejection. The skin is directly accessible for visual monitoring of acute rejection (AR) and for directed biopsy, timely therapeutic intervention, and management of AR. Logically, antirejection drugs, biologics, or other agents delivered locally to the VCA may reduce the need for systemic immunosuppression with its adverse effects. Topical FK 506 (tacrolimus) and steroids have been used in clinical VCA as an adjunct to systemic therapy with unclear beneficial effects. However, there are no commercially available topical formulations for other widely used systemic immunosuppressive drugs such as mycophenolic acid, sirolimus, and everolimus. Investigating the site-specific therapeutic effects and efficacy of systemically active agents may enable optimizing the dosing, frequency, and duration of overall immunosuppression in VCA with minimization or elimination of long-term drug-related toxicity. PMID:23476677

The effect of multiple primary rules on population-based cancer survival

PubMed Central

Weir, Hannah K.; Johnson, Christopher J.; Thompson, Trevor D.

2015-01-01

Purpose Different rules for registering multiple primary (MP) cancers are used by cancer registries throughout the world, making international data comparisons difficult. This study evaluates the effect of Surveillance, Epidemiology, and End Results (SEER) and International Association of Cancer Registries (IACR) MP rules on population-based cancer survival estimates. Methods Data from five US states and six metropolitan area cancer registries participating in the SEER Program were used to estimate age-standardized relative survival (RS%) for first cancers-only and all first cancers matching the selection criteria according to SEER and IACR MP rules for all cancer sites combined and for the top 25 cancer site groups among men and women. Results During 1995–2008, the percentage of MP cancers (all sites, both sexes) increased 25.4 % by using SEER rules (from 14.6 to 18.4 %) and 20.1 % by using IACR rules (from 13.2 to 15.8 %). More MP cancers were registered among females than among males, and SEER rules registered more MP cancers than IACR rules (15.8 vs. 14.4 % among males; 17.2 vs. 14.5 % among females). The top 3 cancer sites with the largest differences were melanoma (5.8 %), urinary bladder (3.5 %), and kidney and renal pelvis (2.9 %) among males, and breast (5.9 %), melanoma (3.9 %), and urinary bladder (3.4 %) among females. Five-year survival estimates (all sites combined) restricted to first primary cancers-only were higher than estimates by using first site-specific primaries (SEER or IACR rules), and for 11 of 21 sites among males and 11 of 23 sites among females. SEER estimates are comparable to IACR estimates for all site-specific cancers and marginally higher for all sites combined among females (RS 62.28 vs. 61.96 %). Conclusion Survival after diagnosis has improved for many leading cancers. However, cancer patients remain at risk of subsequent cancers. Survival estimates based on first cancers-only exclude a large and increasing number of MP cancers. To produce clinically and epidemiologically relevant and less biased cancer survival estimates, data on all cancers should be included in the analysis. The multiple primary rules (SEER or IACR) used to identify primary cancers do not affect survival estimates if all first cancers matching the selection criteria are used to produce site-specific survival estimates. PMID:23558444

77 FR 59598 - Environmental Management Site-Specific Advisory Board, Paducah

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-28

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Paducah AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Paducah. The Federal Advisory Committee Act... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management and...

75 FR 9404 - Environmental Management Site-Specific Advisory Board, Paducah

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-02

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Paducah AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Paducah. The Federal Advisory Committee Act... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management and...

75 FR 61711 - Environmental Management Site-Specific Advisory Board, Paducah

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-06

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Paducah AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Paducah. The Federal Advisory Committee Act... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management and...

75 FR 56526 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Initiative Workshop of the Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management and...

75 FR 66074 - Environmental Management Site-Specific Advisory Board, Paducah

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-27

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Paducah AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Paducah. The Federal Advisory Committee Act... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management and...

75 FR 54600 - Environmental Management Site-Specific Advisory Board, Paducah

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Paducah AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Paducah. The Federal Advisory Committee Act... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management and...

76 FR 5147 - Environmental Management Site-Specific Advisory Board, Paducah

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Paducah AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Paducah. The Federal Advisory Committee Act... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management and...

75 FR 24686 - Environmental Management Site-Specific Advisory Board, Paducah

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Paducah AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Paducah. The Federal Advisory Committee Act... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management and...

Quantum dynamics of water dissociative chemisorption on rigid Ni(111): An approximate nine-dimensional treatment

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

Jiang, Bin, E-mail: bjiangch@ustc.edu.cn, E-mail: hguo@unm.edu; Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131; Song, Hongwei

The quantum dynamics of water dissociative chemisorption on the rigid Ni(111) surface is investigated using a recently developed nine-dimensional potential energy surface. The quantum dynamical model includes explicitly seven degrees of freedom of D{sub 2}O at fixed surface sites, and the final results were obtained with a site-averaging model. The mode specificity in the site-specific results is reported and analyzed. Finally, the approximate sticking probabilities for various vibrationally excited states of D{sub 2}O are obtained considering surface lattice effects and formally all nine degrees of freedom. The comparison with experiment reveals the inaccuracy of the density functional theory and suggestsmore » the need to improve the potential energy surface.« less

Mapping mutational effects along the evolutionary landscape of HIV envelope.

PubMed

Haddox, Hugh K; Dingens, Adam S; Hilton, Sarah K; Overbaugh, Julie; Bloom, Jesse D

2018-03-28

The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at [Formula: see text]100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs-and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env's mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains. © 2018, Haddox et al.

Productivity benefits of warming at regional scale could be offset by detrimental impacts on site level hydrology.

PubMed

Zeng, Qing; Zhang, Yamian; Wen, Li; Li, Zhaxijie; Duo, Hairui; Lei, Guangchun

2017-11-09

Climate change affects the distribution and persistence of wildlife. Broad scale studies have demonstrated that climate change shifts the geographic ranges and phenology of species. These findings are influential for making high level strategies but not practical enough to guide site specific management. In this study, we explored the environment factors affecting the population of Bar-headed Goose in the key breeding site of Qinghai using generalized additive mixed model (GAMM). Our results showed that 1) there were significant increasing trends in climate variables and river flows to the Qinghai Lake; 2) NDVI in the sites decreased significantly despite the regional positive trend induced by the warmer and wetter climate; 3) NDVI at site scale was negatively correlated to lake water level; and 4) the abundance of Bar-headed Goose decreased significantly at all sites. While the abundance was positively related to NDVI at breeding sites, the GAMM revealed an opposite relationship at foraging areas. Our findings demonstrated the multi-facet effects of climate change on population dynamics; and the effect at global/regional scale could be complicated by site level factors.

Using transcriptomic tools to evaluate biological effects across effluent gradients at a diverse set of study sites in Minnesota, USA

EPA Science Inventory

The aim of this overall project was to explore the utility of ?‘omics’ approaches in monitoring aquatic environments where complex, often unknown, stressors make chemical-specific risk assessment untenable. This specific component of the effort examined changes in the fathead min...

Using Web-based Tutorials To Enhance Library Instruction.

ERIC Educational Resources Information Center

Kocour, Bruce G.

2000-01-01

Describes the development of a Web site for library instruction at Carson-Newman College (TN) and its integration into English composition courses. Describes the use of a virtual tour, a tutorial on database searching, tutorials on specific databases, and library guides to specific disciplines to create an effective mechanism for active learning.…

Development of glycosynthases with broad glycan specificity for the efficient glyco-remodeling of antibodies.

PubMed

Shivatare, Sachin S; Huang, Lin-Ya; Zeng, Yi-Fang; Liao, Jung-Yu; You, Tsai-Hong; Wang, Shi-Yun; Cheng, Ting; Chiu, Chih-Wei; Chao, Ping; Chen, Li-Tzu; Tsai, Tsung-I; Huang, Chiu-Chen; Wu, Chung-Yi; Lin, Nan-Horng; Wong, Chi-Huey

2018-06-12

The first systematic investigation of the effect of high mannose, hybrid, and bi- and tri-antennary complex type glycans on the effector functions of antibodies was achieved by the discovery of novel Endo-S2 mutants generated by site-directed mutagenesis as glycosynthases with broad substrate specificity.

Pressure-specific and multiple pressure response of fish assemblages in European running waters☆

PubMed Central

Schinegger, Rafaela; Trautwein, Clemens; Schmutz, Stefan

2013-01-01

We classified homogenous river types across Europe and searched for fish metrics qualified to show responses to specific pressures (hydromorphological pressures or water quality pressures) vs. multiple pressures in these river types. We analysed fish taxa lists from 3105 sites in 16 ecoregions and 14 countries. Sites were pre-classified for 15 selected pressures to separate unimpacted from impacted sites. Hierarchical cluster analysis was used to split unimpacted sites into four homogenous river types based on species composition and geographical location. Classification trees were employed to predict associated river types for impacted sites with four environmental variables. We defined a set of 129 candidate fish metrics to select the best reacting metrics for each river type. The candidate metrics represented tolerances/intolerances of species associated with six metric types: habitat, migration, water quality sensitivity, reproduction, trophic level and biodiversity. The results showed that 17 uncorrelated metrics reacted to pressures in the four river types. Metrics responded specifically to water quality pressures and hydromorphological pressures in three river types and to multiple pressures in all river types. Four metrics associated with water quality sensitivity showed a significant reaction in up to three river types, whereas 13 metrics were specific to individual river types. Our results contribute to the better understanding of fish assemblage response to human pressures at a pan-European scale. The results are especially important for European river management and restoration, as it is necessary to uncover underlying processes and effects of human pressures on aquatic communities. PMID:24003262

77 FR 4027 - Environmental Management Site-Specific Advisory Board, Nevada

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-26

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Nevada AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Nevada. The Federal Advisory Committee Act (Pub... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management, and...

76 FR 80354 - Environmental Management Site-Specific Advisory Board, Nevada

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-23

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Nevada AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Nevada. The Federal Advisory Committee Act (Pub... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management, and...

75 FR 82004 - Environmental Management Site-Specific Advisory Board, Nevada

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-29

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Nevada AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Nevada. The Federal Advisory Committee Act (Pub... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management, and...

78 FR 20311 - Environmental Management Site-Specific Advisory Board Chairs

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-04

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board Chairs AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB) Chairs. The Federal Advisory Committee Act (Pub... Board is to make recommendations to DOE-EM and site management in the areas of environmental restoration...

77 FR 12044 - Environmental Management Site-Specific Advisory Board, Nevada

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-28

... Environmental Management Site-Specific Advisory Board (EM SSAB), Nevada. The Federal Advisory Committee Act (Pub... Board is to make recommendations to DOE-EM and site management in the areas of environmental restoration... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Nevada AGENCY...

76 FR 39080 - Environmental Management Site-Specific Advisory Board, Idaho National Laboratory

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-05

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Idaho National... meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Idaho National Laboratory... recommendations to DOE-EM and site management in the areas of environmental restoration, waste management, and...

Prior knowledge-based approach for associating contaminants with biological effects: A case study in the St. Croix River basin, MN, WI, USA

USGS Publications Warehouse

Schroeder, Anthony L.; Martinovic-Weigelt, Dalma; Ankley, Gerald T.; Lee, Kathy E.; Garcia-Reyero, Natalia; Perkins, Edward J.; Schoenfuss, Heiko L.; Villeneuve, Daniel L.

2017-01-01

Evaluating potential adverse effects of complex chemical mixtures in the environment is challenging. One way to address that challenge is through more integrated analysis of chemical monitoring and biological effects data. In the present study, water samples from five locations near two municipal wastewater treatment plants in the St. Croix River basin, on the border of MN and WI, USA, were analyzed for 127 organic contaminants. Known chemical-gene interactions were used to develop site-specific knowledge assembly models (KAMs) and formulate hypotheses concerning possible biological effects associated with chemicals detected in water samples from each location. Additionally, hepatic gene expression data were collected for fathead minnows (Pimephales promelas) exposed in situ, for 12 d, at each location. Expression data from oligonucleotide microarrays were analyzed to identify functional annotation terms enriched among the differentially-expressed probes. The general nature of many of the terms made hypothesis formulation on the basis of the transcriptome-level response alone difficult. However, integrated analysis of the transcriptome data in the context of the site-specific KAMs allowed for evaluation of the likelihood of specific chemicals contributing to observed biological responses. Thirteen chemicals (atrazine, carbamazepine, metformin, thiabendazole, diazepam, cholesterol, p-cresol, phenytoin, omeprazole, ethyromycin, 17β-estradiol, cimetidine, and estrone), for which there was statistically significant concordance between occurrence at a site and expected biological response as represented in the KAM, were identified. While not definitive, the approach provides a line of evidence for evaluating potential cause-effect relationships between components of a complex mixture of contaminants and biological effects data, which can inform subsequent monitoring and investigation.

Prior knowledge-based approach for associating contaminants with biological effects: A case study in the St. Croix River basin, MN, WI, USA.

PubMed

Schroeder, Anthony L; Martinović-Weigelt, Dalma; Ankley, Gerald T; Lee, Kathy E; Garcia-Reyero, Natalia; Perkins, Edward J; Schoenfuss, Heiko L; Villeneuve, Daniel L

2017-02-01

Evaluating potential adverse effects of complex chemical mixtures in the environment is challenging. One way to address that challenge is through more integrated analysis of chemical monitoring and biological effects data. In the present study, water samples from five locations near two municipal wastewater treatment plants in the St. Croix River basin, on the border of MN and WI, USA, were analyzed for 127 organic contaminants. Known chemical-gene interactions were used to develop site-specific knowledge assembly models (KAMs) and formulate hypotheses concerning possible biological effects associated with chemicals detected in water samples from each location. Additionally, hepatic gene expression data were collected for fathead minnows (Pimephales promelas) exposed in situ, for 12 d, at each location. Expression data from oligonucleotide microarrays were analyzed to identify functional annotation terms enriched among the differentially-expressed probes. The general nature of many of the terms made hypothesis formulation on the basis of the transcriptome-level response alone difficult. However, integrated analysis of the transcriptome data in the context of the site-specific KAMs allowed for evaluation of the likelihood of specific chemicals contributing to observed biological responses. Thirteen chemicals (atrazine, carbamazepine, metformin, thiabendazole, diazepam, cholesterol, p-cresol, phenytoin, omeprazole, ethyromycin, 17β-estradiol, cimetidine, and estrone), for which there was statistically significant concordance between occurrence at a site and expected biological response as represented in the KAM, were identified. While not definitive, the approach provides a line of evidence for evaluating potential cause-effect relationships between components of a complex mixture of contaminants and biological effects data, which can inform subsequent monitoring and investigation. Published by Elsevier Ltd.

Research Resource: Aorta- and Liver-Specific ERα-Binding Patterns and Gene Regulation by Estrogen

PubMed Central

Gordon, Francesca K.; Vallaster, Caroline S.; Westerling, Thomas; Iyer, Lakshmanan K.; Brown, Myles

2014-01-01

Estrogen has vascular protective effects in premenopausal women and in women younger than 60 years who are receiving hormone replacement therapy. However, estrogen also increases the risks of breast and uterine cancers and of venous thromboses linked to up-regulation of coagulation factors in the liver. In mouse models, the vasculoprotective effects of estrogen are mediated by the estrogen receptor α (ERα) transcription factor. Here, through next-generation sequencing approaches, we show that almost all of the genes regulated by 17β-estradiol (E2) differ between mouse aorta and mouse liver, ex vivo, and that this difference is associated with a distinct genomewide distribution of ERα on chromatin. Bioinformatic analysis of E2-regulated promoters and ERα binding site sequences identify several transcription factors that may determine the tissue specificity of ERα binding and E2-regulated genes, including the enrichment of NF-κB, AML1, and AP1 sites in the promoters of E2 down-regulated inflammatory genes in aorta but not liver. The possible vascular-specific functions of these factors suggest ways in which the protective effects of estrogen could be promoted in the vasculature without incurring negative effects in other tissues. PMID:24992180

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

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

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

2009-02-26

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

Phytoplankton responses to temperature increases are constrained by abiotic conditions and community composition.

PubMed

Striebel, Maren; Schabhüttl, Stefanie; Hodapp, Dorothee; Hingsamer, Peter; Hillebrand, Helmut

2016-11-01

Effects of temperature changes on phytoplankton communities seem to be highly context-specific, but few studies have analyzed whether this context specificity depends on differences in the abiotic conditions or in species composition between studies. We present an experiment that allows disentangling the contribution of abiotic and biotic differences in shaping the response to two aspects of temperature change: permanent increase of mean temperature versus pulse disturbance in form of a heat wave. We used natural communities from six different sites of a floodplain system as well as artificially mixed communities from laboratory cultures and grew both, artificial and natural communities, in water from the six different floodplain lakes (sites). All 12 contexts (2 communities × 6 sites) were first exposed to three different temperature levels (12, 18, 24 °C, respectively) and afterward to temperature pulses (4 °C increase for 7 h day(-1)). Temperature-dependent changes in biomass and community composition depended on the initial composition of phytoplankton communities. Abiotic conditions had a major effect on biomass of phytoplankton communities exposed to different temperature conditions, however, the effect of biotic and abiotic conditions together was even more pronounced. Additionally, phytoplankton community responses to pulse temperature effects depended on the warming history. By disentangling abiotic and biotic effects, our study shows that temperature-dependent effects on phytoplankton communities depend on both, biotic and abiotic constraints.

Effects of coal mining, forestry, and road construction on southern Appalachian stream invertebrates and habitats.

PubMed

Gangloff, Michael M; Perkins, Michael; Blum, Peter W; Walker, Craig

2015-03-01

Coal has been extracted via surface and sub-surface mining for decades throughout the Appalachian Mountains. New interest in ridge-top mining has raised concerns about possible waterway impacts. We examined effects of forestry, mining, and road construction-based disturbance on physico-chemistry and macroinvertebrate communities in east-central Tennessee headwater streams. Although 11 of 30 sites failed Tennessee's biocriteria scoring system, invertebrate richness was moderately high and we did not find significant differences in any water chemistry or habitat parameters between sites with passing and failing scores. However, conductivity and dissolved solid concentrations appeared elevated in the majority of study streams. Principal components (PCs) analysis indicated that six PCs accounted for ~77 % of among-site habitat variability. One PC associated with dissolved oxygen and specific conductance explained the second highest proportion of among-site variability after catchment area. Specific conductance was not correlated with catchment area but was strongly correlated with mining activity. Composition and success of multivariate models using habitat PCs to predict macroinvertebrate metrics was highly variable. PC scores associated with water chemistry and substrate composition were most frequently included in significant models. These results suggest that impacts of historical and current coal mining remain a source of water quality and macroinvertebrate community impairment in this region, but effects are subtle. Our results suggest that surface mining may have chronic and system-wide effects on habitat conditions and invertebrate communities in Cumberland Plateau streams.

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

PubMed

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

2016-07-22

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

Functional cis-regulatory modules encoded by mouse-specific endogenous retrovirus

PubMed Central

Sundaram, Vasavi; Choudhary, Mayank N. K.; Pehrsson, Erica; Xing, Xiaoyun; Fiore, Christopher; Pandey, Manishi; Maricque, Brett; Udawatta, Methma; Ngo, Duc; Chen, Yujie; Paguntalan, Asia; Ray, Tammy; Hughes, Ava; Cohen, Barak A.; Wang, Ting

2017-01-01

Cis-regulatory modules contain multiple transcription factor (TF)-binding sites and integrate the effects of each TF to control gene expression in specific cellular contexts. Transposable elements (TEs) are uniquely equipped to deposit their regulatory sequences across a genome, which could also contain cis-regulatory modules that coordinate the control of multiple genes with the same regulatory logic. We provide the first evidence of mouse-specific TEs that encode a module of TF-binding sites in mouse embryonic stem cells (ESCs). The majority (77%) of the individual TEs tested exhibited enhancer activity in mouse ESCs. By mutating individual TF-binding sites within the TE, we identified a module of TF-binding motifs that cooperatively enhanced gene expression. Interestingly, we also observed the same motif module in the in silico constructed ancestral TE that also acted cooperatively to enhance gene expression. Our results suggest that ancestral TE insertions might have brought in cis-regulatory modules into the mouse genome. PMID:28348391

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

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

LAH, J; Shin, D; Manger, R

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

Multiple cis-acting sequence elements are required for efficient splicing of simian virus 40 small-t antigen pre-mRNA.

PubMed Central

Fu, X Y; Colgan, J D; Manley, J L

1988-01-01

We have determined the effects of a number of mutations in the small-t antigen mRNA intron on the alternative splicing pattern of the simian virus 40 early transcript. Expansion of the distance separating the small-t pre-mRNA lariat branch point and the shared large T-small t 3' splice site from 18 to 29 nucleotides (nt) resulted in a relative enhancement of small-t splicing in vivo. This finding, coupled with the observation that large-T pre-RNA splicing in vitro was not affected by this expansion, suggests that small-t splicing is specifically constrained by a short branch point-3' splice site distance. Similarly, the distance separating the 5' splice site and branch point (48 nt) was found to be at or near a minimum for small-t splicing, because deletions in this region as small as 2 nt dramatically reduced the ratio of small-t to large-T mRNA that accumulated in transfected cells. Finally, a specific sequence within the small-t intron, encompassing the upstream branch sites used in large-T splicing, was found to be an important element in the cell-specific pattern of early alternative splicing. Substitutions within this region reduced the ratio of small-t to large-T mRNA produced in HeLa cells but had only minor effects in human 293 cells. Images PMID:2851720

Metal Ion Binding at the Catalytic Site Induces Widely Distributed Changes in a Sequence Specific Protein–DNA Complex

PubMed Central

2016-01-01

Metal ion cofactors can alter the energetics and specificity of sequence specific protein–DNA interactions, but it is unknown if the underlying effects on structure and dynamics are local or dispersed throughout the protein–DNA complex. This work uses EcoRV endonuclease as a model, and catalytically inactive lanthanide ions, which replace the Mg2+ cofactor. Nuclear magnetic resonance (NMR) titrations indicate that four Lu3+ or two La3+ cations bind, and two new crystal structures confirm that Lu3+ binding is confined to the active sites. NMR spectra show that the metal-free EcoRV complex with cognate (GATATC) DNA is structurally distinct from the nonspecific complex, and that metal ion binding sites are not assembled in the nonspecific complex. NMR chemical shift perturbations were determined for 1H–15N amide resonances, for 1H–13C Ile-δ-CH3 resonances, and for stereospecifically assigned Leu-δ-CH3 and Val-γ-CH3 resonances. Many chemical shifts throughout the cognate complex are unperturbed, so metal binding does not induce major conformational changes. However, some large perturbations of amide and side chain methyl resonances occur as far as 34 Å from the metal ions. Concerted changes in specific residues imply that local effects of metal binding are propagated via a β-sheet and an α-helix. Both amide and methyl resonance perturbations indicate changes in the interface between subunits of the EcoRV homodimer. Bound metal ions also affect amide hydrogen exchange rates for distant residues, including a distant subdomain that contacts DNA phosphates and promotes DNA bending, showing that metal ions in the active sites, which relieve electrostatic repulsion between protein and DNA, cause changes in slow dynamics throughout the complex. PMID:27786446

76 FR 21878 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-19

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act... Board: The purpose of the Board is to make recommendations to DOE-EM and site management in the areas of...

75 FR 65615 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-26

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act... the Board: The purpose of the Board is to make recommendations to DOE-EM and site management in the...

75 FR 82003 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-29

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act... the Board: The purpose of the Board is to make recommendations to DOE-EM and site management in the...

77 FR 75626 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-21

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act...: Purpose of the Board: The purpose of the Board is to make recommendations to DOE-EM and site management in...

77 FR 37390 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act... Board: The purpose of the Board is to make recommendations to DOE-EM and site management in the areas of...

77 FR 2283 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-17

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act... Board: The purpose of the Board is to make recommendations to DOE-EM and site management in the areas of...

Investigating temporal field sampling strategies for site-specific calibration of three soil moisture-neutron intensity parameterisation methods

NASA Astrophysics Data System (ADS)

Iwema, J.; Rosolem, R.; Baatz, R.; Wagener, T.; Bogena, H. R.

2015-07-01

The Cosmic-Ray Neutron Sensor (CRNS) can provide soil moisture information at scales relevant to hydrometeorological modelling applications. Site-specific calibration is needed to translate CRNS neutron intensities into sensor footprint average soil moisture contents. We investigated temporal sampling strategies for calibration of three CRNS parameterisations (modified N0, HMF, and COSMIC) by assessing the effects of the number of sampling days and soil wetness conditions on the performance of the calibration results while investigating actual neutron intensity measurements, for three sites with distinct climate and land use: a semi-arid site, a temperate grassland, and a temperate forest. When calibrated with 1 year of data, both COSMIC and the modified N0 method performed better than HMF. The performance of COSMIC was remarkably good at the semi-arid site in the USA, while the N0mod performed best at the two temperate sites in Germany. The successful performance of COSMIC at all three sites can be attributed to the benefits of explicitly resolving individual soil layers (which is not accounted for in the other two parameterisations). To better calibrate these parameterisations, we recommend in situ soil sampled to be collected on more than a single day. However, little improvement is observed for sampling on more than 6 days. At the semi-arid site, the N0mod method was calibrated better under site-specific average wetness conditions, whereas HMF and COSMIC were calibrated better under drier conditions. Average soil wetness condition gave better calibration results at the two humid sites. The calibration results for the HMF method were better when calibrated with combinations of days with similar soil wetness conditions, opposed to N0mod and COSMIC, which profited from using days with distinct wetness conditions. Errors in actual neutron intensities were translated to average errors specifically to each site. At the semi-arid site, these errors were below the typical measurement uncertainties from in situ point-scale sensors and satellite remote sensing products. Nevertheless, at the two humid sites, reduction in uncertainty with increasing sampling days only reached typical errors associated with satellite remote sensing products. The outcomes of this study can be used by researchers as a CRNS calibration strategy guideline.

Tetrazepam: a benzodiazepine which dissociates sedation from other benzodiazepine activities. II. In vitro and in vivo interactions with benzodiazepine binding sites

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

Keane, P.E.; Bachy, A.; Morre, M.

1988-05-01

Tetrazepam is a 1,4-benzodiazepine (BZD) derivative which, in rodents, appears to have very little sedative and ataxic effects. In an attempt to identify the molecular mechanisms underlying this particular pharmacological profile we examined the interaction of tetrazepam with BZD binding sites. Tetrazepam interacted competitively with central and peripheral BZD binding sites and exhibited comparable affinities for both sites. Tetrazepam was approximately one-seventh as potent as diazepam at the central receptor and as potent as diazepam at the peripheral binding site. Tetrazepam did not distinguish type I from type II central BZD receptors, as evidenced by comparable affinities for the cerebellarmore » and hippocampal receptors. In vitro autoradiographic studies showed that tetrazepam displaced (3H)flunitrazepam from rat brain membranes without any clear regional specificity. Like all BZD receptor agonists, tetrazepam exhibited a gamma-aminobutyric acid shift, a photoaffinity shift and potentiated the binding of 35S-t-butyl-bicyclophosphorothionate to rat brain membranes. However, the latter effect was observed at relatively high concentrations of tetrazepam. In vivo, tetrazepam displaced specifically bound (3H)flunitrazepam from mouse brain (ID50, 37 mg/kg p.o. vs 3.5 mg/kg p.o. for diazepam) and from mouse kidney (ID50, 38 mg/kg p.o. vs. 21 mg/kg p.o. for diazepam). It is concluded that tetrazepam is a BZD receptor agonist; the molecular mechanisms which underly the low sedative potential of the drug cannot at present be explained by a particular interaction with either central or peripheral BZD binding sites, but may be related to the drug's relatively weak effect on 35S-t-butyl-bicyclophosphorothionate binding.« less

Liposomal systems as viable drug delivery technology for skin cancer sites with an outlook on lipid-based delivery vehicles and diagnostic imaging inputs for skin conditions'.

PubMed

Akhtar, Naseem; Khan, Riaz A

2016-10-01

Skin cancer is among one of the most common human malignancies wide-spread world-over with mortality statistics rising continuously at an alarming rate. The increasing frequency of these malignancies has marked the need for adopting effective treatment plan coupled with better and site-specific delivery options for the desired therapeutic agent's availability at the affected site. The concurrent delivery approaches to cancerous tissues are under constant challenge and, as a result, are evolving and gaining advancements in terms of delivery modes, therapeutic agents and site-specificity of the therapeutics delivery. The lipid-based liposomal drug delivery is an attractive and emerging option, and which is meticulously shaping up beyond a threshold level to a promising, and viable route for the effective delivery of therapeutic agents and other required injuctions to the skin cancer. An update on liposomal delivery of chemotherapeutic agents, natural-origin compounds, photosensitizer, and DNA repair enzymes as well as other desirable and typical delivery modes employed in drug delivery and in the treatment of skin cancers is discussed in details. Moreover, liposomal delivery of nucleic acid-based therapeutics, i.e., small interfering RNA (siRNA), mRNA therapy, and RGD-linked liposomes are among the other promising novel technology under constant development. The current clinical applicability, viable clinical plans, future prospects including transport feasibility of delivery vesicles and imaging techniques in conjunction with the therapeutic agents is also discussed. The ongoing innovations in liposomal drug delivery technology for skin cancers hold promise for further development of the methodology for better, more effective and site-specific delivery as part of the better treatment plan by ensuring faster drug transport, better and full payload delivery with enough and required concentration of the dose. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of Green Tides in Coastal Nursery Grounds on the Habitat Selection and Individual Performance of Juvenile Fish

PubMed Central

Murillo, Laurence; Randon, Marine; Lebot, Clément

2017-01-01

Coastal ecosystems, which provide numerous essential ecological functions for fish, are threatened by the proliferation of green macroalgae that significantly modify habitat conditions in intertidal areas. Understanding the influence of green tides on the nursery function of these ecosystems is essential to determine their potential effects on fish recruitment success. In this study, the influence of green tides on juvenile fish was examined in an intertidal sandy beach area, the Bay of Saint-Brieuc (Northwestern France), during two annual cycles of green tides with varying levels of intensity. The responses of three nursery-dependent fish species, the pelagic Sprattus sprattus (L.), the demersal Dicentrarchus labrax (L.) and the benthic Pleuronectes platessa L., were analysed to determine the effects of green tides according to species-specific habitat niche and behaviour. The responses to this perturbation were investigated based on habitat selection and a comparison of individual performance between a control and an impacted site. Several indices on different integrative scales were examined to evaluate these responses (antioxidant defence capacity, muscle total lipid, morphometric condition and growth). Based on these analyses, green tides affect juvenile fish differently according to macroalgal density and species-specific tolerance, which is linked to their capacity to move and to their distribution in the water column. A decreasing gradient of sensitivity was observed from benthic to demersal and pelagic fish species. At low densities of green macroalgae, the three species stayed at the impacted site and the growth of plaice was reduced. At medium macroalgal densities, plaice disappeared from the impacted site and the growth of sea bass and the muscle total lipid content of sprat were reduced. Finally, when high macroalgal densities were reached, none of the studied species were captured at the impacted site. Hence, sites affected by green tides are less favourable nursery grounds for all the studied species, with species-specific effects related to macroalgal density. PMID:28125605

Influence of Green Tides in Coastal Nursery Grounds on the Habitat Selection and Individual Performance of Juvenile Fish.

PubMed

Le Luherne, Emilie; Le Pape, Olivier; Murillo, Laurence; Randon, Marine; Lebot, Clément; Réveillac, Elodie

2017-01-01

Coastal ecosystems, which provide numerous essential ecological functions for fish, are threatened by the proliferation of green macroalgae that significantly modify habitat conditions in intertidal areas. Understanding the influence of green tides on the nursery function of these ecosystems is essential to determine their potential effects on fish recruitment success. In this study, the influence of green tides on juvenile fish was examined in an intertidal sandy beach area, the Bay of Saint-Brieuc (Northwestern France), during two annual cycles of green tides with varying levels of intensity. The responses of three nursery-dependent fish species, the pelagic Sprattus sprattus (L.), the demersal Dicentrarchus labrax (L.) and the benthic Pleuronectes platessa L., were analysed to determine the effects of green tides according to species-specific habitat niche and behaviour. The responses to this perturbation were investigated based on habitat selection and a comparison of individual performance between a control and an impacted site. Several indices on different integrative scales were examined to evaluate these responses (antioxidant defence capacity, muscle total lipid, morphometric condition and growth). Based on these analyses, green tides affect juvenile fish differently according to macroalgal density and species-specific tolerance, which is linked to their capacity to move and to their distribution in the water column. A decreasing gradient of sensitivity was observed from benthic to demersal and pelagic fish species. At low densities of green macroalgae, the three species stayed at the impacted site and the growth of plaice was reduced. At medium macroalgal densities, plaice disappeared from the impacted site and the growth of sea bass and the muscle total lipid content of sprat were reduced. Finally, when high macroalgal densities were reached, none of the studied species were captured at the impacted site. Hence, sites affected by green tides are less favourable nursery grounds for all the studied species, with species-specific effects related to macroalgal density.

Thermodynamics of DNA target site recognition by homing endonucleases

PubMed Central

Eastberg, Jennifer H.; Smith, Audrey McConnell; Zhao, Lei; Ashworth, Justin; Shen, Betty W.; Stoddard, Barry L.

2007-01-01

The thermodynamic profiles of target site recognition have been surveyed for homing endonucleases from various structural families. Similar to DNA-binding proteins that recognize shorter target sites, homing endonucleases display a narrow range of binding free energies and affinities, mediated by structural interactions that balance the magnitude of enthalpic and entropic forces. While the balance of ΔH and TΔS are not strongly correlated with the overall extent of DNA bending, unfavorable ΔHbinding is associated with unstacking of individual base steps in the target site. The effects of deleterious basepair substitutions in the optimal target sites of two LAGLIDADG homing endonucleases, and the subsequent effect of redesigning one of those endonucleases to accommodate that DNA sequence change, were also measured. The substitution of base-specific hydrogen bonds in a wild-type endonuclease/DNA complex with hydrophobic van der Waals contacts in a redesigned complex reduced the ability to discriminate between sites, due to nonspecific ΔSbinding. PMID:17947319

Interim pressure garment therapy (4-6 mmHg) and its effect on donor site healing in burn patients: study protocol for a randomised controlled trial.

PubMed

Donovan, Michelle L; Muller, Michael J; Simpson, Claire; Rudd, Michael; Paratz, Jennifer

2016-04-26

Pressure garment therapy (PGT) is well accepted and commonly used by clinicians in the treatment of burns scars and grafts. The medium to high pressures (24-40 mmHg) in these garments can support scar minimisation, and evidence is well documented for this particular application. However, PGT specifically for burn donor sites, of which a sequela is also scarring, is not well documented. This study protocol investigates the impact of a low pressure (4-6 mmHg) interim garment on donor site healing and scarring. With a primary purpose of holding donor dressings in place, the application of the interim pressure garment (IPG) appears to have been twofold. IPGs for donor sites have involved inconsistent application with a focus on securing wound dressing rather than scar management. However, anecdotal and observational evidence suggests that IPGs also make a difference to some patient's scar outcomes for donor sites. This study protocol outlines a randomised controlled trial designed to test the effectiveness of this treatment on reducing scarring to burn donor sites. This study is a single-centre, single (assessor)-blinded, randomised control trial in patients with burns donor sites to their thighs. Patients will be randomly allocated to a control group (with no compression to donor sites) or to an experimental group (with compression to donor sites) as the comparative treatment. Groups will be compared at baseline regarding the important prognostic indicators: donor site location, depth, size, age, and time since graft (5 days). The IPG treatment will be administered post-operatively (on day 5). Follow-up assessments and garment replacement will be undertaken fortnightly for a period of 2 months. This study focuses on a unique area of burns scar management using a low-pressure tubular support garment for the reduction of donor site scars. Such therapy specifically for donor scar management is poorly represented in the literature. This study was designed to test a potentially cost-effective scar prevention for patients with donor sites to the thigh. No known studies of this nature have been carried out to date, and there is a need for rigorous clinical evidence for low-pressure support garments for donor site scar minimisation. Australian New Zealand Clinical Trials Registry identifier ACTRN12610000127000 . Registered 8 Mar 2010.

Survival, growth, and movement of subadult humpback chub, Gila cypha, in the Little Colorado River, Arizona

USGS Publications Warehouse

Dzul, Maria C.; Yackulic, Charles B.; Stone, Dennis M.; Van Haverbeke, David R.

2016-01-01

Ecologists estimate vital rates, such as growth and survival, to better understand population dynamics and identify sensitive life history parameters for species or populations of concern. Here, we assess spatiotemporal variation in growth, movement, density, and survival of subadult humpback chub living in the Little Colorado River, Grand Canyon, AZ from 2001–2002 and 2009–2013. We divided the Little Colorado River into three reaches and used a multistate mark-recapture model to determine rates of movement and differences in survival and density between sites for different cohorts. Additionally, site-specific and year-specific effects on growth were evaluated using a linear model. Results indicate that summer growth was higher for upstream sites compared with downstream sites. In contrast, there was not a consistent spatial pattern across years in winter growth; however, river-wide winter growth was negatively related to the duration of floods from 1 October to 15 May. Apparent survival was estimated to be lower at the most downstream site compared with the upstream sites; however, this could be because in part of increased emigration into the Colorado River at downstream sites. Furthermore, the 2010 cohort (i.e. fish that are age 1 in 2010) exhibited high apparent survival relative to other years. Movement between reaches varied with year, and some years exhibited preferential upstream displacement. Improving understanding of spatiotemporal effects on age 1 humpback chub survival can help inform current management efforts to translocate humpback chub into new locations and give us a better understanding of the factors that may limit this tributary's carrying capacity for humpback chub.

Topographic Change Detection at Select Archeological Sites in Grand Canyon National Park, Arizona, 2006-2007

USGS Publications Warehouse

Collins, Brian D.; Minasian, Diane L.; Kayen, Robert

2009-01-01

Topographic change of archeological sites within the Colorado River corridor of Grand Canyon National Park (GCNP) is a subject of interest to National Park Service managers and other stakeholders in the Glen Canyon Dam Adaptive Management Program. Although long-term topographic change resulting from a variety of natural processes is typical in the Grand Canyon region, a continuing debate exists on whether and how controlled releases from Glen Canyon Dam, located immediately upstream of GCNP, are impacting rates of site erosion, artifact transport, and the preservation of archeological resources. Continued erosion of archeological sites threatens both the archeological resources and our future ability to study evidence of past cultural habitation. Understanding the causes and effects of archaeological site erosion requires a knowledge of several factors including the location and magnitude of the changes occurring in relation to archeological resources, the rate of the changes, and the relative contribution of several potential causes, including sediment depletion associated with managed flows from Glen Canyon Dam, site-specific weather patterns, visitor impacts, and long-term climate change. To obtain this information, highly accurate, spatially specific data are needed from sites undergoing change. Using terrestrial lidar data collection techniques and novel TIN- and GRID-based change-detection post-processing methods, we analyzed topographic data for nine archeological sites. The data were collected using three separate data collection efforts spanning 16 months (May 2006 to September 2007). Our results documented positive evidence of erosion, deposition, or both at six of the nine sites investigated during this time interval. In addition, we observed possible signs of change at two of the other sites. Erosion was concentrated in established gully drainages and averaged 12 cm to 17 cm in depth with maximum depths of 50 cm. Deposition was concentrated at specific locations outside of drainages but generally was spread over larger areas (tens to hundreds of square meters). Maximum depths of deposition averaged 12 cm to 15 cm and reached as much as 35 cm. Overall, we found that the spatial distribution and magnitudes of surface change are specific to each site and that a thorough understanding of the geomorphology, weather, and sand supply is requisite for a complete understanding of the data. Additional work in combining these results with site-specific weather, hydrology, and geomorphology data will assist in the development of working models for determining the causes of the documented topographic changes.

Application of RAD-BCG calculator to Hanford's 300 area shoreline characterization dataset

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

Antonio, Ernest J.; Poston, Ted M.; Tiller, Brett L.

2003-07-01

Abstract. In 2001, a multi-agency study was conducted to characterize potential environmental effects from radiological and chemical contaminants on the near-shore environment of the Columbia River at the 300 Area of the U.S. Department of Energy’s Hanford Site. Historically, the 300 Area was the location of nuclear fuel fabrication and was the main location for research and development activities from the 1940s until the late 1980s. During past waste handling practices uranium, copper, and other heavy metals were routed to liquid waste streams and ponds near the Columbia River shoreline. The Washington State Department of Health and the Pacific Northwestmore » National Laboratory’s Surface Environmental Surveillance Project sampled various environmental components including river water, riverbank spring water, sediment, fishes, crustaceans, bivalve mollusks, aquatic insects, riparian vegetation, small mammals, and terrestrial invertebrates for analyses of radiological and chemical constituents. The radiological analysis results for water and sediment were used as initial input into the RAD-BCG Calculator. The RAD-BCG Calculator, a computer program that uses an Excel® spreadsheet and Visual Basic® software, showed that maximum radionuclide concentrations measured in water and sediment were lower than the initial screening criteria for concentrations to produce dose rates at existing or proposed limits. Radionuclide concentrations measured in biota samples were used to calculate site-specific bioaccumulation coefficients (Biv) to test the utility of the RAD-BCG-Calculator’s site-specific screening phase. To further evaluate site-specific effects, the default Relative Biological Effect (RBE) for internal alpha particle emissions was reduced by half and the program’s kinetic/allometric calculation approach was initiated. The subsequent calculations showed the initial RAD-BCG Calculator results to be conservative, which is appropriate for screening purposes.« less

Effects of mutation at the D-JH junction on affinity, specificity, and idiotypy of anti-progesterone antibody DB3.

PubMed

He, Mingyue; Hamon, Maureen; Liu, Hong; Corper, Adam L; Taussig, Michael J

2006-09-01

The crystal structures of the Fab' fragment of the anti-progesterone monoclonal antibody DB3 and its complexes with steroid haptens have shown that the D-JH junctional residue TrpH100 is a key contributor to binding site interactions with ligands. The indole group of TrpH100 also undergoes a significant conformational change between the bound and unliganded states, effectively opening and closing the combining site pocket. In order to explore the effect of substitutions at this position on steroid recognition, we have carried out mutagenesis on a construct encoding a three-domain single-chain fragment (VH/K) of DB3 expressed in Escherichia coli. TrpH100 was replaced by 13 different amino acids or deleted, and the functional and antigenic properties of the mutated fragments were analyzed. Most substitutions, including small, hydrophobic, hydrophilic, neutral, and negatively charged side chains, were reduced or abolished binding to free progesterone, although binding to progesterone-BSA was partially retained. The reduction in antigen binding was paralleled by alteration of the idiotype associated with the DB3 combining site. In contrast, the replacement of TrpH100 by Arg produced a mutant that retained wild-type antibody affinity and idiotype, but with altered specificity. Significant changes in this mutant included increased relative affinities of 10(4)-fold for progesterone-3-carboxymethyloxime and 10-fold for aetiocholanolone. Our results demonstrate an essential role for the junctional residue H100 in determining steroid-binding specificity and combining site idiotype and show that these properties can be changed by a single amino acid substitution at this position.

Fifteen-year patterns of soil carbon and nitrogen following biomass harvesting

USGS Publications Warehouse

Kurth, Valerie J.; D'Amato, Anthony W.; Palik, Brian J.; Bradford, John B.

2014-01-01

The substitution of forest-derived woody biofuels for fossil fuel energy has garnered increasing attention in recent years, but information regarding the mid- and long-term effects on soil productivity is limited. We investigated 15-yr temporal trends in forest floor and mineral soil (0–30 cm) C and N pools in response to organic matter removal treatments (OMR; stem-only harvest, SOH; whole-tree harvest, WTH; and whole-tree plus forest floor removal, FFR) at three edaphically distinct aspen (Populus tremuloides Michx. and P. grandidentata Michx.) forests in the Great Lakes region. The OMR and temporal effects were generally site specific, and both were most evident in the forest floor and combined profile (mineral soil and forest floor) compared with the mineral soil alone. Forest floor and combined profile C and N pools were generally similar in the SOH and WTH treatments, suggesting that slash retention has little impact on soil C and N in this time frame. Temporal changes in C and N at one of the three sites were consistent with patterns documented following exotic earthworm invasion, but mineral soil pools at the other two sites were stable over time. Power analyses demonstrated that significant effects were more likely to be detected for temporal differences than the effects of OMR and in the combined profile than in the mineral soil. Our findings are consistent with previous work demonstrating that OMR effects on soil C and N pools are site specific and more apparent in the forest floor than the mineral soil.

Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein-Protein Interactions.

PubMed

Pedersen, Søren W; Albertsen, Louise; Moran, Griffin E; Levesque, Brié; Pedersen, Stine B; Bartels, Lina; Wapenaar, Hannah; Ye, Fei; Zhang, Mingjie; Bowen, Mark E; Strømgaard, Kristian

2017-09-15

The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effect of phosphorylation on PSD-95, we used semisynthetic strategies to introduce phosphorylated amino acids at four positions within the PDZ domains and examined the effects on interactions with a large set of binding partners. We observed complex effects on affinity. Most notably, phosphorylation at Y397 induced a significant increase in affinity for stargazin, as confirmed by NMR and single molecule FRET. Additionally, we compared the effects of phosphorylation to phosphomimetic mutations, which revealed that phosphomimetics are ineffective substitutes for tyrosine phosphorylation. Our strategy to generate site-specifically phosphorylated PDZ domains provides a detailed understanding of the role of phosphorylation in the regulation of PSD-95 interactions.

Sorbed atrazine shifts into non-desorbable sites of soil organic matter during aging.

PubMed

Park, Jeong-Hun; Feng, Yucheng; Cho, Sung Yong; Voice, Thomas C; Boyd, Stephen A

2004-11-01

Soil-chemical contact time (aging) is an important determinant of the sorption and desorption characteristics of the organic contaminants and pesticides in the environment. The effects of aging on mechanism-specific sorption and desorption of atrazine were studied in soil and clay slurries. Sorption isotherm and desorption kinetic experiments were performed, and soil-water distribution coefficients and desorption rate parameters were evaluated using linear and non-linear sorption equations and a three-site desorption model, respectively. Aging time for sorption of atrazine in sterilized soil and clay slurries ranged from 2 days to 8 months. Atrazine sorption isotherms were nearly linear (r(2)>0.97) and sorption coefficients were strongly correlated to soil organic carbon content. Sorption distribution coefficients (K(d)) increased with increase in age in all five soils studied, but not for K-montmorillonite. Sorption non-linearity did not increase with increase in age except for the Houghton muck soil. Desorption profiles were well described by the three-site desorption model. The equilibrium site fraction (f(eq)) decreased and the non-desorbable site fraction (f(nd)) increased as a function of aging time in all soils. For K-montmorillonite, f(nd) approximately 0 regardless of aging, showing that aging phenomena are sorbent/mechanism specific. In all soils, it was found that when normalized to soil organic matter content, the concentration of atrazine in desorbable sites was relatively constant, whereas that in non-desorbable site increased. This, and the lack of aging effects on desorption from montmorillonite, suggests that sorption into non-desorbable sites of soil organic matter is primary source of increased atrazine sorption in soils during aging.

Indication of pesticide effects and recolonization in streams.

PubMed

Knillmann, Saskia; Orlinskiy, Polina; Kaske, Oliver; Foit, Kaarina; Liess, Matthias

2018-07-15

The agricultural use of pesticides leads to environmentally relevant pesticide concentrations that cause adverse effects on stream ecosystems. These effects on invertebrate community composition can be identified by the bio-indicator SPEAR pesticides . However, refuge areas have been found to partly confound the indicator. On the basis of three monitoring campaigns of 41 sites in Central Germany, we identified 11 refuge taxa. The refuge taxa, mainly characterized by dispersal-based resilience, were observed only nearby uncontaminated stream sections and independent of the level of pesticide pressure. Through incorporation of this information into the revised SPEAR pesticides indicator, the community structure specifically identified the toxic pressure and no longer depended on the presence of refuge areas. With regard to ecosystem functions, leaf litter degradation was predicted by the revised SPEAR pesticides and the median water temperature at a site (R 2  = 0.38, P = 0.003). Furthermore, we designed the bio-indicator SPEAR refuge to quantify the magnitude of general recolonization at a given stream site. We conclude that the taxonomic composition of aquatic invertebrate communities enables a specific indication of anthropogenic stressors and resilience of ecosystems. Copyright © 2018 Elsevier B.V. All rights reserved.

Migration and site selection of Ornithodiplostomum ptychocheilus (Trematoda: Digenea) metacercariae in the brain of fathead minnows ( Pimephales promelas).

PubMed

Matisz, Chelsea E; Goater, Cameron P; Bray, Douglas

2010-04-01

The migration of subadult parasites to preferred sites within final hosts is well characterized. In contrast, the migration of larval stages of trematodes to specific sites within their second intermediate hosts is poorly understood. We used a serial necropsy approach to characterize the migration of Ornithodiplostomum ptychocheilus diplostomules from the point of cercarial penetration, to encystment within the outermost tissues of the brain of fathead minnows. Diplostomules utilized peripheral nerves to access the central nerve cord, or they used specific cranial nerves to directly access the brain. Within 3 h of exposure to cercariae, 46% of all diplostomules were observed within the medulla of the brain. Diplostomules subsequently utilized specific neural tracts to reach lateral regions of the outermost tissue layer of the optic lobes, the stratum marginale. Diplostomules remained in this layer during their 4-week growth phase, then shifted site to the adjacent meninges for encystment. Characterization of a habitat shift for developing versus encysted metacercariae helps explain the results of previous ecological studies that document transient changes in the effects of metacercariae on the surivival, behaviour, and anti-parasite defences of infected fish.

The potential of magneto-electric nanocarriers for drug delivery

PubMed Central

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

2015-01-01

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

The potential of magneto-electric nanocarriers for drug delivery.

PubMed

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

2014-10-01

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

TLR7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus-like particle vaccines

PubMed Central

Hjelm, Brooke E; Kilbourne, Jacquelyn; Herbst-Kralovetz, Melissa M

2014-01-01

Virus-like particles (VLPs) are an active area of vaccine research, development and commercialization. Mucosal administration of VLPs provides an attractive avenue for delivery of vaccines with the potential to produce robust immune responses. Nasal and oral delivery routes are particularly intriguing due to differential activation of mucosa-associated lymphoid tissues. We compared both intranasal and oral administration of VLPs with a panel of toll-like receptor (TLR) agonists (TLR3, 5, 7, 7/8, and 9) to determine the mucosal adjuvant activity of these immunomodulators. We selected Norwalk virus (NV) VLPs because it is an effective model antigen and an active area of research and commercialization. To prioritize these adjuvants, VLP-specific antibody production in serum (IgG, IgG1, IgG2a), vaginal lavages (IgG, IgA), and fecal pellets (IgA) were measured across a longitudinal timeseries in vaccinated mice. Additional distal mucosal sites (nasal, brochoalveolar, salivary, and gastrointestinal) were evaluated for VLP-specific responses (IgA). Intranasal co-delivery of VLPs with TLR7 or TLR9 agonists produced the most robust and broad-spectrum immune responses, systemically and at distal mucosal sites inducing VLP-specific antibodies at all sites evaluated. In addition, these VLP-specific antibodies blocked binding of NV VLPs to histo-blood group antigen (H type 1), supporting their functionality. Oral administration and/or other TLR agonists tested in the panel did not consistently enhance VLP-specific immune responses. This study demonstrates that intranasal co-delivery of VLPs with TLR7 or TLR9 agonists provides dose-sparing advantages for induction of specific and functional antibody responses against VLPs (i.e., non-replicating antigens) in the respiratory, gastrointestinal, and reproductive tract. PMID:24280723

Forest-Site Planning and Prescription for Control of Annosus Root Disease in Ponderosa Pine and Mixed Conifer Stands

Treesearch

John Nesbitt

1989-01-01

In order to successfully combat pathogens such as annosus root rot, the land manager and pathologist must have periodic dialogue about the pest, its identification, effects, impacts, and cures. The author presents four important topics to structure this dialogue. These are (1) training from the pathologist to the silviculturist or other land manager, (2) site specific...

Mannose-recognition mutant of the galactose/N-acetylgalactosamine-specific C-type lectin CEL-I engineered by site-directed mutagenesis.

PubMed

Moriuchi, Hiromi; Unno, Hideaki; Goda, Shuichiro; Tateno, Hiroaki; Hirabayashi, Jun; Hatakeyama, Tomomitsu

2015-07-01

CEL-I is a galactose/N-acetylgalactosamine-specific C-type lectin isolated from the sea cucumber Cucumaria echinata. Its carbohydrate-binding site contains a QPD (Gln-Pro-Asp) motif, which is generally recognized as the galactose specificity-determining motif in the C-type lectins. In our previous study, replacement of the QPD motif by an EPN (Glu-Pro-Asn) motif led to a weak binding affinity for mannose. Therefore, we examined the effects of an additional mutation in the carbohydrate-binding site on the specificity of the lectin. Trp105 of EPN-CEL-I was replaced by a histidine residue using site-directed mutagenesis, and the binding affinity of the resulting mutant, EPNH-CEL-I, was examined by sugar-polyamidoamine dendrimer assay, isothermal titration calorimetry, and glycoconjugate microarray analysis. Tertiary structure of the EPNH-CEL-I/mannose complex was determined by X-ray crystallographic analysis. Sugar-polyamidoamine dendrimer assay and glycoconjugate microarray analysis revealed a drastic change in the specificity of EPNH-CEL-I from galactose/N-acetylgalactosamine to mannose. The association constant of EPNH-CEL-I for mannose was determined to be 3.17×10(3) M(-1) at 25°C. Mannose specificity of EPNH-CEL-I was achieved by stabilization of the binding of mannose in a correct orientation, in which the EPN motif can form proper hydrogen bonds with 3- and 4-hydroxy groups of the bound mannose. Specificity of CEL-I can be engineered by mutating a limited number of amino acid residues in addition to the QPD/EPN motifs. Versatility of the C-type carbohydrate-recognition domain structure in the recognition of various carbohydrate chains could become a promising platform to develop novel molecular recognition proteins. Copyright © 2015 Elsevier B.V. All rights reserved.

Field-Effect Biosensors for On-Site Detection: Recent Advances and Promising Targets.

PubMed

Choi, Jaebin; Seong, Tae Wha; Jeun, Minhong; Lee, Kwan Hyi

2017-10-01

There is an explosive interest in the immediate and cost-effective analysis of field-collected biological samples, as many advanced biodetection tools are highly sensitive, yet immobile. On-site biosensors are portable and convenient sensors that provide detection results at the point of care. They are designed to secure precision in highly ionic and heterogeneous solutions with minimal hardware. Among various methods that are capable of such analysis, field-effect biosensors are promising candidates due to their unique sensitivity, manufacturing scalability, and integrability with computational circuitry. Recent developments in nanotechnological surface modification show promising results in sensing from blood, serum, and urine. This report gives a particular emphasis on the on-site efficacy of recently published field-effect biosensors, specifically, detection limits in physiological solutions, response times, and scalability. The survey of the properties and existing detection methods of four promising biotargets, exosomes, bacteria, viruses, and metabolites, aims at providing a roadmap for future field-effect and other on-site biosensors. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.

PubMed

Kemp, John P; Medina-Gomez, Carolina; Estrada, Karol; St Pourcain, Beate; Heppe, Denise H M; Warrington, Nicole M; Oei, Ling; Ring, Susan M; Kruithof, Claudia J; Timpson, Nicholas J; Wolber, Lisa E; Reppe, Sjur; Gautvik, Kaare; Grundberg, Elin; Ge, Bing; van der Eerden, Bram; van de Peppel, Jeroen; Hibbs, Matthew A; Ackert-Bicknell, Cheryl L; Choi, Kwangbom; Koller, Daniel L; Econs, Michael J; Williams, Frances M K; Foroud, Tatiana; Zillikens, M Carola; Ohlsson, Claes; Hofman, Albert; Uitterlinden, André G; Davey Smith, George; Jaddoe, Vincent W V; Tobias, Jonathan H; Rivadeneira, Fernando; Evans, David M

2014-06-01

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD.

Phenotypic Dissection of Bone Mineral Density Reveals Skeletal Site Specificity and Facilitates the Identification of Novel Loci in the Genetic Regulation of Bone Mass Attainment

PubMed Central

Estrada, Karol; St Pourcain, Beate; Heppe, Denise H. M.; Warrington, Nicole M.; Oei, Ling; Ring, Susan M.; Kruithof, Claudia J.; Timpson, Nicholas J.; Wolber, Lisa E.; Reppe, Sjur; Gautvik, Kaare; Grundberg, Elin; Ge, Bing; van der Eerden, Bram; van de Peppel, Jeroen; Hibbs, Matthew A.; Ackert-Bicknell, Cheryl L.; Choi, Kwangbom; Koller, Daniel L.; Econs, Michael J.; Williams, Frances M. K.; Foroud, Tatiana; Carola Zillikens, M.; Ohlsson, Claes; Hofman, Albert; Uitterlinden, André G.; Davey Smith, George; Jaddoe, Vincent W. V.; Tobias, Jonathan H.; Rivadeneira, Fernando; Evans, David M.

2014-01-01

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (re = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (re = 0.20–0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n∼9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01×10−37), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31×10−14). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4×10−10). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD. PMID:24945404

Engineering Environmentally-Stable Proteases to Specifically Neutralize Protein Toxins

DTIC Science & Technology

2013-10-01

acids. These sites constitute a variable environment, with the effect of mutations largely isolated to effects on interactions with the P4 side chain. 2...desires to cut. We observe, however, sequence-specific cleavage is much more subtle, depending upon how side chain interactions influence not only...first five substrate amino acids on the acyl side of the scissile bond (denoted P1 through P5, numbering from the scissile bond toward the N-terminus

Engineering Environmentally-Stable Proteases to Specifically Neutralize Protein Toxins

DTIC Science & Technology

2012-10-14

effect of mutations largely isolated to effects on interactions with the P4 side chain. 2) Most mutations at some sites (e.g. 126, 128) decrease...to cut. We observe, however, sequence-specific cleavage is much more subtle, depending upon how side chain interactions influence not only ground...five substrate amino acids on the acyl side of the scissile bond (denoted P1 through P5, numbering from the scissile bond toward the N-terminus of the

Rapid Assessment of Ecosystem Services Provided by Two Mineral Extraction Sites Restored for Nature Conservation in an Agricultural Landscape in Eastern England

PubMed Central

Blaen, Phillip J.; Jia, Li; Peh, Kelvin S.-H.; Field, Rob H.; Balmford, Andrew; MacDonald, Michael A.; Bradbury, Richard B.

2015-01-01

Despite growing recognition that mineral sites restored for nature conservation can enhance local biodiversity, the wider societal benefits provided by this type of restoration relative to alternative options are not well understood. This study addresses this research gap by quantifying differences in ecosystem services provision under two common mineral site after-uses: nature conservation and agriculture. Using a combination of site-specific primary field data, benefits transfer and modelling, we show that for our sites restoration for nature conservation provides a more diverse array of ecosystem services than would be delivered under an agricultural restoration scenario. We also explore the effects of addressing different conservation targets, which we find alter the provision of ecosystem services on a service-specific basis. Highly species-focused intervention areas are associated with increased carbon storage and livestock grazing provision, whereas non-intervention areas are important for carbon sequestration, fishing, recreation and flood risk mitigation. The results of this study highlight the wider societal importance of restored mineral sites and may help conservation managers and planners to develop future restoration strategies that provide benefits for both biodiversity and human well-being. PMID:25894293

Rapid assessment of ecosystem services provided by two mineral extraction sites restored for nature conservation in an agricultural landscape in eastern England.

PubMed

Blaen, Phillip J; Jia, Li; Peh, Kelvin S-H; Field, Rob H; Balmford, Andrew; MacDonald, Michael A; Bradbury, Richard B

2015-01-01

Despite growing recognition that mineral sites restored for nature conservation can enhance local biodiversity, the wider societal benefits provided by this type of restoration relative to alternative options are not well understood. This study addresses this research gap by quantifying differences in ecosystem services provision under two common mineral site after-uses: nature conservation and agriculture. Using a combination of site-specific primary field data, benefits transfer and modelling, we show that for our sites restoration for nature conservation provides a more diverse array of ecosystem services than would be delivered under an agricultural restoration scenario. We also explore the effects of addressing different conservation targets, which we find alter the provision of ecosystem services on a service-specific basis. Highly species-focused intervention areas are associated with increased carbon storage and livestock grazing provision, whereas non-intervention areas are important for carbon sequestration, fishing, recreation and flood risk mitigation. The results of this study highlight the wider societal importance of restored mineral sites and may help conservation managers and planners to develop future restoration strategies that provide benefits for both biodiversity and human well-being.

The Effect of Anatomical Location of Lymph Node Metastases on Cancer Specific Survival in Patients with Clear Cell Renal Cell Carcinoma.

PubMed

Nini, Alessandro; Larcher, Alessandro; Cianflone, Francesco; Trevisani, Francesco; Terrone, Carlo; Volpe, Alessandro; Regis, Federica; Briganti, Alberto; Salonia, Andrea; Montorsi, Francesco; Bertini, Roberto; Capitanio, Umberto

2018-01-01

Positive nodal status (pN1) is an independent predictor of survival in renal cell carcinoma (RCC) patients. However, no study to date has tested whether the location of lymph node (LN) metastases does affect oncologic outcomes in a population submitted to radical nephrectomy (RN) and extended lymph node dissection (eLND). To describe nodal disease dissemination in clear cell RCC (ccRCC) patients and to assess the effect of the anatomical sites and the number of nodal areas affected on cancer specific mortality (CSM). The study included 415 patients who underwent RN and eLND, defined as the removal of hilar, side-specific (pre/paraaortic or pre/paracaval) and interaortocaval LNs for ccRCC, at two institutions. Descriptive statistics were used to depict nodal dissemination in pN1 patients, stratified according to nodal site and number of involved areas. Multivariable Cox regression analyses and Kaplan-Meier curves were used to explore the relationship between pN1 disease features and survival outcomes. Median number of removed LN was 14 (IQR 9-19); 23% of patients were pN1. Among patients with one involved nodal site, 54 and 26% of patients were positive only in side-specific and interaortocaval station, respectively. The most frequent nodal site was the interaortocaval and side-specific one, for right and left ccRCC, respectively. Interaortocaval nodal positivity (HR 2.3, CI 95%: 1.3-3.9, p < 0.01) represented an independent predictor of CSM. When ccRCC patient harbour nodal disease, its spreading can occur at any nodal station without involving the others. The presence of interoartocaval positive nodes does affect oncologic outcomes. Lymph node invasion in patients with clear cell renal cell carcinoma is not following a fixed anatomical pattern. An extended lymph node dissection, during treatment for primary kidney tumour, would aid patient risk stratification and multimodality upfront treatment.

Skeletal dosimetry for external exposure to photons based on µCT images of spongiosa from different bone sites

NASA Astrophysics Data System (ADS)

Kramer, R.; Khoury, H. J.; Vieira, J. W.; Kawrakow, I.

2007-11-01

Micro computed tomography (µCT) images of human spongiosa have recently been used for skeletal dosimetry with respect to external exposure to photon radiation. In this previous investigation, the calculation of equivalent dose to the red bone marrow (RBM) and to the bone surface cells (BSC) was based on five different clusters of micro matrices derived from µCT images of vertebrae, and the BSC equivalent dose for 10 µm thickness of the BSC layer was determined using an extrapolation method. The purpose of this study is to extend the earlier investigation by using µCT images from eight different bone sites and by introducing an algorithm for the direct calculation of the BSC equivalent dose with sub-micro voxel resolution. The results show that for given trabecular bone volume fractions (TBVFs) the whole-body RBM equivalent dose does not depend on bone site-specific properties or imaging parameters. However, this study demonstrates that apart from the TBVF and the BSC layer thickness, the BSC equivalent dose additionally depends on a so-called trabecular bone structure (TBS) effect, i.e. that the contribution of photo-electrons released in trabecular bone to the BSC equivalent dose also depends on the bone site-specific structure of the trabeculae. For a given bone site, the TBS effect is also a function of the thickness of the BSC layer, and it could be shown that this effect would disappear almost completely, should the BSC layer thickness be raised from 10 to 50 µm, according to new radiobiological findings.

In silico site-directed mutagenesis informs species-specific predictions of chemical susceptibility derived from the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool

EPA Science Inventory

The Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was developed to address needs for rapid, cost effective methods of species extrapolation of chemical susceptibility. Specifically, the SeqAPASS tool compares the primary sequence (Level 1), functiona...

Effects of topography on the transport of agricultural chemicals to groundwater in a sand-plain setting

NASA Astrophysics Data System (ADS)

Delin, Geoffrey N.; Landon, Matthew K.

2002-08-01

Geochemical data were collected to investigate the effects of topography and focused recharge on the transport of agricultural chemicals to groundwater through sandy soils. The research was done at a topographically high (upland) site and a depressional (lowland) site within a corn field. Agricultural chemicals that move readily with water were most directly affected by focused recharge to the lowland site. Surface runoff of water to the lowland site was the primary cause for the generally greater flux of chloride, nitrate nitrogen, and sulfate compared with the upland site. Based on data from the unsaturated zone, for example, the average annual fluxes of these chemicals in 1992-1993 were 5.1, 3.4, and 1.7 times greater, respectively, at the lowland site. Study results indicate that consideration should be given to modifying site-specific management farming technology to account for varying recharge rates in different topographic settings. By reducing chemical application rates in topographic depressions, where focused recharge of chemicals occurs because of surface runoff, farmers could improve ground-water quality as well as reduce expenditures for agricultural chemicals.

Effects of topography on the transport of agricultural chemicals to groundwater in a sand-plain setting

USGS Publications Warehouse

Delin, G.N.; Landon, M.K.

2002-01-01

Geochemical data were collected to investigate the effects of topography and focused recharge on the transport of agricultural chemicals to groundwater through sandy soils. The research was done at a topographically high (upland) site and a depressional (lowland) site within a corn field. Agricultural chemicals that move readily with water were most directly affected by focused recharge to the lowland site. Surface runoff of water to the lowland site was the primary cause for the generally greater flux of chloride, nitrate nitrogen, and sulfate compared with the upland site. Based on data from the unsaturated zone, for example, the average annual fluxes of these chemicals in 1992–1993 were 5.1, 3.4, and 1.7 times greater, respectively, at the lowland site. Study results indicate that consideration should be given to modifying site-specific management farming technology to account for varying recharge rates in different topographic settings. By reducing chemical application rates in topographic depressions, where focused recharge of chemicals occurs because of surface runoff, farmers could improve ground-water quality as well as reduce expenditures for agricultural chemicals.

77 FR 12002 - Mount Baker-Snoqualmie National Forest Site-Specific Invasive Plant Treatment Project and Forest...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-28

... these tools, including additional herbicides and application methods to increase treatment effectiveness... organisms than previously approved herbicides and higher effectiveness on particular invasive plants. Thus... examples demonstrate why additional herbicides, methods, and protocols are needed to improve treatment...

Effect of the anatomical site on telomere length and pref-1 gene expression in bovine adipose tissues

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

Yamada, Tomoya, E-mail: toyamada@affrc.go.jp; Higuchi, Mikito; Nakanishi, Naoto

Adipose tissue growth is associated with preadipocyte proliferation and differentiation. Telomere length is a biological marker for cell proliferation. Preadipocyte factor-1 (pref-1) is specifically expressed in preadipocytes and acts as a molecular gatekeeper of adipogenesis. In the present study, we investigated the fat depot-specific differences in telomere length and pref-1 gene expression in various anatomical sites (subcutaneous, intramuscular and visceral) of fattening Wagyu cattle. Visceral adipose tissue expressed higher pref-1 mRNA than did subcutaneous and intramuscular adipose tissues. The telomere length in visceral adipose tissue tended to be longer than that of subcutaneous and intramuscular adipose tissues. The telomere lengthmore » of adipose tissue was not associated with adipocyte size from three anatomical sites. No significant correlation was found between the pref-1 mRNA level and the subcutaneous adipocyte size. In contrast, the pref-1 mRNA level was negatively correlated with the intramuscular and visceral adipocyte size. These results suggest that anatomical sites of adipose tissue affect the telomere length and expression pattern of the pref-1 gene in a fat depot-specific manner. - Highlights: • Visceral adipose tissue express higher pref-1 mRNA than other anatomical sites. • Telomere length in visceral adipose tissue is longer than other anatomical sites. • Telomere length of adipose tissue is not associated with adipocyte size. • Pref-1 mRNA is negatively correlated with intramuscular and visceral adipocyte size.« less

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

PubMed Central

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

2016-01-01

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

Childhood cancers, birthplaces, incinerators and landfill sites.

PubMed

Knox, E

2000-06-01

In all, 70 municipal incinerators, 307 hospital incinerators and 460 toxic-waste landfill sites in Great Britain were examined for evidence of effluents causing childhood cancers. Municipal incinerators had previously shown significant excesses of adult cancers within 7.5 and 3.0 km. The relative risks for adults had been marginal and an analysis of childhood cancers seemed to offer a more sensitive approach. A newly developed technique of analysis compares distances from suspect sources to the birth addresses and to the death addresses of cancer-children who had moved house. A localized hazard, effective at only one of these times, must be preferentially associated with the corresponding address. This creates an asymmetry of migrations towards or away from age-restricted effective sources. The child-cancer/leukaemia data showed no systematic migration-asymmetries around toxic-waste landfill sites; but showed highly significant excesses of migrations away from birthplaces close to municipal incinerators. Relative risks within 5.0 km of these sites were about 2:1. Hospital incinerators gave analogous results. The ratios greatly exceed findings around 'non-combustion' urban sites. Because of their locations, the specific effects of the municipal incinerators could not be separated clearly from those of adjacent industrial sources of combustion-effluents. Both were probably carcinogenic. Landfill waste sites showed no such effect.

Pollution-Induced Community Tolerance To Diagnose Hazardous Chemicals in Multiple Contaminated Aquatic Systems.

PubMed

Rotter, Stefanie; Gunold, Roman; Mothes, Sibylle; Paschke, Albrecht; Brack, Werner; Altenburger, Rolf; Schmitt-Jansen, Mechthild

2015-08-18

Aquatic ecosystems are often contaminated with large numbers of chemicals, which cannot be sufficiently addressed by chemical target analyses. Effect-directed analysis (EDA) enables the identification of toxicants in complex contaminated environmental samples. This study suggests pollution-induced community tolerance (PICT) as a confirmation tool for EDA to identify contaminants which actually impact on local communities. The effects of three phytotoxic compounds local periphyton communities, cultivated at a reference (R-site) and a polluted site (P-site), were assessed to confirm the findings of a former EDA study on sediments. The sensitivities of R- and P-communities to prometryn, tributyltin (TBT) and N-phenyl-2-naphthylamine (PNA) were quantified in short-term toxicity tests and exposure concentrations were determined. Prometryn and PNA concentrations were significantly higher at the P-site, whereas TBT concentrations were in the same range at both sites. Periphyton communities differed in biomass, but algal class composition and diatom diversity were similar. Community tolerance of P-communities was significantly enhanced for prometryn, but not for PNA and TBT, confirming site-specific effects on local periphyton for prometryn only. Thus, PICT enables in situ effect confirmation of phytotoxic compounds at the community level and seems to be suitable to support confirmation and enhance ecological realism of EDA.

Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites

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

Anderson, Courtney M.; Hu, Jianxin; Thomas, Reuben

2017-03-28

Enhancers frequently contain multiple binding sites for the same transcription factor. These homotypic binding sites often exhibit synergy, whereby the transcriptional output from two or more binding sites is greater than the sum of the contributions of the individual binding sites alone. Although this phenomenon is frequently observed, the mechanistic basis for homotypic binding site synergy is poorly understood. Here in this paper, we identify a bona fide cardiac-specific Prkaa2 enhancer that is synergistically activated by homotypic MEF2 binding sites. We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the MEF2C-bound sites by themore » SAP domain-containing co-activator protein myocardin, and we show that paired sites buffer the enhancer from integration site-dependent effects on transcription in vivo. Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechanism underlying synergy in the control of cardiac gene expression in vivo.« less

Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencing

PubMed Central

Chandran, Anandhakumar; Syed, Junetha; Taylor, Rhys D.; Kashiwazaki, Gengo; Sato, Shinsuke; Hashiya, Kaori; Bando, Toshikazu; Sugiyama, Hiroshi

2016-01-01

Chemically engineered small molecules targeting specific genomic sequences play an important role in drug development research. Pyrrole-imidazole polyamides (PIPs) are a group of molecules that can bind to the DNA minor-groove and can be engineered to target specific sequences. Their biological effects rely primarily on their selective DNA binding. However, the binding mechanism of PIPs at the chromatinized genome level is poorly understood. Herein, we report a method using high-throughput sequencing to identify the DNA-alkylating sites of PIP-indole-seco-CBI conjugates. High-throughput sequencing analysis of conjugate 2 showed highly similar DNA-alkylating sites on synthetic oligos (histone-free DNA) and on human genomes (chromatinized DNA context). To our knowledge, this is the first report identifying alkylation sites across genomic DNA by alkylating PIP conjugates using high-throughput sequencing. PMID:27098039

Pervasive positive selection on duplicated and nonduplicated vertebrate protein coding genes.

PubMed

Studer, Romain A; Penel, Simon; Duret, Laurent; Robinson-Rechavi, Marc

2008-09-01

A stringent branch-site codon model was used to detect positive selection in vertebrate evolution. We show that the test is robust to the large evolutionary distances involved. Positive selection was detected in 77% of 884 genes studied. Most positive selection concerns a few sites on a single branch of the phylogenetic tree: Between 0.9% and 4.7% of sites are affected by positive selection depending on the branches. No functional category was overrepresented among genes under positive selection. Surprisingly, whole genome duplication had no effect on the prevalence of positive selection, whether the fish-specific genome duplication or the two rounds at the origin of vertebrates. Thus positive selection has not been limited to a few gene classes, or to specific evolutionary events such as duplication, but has been pervasive during vertebrate evolution.

Quantum and classical dynamics of water dissociation on Ni(111): A test of the site-averaging model in dissociative chemisorption of polyatomic molecules

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

Jiang, Bin; Department of Chemical Physics, University of Science and Technology of China, Hefei 230026; Guo, Hua, E-mail: hguo@unm.edu

Recently, we reported the first highly accurate nine-dimensional global potential energy surface (PES) for water interacting with a rigid Ni(111) surface, built on a large number of density functional theory points [B. Jiang and H. Guo, Phys. Rev. Lett. 114, 166101 (2015)]. Here, we investigate site-specific reaction probabilities on this PES using a quasi-seven-dimensional quantum dynamical model. It is shown that the site-specific reactivity is largely controlled by the topography of the PES instead of the barrier height alone, underscoring the importance of multidimensional dynamics. In addition, the full-dimensional dissociation probability is estimated by averaging fixed-site reaction probabilities with appropriatemore » weights. To validate this model and gain insights into the dynamics, additional quasi-classical trajectory calculations in both full and reduced dimensions have also been performed and important dynamical factors such as the steering effect are discussed.« less

The cleavage specificity of the aspartic protease of cocoa beans involved in the generation of the cocoa-specific aroma precursors.

PubMed

Janek, Katharina; Niewienda, Agathe; Wöstemeyer, Johannes; Voigt, Jürgen

2016-11-15

Particular peptides generated from the vicilin-class(7S) globulin of the cocoa beans by acid-induced proteolysis during cocoa fermentation are essential precursors of the cocoa-specific aroma notes. As revealed by in vitro studies, the formation of the cocoa-specific aroma precursors depends on the particular cleavage specificity of the cocoa aspartic protease, which cannot be substituted by pepsin. Therefore, we have investigated the effects of aspartic protease inhibitors on both enzymes and comparatively studied their cleavage specificities using different protein substrates and MALDI-TOF mass spectrometric analyses of the generated oligopeptides. Three classes of cleavage sites have been identified and characterized: (I) sequences exclusively cleaved by the cocoa enzyme, (II) sequences cleaved by both pepsin and the cocoa enzyme, and (III) those cleaved exclusively by pepsin. In contrast to most aspartic proteases from other origins, basic amino acid residues, particularly lysine, were found to be abundant in the specific cleavage sites of the cocoa enzyme. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantifying the uncertainty in site amplification modeling and its effects on site-specific seismic-hazard estimation in the upper Mississippi embayment and adjacent areas

USGS Publications Warehouse

Cramer, C.H.

2006-01-01

The Mississippi embayment, located in the central United States, and its thick deposits of sediments (over 1 km in places) have a large effect on earthquake ground motions. Several previous studies have addressed how these thick sediments might modify probabilistic seismic-hazard maps. The high seismic hazard associated with the New Madrid seismic zone makes it particularly important to quantify the uncertainty in modeling site amplification to better represent earthquake hazard in seismic-hazard maps. The methodology of the Memphis urban seismic-hazard-mapping project (Cramer et al., 2004) is combined with the reference profile approach of Toro and Silva (2001) to better estimate seismic hazard in the Mississippi embayment. Improvements over previous approaches include using the 2002 national seismic-hazard model, fully probabilistic hazard calculations, calibration of site amplification with improved nonlinear soil-response estimates, and estimates of uncertainty. Comparisons are made with the results of several previous studies, and estimates of uncertainty inherent in site-amplification modeling for the upper Mississippi embayment are developed. I present new seismic-hazard maps for the upper Mississippi embayment with the effects of site geology incorporating these uncertainties.

Specific Conjugation of the Hinge Region for Homogeneous Preparation of Antibody Fragment-Drug Conjugate: A Case Study for Doxorubicin-PEG-anti-CD20 Fab' Synthesis.

PubMed

Zhou, Zhan; Zhang, Jing; Zhang, Yan; Ma, Guanghui; Su, Zhiguo

2016-01-20

Conventional preparation strategies for antibody-drug conjugates (ADCs) result in heterogeneous products with various molecular sizes and species. In this study, we developed a homogeneous preparation strategy by site-specific conjugation of the anticancer drug with an antibody fragment. The model drug doxorubicin (DOX) was coupled to the Fab' fragment of anti-CD20 IgG at its permissive sites through a heterotelechelic PEG linker, generating an antibody fragment-drug conjugate (AFDC). Anti-CD20 IgG was digested and reduced specifically with β-mercaptoethylamine to generate the Fab' fragment with two free mercapto groups in its hinge region. Meanwhile, DOX was conjugated with α-succinimidylsuccinate ω-maleimide polyethylene glycol (NHS-PEG-MAL) to form MAL-PEG-DOX, which was subsequently linked to the free mercapto containing Fab' fragment to form a Fab'-PEG-DOX conjugate. The dual site-specific bioconjugation was achieved through the combination of highly selective reduction of IgG and introduction of heterotelechelic PEG linker. The resulting AFDC provides an utterly homogeneous product, with a definite ratio of one fragment to two drugs. Laser confocal microscopy and cell ELISA revealed that the AFDC could accumulate in the antigen-positive Daudi tumor cell. In addition, the Fab'-PEG-DOX retained appreciable targeting ability and improved antitumor activity, demonstrating an excellent therapeutic effect on the lymphoma mice model for better cure rate and significantly reduced side effects.

Planning for Cost Effectiveness.

ERIC Educational Resources Information Center

Schlaebitz, William D.

1984-01-01

A heat pump life-cycle cost analysis is used to explain the technique. Items suggested for the life-cycle analysis approach include lighting, longer-life batteries, site maintenance, and retaining experts to inspect specific building components. (MLF)

An exposure system for measuring nasal and lung uptake of vapors in rats

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

Dahl, A.R.; Brookins, L.K.; Gerde, P.

1995-12-01

Inhaled gases and vapors often produce biological damage in the nasal cavity and lower respiratory tract. The specific site within the respirator tract at which a gas or vapor is absorbed strongly influences the tissues at risk to potential toxic effects; to predict or to explain tissue or cell specific toxicity of inhaled gases or vapors, the sites at which they are absorbed must be known. The purpose of the work reported here was to develop a system for determining nose and lung absorption of vapors in rats, an animal commonly used in inhalation toxicity studies. In summary, the exposuremore » system described allows us to measure in the rate: (1) nasal absorption and desorption of vapors; (2) net lung uptake of vapors; and (3) the effects of changed breathing parameters on vapor uptake.« less

Unusual Structure of the attB Site of the Site-Specific Recombination System of Lactobacillus delbrueckii Bacteriophage mv4

PubMed Central

Auvray, Frédéric; Coddeville, Michèle; Ordonez, Romy Catoira; Ritzenthaler, Paul

1999-01-01

The temperate phage mv4 integrates its genome into the chromosome of Lactobacillus delbrueckii subsp. bulgaricus by site-specific recombination within the 3′ end of a tRNASer gene. Recombination is catalyzed by the phage-encoded integrase and occurs between the phage attP site and the bacterial attB site. In this study, we show that the mv4 integrase functions in vivo in Escherichia coli and we characterize the bacterial attB site with a site-specific recombination test involving compatible plasmids carrying the recombination sites. The importance of particular nucleotides within the attB sequence was determined by site-directed mutagenesis. The structure of the attB site was found to be simple but rather unusual. A 16-bp DNA fragment was sufficient for function. Unlike most genetic elements that integrate their DNA into tRNA genes, none of the dyad symmetry elements of the tRNASer gene were present within the minimal attB site. No inverted repeats were detected within this site either, in contrast to the lambda site-specific recombination model. PMID:10572145

Microfluidic biosensor for β-Hydroxybutyrate (βHBA) determination of subclinical ketosis diagnosis.

PubMed

Weng, Xuan; Zhao, Wenting; Neethirajan, Suresh; Duffield, Todd

2015-02-12

Determination of β-hydroxybutyrate (βHBA) is a gold standard for diagnosis of Subclinical Ketosis (SCK), a common disease in dairy cows that causes significant economic loss. Early detection of SCK can help reduce the risk of the disease progressing into clinical stage, thus minimizing economic losses on dairy cattle. Conventional laboratory methods are time consuming and labor-intensive, requiring expensive and bulky equipment. Development of portable and robust devices for rapid on-site SCK diagnosis is an effective way to prevent and control ketosis and can significantly aid in the management of dairy animal health. Microfluidic technology provides a rapid, cost-effective way to develop handheld devices for on-farm detection of sub-clinical ketosis. In this study, a highly sensitive microfluidics-based biosensor for on-site SCK diagnosis has been developed. A rapid, low-cost microfluidic biosensor with high sensitivity and specificity was developed for SCK diagnosis. Determination of βHBA was employed as the indicator in the diagnosis of SCK. On-chip detection using miniaturized and cost-effective optical sensor can be finished in 1 minute with a detection limit of 0.05 mM concentration. Developed microfluidic biosensor was successfully tested with the serum samples from dairy cows affected by SCK. The results of the developed biosensor agreed well with two other laboratory methods. The biosensor was characterized by high sensitivity and specificity towards βHBA with a detection limit of 0.05 mM. The developed microfluidic biosensor provides a promising prototype for a cost-effective handheld meter for on-site SCK diagnosis. By using microfluidic method, the detection time is significantly decreased compared to other laboratory methods. Here, we demonstrate a field-deployable device to precisely identify and measure subclinical ketosis by specific labeling and quantification of β-hydroxybutyate in cow blood samples. A real-time on-site detection system will maximize convenience for the farmers.

STATIC AND KINETIC SITE-SPECIFIC PROTEIN-DNA PHOTOCROSSLINKING: ANALYSIS OF BACTERIAL TRANSCRIPTION INITIATION COMPLEXES

PubMed Central

Naryshkin, Nikolai; Druzhinin, Sergei; Revyakin, Andrei; Kim, Younggyu; Mekler, Vladimir; Ebright, Richard H.

2009-01-01

Static site-specific protein-DNA photocrosslinking permits identification of protein-DNA interactions within multiprotein-DNA complexes. Kinetic site-specific protein-DNA photocrosslinking--involving rapid-quench-flow mixing and pulsed-laser irradiation--permits elucidation of pathways and kinetics of formation of protein-DNA interactions within multiprotein-DNA complexes. We present detailed protocols for application of static and kinetic site-specific protein-DNA photocrosslinking to bacterial transcription initiation complexes. PMID:19378179

Water-quality characteristics, including sodium-adsorption ratios, for four sites in the Powder River drainage basin, Wyoming and Montana, water years 2001-2004

USGS Publications Warehouse

Clark, Melanie L.; Mason, Jon P.

2006-01-01

The U.S. Geological Survey, in cooperation with the Wyoming Department of Environmental Quality, monitors streams throughout the Powder River structural basin in Wyoming and parts of Montana for potential effects of coalbed natural gas development. Specific conductance and sodium-adsorption ratios may be larger in coalbed waters than in stream waters that may receive the discharge waters. Therefore, continuous water-quality instruments for specific conductance were installed and discrete water-quality samples were collected to characterize water quality during water years 2001-2004 at four sites in the Powder River drainage basin: Powder River at Sussex, Wyoming; Crazy Woman Creek near Arvada, Wyoming; Clear Creek near Arvada, Wyoming; and Powder River at Moorhead, Montana. During water years 2001-2004, the median specific conductance of 2,270 microsiemens per centimeter at 25 degrees Celsius (?S/cm) in discrete samples from the Powder River at Sussex, Wyoming, was larger than the median specific conductance of 1,930 ?S/cm in discrete samples collected downstream from the Powder River at Moorhead, Montana. The median specific conductance was smallest in discrete samples from Clear Creek (1,180 ?S/cm), which has a dilution effect on the specific conductance for the Powder River at Moorhead, Montana. The daily mean specific conductance from continuous water-quality instruments during the irrigation season showed the same spatial pattern as specific conductance values for the discrete samples. Dissolved sodium, sodium-adsorption ratios, and dissolved solids generally showed the same spatial pattern as specific conductance. The largest median sodium concentration (274 milligrams per liter) and the largest range of sodium-adsorption ratios (3.7 to 21) were measured in discrete samples from the Powder River at Sussex, Wyoming. Median concentrations of sodium and sodium-adsorption ratios were substantially smaller in Crazy Woman Creek and Clear Creek, which tend to decrease sodium concentrations and sodium-adsorption ratios at the Powder River at Moorhead, Montana. Dissolved-solids concentrations in discrete samples were closely correlated with specific conductance values; Pearson's correlation coefficients were 0.98 or greater for all four sites. Regression equations for discrete values of specific conductance and sodium-adsorption ratios were statistically significant (p-values <0.001) at all four sites. The strongest relation (R2=0.92) was at the Powder River at Sussex, Wyoming. Relations on Crazy Woman Creek (R2=0.91) and Clear Creek (R2=0.83) also were strong. The relation between specific conductance and sodium-adsorption ratios was weakest (R2=0.65) at the Powder River at Moorhead, Montana; however, the relation was still significant. These data indicate that values of specific conductance are useful for estimating sodium-adsorption ratios. A regression model called LOADEST was used to estimate dissolved-solids loads for the four sites. The average daily mean dissolved-solids loads varied among the sites during water year 2004. The largest average daily mean dissolved-solids load was calculated for the Powder River at Moorhead, Montana. Although the smallest concentrations of dissolved solids were in samples from Clear Creek, the smallest average daily mean dissolved-solids load was calculated for Crazy Woman Creek. The largest loads occurred during spring runoff, and the smallest loads occurred in late summer, when streamflows typically were smallest. Dissolved-solids loads may be smaller than average during water years 2001-2004 because of smaller than average streamflow as a result of drought conditions.

Spatio-Temporal Variation in Effects of Upwelling on the Fatty Acid Composition of Benthic Filter Feeders in the Southern Benguela Ecosystem: Not All Upwelling Is Equal

PubMed Central

McQuaid, Christopher David; Noyon, Margaux

2016-01-01

Variability in mesoscale nearshore oceanographic conditions plays an important role in the distribution of primary production and food availability for intertidal consumers. Advection of nutrient rich waters by upwelling usually allows the proliferation of diatoms, later replaced by dinoflagellates. We examined upwelling effects on the fatty acid (FA) signature of a benthic intertidal filter feeder to identify its response to pulsed variability in food availability. The study took place in two contrasting seasons and at two upwelling and two non-upwelling sites interspersed within the southern Benguela upwelling system of South Africa. We investigated the FA composition of the adductor muscles and gonads of the mussel Mytilus galloprovincialis to assess how FA are apportioned to the different tissues and whether this changes between upwelling and non-upwelling conditions. In situ temperature loggers used to identify upwelling conditions at the four sites indicated that such events occurred only at the upwelling centres and only in summer. Tissues differed strongly, with gonads presenting a higher proportion of essential FAs. This could reflect the faster turnover rate of gonad tissue or preferential retention of specific FA for reproductive purposes. FA composition did not vary as a direct function of upwelling, but there were strong dissimilarities among sites. Upwelling influenced mussel diets at one upwelling site while at the other, the expected signature of upwelling was displaced downstream of the core of upwelling. Condition Index (CI) and Gonad Index (GI) differed among sites and were not influenced by upwelling, with GI being comparable among sites. In addition, FA proportions were consistent among sites, indicating similar food quality and quantity over time and under upwelling and non-upwelling conditions. This suggests that the influence of upwelling on the west coast of South Africa is pervasive and diffuse, rather than discrete; while nearshore retention or advection of upwelled water is critical and site-specific so that the effects of upwelling differ even among sites categorised as upwelling centres. PMID:27570968

Salt Effect Accelerates Site-Selective Cysteine Bioconjugation

PubMed Central

2016-01-01

Highly efficient and selective chemical reactions are desired. For small molecule chemistry, the reaction rate can be varied by changing the concentration, temperature, and solvent used. In contrast for large biomolecules, the reaction rate is difficult to modify by adjusting these variables because stringent biocompatible reaction conditions are required. Here we show that adding salts can change the rate constant over 4 orders of magnitude for an arylation bioconjugation reaction between a cysteine residue within a four-residue sequence (π-clamp) and a perfluoroaryl electrophile. Biocompatible ammonium sulfate significantly enhances the reaction rate without influencing the site-specificity of π-clamp mediated arylation, enabling the fast synthesis of two site-specific antibody–drug conjugates that selectively kill HER2-positive breast cancer cells. Computational and structure–reactivity studies indicate that salts may tune the reaction rate through modulating the interactions between the π-clamp hydrophobic side chains and the electrophile. On the basis of this understanding, the salt effect is extended to other bioconjugation chemistry, and a new regioselective alkylation reaction at π-clamp cysteine is developed. PMID:27725962

Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity

DOE PAGES

Matthews, Melissa M.; Thomas, Justin M.; Zheng, Yuxuan; ...

2016-04-11

Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. In this paper, we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADARmore » deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. In conclusion, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease.« less

Towards soft robotic devices for site-specific drug delivery.

PubMed

Alici, Gursel

2015-01-01

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

Site-specific methylation of the rat prolactin and growth hormone promoters correlates with gene expression.

PubMed Central

Ngô, V; Gourdji, D; Laverrière, J N

1996-01-01

The methylation patterns of the rat prolactin (rPRL) (positions -440 to -20) and growth hormone (rGH) (positions -360 to -110) promoters were analyzed by bisulfite genomic sequencing. Two normal tissues, the anterior pituitary and the liver, and three rat pituitary GH3 cell lines that differ considerably in their abilities to express both genes were tested. High levels of rPRL gene expression were correlated with hypomethylation of the CpG dinucleotides located at positions -277 and -97, near or within positive cis-acting regulatory elements. For the nine CpG sites analyzed in the rGH promoter, an overall hypomethylation-expression coupling was also observed for the anterior pituitary, the liver, and two of the cell lines. The effect of DNA methylation was tested by measuring the transient expression of the chloramphenicol acetyltransferase reporter gene driven by a regionally methylated rPRL promoter. CpG methylation resulted in a decrease in the activity of the rPRL promoter which was proportional to the number of modified CpG sites. The extent of the inhibition was also found to be dependent on the position of methylated sites. Taken together, these data suggest that site-specific methylation may modulate the action of transcription factors that dictate the tissue-specific expression of the rPRL and rGH genes in vivo. PMID:8668139

MDD-carb: a combinatorial model for the identification of protein carbonylation sites with substrate motifs.

PubMed

Kao, Hui-Ju; Weng, Shun-Long; Huang, Kai-Yao; Kaunang, Fergie Joanda; Hsu, Justin Bo-Kai; Huang, Chien-Hsun; Lee, Tzong-Yi

2017-12-21

Carbonylation, which takes place through oxidation of reactive oxygen species (ROS) on specific residues, is an irreversibly oxidative modification of proteins. It has been reported that the carbonylation is related to a number of metabolic or aging diseases including diabetes, chronic lung disease, Parkinson's disease, and Alzheimer's disease. Due to the lack of computational methods dedicated to exploring motif signatures of protein carbonylation sites, we were motivated to exploit an iterative statistical method to characterize and identify carbonylated sites with motif signatures. By manually curating experimental data from research articles, we obtained 332, 144, 135, and 140 verified substrate sites for K (lysine), R (arginine), T (threonine), and P (proline) residues, respectively, from 241 carbonylated proteins. In order to examine the informative attributes for classifying between carbonylated and non-carbonylated sites, multifarious features including composition of twenty amino acids (AAC), composition of amino acid pairs (AAPC), position-specific scoring matrix (PSSM), and positional weighted matrix (PWM) were investigated in this study. Additionally, in an attempt to explore the motif signatures of carbonylation sites, an iterative statistical method was adopted to detect statistically significant dependencies of amino acid compositions between specific positions around substrate sites. Profile hidden Markov model (HMM) was then utilized to train a predictive model from each motif signature. Moreover, based on the method of support vector machine (SVM), we adopted it to construct an integrative model by combining the values of bit scores obtained from profile HMMs. The combinatorial model could provide an enhanced performance with evenly predictive sensitivity and specificity in the evaluation of cross-validation and independent testing. This study provides a new scheme for exploring potential motif signatures at substrate sites of protein carbonylation. The usefulness of the revealed motifs in the identification of carbonylated sites is demonstrated by their effective performance in cross-validation and independent testing. Finally, these substrate motifs were adopted to build an available online resource (MDD-Carb, http://csb.cse.yzu.edu.tw/MDDCarb/ ) and are also anticipated to facilitate the study of large-scale carbonylated proteomes.

A fresh look at road salt: aquatic toxicity and water-quality impacts on local, regional, and national scales.

PubMed

Corsi, Steven R; Graczyk, David J; Geis, Steven W; Booth, Nathaniel L; Richards, Kevin D

2010-10-01

A new perspective on the severity of aquatic toxicity impact of road salt was gained by a focused research effort directed at winter runoff periods. Dramatic impacts were observed on local, regional, and national scales. Locally, samples from 7 of 13 Milwaukee, Wisconsin area streams exhibited toxicity in Ceriodaphnia dubia and Pimephales promelas bioassays during road-salt runoff. Another Milwaukee stream was sampled from 1996 to 2008 with 72% of 37 samples exhibiting toxicity in chronic bioassays and 43% in acute bioassays. The maximum chloride concentration was 7730 mg/L. Regionally, in southeast Wisconsin, continuous specific conductance was monitored as a chloride surrogate in 11 watersheds with urban land use from 6.0 to 100%. Elevated specific conductance was observed between November and April at all sites, with continuing effects between May and October at sites with the highest specific conductance. Specific conductance was measured as high as 30,800 μS/cm (Cl = 11,200 mg/L). Chloride concentrations exceeded U.S. Environmental Protection Agency (USEPA) acute (860 mg/L) and chronic (230 mg/L) water-quality criteria at 55 and 100% of monitored sites, respectively. Nationally, U.S. Geological Survey historical data were examined for 13 northern and 4 southern metropolitan areas. Chloride concentrations exceeded USEPA water-quality criteria at 55% (chronic) and 25% (acute) of the 168 monitoring locations in northern metropolitan areas from November to April. Only 16% (chronic) and 1% (acute) of sites exceeded criteria from May to October. At southern sites, very few samples exceeded chronic water-quality criteria, and no samples exceeded acute criteria.

76 FR 57981 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act... environmental restoration, waste management and related activities. Tentative Agenda Call to Order...

76 FR 55370 - Environmental Management Site-Specific Advisory Board, Nevada

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-07

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Nevada AGENCY...-Wide Environmental Impact Statement (EIS) Committee of the Environmental Management Site- Specific... the areas of environmental restoration, waste management, and related activities. Purpose of the...

77 FR 29997 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-21

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act... environmental restoration, waste management and related activities. Tentative Agenda Call to Order...

76 FR 50204 - Environmental Management Site-Specific Advisory Board, Nevada

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-12

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Nevada AGENCY...-Wide Environmental Impact Statement (EIS) Committee of the Environmental Management Site- Specific... management in the areas of environmental restoration, waste management, and related activities. Purpose of...

76 FR 78909 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-20

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act... the areas of environmental restoration, waste management, and related activities. Tentative Agenda...

76 FR 36100 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-21

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act... environmental restoration, waste management and related activities. Tentative Agenda Call to Order...

Minimal Data and Site Specific Approaches

EPA Science Inventory

As part of a workshop, Tools for Assessing Stream Dissolved Minerals, approaches and EPA tools are described for site specific development of water quality criteria based on observations from Arkansas streams using minimal data. Discussion topics will include site-specific appro...

Effects of glycosylation on antigenicity and immunogenicity of classical swine fever virus envelope proteins

USDA-ARS?s Scientific Manuscript database

Classical swine fever virus (CSFV) harbors three envelope glycoproteins (E(rns), E1 and E2). Previous studies have demonstrated that removal of specific glycosylation sites within these proteins yielded attenuated and immunogenic CSFV mutants. Here we analyzed the effects of lack of glycosylation of...

The Mediation Effect of Outdoor Recreation Participation on Environmental Attitude-Behavior Correspondence

ERIC Educational Resources Information Center

Thapa, Brijesh

2010-01-01

Outdoor recreation participation has increased over the past decades and is projected for further growth. Given the increase, it is important to assess recreationists' environmental values, activity style, general, and site-specific attitudes and behaviors to promote environmental stewardship, and to develop effective strategies in natural…

EFFECTS OF HEAVY METALS IN SEDIMENTS OF THE MACROINVERTEBRATE COMMUNITY IN THE SHORT CREEK/EMPIRE LAKE AQUATIC SYSTEM, CHEROKEE COUNTY, KANSAS: A RECOMMENDATION FOR SITE-SPECIFIC CRITERIA.

EPA Science Inventory

The study uses statistical analysis techniques to determine the effects of four heavy metals (cadmium, lead, manganese, and zinc) on the macroinvertebrate community using the data collected in the fall 1987.

Offshore oceanographic and environmental monitoring services for the Strategic Petroleum Reserve. Annual report for the Bryan Mound site, September 1982-August 1983. Volume III. Executive summary

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

Hann, R.W. Jr.; Giammona, C.P.; Randall, R.E.

1984-03-01

This report describes the findings for the 12 months of postdisposal study conducted from September 1982 through August 1983. The areas of investigation are benthos, brine plume, data management, nekton, physical oceanography, and water and sediment quality. The specific objectives of this report are: (1) to describe the physical oceanographic and meteorological conditions which have been measured at the offshore diffuser site and in the surrounding waters; (2) to describe the effect of brine discharge on the benthic community in the diffuser site area; (3) to discuss the effect of the brine discharge on the quality of the water andmore » sediment in the vicinity of the diffuser site; (4) to describe the measurement and empirical prediction of the areal and vertical extent of the brine plume; and (5) to characterize the effect of brine discharge on the nekton community in the vicinity of the diffuser. 2 figures.« less

Multisite Reliability of Cognitive BOLD Data

PubMed Central

Brown, Gregory G.; Mathalon, Daniel H.; Stern, Hal; Ford, Judith; Mueller, Bryon; Greve, Douglas N.; McCarthy, Gregory; Voyvodic, Jim; Glover, Gary; Diaz, Michele; Yetter, Elizabeth; Burak Ozyurt, I.; Jorgensen, Kasper W.; Wible, Cynthia G.; Turner, Jessica A.; Thompson, Wesley K.; Potkin, Steven G.

2010-01-01

Investigators perform multi-site functional magnetic resonance imaging studies to increase statistical power, to enhance generalizability, and to improve the likelihood of sampling relevant subgroups. Yet undesired site variation in imaging methods could off-set these potential advantages. We used variance components analysis to investigate sources of variation in the blood oxygen level dependent (BOLD) signal across four 3T magnets in voxelwise and region of interest (ROI) analyses. Eighteen participants traveled to four magnet sites to complete eight runs of a working memory task involving emotional or neutral distraction. Person variance was more than 10 times larger than site variance for five of six ROIs studied. Person-by-site interactions, however, contributed sizable unwanted variance to the total. Averaging over runs increased between-site reliability, with many voxels showing good to excellent between-site reliability when eight runs were averaged and regions of interest showing fair to good reliability. Between-site reliability depended on the specific functional contrast analyzed in addition to the number of runs averaged. Although median effect size was correlated with between-site reliability, dissociations were observed for many voxels. Brain regions where the pooled effect size was large but between-site reliability was poor were associated with reduced individual differences. Brain regions where the pooled effect size was small but between-site reliability was excellent were associated with a balance of participants who displayed consistently positive or consistently negative BOLD responses. Although between-site reliability of BOLD data can be good to excellent, acquiring highly reliable data requires robust activation paradigms, ongoing quality assurance, and careful experimental control. PMID:20932915

Site-specific protein backbone and side-chain NMR chemical shift and relaxation analysis of human vinexin SH3 domain using a genetically encoded {sup 15}N/{sup 19}F-labeled unnatural amino acid

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

Shi, Pan; School of Life Science, University of Science and Technology of China, Hefei, Anhui 230026; Xi, Zhaoyong

Research highlights: {yields} Chemical synthesis of {sup 15}N/{sup 19}F-trifluomethyl phenylalanine. {yields} Site-specific incorporation of {sup 15}N/{sup 19}F-trifluomethyl phenylalanine to SH3. {yields} Site-specific backbone and side chain chemical shift and relaxation analysis. {yields} Different internal motions at different sites of SH3 domain upon ligand binding. -- Abstract: SH3 is a ubiquitous domain mediating protein-protein interactions. Recent solution NMR structural studies have shown that a proline-rich peptide is capable of binding to the human vinexin SH3 domain. Here, an orthogonal amber tRNA/tRNA synthetase pair for {sup 15}N/{sup 19}F-trifluoromethyl-phenylalanine ({sup 15}N/{sup 19}F-tfmF) has been applied to achieve site-specific labeling of SH3 at threemore » different sites. One-dimensional solution NMR spectra of backbone amide ({sup 15}N){sup 1}H and side-chain {sup 19}F were obtained for SH3 with three different site-specific labels. Site-specific backbone amide ({sup 15}N){sup 1}H and side-chain {sup 19}F chemical shift and relaxation analysis of SH3 in the absence or presence of a peptide ligand demonstrated different internal motions upon ligand binding at the three different sites. This site-specific NMR analysis might be very useful for studying large-sized proteins or protein complexes.« less

WAG 2 remedial investigation and site investigation site-specific work plan/health and safety checklist for the sediment transport modeling task

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

Holt, V.L.; Baron, L.A.

1994-05-01

This site-specific Work Plan/Health and Safety Checklist (WP/HSC) is a supplement to the general health and safety plan (HASP) for Waste Area Grouping (WAG) 2 remedial investigation and site investigation (WAG 2 RI&SI) activities [Health and Safety Plan for the Remedial Investigation and Site Investigation of Waste Area Grouping 2 at the Oak Ridge National Laboratory, Oak Ridge, Tennessee (ORNL/ER-169)] and provides specific details and requirements for the WAG 2 RI&SI Sediment Transport Modeling Task. This WP/HSC identifies specific site operations, site hazards, and any recommendations by Oak Ridge National Laboratory (ORNL) health and safety organizations [i.e., Industrial Hygiene (IH),more » Health Physics (HP), and/or Industrial Safety] that would contribute to the safe completion of the WAG 2 RI&SI. Together, the general HASP for the WAG 2 RI&SI (ORNL/ER-169) and the completed site-specific WP/HSC meet the health and safety planning requirements specified by 29 CFR 1910.120 and the ORNL Hazardous Waste Operations and Emergency Response (HAZWOPER) Program Manual. In addition to the health and safety information provided in the general HASP for the WAG 2 RI&SI, details concerning the site-specific task are elaborated in this site-specific WP/HSC, and both documents, as well as all pertinent procedures referenced therein, will be reviewed by all field personnel prior to beginning operations.« less

Transition and Transfer of Remediated Formerly Utilized Sites Remedial Action Program (FUSRAP) Sites from U.S. Army Corps of Engineers (USACE) to U.S. Department of Energy (DOE)

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

Carpenter, Cliff; Castillo, Darina; Fatherly, Nicki

The US Department of Energy (DOE) expects to receive the transfer of 10 FUSRAP Sites from the US Army Corps of Engineers (USACE) over the next 10 years; however, the timing of the transfers is highly dependent upon federal funding of the ongoing remedial actions. When remediation for each site is complete and the 2-year operations and maintenance period has concluded, each site will transfer from USACE to DOE for long-term surveillance and maintenance (LTS&M). US DOE’s Office of Legacy Management (LM) will accept program responsibility for these sites and conduct LTS&M activities required to maintain protectiveness, preserve site-specific knowledge,more » and retain the cleanup and stewardship records while keeping stakeholders informed. Since the last FUSRAP site transfer occurred in 2007, LM in coordination with USACE intends to establish a transition process to promote the seamless transfer of sites from the time when the first record of decision is signed to the completion of FUSRAP activities. The approach to transfer active FUSRAP sites to completed sites status has been historically outlined in foundational documents such as the 1999 Memorandum of Understanding and supporting letters of agreement between the two agencies. As more complex FUSRAP sites are completed, this transition process will provide a model between the two agencies to communicate future long-term care liabilities. Ultimately, the FUSRAP transition process is structured to acquire and preserve site knowledge and information necessary for protecting the environment and public health. As of 2015, LM has transitioned and accepted programmatic responsibility for over 90 sites. From LM’s perspective, successful transition of any site includes understanding the long-term environmental liabilities. LM uses site transition framework requirements from past transitions to develop site-specific transition plans. Site-specific transition plans are developed by LM in coordination with USACE and executed during the 2-year operations and maintenance period. An integrated project team of subject matter experts is assembled to address the conditions of the transitioning site; acquire a site records collection; evaluate site operations and final site conditions and associated risks; identify and contact stakeholders; and document the basis for site LTS&M requirements. While the majority of the transition activities are completed by LM, close coordination between US DOE LM and USACE throughout this process is essential for an effective and seamless transfer to assure that there is no lapse in site protectiveness.« less

Absorption sites of orally administered drugs in the small intestine.

PubMed

Murakami, Teruo

2017-12-01

In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies. Expert opinion: Various factors including: the solubility, lipophilicity, luminal concentration, pKa value, transporter substrate specificity, transporter expression, luminal fluid pH, gastrointestinal transit time, and intestinal metabolism determine the site-dependent intestinal absorption. However, most of the dissolved fraction of orally administered drugs including substrates for ABC and SLC transporters, except for some weakly basic drugs with higher pKa values, are considered to be absorbed sequentially from the proximal small intestine. Securing the solubility and stability of drugs prior to reaching to the main absorption sites and appropriate delivery rates of drugs at absorption sites are important goals for achieving effective pharmacotherapy.

TSAPA: identification of tissue-specific alternative polyadenylation sites in plants.

PubMed

Ji, Guoli; Chen, Moliang; Ye, Wenbin; Zhu, Sheng; Ye, Congting; Su, Yaru; Peng, Haonan; Wu, Xiaohui

2018-06-15

Alternative polyadenylation (APA) is now emerging as a widespread mechanism modulated tissue-specifically, which highlights the need to define tissue-specific poly(A) sites for profiling APA dynamics across tissues. We have developed an R package called TSAPA based on the machine learning model for identifying tissue-specific poly(A) sites in plants. A feature space including more than 200 features was assembled to specifically characterize poly(A) sites in plants. The classification model in TSAPA can be customized by selecting desirable features or classifiers. TSAPA is also capable of predicting tissue-specific poly(A) sites in unannotated intergenic regions. TSAPA will be a valuable addition to the community for studying dynamics of APA in plants. https://github.com/BMILAB/TSAPA. Supplementary data are available at Bioinformatics online.

Reassessment of the NH4 NO3 thermal decomposition technique for calibration of the N2 O isotopic composition.

PubMed

Mohn, Joachim; Gutjahr, Wilhelm; Toyoda, Sakae; Harris, Eliza; Ibraim, Erkan; Geilmann, Heike; Schleppi, Patrick; Kuhn, Thomas; Lehmann, Moritz F; Decock, Charlotte; Werner, Roland A; Yoshida, Naohiro; Brand, Willi A

2016-09-08

In the last few years, the study of N 2 O site-specific nitrogen isotope composition has been established as a powerful technique to disentangle N 2 O emission pathways. This trend has been accelerated by significant analytical progress in the field of isotope-ratio mass-spectrometry (IRMS) and more recently quantum cascade laser absorption spectroscopy (QCLAS). Methods The ammonium nitrate (NH 4 NO 3 ) decomposition technique provides a strategy to scale the 15 N site-specific (SP ≡ δ 15 N α - δ 15 N β ) and bulk (δ 15 N bulk  = (δ 15 N α  + δ 15 N β )/2) isotopic composition of N 2 O against the international standard for the 15 N/ 14 N isotope ratio (AIR-N 2 ). Within the current project 15 N fractionation effects during thermal decomposition of NH 4 NO 3 on the N 2 O site preference were studied using static and dynamic decomposition techniques. The validity of the NH 4 NO 3 decomposition technique to link NH 4 + and NO 3 - moiety-specific δ 15 N analysis by IRMS to the site-specific nitrogen isotopic composition of N 2 O was confirmed. However, the accuracy of this approach for the calibration of δ 15 N α and δ 15 N β values was found to be limited by non-quantitative NH 4 NO 3 decomposition in combination with substantially different isotope enrichment factors for the conversion of the NO 3 - or NH 4 + nitrogen atom into the α or β position of the N 2 O molecule. The study reveals that the completeness and reproducibility of the NH 4 NO 3 decomposition reaction currently confine the anchoring of N 2 O site-specific isotopic composition to the international isotope ratio scale AIR-N 2 . The authors suggest establishing a set of N 2 O isotope reference materials with appropriate site-specific isotopic composition, as community standards, to improve inter-laboratory compatibility. This article is protected by copyright. All rights reserved.

Shuttle abort landing site emergency medical services

NASA Technical Reports Server (NTRS)

Mckenas, David K.; Jennings, Richard T.

1991-01-01

NASA and DOD studies of medical-planning and logistical problems are reviewed as applicable to providing emergency medical care at remote transoceanic abort landing (TAL) sites. Two options are analyzed including a modified surgical response team and a combination physician/medical technician team. The two concepts are examined in terms of cost-effectiveness, specific types of medical support such as blood procurement, and search-and-rescue requirements. It is found that the physician/technician team is more economically efficient, and the description of the concept permits the development of an effective TAL-site astronaut medical-support system. A balance is struck between the competing problems of cost and medical capability by planning for on-scene medical stabilization and air evacuation to DOD tertiary medical centers.

Population normative data for the 10/66 Dementia Research Group cognitive test battery from Latin America, India and China: a cross-sectional survey

PubMed Central

Sosa, Ana Luisa; Albanese, Emiliano; Prince, Martin; Acosta, Daisy; Ferri, Cleusa P; Guerra, Mariella; Huang, Yueqin; Jacob, KS; de Rodriguez, Juan Llibre; Salas, Aquiles; Yang, Fang; Gaona, Ciro; Joteeshwaran, AT; Rodriguez, Guillermina; de la Torre, Gabriela Rojas; Williams, Joseph D; Stewart, Robert

2009-01-01

Background 1) To report site-specific normative values by age, sex and educational level for four components of the 10/66 Dementia Research Group cognitive test battery; 2) to estimate the main and interactive effects of age, sex, and educational level by site; and 3) to investigate the effect of site by region and by rural or urban location. Methods Population-based cross-sectional one phase catchment area surveys were conducted in Cuba, Dominican Republic, Venezuela, Peru, Mexico, China and India. The protocol included the administration of the Community Screening Instrument for Dementia (CSI 'D', generating the COGSCORE measure of global function), and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) verbal fluency (VF), word list memory (WLM, immediate recall) and recall (WLR, delayed recall) tests. Only those free of dementia were included in the analysis. Results Older people, and those with less education performed worse on all four tests. The effect of sex was much smaller and less consistent. There was a considerable effect of site after accounting for compositional differences in age, education and sex. Much of this was accounted for by the effect of region with Chinese participants performing better, and Indian participants worse, than those from Latin America. The effect of region was more prominent for VF and WLM than for COGSCORE and WLR. Conclusion Cognitive assessment is a basic element for dementia diagnosis. Age- and education-specific norms are required for this purpose, while the effect of gender can probably be ignored. The basis of cultural effects is poorly understood, but our findings serve to emphasise that normative data may not be safely generalised from one population to another with quite different characteristics. The minimal effects of region on COGSCORE and WLR are reassuring with respect to the cross-cultural validity of the 10/66 dementia diagnosis, which uses only these elements of the 10/66 battery. PMID:19709405

SUPPORTING THE REDEVELOPMENT OF BROWNFIELD SITES USING SITE-SPECIFIC MANAGEMENT APPROACHES AND REDEVELOPMENT TOOLS (SMART)

EPA Science Inventory

The Site-Specific Management Approaches and Redevelopment Tools (SMART) provides potential solutions for facilitating the redevelopment of brownfield sites. The term "brownfield site" refers to previously developed property whose reuse may be complicated by the presence of hazar...

A systematic identification of species-specific protein succinylation sites using joint element features information.

PubMed

Hasan, Md Mehedi; Khatun, Mst Shamima; Mollah, Md Nurul Haque; Yong, Cao; Guo, Dianjing

2017-01-01

Lysine succinylation, an important type of protein posttranslational modification, plays significant roles in many cellular processes. Accurate identification of succinylation sites can facilitate our understanding about the molecular mechanism and potential roles of lysine succinylation. However, even in well-studied systems, a majority of the succinylation sites remain undetected because the traditional experimental approaches to succinylation site identification are often costly, time-consuming, and laborious. In silico approach, on the other hand, is potentially an alternative strategy to predict succinylation substrates. In this paper, a novel computational predictor SuccinSite2.0 was developed for predicting generic and species-specific protein succinylation sites. This predictor takes the composition of profile-based amino acid and orthogonal binary features, which were used to train a random forest classifier. We demonstrated that the proposed SuccinSite2.0 predictor outperformed other currently existing implementations on a complementarily independent dataset. Furthermore, the important features that make visible contributions to species-specific and cross-species-specific prediction of protein succinylation site were analyzed. The proposed predictor is anticipated to be a useful computational resource for lysine succinylation site prediction. The integrated species-specific online tool of SuccinSite2.0 is publicly accessible.

77 FR 51789 - Environmental Management Site-Specific Advisory Board, Paducah

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-27

... management and related activities. Tentative Agenda Call to Order, Introductions, Review of Agenda... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Paducah AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Paducah. The Federal Advisory Committee Act...

75 FR 64718 - Environmental Management Site-Specific Advisory Board, Hanford

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-20

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Hanford AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Hanford. The Federal Advisory Committee Act.... ADDRESSES: Red Lion Hanford House, 802 George Washington Way, Richland, Washington. FOR FURTHER INFORMATION...

75 FR 8051 - Environmental Management Site-Specific Advisory Board, Hanford

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-23

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Hanford AGENCY... the Environmental Management Site-Specific Advisory Board (EM SSAB), Hanford (known locally as the Hanford Advisory Board [HAB]), River and Plateau, Tank Waste, Public Involvement, Health Safety and...

76 FR 4645 - Environmental Management Site-Specific Advisory Board, Hanford

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Hanford AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Hanford. The Federal Advisory Committee Act.... ADDRESSES: Red Lion Hanford House, 802 George Washington Way, Richland, Washington 99352. FOR FURTHER...

75 FR 19379 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-14

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act... areas of environmental restoration, waste management and related activities. Tentative Agenda Call to...

75 FR 7577 - Environmental Management Site-Specific Advisory Board, Portsmouth

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Portsmouth AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Portsmouth. The Federal Advisory Committee Act... areas of environmental restoration, waste management and related activities. Tentative Agenda: Call to...

76 FR 17118 - Environmental Management Site-Specific Advisory Board Chairs

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-28

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board Chairs AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB) Chairs. The Federal Advisory Committee Act (Pub... areas of environmental restoration, waste management, and related activities. Tentative Agenda Topics...

76 FR 62054 - Environmental Management Site-Specific Advisory Board Chairs

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

... environmental restoration, waste management, and related activities. Tentative Agenda Topics [cir] EM Program... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board Chairs AGENCY... of the Environmental Management Site-Specific Advisory Board (EM SSAB) Chairs. The Federal Advisory...

77 FR 55813 - Environmental Management Site-Specific Advisory Board Chairs

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board Chairs AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB) Chairs. The Federal Advisory Committee Act (Pub... environmental restoration, waste management, and related activities. Tentative Agenda Topics Tuesday, October 2...

Seasonality of Influenza and Respiratory Syncytial Viruses and the Effect of Climate Factors in Subtropical-Tropical Asia Using Influenza-Like Illness Surveillance Data, 2010 -2012.

PubMed

Kamigaki, Taro; Chaw, Liling; Tan, Alvin G; Tamaki, Raita; Alday, Portia P; Javier, Jenaline B; Olveda, Remigio M; Oshitani, Hitoshi; Tallo, Veronica L

2016-01-01

The seasonality of influenza and respiratory syncytial virus (RSV) is well known, and many analyses have been conducted in temperate countries; however, this is still not well understood in tropical countries. Previous studies suggest that climate factors are involved in the seasonality of these viruses. However, the extent of the effect of each climate variable is yet to be defined. We investigated the pattern of seasonality and the effect of climate variables on influenza and RSV at three sites of different latitudes: the Eastern Visayas region and Baguio City in the Philippines, and Okinawa Prefecture in Japan. Wavelet analysis and the dynamic linear regression model were applied. Climate variables used in the analysis included mean temperature, relative and specific humidity, precipitation, and number of rainy days. The Akaike Information Criterion estimated in each model was used to test the improvement of fit in comparison with the baseline model. At all three study sites, annual seasonal peaks were observed in influenza A and RSV; peaks were unclear for influenza B. Ranges of climate variables at the two Philippine sites were narrower and mean variables were significantly different among the three sites. Whereas all climate variables except the number of rainy days improved model fit to the local trend model, their contributions were modest. Mean temperature and specific humidity were positively associated with influenza and RSV at the Philippine sites and negatively associated with influenza A in Okinawa. Precipitation also improved model fit for influenza and RSV at both Philippine sites, except for the influenza A model in the Eastern Visayas. Annual seasonal peaks were observed for influenza A and RSV but were less clear for influenza B at all three study sites. Including additional data from subsequent more years would help to ascertain these findings. Annual amplitude and variation in climate variables are more important than their absolute values for determining their effect on the seasonality of influenza and RSV.

Comparative Toxicology of Libby Amphibole and Naturally Occurring Asbestos

EPA Science Inventory

Summary sentence: Comparative toxicology of Libby amphibole (LA) and site-specific naturally occurring asbestos (NOA) provides new insights on physical properties influencing health effects and mechanisms of asbestos-induced inflammation, fibrosis, and tumorigenesis.Introduction/...

Site-specific PEGylation of human thyroid stimulating hormone to prolong duration of action.

PubMed

Qiu, Huawei; Boudanova, Ekaterina; Park, Anna; Bird, Julie J; Honey, Denise M; Zarazinski, Christine; Greene, Ben; Kingsbury, Jonathan S; Boucher, Susan; Pollock, Julie; McPherson, John M; Pan, Clark Q

2013-03-20

Recombinant human thyroid stimulating hormone (rhTSH or Thyrogen) has been approved for thyroid cancer diagnostics and treatment under a multidose regimen due to its short circulating half-life. To reduce dosing frequency, PEGylation strategies were explored to increase the duration of action of rhTSH. Lysine and N-terminal PEGylation resulted in heterogeneous product profiles with 40% or lower reaction yields of monoPEGylated products. Eleven cysteine mutants were designed based on a structure model of the TSH-TSH receptor (TSHR) complex to create unique conjugation sites on both α and β subunits for site-specific conjugation. Sequential screening of mutant expression level, oligomerization tendency, and conjugation efficiency resulted in the identification of the αG22C rhTSH mutant for stable expression and scale-up PEGylation. The introduced cysteine in the αG22C rhTSH mutant was partially blocked when isolated from conditioned media and could only be effectively PEGylated after mild reduction with cysteine. This produced a higher reaction yield, ~85%, for the monoPEGylated product. Although the mutation had no effect on receptor binding, PEGylation of αG22C rhTSH led to a PEG size-dependent decrease in receptor binding. Nevertheless, the 40 kDa PEG αG22C rhTSH showed a prolonged duration of action compared to rhTSH in a rat pharmacodynamics model. Reverse-phase HPLC and N-terminal sequencing experiments confirmed site-specific modification at the engineered Cys 22 position on the α-subunit. This work is another demonstration of successful PEGylation of a cysteine-knot protein by an engineered cysteine mutation.

Modeling corewood-outerwood transition in loblolly pine using wood specific gravity

Treesearch

Christian R. Mora; H. Lee Allen; Richard F. Daniels; Alexander Clark

2007-01-01

A modified logistic function was used for modeling specific-gravity profiles obtained from X-ray densitometry analysis in 675 loblolly pine (Pinus taeda L.) trees in four regeneration trials. Trees were 21 or 22 years old at the time of the study. The function was used for demarcating corewood, transitional, and outerwood zones. Site and silvicultural effects were...

Fast and automated functional classification with MED-SuMo: an application on purine-binding proteins.

PubMed

Doppelt-Azeroual, Olivia; Delfaud, François; Moriaud, Fabrice; de Brevern, Alexandre G

2010-04-01

Ligand-protein interactions are essential for biological processes, and precise characterization of protein binding sites is crucial to understand protein functions. MED-SuMo is a powerful technology to localize similar local regions on protein surfaces. Its heuristic is based on a 3D representation of macromolecules using specific surface chemical features associating chemical characteristics with geometrical properties. MED-SMA is an automated and fast method to classify binding sites. It is based on MED-SuMo technology, which builds a similarity graph, and it uses the Markov Clustering algorithm. Purine binding sites are well studied as drug targets. Here, purine binding sites of the Protein DataBank (PDB) are classified. Proteins potentially inhibited or activated through the same mechanism are gathered. Results are analyzed according to PROSITE annotations and to carefully refined functional annotations extracted from the PDB. As expected, binding sites associated with related mechanisms are gathered, for example, the Small GTPases. Nevertheless, protein kinases from different Kinome families are also found together, for example, Aurora-A and CDK2 proteins which are inhibited by the same drugs. Representative examples of different clusters are presented. The effectiveness of the MED-SMA approach is demonstrated as it gathers binding sites of proteins with similar structure-activity relationships. Moreover, an efficient new protocol associates structures absent of cocrystallized ligands to the purine clusters enabling those structures to be associated with a specific binding mechanism. Applications of this classification by binding mode similarity include target-based drug design and prediction of cross-reactivity and therefore potential toxic side effects.

Fast and automated functional classification with MED-SuMo: An application on purine-binding proteins

PubMed Central

Doppelt-Azeroual, Olivia; Delfaud, François; Moriaud, Fabrice; de Brevern, Alexandre G

2010-01-01

Ligand–protein interactions are essential for biological processes, and precise characterization of protein binding sites is crucial to understand protein functions. MED-SuMo is a powerful technology to localize similar local regions on protein surfaces. Its heuristic is based on a 3D representation of macromolecules using specific surface chemical features associating chemical characteristics with geometrical properties. MED-SMA is an automated and fast method to classify binding sites. It is based on MED-SuMo technology, which builds a similarity graph, and it uses the Markov Clustering algorithm. Purine binding sites are well studied as drug targets. Here, purine binding sites of the Protein DataBank (PDB) are classified. Proteins potentially inhibited or activated through the same mechanism are gathered. Results are analyzed according to PROSITE annotations and to carefully refined functional annotations extracted from the PDB. As expected, binding sites associated with related mechanisms are gathered, for example, the Small GTPases. Nevertheless, protein kinases from different Kinome families are also found together, for example, Aurora-A and CDK2 proteins which are inhibited by the same drugs. Representative examples of different clusters are presented. The effectiveness of the MED-SMA approach is demonstrated as it gathers binding sites of proteins with similar structure-activity relationships. Moreover, an efficient new protocol associates structures absent of cocrystallized ligands to the purine clusters enabling those structures to be associated with a specific binding mechanism. Applications of this classification by binding mode similarity include target-based drug design and prediction of cross-reactivity and therefore potential toxic side effects. PMID:20162627

Synthesis and binding properties of new selective ligands for the nucleobase opposite the AP site.

PubMed

Abe, Yukiko; Nakagawa, Osamu; Yamaguchi, Rie; Sasaki, Shigeki

2012-06-01

DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3'-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; that is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

USGS Publications Warehouse

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

2017-05-23

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

Sex-specific effect of Pirin gene on bone mineral density in a cohort of 4000 Chinese.

PubMed

Tang, Nelson L S; Liao, Chen Di; Ching, Jasmine K L; Suen, Eddie W C; Chan, Iris H S; Orwoll, Eric; Ho, Suzanne C; Chan, Frank W K; Kwok, Anthony W L; Kwok, Timothy; Woo, Jean; Leung, Ping Chung

2010-02-01

Osteoporosis is a common condition among elderly. Genetic mapping studies repeatedly located the distal short arms of X-chromosome as the quantitative trait loci (QTL) for BMD in mice. Fine mapping of a syntenic segment on Xp22 in a Caucasian female population suggested a moderate association between lumbar spine (LS) BMD and 2 intronic SNPs in the Pirin (PIR) gene, which encodes an iron-binding nuclear protein. This study aimed to examine genetic variations in the PIR gene by a comprehensive tagging method and its sex-specific effects on BMD and osteoporotic risk. Two thousand men and 2000 women aged 65 or above were recruited from the community. BMDs at the LS, femoral neck, total hip and whole body were measured and followed up at 4-year. Genotyping was performed for tagSNPs of PIR gene including adjacent regions, and the PIR haplotypes were inferred using PHASE program. Analysis by linear regression showed a significant association between SNP rs5935970 and LS-BMD, while haplotype T-T-A was significantly associated with BMD of all measured sites. However, none of such associations were found in men. Linear Mixed Model also confirmed the same sex-specific and site-specific effect for longitudinal BMD changes. In addition to confirming the association between BMDs and the PIR gene, we also revealed that this finding is sex-specific, possibly due to an X-linked effect. This study demonstrated the importance of considering sex and genetic interactions in studies of disease predisposition and complex traits. (c) 2009 Elsevier Inc. All rights reserved.

Mapping of RNA accessible sites by extension of random oligonucleotide libraries with reverse transcriptase.

PubMed Central

Allawi, H T; Dong, F; Ip, H S; Neri, B P; Lyamichev, V I

2001-01-01

A rapid and simple method for determining accessible sites in RNA that is independent of the length of target RNA and does not require RNA labeling is described. In this method, target RNA is allowed to hybridize with sequence-randomized libraries of DNA oligonucleotides linked to a common tag sequence at their 5'-end. Annealed oligonucleotides are extended with reverse transcriptase and the extended products are then amplified by using PCR with a primer corresponding to the tag sequence and a second primer specific to the target RNA sequence. We used the combination of both the lengths of the RT-PCR products and the location of the binding site of the RNA-specific primer to determine which regions of the RNA molecules were RNA extendible sites, that is, sites available for oligonucleotide binding and extension. We then employed this reverse transcription with the random oligonucleotide libraries (RT-ROL) method to determine the accessible sites on four mRNA targets, human activated ras (ha-ras), human intercellular adhesion molecule-1 (ICAM-1), rabbit beta-globin, and human interferon-gamma (IFN-gamma). Our results were concordant with those of other researchers who had used RNase H cleavage or hybridization with arrays of oligonucleotides to identify accessible sites on some of these targets. Further, we found good correlation between sites when we compared the location of extendible sites identified by RT-ROL with hybridization sites of effective antisense oligonucleotides on ICAM-1 mRNA in antisense inhibition studies. Finally, we discuss the relationship between RNA extendible sites and RNA accessibility. PMID:11233988

Genome-Wide Progesterone Receptor Binding: Cell Type-Specific and Shared Mechanisms in T47D Breast Cancer Cells and Primary Leiomyoma Cells

PubMed Central

Huang, Lei; Owen, Jonas K.; Xie, Anna; Navarro, Antonia; Monsivais, Diana; Coon V, John S.; Kim, J. Julie; Dai, Yang; Bulun, Serdar E.

2012-01-01

Background Progesterone, via its nuclear receptor (PR), exerts an overall tumorigenic effect on both uterine fibroid (leiomyoma) and breast cancer tissues, whereas the antiprogestin RU486 inhibits growth of these tissues through an unknown mechanism. Here, we determined the interaction between common or cell-specific genome-wide binding sites of PR and mRNA expression in RU486-treated uterine leiomyoma and breast cancer cells. Principal Findings ChIP-sequencing revealed 31,457 and 7,034 PR-binding sites in breast cancer and uterine leiomyoma cells, respectively; 1,035 sites overlapped in both cell types. Based on the chromatin-PR interaction in both cell types, we statistically refined the consensus progesterone response element to G•ACA• • •TGT•C. We identified two striking differences between uterine leiomyoma and breast cancer cells. First, the cis-regulatory elements for HSF, TEF-1, and C/EBPα and β were statistically enriched at genomic RU486/PR-targets in uterine leiomyoma, whereas E2F, FOXO1, FOXA1, and FOXF sites were preferentially enriched in breast cancer cells. Second, 51.5% of RU486-regulated genes in breast cancer cells but only 6.6% of RU486-regulated genes in uterine leiomyoma cells contained a PR-binding site within 5 kb from their transcription start sites (TSSs), whereas 75.4% of RU486-regulated genes contained a PR-binding site farther than 50 kb from their TSSs in uterine leiomyoma cells. RU486 regulated only seven mRNAs in both cell types. Among these, adipophilin (PLIN2), a pro-differentiation gene, was induced via RU486 and PR via the same regulatory region in both cell types. Conclusions Our studies have identified molecular components in a RU486/PR-controlled gene network involved in the regulation of cell growth, cell migration, and extracellular matrix function. Tissue-specific and common patterns of genome-wide PR binding and gene regulation may determine the therapeutic effects of antiprogestins in uterine fibroids and breast cancer. PMID:22272226

External quality-assurance results for the National Atmospheric Deposition Program/National Trends Network during 1991

USGS Publications Warehouse

Nilles, M.A.; Gordon, J.D.; Schroder, L.J.; Paulin, C.E.

1995-01-01

The U.S. Geological Survey used four programs in 1991 to provide external quality assurance for the National Atmospheric Deposition Program/National Trends Network (NADP/NTN). An intersite-comparison program was used to evaluate onsite pH and specific-conductance determinations. The effects of routine sample handling, processing, and shipping of wet-deposition samples on analyte determinations and an estimated precision of analyte values and concentrations were evaluated in the blind-audit program. Differences between analytical results and an estimate of the analytical precision of four laboratories routinely measuring wet deposition were determined by an interlaboratory-comparison program. Overall precision estimates for the precipitation-monitoring system were determined for selected sites by a collocated-sampler program. Results of the intersite-comparison program indicated that 93 and 86 percent of the site operators met the NADP/NTN accuracy goal for pH determinations during the two intersite-comparison studies completed during 1991. The results also indicated that 96 and 97 percent of the site operators met the NADP/NTN accuracy goal for specific-conductance determinations during the two 1991 studies. The effects of routine sample handling, processing, and shipping, determined in the blind-audit program indicated significant positive bias (a=.O 1) for calcium, magnesium, sodium, potassium, chloride, nitrate, and sulfate. Significant negative bias (or=.01) was determined for hydrogen ion and specific conductance. Only ammonium determinations were not biased. A Kruskal-Wallis test indicated that there were no significant (*3t=.01) differences in analytical results from the four laboratories participating in the interlaboratory-comparison program. Results from the collocated-sampler program indicated the median relative error for cation concentration and deposition exceeded eight percent at most sites, whereas the median relative error for sample volume, sulfate, and nitrate concentration at all sites was less than four percent. The median relative error for hydrogen ion concentration and deposition ranged from 4.6 to 18.3 percent at the four sites and as indicated in previous years of the study, was inversely proportional to the acidity of the precipitation at a given site. Overall, collocated-sampling error typically was five times that of laboratory error estimates for most analytes.

SITE-SPECIFIC CHARACTERIZATION OF SOIL RADON POTENTIALS

EPA Science Inventory

The report presents a theoretical basis for measuring site-specific radon potentials. However, the empirical measurements suggest that the precision of such measurements is marginal, leaving an uncertainty of about a factor of 2 in site-specific estimates. Although this may be us...

Site Specific Management of Cotton Production in the United States

USDA-ARS?s Scientific Manuscript database

Site-specific management or precision agriculture, as it is evolving in large-scale crop production, offers promising new methods for managing cotton production for optimized yields, maximized profitability, and minimized environmental pollution. However, adaptation of site-specific theory and meth...

76 FR 68179 - Environmental Management Site-Specific Advisory Board, Idaho National Laboratory

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-03

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Idaho National... November 14, 2011, of the Environmental Management Site-Specific Advisory Board, Idaho National Laboratory...: Robert L. Pence, Federal Coordinator, Department of Energy, Idaho Operations Office, 1955 Fremont Avenue...

77 FR 65374 - Environmental Management Site-Specific Advisory Board, Idaho National Laboratory

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-26

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Idaho National... meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Idaho National Laboratory... management in the areas of environmental restoration, waste management, and related activities. Tentative...

77 FR 11516 - Environmental Management Site-Specific Advisory Board, Paducah

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... materials; excess facilities; future land use and long-term stewardship; risk assessment and management; and... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Paducah AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Paducah. The Federal Advisory Committee Act...

77 FR 2282 - Environmental Management Site-Specific Advisory Board, Paducah

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-17

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Paducah AGENCY... the Environmental Management Site-Specific Advisory Board, Paducah. This notice announces the... scheduling conflicts by members. The next regular meeting will be held on February 16, 2012. DATES: The...

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

USGS Publications Warehouse

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

Specificity of O-glycosylation in enhancing the stability and cellulose binding affinity of Family 1 carbohydrate-binding modules

PubMed Central

Chen, Liqun; Drake, Matthew R.; Resch, Michael G.; Greene, Eric R.; Himmel, Michael E.; Chaffey, Patrick K.; Beckham, Gregg T.; Tan, Zhongping

2014-01-01

The majority of biological turnover of lignocellulosic biomass in nature is conducted by fungi, which commonly use Family 1 carbohydrate-binding modules (CBMs) for targeting enzymes to cellulose. Family 1 CBMs are glycosylated, but the effects of glycosylation on CBM function remain unknown. Here, the effects of O-mannosylation are examined on the Family 1 CBM from the Trichoderma reesei Family 7 cellobiohydrolase at three glycosylation sites. To enable this work, a procedure to synthesize glycosylated Family 1 CBMs was developed. Subsequently, a library of 20 CBMs was synthesized with mono-, di-, or trisaccharides at each site for comparison of binding affinity, proteolytic stability, and thermostability. The results show that, although CBM mannosylation does not induce major conformational changes, it can increase the thermolysin cleavage resistance up to 50-fold depending on the number of mannose units on the CBM and the attachment site. O-Mannosylation also increases the thermostability of CBM glycoforms up to 16 °C, and a mannose disaccharide at Ser3 seems to have the largest themostabilizing effect. Interestingly, the glycoforms with small glycans at each site displayed higher binding affinities for crystalline cellulose, and the glycoform with a single mannose at each of three positions conferred the highest affinity enhancement of 7.4-fold. Overall, by combining chemical glycoprotein synthesis and functional studies, we show that specific glycosylation events confer multiple beneficial properties on Family 1 CBMs. PMID:24821760

Ab initio calculation of electronic structure and magnetic properties of R2Fe14BNx (R = Pr,Nd)

NASA Astrophysics Data System (ADS)

Tian, Guang; Zha, Liang; Yang, Wenyun; Qiao, Guanyi; Wang, Changsheng; Yang, Yingchang; Yang, Jinbo

2018-05-01

The site preference of N atom for R2Fe14BNx (R= Pr, Nd) and the interstitial nitrogen effect on the magnetic properties have been studied by the first-principles method. It was found that the nitrogen is more likely to occupy the 4e site for Pr2Fe14BNx compound, while 4f site for Nd2Fe14BNx. When N atoms entering some specific crystal sites (such as 2a and 4f), the total magnetic moments of these compounds are not reduced, but slightly increased. Although the doping of N may reduce the total magnetic moments of some R2Fe14B compounds in the cases of optimal occupancy, the volumetric effect caused by N doping can still change the electron density distributions of Fe near the Fermi level, improving the magnetic ordering temperature of such compounds.

Programmable graphene doping via electron beam irradiation.

PubMed

Zhou, Yangbo; Jadwiszczak, Jakub; Keane, Darragh; Chen, Ying; Yu, Dapeng; Zhang, Hongzhou

2017-06-29

Graphene is a promising candidate to succeed silicon based devices, and the conventional strategies for fabrication and testing of graphene-based electronics often utilise an electron beam. Here, we report on a systematic study of the effect of electron beam exposure on graphene devices. We realise reversible doping of on-chip graphene using a focused electron beam. Our results demonstrate site-specific control of carrier type and concentration achievable by modulating the charge distribution in the substrate. The effect of substrate-embedded charges on carrier mobility and conductivity of graphene is studied, with a dielectric screening model proposed to explain the effective n-type and p-type doping produced at different beam energies. Multiple logic operations are thus implemented in a single graphene sheet by using site-specific e-beam irradiation. We extend the phenomenon to MoS 2 , generalising it to conductive two-dimensional materials. Our results are of importance to imaging, in situ characterisation and lithographic techniques employed to investigate 2D materials.

A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers

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

Glodzik, Dominik; Morganella, Sandro; Davies, Helen

Somatic rearrangements contribute to the mutagenized landscape of cancer genomes. Here, we systematically interrogated rearrangements in 560 breast cancers by using a piecewise constant fitting approach. We identified 33 hotspots of large (>100 kb) tandem duplications, a mutational signature associated with homologous-recombination-repair deficiency. Notably, these tandem-duplication hotspots were enriched in breast cancer germline susceptibility loci (odds ratio (OR) = 4.28) and breast-specific 'super-enhancer' regulatory elements (OR = 3.54). These hotspots may be sites of selective susceptibility to double-strand-break damage due to high transcriptional activity or, through incrementally increasing copy number, may be sites of secondary selective pressure. Furthermore, the transcriptomicmore » consequences ranged from strong individual oncogene effects to weak but quantifiable multigene expression effects. We thus present a somatic-rearrangement mutational process affecting coding sequences and noncoding regulatory elements and contributing a continuum of driver consequences, from modest to strong effects, thereby supporting a polygenic model of cancer development.« less

A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers

DOE PAGES

Glodzik, Dominik; Morganella, Sandro; Davies, Helen; ...

2017-01-23

Somatic rearrangements contribute to the mutagenized landscape of cancer genomes. Here, we systematically interrogated rearrangements in 560 breast cancers by using a piecewise constant fitting approach. We identified 33 hotspots of large (>100 kb) tandem duplications, a mutational signature associated with homologous-recombination-repair deficiency. Notably, these tandem-duplication hotspots were enriched in breast cancer germline susceptibility loci (odds ratio (OR) = 4.28) and breast-specific 'super-enhancer' regulatory elements (OR = 3.54). These hotspots may be sites of selective susceptibility to double-strand-break damage due to high transcriptional activity or, through incrementally increasing copy number, may be sites of secondary selective pressure. Furthermore, the transcriptomicmore » consequences ranged from strong individual oncogene effects to weak but quantifiable multigene expression effects. We thus present a somatic-rearrangement mutational process affecting coding sequences and noncoding regulatory elements and contributing a continuum of driver consequences, from modest to strong effects, thereby supporting a polygenic model of cancer development.« less

Three-year growth response of young Douglas-fir to nitrogen, calcium, phosphorus, and blended fertilizers in Oregon and Washington

USGS Publications Warehouse

Mainwaring, Douglas B.; Maguire, Douglas A.; Perakis, Steven S.

2014-01-01

Studies of nutrient limitation in Douglas-fir forests of the Pacific Northwest focus predominantly on nitrogen, yet many stands demonstrate negligible or even negative growth response to nitrogen fertilization. To understand what nutrients other than nitrogen may limit forest productivity in this region, we tested six fertilizer treatments for their ability to increase stem volume growth response of dominant and co-dominant trees in young Douglas-fir plantations across a range of foliar and soil chemistry in western Oregon and Washington. We evaluated responses to single applications of urea, lime, calcium chloride, or monosodium phosphate at 16 sites, and to two site-specific nutrients blends at 12 of these sites. Across sites, the average stem volume growth increased marginally with urea, lime, and phosphorus fertilization. Fertilization responses generally aligned with plant and soil indicators of nutrient limitation. Response to nitrogen addition was greatest on soils with low total nitrogen and high exchangeable calcium concentrations. Responses to lime and calcium chloride additions were greatest at sites with low foliar calcium and low soil pH. Response to phosphorus addition was greatest on sites with low foliar phosphorus and high soil pH. Blended fertilizers yielded only marginal growth increases at one site, with no consistent effect across sites. Overall, our results highlight that calcium and phosphorus can be important growth limiting nutrients on specific sites in nitrogen-rich Douglas-fir forests of the Pacific Northwest.

A Web-based approach to blood donor preparation.

PubMed

France, Christopher R; France, Janis L; Kowalsky, Jennifer M; Copley, Diane M; Lewis, Kristin N; Ellis, Gary D; McGlone, Sarah T; Sinclair, Kadian S

2013-02-01

Written and video approaches to donor education have been shown to enhance donation attitudes and intentions to give blood, particularly when the information provides specific coping suggestions for donation-related concerns. This study extends this work by comparing Web-based approaches to donor preparation among donors and nondonors. Young adults (62% female; mean [±SD] age, 19.3 [±1.5] years; mean [range] number of prior blood donations, 1.1 [0-26]; 60% nondonors) were randomly assigned to view 1) a study Web site designed to address common blood donor concerns and suggest specific coping strategies (n = 238), 2) a standard blood center Web site (n = 233), or 3) a control Web site where participants viewed videos of their choice (n = 202). Measures of donation attitude, anxiety, confidence, intention, anticipated regret, and moral norm were completed before and after the intervention. Among nondonors, the study Web site produced greater changes in donation attitude, confidence, intention, and anticipated regret relative to both the standard and the control Web sites, but only differed significantly from the control Web site for moral norm and anxiety. Among donors, the study Web site produced greater changes in donation confidence and anticipated regret relative to both the standard and the control Web sites, but only differed significantly from the control Web site for donation attitude, anxiety, intention, and moral norm. Web-based donor preparation materials may provide a cost-effective way to enhance donation intentions and encourage donation behavior. © 2012 American Association of Blood Banks.

Effects of water-control structures on hydrologic and water-quality characteristics in selected agricultural drainage canals in eastern North Carolina

USGS Publications Warehouse

Treece, M.W.; Jaynes, M.L.

1994-01-01

November of water into and out of tidally affected canals in eastern North Carolina was documented before and after the installation of water-control structures. Water levels in five of the canals downstream from the water-control structures were controlled primarily by water-level fluctuations in estuarine receiving waters. Water-control structures also altered upstream water levels in all canals. Water levels were lowered upstream from tide gates, but increased upstream from flashboard risers. Both types of water-control structures attenuated the release of runoff following rainfall events, but in slightly different ways. Tide gates appeared to reduce peak discharge rates associated with rainfall, and flashboard risers lengthened the duration of runoff release. Tide gates had no apparent effect on pH, dissolved oxygen, suspended-sediment, or total phosphorus concentrations downstream from the structures. Specific conductance measured from composite samples collected with automatic samples increased downstream of tide gates after installation. Median concentrations of nitrite plus nitrate nitrogen were near the minimum detection level throughout the study; however, the number of observations of concentrations exceeding 0.1 milligram per liter dropped significantly after tide gates were installed. Following tide-gate installation, instantaneous loadings of nitrite plus nitrate nitrogen were significantly reduced at one test site, but this reduction was not observed at the other test site. Loadings of other nutrient species and suspended sediment did not change at the tide-gate test sites after tide-gate installation. Specific conductance was lower in the Beaufort County canals than in the Hyde County canals. Although there was a slight increase in median values at the flashboard-riser sites, the mean and maximum values declined substantially downstream from the risers following installation. This decline of specific conductance in the canals occurred despite a large increase of specific conductance in the tidal creek. Flashboard risers had no significant effect on concentrations of dissolved oxygen, suspended sediment, total ammonia plus organic nitrogen, or phosphorus. Maximum concentrations of ammonia nitrogen were smaller at both test sites after riser installation. In addition, concentrations of nitrite plus nitrate nitrogen exceeding 1.0 milligram per liter rarely occurred at the flashboard-riser test sites following installation of the risers. Median loadings of nitrite plus nitrate nitrogen and total nitrogen decreased at one riser test site following flashboard-riser installation. Tide gates and flashboard risers were associated with reductions in concentrations and export of nitrite plus nitrate nitrogen; however, these changes should be interpreted cautiously because reductions were not observed consistently at every site. The hydrology and baseline water-quality characteristics of the two study areas differ, making comparisons of the effectiveness of the two types of water-control structures difficult to interpret. The effects of water-control structures on the hydrology of the drainage canals are more meaningful than the changes in water quality. Tide gates and flashboard risers altered the hydrologic characteristics of the drainage canals and created an environment favorable for nutrient loss or transformation. Both structures retained agricultural drainage upstream, which increased potential storage for infiltration and reduced the potential for surface runoff, sediment, and nutrient transport, and higher peak outflow rates.

Evaluating Protein Structure and Dynamics Using Co-Solvents, Photochemical Triggers, and Site-Specific Spectroscopic Probes

NASA Astrophysics Data System (ADS)

Abaskharon, Rachel M.

As ubiquitous and diverse biopolymers, proteins are dynamic molecules that are constantly engaging in inter- and intramolecular interactions responsible for their structure, fold, and function. Because of this, gaining a comprehensive understanding of the factors that control protein conformation and dynamics remains elusive as current experimental techniques often lack the ability to initiate and probe a specific interaction or conformational transition. For this reason, this thesis aims to develop methods to control and monitor protein conformations, conformational transitions, and dynamics in a site-specific manner, as well as to understand how specific and non-specific interactions affect the protein folding energy landscape. First, by using the co-solvent, trifluoroethanol (TFE), we show that the rate at which a peptide folds can be greatly impacted and thus controlled by the excluded volume effect. Secondly, we demonstrate the utility of several light-responsive molecules and reactions as methods to manipulate and investigate protein-folding processes. Using an azobenzene linker as a photo-initiator, we are able to increase the folding rate of a protein system by an order of magnitude by channeling a sub-population through a parallel, faster folding pathway. Additionally, we utilize a tryptophan-mediated electron transfer process to a nearby disulfide bond to strategically unfold a protein molecule with ultraviolet light. We also demonstrate the potential of two ruthenium polypyridyl complexes as ultrafast phototriggers of protein reactions. Finally, we develop several site-specific spectroscopic probes of protein structure and environment. Specifically, we demonstrate that a 13C-labeled aspartic acid residue constitutes a useful site-specific infrared probe for investigating salt-bridges and hydration dynamics of proteins, particularly in proteins containing several acidic amino acids. We also show that a proline-derivative, 4-oxoproline, possesses novel infrared properties that can be exploited to monitor the cis-trans isomerization process of individual proline residues in proteins.

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

PubMed Central

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

2014-01-01

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

An MRM-based workflow for quantifying cardiac mitochondrial protein phosphorylation in murine and human tissue.

PubMed

Lam, Maggie P Y; Scruggs, Sarah B; Kim, Tae-Young; Zong, Chenggong; Lau, Edward; Wang, Ding; Ryan, Christopher M; Faull, Kym F; Ping, Peipei

2012-08-03

The regulation of mitochondrial function is essential for cardiomyocyte adaptation to cellular stress. While it has long been understood that phosphorylation regulates flux through metabolic pathways, novel phosphorylation sites are continually being discovered in all functionally distinct areas of the mitochondrial proteome. Extracting biologically meaningful information from these phosphorylation sites requires an adaptable, sensitive, specific and robust method for their quantification. Here we report a multiple reaction monitoring-based mass spectrometric workflow for quantifying site-specific phosphorylation of mitochondrial proteins. Specifically, chromatographic and mass spectrometric conditions for 68 transitions derived from 23 murine and human phosphopeptides, and their corresponding unmodified peptides, were optimized. These methods enabled the quantification of endogenous phosphopeptides from the outer mitochondrial membrane protein VDAC, and the inner membrane proteins ANT and ETC complexes I, III and V. The development of this quantitative workflow is a pivotal step for advancing our knowledge and understanding of the regulatory effects of mitochondrial protein phosphorylation in cardiac physiology and pathophysiology. This article is part of a Special Issue entitled: Translational Proteomics. Copyright © 2012 Elsevier B.V. All rights reserved.

The Effects of Recreation Experience, Environmental Attitude, and Biospheric Value on the Environmentally Responsible Behavior of Nature-Based Tourists

NASA Astrophysics Data System (ADS)

Lee, Tsung Hung; Jan, Fen-Hauh

2015-07-01

The scientific understanding of the recreation experience and the environmentally responsible behavior of nature-based tourists is limited. This study examines the relationship among the recreation experience, environmental attitude, biospheric value, and the general and site-specific environmentally responsible behavior of nature-based tourists in Taomi, Liuqiu Island, and Aowanda and Najenshan in Taiwan. A total of 1342 usable questionnaires were collected for this study. The empirical results indicate that the recreation experience influences biospheric value and environmental attitude; subsequently, it then indirectly influences the general and site-specific environmentally responsible behavior of nature-based tourists. Our theoretical behavioral model elucidates previously proposed but unexamined behavioral models among nature-based tourists, and it offers a theoretical framework for researchers, decision makers, managers, and tourists in the field of nature-based tourism. We conclude that when an individual participates in nature-based tourism as described here, these recreation experiences strengthen their environmental attitude and biospheric value, and consequently increase their engagement in both general and site-specific environmentally responsible behaviors.

The effects of recreation experience, environmental attitude, and biospheric value on the environmentally responsible behavior of nature-based tourists.

PubMed

Lee, Tsung Hung; Jan, Fen-Hauh

2015-07-01

The scientific understanding of the recreation experience and the environmentally responsible behavior of nature-based tourists is limited. This study examines the relationship among the recreation experience, environmental attitude, biospheric value, and the general and site-specific environmentally responsible behavior of nature-based tourists in Taomi, Liuqiu Island, and Aowanda and Najenshan in Taiwan. A total of 1342 usable questionnaires were collected for this study. The empirical results indicate that the recreation experience influences biospheric value and environmental attitude; subsequently, it then indirectly influences the general and site-specific environmentally responsible behavior of nature-based tourists. Our theoretical behavioral model elucidates previously proposed but unexamined behavioral models among nature-based tourists, and it offers a theoretical framework for researchers, decision makers, managers, and tourists in the field of nature-based tourism. We conclude that when an individual participates in nature-based tourism as described here, these recreation experiences strengthen their environmental attitude and biospheric value, and consequently increase their engagement in both general and site-specific environmentally responsible behaviors.

Nuclear factor ETF specifically stimulates transcription from promoters without a TATA box.

PubMed

Kageyama, R; Merlino, G T; Pastan, I

1989-09-15

Transcription factor ETF stimulates the expression of the epidermal growth factor receptor (EGFR) gene which does not have a TATA box in the promoter region. Here, we show that ETF recognizes various GC-rich sequences including stretches of deoxycytidine or deoxyguanosine residues and GC boxes with similar affinities. ETF also binds to TATA boxes but with a lower affinity. ETF stimulated in vitro transcription from several promoters without TATA boxes but had little or no effect on TATA box-containing promoters even though they had strong ETF-binding sites. These inactive ETF-binding sites became functional when placed upstream of the EGFR promoter whose own ETF-binding sites were removed. Furthermore, when a TATA box was introduced into the EGFR promoter, the responsiveness to ETF was abolished. These results indicate that ETF is a specific transcription factor for promoters which do not contain TATA elements.

Expansion of Protein Farnesyltransferase Specificity Using “Tunable” Active Site Interactions

PubMed Central

Hougland, James L.; Gangopadhyay, Soumyashree A.; Fierke, Carol A.

2012-01-01

Post-translational modifications play essential roles in regulating protein structure and function. Protein farnesyltransferase (FTase) catalyzes the biologically relevant lipidation of up to several hundred cellular proteins. Site-directed mutagenesis of FTase coupled with peptide selectivity measurements demonstrates that molecular recognition is determined by a combination of multiple interactions. Targeted randomization of these interactions yields FTase variants with altered and, in some cases, bio-orthogonal selectivity. We demonstrate that FTase specificity can be “tuned” using a small number of active site contacts that play essential roles in discriminating against non-substrates in the wild-type enzyme. This tunable selectivity extends in vivo, with FTase variants enabling the creation of bioengineered parallel prenylation pathways with altered substrate selectivity within a cell. Engineered FTase variants provide a novel avenue for probing both the selectivity of prenylation pathway enzymes and the effects of prenylation pathway modifications on the cellular function of a protein. PMID:22992747

Sensitive, site-specific, and stable vibrational probe of local protein environments: 4-azidomethyl-L-phenylalanine.

PubMed

Bazewicz, Christopher G; Liskov, Melanie T; Hines, Kevin J; Brewer, Scott H

2013-08-01

We have synthesized the unnatural amino acid (UAA), 4-azidomethyl-L-phenylalanine (pN₃CH₂Phe), to serve as an effective vibrational reporter of local protein environments. The position, extinction coefficient, and sensitivity to local environment of the azide asymmetric stretch vibration of pN₃CH₂Phe are compared to the vibrational reporters: 4-cyano-L-phenylalanine (pCNPhe) and 4-azido-L-phenylalanine (pN₃Phe). This UAA was genetically incorporated in a site-specific manner utilizing an engineered, orthogonal aminoacyl-tRNA synthetase in response to an amber codon with high efficiency and fidelity into two distinct sites in superfolder green fluorescent protein (sfGFP). This allowed for the dependence of the azide asymmetric stretch vibration of pN₃CH₂Phe to different protein environments to be measured. The photostability of pN₃CH₂Phe was also measured relative to the photoreactive UAA, pN₃Phe.

77 FR 76475 - Environmental Management Site-Specific Advisory Board, Northern New Mexico

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Northern New Mexico... the Environmental Management Site-Specific Advisory Board (EM SSAB), Northern New Mexico. The Federal... INFORMATION CONTACT: Menice Santistevan, Northern New Mexico Citizens' Advisory Board (NNMCAB), 94 Cities of...

75 FR 24685 - Environmental Management Site-Specific Advisory Board, Idaho National Laboratory

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Idaho National... meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Idaho National Laboratory... prior to the meeting. ADDRESSES: Hilton Garden Inn, 700 Lindsay Boulevard, Idaho Falls, Idaho 83402. FOR...

77 FR 38276 - Environmental Management Site-Specific Advisory Board, Idaho National Laboratory

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-27

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Idaho National... a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Idaho National... times prior to the meeting. ADDRESSES: Red Lion Hotel, 1555 Pocatello Creek Road, Pocatello, Idaho 83201...

76 FR 11773 - Environmental Management Site-Specific Advisory Board, Northern New Mexico

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-03

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Northern New Mexico... the Environmental Management Site-Specific Advisory Board (EM SSAB), Northern New Mexico. The Federal... Courtyard by Marriott, 3347 Cerrillos Road, Santa Fe, New Mexico 87507. FOR FURTHER INFORMATION CONTACT...

Arabidopsis Polycomb Repressive Complex 2 binding sites contain putative GAGA factor binding motifs within coding regions of genes

PubMed Central

2013-01-01

Background Polycomb Repressive Complex 2 (PRC2) is an essential regulator of gene expression that maintains genes in a repressed state by marking chromatin with trimethylated Histone H3 lysine 27 (H3K27me3). In Arabidopsis, loss of PRC2 function leads to pleiotropic effects on growth and development thought to be due to ectopic expression of seed and embryo-specific genes. While there is some understanding of the mechanisms by which specific genes are targeted by PRC2 in animal systems, it is still not clear how PRC2 is recruited to specific regions of plant genomes. Results We used ChIP-seq to determine the genome-wide distribution of hemagglutinin (HA)-tagged FERTLIZATION INDEPENDENT ENDOSPERM (FIE-HA), the Extra Sex Combs homolog protein present in all Arabidopsis PRC2 complexes. We found that the FIE-HA binding sites co-locate with a subset of the H3K27me3 sites in the genome and that the associated genes were more likely to be de-repressed in mutants of PRC2 components. The FIE-HA binding sites are enriched for three sequence motifs including a putative GAGA factor binding site that is also found in Drosophila Polycomb Response Elements (PREs). Conclusions Our results suggest that PRC2 binding sites in plant genomes share some sequence features with Drosophila PREs. However, unlike Drosophila PREs which are located in promoters and devoid of H3K27me3, Arabidopsis FIE binding sites tend to be in gene coding regions and co-localize with H3K27me3. PMID:24001316

Click-MS: Tagless Protein Enrichment Using Bioorthogonal Chemistry for Quantitative Proteomics.

PubMed

Smits, Arne H; Borrmann, Annika; Roosjen, Mark; van Hest, Jan C M; Vermeulen, Michiel

2016-12-16

Epitope-tagging is an effective tool to facilitate protein enrichment from crude cell extracts. Traditionally, N- or C-terminal fused tags are employed, which, however, can perturb protein function. Unnatural amino acids (UAAs) harboring small reactive handles can be site-specifically incorporated into proteins, thus serving as a potential alternative for conventional protein tags. Here, we introduce Click-MS, which combines the power of site-specific UAA incorporation, bioorthogonal chemistry, and quantitative mass spectrometry-based proteomics to specifically enrich a single protein of interest from crude mammalian cell extracts. By genetic encoding of p-azido-l-phenylalanine, the protein of interest can be selectively captured using copper-free click chemistry. We use Click-MS to enrich proteins that function in different cellular compartments, and we identify protein-protein interactions, showing the great potential of Click-MS for interaction proteomics workflows.

Mutations altering the cleavage specificity of a homing endonuclease

PubMed Central

Seligman, Lenny M.; Chisholm, Karen M.; Chevalier, Brett S.; Chadsey, Meggen S.; Edwards, Samuel T.; Savage, Jeremiah H.; Veillet, Adeline L.

2002-01-01

The homing endonuclease I-CreI recognizes and cleaves a particular 22 bp DNA sequence. The crystal structure of I-CreI bound to homing site DNA has previously been determined, leading to a number of predictions about specific protein–DNA contacts. We test these predictions by analyzing a set of endonuclease mutants and a complementary set of homing site mutants. We find evidence that all structurally predicted I-CreI/DNA contacts contribute to DNA recognition and show that these contacts differ greatly in terms of their relative importance. We also describe the isolation of a collection of altered specificity I-CreI derivatives. The in vitro DNA-binding and cleavage properties of two such endonucleases demonstrate that our genetic approach is effective in identifying homing endonucleases that recognize and cleave novel target sequences. PMID:12202772

Probing the rate-limiting step for intramolecular transfer of a transcription factor between specific sites on the same DNA molecule by (15)Nz-exchange NMR spectroscopy.

PubMed

Ryu, Kyoung-Seok; Tugarinov, Vitali; Clore, G Marius

2014-10-15

The kinetics of translocation of the homeodomain transcription factor HoxD9 between specific sites of the same or opposite polarities on the same DNA molecule have been studied by (15)Nz-exchange NMR spectroscopy. We show that exchange occurs by two facilitated diffusion mechanisms: a second-order intermolecular exchange reaction between specific sites located on different DNA molecules without the protein dissociating into free solution that predominates at high concentrations of free DNA, and a first-order intramolecular process involving direct transfer between specific sites located on the same DNA molecule. Control experiments using a mixture of two DNA molecules, each possessing only a single specific site, indicate that transfer between specific sites by full dissociation of HoxD9 into solution followed by reassociation is too slow to measure by z-exchange spectroscopy. Intramolecular transfer with comparable rate constants occurs between sites of the same and opposing polarity, indicating that both rotation-coupled sliding and hopping/flipping (analogous to geminate recombination) occur. The half-life for intramolecular transfer (0.5-1 s) is many orders of magnitude larger than the calculated transfer time (1-100 μs) by sliding, leading us to conclude that the intramolecular transfer rates measured by z-exchange spectroscopy represent the rate-limiting step for a one-base-pair shift from the specific site to the immediately adjacent nonspecific site. At zero concentration of added salt, the intramolecular transfer rate constants between sites of opposing polarity are smaller than those between sites of the same polarity, suggesting that hopping/flipping may become rate-limiting at very low salt concentrations.

40 CFR Table 6 to Subpart Fff of... - Site-Specific Compliance Schedules and Increments of Progress a

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 8 2011-07-01 2011-07-01 false Site-Specific Compliance Schedules and... Constructed on or Before September 20, 1994 Pt. 62, Subpt. FFF, Table 6 Table 6 to Subpart FFF of Part 62—Site-Specific Compliance Schedules and Increments of Progress a Affected facilities at the following MWC sites...

40 CFR Table 6 to Subpart Fff of... - Site-Specific Compliance Schedules and Increments of Progress a

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Site-Specific Compliance Schedules and... Constructed on or Before September 20, 1994 Pt. 62, Subpt. FFF, Table 6 Table 6 to Subpart FFF of Part 62—Site-Specific Compliance Schedules and Increments of Progress a Affected facilities at the following MWC sites...

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

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

NONE

1995-09-01

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

Targeting of Magnetic Nanoparticle-coated Microbubbles to the Vascular Wall Empowers Site-specific Lentiviral Gene Delivery in vivo.

PubMed

Heun, Yvonn; Hildebrand, Staffan; Heidsieck, Alexandra; Gleich, Bernhard; Anton, Martina; Pircher, Joachim; Ribeiro, Andrea; Mykhaylyk, Olga; Eberbeck, Dietmar; Wenzel, Daniela; Pfeifer, Alexander; Woernle, Markus; Krötz, Florian; Pohl, Ulrich; Mannell, Hanna

2017-01-01

In the field of vascular gene therapy, targeting systems are promising advancements to improve site-specificity of gene delivery. Here, we studied whether incorporation of magnetic nanoparticles (MNP) with different magnetic properties into ultrasound sensitive microbubbles may represent an efficient way to enable gene targeting in the vascular system after systemic application. Thus, we associated novel silicon oxide-coated magnetic nanoparticle containing microbubbles (SO-Mag MMB) with lentiviral particles carrying therapeutic genes and determined their physico-chemical as well as biological properties compared to MMB coated with polyethylenimine-coated magnetic nanoparticles (PEI-Mag MMB). While there were no differences between both MMB types concerning size and lentivirus binding, SO-Mag MMB exhibited superior characteristics regarding magnetic moment, magnetizability as well as transduction efficiency under static and flow conditions in vitro . Focal disruption of lentiviral SO-Mag MMB by ultrasound within isolated vessels exposed to an external magnetic field decisively improved localized VEGF expression in aortic endothelium ex vivo and enhanced the angiogenic response. Using the same system in vivo , we achieved a highly effective, site-specific lentiviral transgene expression in microvessels of the mouse dorsal skin after arterial injection. Thus, we established a novel lentiviral MMB technique, which has great potential towards site-directed vascular gene therapy.

Multi-element compound specific stable isotope analysis of chlorinated aliphatic contaminants derived from chlorinated pitches.

PubMed

Filippini, Maria; Nijenhuis, Ivonne; Kümmel, Steffen; Chiarini, Veronica; Crosta, Giovanni; Richnow, Hans H; Gargini, Alessandro

2018-05-30

Tetrachloroethene and trichloroethene are typical by-products of the industrial production of chloromethanes. These by-products are known as "chlorinated pitches" and were often dumped in un-contained waste disposal sites causing groundwater contaminations. Previous research showed that a strongly depleted stable carbon isotope signature characterizes chlorinated compounds associated with chlorinated pitches whereas manufactured commercial compounds have more enriched carbon isotope ratios. The findings were restricted to a single case study and one element (i.e. carbon). This paper presents a multi-element Compound-Specific Stable Isotope Analysis (CSIA, including carbon, chlorine and hydrogen) of chlorinated aliphatic contaminants originated from chlorinated pitches at two sites with different hydrogeology and different producers of chloromethanes. The results show strongly depleted carbon signatures at both sites whereas the chlorine and the hydrogen signatures are comparable to those presented in the literature for manufactured commercial compounds. Multi-element CSIA allowed the identification of sources and site-specific processes affecting chloroethene transformation in groundwater as a result of emergency remediation measures. CSIA turned out to be an effective forensic tool to address the liability for the contamination, leading to a conviction for the crimes of unintentional aggravated public water supply poisoning and environmental disaster. Copyright © 2018 Elsevier B.V. All rights reserved.

Maillard Proteomics: Opening New Pages

PubMed Central

Soboleva, Alena; Schmidt, Rico; Vikhnina, Maria; Grishina, Tatiana; Frolov, Andrej

2017-01-01

Protein glycation is a ubiquitous non-enzymatic post-translational modification, formed by reaction of protein amino and guanidino groups with carbonyl compounds, presumably reducing sugars and α-dicarbonyls. Resulting advanced glycation end products (AGEs) represent a highly heterogeneous group of compounds, deleterious in mammals due to their pro-inflammatory effect, and impact in pathogenesis of diabetes mellitus, Alzheimer’s disease and ageing. The body of information on the mechanisms and pathways of AGE formation, acquired during the last decades, clearly indicates a certain site-specificity of glycation. It makes characterization of individual glycation sites a critical pre-requisite for understanding in vivo mechanisms of AGE formation and developing adequate nutritional and therapeutic approaches to reduce it in humans. In this context, proteomics is the methodology of choice to address site-specific molecular changes related to protein glycation. Therefore, here we summarize the methods of Maillard proteomics, specifically focusing on the techniques providing comprehensive structural and quantitative characterization of glycated proteome. Further, we address the novel break-through areas, recently established in the field of Maillard research, i.e., in vitro models based on synthetic peptides, site-based diagnostics of metabolism-related diseases (e.g., diabetes mellitus), proteomics of anti-glycative defense, and dynamics of plant glycated proteome during ageing and response to environmental stress. PMID:29231845

A neural network based methodology to predict site-specific spectral acceleration values

NASA Astrophysics Data System (ADS)

Kamatchi, P.; Rajasankar, J.; Ramana, G. V.; Nagpal, A. K.

2010-12-01

A general neural network based methodology that has the potential to replace the computationally-intensive site-specific seismic analysis of structures is proposed in this paper. The basic framework of the methodology consists of a feed forward back propagation neural network algorithm with one hidden layer to represent the seismic potential of a region and soil amplification effects. The methodology is implemented and verified with parameters corresponding to Delhi city in India. For this purpose, strong ground motions are generated at bedrock level for a chosen site in Delhi due to earthquakes considered to originate from the central seismic gap of the Himalayan belt using necessary geological as well as geotechnical data. Surface level ground motions and corresponding site-specific response spectra are obtained by using a one-dimensional equivalent linear wave propagation model. Spectral acceleration values are considered as a target parameter to verify the performance of the methodology. Numerical studies carried out to validate the proposed methodology show that the errors in predicted spectral acceleration values are within acceptable limits for design purposes. The methodology is general in the sense that it can be applied to other seismically vulnerable regions and also can be updated by including more parameters depending on the state-of-the-art in the subject.

Epigenetics mediate environment : gene effects on occupational sensitization.

PubMed

Pacheco, Karin A

2012-04-01

Epigenetics is the study of stable modifications of fixed genomes that direct which genes are expressed and which are silenced. Epigenetic changes are modulated by environmental exposures, making epigenetics the interface between genes and environment. This has particular relevance in understanding the effect of occupational exposures on the expression of allergic disease. The goal of this review is to describe how epigenetic changes affect transcription potential, and to examine more closely the effect of specific environmental and occupational exposures on epigenetic variations that alter allergy gene transcripts and the inflammatory milieu. Gene transcription is activated when specific CpG sites are demethylated and histones are acetylated, and, conversely, silenced when sites are methylated and histones deacetylated. The development of Th1 and Th2 phenotypes, and expression of Treg cells, are now known to be modulated by epigenetic mechanisms. Workplace exposures such as tobacco smoke, particulates, diesel exhaust, polyaromatic hydrocarbons, ozone, and endotoxin, among others, suppress Treg development, and enhance expression of inflammatory cytokines and allergic phenotypes by epigenetic means. Epigenetic manipulation to open and close transcription sites provides flexibility of gene expression in response to changing environmental cues. It may also be the window whereby allergic disease in the workplace can be reduced by targeted environmental interventions.

Multi-Stakeholder Decision Aid for Improved Prioritization of the Public Health Impact of Climate Sensitive Infectious Diseases

PubMed Central

Hongoh, Valerie; Michel, Pascal; Gosselin, Pierre; Samoura, Karim; Ravel, André; Campagna, Céline; Cissé, Hassane Djibrilla; Waaub, Jean-Philippe

2016-01-01

The effects of climate change on infectious diseases are an important global health concern and necessitate decisions for allocation of resources. Economic tools have been used previously; however, how prioritization results might differ when done using broader considerations identified by local stakeholders has yet to be assessed. A multicriteria decision analysis (MCDA) approach was used to assess multi-stakeholder expressed concerns around disease prioritization via focus groups held in Quebec and Burkina Faso. Stakeholders weighted criteria and comparisons were made across study sites. A pilot disease prioritization was done to examine effects on disease rankings. A majority of identified criteria were common to both sites. The effect of context specific criteria and weights resulted in similar yet distinct prioritizations of diseases. The presence of consistent criteria between sites suggests that common concerns exist for prioritization; however, context-specific adjustments reveal much regarding resource availability, capacity and concerns that should be considered as this impacts disease ranking. Participatory decision aid approaches facilitate rich knowledge exchange and problem structuring. Furthermore, given multiple actors in low- and middle-income countries settings, multi-actor collaborations across non-governmental organizations, local government and community are important. Formal mechanisms such as MCDA provide means to foster consensus, shared awareness and collaboration. PMID:27077875

Interleukin 2 transcription factors as molecular targets of cAMP inhibition: delayed inhibition kinetics and combinatorial transcription roles

PubMed Central

1994-01-01

Elevation of cAMP can cause gene-specific inhibition of interleukin 2 (IL-2) expression. To investigate the mechanism of this effect, we have combined electrophoretic mobility shift assays and in vivo genomic footprinting to assess both the availability of putative IL-2 transcription factors in forskolin-treated cells and the functional capacity of these factors to engage their sites in vivo. All observed effects of forskolin depended upon protein kinase A, for they were blocked by introduction of a dominant negative mutant subunit of protein kinase A. In the EL4.E1 cell line, we report specific inhibitory effects of cAMP elevation both on NF-kappa B/Rel family factors binding at -200 bp, and on a novel, biochemically distinct "TGGGC" factor binding at -225 bp with respect to the IL-2 transcriptional start site. Neither NF-AT nor AP-1 binding activities are detectably inhibited in gel mobility shift assays. Elevation of cAMP inhibits NF-kappa B activity with delayed kinetics in association with a delayed inhibition of IL-2 RNA accumulation. Activation of cells in the presence of forskolin prevents the maintenance of stable protein- DNA interactions in vivo, not only at the NF-kappa B and TGGGC sites of the IL-2 enhancer, but also at the NF-AT, AP-1, and other sites. This result, and similar results in cyclosporin A-treated cells, imply that individual IL-2 transcription factors cannot stably bind their target sequences in vivo without coengagement of all other distinct factors at neighboring sites. It is proposed that nonhierarchical, cooperative enhancement of binding is a structural basis of combinatorial transcription factor action at the IL-2 locus. PMID:8113685

Nutrient addition differentially affects ecological processes of Avicennia germinans in nitrogen versus phosphorus limited mangrove ecosystems

USGS Publications Warehouse

Feller, Ilka C.; Lovelock, C.E.; McKee, K.L.

2007-01-01

Nutrient over-enrichment is a major threat to marine environments, but system-specific attributes of coastal ecosystems may result in differences in their sensitivity and susceptibility to eutrophication. We used fertilization experiments in nitrogen (N)- and phosphorus (P)-limited mangrove forests to test the hypothesis that alleviating different kinds of nutrient limitation may have different effects on ecosystem structure and function in natural systems. We compared a broad range of ecological processes to determine if these systems have different thresholds where shifts might occur in nutrient limitation. Growth responses indicated N limitation in Avicennia germinans (black mangrove) forests in the Indian River Lagoon (IRL), Florida, and P limitation at Twin Cays, Belize. When nutrient deficiency was relieved, A. germinans grew out of its stunted form by increasing wood relative to leaf biomass and shoot length relative to lateral growth. At the P-limited site, P enrichment (+P) increased specific leaf area, N resorption, and P uptake, but had no effect on P resorption. At the N-limited site, +N increased both N and P resorption, but did not alter biomass allocation. Herbivory was greater at the P-limited site and was unaffected by +P, whereas +N led to increased herbivory at the N-limited site. The responses to nutrient enrichment depended on the ecological process and limiting nutrient and suggested that N- versus P-limited mangroves do have different thresholds. +P had a greater effect on more ecological processes at Twin Cays than did +N at the IRL, which indicated that the P-limited site was more sensitive to nutrient loading. Because of this sensitivity, eutrophication is more likely to cause a shift in nutrient limitation at P-limited Twin Cays than N-limited IRL. ?? 2007 Springer Science+Business Media, LLC.

78 FR 12067 - Extreme Weather Effects on Medical Device Safety and Quality

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

... medicines at home, and dialysis machines in outpatient centers. The specific risks to patients and the best... impacted your manufacturing site? What were the lessons learned during the recovery process as you returned...

Transportation planning effectiveness: twenty case studies

DOT National Transportation Integrated Search

1977-12-31

This document consists of 20 site-specific case studies of urban area experience with the Technical Study Grant Program of the Urban Mass Transportation Administration (UMTA). The objective of the case studies is to determine how the Technical Study ...

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.

Influence of site preparation and stock size on the establishment of Arizona cypress plantings in the Middle Rio Grande Region

Treesearch

Mark Loveall; Richard P. Maiers; John T. Harrington

2002-01-01

Establishment of tree plantings in arid and semi-arid regions where available irrigation water is limited is often costly and problematic. This study examined the effects of site preparation, specifically V-ditching and use of synthetic weed barrier alone and in combination, and stock size based on container volume on early, 1- and 6- month, mid, 12- and 15-month, and...

Spatial resolution of pace mapping of idiopathic ventricular tachycardia/ectopy originating in the right ventricular outflow tract.

PubMed

Bogun, Frank; Taj, Majid; Ting, Michael; Kim, Hyungjin Myra; Reich, Stephen; Good, Eric; Jongnarangsin, Krit; Chugh, Aman; Pelosi, Frank; Oral, Hakan; Morady, Fred

2008-03-01

Pace mapping has been used to identify the site of origin of focal ventricular arrhythmias. The spatial resolution of pace mapping has not been adequately quantified using currently available three-dimensional mapping systems. The purpose of this study was to determine the spatial resolution of pace mapping in patients with idiopathic ventricular tachycardia or premature ventricular contractions originating in the right ventricular outflow tract. In 16 patients with idiopathic ventricular tachycardia/ectopy from the right ventricular outflow tract, comparisons and classifications of pace maps were performed by two observers (good pace map: match >10/12 leads; inadequate pace map: match < or =10/12 leads) and a customized MATLAB 6.0 program (assessing correlation coefficient and normalized root mean square of the difference (nRMSd) between test and template signals). With an electroanatomic mapping system, the correlation coefficient of each pace map was correlated with the distance between the pacing site and the effective ablation site. The endocardial area within the 10-ms activation isochrone was measured. The ablation procedure was effective in all patients. Sites with good pace maps had a higher correlation coefficient and lower nRMSd than sites with inadequate pace maps (correlation coefficient: 0.96 +/- 0.03 vs 0.76 +/- 0.18, P <.0001; nRMSd: 0.41 +/- 0.16 vs 0.89 +/- 0.39, P <.0001). Using receiver operating characteristic curves, appropriate cutoff values were >0.94 for correlation coefficient (sensitivity 81%, specificity 89%) and < or =0.54 for nRMSd (sensitivity 76%, specificity 80%). Good pace maps were located a mean of 7.3 +/- 5.0 mm from the effective ablation site and had a mean activation time of -24 +/- 7 ms. However, in 3 (18%) of 16 patients, the best pace map was inadequate at the effective ablation site, with an endocardial activation time at these sites of -25 +/- 12 ms. Pace maps with correlation coefficient > or =0.94 were confined to an area of 1.8 +/- 0.6 cm2. The 10-ms isochrone measured 1.2 +/- 0.7 cm2. The spatial resolution of a good pace map for targeting ventricular tachycardia/ectopy is 1.8 cm2 in the right ventricular outflow tract and therefore is inferior to the spatial resolution of activation mapping as assessed by isochronal activation. In approximately 20% of patients, pace mapping is unreliable in identifying the site of origin, possibly due a deeper site of origin and preferential conduction via fibers connecting the focus to the endocardial surface.

Enhancement and inhibition of microbial activity in hydrocarbon- contaminated arctic soils: Implications for nutrient-amended bioremediation

USGS Publications Warehouse

Braddock, J.F.; Ruth, M.L.; Catterall, P.H.; Walworth, J.L.; McCarthy, K.A.

1997-01-01

Bioremediation is being used or proposed as a treatment option at many hydrocarbon-contaminated sites. One such site is a former bulk-fuel storage facility near Barrow, AK, where contamination persists after approximately 380 m3 of JP-5 was spilled in 1970. The soil at the site is primarily coarse sand with low organic carbon (<1%) end low moisture (1-3%) contents. We examined the effects of nutrient additions on microorganisms in contaminated soil from this site in laboratory microcosms and in mesocosms incubated for 6 weeks in the field. Nitrogen was the major limiting nutrient in this system, but microbial populations and activity were maximally enhanced by additions of both nitrogen and phosphorus. When nutrients were added to soil in the field at three levels of N:P (100:45, 200:90, and 300:135 mg/kg soil), the greatest stimulation in microbial activity occurred at the lowest, rather than the highest, level of nutrient addition. The total soil-water potentials ranged from -2 to -15 bar with increasing levels of fertilizer. Semivolatile hydrocarbon concentrations declined significantly only in the soils treated at the low fertilizer level. These results indicate that an understanding of nutrient effects at a specific site is essential for successful bioremediation.Bioremediation is being used or proposed as a treatment option at many hydrocarbon-contaminated sites. One such site is a former bulk-fuel storage facility near Barrow, AK, where contamination persists after approximately 380 m3 of JP-5 was spilled in 1970. The soil at the site is primarily coarse sand with low organic carbon (<1%) and low moisture (1-3%) contents. We examined the effects of nutrient additions on microorganisms in contaminated soil from this site in laboratory microcosms and in mesocosms incubated for 6 weeks in the field. Nitrogen was the major limiting nutrient in this system, but microbial populations and activity were maximally enhanced by additions of both nitrogen and phosphorus. When nutrients were added to soil in the field at three levels of N:P (100:45, 200:90, and 300:135 mg/kg soil), the greatest stimulation in microbial activity occurred at the lowest, rather than the highest, level of nutrient addition. The total soil-water potentials ranged from -2 to -15 bar with increasing levels of fertilizer. Semi-volatile hydrocarbon concentrations declined significantly only in the soils treated at the low fertilizer level. These results indicate that an understanding of nutrient effects at a specific site is essential for successful bioremediation.

Enzyme Prodrug Therapy Achieves Site-Specific, Personalized Physiological Responses to the Locally Produced Nitric Oxide

PubMed Central

2018-01-01

Nitric oxide (NO) is a highly potent but short-lived endogenous radical with a wide spectrum of physiological activities. In this work, we developed an enzymatic approach to the site-specific synthesis of NO mediated by biocatalytic surface coatings. Multilayered polyelectrolyte films were optimized as host compartments for the immobilized β-galactosidase (β-Gal) enzyme through a screen of eight polycations and eight polyanions. The lead composition was used to achieve localized production of NO through the addition of β-Gal–NONOate, a prodrug that releases NO following enzymatic bioconversion. The resulting coatings afforded physiologically relevant flux of NO matching that of the healthy human endothelium. The antiproliferative effect due to the synthesized NO in cell culture was site-specific: within a multiwell dish with freely shared media and nutrients, a 10-fold inhibition of cell growth was achieved on top of the biocatalytic coatings compared to the immediately adjacent enzyme-free microwells. The physiological effect of NO produced via the enzyme prodrug therapy was validated ex vivo in isolated arteries through the measurement of vasodilation. Biocatalytic coatings were deposited on wires produced using alloys used in clinical practice and successfully mediated a NONOate concentration-dependent vasodilation in the small arteries of rats. The results of this study present an exciting opportunity to manufacture implantable biomaterials with physiological responses controlled to the desired level for personalized treatment. PMID:29570264

An international ecological study of adult height in relation to cancer incidence for 24 anatomical sites.

PubMed

Jiang, Yannan; Marshall, Roger J; Walpole, Sarah C; Prieto-Merino, David; Liu, Dong-Xu; Perry, Jo K

2015-03-01

Anthropometric indices associated with childhood growth and height attained in adulthood, have been associated with an increased incidence of certain malignancies. To evaluate the cancer-height relationship, we carried out a study using international data, comparing various cancer rates with average adult height of women and men in different countries. An ecological analysis of the relationship between country-specific cancer incidence rates and average adult height was conducted for twenty-four anatomical cancer sites. Age-standardized rates were obtained from GLOBOCAN 2008. Average female (112 countries) and male (65 countries) heights were sourced and compiled primarily from national health surveys. Graphical and weighted regression analysis was conducted, taking into account BMI and controlling for the random effect of global regions. A significant positive association between a country's average adult height and the country's overall cancer rate was observed in both men and women. Site-specific cancer incidence for females was positively associated with height for most cancers: lung, kidney, colorectum, bladder, melanoma, brain and nervous system, breast, non-Hodgkin lymphoma, multiple myeloma, corpus uteri, ovary, and leukemia. A significant negative association was observed with cancer of the cervix uteri. In males, site-specific cancer incidence was positively associated with height for cancers of the brain and nervous system, kidney, colorectum, non-Hodgkin lymphoma, multiple myeloma, prostate, testicular, lip and oral cavity, and melanoma. Incidence of cancer was associated with tallness in the majority of anatomical/cancer sites investigated. The underlying biological mechanisms are unclear, but may include nutrition and early-life exposure to hormones, and may differ by anatomical site.

Batrachotoxin Changes the Properties of the Muscarinic Receptor in Rat Brain and Heart: Possible Interaction(s) between Muscarinic Receptors and Sodium Channels

NASA Astrophysics Data System (ADS)

Cohen-Armon, Malca; Kloog, Yoel; Henis, Yoav I.; Sokolovsky, Mordechai

1985-05-01

The effects of Na+-channel activator batrachotoxin (BTX) on the binding properties of muscarinic receptors in homogenates of rat brain and heart were studied. BTX enhanced the affinity for the binding of the agonists carbamoylcholine and acetylcholine to the muscarinic receptors in brainstem and ventricle, but not in the cerebral cortex. Analysis of the data according to a two-site model for agonist binding indicated that the effect of BTX was to increase the affinity of the agonists to the high-affinity site. Guanyl nucleotides, known to induce interconversion of high-affinity agonist binding sites to the low-affinity state, canceled the effect of BTX on carbamoylcholine and acetylcholine binding. BTX had no effect on the binding of the agonist oxotremorine or on the binding of the antagonist [3H]-N-methyl-4-piperidyl benzilate. The local anesthetics dibucaine and tetracaine antagonized the effect of BTX on the binding of muscarinic agonists at concentrations known to inhibit the activation of Na+ channels by BTX. On the basis of these findings, we propose that in specific tissues the muscarinic receptors may interact with the BTX binding site (Na+ channels).

75 FR 64719 - Environmental Management Site-Specific Advisory Board, Northern New Mexico

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-20

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Northern New Mexico... the Environmental Management Site-Specific Advisory Board (EM SSAB), Northern New Mexico. The Federal... at Santa Fe, 750 North St. Francis Drive, Santa Fe, New Mexico. FOR FURTHER INFORMATION CONTACT...

76 FR 22090 - Environmental Management Site-Specific Advisory Board, Northern New Mexico

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-20

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Northern New Mexico... the Environmental Management Site-Specific Advisory Board (EM SSAB), Northern New Mexico. The Federal... a.m.-5 p.m. ADDRESSES: Santa Claran Hotel, 464 North Riverside Drive, Espanola, New Mexico 87532...

75 FR 8050 - Environmental Management Site-Specific Advisory Board, Hanford

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-23

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Hanford AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Hanford. The Federal Advisory Committee Act...: The meeting is open to the public. The EM SSAB, Hanford, welcomes the attendance of the public at its...

76 FR 20651 - Environmental Management Site-Specific Advisory Board Chairs

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board Chairs AGENCY... a meeting on April 13-14, 2011 of the Environmental Management Site-Specific Advisory Board Chairs... R. Butler, Acting Deputy Committee Management Officer. [FR Doc. 2011-8970 Filed 4-8-11; 4:15 pm...

FLP recombinase-mediated site-specific recombination in silkworm, Bombyx mori

USDA-ARS?s Scientific Manuscript database

A comprehensive understanding of gene function and the production of site-specific genetically modified mutants are two major goals of genetic engineering in the post-genomic era. Although site-specific recombination systems have been powerful tools for genome manipulation of many organisms, they h...

75 FR 56527 - Environmental Management Site-Specific Advisory Board, Idaho National Laboratory

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Idaho National... meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Idaho National Laboratory... prior to the meeting. ADDRESSES: Coeur d'Alene Resort, 115 South Second Street, Coeur d'Alene, Idaho...

40 CFR 98.468 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... design capacity, the calculation must include a site-specific density. If the design capacity is within... process that can reasonably be expected to change the site-specific waste density, the site-specific waste density must be redetermined and the design capacity must be recalculated based on the new waste density...

40 CFR 98.468 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... design capacity, the calculation must include a site-specific density. If the design capacity is within... process that can reasonably be expected to change the site-specific waste density, the site-specific waste density must be redetermined and the design capacity must be recalculated based on the new waste density...

75 FR 53280 - Environmental Management Site-Specific Advisory Board, Northern New Mexico

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Northern New Mexico... the Environmental Management Site-Specific Advisory Board (EM SSAB), Northern New Mexico. The Federal... Inn and Conference Center, 1508 Paseo Del Pueblo Sur, Taos, New Mexico 87571. FOR FURTHER INFORMATION...

Stand level height-diameter mixed effects models: parameters fitted using loblolly pine but calibrated for sweetgum

Treesearch

Curtis L. Vanderschaaf

2008-01-01

Mixed effects models can be used to obtain site-specific parameters through the use of model calibration that often produces better predictions of independent data. This study examined whether parameters of a mixed effect height-diameter model estimated using loblolly pine plantation data but calibrated using sweetgum plantation data would produce reasonable...

Effective Leadership in Vocational Education and Training. CRLRA Discussion Paper.

ERIC Educational Resources Information Center

Falk, Ian; Smith, Tony

The question of the extent to which effective leadership in vocational education and training (VET) depends on the specific context in which it occurs was examined. Data were collected from the following sources: an intensive literature analysis; studies of purposive sample of 12 diverse VET sites across Australia; and individual interviews with…

Modeling the hydrologic impacts of forest harvesting on Florida flatwoods

Treesearch

Ge Sun; Hans Rierkerk; Nicholas B. Comerford

1998-01-01

The great temporal and spatial variability of pine flatwoods hydrology suggests traditional short-term field methods may not be effective in evaluating the hydrologic effects of forest management. The flatwoods model was developed, calibrated and validated specifically for the cypress wetland-pine upland landscape. The model was applied to two typical flatwoods sites...

78 FR 14088 - Environmental Management Site-Specific Advisory Board, Savannah River Site

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-04

...This notice announces a meeting of the Environmental Management Site-Specific Advisory Board (EM SSAB), Savannah River Site. The Federal Advisory Committee Act requires that public notice of this meeting be announced in the Federal Register.

Radiological bioconcentration factors for aquatic, terrestrial, and wetland ecosystems at the Savannah River site

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

Friday, G.P.; Cummins, C.L.; Schwartzman, A.L.

Since the early 1950s, the Savannah River Site (SRS) released over 50 radionuclides into the environment while producing nuclear defense materials. These releases directly exposed aquatic and terrestrial biota to ionizing radiation from surface water, soil, and sediment, and also indirectly by the ingestion of items in the food chain. As part of new missions to develop waste management strategies and identify cost-effective environmental restoration options, knowledge concerning the uptake and distribution of these radionuclides is essential. This report compiles and summarizes site-specific bioconcentration factors for selected radionuclides released at SRS.

PACS project management utilizing web-based tools

NASA Astrophysics Data System (ADS)

Patel, Sunil; Levin, Brad; Gac, Robert J., Jr.; Harding, Douglas, Jr.; Chacko, Anna K.; Radvany, Martin; Romlein, John R.

2000-05-01

As Picture Archiving and Communications Systems (PACS) implementations become more widespread, the management of deploying large, multi-facility PACS will become a more frequent occurrence. The tools and usability of the World Wide Web to disseminate project management information obviates time, distance, participant availability, and data format constraints, allowing for the effective collection and dissemination of PACS planning, implementation information, for a potentially limitless number of concurrent PACS sites. This paper will speak to tools, such as (1) a topic specific discussion board, (2) a 'restricted' Intranet, within a 'project' Intranet. We will also discuss project specific methods currently in use in a leading edge, regional PACS implementation concerning the sharing of project schedules, physical drawings, images of implementations, site-specific data, point of contacts lists, project milestones, and a general project overview. The individual benefits realized for the end user from each tool will also be covered. These details will be presented, balanced with a spotlight on communication as a critical component of any project management undertaking. Using today's technology, the web arguably provides the most cost and resource effective vehicle to facilitate the broad based, interactive sharing of project information.

Cost-effectiveness of on-site versus off-site collaborative care for depression in rural FQHCs.

PubMed

Pyne, Jeffrey M; Fortney, John C; Mouden, Sip; Lu, Liya; Hudson, Teresa J; Mittal, Dinesh

2015-05-01

Collaborative care for depression in primary care settings is effective and cost-effective. However, there is minimal evidence to support the choice of on-site versus off-site models. This study examined the cost-effectiveness of on-site practice-based collaborative care (PBCC) versus off-site telemedicine-based collaborative care (TBCC) for depression in federally qualified health centers (FQHCs). In a multisite, randomized, pragmatic comparative cost-effectiveness trial, 19,285 patients were screened for depression, 2,863 (14.8%) screened positive, and 364 were enrolled. Telephone interview data were collected at baseline and at six, 12, and 18 months. Base case analysis used Arkansas FQHC health care costs, and secondary analysis used national cost estimates. Effectiveness measures were depression-free days and quality-adjusted life years (QALYs) derived from depression-free days, the 12-Item Short-Form Survey, and the Quality of Well-Being (QWB) Scale. Nonparametric bootstrap with replacement methods were used to generate an empirical joint distribution of incremental costs and QALYs and acceptability curves. The TBCC intervention resulted in more depression-free days and QALYs but at a greater cost than the PBCC intervention. The disease-specific (depression-free day) and generic (QALY) incremental cost-effectiveness ratios (ICERs) were below their respective ICER thresholds for implementation, suggesting that the TBCC intervention was more cost effective than the PBCC intervention. These results support the cost-effectiveness of TBCC in medically underserved primary care settings. Information about whether to insource (make) or outsource (buy) depression care management is important, given the current interest in patient-centered medical homes, value-based purchasing, and bundled payments for depression care.

Improved ATLAS HammerCloud Monitoring for Local Site Administration

NASA Astrophysics Data System (ADS)

Böhler, M.; Elmsheuser, J.; Hönig, F.; Legger, F.; Mancinelli, V.; Sciacca, G.

2015-12-01

Every day hundreds of tests are run on the Worldwide LHC Computing Grid for the ATLAS, and CMS experiments in order to evaluate the performance and reliability of the different computing sites. All this activity is steered, controlled, and monitored by the HammerCloud testing infrastructure. Sites with failing functionality tests are auto-excluded from the ATLAS computing grid, therefore it is essential to provide a detailed and well organized web interface for the local site administrators such that they can easily spot and promptly solve site issues. Additional functionality has been developed to extract and visualize the most relevant information. The site administrators can now be pointed easily to major site issues which lead to site blacklisting as well as possible minor issues that are usually not conspicuous enough to warrant the blacklisting of a specific site, but can still cause undesired effects such as a non-negligible job failure rate. This paper summarizes the different developments and optimizations of the HammerCloud web interface and gives an overview of typical use cases.

Effects of low-level radioactive-waste disposal on water chemistry in the unsaturated zone at a site near Sheffield, Illinois, 1982-84

USGS Publications Warehouse

Peters, C.A.; Striegl, Robert G.; Mills, P.C.; Healy, R.W.

1992-01-01

A 1982-84 field study defined the chemistry of water collected from the unsaturated zone at a low-level radioactive-waste disposal site near Sheffield, Bureau County, Ill. Chemical data were evaluated to determine the principal, naturally occurring geochemical reactions in the unsaturated zone and to evaluate waste-induced effects on pore-water chemistry. Samples of precipitation, unsaturated-zone pore water, and saturated-zone water were analyzed for specific conductance, pH, alkalinity, major cations and anions, dissolved organic carbon, gross alpha and beta radiation, and tritium. Little change in concentration of most major constituents in the unsaturated-zone water was observed with respect to depth or distance from disposal trenches. Tritium and dissolved organic carbon concentrations were, however, dependent on proximity to trenches. The primary reactions, both on-site and off-site, were carbonate and clay dissolution, cation exchange, and the oxidation of pyrite. The major difference between on-site and off-site inorganic water chemistry resulted from the removal of the Roxana Silt and the Radnor Till Member of the Glasford Formation from on-site. Off-site, the Roxana Silt contributed substantial quantities of sodium to solution from montmorillonite dissolution and associated cation-exchange reactions. The Radnor Till Member provided exchange surfaces for magnesium. Precipitation at the site had an ionic composition of calcium zinc sulfate and an average pH of 4.6. Within 0.3 meter of the land surface, infiltrating rainwater or snowmelt changed to an ionic composition of calcium sulfate off-site and calcium bicarbonate on-site and had an average pH of 7.9; below that depth, pH averaged 7.5 and the ionic composition generally was calcium magnesium bicarbonate. Alkalinity and specific conductance differed primarily according to composition of geologic materials. Tritium concentrations ranged from 0.2 (detection limit) to 1,380 nanocuries per liter. The methods of constructing, installing, and sampling with lysimeters were evaluated to ensure data reliability. These evaluations indicate that, with respect to most constituents, the samples retrieved from the lysimeters accurately represented pore-water chemistry.

Effects of low-level radioactive-waste disposal on water chemistry in the unsaturated zone at a site near Sheffield, Illinois, 1982-84

USGS Publications Warehouse

Peters, C.A.; Striegl, Robert G.; Mills, P.C.; Healy, R.W.

1992-01-01

A 1982-84 field study defined the chemistry of water collected from the unsaturated zone at a low-level radioactive-waste disposal site near Sheffield, Bureau County, Illinois. Chemical data were evaluated to determine the principal naturally occurring geochemical reactions in the unsaturated zone and to evaluate waste-induced effects on pore-water chemistry. Samples of precipitation, unsaturated-zone pore water, and saturated-zone water were analyzed for specific conductance, pH, alkalinity, major cations and anions, dissolved organic carbon, gross alpha and beta radiation, and tritium. Little change in concentration of most major constituents in the unsaturated-zone water was observed with respect to depth or distance from disposal trenches. Tritium and dissolved organic carbon concentrations were, however, dependent on proximity to trenches. The primary reactions, both on- site and off-site, were carbonate and clay dissolution, cation exchange, and the oxidation of pyrite. The major difference between on-site and off-site inorganic water chemistry resulted from the removal of the Roxana Silt and the Radnor Till Member of the Glasford Formation from on-site. Off-site, the Roxana Silt contributed substantial quantities of sodium to solution from montmorillonite dissolution and associated cation-exchange reactions. The Radnor Till Member provided exchange surfaces for magnesium. Precipitation at the site had an ionic composition of calcium zinc sulfate and an average pH of 4.6. Within 0.3 meter of the land surface, infiltrating rain water or snowmelt changed to an ionic canposition of calcium sulfate off-site and calcium bicarbonate on-site and had an average pH of 7.9; below that depth, pH averaged 7.5 and the ionic composition generally was calcium magnesium bicarbonate. Alkalinity and specific conductance differed primarily according to composition of geologic materials. Tritium concentrations ranged from 0.2 (detection limit) to 1,380 nanocuries per liter. The methods of constructing, installing, and sampling with lysimeters were evaluated to ensure data reliability. These evaluations indicate that, with respect to most constituents, the samples retrieved from the lysimeters accurately represented pore-water chemistry.

Two-step interrogation then recognition of DNA binding site by Integration Host Factor: an architectural DNA-bending protein.

PubMed

Velmurugu, Yogambigai; Vivas, Paula; Connolly, Mitchell; Kuznetsov, Serguei V; Rice, Phoebe A; Ansari, Anjum

2018-02-28

The dynamics and mechanism of how site-specific DNA-bending proteins initially interrogate potential binding sites prior to recognition have remained elusive for most systems. Here we present these dynamics for Integration Host factor (IHF), a nucleoid-associated architectural protein, using a μs-resolved T-jump approach. Our studies show two distinct DNA-bending steps during site recognition by IHF. While the faster (∼100 μs) step is unaffected by changes in DNA or protein sequence that alter affinity by >100-fold, the slower (1-10 ms) step is accelerated ∼5-fold when mismatches are introduced at DNA sites that are sharply kinked in the specific complex. The amplitudes of the fast phase increase when the specific complex is destabilized and decrease with increasing [salt], which increases specificity. Taken together, these results indicate that the fast phase is non-specific DNA bending while the slow phase, which responds only to changes in DNA flexibility at the kink sites, is specific DNA kinking during site recognition. Notably, the timescales for the fast phase overlap with one-dimensional diffusion times measured for several proteins on DNA, suggesting that these dynamics reflect partial DNA bending during interrogation of potential binding sites by IHF as it scans DNA.

GPS-PAIL: prediction of lysine acetyltransferase-specific modification sites from protein sequences.

PubMed

Deng, Wankun; Wang, Chenwei; Zhang, Ying; Xu, Yang; Zhang, Shuang; Liu, Zexian; Xue, Yu

2016-12-22

Protein acetylation catalyzed by specific histone acetyltransferases (HATs) is an essential post-translational modification (PTM) and involved in the regulation a broad spectrum of biological processes in eukaryotes. Although several ten thousands of acetylation sites have been experimentally identified, the upstream HATs for most of the sites are unclear. Thus, the identification of HAT-specific acetylation sites is fundamental for understanding the regulatory mechanisms of protein acetylation. In this work, we first collected 702 known HAT-specific acetylation sites of 205 proteins from the literature and public data resources, and a motif-based analysis demonstrated that different types of HATs exhibit similar but considerably distinct sequence preferences for substrate recognition. Using 544 human HAT-specific sites for training, we constructed a highly useful tool of GPS-PAIL for the prediction of HAT-specific sites for up to seven HATs, including CREBBP, EP300, HAT1, KAT2A, KAT2B, KAT5 and KAT8. The prediction accuracy of GPS-PAIL was critically evaluated, with a satisfying performance. Using GPS-PAIL, we also performed a large-scale prediction of potential HATs for known acetylation sites identified from high-throughput experiments in nine eukaryotes. Both online service and local packages were implemented, and GPS-PAIL is freely available at: http://pail.biocuckoo.org.

GPS-PAIL: prediction of lysine acetyltransferase-specific modification sites from protein sequences

PubMed Central

Deng, Wankun; Wang, Chenwei; Zhang, Ying; Xu, Yang; Zhang, Shuang; Liu, Zexian; Xue, Yu

2016-01-01

Protein acetylation catalyzed by specific histone acetyltransferases (HATs) is an essential post-translational modification (PTM) and involved in the regulation a broad spectrum of biological processes in eukaryotes. Although several ten thousands of acetylation sites have been experimentally identified, the upstream HATs for most of the sites are unclear. Thus, the identification of HAT-specific acetylation sites is fundamental for understanding the regulatory mechanisms of protein acetylation. In this work, we first collected 702 known HAT-specific acetylation sites of 205 proteins from the literature and public data resources, and a motif-based analysis demonstrated that different types of HATs exhibit similar but considerably distinct sequence preferences for substrate recognition. Using 544 human HAT-specific sites for training, we constructed a highly useful tool of GPS-PAIL for the prediction of HAT-specific sites for up to seven HATs, including CREBBP, EP300, HAT1, KAT2A, KAT2B, KAT5 and KAT8. The prediction accuracy of GPS-PAIL was critically evaluated, with a satisfying performance. Using GPS-PAIL, we also performed a large-scale prediction of potential HATs for known acetylation sites identified from high-throughput experiments in nine eukaryotes. Both online service and local packages were implemented, and GPS-PAIL is freely available at: http://pail.biocuckoo.org. PMID:28004786

76 FR 24831 - Site-Specific Analyses for Demonstrating Compliance With Subpart C Performance Objectives

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-03

... available under ADAMS accession number ML111040419, and the ``Technical Analysis Supporting Definition of... NUCLEAR REGULATORY COMMISSION 10 CFR Part 61 RIN 3150-AI92 [NRC-2011-0012] Site-Specific Analyses...-level radioactive waste disposal facilities to conduct site-specific analyses to demonstrate compliance...

75 FR 11872 - Environmental Management Site-Specific Advisory Board, Idaho National Laboratory

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Idaho National... Site- Specific Advisory Board, Idaho National Laboratory to be held on March 16, 2010 75 FR 9590. In that notice, the meeting address was Hilton Garden Inn, 700 Lindsay Boulevard, Idaho Falls, Idaho 83402...

Cyclophilin A as a potential genetic adjuvant to improve HIV-1 Gag DNA vaccine immunogenicity by eliciting broad and long-term Gag-specific cellular immunity in mice.

PubMed

Hou, Jue; Zhang, Qicheng; Liu, Zheng; Wang, Shuhui; Li, Dan; Liu, Chang; Liu, Ying; Shao, Yiming

2016-01-01

Previous research has shown that host Cyclophilin A (CyPA) can promote dendritic cell maturation and the subsequent innate immune response when incorporated into an HIV-1 Gag protein to circumvent the resistance of dendritic cells to HIV-1 infection. This led us to hypothesize that CyPA may improve HIV-1 Gag-specific vaccine immunogenicity via binding with Gag antigen. The adjuvant effect of CyPA was evaluated using a DNA vaccine with single or dual expression cassettes. Mouse studies indicated that CyPA specifically and markedly promoted HIV-1 Gag-specific cellular immunity but not an HIV-1 Env-specific cellular response. The Gag/CyPA dual expression cassettes stimulated a greater Gag-specific cellular immune response, than Gag immunization alone. Furthermore, CyPA induced a broad Gag-specific T cell response and strong cellular immunity that lasted up to 5 months. In addition, CyPA skewed to cellular rather than humoral immunity. To investigate the mechanisms of the adjuvant effect, site-directed mutagenesis in CyPA, including active site residues H54Q and F60A resulted in mutants that were co-expressed with Gag in dual cassettes. The immune response to this vaccine was analyzed in vivo. Interestingly, the wild type CyPA markedly increased Gag cellular immunity, but the H54Q and F60A mutants drastically reduced CyPA adjuvant activation. Therefore, we suggest that the adjuvant effect of CyPA was based on Gag-CyPA-specific interactions. Herein, we report that Cyclophilin A can augment HIV-1 Gag-specific cellular immunity as a genetic adjuvant in multiplex DNA immunization strategies, and that activity of this adjuvant is specific, broad, long-term, and based on Gag-CyPA interaction.

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

EPA Pesticide Factsheets

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

Annotated Administrative Record Site-Specific Document Index, American Drum & Pallet Co. Removal Site, Memphis, Shelby County, Tennessee

EPA Pesticide Factsheets

Contains annotated index of site specific documents for the American Drum & Pallet Co. Removal Site in Memphis, Shelby County, Tennessee, January 9, 2008 Region ID: 04 DocID: 10517016, DocDate: 01-09-2008

Trends in major-ion constituents and properties for selected sampling sites in the Tongue and Powder River watersheds, Montana and Wyoming, based on data collected during water years 1980-2010

USGS Publications Warehouse

Sando, Steven K.; Vecchia, Aldo V.; Barnhart, Elliott P.; Sando, Thomas R.; Clark, Melanie L.; Lorenz, David L.

2014-01-01

The primary purpose of this report is to present information relating to flow-adjusted temporal trends in major-ion constituents and properties for 16 sampling sites in the Tongue and Powder River watersheds based on data collected during 1980–2010. In association with this primary purpose, the report presents background information on major-ion characteristics (including specific conductance, calcium, magnesium, potassium, sodium adsorption ratio, sodium, alkalinity, chloride, fluoride, dissolved sulfate, and dissolved solids) of the sampling sites and coal-bed methane (CBM) produced water (groundwater pumped from coal seams) in the site watersheds, trend analysis methods, streamflow conditions, and factors that affect trend results. The Tongue and Powder River watersheds overlie the Powder River structural basin (PRB) in northeastern Wyoming and southeastern Montana. Limited extraction of coal-bed methane (CBM) from the PRB began in the early 1990’s, and increased dramatically during the late 1990’s and early 2000’s. CBM-extraction activities produce discharges of water with high concentrations of dissolved solids (particularly sodium and bicarbonate ions) relative to most stream water in the Tongue and Powder River watersheds. Water-quality of CBM produced water is of concern because of potential effects of sodium on agricultural soils and potential effects of bicarbonate on aquatic biota. Two parametric trend-analysis methods were used in this study: the time-series model (TSM) and ordinary least squares regression (OLS) on time, streamflow, and season. The TSM was used to analyze trends for 11 of the 16 study sites. For five sites, data requirements of the TSM were not met and OLS was used to analyze trends. Two primary 10-year trend-analysis periods were selected. Trend-analysis period 1 (water years 1986–95; hereinafter referred to as period 1) was selected to represent variability in major-ion concentrations in the Tongue and Powder River watersheds before potential effects of CBM-extraction activities. Trend analysis period 2 (water years 2001–10; hereinafter referred to as period 2) was selected because it encompassed substantial CBM-extraction activities and therefore might indicate potential effects of CBM-extraction activities on water quality of receiving streams in the Tongue and Powder River watersheds. For sites that did not satisfy data requirements for the TSM, OLS was used to analyze trends for period 2 (if complete data were available) or a 6-year period (2005–10). Flow-rate characteristics of CBM-produced water were estimated to allow general comparisons with streamflow characteristics of the sampling sites. The information on flow-rate characteristics of CBM-produced water in relation to streamflow does not account for effects of disposal, treatment, or other remediation activities on the potential quantitative effects of CBM-produced water on receiving streams. In many places, CBM-produced water is discharged into impoundments or channels in upper reaches of tributary watersheds where water infiltrates and does not directly contribute to streamflow. For Tongue River at State line (site 4) mean annual pumping rate of CBM-produced water during water years 2001–10 (hereinafter referred to as mean CBM pumping rate) was 6 percent of the mean of annual median streamflows during water years 2001–10 (hereinafter referred to as 2001–10 median streamflow). For main-stem Tongue River sites 5, 7, and 10, mean CBM pumping rate was 8–12 percent of 2001–10 median streamflow. For main-stem Powder River sites (sites 12, 13, and 16), mean CBM pumping rates were 26, 28, and 34 percent of 2001–10 median streamflows, respectively. For main-stem Tongue River sites analyzed by using the TSM and downstream from substantial CBM-extraction activities [Tongue River at State line (site 4), Tongue River at Tongue River Dam (site 5), Tongue River at Birney Day School (site 7), and Tongue River at Miles City (site 10)], generally small significant or nonsignificant decreases in most constituents are indicated for period 1. For period 2 for these sites, the TSM trend results do not allow confident conclusions concerning detection of effects of CBM-extraction activities on stream water quality. Detection of significant trends in major-ion constituents and properties for period 2 generally was infrequent, and direction, magnitudes, and significance of fitted trends were not strongly consistent with relative differences in water quality between stream water and CBM-produced water. The TSM indicated significant or generally large magnitude increases in median values of sodium adsorption ratio (SAR), sodium, and alkalinity for period 2 for sites 5 and 7, which might indicate potential effects of CBM-extraction activities on stream water. However, other factors, including operations of Tongue River Reservoir, irrigation activities, contributions of saline groundwater, and operations of the Decker coal mine, confound confident determination of causes of detected significant trends for sites 5 and 7. For all mainstem Tongue River sites, trends for period 2 generally are within ranges of those for period 1 before substantial CBM-extraction activities. For main-stem Powder River sites analyzed by using the TSM [Powder River at Sussex (site 11), Powder River at Arvada (site 12), Powder River at Moorhead (site 13), and Powder River near Locate (site 16)], significant or generally large magnitude decreases in median values of SAR, sodium, estimated alkalinity, chloride, fluoride, specific conductance, and dissolved solids are indicated for period 1. Patterns in trend results for period 1 for main-stem Powder River sites are consistent with effects of Salt Creek oil-brine reinjection that started in 1990. Trend results for all main-stem Powder River sites downstream from substantial CBM-extraction activities (sites 12, 13, and 16) indicate evidence of potential effects of CBM-extraction activities on stream water quality, although evidence is stronger for sites 12 and 13 than for site 16. Evidence in support of potential CBM effects includes significant increases in median values of SAR, sodium, and estimated alkalinity for period 2 for sites 12, 13, and 16 that are consistent with relative differences between stream water and CBM-produced water. Significant increases in median values of these constituents for period 2 are not indicated for Powder River at Sussex (site 11) upstream from substantial CBM-extraction activities. In interpreting the trend results, it is notable that the fitted trends evaluate changes in median concentrations and also notable that changes in median concentrations that might be attributed to CBM-extraction activities probably are more strongly evident during low to median streamflow conditions than during mean to high streamflow conditions. This observation is relevant in assessing trend results in relation to specific water-quality concerns, including effects of water-quality changes on irrigators and effects on stream biota and ecology.

Effects of streamflow diversion on a fish population: combining empirical data and individual-based models in a site-specific evaluation

Treesearch

Bret C. Harvey; Jason L. White; Rodney J. Nakamoto; Steven F. Railsback

2014-01-01

Resource managers commonly face the need to evaluate the ecological consequences of specific water diversions of small streams. We addressed this need by conducting 4 years of biophysical monitoring of stream reaches above and below a diversion and applying two individual-based models of salmonid fish that simulated different levels of behavioral complexity. The...

Heat stress management program improving worker health and operational effectiveness: a case study.

PubMed

Huss, Rosalyn G; Skelton, Scott B; Alvis, Kimberly L; Shane, Leigh A

2013-03-01

Heat stress monitoring is a vital component of an effective health and safety program when employees work in exceptionally warm environments. Workers at hazardous waste sites often wear personal protective equipment (PPE), which increases the body heat stress load. No specific Occupational Safety and Health Administration (OSHA) regulations address heat stress; however, OSHA does provide several guidance documents to assist employers in addressing this serious workplace health hazard. This article describes a heat stress and surveillance plan implemented at a hazardous waste site as part of the overall health and safety program. The PPE requirement for work at this site, coupled with extreme environmental temperatures, made heat stress a significant concern. Occupational health nurses and industrial hygienists developed a monitoring program for heat stress designed to prevent the occurrence of significant heat-related illness in site workers. The program included worker education on the signs of heat-related illness and continuous physiologic monitoring to detect early signs of heat-related health problems. Biological monitoring data were collected before workers entered the exclusion zone and on exiting the zone following decontamination. Sixty-six site workers were monitored throughout site remediation. More than 1,700 biological monitoring data points were recorded. Outcomes included improved worker health and safety, and increased operational effectiveness. Copyright 2013, SLACK Incorporated.

A Fresh Look at Road Salt: Aquatic Toxicity and Water-Quality Impacts on Local, Regional, and National Scales

PubMed Central

2010-01-01

A new perspective on the severity of aquatic toxicity impact of road salt was gained by a focused research effort directed at winter runoff periods. Dramatic impacts were observed on local, regional, and national scales. Locally, samples from 7 of 13 Milwaukee, Wisconsin area streams exhibited toxicity in Ceriodaphnia dubia and Pimephales promelas bioassays during road-salt runoff. Another Milwaukee stream was sampled from 1996 to 2008 with 72% of 37 samples exhibiting toxicity in chronic bioassays and 43% in acute bioassays. The maximum chloride concentration was 7730 mg/L. Regionally, in southeast Wisconsin, continuous specific conductance was monitored as a chloride surrogate in 11 watersheds with urban land use from 6.0 to 100%. Elevated specific conductance was observed between November and April at all sites, with continuing effects between May and October at sites with the highest specific conductance. Specific conductance was measured as high as 30 800 μS/cm (Cl = 11 200 mg/L). Chloride concentrations exceeded U.S. Environmental Protection Agency (USEPA) acute (860 mg/L) and chronic (230 mg/L) water-quality criteria at 55 and 100% of monitored sites, respectively. Nationally, U.S. Geological Survey historical data were examined for 13 northern and 4 southern metropolitan areas. Chloride concentrations exceeded USEPA water-quality criteria at 55% (chronic) and 25% (acute) of the 168 monitoring locations in northern metropolitan areas from November to April. Only 16% (chronic) and 1% (acute) of sites exceeded criteria from May to October. At southern sites, very few samples exceeded chronic water-quality criteria, and no samples exceeded acute criteria. PMID:20806974

Nicotinic acetylcholine receptor probed with a photoactivatable agonist: improved labeling specificity by addition of CeIV/glutathione. Extension to laser flash photolabeling.

PubMed

Grutter, T; Goeldner, M; Kotzyba-Hibert, F

1999-06-08

The molecular structure of Torpedo marmorata acetylcholine binding sites has been investigated previously by photoaffinity labeling. However, besides the nicotine molecule [Middleton et al. (1991) Biochemistry 30, 6987-6997], all other photosensitive probes used for this purpose interacted only with closed receptor states. In the perspective of mapping the functional activated state, we synthesized and developed a new photoactivatable agonist of nAChR capable of alkylation of the acetylcholine (ACh) binding sites, as reported previously [Kotzyba-Hibert et al. (1997) Bioconjugate Chem. 8, 472-480]. Here, we describe the setup of experimental conditions that were made in order to optimize the photolabeling reaction and in particular its specificity. We found that subsequent addition of the oxidant ceric ion (CeIV) and reduced glutathione before the photolabeling step lowered considerably nonspecific labeling (over 90% protection with d-tubocurarine) without affecting the binding properties of the ACh binding sites. As a consequence, irradiation at 360 nm for 20 min in these new conditions gave satisfactory coupling yields (7.5%). A general mechanism was proposed to explain the successive reactions occurring and their drastic effect on the specificity of the labeling reaction. Last, these incubation conditions can be extended to nanosecond pulsed laser photolysis leading to the same specific photoincorporation as for usual irradiations (8.5% coupling yield of ACh binding sites, 77% protection with carbamylcholine). Laser flash photocoupling of a diazocyclohexadienoyl probe on nAChR was achieved for the first time. Taken together, these data indicate that future investigation of the molecular dynamics of allosteric transitions occurring at the activated ACh binding sites should be possible.

A fresh look at road salt: Aquatic toxicity and water-quality impacts on local, regional, and national scales

USGS Publications Warehouse

Corsi, S.R.; Graczyk, D.J.; Geis, S.W.; Booth, N.L.; Richards, K.D.

2010-01-01

A new perspective on the severity of aquatic toxicity impact of road salt was gained by a focused research effort directed at winter runoff periods. Dramatic impacts were observed on local, regional, and national scales. Locally, samples from 7 of 13 Milwaukee, Wisconsin area streams exhibited toxicity in Ceriodaphnia dubia and Pimephales promelas bioassays during road-salt runoff. Another Milwaukee stream was sampled from 1996 to 2008 with 72% of 37 samples exhibiting toxicity in chronic bioassays and 43% in acute bioassays. The maximum chloride concentration was 7730 mg/L. Regionally, in southeast Wisconsin, continuous specific conductance was monitored as a chloride surrogate in 11 watersheds with urban land use from 6.0 to 100%. Elevated specific conductance was observed between November and April at all sites, with continuing effects between May and October at sites with the highest specific conductance. Specific conductance was measured as high as 30 800 ??S/cm (Cl = 11 200 mg/L). Chloride concentrations exceeded U.S. Environmental Protection Agency (USEPA) acute (860 mg/L) and chronic (230 mg/L) water-quality criteria at 55 and 100% of monitored sites, respectively. Nationally, U.S. Geological Survey historical data were examined for 13 northern and 4 southern metropolitan areas. Chloride concentrations exceeded USEPA water-quality criteria at 55% (chronic) and 25% (acute) of the 168 monitoring locations in northern metropolitan areas from November to April. Only 16% (chronic) and 1% (acute) of sites exceeded criteria from May to October. At southern sites, very few samples exceeded chronic water-quality criteria, and no samples exceeded acute criteria. ?? 2010 American Chemical Society.

A Review of Nanoparticle Photosensitizer Drug Delivery Uptake Systems for Photodynamic Treatment of Lung Cancer.

PubMed

Gift, Mokwena Mpho; Ann, Kruger Cherie; Ivan, Mfouo-Tynga; Heidi, Abrahamse

2018-03-24

Lung cancer is a leading cause of cancer related deaths worldwide and so current research is focused on trying to improve treatment modalities, such as photodynamic therapy (PDT). PDT has 3 fundamental factors, namely a photosensitizer (PS) drug, light and oxygen. When a PS drug is administered to a patient, it can either passively or actively accumulate within a tumour site and once exposed to a specific wavelength of light, it is stimulated to produce reactive oxygen species (ROS), resulting in tumour destruction. However, the efficacy of ROS generation for tumour destruction is highly dependent on the accumulation of the PS in tumour cells. Thus PS selective / targeted uptake and delivery in tumour cells is a crucial factor in PDT cancer drug absorption studies. Generally, within non-targeted drug delivery mechanisms, only small amounts of PS is able to passively accumulates in tumour sites due to the enhanced permeability and retention (EPR) effect and the remainder distributes into healthy tissues, causing side effects. Thus to improve the efficacy of PDT, research is currently focused on the development of specific receptor based photosynthetic nanocarrier drugs, which promotes the active uptake and absorption of PS drugs in tumour sites only, avoiding unwanted side effects. The aim of this review is to focus on current non-targeted passive versus specifically active targeted PS nanoparticle drug delivery systems, that have been investigated for the PDT treatment of lung cancer and so to deduce its efficacy and recent advancements. Copyright © 2018. Published by Elsevier B.V.

LHRH-pituitary plasma membrane binding: the presence of specific binding sites in other tissues.

PubMed

Marshall, J C; Shakespear, R A; Odell, W D

1976-11-01

Two specific binding sites for LHRH are present on plasma membranes prepared from rat and bovine anterior pituitary glands. One site is of high affinity (K = 2X108 1/MOL) and the second is of lower affinity (8-5X105 1/mol) and much greater capacity. Studies on membrane fractions prepared from other tissues showed the presence of a single specific site for LHRH. The kinetics and specificity of this site were similar to those of the lower affinity pituitary receptor. These results indicate that only pituitary membranes possess the higher affinity binding site and suggest that the low affinity site is not of physiological importance in the regulation of gonadotrophin secretion. After dissociation from membranes of non-pituitary tissues 125I-LHRH rebound to pituitary membrane preparations. Thus receptor binding per se does not result in degradation of LHRH and the function of these peripheral receptors remains obscure.

Onco-Regulon: an integrated database and software suite for site specific targeting of transcription factors of cancer genes

PubMed Central

Tomar, Navneet; Mishra, Akhilesh; Mrinal, Nirotpal; Jayaram, B.

2016-01-01

Transcription factors (TFs) bind at multiple sites in the genome and regulate expression of many genes. Regulating TF binding in a gene specific manner remains a formidable challenge in drug discovery because the same binding motif may be present at multiple locations in the genome. Here, we present Onco-Regulon (http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm), an integrated database of regulatory motifs of cancer genes clubbed with Unique Sequence-Predictor (USP) a software suite that identifies unique sequences for each of these regulatory DNA motifs at the specified position in the genome. USP works by extending a given DNA motif, in 5′→3′, 3′ →5′ or both directions by adding one nucleotide at each step, and calculates the frequency of each extended motif in the genome by Frequency Counter programme. This step is iterated till the frequency of the extended motif becomes unity in the genome. Thus, for each given motif, we get three possible unique sequences. Closest Sequence Finder program predicts off-target drug binding in the genome. Inclusion of DNA-Protein structural information further makes Onco-Regulon a highly informative repository for gene specific drug development. We believe that Onco-Regulon will help researchers to design drugs which will bind to an exclusive site in the genome with no off-target effects, theoretically. Database URL: http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm PMID:27515825

MINIMIZING COGNITIVE ERRORS IN SITE-SPECIFIC CAUSAL ASSESSMENT

EPA Science Inventory

Interest in causal investigations in aquatic systems has been a natural outgrowth of the increased use of biological monitoring to characterize the condition of resources. Although biological monitoring approaches are critical tools for detecting whether effects are occurring, t...

Modelling Carbon Emissions in Calluna vulgaris-Dominated Ecosystems when Prescribed Burning and Wildfires Interact.

PubMed

Santana, Victor M; Alday, Josu G; Lee, HyoHyeMi; Allen, Katherine A; Marrs, Rob H

2016-01-01

A present challenge in fire ecology is to optimize management techniques so that ecological services are maximized and C emissions minimized. Here, we modeled the effects of different prescribed-burning rotation intervals and wildfires on carbon emissions (present and future) in British moorlands. Biomass-accumulation curves from four Calluna-dominated ecosystems along a north-south gradient in Great Britain were calculated and used within a matrix-model based on Markov Chains to calculate above-ground biomass-loads and annual C emissions under different prescribed-burning rotation intervals. Additionally, we assessed the interaction of these parameters with a decreasing wildfire return intervals. We observed that litter accumulation patterns varied between sites. Northern sites (colder and wetter) accumulated lower amounts of litter with time than southern sites (hotter and drier). The accumulation patterns of the living vegetation dominated by Calluna were determined by site-specific conditions. The optimal prescribed-burning rotation interval for minimizing annual carbon emissions also differed between sites: the optimal rotation interval for northern sites was between 30 and 50 years, whereas for southern sites a hump-backed relationship was found with the optimal interval either between 8 to 10 years or between 30 to 50 years. Increasing wildfire frequency interacted with prescribed-burning rotation intervals by both increasing C emissions and modifying the optimum prescribed-burning interval for minimum C emission. This highlights the importance of studying site-specific biomass accumulation patterns with respect to environmental conditions for identifying suitable fire-rotation intervals to minimize C emissions.

Appreciating "Thirdspace": An Alternative Way of Viewing and Valuing Site-Specific Dance Performance

ERIC Educational Resources Information Center

Munjee, Tara

2014-01-01

Site-specific dance performance involves the presentation of choreography in connection with a site. The context of the site combined with a viewer's personal history, beliefs, and identity impact the reading and appreciation of the performance. Although both stage and site dance performance valuing elicit multiple interpretations of artistic…

Maternally expressed PGK-Cre transgene as a tool for early and uniform activation of the Cre site-specific recombinase.

PubMed

Lallemand, Y; Luria, V; Haffner-Krausz, R; Lonai, P

1998-03-01

A transgenic mouse strain with early and uniform expression of the Cre site-specific recombinase is described. In this strain, PGK-Crem, Cre is driven by the early acting PGK-1 promoter, but, probably due to cis effects at the integration site, the recombinase is under dominant maternal control. When Cre is transmitted by PGK-Crem females mated to males that carry a reporter transgene flanked by loxP sites, even offspring that do not inherit PGK-Cre delete the target gene. It follows that in the PGK-Crem female Cre activity commences in the diploid phase of oogenesis. In PGK-Crem crosses complete recombination was observed in all organs, including testis and ovary. We prepared a mouse stock that is homozygous for PGK-Crem and at the albino (c) locus. This strain will be useful for the early and uniform induction of ectopic and dominant negative mutations, for the in vivo removal of selective elements from targeted mutations and in connection with the manipulation of targeted loci in 'knock in' and related technologies.

Induction of strong anti-HIV cellular immunity by a combination of Clostridium perfringens expressing HIV gag and virus like particles.

PubMed

Pegu, Poonam; Helmus, Ruth; Gupta, Phalguni; Tarwater, Patrick; Caruso, Lori; Shen, Chengli; Ross, Ted; Chen, Yue

2011-12-01

The lower gastrointestinal tract is a major mucosal site of HIV entry and initial infection. Thus, the induction of strong cellular immune responses at this mucosal site will be an important feature of an effective HIV vaccine. We have used a novel prime-boost vaccination approach to induce immune responses at mucosal sites. Orally delivered recombinant Clostridium perfringens expressing HIV-1 gag (Cp-Gag) was evaluated for induction of HIV-1 Gag specific T cell responses in a prime-boost model with intranasal inoculation of HIV-1 virus like particles (VLP). HIV-1 specific cellular immune responses in both the effector (Lamina propria) and inductive sites (Peyer's patches) of the gastrointestinal (GI) tract were significantly higher in mice immunized using Cp-Gag and VLPs in a prime-boost approach compared to mice immunized with either Cp-Gag or VLPs alone. Such cellular immune response was found to be mediated by both CD8(+) and CD4(+) T cells. Such a strong mucosal immune response could be very useful in developing a mucosal vaccine against HIV-1.

Analysis of the site-specific carbon isotope composition of propane by gas source isotope ratio mass spectrometer

NASA Astrophysics Data System (ADS)

Piasecki, Alison; Sessions, Alex; Lawson, Michael; Ferreira, A. A.; Neto, E. V. Santos; Eiler, John M.

2016-09-01

Site-specific isotope ratio measurements potentially provide valuable information about the formation and degradation of complex molecules-information that is lost in conventional bulk isotopic measurements. Here we discuss the background and possible applications of such measurements, and present a technique for studying the site-specific carbon isotope composition of propane at natural abundance based on mass spectrometric analysis of the intact propane molecule and its fragment ions. We demonstrate the feasibility of this approach through measurements of mixtures of natural propane and propane synthesized with site-specific 13C enrichment, and we document the limits of precision of our technique. We show that mass balance calculations of the bulk δ13C of propane based on our site-specific measurements is generally consistent with independent constraints on bulk δ13C. We further demonstrate the accuracy of the technique, and illustrate one of its simpler applications by documenting the site-specific carbon isotope signature associated with gas phase diffusion of propane, confirming that our measurements conform to the predictions of the kinetic theory of gases. This method can be applied to propane samples of moderate size (tens of micromoles) isolated from natural gases. Thus, it provides a means of studying the site-specific stable isotope systematics of propane at natural isotope abundances on sample sizes that are readily recovered from many natural environments. This method may also serve as a model for future techniques that apply high-resolution mass spectrometry to study the site-specific isotopic distributions of larger organic molecules, with potential applications to biosynthesis, forensics and other geochemical subjects.

Studies of bioactivity, conformation and pharmacokinetic profiles of site-specific PEGylated thymosin alpha 1 derivatives.

PubMed

Qie, Jiankun; Ma, Jinbo; Wang, Liangyou; Xu, Xiaoyu; Zheng, Jianquan; Dong, Sijian; Xie, Jianwei; Sun, Huixian; Zhou, Wenxia; Qi, Chunhui; Zhao, Xiunan; Zhang, Yongxiang; Liu, Keliang

2007-08-01

Site-specific mono-PEGylations were performed in different conformational regions of Thymosin alpha 1 (T alpha 1) by introducing one cysteine residue into the chosen site and coupling with thiol-specific mPEG-MAL reagent. Results demonstrated that PEGylated sites and regions influenced the conformations and pharmacokinetic profiles of the peptide greatly with following order: alpha-helix, beta-turn, random coil and terminals, but little on the immunoactivity.

Structure And Specificity of a Quorum-Quenching Lactonase (AiiB) From Agrobacterium Tumefaciens

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

Liu, D.; Thomas, P.W.; Momb, J.

2009-06-03

N-Acyl-l-homoserine lactone (AHL) mediated quorum-sensing regulates virulence factor production in a variety of Gram-negative bacteria. Proteins capable of degrading these autoinducers have been called 'quorum-quenching' enzymes, can block many quorum-sensing dependent phenotypes, and represent potentially useful reagents for clinical, agricultural, and industrial applications. The most characterized quorum-quenching enzymes to date are the AHL lactonases, which are metalloproteins that belong to the metallo-beta-lactamase superfamily. Here, we report the cloning, heterologous expression, purification, metal content, substrate specificity, and three-dimensional structure of AiiB, an AHL lactonase from Agrobacterium tumefaciens. Much like a homologous AHL lactonase from Bacillus thuringiensis, AiiB appears to be amore » metal-dependent AHL lactonase with broad specificity. A phosphate dianion is bound to the dinuclear zinc site and the active-site structure suggests specific mechanistic roles for an active site tyrosine and aspartate. To our knowledge, this is the second representative structure of an AHL lactonase and the first of an AHL lactonase from a microorganism that also produces AHL autoinducers. This work should help elucidate the hydrolytic ring-opening mechanism of this family of enzymes and also facilitate the design of more effective quorum-quenching catalysts.« less

On-site detection of stacked genetically modified soybean based on event-specific TM-LAMP and a DNAzyme-lateral flow biosensor.

PubMed

Cheng, Nan; Shang, Ying; Xu, Yuancong; Zhang, Li; Luo, Yunbo; Huang, Kunlun; Xu, Wentao

2017-05-15

Stacked genetically modified organisms (GMO) are becoming popular for their enhanced production efficiency and improved functional properties, and on-site detection of stacked GMO is an urgent challenge to be solved. In this study, we developed a cascade system combining event-specific tag-labeled multiplex LAMP with a DNAzyme-lateral flow biosensor for reliable detection of stacked events (DP305423× GTS 40-3-2). Three primer sets, both event-specific and soybean species-specific, were newly designed for the tag-labeled multiplex LAMP system. A trident-like lateral flow biosensor displayed amplified products simultaneously without cross contamination, and DNAzyme enhancement improved the sensitivity effectively. After optimization, the limit of detection was approximately 0.1% (w/w) for stacked GM soybean, which is sensitive enough to detect genetically modified content up to a threshold value established by several countries for regulatory compliance. The entire detection process could be shortened to 120min without any large-scale instrumentation. This method may be useful for the in-field detection of DP305423× GTS 40-3-2 soybean on a single kernel basis and on-site screening tests of stacked GM soybean lines and individual parent GM soybean lines in highly processed foods. Copyright © 2017 Elsevier B.V. All rights reserved.

Stimulation, Inhibition, or Stabilization of Na,K-ATPase Caused by Specific Lipid Interactions at Distinct Sites

PubMed Central

Habeck, Michael; Haviv, Haim; Katz, Adriana; Kapri-Pardes, Einat; Ayciriex, Sophie; Shevchenko, Andrej; Ogawa, Haruo; Toyoshima, Chikashi; Karlish, Steven J. D.

2015-01-01

The activity of membrane proteins such as Na,K-ATPase depends strongly on the surrounding lipid environment. Interactions can be annular, depending on the physical properties of the membrane, or specific with lipids bound in pockets between transmembrane domains. This paper describes three specific lipid-protein interactions using purified recombinant Na,K-ATPase. (a) Thermal stability of the Na,K-ATPase depends crucially on a specific interaction with 18:0/18:1 phosphatidylserine (1-stearoyl-2-oleoyl-sn-glycero-3-phospho-l-serine; SOPS) and cholesterol, which strongly amplifies stabilization. We show here that cholesterol associates with SOPS, FXYD1, and the α subunit between trans-membrane segments αTM8 and -10 to stabilize the protein. (b) Polyunsaturated neutral lipids stimulate Na,K-ATPase turnover by >60%. A screen of the lipid specificity showed that 18:0/20:4 and 18:0/22:6 phosphatidylethanolamine (PE) are the optimal phospholipids for this effect. (c) Saturated phosphatidylcholine and sphingomyelin, but not saturated phosphatidylserine or PE, inhibit Na,K-ATPase activity by 70–80%. This effect depends strongly on the presence of cholesterol. Analysis of the Na,K-ATPase activity and E1-E2 conformational transitions reveals the kinetic mechanisms of these effects. Both stimulatory and inhibitory lipids poise the conformational equilibrium toward E2, but their detailed mechanisms of action are different. PE accelerates the rate of E1 → E2P but does not affect E2(2K)ATP → E13NaATP, whereas sphingomyelin inhibits the rate of E2(2K)ATP → E13NaATP, with very little effect on E1 → E2P. We discuss these lipid effects in relation to recent crystal structures of Na,K-ATPase and propose that there are three separate sites for the specific lipid interactions, with potential physiological roles to regulate activity and stability of the pump. PMID:25533463

Harmonization of multi-site diffusion tensor imaging data.

PubMed

Fortin, Jean-Philippe; Parker, Drew; Tunç, Birkan; Watanabe, Takanori; Elliott, Mark A; Ruparel, Kosha; Roalf, David R; Satterthwaite, Theodore D; Gur, Ruben C; Gur, Raquel E; Schultz, Robert T; Verma, Ragini; Shinohara, Russell T

2017-11-01

Diffusion tensor imaging (DTI) is a well-established magnetic resonance imaging (MRI) technique used for studying microstructural changes in the white matter. As with many other imaging modalities, DTI images suffer from technical between-scanner variation that hinders comparisons of images across imaging sites, scanners and over time. Using fractional anisotropy (FA) and mean diffusivity (MD) maps of 205 healthy participants acquired on two different scanners, we show that the DTI measurements are highly site-specific, highlighting the need of correcting for site effects before performing downstream statistical analyses. We first show evidence that combining DTI data from multiple sites, without harmonization, may be counter-productive and negatively impacts the inference. Then, we propose and compare several harmonization approaches for DTI data, and show that ComBat, a popular batch-effect correction tool used in genomics, performs best at modeling and removing the unwanted inter-site variability in FA and MD maps. Using age as a biological phenotype of interest, we show that ComBat both preserves biological variability and removes the unwanted variation introduced by site. Finally, we assess the different harmonization methods in the presence of different levels of confounding between site and age, in addition to test robustness to small sample size studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Is Exposure to an Effective Contingency Management Intervention Associated with More Positive Provider Beliefs?

PubMed Central

Kirby, Kimberly C.; Carpenedo, Carolyn M.; Stitzer, Maxine L.; Dugosh, Karen L.; Petry, Nancy M.; Roll, John M.; Saladin, Michael E.; Cohen, Allan J.; Hamilton, John; Reese, Karen; Sillo, Gina R.; Stabile, Patricia Quinn; Sterling, Robert C.

2011-01-01

This study empirically examined opinions of treatment providers regarding Contingency Management (CM) programs while controlling for experience with a specific efficacious CM program. In addition to empirically describing provider opinions, we examined whether the opinions of providers at the sites that implemented the CM program were more positive than those of matched providers at sites that did not implement it. Participants from 7 CM treatment sites (n = 76) and 7 matched non-participating sites (n = 69) within the same nodes of NIDA's Clinical Trials Network completed the Provider Survey of Incentives (PSI), which assesses positive and negative beliefs about incentive programs. An intent-to-treat analysis found no differences in the PSI summary scores of providers in CM program vs. matched sites, but correcting for experience with tangible incentives showed significant differences, with providers from CM sites reporting more positive opinions than those from matched sites. Some differences were found in opinions regarding costs of incentives and these generally indicated that participants from CM sites were more likely to see the costs as worthwhile. The results from the study suggest that exposing community treatment providers to incentive programs may itself be an effective strategy in prompting the dissemination of CM interventions. PMID:22116009

Site Effects in the City of Port au Prince (Haiti) Inferred From 2010 Earthquake Aftershocks Recordings.

NASA Astrophysics Data System (ADS)

ST Fleur, S.; Courboulex, F.; Bertrand, E.; Deschamps, A.; Mercier De Lepinay, B. F.; Boisson, D.; Prepetit, C.; Hough, S. E.

2014-12-01

The Haitian earthquake of 12 January 2010 (Mw=7) caused an unprecedented disaster in Port-au-Prince as well as in smaller cities close to the epicenter. The extent of damage appears to be initially attributed to the proximity of the earthquake in Port-au-Prince, the extreme vulnerability of many structures, and a high population density. However, the damage distribution for this earthquake suggests a general correlation of damage with small-scale topographical features and local geological structure. The main objective of this work is to investigate site effects in the city of Port-au-Prince. It is also to better define the response of different sites to earthquakes and establish transfer functions between each site and a particular site defined as a reference site. Specific soil columns is determined in the vicinity of each station in order to carry out 1D simulations of soil response at these sites. About 90 earthquakes (2

Spatial demographic models to inform conservation planning of golden eagles in renewable energy landscapes

USGS Publications Warehouse

Wiens, J. David; Schumaker, Nathan H.; Inman, Richard D.; Esque, Todd C.; Longshore, Kathleen M.; Nussear, Kenneth E

2017-01-01

Spatial demographic models can help guide monitoring and management activities targeting at-risk species, even in cases where baseline data are lacking. Here, we provide an example of how site-specific changes in land use and anthropogenic stressors can be incorporated into a spatial demographic model to investigate effects on population dynamics of Golden Eagles (Aquila chrysaetos). Our study focused on a population of Golden Eagles exposed to risks associated with rapid increases in renewable energy development in southern California, U.S.A. We developed a spatially explicit, individual-based simulation model that integrated empirical data on demography of Golden Eagles with spatial data on the arrangement of nesting habitats, prey resources, and planned renewable energy development sites. Our model permitted simulated eagles of different stage-classes to disperse, establish home ranges, acquire prey resources, prospect for breeding sites, and reproduce. The distribution of nesting habitats, prey resources, and threats within each individual's home range influenced movement, reproduction, and survival. We used our model to explore potential effects of alternative disturbance scenarios, and proposed conservation strategies, on the future distribution and abundance of Golden Eagles in the study region. Results from our simulations suggest that probable increases in mortality associated with renewable energy infrastructure (e.g., collisions with wind turbines and vehicles, electrocution on power poles) could have negative consequences for population trajectories, but that site-specific conservation actions could reduce the magnitude of negative effects. Our study demonstrates the use of a flexible and expandable modeling framework to incorporate spatially dependent processes when determining relative effects of proposed management options to Golden Eagles and their habitats.

M13 phage peptide ZL4 exerts its targeted binding effect on schistosoma japonicum via alkaline phosphatase.

PubMed

Liu, Yan; Yang, Shenghui; Xiao, Jianhua; Yu, Liang; Chen, Li; Zou, Ju; Wang, Kegeng; Tan, Sijie; Yu, Zhengyang; Zeng, Qingren

2015-01-01

The present study was to determine the targeting effect of M13 phage peptide ZL4 (MppZL4) on Schistosoma japonicum (S.j). Mice infected with S.j were injected with MppZL4. Real-time PCR was used to detect the distribution and metabolism of MppZL4 in the livers and lungs of mice. In vivo refusion test was performed to detect the targeting of MppZL4. Western blotting was employed to determine the expression of MppZL4. Live imaging was used to detect the distribution of oligopeptide MppZL4. Immunohistochemistry was employed to determine MppZL4 location on adult S.j body surface. Gomori method was employed to detect the influence of oligopeptide MppZL4 on alkaline phosphatase activity. The distribution and metabolism of MppZL4 and M13KE are not significantly different from each other at each time point. The abundance of MppZL4 is changed as S.j migrates in mice. The targeted binding effect of MppZL4 varies at different stages. ZL4 oligopeptide targets S.j in mice. The specific binding sites of MppZL4 on S.j body are mainly located in syncytial cells. The binding sites of MppZL4 on S.j body surface might be ALP or ALP-related proteins. MppZL4 had targeted binding effect on S.j with its binding site being associated with proteins related to S.j alkaline phosphatase. S.j tegument had a specifically binding site with exogenous peptides, offering new means to explore the interactions between hosts and parasites. Additionally, MppZL4 can possibly be used as targeting molecules in worm-resistant drugs or as tracing molecules in imaging diagnosis technologies.

Cross-cultural and site-based influences on demographic, well-being, and social network predictors of risk perception in hazard and disaster settings in Ecuador and Mexico: predictors of risk perception in hazard and disaster settings in Ecuador and Mexico.

PubMed

Jones, Eric C; Faas, Albert J; Murphy, Arthur D; Tobin, Graham A; Whiteford, Linda M; McCarty, Christopher

2013-03-01

Although virtually all comparative research about risk perception focuses on which hazards are of concern to people in different culture groups, much can be gained by focusing on predictors of levels of risk perception in various countries and places. In this case, we examine standard and novel predictors of risk perception in seven sites among communities affected by a flood in Mexico (one site) and volcanic eruptions in Mexico (one site) and Ecuador (five sites). We conducted more than 450 interviews with questions about how people feel at the time (after the disaster) regarding what happened in the past, their current concerns, and their expectations for the future. We explore how aspects of the context in which people live have an effect on how strongly people perceive natural hazards in relationship with demographic, well-being, and social network factors. Generally, our research indicates that levels of risk perception for past, present, and future aspects of a specific hazard are similar across these two countries and seven sites. However, these contexts produced different predictors of risk perception-in other words, there was little overlap between sites in the variables that predicted the past, present, or future aspects of risk perception in each site. Generally, current stress was related to perception of past danger of an event in the Mexican sites, but not in Ecuador; network variables were mainly important for perception of past danger (rather than future or present danger), although specific network correlates varied from site to site across the countries.

Deconstructing thermodynamic parameters of a coupled system from site-specific observables.

PubMed

Chowdhury, Sandipan; Chanda, Baron

2010-11-02

Cooperative interactions mediate information transfer between structural domains of a protein molecule and are major determinants of protein function and modulation. The prevalent theories to understand the thermodynamic origins of cooperativity have been developed to reproduce the complex behavior of a global thermodynamic observable such as ligand binding or enzyme activity. However, in most cases the measurement of a single global observable cannot uniquely define all the terms that fully describe the energetics of the system. Here we establish a theoretical groundwork for analyzing protein thermodynamics using site-specific information. Our treatment involves extracting a site-specific parameter (defined as χ value) associated with a structural unit. We demonstrate that, under limiting conditions, the χ value is related to the direct interaction terms associated with the structural unit under observation and its intrinsic activation energy. We also introduce a site-specific interaction energy term (χ(diff)) that is a function of the direct interaction energy of that site with every other site in the system. When combined with site-directed mutagenesis and other molecular level perturbations, analyses of χ values of site-specific observables may provide valuable insights into protein thermodynamics and structure.

The Connectivity Between Site-Specific Life Cycle Impact Assessment and Site-Specific Weighting

EPA Science Inventory

The goal of many LCIAs is to come to a single score with all of the impacts from a wide variety of impact assessments weighted to form this single score. My past experiences with developing site-specific impact assessment methodologies and how this can change the valuation porti...

44 CFR 354.5 - Description of site-specific, plume pathway EPZ biennial exercise-related component services and...

Code of Federal Regulations, 2012 CFR

2012-10-01

..., plume pathway EPZ biennial exercise-related component services and other services. 354.5 Section 354.5... Description of site-specific, plume pathway EPZ biennial exercise-related component services and other... will assess fees on licensees include the following: (a) Site-specific, plume pathway EPZ biennial...

Statistical Analysis for Multisite Trials Using Instrumental Variables with Random Coefficients

ERIC Educational Resources Information Center

Raudenbush, Stephen W.; Reardon, Sean F.; Nomi, Takako

2012-01-01

Multisite trials can clarify the average impact of a new program and the heterogeneity of impacts across sites. Unfortunately, in many applications, compliance with treatment assignment is imperfect. For these applications, we propose an instrumental variable (IV) model with person-specific and site-specific random coefficients. Site-specific IV…

40 CFR 141.720 - Inactivation toolbox components.

Code of Federal Regulations, 2013 CFR

2013-07-01

... between the indicated values: Log credit = (0.0397 × (1.09757)Temp) × CT. (c) Site-specific study. The... this section on a site-specific basis. The State must base this approval on a site-specific study a... in this table are applicable only to post-filter applications of UV in filtered systems and to...

40 CFR 141.720 - Inactivation toolbox components.

Code of Federal Regulations, 2010 CFR

2010-07-01

... between the indicated values: Log credit = (0.0397 × (1.09757)Temp) × CT. (c) Site-specific study. The... this section on a site-specific basis. The State must base this approval on a site-specific study a... in this table are applicable only to post-filter applications of UV in filtered systems and to...

40 CFR 141.720 - Inactivation toolbox components.

Code of Federal Regulations, 2011 CFR

2011-07-01

... between the indicated values: Log credit = (0.0397 × (1.09757)Temp) × CT. (c) Site-specific study. The... this section on a site-specific basis. The State must base this approval on a site-specific study a... in this table are applicable only to post-filter applications of UV in filtered systems and to...

40 CFR 141.720 - Inactivation toolbox components.

Code of Federal Regulations, 2012 CFR

2012-07-01

... between the indicated values: Log credit = (0.0397 × (1.09757)Temp) × CT. (c) Site-specific study. The... this section on a site-specific basis. The State must base this approval on a site-specific study a... in this table are applicable only to post-filter applications of UV in filtered systems and to...