Remediation management of complex sites using an adaptive site management approach.

Science.gov (United States)

Price, John; Spreng, Carl; Hawley, Elisabeth L; Deeb, Rula

2017-12-15

Complex sites require a disproportionate amount of resources for environmental remediation and long timeframes to achieve remediation objectives, due to their complex geologic conditions, hydrogeologic conditions, geochemical conditions, contaminant-related conditions, large scale of contamination, and/or non-technical challenges. A recent team of state and federal environmental regulators, federal agency representatives, industry experts, community stakeholders, and academia worked together as an Interstate Technology & Regulatory Council (ITRC) team to compile resources and create new guidance on the remediation management of complex sites. This article summarizes the ITRC team's recommended process for addressing complex sites through an adaptive site management approach. The team provided guidance for site managers and other stakeholders to evaluate site complexities and determine site remediation potential, i.e., whether an adaptive site management approach is warranted. Adaptive site management was described as a comprehensive, flexible approach to iteratively evaluate and adjust the remedial strategy in response to remedy performance. Key aspects of adaptive site management were described, including tools for revising and updating the conceptual site model (CSM), the importance of setting interim objectives to define short-term milestones on the journey to achieving site objectives, establishing a performance model and metrics to evaluate progress towards meeting interim objectives, and comparing actual with predicted progress during scheduled periodic evaluations, and establishing decision criteria for when and how to adapt/modify/revise the remedial strategy in response to remedy performance. Key findings will be published in an ITRC Technical and Regulatory guidance document in 2017 and free training webinars will be conducted. More information is available at www.itrc-web.org. Copyright © 2017 Elsevier Ltd. All rights reserved.

MNAtoolbox: A Monitored Natural Attenuation Site Screening Program

Energy Technology Data Exchange (ETDEWEB)

Borns, David J.; Brady, Patrick V.; Brady, Warren D.; Krupka, Kenneth M.; Spalding, Brian P.; Waters, Robert D.; Zhang, Pengchu

1999-07-12

Screening of sites for the potential application and reliance upon monitored natural attenuation (MNA) can be done using MNAtoolbox, a web-based tool for estimating extent of biodegradation, chemical transformation, and dilution. MNAtoolbox uses site-specific input data, where available (default parameters are taken from the literature), to roughly quantify the nature and extent of attenuation at a particular site. Use of MNAtoolbox provides 3 important elements of site evaluation: (1) Identifies likely attenuation pathways, (2) Clearly identifies sites where MNA is inappropriate, and (3) Evaluates data requirements for subsequent reliance on MNA as a sole or partial corrective action.

Screening of groundwater remedial alternatives for brownfield sites: a comprehensive method integrated MCDA with numerical simulation.

Science.gov (United States)

Li, Wei; Zhang, Min; Wang, Mingyu; Han, Zhantao; Liu, Jiankai; Chen, Zhezhou; Liu, Bo; Yan, Yan; Liu, Zhu

2018-06-01

Brownfield sites pollution and remediation is an urgent environmental issue worldwide. The screening and assessment of remedial alternatives is especially complex owing to its multiple criteria that involves technique, economy, and policy. To help the decision-makers selecting the remedial alternatives efficiently, the criteria framework conducted by the U.S. EPA is improved and a comprehensive method that integrates multiple criteria decision analysis (MCDA) with numerical simulation is conducted in this paper. The criteria framework is modified and classified into three categories: qualitative, semi-quantitative, and quantitative criteria, MCDA method, AHP-PROMETHEE (analytical hierarchy process-preference ranking organization method for enrichment evaluation) is used to determine the priority ranking of the remedial alternatives and the solute transport simulation is conducted to assess the remedial efficiency. A case study was present to demonstrate the screening method in a brownfield site in Cangzhou, northern China. The results show that the systematic method provides a reliable way to quantify the priority of the remedial alternatives.

Comparison of tree coring and soil gas sampling for screening of contaminated sites

DEFF Research Database (Denmark)

Nielsen, Mette Algreen; Stalder, Marcel; Riis, Charlotte

and then identify high risk areas. The uptake of BTEX into trees varies to a greater extent with the tree species and the site conditions than chlorinated solvents, which lead to greater uncertainty. Both methods have their advantages and disadvantages. Hence, the methods supplement each other. Based on results......Site characterization is often time consuming and a financial burden for the site owners, which raises a demand for rapid and inexpensive (pre)screening methods. Phytoscreening by tree coring has shown to be a useful tool to detect subsurface contamination, especially of chlorinated solvents...... suitable as initial screening methods for site characterization. The aim of this study is to compare tree coring and soil gas sampling to evaluate to which extent tree coring may supplement or substitute soil gas sampling as a site contaminant screening tool. And where both methods are feasible, evaluate...

Reactions, accuracy and response complexity of numerical typing on touch screens.

Science.gov (United States)

Lin, Cheng-Jhe; Wu, Changxu

2013-01-01

Touch screens are popular nowadays as seen on public kiosks, industrial control panels and personal mobile devices. Numerical typing is one frequent task performed on touch screens, but this task on touch screen is subject to human errors and slow responses. This study aims to find innate differences of touch screens from standard physical keypads in the context of numerical typing by eliminating confounding issues. Effects of precise visual feedback and urgency of numerical typing were also investigated. The results showed that touch screens were as accurate as physical keyboards, but reactions were indeed executed slowly on touch screens as signified by both pre-motor reaction time and reaction time. Provision of precise visual feedback caused more errors, and the interaction between devices and urgency was not found on reaction time. To improve usability of touch screens, designers should focus more on reducing response complexity and be cautious about the use of visual feedback. The study revealed that slower responses on touch screens involved more complex human cognition to formulate motor responses. Attention should be given to designing precise visual feedback appropriately so that distractions or visual resource competitions can be avoided to improve human performance on touch screens.

The disposal of Canada's nuclear fuel waste: site screening and site evaluation technology

International Nuclear Information System (INIS)

Davison, C.C.; Brown, A.; Everitt, R.A.; Gascoyne, M.; Kozak, E.T.; Lodha, G.S.; Martin, C.D.; Soonawala, N.M.; Stevenson, D.R.; Thorne, G.A.; Whitaker, S.H.

1994-06-01

The concept for the disposal of Canada's nuclear fuel waste is to dispose of the waste in an underground vault, nominally at 500 m to 1000 m depth, at a suitable site in plutonic rock of the Canadian Shield. The feasibility of this concept and assessments of its impact on the environment and human health, will be documented by AECL in an Environmental Impact Statement (EIS). This report is one of nine primary references for the EIS. It describes the approach and methods that would be used during the siting stage of the disposal project to identify a preferred candidate disposal site and to confirm its suitability for constructing a disposal facility. The siting stage is divided into two distinct but closely related substages, site screening and site evaluation. Site screening would mainly involve reconnaissance investigations of siting regions of the Shield to identify potential candidate areas where suitable vault locations are likely to exist. Site screening would identify a small number of candidate areas where further detailed investigations were warranted. Site evaluation would involve progressively more detailed surface and subsurface investigations of the candidate areas to first identify potentially suitable vault locations within the candidate areas, and then characterize these potential disposal sites to identify the preferred candidate location for constructing the disposal vault. Site evaluation would conclude with the construction of exploratory shafts and tunnels at the preferred vault location, and underground characterization would be done to confirm the suitability of the preferred candidate site. An integrated program of geological, geophysical, hydrogeological, geochemical and geomechanical investigations would be implemented to obtain the geoscience information needed to assess the suitability of the candidate siting areas and candidate sites for locating a disposal vault. The candidate siting areas and candidate disposal vault sites would be

Detection of secondary binding sites in proteins using fragment screening.

Science.gov (United States)

Ludlow, R Frederick; Verdonk, Marcel L; Saini, Harpreet K; Tickle, Ian J; Jhoti, Harren

2015-12-29

Proteins need to be tightly regulated as they control biological processes in most normal cellular functions. The precise mechanisms of regulation are rarely completely understood but can involve binding of endogenous ligands and/or partner proteins at specific locations on a protein that can modulate function. Often, these additional secondary binding sites appear separate to the primary binding site, which, for example for an enzyme, may bind a substrate. In previous work, we have uncovered several examples in which secondary binding sites were discovered on proteins using fragment screening approaches. In each case, we were able to establish that the newly identified secondary binding site was biologically relevant as it was able to modulate function by the binding of a small molecule. In this study, we investigate how often secondary binding sites are located on proteins by analyzing 24 protein targets for which we have performed a fragment screen using X-ray crystallography. Our analysis shows that, surprisingly, the majority of proteins contain secondary binding sites based on their ability to bind fragments. Furthermore, sequence analysis of these previously unknown sites indicate high conservation, which suggests that they may have a biological function, perhaps via an allosteric mechanism. Comparing the physicochemical properties of the secondary sites with known primary ligand binding sites also shows broad similarities indicating that many of the secondary sites may be druggable in nature with small molecules that could provide new opportunities to modulate potential therapeutic targets.

Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.

Directory of Open Access Journals (Sweden)

Scott B Vafai

Full Text Available Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS. Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology.

Small molecule inhibitors of the LEDGF site of human immunodeficiency virus integrase identified by fragment screening and structure based design.

Directory of Open Access Journals (Sweden)

Thomas S Peat

Full Text Available A fragment-based screen against human immunodeficiency virus type 1 (HIV integrase led to a number of compounds that bound to the lens epithelium derived growth factor (LEDGF binding site of the integrase catalytic core domain. We determined the crystallographic structures of complexes of the HIV integrase catalytic core domain for 10 of these compounds and quantitated the binding by surface plasmon resonance. We demonstrate that the compounds inhibit the interaction of LEDGF with HIV integrase in a proximity AlphaScreen assay, an assay for the LEDGF enhancement of HIV integrase strand transfer and in a cell based assay. The compounds identified represent a potential framework for the development of a new series of HIV integrase inhibitors that do not bind to the catalytic site of the enzyme.

Cost-effective on-site screening for anaemia in pregnancy in primary ...

African Journals Online (AJOL)

syphilis serology. Results are returned days or weeks later depending on local circumstances.2 For some mobile clinics in rural areas, this delay may be as long as a month. On-site screening for ... probably anaemic still require a diagnostic test to determine ... accurate and cheap screening for and diagnosis of anaemia,.

A 6-year study of mammographic compression force: Practitioner variability within and between screening sites

International Nuclear Information System (INIS)

Mercer, Claire E.; Szczepura, Katy; Kelly, Judith; Millington, Sara R.; Denton, Erika R.E.; Borgen, Rita; Hilton, Beverley; Hogg, Peter

2015-01-01

Background: The application of compression force in mammography is more heavily influenced by the practitioner rather than the client. This can affect client experience, radiation dose and image quality. This research investigates practitioner compression force variation over a six year screening cycle in three different screening units. Methods: Data were collected from three consecutive screening events in three breast screening sites. Recorded data included: practitioner code, applied compression force (N), breast thickness (mm), BI-RADS ® density category. Exclusion criteria included: previous breast surgery, previous/ongoing assessment and breast implants. 975 clients (2925 client visits, 11,700 mammogram images) met inclusion criteria across three sites. Data analysis assessed practitioner and site variation of compression force and breast thickness. Results: Practitioners across three breast screening sites behave differently in the application of compression force. Two of the three sites demonstrate variability within themselves though they demonstrated no significant difference in mean, first and third quartile compression force and breast thickness values CC (p > 0.5), MLO (p > 0.1) between themselves. However, in the third site, where mandate dictates a minimum compression force is applied, greater consistency was demonstrated between practitioners and clients; a significant difference in mean, first and third quartile compression force and breast thickness values (p < 0.001) was demonstrated between this site and the other two sites. Conclusion: Variability within these two sites and between the three sites could result in variations. Stabilisation of these variations may have a positive impact on image quality, radiation dose reduction, re-attendance levels and potentially cancer detection. The large variation in compression forces could negatively impact on client experience between the units and within a unit. Further research is required to

Comparison of allele-specific PCR, created restriction-site PCR, and PCR with primer-introduced restriction analysis methods used for screening complex vertebral malformation carriers in Holstein cattle

Science.gov (United States)

Altınel, Ahmet

2017-01-01

Complex vertebral malformation (CVM) is an inherited, autosomal recessive disorder of Holstein cattle. The aim of this study was to compare sensitivity, specificity, positive and negative predictive values, accuracy, and rapidity of allele-specific polymerase chain reaction (AS-PCR), created restriction-site PCR (CRS-PCR), and PCR with primer-introduced restriction analysis (PCR-PIRA), three methods used in identification of CVM carriers in a Holstein cattle population. In order to screen for the G>T mutation in the solute carrier family 35 member A3 (SLC35A3) gene, DNA sequencing as the gold standard method was used. The prevalence of carriers and the mutant allele frequency were 3.2% and 0.016, respectively, among Holstein cattle in the Thrace region of Turkey. Among the three methods, the fastest but least accurate was AS-PCR. Although the rapidity of CRS-PCR and PCR-PIRA were nearly equal, the accuracy of PCR-PIRA was higher than that of CRS-PCR. Therefore, among the three methods, PCR-PIRA appears to be the most efficacious for screening of mutant alleles when identifying CVM carriers in a Holstein cattle population. PMID:28927256

Effects of organizational complexity and resources on construction site risk.

Science.gov (United States)

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.

Monitored Retrievable Storage facility site screening and evaluation report

International Nuclear Information System (INIS)

1985-05-01

The Nuclear Waste Policy Act of 1982 directs the Department of Energy to ''complete a detailed study of the need for and feasibility of, and to submit to the Congress a proposal for, the construction of one or more monitored retrievable storage facilities for high level radioactive waste and spent nuclear fuel.'' The Act directs that the proposal includes site specific designs. Further, the proposal is to include, ''for the first such facility, at least three alternative sites and at least five alternative combinations of such proposed sites and facility designs hor-ellipsis'' as well as a recommendation of ''the combination among the alternatives that the Secretary deems preferable.'' An MRS Site Screening Task Force has been formed to help identify and evaluate potential MRS facility sites within a preferred region and with the application of a siting process and criteria developed by the DOE. The activities of the Task Force presented in this report, all site evaluations (sections 13 through 16) where the rationale for the site evaluations are presented, along with each evaluation and findings of the Task Force. This is Volume 3 of a three volume document. References are also included in this volume

Monitored retrievable storage facility site screening and evaluation report

International Nuclear Information System (INIS)

1985-05-01

The Nuclear Waste Policy Act of 1982 directs the Department of Energy to ''complete a detailed study of the need for and feasibility of, and to submit to the Congress a proposal for, the construction of one or more monitored retrievable storage facilities for high level radioactive waste and spent nuclear fuel.'' The Act directs that the proposal includes site specific designs. Further, the proposal is to include, ''for the first such facility, at least three alternative sites and at least five alternative combinations of such proposed sites and facility designs hor-ellipsis'' as well as a recommendation of ''the combination among the alternatives that the Secretary deems preferable.'' An MRS Site Screening Task Force has been formed to help identify and evaluate potential MRS facility sites within a preferred region and with the application of a siting process and criteria developed by the DOE. The activities of the Task Force presented in this report include: site evaluations (sections 10 through 12) where the rationale for the site evaluations are presented, along with each evaluation and findings of the Task Force. This in Volume 2 of a three volume document

Monitored retrievable storage facility site screening and evaluation report

Energy Technology Data Exchange (ETDEWEB)

none,

1985-05-01

The Nuclear Waste Policy Act of 1982 directs the Department of Energy to complete a detailed study of the need for and feasibility of, and to submit to the Congress a proposal for, the construction of one or more monitored retrievable storage facilities for high level radioactive waste and spent nuclear fuel.'' The Act directs that the proposal includes site specific designs. Further, the proposal is to include, for the first such facility, at least three alternative sites and at least five alternative combinations of such proposed sites and facility designs{hor ellipsis}'' as well as a recommendation of the combination among the alternatives that the Secretary deems preferable.'' An MRS Site Screening Task Force has been formed to help identify and evaluate potential MRS facility sites within a preferred region and with the application of a siting process and criteria developed by the DOE. The activities of the Task Force presented in this report include: site evaluations (sections 10 through 12) where the rationale for the site evaluations are presented, along with each evaluation and findings of the Task Force. This in Volume 2 of a three volume document.

DARC 2.0: Improved Docking and Virtual Screening at Protein Interaction Sites.

Directory of Open Access Journals (Sweden)

Ragul Gowthaman

Full Text Available Over the past decade, protein-protein interactions have emerged as attractive but challenging targets for therapeutic intervention using small molecules. Due to the relatively flat surfaces that typify protein interaction sites, modern virtual screening tools developed for optimal performance against "traditional" protein targets perform less well when applied instead at protein interaction sites. Previously, we described a docking method specifically catered to the shallow binding modes characteristic of small-molecule inhibitors of protein interaction sites. This method, called DARC (Docking Approach using Ray Casting, operates by comparing the topography of the protein surface when "viewed" from a vantage point inside the protein against the topography of a bound ligand when "viewed" from the same vantage point. Here, we present five key enhancements to DARC. First, we use multiple vantage points to more accurately determine protein-ligand surface complementarity. Second, we describe a new scheme for rapidly determining optimal weights in the DARC scoring function. Third, we incorporate sampling of ligand conformers "on-the-fly" during docking. Fourth, we move beyond simple shape complementarity and introduce a term in the scoring function to capture electrostatic complementarity. Finally, we adjust the control flow in our GPU implementation of DARC to achieve greater speedup of these calculations. At each step of this study, we evaluate the performance of DARC in a "pose recapitulation" experiment: predicting the binding mode of 25 inhibitors each solved in complex with its distinct target protein (a protein interaction site. Whereas the previous version of DARC docked only one of these inhibitors to within 2 Å RMSD of its position in the crystal structure, the newer version achieves this level of accuracy for 12 of the 25 complexes, corresponding to a statistically significant performance improvement (p < 0.001. Collectively then, we find

Attitudes to Chlamydia screening elicited using the social networking site Facebook for subject recruitment.

Science.gov (United States)

Ahmed, Navera; Jayasinghe, Yasmin; Wark, John D; Fenner, Yeshe; Moore, Elya E; Tabrizi, Sepehr N; Fletcher, Ashley; Garland, Suzanne M

2013-07-01

Chlamydia (Chlamydia trachomatis) is the commonest bacterial sexually transmissible infection worldwide and contributes to significant morbidity in females. We examined potential barriers and facilitating factors for screening in young Victorian women, using the social networking site, Facebook to recruit participants. This was part of a larger study on young women's health that assessed the feasibility of using social networking sites for recruitment. An advertisement was placed on Facebook between May and September 2010, and was visible to eligible women. Women who clicked on the advertisement and expressed their interest in participating were invited to complete a questionnaire either at a study site or online. In total, 278 participants completed the survey, with 76% reporting willingness to participate in chlamydia screening by recruitment via an online system. Overall, 73% of participants indicated they were comfortable providing a urine sample collected at home for chlamydia screening, with older participants less comfortable with this method (P=0.02, odds ratio (OR)=0.09, 95% confidence interval (CI)=0.01-0.7). Participants expressed comfort with their Pap smear and chlamydia screening being performed together (92.7%), especially those who were aware of human papillomavirus (P<0.01, OR=2.5, 95% CI=1.3-4.7). This study demonstrated willingness by young Victorian women using Facebook to participate in screening for chlamydia. There was strong acceptance of self-collected sampling, and of combined chlamydia and cervical cytology screening. Facebook may therefore be a feasible way for improving screening coverage at a population level.

Early Detection and Screening for Breast Cancer.

Science.gov (United States)

Coleman, Cathy

2017-05-01

To review the history, current status, and future trends related to breast cancer screening. Peer-reviewed articles, web sites, and textbooks. Breast cancer remains a complex, heterogeneous disease. Serial screening with mammography is the most effective method to detect early stage disease and decrease mortality. Although politics and economics may inhibit organized mammography screening programs in many countries, the judicious use of proficient clinical and self-breast examination can also identify small tumors leading to reduced morbidity. Oncology nurses have exciting opportunities to lead, facilitate, and advocate for delivery of high-quality screening services targeting individuals and communities. A practical approach is needed to translate the complexities and controversies surrounding breast cancer screening into improved care outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Screened Coulomb interactions in metallic alloys. II. Screening beyond the single-site and atomic-sphere approximations

DEFF Research Database (Denmark)

Ruban, Andrei; Simak, S.I.; Korzhavyi, P.A.

2002-01-01

-electron potential and energy. In the case of a random alloy such interactions can be accounted for only by lifting the atomic-sphere and single-site approximations, in order to include the polarization due to local environment effects. Nevertheless, a simple parametrization of the screened Coulomb interactions...... for the ordinary single-site methods, including the generalized perturbation method, is still possible. We obtained such a parametrization for bulk and surface NiPt alloys, which allows one to obtain quantitatively accurate effective interactions in this system....

Distinguishing Binders from False Positives by Free Energy Calculations: Fragment Screening Against the Flap Site of HIV Protease

Science.gov (United States)

2015-01-01

Molecular docking is a powerful tool used in drug discovery and structural biology for predicting the structures of ligand–receptor complexes. However, the accuracy of docking calculations can be limited by factors such as the neglect of protein reorganization in the scoring function; as a result, ligand screening can produce a high rate of false positive hits. Although absolute binding free energy methods still have difficulty in accurately rank-ordering binders, we believe that they can be fruitfully employed to distinguish binders from nonbinders and reduce the false positive rate. Here we study a set of ligands that dock favorably to a newly discovered, potentially allosteric site on the flap of HIV-1 protease. Fragment binding to this site stabilizes a closed form of protease, which could be exploited for the design of allosteric inhibitors. Twenty-three top-ranked protein–ligand complexes from AutoDock were subject to the free energy screening using two methods, the recently developed binding energy analysis method (BEDAM) and the standard double decoupling method (DDM). Free energy calculations correctly identified most of the false positives (≥83%) and recovered all the confirmed binders. The results show a gap averaging ≥3.7 kcal/mol, separating the binders and the false positives. We present a formula that decomposes the binding free energy into contributions from the receptor conformational macrostates, which provides insights into the roles of different binding modes. Our binding free energy component analysis further suggests that improving the treatment for the desolvation penalty associated with the unfulfilled polar groups could reduce the rate of false positive hits in docking. The current study demonstrates that the combination of docking with free energy methods can be very useful for more accurate ligand screening against valuable drug targets. PMID:25189630

Functional Complexity and Web Site Design : Evaluating the Online Presence of UNESCO World Heritage Sites

NARCIS (Netherlands)

De Jong, Menno D.T.; Wu, Yuguang

2018-01-01

Functional complexity is a widespread and underresearched phenomenon in Web sites. This article explores a specific case of functional complexity by analyzing the content of UNESCO World Heritage Web sites, which have to meet demands from both World Heritage and tourism perspectives. Based on a

Prostate cancer guidelines on Web 2.0-based sites: the screening dilemma continues online.

Science.gov (United States)

Friedman, Daniela B; Koskan, Alexis; Rose, India D

2011-03-01

Little is known about prostate cancer (PrCA) screening information on participatory, interactive, and consumer-generated websites collectively referred to as Web 2.0. A content analysis was conducted of PrCA resources on four highly trafficked Web 2.0 social bookmarking sites. A total of 127 webpages were analyzed. Most content was from news websites (48.9%) and blogs (37.8%). PrCA screening was mentioned on 95.3% of pages; only 30.7% discussed the prostate-specific antigen test. Less than half (43.8%) mentioned current screening guidelines. PrCA content is inconsistent on Web 2.0 sites. Future research should assess the readability and usability of Web 2.0 cancer resources.

Computational discovery of picomolar Q(o) site inhibitors of cytochrome bc1 complex.

Science.gov (United States)

Hao, Ge-Fei; Wang, Fu; Li, Hui; Zhu, Xiao-Lei; Yang, Wen-Chao; Huang, Li-Shar; Wu, Jia-Wei; Berry, Edward A; Yang, Guang-Fu

2012-07-11

A critical challenge to the fragment-based drug discovery (FBDD) is its low-throughput nature due to the necessity of biophysical method-based fragment screening. Herein, a method of pharmacophore-linked fragment virtual screening (PFVS) was successfully developed. Its application yielded the first picomolar-range Q(o) site inhibitors of the cytochrome bc(1) complex, an important membrane protein for drug and fungicide discovery. Compared with the original hit compound 4 (K(i) = 881.80 nM, porcine bc(1)), the most potent compound 4f displayed 20 507-fold improved binding affinity (K(i) = 43.00 pM). Compound 4f was proved to be a noncompetitive inhibitor with respect to the substrate cytochrome c, but a competitive inhibitor with respect to the substrate ubiquinol. Additionally, we determined the crystal structure of compound 4e (K(i) = 83.00 pM) bound to the chicken bc(1) at 2.70 Å resolution, providing a molecular basis for understanding its ultrapotency. To our knowledge, this study is the first application of the FBDD method in the discovery of picomolar inhibitors of a membrane protein. This work demonstrates that the novel PFVS approach is a high-throughput drug discovery method, independent of biophysical screening techniques.

Uncertainty of mass discharge estimation from contaminated sites at screening level

DEFF Research Database (Denmark)

Thomsen, Nanna Isbak; Troldborg, M.; McKnight, Ursula S.

Contaminated sites threaten groundwater resources worldwide. The number of contaminated sites is large and there are too few economic resources available to ensure a thorough investigation and remediation of them all. Risk assessment must already be done at a screening level in order to ensure...... consider possible source and hydrogeological descriptions, where each model is believed to be a realistic representation of the given site, based on the current level of information. Parameter uncertainty is quantified using Monte Carlo simulations. For each conceptual model we calculate a transient mass...

U.S. Department of Energy's site screening, site selection, and initial characterization for storage of CO2 in deep geological formations

Science.gov (United States)

Rodosta, T.D.; Litynski, J.T.; Plasynski, S.I.; Hickman, S.; Frailey, S.; Myer, L.

2011-01-01

The U.S. Department of Energy (DOE) is the lead Federal agency for the development and deployment of carbon sequestration technologies. As part of its mission to facilitate technology transfer and develop guidelines from lessons learned, DOE is developing a series of best practice manuals (BPMs) for carbon capture and storage (CCS). The "Site Screening, Site Selection, and Initial Characterization for Storage of CO2 in Deep Geological Formations" BPM is a compilation of best practices and includes flowchart diagrams illustrating the general decision making process for Site Screening, Site Selection, and Initial Characterization. The BPM integrates the knowledge gained from various programmatic efforts, with particular emphasis on the Characterization Phase through pilot-scale CO2 injection testing of the Validation Phase of the Regional Carbon Sequestration Partnership (RCSP) Initiative. Key geologic and surface elements that suitable candidate storage sites should possess are identified, along with example Site Screening, Site Selection, and Initial Characterization protocols for large-scale geologic storage projects located across diverse geologic and regional settings. This manual has been written as a working document, establishing a framework and methodology for proper site selection for CO2 geologic storage. This will be useful for future CO2 emitters, transporters, and storage providers. It will also be of use in informing local, regional, state, and national governmental agencies of best practices in proper sequestration site selection. Furthermore, it will educate the inquisitive general public on options and processes for geologic CO2 storage. In addition to providing best practices, the manual presents a geologic storage resource and capacity classification system. The system provides a "standard" to communicate storage and capacity estimates, uncertainty and project development risk, data guidelines and analyses for adequate site characterization, and

Solid waste management complex site development plan

International Nuclear Information System (INIS)

Greager, T.M.

1994-01-01

The main purpose of this Solid Waste Management Complex Site Development Plan is to optimize the location of future solid waste treatment and storage facilities and the infrastructure required to support them. An overall site plan is recommended. Further, a series of layouts are included that depict site conditions as facilities are constructed at the SWMC site. In this respect the report serves not only as the siting basis for future projects, but provides siting guidance for Project W-112, as well. The plan is intended to function as a template for expected growth of the site over the next 30 years so that future facilities and infrastructure will be properly integrated

Solid waste management complex site development plan

Energy Technology Data Exchange (ETDEWEB)

Greager, T.M.

1994-09-30

The main purpose of this Solid Waste Management Complex Site Development Plan is to optimize the location of future solid waste treatment and storage facilities and the infrastructure required to support them. An overall site plan is recommended. Further, a series of layouts are included that depict site conditions as facilities are constructed at the SWMC site. In this respect the report serves not only as the siting basis for future projects, but provides siting guidance for Project W-112, as well. The plan is intended to function as a template for expected growth of the site over the next 30 years so that future facilities and infrastructure will be properly integrated.

Monitored Retrievable Storage facility site screening and evaluation report

Energy Technology Data Exchange (ETDEWEB)

none,

1985-05-01

The Nuclear Waste Policy Act of 1982 directs the Department of Energy to complete a detailed study of the need for and feasibility of, and to submit to the Congress a proposal for, the construction of one or more monitored retrievable storage facilities for high level radioactive waste and spent nuclear fuel.'' The Act directs that the proposal includes site specific designs. Further, the proposal is to include, for the first such facility, at least three alternative sites and at least five alternative combinations of such proposed sites and facility designs {hor ellipsis}'' as well as a recommendation of the combination among the alternatives that the Secretary deems preferable.'' An MRS Site Screening Task Force has been formed to help identify and evaluate potential MRS facility sites within a preferred region and with the application of a siting process and criteria developed by the DOE. The activities of the Task Force presented in this report, all site evaluations (sections 13 through 16) where the rationale for the site evaluations are presented, along with each evaluation and findings of the Task Force. This is Volume 3 of a three volume document. References are also included in this volume.

Virtual Screening of Receptor Sites for Molecularly Imprinted Polymers.

Science.gov (United States)

Bates, Ferdia; Cela-Pérez, María Concepción; Karim, Kal; Piletsky, Sergey; López-Vilariño, José Manuel

2016-08-01

Molecularly Imprinted Polymers (MIPs) are highly advantageous in the field of analytical chemistry. However, interference from secondary molecules can also impede capture of a target by a MIP receptor. This greatly complicates the design process and often requires extensive laboratory screening which is time consuming, costly, and creates substantial waste products. Herein, is presented a new technique for screening of "virtually imprinted receptors" for rebinding of the molecular template as well as secondary structures, correlating the virtual predictions with experimentally acquired data in three case studies. This novel technique is particularly applicable to the evaluation and prediction of MIP receptor specificity and efficiency in complex aqueous systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cell-based land use screening procedure for regional siting analysis

International Nuclear Information System (INIS)

Jalbert, J.S.; Dobson, J.E.

1976-01-01

An energy facility site-screening methodology which permits the land resource planner to identify candidate siting areas was developed. Through the use of spatial analysis procedures and computer graphics, a selection of candidate areas is obtained. Specific sites then may be selected from among candidate areas for environmental impact analysis. The computerized methodology utilizes a cell-based geographic information system for specifying the suitability of candidate areas for an energy facility. The criteria to be considered may be specified by the user and weighted in terms of importance. Three primary computer programs have been developed. These programs produce thematic maps, proximity calculations, and suitability calculations. Programs are written so as to be transferrable to regional planning or regulatory agencies to assist in rational and comprehensive power plant site identification and analysis

Identification of Multiple Druggable Secondary Sites by Fragment Screening against DC-SIGN.

Science.gov (United States)

Aretz, Jonas; Baukmann, Hannes; Shanina, Elena; Hanske, Jonas; Wawrzinek, Robert; Zapol'skii, Viktor A; Seeberger, Peter H; Kaufmann, Dieter E; Rademacher, Christoph

2017-06-12

DC-SIGN is a cell-surface receptor for several pathogenic threats, such as HIV, Ebola virus, or Mycobacterium tuberculosis. Multiple attempts to develop inhibitors of the underlying carbohydrate-protein interactions have been undertaken in the past fifteen years. Still, drug-like DC-SIGN ligands are sparse, which is most likely due to its hydrophilic, solvent-exposed carbohydrate-binding site. Herein, we report on a parallel fragment screening against DC-SIGN applying SPR and a reporter displacement assay, which complements previous screenings using 19 F NMR spectroscopy and chemical fragment microarrays. Hit validation by SPR and 1 H- 15 N HSQC NMR spectroscopy revealed that although no fragment bound in the primary carbohydrate site, five secondary sites are available to harbor drug-like molecules. Building on key interactions of the reported fragment hits, these pockets will be targeted in future approaches to accelerate the development of DC-SIGN inhibitors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Screening criteria of volcanic hazards aspect in the NPP site evaluation

International Nuclear Information System (INIS)

Nur Siwhan

2013-01-01

Studies have been conducted on the completeness of regulation in Indonesia particularly on volcanic hazards aspects in the evaluation of nuclear power plant site. Volcanic hazard aspect needed to identify potential external hazards that may endanger the safety of the operation of nuclear power plants. There are four stages for evaluating volcanic hazards, which are initial assessment, characterization sources of volcanic activity in the future, screening volcanic hazards and assessment of capable volcanic hazards. This paper discuss the third stage of the general evaluation which is the screening procedure of volcanic hazards. BAPETEN Chairman Regulation No. 2 Year of 2008 has only one screening criteria for missile volcanic phenomena, so it required screening criteria for other hazard phenomena that are pyroclastic flow density; lava flows; avalanche debris materials; lava; opening hole new eruptions, volcano missile; tsunamis; ground deformation; and hydrothermal system and ground water anomaly. (author)

High-Throughput and Rapid Screening of Low-Mass Hazardous Compounds in Complex Samples.

Science.gov (United States)

Wang, Jing; Liu, Qian; Gao, Yan; Wang, Yawei; Guo, Liangqia; Jiang, Guibin

2015-07-07

Rapid screening and identification of hazardous chemicals in complex samples is of extreme importance for public safety and environmental health studies. In this work, we report a new method for high-throughput, sensitive, and rapid screening of low-mass hazardous compounds in complex media without complicated sample preparation procedures. This method is achieved based on size-selective enrichment on ordered mesoporous carbon followed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analysis with graphene as a matrix. The ordered mesoporous carbon CMK-8 can exclude interferences from large molecules in complex samples (e.g., human serum, urine, and environmental water samples) and efficiently enrich a wide variety of low-mass hazardous compounds. The method can work at very low concentrations down to part per trillion (ppt) levels, and it is much faster and more facile than conventional methods. It was successfully applied to rapidly screen and identify unknown toxic substances such as perfluorochemicals in human serum samples from athletes and workers. Therefore, this method not only can sensitively detect target compounds but also can identify unknown hazardous compounds in complex media.

PATTERN BASED DETECTION OF POTENTIALLY DRUGGABLE BINDING SITES BY LIGAND SCREENING

Directory of Open Access Journals (Sweden)

Uttam Pal

2018-03-01

Full Text Available This article describes an innovative way of finding the potentially druggable sites on a target protein, which can be used for orthosteric and allosteric lead detection in a single virtual screening setup. Druggability estimation for an alternate binding site other than the canonical ligand-binding pocket of an enzyme is rewarding for several inherent benefits. Allostery is a direct and efficient way of regulating biomacromolecule function. The allosteric modulators can fine-tune protein mechanics. Besides, allosteric sites are evolutionarily less conserved/more diverse even in very similarly related proteins, thus, provides high degree of specificity in targeting a particular protein. Therefore, targeting of allosteric sites is gaining attention as an emerging strategy in rational drug design. However, the experimental approaches provide a limited degree of characterization of new allosteric sites. Computational approaches are useful to analyze and select potential allosteric sites for drug discovery. Here, the use of molecular docking, which has become an integral part of the drug discovery process, has been discussed to predict the druggability of novel allosteric sites as well as the active site on target proteins by ligand screening. Genetic algorithm was used for docking and the whole protein was placed in the search space. For each ligand in the library of small molecules, the genetic algorithm was run for multiple times to populate all the druggable sites in the target protein, which was then translated into two dimensional density maps or “patterns”. High density clusters were observed for lead like molecules in these pattern diagrams. Each cluster in such a pattern diagram indicated a plausible binding site and the density gave its druggability score in terms of weighted probabilities. The patterns were filtered to find the leads for each of the druggable sites on the target protein. Such a novel pattern based analysis of the

Land use suitability screening for power plant sites in Maryland

International Nuclear Information System (INIS)

Dobson, J.E.

1975-01-01

Since 1974 Oak Ridge National Laboratory (ORNL) has been engaged in developing an automated procedure for land use suitability screening. The Nuclear Regulatory Commission has funded the project to aid in the selection of power plant sites in Maryland. Its purpose is to identify candidate areas from which specific candidate sites can be chosen for detailed analyses. The ORNL approach assures that certain key variables are examined empirically for every cell in the study region before candidate sites are selected. Each variable is assigned an importance weight and compatibility score based upon its effect on the economic, social, or ecologic costs associated with construction in a given cell. The weighted scores for each variable are aggregated and output as a suitability score for each cell

An off-site screening process for the public in radiation emergencies and disasters

International Nuclear Information System (INIS)

Yoon, Seok Won; Ho, Ha Wi; Jin, Young Woo

2016-01-01

A contamination screening process for the local population in radiation emergencies is discussed. We present an overview of the relevant Korean governmental regulations that underpin the development of an effective response system. Moreover, case studies of foreign countries responding to mass casualties are presented, and indicate that responses should be able to handle a large demand for contamination screening of the local public as well as screening of the immediate victims of the incident. We propose operating procedures for an off-site contamination screening post operated by the local government for members of the public who have not been directly harmed in the accident. In order to devise screening categories, sorting strategies assessing contamination and exposure are discussed, as well as a psychological response system. This study will lead to the effective operation of contamination screening clinics if an accident occurs. Furthermore, the role of contamination screening clinics in the overall context of the radiation emergency treatment system should be clearly established

Rigorous Screening Technology for Identifying Suitable CO2 Storage Sites II

Energy Technology Data Exchange (ETDEWEB)

George J. Koperna Jr.; Vello A. Kuuskraa; David E. Riestenberg; Aiysha Sultana; Tyler Van Leeuwen

2009-06-01

This report serves as the final technical report and users manual for the 'Rigorous Screening Technology for Identifying Suitable CO2 Storage Sites II SBIR project. Advanced Resources International has developed a screening tool by which users can technically screen, assess the storage capacity and quantify the costs of CO2 storage in four types of CO2 storage reservoirs. These include CO2-enhanced oil recovery reservoirs, depleted oil and gas fields (non-enhanced oil recovery candidates), deep coal seems that are amenable to CO2-enhanced methane recovery, and saline reservoirs. The screening function assessed whether the reservoir could likely serve as a safe, long-term CO2 storage reservoir. The storage capacity assessment uses rigorous reservoir simulation models to determine the timing, ultimate storage capacity, and potential for enhanced hydrocarbon recovery. Finally, the economic assessment function determines both the field-level and pipeline (transportation) costs for CO2 sequestration in a given reservoir. The screening tool has been peer reviewed at an Electrical Power Research Institute (EPRI) technical meeting in March 2009. A number of useful observations and recommendations emerged from the Workshop on the costs of CO2 transport and storage that could be readily incorporated into a commercial version of the Screening Tool in a Phase III SBIR.

Diffusion of Sites versus Polymers in Polyelectrolyte Complexes and Multilayers.

Science.gov (United States)

Fares, Hadi M; Schlenoff, Joseph B

2017-10-18

It has long been assumed that the spontaneous formation of materials such as complexes and multilayers from charged polymers depends on (inter)diffusion of these polyelectrolytes. Here, we separately examine the mass transport of polymer molecules and extrinsic sites-charged polyelectrolyte repeat units balanced by counterions-within thin films of polyelectrolyte complex, PEC, using sensitive isotopic labeling techniques. The apparent diffusion coefficients of these sites within PEC films of poly(diallyldimethylammonium), PDADMA, and poly(styrenesulfonate), PSS, are at least 2 orders of magnitude faster than the diffusion of polyelectrolytes themselves. This is because site diffusion requires only local rearrangements of polyelectrolyte repeat units, placing far fewer kinetic limitations on the assembly of polyelectrolyte complexes in all of their forms. Site diffusion strongly depends on the salt concentration (ionic strength) of the environment, and diffusion of PDADMA sites is faster than that of PSS sites, accounting for the asymmetric nature of multilayer growth. Site diffusion is responsible for multilayer growth in the linear and into the exponential regimes, which explains how PDADMA can mysteriously "pass through" layers of PSS. Using quantitative relationships between site diffusion coefficient and salt concentration, conditions were identified that allowed the diffusion length to always exceed the film thickness, leading to full exponential growth over 3 orders of magnitude thickness. Both site and polymer diffusion were independent of molecular weight, suggesting that ion pairing density is a limiting factor. Polyelectrolyte complexes are examples of a broader class of dynamic bulk polymeric materials that (self-) assemble via the transport of cross-links or defects rather than actual molecules.

Rapid screening for nuclear genes mutations in isolated respiratory chain complex I defects.

Science.gov (United States)

Pagniez-Mammeri, Hélène; Lombes, Anne; Brivet, Michèle; Ogier-de Baulny, Hélène; Landrieu, Pierre; Legrand, Alain; Slama, Abdelhamid

2009-04-01

Complex I or reduced nicotinamide adenine dinucleotide (NADH): ubiquinone oxydoreductase deficiency is the most common cause of respiratory chain defects. Molecular bases of complex I deficiencies are rarely identified because of the dual genetic origin of this multi-enzymatic complex (nuclear DNA and mitochondrial DNA) and the lack of phenotype-genotype correlation. We used a rapid method to screen patients with isolated complex I deficiencies for nuclear genes mutations by Surveyor nuclease digestion of cDNAs. Eight complex I nuclear genes, among the most frequently mutated (NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS7, NDUFS8, NDUFV1 and NDUFV2), were studied in 22 cDNA fragments spanning their coding sequences in 8 patients with a biochemically proved complex I deficiency. Single nucleotide polymorphisms and missense mutations were detected in 18.7% of the cDNA fragments by Surveyor nuclease treatment. Molecular defects were detected in 3 patients. Surveyor nuclease screening is a reliable method for genotyping nuclear complex I deficiencies, easy to interpret, and limits the number of sequence reactions. Its use will enhance the possibility of prenatal diagnosis and help us for a better understanding of complex I molecular defects.

Comparison of three field screening techniques for delineating petroleum hydrocarbon plumes in groundwater at a site in the southern Carson Desert, Nevada

International Nuclear Information System (INIS)

Smuin, D.R.

1993-01-01

Three types of field screening techniques used in the characterization of potentially contaminated sites at Naval Air Station Fallon, Nevada, are compared. The methods and results for each technique are presented. The three techniques include soil-gas surveys, electromagnetic geophysical surveys, and groundwater test hole screening. Initial screening at the first study site included two soil-gas surveys and electromagnetic geophysical studies. These screening methods identified I areas of contamination; however, results were inconclusive. Therefore groundwater test hole screening was performed. Groundwater screening consisted of auger drilling down to the shallow alluvial aquifer. Groundwater samples were collected from the open drill hole with a bailer. On-site head-space analyses for volatile organic compounds (VOCS) were performed using a portable gas chromatograph (GC). Five areas of floating petroleum hydrocarbon product were identified along with the overall dissolved contaminant plume boundaries. Well placement was re-evaluated, and well sites were relocated based on the screening information. The most effective technique for identification of petroleum hydrocarbon-contaminant plumes was groundwater test hole screening. Groundwater screening was subsequently performed at 19 other sites. A total of 450 test holes were analyzed resulting in the delineation of six plumes

Method for screening the Nevada Test Site and contiguous areas for nuclear waste repository locations

International Nuclear Information System (INIS)

Sinnock, S.; Fernandez, J.A.; Neal, J.T.; Stephens, H.P.; Hartway, B.L.; Los Alamos Technical Associates, Inc., NM)

1982-01-01

This paper outlines the general concepts of a technical method for systematic screening of the Nevada Test Site (NTS), Nye County, Nevada, for potentially suitable nuclear waste repository locations. After a general discussion of the organization and the purpose of the current screening activity, the paper addresses the steps of the screening method. These steps include: hierarchically organizing technical objectives for repository performance (an objectives tree); identifying and mapping pertinent physical characteristics of a site and its setting (physical attributes); relating the physical conditions to the objectives (favorability curves); identifying alternative locations and numerically evaluating their relative merits; investigating the effects of subjective judgments on the evaluations (sensitivity analyses); documenting the assumptions, logic, and results of the method. 19 references, 10 figures

Statistical screening of input variables in a complex computer code

International Nuclear Information System (INIS)

Krieger, T.J.

1982-01-01

A method is presented for ''statistical screening'' of input variables in a complex computer code. The object is to determine the ''effective'' or important input variables by estimating the relative magnitudes of their associated sensitivity coefficients. This is accomplished by performing a numerical experiment consisting of a relatively small number of computer runs with the code followed by a statistical analysis of the results. A formula for estimating the sensitivity coefficients is derived. Reference is made to an earlier work in which the method was applied to a complex reactor code with good results

Band-selective excited ultrahigh resolution PSYCHE-TOCSY: fast screening of organic molecules and complex mixtures.

Science.gov (United States)

Kakita, Veera Mohana Rao; Vemulapalli, Sahithya Phani Babu; Bharatam, Jagadeesh

2016-04-01

Precise assignments of (1) H atomic sites and establishment of their through-bond COSY or TOCSY connectivity are crucial for molecular structural characterization by using (1) H NMR spectroscopy. However, this exercise is often hampered by signal overlap, primarily because of (1) H-(1) H scalar coupling multiplets, even at typical high magnetic fields. The recent developments in homodecoupling strategies for effectively suppressing the coupling multiplets into nice singlets (pure-shift), particularly, Morris's advanced broadband pure-shift yielded by chirp excitation (PSYCHE) decoupling and ultrahigh resolution PSYCHE-TOCSY schemes, have shown new possibilities for unambiguous structural elucidation of complex organic molecules. The superior broadband PSYCHE-TOCSY exhibits enhanced performance over the earlier TOCSY methods, which however warrants prolonged experimental times due to the requirement of large number of dwell increments along the indirect dimension. Herein, we present fast and band-selective analog of the broadband PSYCHE-TOCSY, which is useful for analyzing complex organic molecules that exhibit characteristic yet crowded spectral regions. The simple pulse scheme relies on band-selective excitation (BSE) followed by PSYCHE homodecoupling in the indirect dimension. The BSE-PSYCHE-TOCSY has been exemplified for Estradiol and a complex carbohydrate mixture comprised of six constituents of closely comparable molecular weights. The experimental times are greatly reduced viz., ~20 fold for Estradiol and ~10 fold for carbohydrate mixture, with respect to the broadband PSYCHE-TOCSY. Furthermore, unlike the earlier homonuclear band-selective decoupling, the BSE-PSYCHE-decoupling provides fully decoupled pure-shift spectra for all the individual chemical sites within the excited band. The BSE-PSYCHE-TOCSY is expected to have significant potential for quick screening of complex organic molecules and mixtures at ultrahigh resolution. Copyright © 2015 John Wiley

Cardiac Arrhythmia: In vivo screening in the zebrafish to overcome complexity in drug discovery.

Science.gov (United States)

Macrae, Calum A

2010-07-01

IMPORTANCE OF THE FIELD: Cardiac arrhythmias remain a major challenge for modern drug discovery. Clinical events are paroxysmal, often rare and may be asymptomatic until a highly morbid complication. Target selection is often based on limited information and though highly specific agents are identified in screening, the final efficacy is often compromised by unanticipated systemic responses, a narrow therapeutic index and substantial toxicities. AREAS COVERED IN THIS REVIEW: Our understanding of complexity of arrhythmogenesis has grown dramatically over the last two decades, and the range of potential disease mechanisms now includes pathways previously thought only tangentially involved in arrhythmia. This review surveys the literature on arrhythmia mechanisms from 1965 to the present day, outlines the complex biology underlying potentially each and every rhythm disturbance, and highlights the problems for rational target identification. The rationale for in vivo screening is described and the utility of the zebrafish for this approach and for complementary work in functional genomics is discussed. Current limitations of the model in this setting and the need for careful validation in new disease areas are also described. WHAT THE READER WILL GAIN: An overview of the complex mechanisms underlying most clinical arrhythmias, and insight into the limits of ion channel conductances as drug targets. An introduction to the zebrafish as a model organism, in particular for cardiovascular biology. Potential approaches to overcoming the hurdles to drug discovery in the face of complex biology including in vivo screening of zebrafish genetic disease models. TAKE HOME MESSAGE: In vivo screening in faithful disease models allows the effects of drugs on integrative physiology and disease biology to be captured during the screening process, in a manner agnostic to potential drug target or targets. This systematic strategy bypasses current gaps in our understanding of disease

Proteomic screen for multiprotein complexes in synaptic plasma membrane from rat hippocampus by blue native gel electrophoresis and tandem mass spectrometry.

Science.gov (United States)

Li, Xuanwen; Xie, Chunliang; Jin, Qihui; Liu, Mingjun; He, Quanyuan; Cao, Rui; Lin, Yong; Li, Jianglin; Li, Yan; Chen, Ping; Liang, Songping

2009-07-01

Neuronal synapses are specialized sites for information exchange between neurons. Many diseases, such as addiction and mood disorders, likely result from altered expression of synaptic proteins, or altered formation of synaptic complexes involved in neurotransmission or neuroplasticity. A detailed description of native multiprotein complexes in synaptic plasma membranes (PM) is therefore essential for understanding biological mechanisms and disease processes. For the first time in this study, two-dimensional Blue Native/SDS-PAGE electrophoresis, combined with tandem mass spectrometry, was used to screen multiprotein complexes in synaptic plasma membranes from rat hippocampus. As a result, 514 unique proteins were identified, of which 36% were integral membrane proteins. In addition, 19 potentially novel and known heterooligomeric multiprotein complexes were found, such as the SNARE and ATPase complexes. A potentially novel protein complex, involving syntaxin, synapsin I and Na+/K+ ATPase alpha-1, was further confirmed by co-immunoprecipitation and immunofluorescence staining. As demonstrated here, Blue Native-PAGE is a powerful tool for the separation of hydrophobic membrane proteins. The combination of Blue Native-PAGE and mass spectrometry could systematically identify multiprotein complexes.

Performance Potential at one Complex, Specific Site

DEFF Research Database (Denmark)

Laursen, Bjørn

2015-01-01

disciplines: performance, drama, dance and music. Complex rules of “borders” between audience and actors/performers appeared to be present and active during this long happening. Different narrative genres were active simultaneously during the experimental session. A lot of complex and surprising phenomena...... and combinations of spatial, dramaturgical, narrative and interactive challenges, which appear to be of special interest for the kind of experiences an audience might gather in a site like this, originally created with totally different intentions. Or was it?...

Genomic screening for dissection of a complex disease: The multiple sclerosis phenotype

Energy Technology Data Exchange (ETDEWEB)

Haines, J.L.; Bazyk, A.; Gusella, J.F. [Massachusetts General Hospital, Boston, MA (United States)] [and others

1994-09-01

Application of positional cloning to diseases with a complex etiology is fraught with problems. These include undefined modes of inheritance, heterogeneity, and epistasis. Although microsatellite markers now make genotyping the genome a straightforward task, no single analytical method is available to efficiently and accurately use these data for a complex disease. We have developed a multi-stage genomic screening strategy which uses a combination of non-parametric approaches (Affected Pedigree Member (APM) linkage analysis and robust sib pair analysis (SP)), and the parametric lod score approach (using four different genetic models). To warrant follow-up, a marker must have two or more of: a nominal P value of 0.05 or less on the non-parametric tests, or a lod score greater than 1.0 for any model. Two adjacent markers each fulfilling one criterion are also considered for follow-up. These criteria were determined both by simulation studies and our empirical experience in screening a large number of other disorders. We applied this approach to multiple sclerosis (MS), a complex neurological disorder with a strong but ill-defined genetic component. Analysis of the first 91 markers from our screen of 55 multiplex families found 5 markers which met the SP criteria, 13 markers which met the APM criteria, and 8 markers which met the lod score criteria. Five regions (on chromosomes 2, 4, 7, 14, and 19) met our overall criteria. However, no single method identified all of these regions, suggesting that each method is sensitive to various (unknown) influences. The chromosome 14 results were not supported by follow-up typing and analysis of markers in that region, but the chromosome 19 results remain well supported. Updated screening results will be presented.

A GIS based screening tool for locating and ranking of suitable stormwater harvesting sites in urban areas.

Science.gov (United States)

Inamdar, P M; Cook, S; Sharma, A K; Corby, N; O'Connor, J; Perera, B J C

2013-10-15

There is the need to re-configure current urban water systems to achieve the objective of sustainable water sensitive cities. Stormwater represents a valuable alternative urban water source to reduce pressure on fresh water resources, and to mitigate the environmental impact of urban stormwater runoff. The selection of suitable urban stormwater harvesting sites is generally based on the judgement of water planners, who are faced with the challenge of considering multiple technical and socio-economic factors that influence the site suitability. To address this challenge, the present study developed a robust GIS based screening methodology for identifying potentially suitable stormwater harvesting sites in urban areas as a first pass for then more detailed investigation. The study initially evaluated suitability based on the match between harvestable runoff and demand through a concept of accumulated catchments. Drainage outlets of these accumulated catchments were considered as potential stormwater harvesting sites. These sites were screened and ranked under screening parameters namely demand, ratio of runoff to demand and weighted demand distance. The methodology described in this paper was successfully applied to a case study in Melbourne, Australia in collaboration with the local water utility. The methodology was found to be effective in supporting the selection of priority sites for stormwater harvesting schemes, as it provided the basis to identify, short-list and rank sites for further detailed investigation. The rapid identification of suitable sites for stormwater harvesting can assist planners in prioritising schemes in areas that will have the most impact on reducing potable water demand. Copyright © 2013 Elsevier Ltd. All rights reserved.

Implementation of a DOD ELAP Conforming Quality System at a FUSRAP Site Field Temporary Radiological Screening Laboratory - 13500

International Nuclear Information System (INIS)

Winters, M.S.; McElheny, G.; Houston, L.M.; Masset, M.R.; Spector, H.L.

2013-01-01

A case study is presented on specific program elements that supported the transition of a temporary field radiological screening lab to an accredited operation capable of meeting client quality objectives for definitive results data. The temporary field lab is located at the Formerly Utilized Sites Remedial Action Program Linde Site in Tonawanda, NY. The site is undergoing remediation under the direction of the United States Army Corps of Engineers - Buffalo District, with Cabrera Services Inc. as the remediation contractor and operator of the on-site lab. Analysis methods employed in the on-site lab include gross counting of alpha and beta particle activity on swipes and air filters and gamma spectroscopy of soils and other solid samples. A discussion of key program elements and lessons learned may help other organizations considering pursuit of accreditation for on-site screening laboratories. (authors)

CHRONIC ZINC SCREENING WATER EFFECT RATIO FOR THE H-12 OUTFALL, SAVANNAH RIVER SITE

Energy Technology Data Exchange (ETDEWEB)

Coughlin, D.; Looney, B.; Millings, M.

2009-01-13

In response to proposed Zn limits for the NPDES outfall H-12, a Zn screening Water Effects Ratio (WER) study was conducted to determine if a full site-specific WER is warranted. Using standard assumptions for relating the lab results to the stream, the screening WER data were consistent with the proposed Zn limit and suggest that a full WER would result in a similar limit. Addition of a humate amendment to the outfall water reduced Zn toxicity, but the toxicity reduction was relatively small and unlikely to impact proposed Zn limits. The screening WER data indicated that the time and expense required to perform a full WER for Zn is not warranted.

Hydrology and Oceanography Analysis Regarding The NPP Site Screening Process at Banten Province

International Nuclear Information System (INIS)

Yarianto-S-Budi-Susilo

2007-01-01

Regarding the NPP development in the future, it is needed to make inventory of potential site in the Java Island as well as in the outside Java Island. The NPP site inventory availability is to answer the energy demand challenge. Site screening process should be performed in accordance with the IAEA safety standard regarding the site selection, investigating several aspects related to the NPP safety (exclusion, safety and suitability factor) in the large area to obtain potential site candidates. For the site survey stage of hydrology and oceanography aspects, the analysis are more focused on the tidal phenomena along the north coastline, bathymetry, water resource, and hydrology system in the Banten Province. The method used are secondary data collection, field confirmation and internet searching. The result of the study showed that Tanjung Pujut and Tanjung Pasir are suitable based on the bathymetry and water intake facility consideration. Meanwhile Tanjung Kait and Tanjung Pasir more suitable considering tsunami aspects that may be generated by Krakatau Volcano. (author)

Identification and screening of hazards for the external event PRA - External hazard identification, screening and studies for a new plant site

International Nuclear Information System (INIS)

Hellander, Juho

2014-01-01

Fennovoima is constructing a new nuclear power plant on a greenfield site in Northern Finland. Various evaluations for site-specific hazards are needed to ensure sufficient plant design basis values, proper design solutions and to provide input for the PRA model. This paper presents the general process used in identifying the relevant site-specific external hazards. The applicable legislative requirements, guides and standards regarding external hazards and external event PRA shall be identified. Based on these, an initial comprehensive list of events should be compiled. The initial list shall be filtered to exclude irrelevant events. Events can be screened out if the probability is very low or if the consequences are only mild. Events with similar consequences should be combined. Events can be grouped in several ways, and in this paper the risks are categorized into events related to air, water bodies, ground and human behaviour. In addition, the simultaneously occurring combinations of events should be identified. The paper also summarizes some hazard studies already performed and required in the future in Fennovoima's project. A comprehensive study is ongoing related to earthquake risks. The study aims at identifying all relevant seismic sources and taking into account various expert opinions in seismic modelling. Also frazil ice and anchor ice studies are being performed to eliminate the risk of cooling water intake blockage due to ice. In addition, some other study areas are mentioned. This paper presented a list of Finnish and international guides and standards useful in evaluating external hazards. Also a methodology was presented to identify and screen site-specific hazards in a new nuclear power plant project. The screened list of relevant events for the Hanhikivi site requiring further studies was presented. Also the studies needed in different phases of a new nuclear power plant project were discussed. Some specific studies regarding earthquakes and

Evaluation of geochemical properties used in area-to-location screening for a nuclear waste repository at the Nevada Test Site

International Nuclear Information System (INIS)

Purson, J.D.

1983-03-01

The area-to-location screening of a potential site for a nuclear waste repository is dependent on geologic compatibility. Specifically, the geochemical properties of candidate locations are significant in the overall site evaluation. This report describes three geochemical factors or attributes and their application to an area-to-location screening of the southwestern quadrant of the Nevada Test Site and contiguous areas. These are only 3 of 31 attributes examined in the screening process. Geochemical and rock media considerations relevant to site screening include: (1) retardation by hydraulics - a study of ground-water movement through fractures vs a permeable matrix; (2) thermal stability of minerals - a measurement of undesirable mineral assemblages in the rock; and (3) retardation by sorption - an evaluation of the total sorptive capacity at a location, based on stratigraphy and lithology. Twelve potential host rocks situated in 20 locations are examined; 2 of these have consistently fewer favorable characteristics, and 6 others have generally fewer favorable characteristics than the 4 remaining rock units. The four units that appear most favorable by geochemical measures are the tuffaceous beds of Calico Hills, granite intrusives, the densely welded Topopah Spring tuff, and the Crater Flat Tuff at Yucca Mountain

Automated NMR fragment based screening identified a novel interface blocker to the LARG/RhoA complex.

Directory of Open Access Journals (Sweden)

Jia Gao

Full Text Available The small GTPase cycles between the inactive GDP form and the activated GTP form, catalyzed by the upstream guanine exchange factors. The modulation of such process by small molecules has been proven to be a fruitful route for therapeutic intervention to prevent the over-activation of the small GTPase. The fragment based approach emerging in the past decade has demonstrated its paramount potential in the discovery of inhibitors targeting such novel and challenging protein-protein interactions. The details regarding the procedure of NMR fragment screening from scratch have been rarely disclosed comprehensively, thus restricts its wider applications. To achieve a consistent screening applicable to a number of targets, we developed a highly automated protocol to cover every aspect of NMR fragment screening as possible, including the construction of small but diverse libray, determination of the aqueous solubility by NMR, grouping compounds with mutual dispersity to a cocktail, and the automated processing and visualization of the ligand based screening spectra. We exemplified our streamlined screening in RhoA alone and the complex of the small GTPase RhoA and its upstream guanine exchange factor LARG. Two hits were confirmed from the primary screening in cocktail and secondary screening over individual hits for LARG/RhoA complex, while one of them was also identified from the screening for RhoA alone. HSQC titration of the two hits over RhoA and LARG alone, respectively, identified one compound binding to RhoA.GDP at a 0.11 mM affinity, and perturbed the residues at the switch II region of RhoA. This hit blocked the formation of the LARG/RhoA complex, validated by the native gel electrophoresis, and the titration of RhoA to ¹⁵N labeled LARG in the absence and presence the compound, respectively. It therefore provides us a starting point toward a more potent inhibitor to RhoA activation catalyzed by LARG.

Screening of extremotolerant fungi for the bioremediation of hydrocarbon contaminated sites

Science.gov (United States)

Poyntner, Caroline; Blasi, Barbara; Prenafeta, Francesc; Sterflinger, Katja

2015-04-01

Bioremediation can be used to treat contaminated sites, by taking advantage of microorganisms which have the potential to degrade a wide range of contaminants. While research has been focused mainly on bacteria, the knowledge on other microorganisms, especially fungal communities, is still limited. However, the use of fungi may have advantages compared to bacteria. Extremophile fungi like the black yeasts can withstand high levels of environmental stress (e.g. range of pH, water availability and temperature, presence of toxic chemicals). Therefore they might be applicable in situations, where bacterial communities show limited performance. In order to identify fungi which are good candidates for bioremediation application, a selection of 163 fungal strains, mostly from the group of the black yeasts, was tested for their capability to degrade three different pollutants: hexadecane, toluene, and polychlorinated biphenyl 126, which were used as model compounds for aliphatic hydrocarbons, aromatic hydrocarbons and polychlorinated biphenyls. These chemicals are frequently found in sites contaminated by oil, gas and coal. The screening was based on a two-step selection approach. As a first step, a high throughput method was developed to screen the relatively large amount of fungal strains regarding their tolerance to the contaminants. A microtiter plate based method was developed for monitoring fungal growth in the presence of the selected contaminants photometrically with a Tecan reader. Twenty five strains out of 163, being species of the genera Cladophilaophora, Scedosporium and Exophiala, showed the ability to grow on at least 2 hydrocarbons, and are therefore the most promising candidates for further tests. In a second step, degradation of the contaminants was investigated in more detail for a subset of the screened fungi. This was done by closing the carbon balance in sealed liquid cultures in which the selected pollutant was introduce as the sole source of carbon

Preliminary screening analysis of the off-site environment downstream of the US Department of Energy Oak Ridge Reservation

International Nuclear Information System (INIS)

Blaylock, B.G.; Hoffman, F.O.; Frank, M.L.

1990-01-01

Operations and waste disposal activities at the Y-12 Plant, the Oak Ridge National Laboratory (ORNL), and the Oak Ridge Gaseous Diffusion Plant (ORGDP), located on the US Department of Energy (DOE) Oak Ridge Reservation (ORR) in eastern Tennessee, have introduced airborne, liquid, and solid wastes into the surrounding environment. Some of these wastes may affect off-site areas by entering local streams that ultimately drain into the Clinch River. Previously reported concentrations of radionuclides, metals, and organic compounds in water, sediment, and biota of the Clinch River and Watts Bar Reservoir suggest the presence of contaminants of possible concern to the protection of human health and the environment. A preliminary screening was conducted of contaminants in the off-site surface water environments downstream of the DOE ORR. This screening analysis represents part of a scoping phase of the Clinch River Resource Conservation and Recovery Facilities Investigation (CRRFI). The purpose of this preliminary screening analysis is to use existing data on off-site contaminant concentrations to identify and prioritize potential contaminants of concern for further evaluation and investigation. The primary objective of this screening analysis is to ensure that CRRFI sampling and analysis efforts focus on those contaminants that may possibly contribute to human health or environmental risk. 8 refs., 3 figs., 6 tabs

Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites

Science.gov (United States)

Brautigam, Chad A; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K; Walz, Thomas

2017-01-01

The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly. PMID:28949297

Optimal number of coarse-grained sites in different components of large biomolecular complexes.

Science.gov (United States)

Sinitskiy, Anton V; Saunders, Marissa G; Voth, Gregory A

2012-07-26

The computational study of large biomolecular complexes (molecular machines, cytoskeletal filaments, etc.) is a formidable challenge facing computational biophysics and biology. To achieve biologically relevant length and time scales, coarse-grained (CG) models of such complexes usually must be built and employed. One of the important early stages in this approach is to determine an optimal number of CG sites in different constituents of a complex. This work presents a systematic approach to this problem. First, a universal scaling law is derived and numerically corroborated for the intensity of the intrasite (intradomain) thermal fluctuations as a function of the number of CG sites. Second, this result is used for derivation of the criterion for the optimal number of CG sites in different parts of a large multibiomolecule complex. In the zeroth-order approximation, this approach validates the empirical rule of taking one CG site per fixed number of atoms or residues in each biomolecule, previously widely used for smaller systems (e.g., individual biomolecules). The first-order corrections to this rule are derived and numerically checked by the case studies of the Escherichia coli ribosome and Arp2/3 actin filament junction. In different ribosomal proteins, the optimal number of amino acids per CG site is shown to differ by a factor of 3.5, and an even wider spread may exist in other large biomolecular complexes. Therefore, the method proposed in this paper is valuable for the optimal construction of CG models of such complexes.

Network Screening for Smarter Road Sites: A Regional Case

Directory of Open Access Journals (Sweden)

Attila Grieco

2014-05-01

Full Text Available Road safety has been a main societal and policy issue in many European countries since the early years of last decade. After the 2000-2010 Road Safety Programme launched by the European Commission, in 2011 the Commission adopted the new 2020 programme, even more demanding than the previous. As the societal consequences of road casualties are increasingly perceived as a core dimension of smart mobility, road safety system is now facing new challenges. Current mobility shifts to softer and greener transportation means raise new safety concerns for an increasingly larger share of vulnerable road users. The need to integrate road safety requirements with other residential, mobility, and environmental policies calls for a more detailed understanding of the phenomenon at different spatial levels and with different observation lenses. The pilot study described in this paper is a contribution to this end. It aims at identifying the accident prone sites of the regional road network to help prioritizing safety interventions, by the regional administration having road planning responsibilities. The study develops a screening approach to select hazardous road locations, outside urban premises, from the Piedmont provincial and state roads. The most recent data for the 2010-2012 years were considered, drawn from the ISTAT road accident database, managed by the CMRSS. The procedure consists of the following steps: identification of the elementary road sections to be screened, through a GIS analysis; definition of the screening groups (road sections have been subdivided in 4 length classes; definition of the selection criteria, with two severity thresholds based on the crash density; classification of the elementary road sections by severity thresholds.

Online information about risks and benefits of screening mammography in 10 European countries: An observational Web sites analysis.

Science.gov (United States)

Spagnoli, Laura; Navaro, Monica; Ferrara, Pietro; Del Prete, Viola; Attena, Francesco

2018-06-01

Most publications about breast cancer do not provide accurate and comprehensive information, giving few or no data about risk/benefit ratios. We conducted a comparative study among 10 European countries about health information on breast cancer screening, assessing the first 10 Web sites addressing the general public that appeared following an Internet search.With the help of medical residents involved in the EuroNet MRPH Association, we analyzed the first 30 results of an Internet search in 10 European countries to determine the first 10 sites that offered screening mammography. We searched for the following information: source of information, general information on mammography and breast cancer screening, potential harms and risks (false positives, false positives after biopsy, false negatives, interval cancer, overdiagnosis, lead-time bias, and radiation exposure), and potential benefits (reduced mortality and increased survival).The United Kingdom provided the most information: 39 of all 70 possible identified risks (56%) were reported on its sites. Five nations presented over 35% of the possible information (United Kingdom, Spain, France, Ireland, and Italy); the others were under 30% (Portugal, Poland, Slovenia, Netherlands, and Croatia). Regarding the benefits, sites offering the most complete information were those in France (95%) and Poland (90%).Our results suggest that, despite consensus in the scientific community about providing better information to citizens, further efforts are needed to improve information about breast cancer screening. That conclusion also applies to countries showing better results. We believe that there should be greater coordination in this regard throughout Europe.

Model synthetic complexes of the hydrogenase with different protonation sites; Complexes synthetiques modeles de l'hydrogenase avec differents sites de protonation

Energy Technology Data Exchange (ETDEWEB)

Capon, J.F.; Gloaguen, F.; Morvan, D.; Schollhammer, Ph.; Talarmin, J.; Yaouanc, J.J. [Universite de Bretagne Occidentale, UMR CNRS 6521, Chimie, Electrochimie Moleculaires et Chimie Analytique, Faculte des Sciences, 29 - Brest (France)

2005-07-01

The data obtained until now seem to indicate that the hydrogen production by hydrogenases induces a proton-hydride coupling. In taking the structures of theses enzymes active sites (determined by X-ray diffraction) as a basis, it can be thought that this proton-hydride coupling is facilitated by the juxtaposition of two protonation sites, the metallic center M and the basic group of an E ligand of the coordination sphere. Contrarily to the supposed running of the hydrogenases enzymes, the homogeneous catalysts of the protons reduction, described in the literature, present a reactivity which is either on an alone metallic site or on a metal-metal bond. This work deals then with the preparation of complexes having two juxtaposed protonation sites. Some iron dinuclear compounds have been synthesized and their properties studied. (O.M.)

A cost-saving statistically based screening technique for focused sampling of a lead-contaminated site

International Nuclear Information System (INIS)

Moscati, A.F. Jr.; Hediger, E.M.; Rupp, M.J.

1986-01-01

High concentrations of lead in soils along an abandoned railroad line prompted a remedial investigation to characterize the extent of contamination across a 7-acre site. Contamination was thought to be spotty across the site reflecting its past use in battery recycling operations at discrete locations. A screening technique was employed to delineate the more highly contaminated areas by testing a statistically determined minimum number of random samples from each of seven discrete site areas. The approach not only quickly identified those site areas which would require more extensive grid sampling, but also provided a statistically defensible basis for excluding other site areas from further consideration, thus saving the cost of additional sample collection and analysis. The reduction in the number of samples collected in ''clean'' areas of the site ranged from 45 to 60%

Screening and identification of sites for a proposed Monitored Retrievable Storage Facility

International Nuclear Information System (INIS)

1985-04-01

The Director, Office of Civilian Radioactive Waste Management (OCRWM), Department of Energy (DOE), has identified the Clinch River Breeder Reactor site, the DOE Oak Ridge Reservation and the Tennessee Valley Authority (TVA) Hartsville Nuclear Plant site as preferred and alternative sites, respectively, for development of site-specific designs as part of the proposal for construction of an integrated Monitored Retrievable Storage (MRS) Facility. The proposal, developed pursuant to Section 141 (b) of the Nuclear Waste Policy Act of 1982, will be submitted to Congress in January 1986. The Director expects to propose to Congress that an MRS be constructed at the perferred site. His judgment could change based on information to be developed between now and January 1986. The decision to construct an MRS facility and final site selection are reserved by Congress for itself. The Director's judgment is based on the results of a rigorous site screening and evaluation process described in this report. The three sites were selected from among eleven sites evaluated in detail. The Clinch River Breeder Reactor site, owned by the Tennessee Valley Authority, was identified as the preferred site. It has several particularly desirable features including: (1) federal ownership and control by the Department of Energy; (2) particularly good transportation access (five miles to the nearest interstate highway and direct rail access); (3) site characteristics and current data base judged by the NRC in 1983 as sufficient for granting a limited work authorization for the now cancelled breeder reactor; and (4) a technical community in the vicinity of site which can provide experienced nuclear facility support functions. 6 figs., 2 tabs

Maryland Power Plant Siting Project: an application of the ORNL-Land Use Screening Procedure

International Nuclear Information System (INIS)

Dobson, J.E.

1975-01-01

Since 1974 the Resource Analysis Group in the Regional and Urban Studies Section of the Oak Ridge National Laboratory (ORNL) has been engaged in developing a procedure for regional and local siting analysis known as the ORNL Land Use Screening Procedure (LUSP). This document is the final report of the Maryland Power Plant Siting Project (MPPSP) in which the ORNL LUSP was used to identify candidate areas for power plant sites in northern Maryland. Numerous candidate areas are identified on the basis of four different siting objectives: the minimization of adverse ecologic impact, the minimization of adverse socioeconomic impact, the minimization of construction and operating costs, and a composite of all siting objectives. Siting criteria have been defined for each of these objectives through group processing techniques administered to four different groups of siting specialists. The siting priorities and opinions of each group have been expressed quantitatively and applied to a geographic information system containing 52 variables for each 91.8-acre cell in the northern eight counties of Maryland

Maryland Power Plant Siting Project: an application of the ORNL-Land Use Screening Procedure

Energy Technology Data Exchange (ETDEWEB)

Dobson, J.E.

1975-01-01

Since 1974 the Resource Analysis Group in the Regional and Urban Studies Section of the Oak Ridge National Laboratory (ORNL) has been engaged in developing a procedure for regional and local siting analysis known as the ORNL Land Use Screening Procedure (LUSP). This document is the final report of the Maryland Power Plant Siting Project (MPPSP) in which the ORNL LUSP was used to identify candidate areas for power plant sites in northern Maryland. Numerous candidate areas are identified on the basis of four different siting objectives: the minimization of adverse ecologic impact, the minimization of adverse socioeconomic impact, the minimization of construction and operating costs, and a composite of all siting objectives. Siting criteria have been defined for each of these objectives through group processing techniques administered to four different groups of siting specialists. The siting priorities and opinions of each group have been expressed quantitatively and applied to a geographic information system containing 52 variables for each 91.8-acre cell in the northern eight counties of Maryland.

Screening of Potential Remediation Methods for the 200-ZP-1 Operable Unit at the Hanford Site

Energy Technology Data Exchange (ETDEWEB)

Truex, Michael J.; Nimmons, Michael J.; Johnson, Christian D.; Dresel, P EVAN.; Murray, Christopher J.

2006-08-07

A screening-level evaluation of potential remediation methods for application to the contaminants of concern (COC) in the 200-ZP-1 Operable Unit at the Hanford Site was conducted based on the methods outlined in the Guidance for Conducting Remedial Investigations and Feasibility Studies under CERCLA Interim Final. The scope of this screening was to identify the most promising remediation methods for use in the more detailed analysis of remediation alternatives that will be conducted as part of the full feasibility study. The screening evaluation was conducted for the primary COC (potential major risk drivers). COC with similar properties were grouped for the screening evaluation. The screening evaluation was conducted in two primary steps. The initial screening step evaluated potential remediation methods based on whether they can be effectively applied within the environmental setting of the 200-ZP-1 Operable Unit for the specified contaminants. In the second step, potential remediation methods were screened using scoping calculations to estimate the scale of infrastructure, overall quantities of reagents, and conceptual approach for applying the method for each defined grouping of COC. Based on these estimates, each method was screened with respect to effectiveness, implementability, and relative cost categories of the CERCLA feasibility study screening process defined in EPA guidance.

Evaluation of the on-site immunoassay drug-screening device Triage-TOX in routine forensic autopsy.

Science.gov (United States)

Tominaga, Mariko; Michiue, Tomomi; Maeda, Hitoshi

2015-11-01

Instrumental identification of drugs with quantification is essential in forensic toxicology, while on-site immunoassay urinalysis drug-screening devices conveniently provide preliminary information when adequately used. However, suitable or sufficient urine specimens are not always available. The present study evaluated the efficacy of a new on-site immunoassay drug-screening device Triage-TOX (Alere Inc., San Diego, CA, USA), which has recently been developed to provide objective data on the one-step automated processor, using 51 urine and 19 pericardial fluid samples from 66 forensic autopsy cases, compared with Triage-Drug of Abuse (DOA) and Monitect-9. For benzodiazepines, the positive predictive value and specificity of Triage-TOX were higher than those of Triage-DOA; however, sensitivity was higher with Monitect-9, despite frequent false-positives. The results for the other drugs with the three devices also included a few false-negatives and false-positives. These observations indicate the applicability of Triage-TOX in preliminary drug screening using urine or alternative materials in routine forensic autopsy, when a possible false-negative is considered, especially for benzodiazepines, providing objective information; however, the combined use of another device such as Monitect-9 can help minimize misinterpretation prior to instrumental analysis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Usability and Accessibility of eBay by Screen Reader

Science.gov (United States)

Buzzi, Maria Claudia; Buzzi, Marina; Leporini, Barbara; Akhter, Fahim

The evolution of Information and Communication Technology and the rapid growth of the Internet have fuelled a great diffusion of eCommerce websites. Usually these sites have complex layouts crowded with active elements, and thus are difficult to navigate via screen reader. Interactive environments should be properly designed and delivered to everyone, including the blind, who usually use screen readers to interact with their computers. In this paper we investigate the interaction of blind users with eBay, a popular eCommerce website, and discuss how using the W3C Accessible Rich Internet Applications (WAI-ARIA) suite could improve the user experience when navigating via screen reader.

Screening and comparison of remedial alternatives for the South Field and flyash piles at the Fernald site

International Nuclear Information System (INIS)

Bumb, A.C.; Jones, G.N.

1996-05-01

The South Field, the Inactive Flyash Pile, and the Active Flyash Pile are in close proximity to each other and are part of Operable Unit 2 (OU2) at the Fernald Environmental Management Project (FEMP). The baseline risk assessment indicated that the exposure pathways which pose the most significant risk are external radiation from radionuclides in surface soils and use of uranium contaminated groundwater. This paper presents screening and comparison of various remedial alternatives considered to mitigate risks from the groundwater pathway. Eight remedial alternatives were developed which consisted of consolidation and capping, excavation and off-site disposal with or without treatment, excavation and on-site disposal with or without treatment and combinations of these. Risk-based source (soil) preliminary remediation levels (PRLs) and waste acceptance criteria (WACs) were developed for consolidation and capping, excavation, and on-site disposal cell. The PRLs and WACs were developed using an integrated modeling tool consisting of an infiltration model, a surface water model, a vadose zone model, and a three-dimensional contaminant migration model in saturated media. The PRLs and WACs were then used to determine need for soil treatment, determine excavation volumes, and screen remedial alternatives. The selected remedial alternative consisted of excavation and on-site disposal with off-site disposal of the fraction exceeding the WAC

Alternative Endpoints and Approaches for the Remediation of Contaminated Groundwater at Complex Sites - 13426

International Nuclear Information System (INIS)

Deeb, Rula A.; Hawley, Elisabeth L.

2013-01-01

The goal of United States (U.S.) Department of Energy's (DOE)'s environmental remediation programs is to restore groundwater to beneficial use, similar to many other Federal and state environmental cleanup programs. Based on past experience, groundwater remediation to pre-contamination conditions (i.e., drinking water standards or non-detectable concentrations) can be successfully achieved at many sites. At a subset of the most complex sites, however, complete restoration is not likely achievable within the next 50 to 100 years using today's technology. This presentation describes several approaches used at complex sites in the face of these technical challenges. Many complex sites adopted a long-term management approach, whereby contamination was contained within a specified area using active or passive remediation techniques. Consistent with the requirements of their respective environmental cleanup programs, several complex sites selected land use restrictions and used risk management approaches to accordingly adopt alternative cleanup goals (alternative endpoints). Several sites used long-term management designations and approaches in conjunction with the alternative endpoints. Examples include various state designations for groundwater management zones, technical impracticability (TI) waivers or greater risk waivers at Superfund sites, and the use of Monitored Natural Attenuation (MNA) or other passive long-term management approaches over long time frames. This presentation will focus on findings, statistics, and case studies from a recently-completed report for the Department of Defense's Environmental Security Technology Certification Program (ESTCP) (Project ER-0832) on alternative endpoints and approaches for groundwater remediation at complex sites under a variety of Federal and state cleanup programs. The primary objective of the project was to provide environmental managers and regulators with tools, metrics, and information needed to evaluate

Alternative Endpoints and Approaches for the Remediation of Contaminated Groundwater at Complex Sites - 13426

Energy Technology Data Exchange (ETDEWEB)

Deeb, Rula A.; Hawley, Elisabeth L. [ARCADIS, U.S., 2000 Powell St., 7th Floor, Emeryville, California 94608 (United States)

2013-07-01

The goal of United States (U.S.) Department of Energy's (DOE)'s environmental remediation programs is to restore groundwater to beneficial use, similar to many other Federal and state environmental cleanup programs. Based on past experience, groundwater remediation to pre-contamination conditions (i.e., drinking water standards or non-detectable concentrations) can be successfully achieved at many sites. At a subset of the most complex sites, however, complete restoration is not likely achievable within the next 50 to 100 years using today's technology. This presentation describes several approaches used at complex sites in the face of these technical challenges. Many complex sites adopted a long-term management approach, whereby contamination was contained within a specified area using active or passive remediation techniques. Consistent with the requirements of their respective environmental cleanup programs, several complex sites selected land use restrictions and used risk management approaches to accordingly adopt alternative cleanup goals (alternative endpoints). Several sites used long-term management designations and approaches in conjunction with the alternative endpoints. Examples include various state designations for groundwater management zones, technical impracticability (TI) waivers or greater risk waivers at Superfund sites, and the use of Monitored Natural Attenuation (MNA) or other passive long-term management approaches over long time frames. This presentation will focus on findings, statistics, and case studies from a recently-completed report for the Department of Defense's Environmental Security Technology Certification Program (ESTCP) (Project ER-0832) on alternative endpoints and approaches for groundwater remediation at complex sites under a variety of Federal and state cleanup programs. The primary objective of the project was to provide environmental managers and regulators with tools, metrics, and information needed

Identification of chromatin-associated regulators of MSL complex targeting in Drosophila dosage compensation.

Directory of Open Access Journals (Sweden)

Erica Larschan

Full Text Available Sex chromosome dosage compensation in Drosophila provides a model for understanding how chromatin organization can modulate coordinate gene regulation. Male Drosophila increase the transcript levels of genes on the single male X approximately two-fold to equal the gene expression in females, which have two X-chromosomes. Dosage compensation is mediated by the Male-Specific Lethal (MSL histone acetyltransferase complex. Five core components of the MSL complex were identified by genetic screens for genes that are specifically required for male viability and are dispensable for females. However, because dosage compensation must interface with the general transcriptional machinery, it is likely that identifying additional regulators that are not strictly male-specific will be key to understanding the process at a mechanistic level. Such regulators would not have been recovered from previous male-specific lethal screening strategies. Therefore, we have performed a cell culture-based, genome-wide RNAi screen to search for factors required for MSL targeting or function. Here we focus on the discovery of proteins that function to promote MSL complex recruitment to "chromatin entry sites," which are proposed to be the initial sites of MSL targeting. We find that components of the NSL (Non-specific lethal complex, and a previously unstudied zinc-finger protein, facilitate MSL targeting and display a striking enrichment at MSL entry sites. Identification of these factors provides new insight into how MSL complex establishes the specialized hyperactive chromatin required for dosage compensation in Drosophila.

DARC: Mapping Surface Topography by Ray-Casting for Effective Virtual Screening at Protein Interaction Sites.

Science.gov (United States)

Gowthaman, Ragul; Miller, Sven A; Rogers, Steven; Khowsathit, Jittasak; Lan, Lan; Bai, Nan; Johnson, David K; Liu, Chunjing; Xu, Liang; Anbanandam, Asokan; Aubé, Jeffrey; Roy, Anuradha; Karanicolas, John

2016-05-12

Protein-protein interactions represent an exciting and challenging target class for therapeutic intervention using small molecules. Protein interaction sites are often devoid of the deep surface pockets presented by "traditional" drug targets, and crystal structures reveal that inhibitors typically engage these sites using very shallow binding modes. As a consequence, modern virtual screening tools developed to identify inhibitors of traditional drug targets do not perform as well when they are instead deployed at protein interaction sites. To address the need for novel inhibitors of important protein interactions, here we introduce an alternate docking strategy specifically designed for this regime. Our method, termed DARC (Docking Approach using Ray-Casting), matches the topography of a surface pocket "observed" from within the protein to the topography "observed" when viewing a potential ligand from the same vantage point. We applied DARC to carry out a virtual screen against the protein interaction site of human antiapoptotic protein Mcl-1 and found that four of the top-scoring 21 compounds showed clear inhibition in a biochemical assay. The Ki values for these compounds ranged from 1.2 to 21 μM, and each had ligand efficiency comparable to promising small-molecule inhibitors of other protein-protein interactions. These hit compounds do not resemble the natural (protein) binding partner of Mcl-1, nor do they resemble any known inhibitors of Mcl-1. Our results thus demonstrate the utility of DARC for identifying novel inhibitors of protein-protein interactions.

Restriction digest screening facilitates efficient detection of site-directed mutations introduced by CRISPR in C. albicans UME6.

Science.gov (United States)

Evans, Ben A; Smith, Olivia L; Pickerill, Ethan S; York, Mary K; Buenconsejo, Kristen J P; Chambers, Antonio E; Bernstein, Douglas A

2018-01-01

Introduction of point mutations to a gene of interest is a powerful tool when determining protein function. CRISPR-mediated genome editing allows for more efficient transfer of a desired mutation into a wide range of model organisms. Traditionally, PCR amplification and DNA sequencing is used to determine if isolates contain the intended mutation. However, mutation efficiency is highly variable, potentially making sequencing costly and time consuming. To more efficiently screen for correct transformants, we have identified restriction enzymes sites that encode for two identical amino acids or one or two stop codons. We used CRISPR to introduce these restriction sites directly upstream of the Candida albicans UME6 Zn 2+ -binding domain, a known regulator of C. albicans filamentation. While repair templates coding for different restriction sites were not equally successful at introducing mutations, restriction digest screening enabled us to rapidly identify isolates with the intended mutation in a cost-efficient manner. In addition, mutated isolates have clear defects in filamentation and virulence compared to wild type C. albicans . Our data suggest restriction digestion screening efficiently identifies point mutations introduced by CRISPR and streamlines the process of identifying residues important for a phenotype of interest.

Colorimetric method for enzymatic screening assay of ATP using Fe(III)-xylenol orange complex formation.

Science.gov (United States)

Ishida, Akihiko; Yamada, Yasuko; Kamidate, Tamio

2008-11-01

In hygiene management, recently there has been a significant need for screening methods for microbial contamination by visual observation or with commonly used colorimetric apparatus. The amount of adenosine triphosphate (ATP) can serve as the index of a microorganism. This paper describes the development of a colorimetric method for the assay of ATP, using enzymatic cycling and Fe(III)-xylenol orange (XO) complex formation. The color characteristics of the Fe(III)-XO complexes, which show a distinct color change from yellow to purple, assist the visual observation in screening work. In this method, a trace amount of ATP was converted to pyruvate, which was further amplified exponentially with coupled enzymatic reactions. Eventually, pyruvate was converted to the Fe(III)-XO complexes through pyruvate oxidase reaction and Fe(II) oxidation. As the assay result, yellow or purple color was observed: A yellow color indicates that the ATP concentration is lower than the criterion of the test, and a purple color indicates that the ATP concentration is higher than the criterion. The method was applied to the assay of ATP extracted from Escherichia coli cells added to cow milk.

Demonstration of an initial screening phase for site selection for low level radioactive waste burial - an evaluation of relevant IAEA guidelines

International Nuclear Information System (INIS)

1984-04-01

Low level radioactive wastes, arising from the use of radioisotopes in medicine and industry are accumulating throughout Australia. The rate of accumulation has not been large and storage of these wastes close to the point of use has proved practicable to date, but consideration must now be given to a central repository or repositories for these low level wastes. This report considers the question of selecting a site suitable for disposal of wastes by shallow ground burial. It attempts to asses the practicability of using factors suggested by the IAEA for the initial phase of site screening. The screening process described has essentially two stages. In the first, New South Wales was divided into broad structural units and these ranked in order of suitability. In the second stage, survey sites in which thick clay beds outcropped were delineated in the five highest ranking structural units. These survey sites were ranked on the basis of various geomorphological properties which largely described the hydrogeology of the site

Screening Mixtures of Small Molecules for Binding to Multiple Sites on the Surface Tetanus Toxin C Fragment by Bioaffinity NMR

International Nuclear Information System (INIS)

Cosman, M; Zeller, L; Lightstone, F C; Krishnan, V V; Balhorn, R

2002-01-01

The clostridial neurotoxins include the closely related tetanus (TeNT) and botulinum (BoNT) toxins. Botulinum toxin is used to treat severe muscle disorders and as a cosmetic wrinkle reducer. Large quantities of botulinum toxin have also been produced by terrorists for use as a biological weapon. Because there are no known antidotes for these toxins, they thus pose a potential threat to human health whether by an accidental overdose or by a hostile deployment. Thus, the discovery of high specificity and affinity compounds that can inhibit their binding to neural cells can be used as antidotes or in the design of chemical detectors. Using the crystal structure of the C fragment of the tetanus toxin (TetC), which is the cell recognition and cell surface binding domain, and the computational program DOCK, sets of small molecules have been predicted to bind to two different sites located on the surface of this protein. While Site-1 is common to the TeNT and BoNTs, Site-2 is unique to TeNT. Pairs of these molecules from each site can then be linked together synthetically to thereby increase the specificity and affinity for this toxin. Electrospray ionization mass spectroscopy was used to experimentally screen each compound for binding. Mixtures containing binders were further screened for activity under biologically relevant conditions using nuclear magnetic resonance (NMR) methods. The screening of mixtures of compounds offers increased efficiency and throughput as compared to testing single compounds and can also evaluate how possible structural changes induced by the binding of one ligand can influence the binding of the second ligand. In addition, competitive binding experiments with mixtures containing ligands predicted to bind the same site could identify the best binder for that site. NMR transfer nuclear Overhauser effect (trNOE) confirm that TetC binds doxorubicin but that this molecule is displaced by N-acetylneuraminic acid (sialic acid) in a mixture that

Developing the clinical components of a complex intervention for a glaucoma screening trial: a mixed methods study

Directory of Open Access Journals (Sweden)

2011-04-01

Full Text Available Abstract Background Glaucoma is a leading cause of avoidable blindness worldwide. Open angle glaucoma is the most common type of glaucoma. No randomised controlled trials have been conducted evaluating the effectiveness of glaucoma screening for reducing sight loss. It is unclear what the most appropriate intervention to be evaluated in any glaucoma screening trial would be. The purpose of this study was to develop the clinical components of an intervention for evaluation in a glaucoma (open angle screening trial that would be feasible and acceptable in a UK eye-care service. Methods A mixed-methods study, based on the Medical Research Council (MRC framework for complex interventions, integrating qualitative (semi-structured interviews with 46 UK eye-care providers, policy makers and health service commissioners, and quantitative (economic modelling methods. Interview data were synthesised and used to revise the screening interventions compared within an existing economic model. Results The qualitative data indicated broad based support for a glaucoma screening trial to take place in primary care, using ophthalmic trained technical assistants supported by optometry input. The precise location should be tailored to local circumstances. There was variability in opinion around the choice of screening test and target population. Integrating the interview findings with cost-effectiveness criteria reduced 189 potential components to a two test intervention including either optic nerve photography or screening mode perimetry (a measure of visual field sensitivity with or without tonometry (a measure of intraocular pressure. It would be more cost-effective, and thus acceptable in a policy context, to target screening for open angle glaucoma to those at highest risk but for both practicality and equity arguments the optimal strategy was screening a general population cohort beginning at age forty. Conclusions Interventions for screening for open angle

Descriptions of representative contaminated sites and facilities within the DOE complex

International Nuclear Information System (INIS)

Short, S.M.; Buck, J.W.; Clark, L.L.; Fletcher, J.F.; Glantz, C.S.; Holdren, G.R.; Huesties, L.R.; Williams, M.D.; Oates, L.

1994-10-01

The U.S. Department of Energy (DOE) has initiated efforts to prepare a Programmatic Environmental Impact Statement (PEIS) that will analyze the existing environmental restoration and waste management program and evaluate alternatives for an integrated program. The alternatives being evaluated include (1) a open-quotes No Actionclose quotes alternative as required by the National Environmental Policy Act (NEPA), (2) an Applicable, Relevant, and Appropriate Requirements (ARAR)-driven alternative, (3) a land-use-driven alternative, (4) a health-risk-driven alternative, and (5) a combination land-use and health-risk-driven alternative. The analytical approach being taken to evaluate each of these alternatives is to perform a remedial engineering analysis and human health and ecosystem effects analyses on every contaminated site and facility in the DOE complex. One of Pacific Northwest Laboratory's (PNL) roles in this approach has been to compile the source term and environmental setting data needed to drive each of these analyses. To date, over 10,000 individual contaminated sites and facilities located throughout the DOE complex of installations have been identified and at least some minimal data compiled on each. The PEIS analyses have been appreciably simplified by categorizing all of these contaminated sites and facilities into six broad categories: (1) contaminated buildings, (2) contaminated soils, (3) solid waste sites (e.g., burial grounds), (4) liquid containment structures (e.g., tanks), (5) surface water sites, and (6) contaminated groundwater sites. A report containing a complete description of each of these thousands of contaminated sites and facilities would be tremendously large and unwildy, as would separate reports describing the application of the analytical methodologies to each

Evaluation of sexual history-based screening of anatomic sites for chlamydia trachomatis and neisseria gonorrhoeae infection in men having sex with men in routine practice

Directory of Open Access Journals (Sweden)

Jansen Casper L

2011-07-01

Full Text Available Abstract Background Sexually transmitted infection (STI screening programmes are implemented in many countries to decrease burden of STI and to improve sexual health. Screening for Chlamydia trachomatis and Neisseria gonorrhoeae has a prominent role in these protocols. Most of the screening programmes concerning men having sex with men (MSM are based on opportunistic urethral testing. In The Netherlands, a history-based approach is used. The aim of this study is to evaluate the protocol of screening anatomic sites for C. trachomatis and N. gonorrhoeae infection based on sexual history in MSM in routine practice in The Netherlands. Methods All MSM visiting the clinic for STI in The Hague are routinely asked about their sexual practice during consulting. As per protocol, tests for urogenital, oropharyngeal and anorectal infection are obtained based on reported site(s of sexual contact. All consultations are entered into a database as part of the national STI monitoring system. Data of an 18 months period were retrieved from this database and analysed. Results A total of 1455 consultations in MSM were registered during the study period. The prevalence of C. trachomatis and N. gonorrhoeae per anatomic site was: urethral infection 4.0% respectively and 2.8%, oropharynx 1.5% and 4.2%, and anorectum 8.2% and 6.0%. The majority of chlamydia cases (72% involved a single anatomic site, which was especially manifest for anorectal infections (79%, while 42% of gonorrhoea cases were single site. Twenty-six percent of MSM with anorectal chlamydia and 17% with anorectal gonorrhoea reported symptoms of proctitis; none of the oropharyngeal infections were symptomatic. Most cases of anorectal infection (83% and oropharyngeal infection (100% would have remained undiagnosed with a symptom-based protocol. Conclusions The current strategy of sexual-history based screening of multiple anatomic sites for chlamydia and gonorrhoea in MSM is a useful and valid guideline

Unifying screening processes within the PROSPR consortium: a conceptual model for breast, cervical, and colorectal cancer screening.

Science.gov (United States)

Beaber, Elisabeth F; Kim, Jane J; Schapira, Marilyn M; Tosteson, Anna N A; Zauber, Ann G; Geiger, Ann M; Kamineni, Aruna; Weaver, Donald L; Tiro, Jasmin A

2015-06-01

General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Study of Learners' Preference for Visual Complexity on Small Screens of Mobile Computers Using Neural Networks

Science.gov (United States)

Wang, Lan-Ting; Lee, Kun-Chou

2014-01-01

The vision plays an important role in educational technologies because it can produce and communicate quite important functions in teaching and learning. In this paper, learners' preference for the visual complexity on small screens of mobile computers is studied by neural networks. The visual complexity in this study is divided into five…

Screening the efficient biological prospects of triazole allied mixed ligand metal complexes

Science.gov (United States)

Utthra, Ponnukalai Ponya; Kumaravel, Ganesan; Raman, Natarajan

2017-12-01

Triazole appended mixed ligand complexes (1-8) of the general formula [ML (bpy/phen)2]Cl2, where M = Cu(II), Co(II), Ni(II) and Zn(II), L = triazole appended Schiff base (E)sbnd N-(4-nitrobenzylidene)-1H-1,2,4-triazol-3-amine and bpy/phen = 2,2‧-bipyridine/1,10-phenanthroline, have been synthesized. The design and synthesis of this elaborate ligand has been performed with the aim of increasing stability and conjugation of 1,2,4 triazole, whose Schiff base derivatives are known as biologically active compounds thereby exploring their DNA binding affinity and other biological applications. The compounds have been comprehensively characterized by elemental analysis, spectroscopic methods (IR, UV-Vis, EPR, 1H and 13C NMR spectroscopy), ESI mass spectrometry and magnetic susceptibility measurements. The complexes were found to exhibit octahedral geometry. The complexes 1-8 were subjected to DNA binding techniques evaluated using UV-Vis absorption, CV, CD, Fluorescence spectroscopy and hydrodynamic measurements. Complex 5 showed a Kb value of 3.9 × 105 M-1. The DNA damaging efficacy for the complexes was observed to be high compared to the ligand. The antimicrobial screening of the compounds against bacterial and fungal strains indicates that the complexes possess excellent antimicrobial activity than the ligand. The overall biological activity of the complexes with phen as a co-ligand possessed superior potential than the ligand.

Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics

Science.gov (United States)

Lau, Wan F.; Withka, Jane M.; Hepworth, David; Magee, Thomas V.; Du, Yuhua J.; Bakken, Gregory A.; Miller, Michael D.; Hendsch, Zachary S.; Thanabal, Venkataraman; Kolodziej, Steve A.; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S.; Love, Robert; Charlton, Maura E.; Hughes, Samantha; van Hoorn, Willem P.; Mills, James E.

2011-07-01

Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

Molecular screening of compounds to the predicted Protein-Protein Interaction site of Rb1-E7 with p53- E6 in HPV

Science.gov (United States)

Shaikh, Faraz; Sanehi, Parvish; Rawal, Rakesh

2012-01-01

Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. Human Papillomaviruses (HPVs) which are heterogeneous groups of small double stranded DNA viruses are considered as the primary cause of cervical cancer, involved in 90% of all Cervical Cancers. Two early HPV genes, E6 and E7, are known to play crucial role in tumor formation. E6 binds with p53 and prevents its translocation and thereby inhibit the ability of p53 to activate or repress target genes. E7 binds to hypophosphorylated Rb and thereby induces cells to enter into premature S-phase by disrupting Rb-E2F complexes. The strategy of the research work was to target the site of interaction of Rb1 -E7 & p53-E6. A total of 88 compounds were selected for molecular screening, based on comprehensive literature survey for natural compounds with anti-cancer activity. Molecular docking analysis was carried out with Molegro Virtual Docker, to screen the 88 chosen compounds and rank them according to their binding affinity towards the site of interaction of the viral oncoproteins and human tumor suppressor proteins. The docking result revealed that Nicandrenone a member of Withanolides family of chemical compounds as the most likely molecule that can be used as a candidate drug against HPV induced cervical cancer. Abbreviations HPV - Human Papiloma Virus, HTSP - Human Tumor Suppressor Proteins, VOP - Viral oncoproteins. PMID:22829740

Carotenoid-binding sites of the major light-harvesting complex II of higher plants

NARCIS (Netherlands)

Croce, Roberta; Weiss, Saskia; Bassi, Roberto

1999-01-01

Recombinant light-harvesting complex II (LHCII) proteins with modified carotenoid composition have been obtained by in vitro reconstitution of the Lhcb1 protein overexpressed in bacteria. The monomeric protein possesses three xanthophyll-binding sites. The L1 and L2 sites, localized by electron

Optimization of wind farm micro-siting for complex terrain using greedy algorithm

International Nuclear Information System (INIS)

Song, M.X.; Chen, K.; He, Z.Y.; Zhang, X.

2014-01-01

An optimization approach based on greedy algorithm for optimization of wind farm micro-siting is presented. The key of optimizing wind farm micro-siting is the fast and accurate evaluation of the wake flow interactions of wind turbines. The virtual particle model is employed for wake flow simulation of wind turbines, which makes the present method applicable for non-uniform flow fields on complex terrains. In previous bionic optimization method, within each step of the optimization process, only the power output of the turbine that is being located or relocated is considered. To aim at the overall power output of the wind farm comprehensively, a dependent region technique is introduced to improve the estimation of power output during the optimization procedure. With the technique, the wake flow influences can be reduced more efficiently during the optimization procedure. During the optimization process, the turbine that is being added will avoid being affected other turbines, and avoid affecting other turbine in the meantime. The results from the numerical calculations demonstrate that the present method is effective for wind farm micro-siting on complex terrain, and it produces better solutions in less time than the previous bionic method. - Highlights: • Greedy algorithm is applied to wind farm micro-siting problem. • The present method is effective for optimization on complex terrains. • Dependent region is suggested to improve the evaluation of wake influences. • The present method has better performance than the bionic method

Screening of CHP Potential at Federal Sites in Select Regions of the U.S.

Energy Technology Data Exchange (ETDEWEB)

Energy Nexus Group, . .

2002-02-25

sizing CHP to thermal and electrical estimates. The table below is a summary of findings of CHP potential for those federal facilities that chose to participate in the screening process. The study focused on three U.S. regions: California, Texas, and New York/New England. All federal facilities in these three regions with reported building space greater than 100,000 square feet were initial targets to contact and offer CHP screening services. Ranking criteria were developed to screen sites for near term CHP potential. The potential site list was pared down for a variety of reasons including site- specific and agency wide decisions not to participate, desk audit assessments, and untraceable contact information. The results are based upon the voluntary participation of those sites we were able to contact, so they reflect a fraction of the total potential CHP opportunities at federal government facilities.

Identification of B. anthracis N(5)-carboxyaminoimidazole ribonucleotide mutase (PurE) active site binding compounds via fragment library screening.

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Lei, Hao; Jones, Christopher; Zhu, Tian; Patel, Kavankumar; Wolf, Nina M; Fung, Leslie W-M; Lee, Hyun; Johnson, Michael E

2016-02-15

The de novo purine biosynthesis pathway is an attractive target for antibacterial drug design, and PurE from this pathway has been identified to be crucial for Bacillus anthracis survival in serum. In this study we adopted a fragment-based hit discovery approach, using three screening methods-saturation transfer difference nucleus magnetic resonance (STD-NMR), water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR, and surface plasmon resonance (SPR), against B. anthracis PurE (BaPurE) to identify active site binding fragments by initially testing 352 compounds in a Zenobia fragment library. Competition STD NMR with the BaPurE product effectively eliminated non-active site binding hits from the primary hits, selecting active site binders only. Binding affinities (dissociation constant, KD) of these compounds varied between 234 and 301μM. Based on test results from the Zenobia compounds, we subsequently developed and applied a streamlined fragment screening strategy to screen a much larger library consisting of 3000 computationally pre-selected fragments. Thirteen final fragment hits were confirmed to exhibit binding affinities varying from 14μM to 700μM, which were categorized into five different basic scaffolds. All thirteen fragment hits have ligand efficiencies higher than 0.30. We demonstrated that at least two fragments from two different scaffolds exhibit inhibitory activity against the BaPurE enzyme. Published by Elsevier Ltd.

Search for over 2000 current and legacy micropollutants on a wastewater infiltration site with a UPLC-high resolution MS target screening method.

Science.gov (United States)

Wode, Florian; van Baar, Patricia; Dünnbier, Uwe; Hecht, Fabian; Taute, Thomas; Jekel, Martin; Reemtsma, Thorsten

2015-02-01

A target screening method using ultra high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was developed. The method was applied to 14 groundwater and 11 surface water samples of a former wastewater infiltration site, where raw wastewater was applied until 1985 and treated wastewater is applied since 2005. The measured data are compared with mass spectrometric data of over 2000 organic micropollutants (OMPs), including pharmaceuticals, personal care products, pesticides, industrial chemicals and metabolites of these classes. A total number of 151 and 159 OMPs were detected in groundwater and surface water, respectively, of which 12 have not been reported before in these matrices. Among these 12 compounds were 11 pharmaceuticals and one personal care product. The identity of 55 of the detected OMPs (35%) was verified by analysis of standard compounds. Based on the distribution in the study area, two groups of OMPs were clearly distinguished: current OMPs introduced with treated municipal wastewater since 2005 and legacy OMPs originating from infiltration of untreated wastewater until 1985. A third group included OMPs contained in historic as well as in current wastewater. During infiltration, OMPs with molecular mass >500 g/mol and log DOW > 3.9 were preferentially removed. Speciation had a strong impact with cationic OMPs showing high, neutral OMPs medium and anionic OMPs lowest elimination during infiltration. This target screening method proved useful to study a wide range of compounds, even in retrospect and at sites with poorly documented history and with a complex and variable hydrological situation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Distinguishing Active Site Characteristics of Chlorite Dismutases with Their Cyanide Complexes.

Science.gov (United States)

Geeraerts, Zachary; Celis, Arianna I; Mayfield, Jeffery A; Lorenz, Megan; Rodgers, Kenton R; DuBois, Jennifer L; Lukat-Rodgers, Gudrun S

2018-03-06

O 2 -evolving chlorite dismutases (Clds) efficiently convert chlorite (ClO 2 - ) to O 2 and Cl - . Dechloromonas aromatica Cld ( DaCld) is a highly active chlorite-decomposing homopentameric enzyme, typical of Clds found in perchlorate- and chlorate-respiring bacteria. The Gram-negative, human pathogen Klebsiella pneumoniae contains a homodimeric Cld ( KpCld) that also decomposes ClO 2 - , albeit with an activity 10-fold lower and a turnover number lower than those of DaCld. The interactions between the distal pocket and heme ligand of the DaCld and KpCld active sites have been probed via kinetic, thermodynamic, and spectroscopic behaviors of their cyanide complexes for insight into active site characteristics that are deterministic for chlorite decomposition. At 4.7 × 10 -9 M, the K D for the KpCld-CN - complex is 2 orders of magnitude smaller than that of DaCld-CN - and indicates an affinity for CN - that is greater than that of most heme proteins. The difference in CN - affinity between Kp- and DaClds is predominantly due to differences in k off . The kinetics of binding of cyanide to DaCld, DaCld(R183Q), and KpCld between pH 4 and 8.5 corroborate the importance of distal Arg183 and a p K a of ∼7 in stabilizing complexes of anionic ligands, including the substrate. The Fe-C stretching and FeCN bending modes of the DaCld-CN - (ν Fe-C , 441 cm -1 ; δ FeCN , 396 cm -1 ) and KpCld-CN - (ν Fe-C , 441 cm -1 ; δ FeCN , 356 cm -1 ) complexes reveal differences in their FeCN angle, which suggest different distal pocket interactions with their bound cyanide. Conformational differences in their catalytic sites are also reported by the single ferrous KpCld carbonyl complex, which is in contrast to the two conformers observed for DaCld-CO.

Studies on numerical site calibration over complex terrain for wind turbines

Institute of Scientific and Technical Information of China (English)

Daisuke; MATSUSHITA; Hikaru; MATSUMIYA; Yoshinori; HARA; Satoshi; WATANABE; Akinori; FURUKAWA

2010-01-01

The estimation of wind turbine performance over complex terrain is very difficult because of the document of standard IEC61400-12 is adapted for flat or slightly complex topography.And the cost of constructing a meteorological mast is higher with scaling wind turbine up.We have proposed a numerical site calibration(NSC) technique in order to estimate the inflow velocity at the position of wind turbine by using CFD tool to calculate the flow field around the site.The present paper shows the problems for the procedure of NSC in which a commercial nonlinear CFD tool and the improvement method are used to gain a more accurate result.It is clarified that the wind turbine performance which is estimated by using the wind speed on the meteorological mast has a good result for annual energy production.

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

Science.gov (United States)

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

2017-08-08

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

Non-animal photosafety screening for complex cosmetic ingredients with photochemical and photobiochemical assessment tools.

Science.gov (United States)

Nishida, Hayato; Hirota, Morihiko; Seto, Yoshiki; Suzuki, Gen; Kato, Masashi; Kitagaki, Masato; Sugiyama, Mariko; Kouzuki, Hirokazu; Onoue, Satomi

2015-08-01

Previously, a non-animal screening approach was proposed for evaluating photosafety of cosmetic ingredients by means of in vitro photochemical and photobiochemical assays; however, complex cosmetic ingredients, such as plant extracts and polymers, could not be evaluated because their molecular weight is often poorly defined and so their molar concentration cannot be calculated. The aim of the present investigation was to establish a photosafety screen for complex cosmetic ingredients by using appropriately modified in vitro photosafety assays. Twenty plant extracts were selected as model materials on the basis of photosafety information, and their phototoxic potentials were assessed by means of ultraviolet (UV)/visible light (VIS) spectral analysis, reactive oxygen species (ROS)/micellar ROS (mROS) assays, and 3T3 neutral red uptake phototoxicity testing (3T3 NRU PT). The maximum UV/VIS absorption value was employed as a judgment factor for evaluating photoexcitability of samples, and the value of 1.0 was adopted as a tentative criterion for photosafety identification. The ROS/mROS assays were conducted at 50 μg/mL, and no false negative prediction was obtained. Furthermore, the ROS/mROS assays at 50 μg/mL had a similar predictive capacity to the ROS/mROS assays in the previous study. A systematic tiered approach for simple and rapid non-animal photosafety evaluation of complex cosmetic ingredients can be constructed using these modified in vitro photochemical assays. Copyright © 2015 Elsevier Inc. All rights reserved.

Dual Binding Site and Selective Acetylcholinesterase Inhibitors Derived from Integrated Pharmacophore Models and Sequential Virtual Screening

Directory of Open Access Journals (Sweden)

Shikhar Gupta

2014-01-01

Full Text Available In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer’s randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties.

The drinking habits of users of an alcohol screening web site in Slovenia

Directory of Open Access Journals (Sweden)

Marko Kolšek

2011-09-01

Full Text Available Background: Heavy drinking is responsible for major health and social problems. Slovenia has few epidemiological studies about drinking, none of them have used the AUDIT questionnaire. Pilot studies have indicated that a Webbased screening is likely to be acceptable to young heavy drinkers. Methods: Cross sectional study. Visitors of a free website, older then 10 years, were offered screening with the Alcohol Use Disorder Identification Test (AUDIT. Their demographic data and information about their drinking habits were collected. All users who completed the questionnaire received a specially prepared feed-back message with an evaluation of their drinking. Data from the database for the first four months were collected for analysis on February 1, 2009. Results: In four months 3329 users filled in the questionnaire, 69.2 % completed it and 1790 participans completed it for themselves. Their mean age was 28.9 years, 62.7 % were between 19 and 34 years. 41 % were single, 49.4 % had finnished the secondary school. 0.1 % of men did not drink alcohol at all, 57.7 % drank hazardous or harmful amounts of alcohol. 50.6 % of women did not have risky drinking habits. Mean baseline AUDIT scores were 8.8 ± 1.3, 9.79 ± 2.1 for men and 7.68 ± 4.7 for women. Conclusions: The alcohol screening website was widely used, especially by young people. The percentage of hazardous male drinkers accessing the site was high. The website seems to be an accessible and useful tool for young people and it could contribute to health promotion and constitute an easier alternative to screening for hazardous and harmful drinking.

Tunable Mobility in Double-Gated MoTe2 Field-Effect Transistor: Effect of Coulomb Screening and Trap Sites.

Science.gov (United States)

Ji, Hyunjin; Joo, Min-Kyu; Yi, Hojoon; Choi, Homin; Gul, Hamza Zad; Ghimire, Mohan Kumar; Lim, Seong Chu

2017-08-30

There is a general consensus that the carrier mobility in a field-effect transistor (FET) made of semiconducting transition-metal dichalcogenides (s-TMDs) is severely degraded by the trapping/detrapping and Coulomb scattering of carriers by ionic charges in the gate oxides. Using a double-gated (DG) MoTe 2 FET, we modulated and enhanced the carrier mobility by adjusting the top- and bottom-gate biases. The relevant mechanism for mobility tuning in this device was explored using static DC and low-frequency (LF) noise characterizations. In the investigations, LF-noise analysis revealed that for a strong back-gate bias the Coulomb scattering of carriers by ionized traps in the gate dielectrics is strongly screened by accumulation charges. This significantly reduces the electrostatic scattering of channel carriers by the interface trap sites, resulting in increased mobility. The reduction of the number of effective trap sites also depends on the gate bias, implying that owing to the gate bias, the carriers are shifted inside the channel. Thus, the number of active trap sites decreases as the carriers are repelled from the interface by the gate bias. The gate-controlled Coulomb-scattering parameter and the trap-site density provide new handles for improving the carrier mobility in TMDs, in a fundamentally different way from dielectric screening observed in previous studies.

Membrane Contact Sites: Complex Zones for Membrane Association and Lipid Exchange

Science.gov (United States)

Quon, Evan; Beh, Christopher T.

2015-01-01

Lipid transport between membranes within cells involves vesicle and protein carriers, but as agents of nonvesicular lipid transfer, the role of membrane contact sites has received increasing attention. As zones for lipid metabolism and exchange, various membrane contact sites mediate direct associations between different organelles. In particular, membrane contact sites linking the plasma membrane (PM) and the endoplasmic reticulum (ER) represent important regulators of lipid and ion transfer. In yeast, cortical ER is stapled to the PM through membrane-tethering proteins, which establish a direct connection between the membranes. In this review, we consider passive and facilitated models for lipid transfer at PM–ER contact sites. Besides the tethering proteins, we examine the roles of an additional repertoire of lipid and protein regulators that prime and propagate PM–ER membrane association. We conclude that instead of being simple mediators of membrane association, regulatory components of membrane contact sites have complex and multilayered functions. PMID:26949334

Acute toxicity screening of Hanford Site waste grouts using aquatic invertebrates

International Nuclear Information System (INIS)

Rebagay, T.V.; Dodd, D.A.; Lockrem, L.L.; Voogd, J.A.

1993-01-01

Liquid wastes containing radioactive, hazardous, and regulated chemicals have been generated throughout the 50 years operation of the Hanford Site of the US Department of Energy near Richland, Washington. The current strategy for the disposal of the low-level radioactive portion of these wastes involves immobilization of the waste in the form of grout. Because the potential risk of animal and plant exposure to grouts is unknown, acute toxicity screening of grouts is needed. Grouts were prepared by mixing a surrogate nonradioactive liquid waste with a blend consisting of cement, fly ash, and clay. Aqueous extracts of the grout were then screened for acute toxicity using aquatic invertebrates as test organisms and a fluorogenic substrate as the toxic stress indicator. After a 1-hour exposure of juvenile daphnids (D, magna, D. pulex, and C. dubia) to the grout extracts followed by a 15-minute reaction with the fluorogenic substrate, the degree of in vivo enzymatic inhibition was measured by the number of resulting fluorescent daphnids. The EC50 values calculated by probit analysis were 2,877 mg/L, 2,983 mg/L, and 3,174 mg/L for D. pulex, D. magna, and C. dubia, respectively. The slight difference in the responses may be attributed to the subjective pass-fail scoring of the fluorescence criterion. The results indicated that the grout studied is nonhazardous and nondangerous

The Screening India′s Twin Epidemic: Study design and methodology (SITE-1

Directory of Open Access Journals (Sweden)

Shashank R Joshi

2011-01-01

Full Text Available Objectives: The recent years have seen a surge in the prevalence of both diabetes and hypertension. Significant demographic variations reported on the prevalence patterns of diabetes and hypertension in India establish a clear need for a nation-wide surveillance study. The Screening India′s Twin Epidemic (SITE study aimed at collecting information on the prevalence of diagnosed and undiagnosed diabetes and hypertension cases in outpatient settings in major Indian states to better understand disease management, as well as to estimate the extent of underlying risk factors. Materials and Methods: During 2009-2010, SITE was conducted in eight states, in waves - one state at a time. It was planned to recruit about 2000 patients from 100 centers per wave. Each center enrolled the first 10 eligible patients (≥18 years of age, not pregnant, signed data release consent form, and ready to undergo screening tests per day on two consecutive days. Patient demographics, medical history, and laboratory investigation results were collected and statistically interpreted. The protocol defined diabetes and hypertension as per the American Diabetes Association (ADA and Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 recommendations, respectively. Results: After the first two pilot phases in Maharashtra and Delhi, the protocol was refined and the laboratory investigations were simplified to be further employed for all other states, namely, Tamil Nadu, West Bengal, Karnataka, Andhra Pradesh, Madhya Pradesh, and Gujarat. Conclusion: SITE′s nation-wide approach will provide a real-world perspective on diabetes and hypertension and its contributing risk factors. Results from the study will raise awareness on the need for early diagnosis and management of these diseases to reduce complications.

Evaluation of Two Statistical Methods Provides Insights into the Complex Patterns of Alternative Polyadenylation Site Switching

Science.gov (United States)

Li, Jie; Li, Rui; You, Leiming; Xu, Anlong; Fu, Yonggui; Huang, Shengfeng

2015-01-01

Switching between different alternative polyadenylation (APA) sites plays an important role in the fine tuning of gene expression. New technologies for the execution of 3’-end enriched RNA-seq allow genome-wide detection of the genes that exhibit significant APA site switching between different samples. Here, we show that the independence test gives better results than the linear trend test in detecting APA site-switching events. Further examination suggests that the discrepancy between these two statistical methods arises from complex APA site-switching events that cannot be represented by a simple change of average 3’-UTR length. In theory, the linear trend test is only effective in detecting these simple changes. We classify the switching events into four switching patterns: two simple patterns (3’-UTR shortening and lengthening) and two complex patterns. By comparing the results of the two statistical methods, we show that complex patterns account for 1/4 of all observed switching events that happen between normal and cancerous human breast cell lines. Because simple and complex switching patterns may convey different biological meanings, they merit separate study. We therefore propose to combine both the independence test and the linear trend test in practice. First, the independence test should be used to detect APA site switching; second, the linear trend test should be invoked to identify simple switching events; and third, those complex switching events that pass independence testing but fail linear trend testing can be identified. PMID:25875641

American College of Radiology Accreditation Program for mammographic screening sites: Physical evaluation criteria

International Nuclear Information System (INIS)

Hendrick, R.E.; Haus, A.G.; Hubbard, L.B.; Lasky, H.J.; McCrohan, J.; McLelland, R.; Rothenberg, L.N.; Tanner, R.L.; Zinninger, M.D.

1987-01-01

The American College of Radiology has initiated a program for the accreditation of mammographic screening sites, which includes evaluation by mail of image quality and average glandular breast dose. Image quality is evaluated by use of a specially designed phantom (a modified RMI 152D Mammographic Phantom) containing simulated microcalcifications, fibrils and masses. Average glandular dose to a simulated 4.5-cm-thick (50% glandular, 50% fat) compressed breast is evaluated by thermoluminescent dosimeter measurements of entrance exposure and half value layer. Standards for acceptable image quality and patient doses are presented and preliminary results of the accreditation program are discussed

Identification of the site where the electron transfer chain of plant mitochondria is stimulated by electrostatic charge screening.

NARCIS (Netherlands)

Krab, K.; Wagner, M.J.; Wagner, A.M.; Moller, I.M.

2000-01-01

Modular kinetic analysis was used to determine the sites in plant mitochondria where charge-screening stimulates the rate of electron transfer from external NAD(P)H to oxygen. In mitochondria isolated from potato (Solanum tuberosum L.) tuber callus, stimulation of the rate of oxygen uptake was

Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.

Directory of Open Access Journals (Sweden)

Mohan Babu

2014-02-01

Full Text Available Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI screens can provide insights into the biological role(s of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.

Discussion of quantitative assessment index system of suitability of the site for geological disposal repository of high-level radioactive waste

International Nuclear Information System (INIS)

Su Rui; Wang Ju

2014-01-01

Site selection and suitability assessment of site are one of important tasks of research and development of geological disposal engineering for high-level radioactive waste (HLW). Quantitative assessment of suitability of the site is based on the scientific, reasonable and operational index system. The discussion of index screening of quantitative assessment of suitability of the site is conducted. Principle of index screening is presented and index systems are established for different stages of site selection, including planning stage of site selection, region or area investigation stage, site characterization and site confirmation stage. But the considerations are taken of the complexity of site selection of geological disposal engineering for HLW and itself development of quantitative assessment method, so improvement of the index systems presented above is needed in the further. (authors)

Immunoassay of blood spot TSH; development of a rapid two-site immunoradiometric assay and comparison with radioimmunoassay as a screening method for neonatal hypothyroidism

International Nuclear Information System (INIS)

Sutherland, R.M.; Ratcliffe, J.G.; Chapman, R.S.

1982-01-01

The development of a two-site immunoradiometric assay (IRMA) for thyrotropin (TSH) eluted from dried blood filter paper discs is described and compared with a conventional TSH radioimmunoassay (RIA) as a screening procedure for neonatal hypothyroidism. The two-site IRMA involves a primary incubation of excess labelled TSH antibody and the blood disc for 16-18 h at pH 8 and a secondary 3 h incubation under agitation, with solid phase TSH antibody. Bound and free fractions are separated by a semi-automated washing procedure. It is concluded that the two-site TSH IRMA has advantages over conventional RIA in speed, sensitivity, precision and ruggedness and can be recommended as an efficient screening procedure for neonatal hypothyroidism. (Auth.)

A Learning Collaborative Approach to Improve Primary Care STI Screening.

Science.gov (United States)

McKee, M Diane; Alderman, Elizabeth; York, Deborah V; Blank, Arthur E; Briggs, Rahil D; Hoidal, Kelsey E S; Kus, Christopher; Lechuga, Claudia; Mann, Marie; Meissner, Paul; Patel, Nisha; Racine, Andrew D

2017-10-01

The Bronx Ongoing Pediatric Screening (BOPS) project sought to improve screening for sexual activity and sexually transmitted infections (gonorrhea and chlamydia [GCC] and HIV) in a primary care network, employing a modified learning collaborative, real-time clinical data feedback to practices, improvement coaching, and a pay-for-quality monetary incentive. Outcomes are compared for 11 BOPS-participating sites and 10 non-participating sites. The quarterly median rate for documenting sexual activity status increased from 55% to 88% (BOPS sites) and from 13% to 74% (non-BOPS sites). GCC screening of sexually active youth increased at BOPS and non-BOPS sites. Screening at non-health care maintenance visits improved more at BOPS than non-BOPS sites. Data from nonparticipating sites suggests that introduction of an adolescent EMR template or other factors improved screening rates regardless of BOPS participation; BOPS activities appear to promote additional improvement of screening during non-health maintenance visits.

Treatment Complexity in Cystic Fibrosis: Trends over Time and Associations with Site-Specific Outcomes

Science.gov (United States)

Sawicki, Gregory S.; Ren, Clement L.; Konstan, Michael W.; Millar, Stefanie J.; Pasta, David J.; Quittner, Alexandra L.

2014-01-01

Background Patients with cystic fibrosis (CF) have increasing treatment complexity and high treatment burden. We describe trends in treatment complexity and evaluate its relationship with health outcomes. Methods Using Epidemiologic Study of Cystic Fibrosis (ESCF) data, we developed a treatment complexity score (TCS) from 37 chronic therapies and assessed change by age group (6–13, 14–17, and 18+ years) over a three year period. Differences in average site TCS were evaluated by quartiles based on FEV1, BMI, or Treatment Burden score on the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results TCS scores were calculated for 7252 individual patients (42% child, 16% adolescent, 43% adult) across 153 sites. In 2003, mean TCS was 11.1 for children, 11.8 for adolescents, and 12.1 for adults. In all 3 age groups, TCS increased over 3 years; the increase in TCS from 2003–2005 for children was 1.25 (95% CI 1.16–1.34), for adolescents 0.77 (0.62–0.93), and for adults 1.20 (1.08–1.31) (all pbased on FEV1 quartile. Mean TCS was higher in the highest BMI z-score quartile. Across all 3 versions of the CFQ-R, mean TCS was lower at sites in the highest quartiles (lowest burden) for CFQ-R Treatment Burden scores. Conclusion Treatment complexity was highest among adults with CF, although over 3 years, we observed a significant increase in treatment complexity in all age groups. Such increases in treatment complexity pose a challenge to patient self-management and adherence. Future research is needed to understand the associations between treatment complexity and subsequent health outcomes to reduce treatment burden and improve disease management. PMID:23352205

Using In Silico Fragmentation to Improve Routine Residue Screening in Complex Matrices

Science.gov (United States)

Kaufmann, Anton; Butcher, Patrick; Maden, Kathryn; Walker, Stephan; Widmer, Mirjam

2017-12-01

Targeted residue screening requires the use of reference substances in order to identify potential residues. This becomes a difficult issue when using multi-residue methods capable of analyzing several hundreds of analytes. Therefore, the capability of in silico fragmentation based on a structure database ("suspect screening") instead of physical reference substances for routine targeted residue screening was investigated. The detection of fragment ions that can be predicted or explained by in silico software was utilized to reduce the number of false positives. These "proof of principle" experiments were done with a tool that is integrated into a commercial MS vendor instrument operating software (UNIFI) as well as with a platform-independent MS tool (Mass Frontier). A total of 97 analytes belonging to different chemical families were separated by reversed phase liquid chromatography and detected in a data-independent acquisition (DIA) mode using ion mobility hyphenated with quadrupole time of flight mass spectrometry. The instrument was operated in the MSE mode with alternating low and high energy traces. The fragments observed from product ion spectra were investigated using a "chopping" bond disconnection algorithm and a rule-based algorithm. The bond disconnection algorithm clearly explained more analyte product ions and a greater percentage of the spectral abundance than the rule-based software (92 out of the 97 compounds produced ≥1 explainable fragment ions). On the other hand, tests with a complex blank matrix (bovine liver extract) indicated that the chopping algorithm reports significantly more false positive fragments than the rule based software. [Figure not available: see fulltext.

Charge Transfer at the Qo-Site of the Cytochrome bc1 Complex Leads to Superoxide Production

DEFF Research Database (Denmark)

Bøgh Salo, Adrian; Husen, Peter; Solov'yov, Ilia A

2017-01-01

The cytochrome bc1 complex is the third protein complex in the electron transport chain of mitochondria or photosynthetic bacteria, and it serves to create an electrochemical gradient across a cellular membrane, which is used to drive ATP synthesis. The purpose of this study is to investigate...... interactions involving an occasionally trapped oxygen molecule (O2) at the so-called Qo site of the bc1 complex, which is one of the central active sites of the protein complex, where redox reactions are expected to occur. The investigation focuses on revealing the possibility of the oxygen molecule...... to influence the normal operation of the bc1 complex and acquire an extra electron, thus becoming superoxide, a biologically toxic free radical. The process is modeled by applying quantum chemical calculations to previously performed classical molecular dynamics simulations. Investigations reveal several...

A Historical Evaluation of the U15 Complex, Nevada National Security Site, Nye County, Nevada

Energy Technology Data Exchange (ETDEWEB)

Drollinger, Harold [Desert Research Inst., Nevada University, Reno, NV (United States); Holz, Barbara A. [Desert Research Inst., Nevada University, Reno, NV (United States); Bullard, Thomas F. [Desert Research Inst., Nevada University, Reno, NV (United States); Goldenberg, Nancy G. [Desert Research Inst., Nevada University, Reno, NV (United States); Ashbaugh, Laurence J. [Desert Research Inst., Nevada University, Reno, NV (United States); Griffin, Wayne R. [Desert Research Inst., Nevada University, Reno, NV (United States)

2014-01-01

This report presents a historical evaluation of the U15 Complex on the Nevada National Security Site (NNSS) in southern Nevada. The work was conducted by the Desert Research Institute at the request of the U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office and the U.S. Department of Defense, Defense Threat Reduction Agency. Three underground nuclear tests and two underground nuclear fuel storage experiments were conducted at the complex. The nuclear tests were Hard Hat in 1962, Tiny Tot in 1965, and Pile Driver in 1966. The Hard Hat and Pile Driver nuclear tests involved different types of experiment sections in test drifts at various distances from the explosion in order to determine which sections could best survive in order to design underground command centers. The Tiny Tot nuclear test involved an underground cavity in which the nuclear test was executed. It also provided data in designing underground structures and facilities to withstand a nuclear attack. The underground nuclear fuel storage experiments were Heater Test 1 from 1977 to 1978 and Spent Fuel Test - Climax from 1978 to 1985. Heater Test 1 was used to design the later Spent Fuel Test - Climax experiment. The latter experiment was a model of a larger underground storage facility and primarily involved recording the conditions of the spent fuel and the surrounding granite medium. Fieldwork was performed intermittently in the summers of 2011 and 2013, totaling 17 days. Access to the underground tunnel complex is sealed and unavailable. Restricted to the surface, four buildings, four structures, and 92 features associated with nuclear testing and fuel storage experiment activities at the U15 Complex have been recorded. Most of these are along the west side of the complex and next to the primary access road and are characteristic of an industrial mining site, albeit one with scientific interests. The geomorphological fieldwork was conducted over three days in the

A Historical Evaluation of the U15 Complex, Nevada National Security Site, Nye County, Nevada

Energy Technology Data Exchange (ETDEWEB)

Drollinger, Harold [Desert Research Inst., Nevada University, Reno, NV (United States); Holz, Barbara A. [Desert Research Inst., Nevada University, Reno, NV (United States); Bullard, Thomas F. [Desert Research Inst., Nevada University, Reno, NV (United States); Goldenberg, Nancy G. [Desert Research Inst., Nevada University, Reno, NV (United States); Ashbaugh, Laurence J. [Desert Research Inst., Nevada University, Reno, NV (United States); Griffin, Wayne R. [Desert Research Inst., Nevada University, Reno, NV (United States)

2014-01-09

This report presents a historical evaluation of the U15 Complex on the Nevada National Security Site (NNSS) in southern Nevada. The work was conducted by the Desert Research Institute at the request of the U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office and the U.S. Department of Defense, Defense Threat Reduction Agency. Three underground nuclear tests and two underground nuclear fuel storage experiments were conducted at the complex. The nuclear tests were Hard Hat in 1962, Tiny Tot in 1965, and Pile Driver in 1966. The Hard Hat and Pile Driver nuclear tests involved different types of experiment sections in test drifts at various distances from the explosion in order to determine which sections could best survive in order to design underground command centers. The Tiny Tot nuclear test involved an underground cavity in which the nuclear test was executed. It also provided data in designing underground structures and facilities to withstand a nuclear attack. The underground nuclear fuel storage experiments were Heater Test 1 from 1977 to 1978 and Spent Fuel Test - Climax from 1978 to 1985. Heater Test 1 was used to design the later Spent Fuel Test - Climax experiment. The latter experiment was a model of a larger underground storage facility and primarily involved recording the conditions of the spent fuel and the surrounding granite medium. Fieldwork was performed intermittently in the summers of 2011 and 2013, totaling 17 days. Access to the underground tunnel complex is sealed and unavailable. Restricted to the surface, four buildings, four structures, and 92 features associated with nuclear testing and fuel storage experiment activities at the U15 Complex have been recorded. Most of these are along the west side of the complex and next to the primary access road and are characteristic of an industrial mining site, albeit one with scientific interests. The geomorphological fieldwork was conducted over three days in the

Mutations at the Qo-Site of the Cytochrome bc1 Complex Strongly Affect Oxygen Binding

DEFF Research Database (Denmark)

Husen, Peter; Solov'yov, Ilia A

2017-01-01

The homodimeric bc1 protein complex is embedded in membranes of mitochondria and photosynthetic bacteria, where it transports protons across the membrane to maintain an electrostatic potential used to drive ATP synthesis as part of the respiratory or photosynthetic pathways. The reaction cycle...... at the Qo-sites, and, moreover, different behavior of the two monomers of the bc1 complex is observed. The conformational differences at the Qo-sites of the two monomers are studied in detail and discussed. The anionic form of semiquinone was identified as leading to the greatest opportunity for side...

Site locality identification study: Hanford Site. Volume II. Data cataloging

International Nuclear Information System (INIS)

1980-07-01

Data compilation and cataloging for the candidate site locality identification study were conducted in order to provide a retrievable data cataloging system for the present siting study and future site evaluation and licensng processes. This task occurred concurrently with and also independently of other tasks of the candidate site locality identification study. Work in this task provided the data utilized primarily in the development and application of screening and ranking processes to identify candidate site localities on the Hanford Site. The overall approach included two steps: (1) data acquisition and screening; and (2) data compilation and cataloging. Data acquisition and screening formed the basis for preliminary review of data sources with respect to their probable utilization in the candidate site locality identification study and review with respect to the level of completeness and detail of the data. The important working assumption was that the data to be used in the study be based on existing and available published and unpublished literature. The data compilation and cataloging provided the basic product of the Task; a retrievable data cataloging system in the form of an annotated reference list and key word index and an index of compiled data. The annotated reference list and key word index are cross referenced and can be used to trace and retrieve the data sources utilized in the candidate site locality identification study

A quantitative 14-3-3 interaction screen connects the nuclear exosome targeting complex to the DNA damage response

DEFF Research Database (Denmark)

Blasius, Melanie; Wagner, Sebastian A; Choudhary, Chuna Ram

2014-01-01

RNA metabolism is altered following DNA damage, but the underlying mechanisms are not well understood. Through a 14-3-3 interaction screen for DNA damage-induced protein interactions in human cells, we identified protein complexes connected to RNA biology. These include the nuclear exosome...

Surface complexation modeling of uranyl adsorption on corrensite from the Waste Isolation Pilot Plant Site

Energy Technology Data Exchange (ETDEWEB)

Park, Sang-Won; Leckie, J.O. [Stanford Univ., CA (United States); Siegel, M.D. [Sandia National Labs., Albuquerque, NM (United States)

1995-09-01

Corrensite is the dominant clay mineral in the Culebra Dolomite at the Waste Isolation Pilot Plant. The surface characteristics of corrensite, a mixed chlorite/smectite clay mineral, have been studied. Zeta potential measurements and titration experiments suggest that the corrensite surface contains a mixture of permanent charge sites on the basal plane and SiOH and AlOH sites with a net pH-dependent charge at the edge of the clay platelets. Triple-layer model parameters were determined by the double extrapolation technique for use in chemical speciation calculations of adsorption reactions using the computer program HYDRAQL. Batch adsorption studies showed that corrensite is an effective adsorbent for uranyl. The pH-dependent adsorption behavior indicates that adsorption occurs at the edge sites. Adsorption studies were also conducted in the presence of competing cations and complexing ligands. The cations did not affect uranyl adsorption in the range studied. This observation lends support to the hypothesis that uranyl adsorption occurs at the edge sites. Uranyl adsorption was significantly hindered by carbonate. It is proposed that the formation of carbonate uranyl complexes inhibits uranyl adsorption and that only the carbonate-free species adsorb to the corrensite surface. The presence of the organic complexing agents EDTA and oxine also inhibits uranyl sorption.

Surface complexation modeling of uranyl adsorption on corrensite from the Waste Isolation Pilot Plant Site

International Nuclear Information System (INIS)

Park, Sang-Won; Leckie, J.O.; Siegel, M.D.

1995-09-01

Corrensite is the dominant clay mineral in the Culebra Dolomite at the Waste Isolation Pilot Plant. The surface characteristics of corrensite, a mixed chlorite/smectite clay mineral, have been studied. Zeta potential measurements and titration experiments suggest that the corrensite surface contains a mixture of permanent charge sites on the basal plane and SiOH and AlOH sites with a net pH-dependent charge at the edge of the clay platelets. Triple-layer model parameters were determined by the double extrapolation technique for use in chemical speciation calculations of adsorption reactions using the computer program HYDRAQL. Batch adsorption studies showed that corrensite is an effective adsorbent for uranyl. The pH-dependent adsorption behavior indicates that adsorption occurs at the edge sites. Adsorption studies were also conducted in the presence of competing cations and complexing ligands. The cations did not affect uranyl adsorption in the range studied. This observation lends support to the hypothesis that uranyl adsorption occurs at the edge sites. Uranyl adsorption was significantly hindered by carbonate. It is proposed that the formation of carbonate uranyl complexes inhibits uranyl adsorption and that only the carbonate-free species adsorb to the corrensite surface. The presence of the organic complexing agents EDTA and oxine also inhibits uranyl sorption

Unsymmetrical dizinc complexes as models for the active sites of phosphohydrolases.

Science.gov (United States)

Jarenmark, Martin; Csapó, Edit; Singh, Jyoti; Wöckel, Simone; Farkas, Etelka; Meyer, Franc; Haukka, Matti; Nordlander, Ebbe

2010-09-21

The unsymmetrical dinucleating ligand 2-(N-isopropyl-N-((2-pyridyl)methyl)aminomethyl)-6-(N-(carboxylmethyl)-N-((2-pyridyl)methyl)aminomethyl)-4-methylphenol (IPCPMP or L) has been synthesized to model the active site environment of dinuclear metallohydrolases. It has been isolated as the hexafluorophosphate salt H(4)IPCPMP(PF(6))(2) x 2 H(2)O (H(4)L), which has been structurally characterized, and has been used to form two different Zn(II) complexes, [{Zn(2)(IPCPMP)(OAc)}(2)][PF(6)](2) (2) and [{Zn(2)(IPCPMP)(Piv)}(2)][PF(6)](2) (3) (OAc = acetate; Piv = pivalate). The crystal structures of and show that they consist of tetranuclear complexes with very similar structures. Infrared spectroscopy and mass spectrometry indicate that the tetranuclear complexes dissociate into dinuclear complexes in solution. Potentiometric studies of the Zn(II):IPCPMP system in aqueous solution reveal that a mononuclear complex is surprisingly stable at low pH, even at a 2:1 Zn(II):L ratio, but a dinuclear complex dominates at high pH and transforms into a dihydroxido complex by a cooperative deprotonation of two, probably terminally coordinated, water molecules. A kinetic investigation indicates that one of these hydroxides is the active nucleophile in the hydrolysis of bis(2,4-dinitrophenyl)phosphate (BDNPP) enhanced by complex 2, and mechanistic proposals are presented for this reaction as well as the previously reported transesterification of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) promoted by Zn(II) complexes of IPCPMP.

Complex-scaling of screened Coulomb potentials for resonance calculations utilizing the modified Bessel functions

Science.gov (United States)

Jiao, Li-Guang; Ho, Yew Kam

2014-05-01

The screened Coulomb potential (SCP) has been extensively used in atomic physics, nuclear physics, quantum chemistry and plasma physics. However, an accurate calculation for atomic resonances under SCP is still a challenging task for various methods. Within the complex-scaling computational scheme, we have developed a method utilizing the modified Bessel functions to calculate doubly-excited resonances in two-electron atomic systems with configuration interaction-type basis. To test the validity of our method, we have calculated S- and P-wave resonance states of the helium atom with various screening strengths, and have found good agreement with earlier calculations using different methods. Our present method can be applied to calculate high-lying resonances associated with high excitation thresholds of the He+ ion, and with high-angular-momentum states. The derivation and calculation details of our present investigation together with new results of high-angular-momentum states will be presented at the meeting. Supported by NSC of Taiwan.

Implementation of nutrition risk screening using the Malnutrition Universal Screening Tool across a large metropolitan health service.

Science.gov (United States)

Cooper, P L; Raja, R; Golder, J; Stewart, A J; Shaikh, R F; Apostolides, M; Savva, J; Sequeira, J L; Silvers, M A

2016-12-01

A standardised nutrition risk screening (NRS) programme with ongoing education is recommended for the successful implementation of NRS. This project aimed to develop and implement a standardised NRS and education process across the adult bed-based services of a large metropolitan health service and to achieve a 75% NRS compliance at 12 months post-implementation. A working party of Monash Health (MH) dietitians and a nutrition technician revised an existing NRS medical record form consisting of the Malnutrition Universal Screening Tool and nutrition management guidelines. Nursing staff across six MH hospital sites were educated in the use of this revised form and there was a formalised implementation process. Support from Executive Management, nurse educators and the Nutrition Risk Committee ensured the incorporation of NRS into nursing practice. Compliance audits were conducted pre- and post-implementation. At 12 months post-implementation, organisation-wide NRS compliance reached 34.3%. For those wards that had pre-implementation NRS performed by nursing staff, compliance increased from 7.1% to 37.9% at 12 months (P Audit', which is reported 6-monthly to the Nutrition Risk Committee and site Quality and Safety Committees. NRS compliance improved at MH with strong governance support and formalised implementation; however, the overall compliance achieved appears to have been affected by the complexity and diversity of multiple healthcare sites. Ongoing education, regular auditing and establishment of NRS routines and ward practices is recommended to further improve compliance. © 2016 The British Dietetic Association Ltd.

Evaluating the adequacy of a reference site pool for ecological assessments in environmentally complex regions

Science.gov (United States)

Ode, Peter R.; Rehn, Andrew C.; Mazor, Raphael D.; Schiff, Kenneth C.; Stein, Eric D.; May, Jason; Brown, Larry R.; Herbst, David B.; Gillette, D.D.; Lunde, Kevin; Hawkins, Charles P.

2016-01-01

Many advances in the field of bioassessment have focused on approaches for objectively selecting the pool of reference sites used to establish expectations for healthy waterbodies, but little emphasis has been placed on ways to evaluate the suitability of the reference-site pool for its intended applications (e.g., compliance assessment vs ambient monitoring). These evaluations are critical because an inadequately evaluated reference pool may bias assessments in some settings. We present an approach for evaluating the adequacy of a reference-site pool for supporting biotic-index development in environmentally heterogeneous and pervasively altered regions. We followed common approaches for selecting sites with low levels of anthropogenic stress to screen 1985 candidate stream reaches to create a pool of 590 reference sites for assessing the biological integrity of streams in California, USA. We assessed the resulting pool of reference sites against 2 performance criteria. First, we evaluated how well the reference-site pool represented the range of natural gradients present in the entire population of streams as estimated by sites sampled through probabilistic surveys. Second, we evaluated the degree to which we were successful in rejecting sites influenced by anthropogenic stress by comparing biological metric scores at reference sites with the most vs fewest potential sources of stress. Using this approach, we established a reference-site pool with low levels of human-associated stress and broad coverage of environmental heterogeneity. This approach should be widely applicable and customizable to particular regional or programmatic needs.

Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA.

Science.gov (United States)

Prati, Federica; Zuccotto, Fabio; Fletcher, Daniel; Convery, Maire A; Fernandez-Menendez, Raquel; Bates, Robert; Encinas, Lourdes; Zeng, Jingkun; Chung, Chun-Wa; De Dios Anton, Paco; Mendoza-Losana, Alfonso; Mackenzie, Claire; Green, Simon R; Huggett, Margaret; Barros, David; Wyatt, Paul G; Ray, Peter C

2018-04-06

Our findings reported herein provide support for the benefits of including functional group complexity (FGC) within fragments when screening against protein targets such as Mycobacterium tuberculosis InhA. We show that InhA fragment actives with FGC maintained their binding pose during elaboration. Furthermore, weak fragment hits with functional group handles also allowed for facile fragment elaboration to afford novel and potent InhA inhibitors with good ligand efficiency metrics for optimization. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Fluorographene as a Mass Spectrometry Probe for High-Throughput Identification and Screening of Emerging Chemical Contaminants in Complex Samples.

Science.gov (United States)

Huang, Xiu; Liu, Qian; Huang, Xiaoyu; Nie, Zhou; Ruan, Ting; Du, Yuguo; Jiang, Guibin

2017-01-17

Mass spectrometry techniques for high-throughput analysis of complex samples are of profound importance in many areas such as food safety, omics studies, and environmental health science. Here we report the use of fluorographene (FG) as a new mass spectrometry probe for high-throughput identification and screening of emerging chemical contaminants in complex samples. FG was facilely synthesized by one-step exfoliation of fluorographite. With FG as a matrix or probe in matrix-assisted or surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (MALDI- or SELDI-TOF MS), higher sensitivity (detection limits at ppt or subppt levels), and better reproducibility were achieved than with other graphene-based materials due to the unique chemical structure and self-assembly properties of FG. The method was validated with different types of real complex samples. By using FG as a SELDI probe, we could easily detect trace amount of bisphenol S in paper products and high-fat canned food samples. Furthermore, we have successfully identified and screened as many as 28 quaternary ammonium halides in sewage sludge samples collected from municipal wastewater treatment plants. These results demonstrate that FG probe is a powerful tool for high-throughput analysis of complex samples by MS.

Crystal structure of importin-{alpha} complexed with a classic nuclear localization sequence obtained by oriented peptide library screening

Energy Technology Data Exchange (ETDEWEB)

Takeda, A.A.S.; Fontes, M.R.M. [UNESP, Universidade Estadual Paulista, Botucatu, SP (Brazil); Yang, S.N.Y. [University of Melbourne, Melbourne (Australia); Harris, J.M. [Queensland University of Technology, Brisbane (Australia); Jans, D.A. [Monash University, Clayton (Australia); Kobe, B. [University of Queensland, Brisbane, QU (Australia)

2012-07-01

Full text: Importin-{alpha} (Imp{alpha}) plays a role in the classical nuclear import pathway, binding to cargo proteins with activities in the nucleus. Different Imp{alpha} paralogs responsible for specific cargos can be found in a single organism. The cargos contain nuclear localization sequences (NLSs), which are characterized by one or two clusters of basic amino acids (monopartite and bipartite NLSs, respectively). In this work we present the crystal structure of Imp{alpha} from M. musculus (residues 70-529, lacking the auto inhibitory domain) bound to a NLS peptide (pepTM). The peptide corresponds to the optimal sequence obtained by an oriented peptide library experiment designed to probe the specificity of the major NLS binding site. The peptide library used five degenerate positions and identified the sequence KKKRR as the optimal sequence for binding to this site for mouse Imp{alpha} (70-529). The protein was obtained using an E. coli expression system and purified by affinity chromatography followed by an ion exchange chromatography. A single crystal of Imp{alpha} -pepTM complex was grown by the hanging drop method. The data were collected using the Synchrotron Radiation Source LNLS, Brazil and processed to 2.3. Molecular replacement techniques were used to determine the crystal structure. Electron density corresponding to the peptide was present in both major and minor binding sites The peptide is bound to Imp{alpha} similar as the simian virus 40 (SV40) large tumour (T)-antigen NLS. Binding assays confirmed that the peptide bound to Imp{alpha} with low nM affinities. This is the first time that structural information has been linked to an oriented peptide library screening approach for importin-{alpha}; the results will contribute to understanding of the sequence determinants of classical NLSs, and may help identify as yet unidentified classical NLSs in novel proteins. (author)

Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.

Science.gov (United States)

Huschmann, Franziska U; Linnik, Janina; Sparta, Karine; Ühlein, Monika; Wang, Xiaojie; Metz, Alexander; Schiebel, Johannes; Heine, Andreas; Klebe, Gerhard; Weiss, Manfred S; Mueller, Uwe

2016-05-01

Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein-ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin-fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity.

Structures of endothiapepsin–fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library

Science.gov (United States)

Huschmann, Franziska U.; Linnik, Janina; Sparta, Karine; Ühlein, Monika; Wang, Xiaojie; Metz, Alexander; Schiebel, Johannes; Heine, Andreas; Klebe, Gerhard; Weiss, Manfred S.; Mueller, Uwe

2016-01-01

Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein–ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin–fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity. PMID:27139825

Mobile loading transuranic waste at small quantity sites in the Department of Energy complex-10523

International Nuclear Information System (INIS)

Carter, Mitch; Howard, Bryan; Weyerman, Wade; Mctaggart, Jerri

2009-01-01

Los Alamos National Laboratory, Carlsbad Office (LANL-CO), operates mobile loading operations for all of the large and small quantity transuranic (TRU) waste sites in the Department of Energy (DOE) complex. The mobile loading team performs loading and unloading evolutions for both contact handled (CH) and remote handled (RH) waste. For small quantity sites, many of which have yet to remove their TRU waste, the mobile loading team will load shipments that will ship to Idaho National Laboratory, a centralization site, or ship directly to the Waste Isolation Pilot Plant (WIPP). For example, Argonne National Laboratory and General Electric Vallecitos Nuclear Center have certified programs for RH waste so they will ship their RH waste directly to WIPP. Many of the other sites will ship their waste to Idaho for characterization and certification. The Mobile Loading Units (MLU) contain all of the necessary equipment needed to load CH and RH waste into the appropriate shipping vessels. Sites are required to provide additional equipment, such as cranes, fork trucks, and office space. The sites are also required to provide personnel to assist in the shipping operations. Each site requires a site visit from the mobile loading team to ensure that all of the necessary site equipment, site requirements and space for shipping can be provided. The mobile loading team works diligently with site representatives to ensure that all safety and regulatory requirements are met. Once the waste is ready and shipping needs are met, the mobile loading team can be scheduled to ship the waste. The CH MLU is designed to support TRUPACT-II and HalfPACT loading activities wherever needed within the DOE complex. The team that performs the mobile loading operation has obtained national certification under DOE for TRUPACT-II and HalfPACT loading and shipment certification. The RH MLU is designed to support removable lid canister (RLC) and RH-72B cask loading activities wherever needed within the DOE

AMMOS: Automated Molecular Mechanics Optimization tool for in silico Screening

Directory of Open Access Journals (Sweden)

Pajeva Ilza

2008-10-01

Full Text Available Abstract Background Virtual or in silico ligand screening combined with other computational methods is one of the most promising methods to search for new lead compounds, thereby greatly assisting the drug discovery process. Despite considerable progresses made in virtual screening methodologies, available computer programs do not easily address problems such as: structural optimization of compounds in a screening library, receptor flexibility/induced-fit, and accurate prediction of protein-ligand interactions. It has been shown that structural optimization of chemical compounds and that post-docking optimization in multi-step structure-based virtual screening approaches help to further improve the overall efficiency of the methods. To address some of these points, we developed the program AMMOS for refining both, the 3D structures of the small molecules present in chemical libraries and the predicted receptor-ligand complexes through allowing partial to full atom flexibility through molecular mechanics optimization. Results The program AMMOS carries out an automatic procedure that allows for the structural refinement of compound collections and energy minimization of protein-ligand complexes using the open source program AMMP. The performance of our package was evaluated by comparing the structures of small chemical entities minimized by AMMOS with those minimized with the Tripos and MMFF94s force fields. Next, AMMOS was used for full flexible minimization of protein-ligands complexes obtained from a mutli-step virtual screening. Enrichment studies of the selected pre-docked complexes containing 60% of the initially added inhibitors were carried out with or without final AMMOS minimization on two protein targets having different binding pocket properties. AMMOS was able to improve the enrichment after the pre-docking stage with 40 to 60% of the initially added active compounds found in the top 3% to 5% of the entire compound collection

Patient-completed or symptom-based screening tools for endometriosis: a scoping review.

Science.gov (United States)

Surrey, Eric; Carter, Cathryn M; Soliman, Ahmed M; Khan, Shahnaz; DiBenedetti, Dana B; Snabes, Michael C

2017-08-01

The objective of this review was to evaluate existing patient-completed screening questionnaires and/or symptom-based predictive models with respect to their potential for use as screening tools for endometriosis in adult women. Validated instruments were of particular interest. We conducted structured searches of PubMed and targeted searches of the gray literature to identify studies reporting on screening instruments used in endometriosis. Studies were screened according to inclusion and exclusion criteria that followed the PICOS (population, intervention, comparison, outcomes, study design) framework. A total of 16 studies were identified, of which 10 described measures for endometriosis in general, 2 described measures for endometriosis at specific sites, and 4 described measures for deep-infiltrating endometriosis. Only 1 study evaluated a questionnaire that was solely patient-completed. Most measures required physician, imaging, or laboratory assessments in addition to patient-completed questionnaires, and several measures relied on complex scoring. Validation for use as a screening tool in adult women with potential endometriosis was lacking in all studies, as most studies focused on diagnosis versus screening. This literature review did not identify any fully validated, symptom-based, patient-reported questionnaires for endometriosis screening in adult women.

Quattor: managing (complex) grid sites

International Nuclear Information System (INIS)

Jouvin, M

2008-01-01

Quattor is a tool developed to efficiently manage fabrics with hundreds or thousands of Linux machines, while still being able to manage smaller clusters easily. It was originally developed inside the European Data Grid (EDG) project and is now in use at more than 50 grid sites running gLite middleware, ranging from small LCG T3s to very large sites like CERN. Quattor's ability to factorize and to reuse common parts of service configurations permitted the development of the QWG templates: a complete set of standard templates to configure the OS and gLite middleware. Any site can just import and customize the configuration without editing the bulk of the templates. Collaboration around these templates results in a very efficient sharing of installation and configuration information between those sites using them

Worry Is Good for Breast Cancer Screening: A Study of Female Relatives from the Ontario Site of the Breast Cancer Family Registry

International Nuclear Information System (INIS)

Zhang, L.; Knight, J. A.; Andrulis, I. L.; Chiarelli, A. M.; Glendon, G.; Ritvo, P.

2012-01-01

Few prospective studies have examined associations between breast cancer worry and screening behaviours in women with elevated breast cancer risks based on family history. Methods. This study included 901 high familial risk women, aged 23-71 years, from the Ontario site of the Breast Cancer Family Registry. Self-reported breast screening behaviours at year-one followup were compared between women at low (N=305), medium ( N=433), and high (N=163) levels of baseline breast cancer worry using logistic regression. Nonlinear relationships were assessed using likelihood ratio tests. Results. A significant non-linear inverted “U” relationship was observed between breast cancer worry and mammography screening (π=0. 034) for all women, where women at either low or high worry levels were less likely than those at medium to have a screening mammogram. A similar significant non-linear inverted “U” relationship was also found among all women and women at low familial risk for worry and screening clinical breast examinations (CBEs). Conclusions. Medium levels of cancer worries predicted higher rates of screening mammography and CBE among high-risk women

Screening of Potential Lead Molecule as Novel MurE Inhibitor: Virtual Screening, Molecular Dynamics and In Vitro Studies.

Science.gov (United States)

Zaveri, Kunal; Kiranmayi, Patnala

2017-01-01

The prevalence of multi-drug resistance S. aureus is one of the most challenging tasks for the treatment of nosocomial infections. Proteins and enzymes of peptidoglycan biosynthesis pathway are one among the well-studied targets, but many of the enzymes are unexplored as targets. MurE is one such enzyme featured to be a promising target. As MurE plays an important role in ligating the L-lys to stem peptide at third position that is crucial for peptidoglycan synthesis. To screen the potential MurE inhibitor by in silico approach and evaluate the best potential lead molecule by in vitro methods. In the current study, we have employed structure based virtual screening targeting the active site of MurE, followed by Molecular dynamics and in vitro studies. Virtual screening resulted in successful screening of potential lead molecule ((2R)-2-[[1-[(2R)- 2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan). The molecular dynamics of the MurE and Lead molecule complex emphasizes that lead molecule has shown stable interactions with active site residues Asp 406 and with Glu 460. In vitro studies demonstrate that the lead molecule shows antibacterial activity close to standard antibiotic Vancomycin and higher than that of Ampicillin, Streptomycin and Rifampicin. The MIC of lead molecule at 50μg/mL was observed to be 3.75 μg/mL, MBC being bactericidal with value of 6.25 μg/mL, cytotoxicity showing 34.44% and IC50 of 40.06μg/mL. These results suggest ((2R)-2-[[1-[(2R)-2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan) as a promising lead molecule for developing a MurE inhibitor against treatment of S. aureus infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

APC-PCI complex levels for screening of AAA in patients with peripheral atherosclerosis.

Science.gov (United States)

Zarrouk, Moncef; Keshavarz, Kave; Lindblad, Bengt; Gottsäter, Anders

2013-11-01

To evaluate the use of activated protein C-protein C inhibitor (APC-PCI) complex levels for detection of abdominal aortic aneurysm (AAA) in patients with peripheral atherosclerotic disease (PAD). APC-PCI levels and aortic diameter evaluated in 511 PAD patients without previously known AAA followed-up concerning survival for 4.8(0.5) years. AAA was found in 13% of patients. Aortic diameter correlated (r = 0.138; p = 0.002) with APC-PCI levels which were higher (0.40[0.45] vs. 0.30[0.49] μg/l; p = 0.004) in patients with AAA. This difference persisted in multivariate analysis (p = 0.029). A threshold value of APC-PCI ≥0.15 μg/L showed a specificity of 11%, a sensitivity of 97% and a negative predictive value of 96% for an AAA diagnosis. APC-PCI levels were higher in patients with AAA, and showed high sensitivity but low specificity for the diagnosis and can therefore not be considered as a screening tool in PAD patients. An AAA prevalence of 13% in patients with PAD indicates a need for AAA screening within this population.

High-performance liquid chromatography coupled with post-column dual-bioactivity assay for simultaneous screening of xanthine oxidase inhibitors and free radical scavengers from complex mixture.

Science.gov (United States)

Li, D Q; Zhao, J; Li, S P

2014-06-06

Xanthine oxidase (XO) can catalyze hypoxanthine and xanthine to generate uric acid and reactive oxygen species (ROS), including superoxide anion radical (O₂(•-)) and hydrogen peroxide. XO inhibitors and free radical scavengers are beneficial to the treatment of gout and many related diseases. In the present study, an on-line high-performance liquid chromatography (HPLC) coupled with post-column dual-bioactivity assay was established and successfully applied to simultaneously screening of XO inhibitors and free radical scavengers from a complex mixture, Oroxylum indicum extract. The integrated system of HPLC separation, bioactivity screening and mass spectrometry identification was proved to be simple and effective for rapid and sensitive screening of individual bioactive compounds in complex mixtures. Copyright © 2014 Elsevier B.V. All rights reserved.

Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug-binding site

OpenAIRE

Handing, Katarzyna B.; Shabalin, Ivan G.; Szlachta, Karol; Majorek, Karolina A.; Minor, Wladek

2016-01-01

Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1 ?. Cetirizine is bound in two sites ? a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizi...

Nutrition screening: science behind simplicity

African Journals Online (AJOL)

Nutrition screening triggers entry into the nutrition care process.1 Screening has informally been described as simple, quick or low-intensity proxy for more complex procedures. More formal definitions for the nutrition setting have been proposed, describing nutrition screening as a process of identifying patients, clients, or ...

Growing complexity of (expanded) carrier screening: Direct-to-consumer, physician-mediated, and clinic-based offers.

Science.gov (United States)

Chokoshvili, Davit; Vears, Danya F; Borry, Pascal

2017-10-01

Since the introduction of out-of-hospital health-related genetic tests more than a decade ago, the landscape of genetic testing services has grown in complexity. Although initially most genetic tests for health purposes were offered as direct-to-consumer services, that is, without the mediation of a medical professional, currently many commercial providers require that their tests be ordered by a licensed physician. At the same time, some commercially developed health-related genetic tests are gaining support from the professional medical community and are finding their way into clinical practice. Therefore, we differentiated between three types of genetic testing offers: direct-to-consumer, physician-mediated, and clinic-based genetic testing. Expanded carrier screening tests for recessive disorders are currently available through all the three models of genetic testing. Herein, we review the present landscape of expanded carrier screening offers by highlighting the distinct issues associated with each of the three types of genetic testing. Copyright © 2017. Published by Elsevier Ltd.

Review of MRSA screening and antibiotics prophylaxis in orthopaedic trauma patients; The risk of surgical site infection with inadequate antibiotic prophylaxis in patients colonized with MRSA.

Science.gov (United States)

Iqbal, H J; Ponniah, N; Long, S; Rath, N; Kent, M

2017-07-01

The primary aim of this study was to determine whether orthopaedic trauma patients receive appropriate antibiotic prophylaxis keeping in view the results of their MRSA screening. The secondary aim was to analyse the risk of developing MRSA surgical site infection with and without appropriate antibiotic prophylaxis in those colonized with MRSA. We reviewed 400 consecutive orthopaedic trauma patient episodes. Preoperative MRSA screening results, operative procedures, prophylactic antibiotics and postoperative course were explored. In addition to these consecutive patients, the hospital MRSA database over the previous 5 years identified 27 MRSA colonized acute trauma patients requiring surgery. Of the 400 consecutive patient episodes, 395(98.7%) had MRSA screening performed on admission. However, in 236 (59.0%) cases, the results were not available before the surgery. Seven patient episodes (1.8%) had positive MRSA colonization. Analysis of 27 MRSA colonized patients revealed that 20(74%) patients did not have the screening results available before the surgery. Only 5(18.5%) received Teicoplanin and 22(81.4%) received cefuroxime for antibiotic prophylaxis before their surgery. Of those receiving cefuroxime, five (22.73%) patients developed postoperative MRSA surgical site infection (SSI) but none of those (0%) receiving Teicoplanin had MRSA SSI. The absolute risk reduction for SSI with Teicoplanin as antibiotic prophylaxis was 22.73% (CI=5.22%-40.24%) and NNT (Number Needed to Treat) was 5 (CI=2.5-19.2) CONCLUSION: Lack of available screening results before the surgery may lead to inadequate antibiotic prophylaxis increasing the risk of MRSA surgical site infection. Glycopeptide (e.g.Teicoplanin) prophylaxis should be considered when there is history of MRSA colonization or MRSA screening results are not available before the surgery. Copyright © 2017. Published by Elsevier Ltd.

Virtual Screening and Prediction of Site of Metabolism for Cytochrome P450 1A2 Ligands

DEFF Research Database (Denmark)

Vasanthanathan, P.; Hritz, Jozef; Taboureau, Olivier

2009-01-01

questions have been addressed: 1. Binding orientations and conformations were successfully predicted for various substrates. 2. A virtual screen was performed with satisfying enrichment rates. 3. A classification of individual compounds into active and inactive was performed. It was found that while docking...... can be used successfully to address the first two questions, it seems to be more difficult to perform the classification. Different scoring functions were included, and the well-characterized water molecule in the active site was included in various ways. Results are compared to experimental data...

Just-in-Time Compound Pooling Increases Primary Screening Capacity without Compromising Screening Quality.

Science.gov (United States)

Elkin, L L; Harden, D G; Saldanha, S; Ferguson, H; Cheney, D L; Pieniazek, S N; Maloney, D P; Zewinski, J; O'Connell, J; Banks, M

2015-06-01

Compound pooling, or multiplexing more than one compound per well during primary high-throughput screening (HTS), is a controversial approach with a long history of limited success. Many issues with this approach likely arise from long-term storage of library plates containing complex mixtures of compounds at high concentrations. Due to the historical difficulties with using multiplexed library plates, primary HTS often uses a one-compound-one-well approach. However, as compound collections grow, innovative strategies are required to increase the capacity of primary screening campaigns. Toward this goal, we have developed a novel compound pooling method that increases screening capacity without compromising data quality. This method circumvents issues related to the long-term storage of complex compound mixtures by using acoustic dispensing to enable "just-in-time" compound pooling directly in the assay well immediately prior to assay. Using this method, we can pool two compounds per well, effectively doubling the capacity of a primary screen. Here, we present data from pilot studies using just-in-time pooling, as well as data from a large >2-million-compound screen using this approach. These data suggest that, for many targets, this method can be used to vastly increase screening capacity without significant reduction in the ability to detect screening hits. © 2015 Society for Laboratory Automation and Screening.

Initial screening of thermal desorption for soil remediation

International Nuclear Information System (INIS)

Yezzi, J.J. Jr.; Tafuri, A.N.; Rosenthal, S.; Troxler, W.L.

1994-01-01

Petroleum-contaminated soils--caused by spills, leaks, and accidental discharges--exist at many sites throughout the United States. Thermal desorption technologies which are increasingly being employed to treat these soils, have met soil cleanup criteria for a variety of petroleum products. Currently the United States Environmental Protection Agency is finalizing a technical report entitled Use of Thermal Desorption for Treating Petroleum-Contaminated Soils to assist remedial project managers, site owners, remediation contractors, and equipment vendors in evaluating the use of thermal desorption technologies for petroleum-contaminated soil applications. The report will present a three-level screening method to help a reader predict the success of applying thermal desorption at a specific site. The objective of screening level one is to determine the likelihood of success in a specific application of thermal desorption. It will take into account procedures for collecting and evaluating data on site characteristics, contaminant characteristics, soil characteristics, and regulatory requirements. This level will establish whether or not thermal desorption should be evaluated further for site remediation, whether treatment should occur on-site or off-site, and if on-site is a viable option, what system size will be most cost-effective. The scope of this paper addresses only screening level one which provides a preliminary assessment of the applicability of thermal desorption to a particular site. This topic encompasses worksheets that are an integral part of the ''user friendly'' screening process. Level one screening provides a foundation for the subsequent two levels which follow a similar ''user friendly'' worksheet approach to evaluating thermal desorption technologies and establishing costs for thermal desorption in an overall remediation project

Synthesis, physico-chemical and antimicrobial screening studies on 14 and 16-membered hexaazamacrocyclic complexes bearing pendant amine groups

Directory of Open Access Journals (Sweden)

Shakir Mohammad

2006-01-01

Full Text Available The synthesis and characterization of a series of 14 and 16-membered hexaazamacrocyclic complexes, which were obtained via template condensation of 1,2- diaminoethane or 1,3-diaminopropane, formaldehyde and hydrazine hydrate in the presence of first row transition metal salts are reported. Complexes of the types, [ML¹(NO32]; [CuL¹](NO32 and [ML²Cl2]; [CuL²]Cl2 (where M = Co(II, Ni(II and Zn(II, were obtained. Elemental analyses, IR spectra, ¹H NMR, EPR, UV-Vis, magnetic susceptibility and conductivity measurements have ascertained the overall geometry and stereochemistry of the complexes. An octahedral geometry has been suggested for all the complexes, except for copper compounds, in which the metal centre coordinates to the four nitrogen atoms of macrocyclic ligand in a square planar fashion. These complexes were screened against different fungi and bacteria in vitro and were found to be potentially active in the concentration 5 mg mL-1.

The Current State of Screening and Decolonization for the Prevention of Staphylococcus aureus Surgical Site Infection After Total Hip and Knee Arthroplasty.

Science.gov (United States)

Weiser, Mitchell C; Moucha, Calin S

2015-09-02

The most common pathogens in surgical site infections after total hip and knee arthroplasty are methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and coagulase-negative staphylococci. Patients colonized with MSSA or MRSA have an increased risk for a staphylococcal infection at the site of a total hip or knee arthroplasty. Most colonized individuals who develop a staphylococcal infection at the site of a total hip or total knee arthroplasty have molecularly identical S. aureus isolates in their nares and wounds. Screening and nasal decolonization of S. aureus can potentially reduce the rates of staphylococcal surgical site infection after total hip and total knee arthroplasty. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Distance to screening site and non-participation in screening for breast cancer

DEFF Research Database (Denmark)

Jensen, L F; Pedersen, A F; Andersen, B

2013-01-01

Dette studie undersøger, om der er en sammenhæng mellem afstand til screeningsenhederne og deltagelse i screening for brystkræft. Resultaterne viser, at kvinder, som bor tæt på screeningsenheden, og kvinder, som bor længere væk, er mere tilbøjelige til ikke at deltage i første screeningsrunde. Ved...

Screening methodology for site selection of a nuclear waste repository in shale formations in Germany

International Nuclear Information System (INIS)

Hoth, P.; Krull, P.; Wirth, H.

2004-01-01

The radioactive waste disposal policy in the Federal Republic of Germany is based on the principle that all types of radioactive waste must be disposed of in deep geological formations. Because of the favourable properties of rock salt and the existence of thick rock salt formations in Germany, so far most of the research in the field of radioactive waste disposal sites was focused on the study of the use of rock salt. In addition, German research organisations have also conducted generic research and development projects in alternative geological formations (Wanner and Brauer, 2001), but a comprehensive evaluation of their utilisation has been only done for parts of the crystalline rocks in Germany. Research projects on argillaceous rocks started relatively late, so that German experience is mainly connected to German research work with the corresponding European Underground Research Laboratories and the exploration of the former Konrad iron mine as a potential repository site for radioactive waste with negligible heat generation. The German Federal Government has signed in 2001 an agreement with national utility companies to end electricity generation by nuclear power. This decision affected the entire German radioactive waste isolation strategy and especially the repository projects. The utility companies agreed upon standstill of exploration at the Gorleben site and the Federal Ministry for the Environment tries to establish a new comprehensive procedure for the selection of a repository site, built upon well-founded criteria incorporating public participation. Step 3 of the planning includes the examination of further sites in Germany and the comparison with existing sites and concepts. Under these circumstances, argillaceous rock (clay and shale) formations are now a special area of interest in Germany and the development of a screening methodology was required for the evaluation of shales as host and barrier rocks for nuclear waste repositories. (author)

Leveraging structure determination with fragment screening for infectious disease drug targets: MECP synthase from Burkholderia pseudomallei

Energy Technology Data Exchange (ETDEWEB)

Begley, Darren W.; Hartley, Robert C.; Davies, Douglas R.; Edwards, Thomas E.; Leonard, Jess T.; Abendroth, Jan; Burris, Courtney A.; Bhandari, Janhavi; Myler, Peter J.; Staker, Bart L.; Stewart, Lance J. (UWASH); (Emerald)

2011-09-28

As part of the Seattle Structural Genomics Center for Infectious Disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. We have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. In this study, we report fragment screening methods and structure determination results for 2C-methyl-D-erythritol-2,4-cyclo-diphosphate (MECP) synthase from Burkholderia pseudomallei, the gram-negative bacterium which causes melioidosis. Screening by nuclear magnetic resonance spectroscopy as well as crystal soaking followed by X-ray diffraction led to the identification of several small molecules which bind this enzyme in a critical metabolic pathway. A series of complex structures obtained with screening hits reveal distinct binding pockets and a range of small molecules which form complexes with the target. Additional soaks with these compounds further demonstrate a subset of fragments to only bind the protein when present in specific combinations. This ensemble of fragment-bound complexes illuminates several characteristics of MECP synthase, including a previously unknown binding surface external to the catalytic active site. These ligand-bound structures now serve to guide medicinal chemists and structural biologists in rational design of novel inhibitors for this enzyme.

CSBB-ConeExclusion, adapting structure based solution virtual screening to libraries on solid support.

Science.gov (United States)

Shave, Steven; Auer, Manfred

2013-12-23

Combinatorial chemical libraries produced on solid support offer fast and cost-effective access to a large number of unique compounds. If such libraries are screened directly on-bead, the speed at which chemical space can be explored by chemists is much greater than that addressable using solution based synthesis and screening methods. Solution based screening has a large supporting body of software such as structure-based virtual screening tools which enable the prediction of protein-ligand complexes. Use of these techniques to predict the protein bound complexes of compounds synthesized on solid support neglects to take into account the conjugation site on the small molecule ligand. This may invalidate predicted binding modes, the linker may be clashing with protein atoms. We present CSBB-ConeExclusion, a methodology and computer program which provides a measure of the applicability of solution dockings to solid support. Output is given in the form of statistics for each docking pose, a unique 2D visualization method which can be used to determine applicability at a glance, and automatically generated PyMol scripts allowing visualization of protein atom incursion into a defined exclusion volume. CSBB-ConeExclusion is then exemplarically used to determine the optimum attachment point for a purine library targeting cyclin-dependent kinase 2 CDK2.

Requirement of histidine 217 for ubiquinone reductase activity (Qi site) in the cytochrome bc1 complex.

Science.gov (United States)

Gray, K A; Dutton, P L; Daldal, F

1994-01-25

Folding models suggest that the highly conserved histidine 217 of the cytochrome b subunit from the cytochrome bc1 complex is close to the quinone reductase (Qi) site. This histidine (bH217) in the cytochrome b polypeptide of the photosynthetic bacterium Rhodobacter capsulatus has been replaced with three other residues, aspartate (D), arginine (R), and leucine (L). bH217D and bH217R are able to grow photoheterotrophically and contain active cytochrome bc1 complexes (60% of wild-type activity), whereas the bH217L mutant is photosynthetically incompetent and contains a cytochrome bc1 complex that has only 10% of the wild-type activity. Single-turnover flash-activated electron transfer experiments show that cytochrome bH is reduced via the Qo site with near native rates in the mutant strains but that electron transfer between cytochrome bH and quinone bound at the Qi site is greatly slowed. These results are consistent with redox midpoint potential (Em) measurements of the cytochrome b subunit hemes and the Qi site quinone. The Em values of cyt bL and bH are approximately the same in the mutants and wild type, although the mutant strains have a larger relative concentration of what may be the high-potential form of cytochrome bH, called cytochrome b150. However, the redox properties of the semiquinone at the Qi site are altered significantly. The Qi site semiquinone stability constant of bH217R is 10 times higher than in the wild type, while in the other two strains (bH217D and bH217L) the stability constant is much lower than in the wild type. Thus H217 appears to have major effects on the redox properties of the quinone bound at the Qi site. These data are incorporated into a suggestion that H217 forms part of the binding pocket of the Qi site in a manner reminiscent of the interaction between quinone bound at the Qb site and H190 of the L subunit of the bacterial photosynthetic reaction center.

Addressing the Complexities of Big Data Analytics in Healthcare: The Diabetes Screening Case

Directory of Open Access Journals (Sweden)

Daswin De Silva

2015-09-01

Full Text Available The healthcare industry generates a high throughput of medical, clinical and omics data of varying complexity and features. Clinical decision-support is gaining widespread attention as medical institutions and governing bodies turn towards better management of this data for effective and efficient healthcare delivery and quality assured outcomes. Amass of data across all stages, from disease diagnosis to palliative care, is further indication of the opportunities and challenges to effective data management, analysis, prediction and optimization techniques as parts of knowledge management in clinical environments. Big Data analytics (BDA presents the potential to advance this industry with reforms in clinical decision-support and translational research. However, adoption of big data analytics has been slow due to complexities posed by the nature of healthcare data. The success of these systems is hard to predict, so further research is needed to provide a robust framework to ensure investment in BDA is justified. In this paper we investigate these complexities from the perspective of updated Information Systems (IS participation theory. We present a case study on a large diabetes screening project to integrate, converge and derive expedient insights from such an accumulation of data and make recommendations for a successful BDA implementation grounded in a participatory framework and the specificities of big data in healthcare context.

Recycled Uranium Mass Balance Project Y-12 National Security Complex Site Report

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-12-01

This report has been prepared to summarize the findings of the Y-12 National Security Complex (Y-12 Complex) Mass Balance Project and to support preparation of associated U. S. Department of Energy (DOE) site reports. The project was conducted in support of DOE efforts to assess the potential for health and environmental issues resulting from the presence of transuranic (TRU) elements and fission products in recycled uranium (RU) processed by DOE and its predecessor agencies. The United States government used uranium in fission reactors to produce plutonium and tritium for nuclear weapons production. Because uranium was considered scarce relative to demand when these operations began almost 50 years ago, the spent fuel from U.S. fission reactors was processed to recover uranium for recycling. The estimated mass balance for highly enriched RU, which is of most concern for worker exposure and is the primary focus of this project, is summarized in a table. A discrepancy in the mass balance between receipts and shipments (plus inventory and waste) reflects an inability to precisely distinguish between RU and non-RU shipments and receipts involving the Y-12 Complex and Savannah River. Shipments of fresh fuel (non-RU) and sweetener (also non-RU) were made from the Y-12 Complex to Savannah River along with RU shipments. The only way to distinguish between these RU and non-RU streams using available records is by enrichment level. Shipments of {le}90% enrichment were assumed to be RU. Shipments of >90% enrichment were assumed to be non-RU fresh fuel or sweetener. This methodology using enrichment level to distinguish between RU and non-RU results in good estimates of RU flows that are reasonably consistent with Savannah River estimates. Although this is the best available means of distinguishing RU streams, this method does leave a difference of approximately 17.3 MTU between receipts and shipments. Slightly depleted RU streams received by the Y-12 Complex from ORGDP and

Engineering aspects of Passavant screening

International Nuclear Information System (INIS)

Siddle, K.R.; Sharma, R.K.

1978-01-01

The Passavant screen was developed in Europe almost 30 years ago. The Passavant screen is a vertical traveling screen; however, the basic difference between the conventional vertical traveling screen and the Passavant screen is that in the conventional screen water passes through the front screen belt and then the back screen belt, whereas in the Passavant screen the water enters in between the two belts and passes laterally through either of the belts. Thus, theoretically, the screening surface of the Passavant screen is doubled as compared to the same size conventional vertical traveling screen. Various design and operational modifications of the Passavant screen are possible to yield optimum design and performance characteristics which make it amenable to installation at power plants for safe removal of not only fish but also smaller organisms such as fish eggs and larvae. In this paper, details of the screen design and operational characteristics are discussed with notes on how these features can be modified to suit site- and organism-specific requirements

Hazard screening application guide

International Nuclear Information System (INIS)

1992-06-01

The basic purpose of hazard screening is to group precesses, facilities, and proposed modifications according to the magnitude of their hazards so as to determine the need for and extent of follow on safety analysis. A hazard is defined as a material, energy source, or operation that has the potential to cause injury or illness in human beings. The purpose of this document is to give guidance and provide standard methods for performing hazard screening. Hazard screening is applied to new and existing facilities and processes as well as to proposed modifications to existing facilities and processes. The hazard screening process evaluates an identified hazards in terms of the effects on people, both on-site and off-site. The process uses bounding analyses with no credit given for mitigation of an accident with the exception of certain containers meeting DOT specifications. The process is restricted to human safety issues only. Environmental effects are addressed by the environmental program. Interfaces with environmental organizations will be established in order to share information

iScreen: Image-Based High-Content RNAi Screening Analysis Tools.

Science.gov (United States)

Zhong, Rui; Dong, Xiaonan; Levine, Beth; Xie, Yang; Xiao, Guanghua

2015-09-01

High-throughput RNA interference (RNAi) screening has opened up a path to investigating functional genomics in a genome-wide pattern. However, such studies are often restricted to assays that have a single readout format. Recently, advanced image technologies have been coupled with high-throughput RNAi screening to develop high-content screening, in which one or more cell image(s), instead of a single readout, were generated from each well. This image-based high-content screening technology has led to genome-wide functional annotation in a wider spectrum of biological research studies, as well as in drug and target discovery, so that complex cellular phenotypes can be measured in a multiparametric format. Despite these advances, data analysis and visualization tools are still largely lacking for these types of experiments. Therefore, we developed iScreen (image-Based High-content RNAi Screening Analysis Tool), an R package for the statistical modeling and visualization of image-based high-content RNAi screening. Two case studies were used to demonstrate the capability and efficiency of the iScreen package. iScreen is available for download on CRAN (http://cran.cnr.berkeley.edu/web/packages/iScreen/index.html). The user manual is also available as a supplementary document. © 2014 Society for Laboratory Automation and Screening.

Thermomechanical study of complex structures in the aperture of superconducting magnets: Application to the design of the High-Luminosity LHC shielded beam screen

CERN Document Server

AUTHOR|(CDS)2086332; Aurisicchio, Marco

In the framework of the High-Luminosity Large Hadron Collider (HL-LHC) project, a complex structure, known as the beam screen, will be installed by 2024 in the aperture of the inner triplet superconducting magnets nearby the ATLAS and CMS experiments. The beam screen is an octagonal shaped pipe that shields the 1.9 K magnet cryogenic system from the heat loads and damage to the magnet coils that would be otherwise induced by the highly penetrating collision debris. It also ensures that the vacuum conditions, required for the stability of the beam, are met. This thesis describes the design of the beam screen and proposes extensions to important components and features. The unknown physical properties of the beam screen materials have been characterised. The thermal behaviour of the beam screen during normal working conditions has been optimised by simulations and validated by measurements. The behaviour of the beam screen during a magnet quench, a resistive transition of the superconducting magnet, has been st...

Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer's-Associated Aβ Oligomers.

Directory of Open Access Journals (Sweden)

Kyle C Wilcox

Full Text Available Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs. AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs. This method gives a soluble membrane protein library (SMPL--a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer's model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can

Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer's-Associated Aβ Oligomers.

Science.gov (United States)

Wilcox, Kyle C; Marunde, Matthew R; Das, Aditi; Velasco, Pauline T; Kuhns, Benjamin D; Marty, Michael T; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G; Klein, William L

2015-01-01

Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs). This method gives a soluble membrane protein library (SMPL)--a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer's model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can facilitate drug discovery

On-site and off-site forensic analysis capabilities for proliferation and terrorism prevention

International Nuclear Information System (INIS)

Whipple, R.E.; Nunes, P.J.; Reynolds, J.G.; Alcaraz, A.; Hart, B.R.

2004-01-01

Full text: We will present current on-site technologies that can be utilized for the screening of explosives, chemical agents, and environmental contaminants. These techniques must have the capability to detect various hazardous materials at very low levels, since they pose a major challenge for first responders. Specifically, the technology must detect concealed explosives or chemical agents on-site rapidly. Lawrence Livermore National Laboratory (LLNL) is currently developing several different high explosive screening and detection technologies for field use. Two technologies that have demonstrated an ability to screen for explosives at low levels are colorimetric spot tests and thin layer chromatography (TLC). Another technology that has demonstrated usefulness for the on-site analysis of unknowns is portable gas chromatography-mass spectrometry (GC-MS) with solid phase micro-extraction (SPME) sampling. Several examples utilizing these technologies and their usefulness will be presented. In addition to developing on-site screening methods, LLNL is an Organization for the Prohibition of Chemical Weapons (OPCW) designated laboratory and is certified to accept CW suspect samples. Currently, LLNL is expanding its ISO-17025 certification to include nuclear forensics and explosives. These off-site forensic analysis capabilities and certified procedures will support the needs for homeland security. We will highlight some of the ISO-17025 requirements to accredit procedures, handle samples, and reports. Work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract W-7405-ENG-48

On-site and off-site forensic analysis capabilities for proliferation and terrorism prevention

International Nuclear Information System (INIS)

Hart, B.R.; Whipple, R.E.; Nunes, P.J.; Reynolds, J.G.; Alcaraz, A.

2004-01-01

We present current on-site technologies that can be utilized for the screening of explosives, chemical agents, and environmental contaminants. These techniques must have the capability to detect various hazardous materials at very low levels, since they pose a major challenge for first responders. Specifically, the technology must detect concealed explosives or chemical agents on-site rapidly. Lawrence Livermore National Laboratory (LLNL) is currently developing several different high explosive screening and detection technologies for field use. Two technologies that have demonstrated an ability to screen for explosives at low levels are colorimetric spot tests and thin layer chromatography (TLC). Another technology that has demonstrated usefulness for the on-site analysis of unknowns is portable gas chromatography-mass spectrometry (GC-MS) with solid phase micro-extraction (SPME) sampling. Several examples utilizing these technologies and their usefulness will be presented. In addition to developing on-site screening methods, LLNL is an Organization for the Prohibition of Chemical Weapons (OPCW) designated laboratory and is certified to accept CW suspect samples. Currently, LLNL is expanding its ISO-17025 certification to include nuclear forensics and explosives. These off-site forensic analysis capabilities and certified procedures will support the needs for homeland security. We will highlight some of the ISO-17025 requirements to accredit procedures, handle samples, and reports. Work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract W-7405-ENG-48. (author)

STRP Screening Sets for the human genome at 5 cM density

Directory of Open Access Journals (Sweden)

Marth Gabor

2003-02-01

Full Text Available Abstract Background Short tandem repeat polymorphisms (STRPs are powerful tools for gene mapping and other applications. A STRP genome scan of 10 cM is usually adequate for mapping single gene disorders. However mapping studies involving genetically complex disorders and especially association (linkage disequilibrium often require higher STRP density. Results We report the development of two separate 10 cM human STRP Screening Sets (Sets 12 and 52 which span all chromosomes. When combined, the two Sets contain a total of 782 STRPs, with average STRP spacing of 4.8 cM, average heterozygosity of 0.72, and total sex-average coverage of 3535 cM. The current Sets are comprised almost entirely of STRPs based on tri- and tetranucleotide repeats. We also report correction of primer sequences for many STRPs used in previous Screening Sets. Detailed information for the new Screening Sets is available from our web site: http://research.marshfieldclinic.org/genetics. Conclusion Our new human STRP Screening Sets will improve the quality and cost effectiveness of genotyping for gene mapping and other applications.

Single site mutations in the hetero-oligomeric Mrp antiporter from alkaliphilic Bacillus pseudofirmus OF4 that affect Na+/H+ antiport activity, sodium exclusion, individual Mrp protein levels, or Mrp complex formation.

Science.gov (United States)

Morino, Masato; Natsui, Shinsuke; Ono, Tomohiro; Swartz, Talia H; Krulwich, Terry A; Ito, Masahiro

2010-10-01

Mrp systems are widely distributed and structurally complex cation/proton antiporters. Antiport activity requires hetero-oligomeric complexes of all six or seven hydrophobic Mrp proteins (MrpA-MrpG). Here, a panel of site-directed mutants in conserved or proposed motif residues was made in the Mrp Na(+)(Li(+))/H(+) antiporter from an alkaliphilic Bacillus. The mutant operons were expressed in antiporter-deficient Escherichia coli KNabc and assessed for antiport properties, support of sodium resistance, membrane levels of each Mrp protein, and presence of monomeric and dimeric Mrp complexes. Antiport did not depend on a VFF motif or a conserved tyrosine pair, but a role for a conserved histidine in a potential quinone binding site of MrpA was supported. The importance of several acidic residues for antiport was confirmed, and the importance of additional residues was demonstrated (e.g. three lysine residues conserved across MrpA, MrpD, and membrane-bound respiratory Complex I subunits (NuoL/M/N)). The results extended indications that MrpE is required for normal membrane levels of other Mrp proteins and for complex formation. Moreover, mutations in several other Mrp proteins lead to greatly reduced membrane levels of MrpE. Thus, changes in either of the two Mrp modules, MrpA-MrpD and MrpE-MrpG, influence the other. Two mutants, MrpB-P37G and MrpC-Q70A, showed a normal phenotype but lacked the MrpA-MrpG monomeric complex while retaining the dimeric hetero-oligomeric complex. Finally, MrpG-P81A and MrpG-P81G mutants exhibited no antiport activity but supported sodium resistance and a low [Na(+)](in). Such mutants could be used to screen hypothesized but uncharacterized sodium efflux functions of Mrp apart from Na(+) (Li(+))/H(+) antiport.

The Emergence of Second-Screen Gatekeeping

DEFF Research Database (Denmark)

Jensen, Mads Hvas

2016-01-01

Legacy media have recently started to include material from social network sites in televised events, including election debates, to enhance the viewing experience of users and to enable interactions between viewers and political candidates. Decisions about which material and which users to include...... on the screen comprise a new arena for the gatekeeping function of the established media. In this paper, I introduce the concept of second-screen gatekeeping as a theoretical framework for understanding the gatekeeping practice taking place between the first and the second screens. To examine this emergent...... practice of second-screen gatekeeping, the paper introduces an empirical study of the selection process of material from social network sites in the live-broadcast election debates on Denmark’s two leading television channels, the public service institution DR1 and the commercial station TV2, in the run...

An unexpected phosphate binding site in Glyceraldehyde 3-Phosphate Dehydrogenase: Crystal structures of apo, holo and ternary complex of Cryptosporidium parvum enzyme

Energy Technology Data Exchange (ETDEWEB)

Cook, William J; Senkovich, Olga; Chattopadhyay, Debasish; (UAB)

2009-06-08

The structure, function and reaction mechanism of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) have been extensively studied. Based on these studies, three anion binding sites have been identified, one 'Ps' site (for binding the C-3 phosphate of the substrate) and two sites, 'Pi' and 'new Pi', for inorganic phosphate. According to the original flip-flop model, the substrate phosphate group switches from the 'Pi' to the 'Ps' site during the multistep reaction. In light of the discovery of the 'new Pi' site, a modified flip-flop mechanism, in which the C-3 phosphate of the substrate binds to the 'new Pi' site and flips to the 'Ps' site before the hydride transfer, was proposed. An alternative model based on a number of structures of B. stearothermophilus GAPDH ternary complexes (non-covalent and thioacyl intermediate) proposes that in the ternary Michaelis complex the C-3 phosphate binds to the 'Ps' site and flips from the 'Ps' to the 'new Pi' site during or after the redox step. We determined the crystal structure of Cryptosporidium parvum GAPDH in the apo and holo (enzyme + NAD) state and the structure of the ternary enzyme-cofactor-substrate complex using an active site mutant enzyme. The C. parvum GAPDH complex was prepared by pre-incubating the enzyme with substrate and cofactor, thereby allowing free movement of the protein structure and substrate molecules during their initial encounter. Sulfate and phosphate ions were excluded from purification and crystallization steps. The quality of the electron density map at 2{angstrom} resolution allowed unambiguous positioning of the substrate. In three subunits of the homotetramer the C-3 phosphate group of the non-covalently bound substrate is in the 'new Pi' site. A concomitant movement of the phosphate binding loop is observed in these three subunits. In the fourth subunit the C-3 phosphate

An unexpected phosphate binding site in Glyceraldehyde 3-Phosphate Dehydrogenase: Crystal structures of apo, holo and ternary complex of Cryptosporidium parvum enzyme

Directory of Open Access Journals (Sweden)

Chattopadhyay Debasish

2009-02-01

Full Text Available Abstract Background The structure, function and reaction mechanism of glyceraldehyde 3-phosphate dehydrogenase (GAPDH have been extensively studied. Based on these studies, three anion binding sites have been identified, one 'Ps' site (for binding the C-3 phosphate of the substrate and two sites, 'Pi' and 'new Pi', for inorganic phosphate. According to the original flip-flop model, the substrate phosphate group switches from the 'Pi' to the 'Ps' site during the multistep reaction. In light of the discovery of the 'new Pi' site, a modified flip-flop mechanism, in which the C-3 phosphate of the substrate binds to the 'new Pi' site and flips to the 'Ps' site before the hydride transfer, was proposed. An alternative model based on a number of structures of B. stearothermophilus GAPDH ternary complexes (non-covalent and thioacyl intermediate proposes that in the ternary Michaelis complex the C-3 phosphate binds to the 'Ps' site and flips from the 'Ps' to the 'new Pi' site during or after the redox step. Results We determined the crystal structure of Cryptosporidium parvum GAPDH in the apo and holo (enzyme + NAD state and the structure of the ternary enzyme-cofactor-substrate complex using an active site mutant enzyme. The C. parvum GAPDH complex was prepared by pre-incubating the enzyme with substrate and cofactor, thereby allowing free movement of the protein structure and substrate molecules during their initial encounter. Sulfate and phosphate ions were excluded from purification and crystallization steps. The quality of the electron density map at 2Å resolution allowed unambiguous positioning of the substrate. In three subunits of the homotetramer the C-3 phosphate group of the non-covalently bound substrate is in the 'new Pi' site. A concomitant movement of the phosphate binding loop is observed in these three subunits. In the fourth subunit the C-3 phosphate occupies an unexpected site not seen before and the phosphate binding loop remains in

Description of a Multipurpose Processing and Storage Complex for the Hanford Site's radioactive material

International Nuclear Information System (INIS)

Nyman, D.H.; Wolfe, B.A.; Hoertkorn, T.R.

1993-05-01

The mission of the US Department of Energy's (DOE) Hanford Site has changed from defense nuclear materials production to that of waste management/disposal and environmental restoration. ne Multipurpose Processing and Storage Complex (MPSC) is being designed to process discarded waste tank internal hardware contaminated with mixed wastes, failed melters from the vitrification plant, and other Hanford Site high-level solid waste. The MPSC also will provide interim storage of other radioactive materials (irradiated fuel, canisters of vitrified high-level waste [HLW], special nuclear material [SNM], and other designated radioactive materials)

Optimization Review: Bunker Hill Mining and Metallurgical Complex Superfund Site, Central Treatment Plant (CTP), Kellogg, Shoshone County, Idaho

Science.gov (United States)

The Bunker Hill Mining and Metallurgical Complex Superfund Site includes all areas of the Coeur d’Alene Basin where mining-related contamination occurred and encompasses a 21-square mile “Box” along Interstate 90 surrounding the former smelter complex.

Label-free Fab and Fc affinity/avidity profiling of the antibody complex half-life for polyclonal and monoclonal efficacy screening.

Science.gov (United States)

Read, Thomas; Olkhov, Rouslan V; Williamson, E Diane; Shaw, Andrew M

2015-09-01

A unified approach to affinity screening for Fab and Fc interactions of an antibody for its antigen and FcγR receptor has been developed. An antigen array is used for the Fab affinity and cross-reactivity screening and protein A/G proxy is the FcγR receptor. The affinities are derived using a simple 1:1 binding model with a consistent error analysis. The association and dissociation kinetics are measured over optimised times for accurate determination. The Fab/Fc affinities are derived for ten antibodies: mAb-actin (mouse), pAb-BSA (sheep), pAb-collagen V (rabbit), pAb-CRP (goat), mAb-F1 (mouse), mAbs (mouse) 7.3, 12.3, 29.3, 36.3 and 46.3 raised against LcrV in Yersinia pestis. The rate of the dissociation of antigen-antibody complexes relates directly to their immunological function as does the Fc-FcγR complex and a new half-life plot has been defined with a Fab/Fc half-life range of 17-470 min. The upper half-life value points to surface avidity. Two antibodies that are protective as an immunotherapy define a Fab half-life >250 min and an Fc half-life >50 min as characteristics of ideal interactions which can form the basis of an antibody screen for immunotherapy.

Identification of Ubiquinol Binding Motifs at the Qo-Site of the Cytochrome bc1 Complex

DEFF Research Database (Denmark)

Barragan, Angela M.; Crofts, Antony R.; Schulten, Klaus

2015-01-01

for the function of the bc1 complex is the initial redox process that involves a bifurcated electron transfer in which the two electrons from a quinol substrate are passed to different electron acceptors in the bc1 complex. The electron transfer is coupled to proton transfer. The overall mechanism of quinol...... all atom molecular dynamics and quantum chemical calculations to reveal the binding modes of quinol at the Qo-site of the bc1 complex from Rhodobacter capsulatus. The calculations suggest a novel configuration of amino acid residues responsible for quinol binding and support a mechanism for proton...

An Efficient Approach to Screening Epigenome-Wide Data

Directory of Open Access Journals (Sweden)

Meredith A. Ray

2016-01-01

Full Text Available Screening cytosine-phosphate-guanine dinucleotide (CpG DNA methylation sites in association with some covariate(s is desired due to high dimensionality. We incorporate surrogate variable analyses (SVAs into (ordinary or robust linear regressions and utilize training and testing samples for nested validation to screen CpG sites. SVA is to account for variations in the methylation not explained by the specified covariate(s and adjust for confounding effects. To make it easier to users, this screening method is built into a user-friendly R package, ttScreening, with efficient algorithms implemented. Various simulations were implemented to examine the robustness and sensitivity of the method compared to the classical approaches controlling for multiple testing: the false discovery rates-based (FDR-based and the Bonferroni-based methods. The proposed approach in general performs better and has the potential to control both types I and II errors. We applied ttScreening to 383,998 CpG sites in association with maternal smoking, one of the leading factors for cancer risk.

Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description.

Science.gov (United States)

Spyrakis, Francesca; Cavasotto, Claudio N

2015-10-01

Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical "structural" issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns. Copyright © 2015 Elsevier Inc. All rights reserved.

Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer?s-Associated A? Oligomers

OpenAIRE

Wilcox, Kyle C.; Marunde, Matthew R.; Das, Aditi; Velasco, Pauline T.; Kuhns, Benjamin D.; Marty, Michael T.; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G.; Klein, William L.

2015-01-01

Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein int...

Process for determining the remediation category of hazardous substance sites

International Nuclear Information System (INIS)

Sieben, A.K.

1994-01-01

An evaluation process has been developed that aids in selecting the appropriate remediation category of hazardous substance sites. Three general remediation categories have been established: No further Action: Potential Early Action: and Defer for RI/FS or Transition/Decontamination and Decommissioning. This evaluation method is a preliminary screening process only and will not identify the most appropriate remediation alternative for each site. The remedy selection process can proceed only after a remediation category is determined for each site. All sites are evaluated at a preliminary screening level to determine the general remediation category. After the first screen, a secondary evaluation is performed on both the PEA sites and the DEFER sites. For PEAs, this secondary evaluation will incorporate additional specific factors, such as a screening level risk assessment. For the DEFER sites feasibility factors will be used to distinguish between the sites which should undergo a normal RI/FS and the sites which will be recommended to be remediated in association with D ampersand D of buildings. Ultimately, all of the sites will be placed into one of four remediation categories

Effects of screened Coulomb (Yukawa) and exponential-cosine-screened Coulomb potentials on photoionization of H and He+

International Nuclear Information System (INIS)

Lin, C.Y.; Ho, Y.K.

2010-01-01

The screening effects due to the exponential-cosine-screened Coulomb and screened Coulomb (Yukawa) potentials on photoionization processes are explored within the framework of complex coordinate rotation method. The energy levels of H and He + in both screened potentials shifted with various Debye screening lengths are presented. The photoionization cross sections illustrate the considerable screening effects on photoionization processes in low energy region. The shape resonances can be found near ionization thresholds for certain of Debye screening lengths. The relations between the appearance of resonances and the existence of quasi-bound states under shielding conditions are discussed. (authors)

Performance of the flow cytometric E-screen assay in screening estrogenicity of pure compounds and environmental samples

Energy Technology Data Exchange (ETDEWEB)

Vanparys, Caroline, E-mail: caroline.vanparys@ua.ac.be [Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Antwerp (Belgium); Depiereux, Sophie; Nadzialek, Stephanie [Research Unit in Organismal Biology (URBO), University of Namur (FUNDP), Namur (Belgium); Robbens, Johan; Blust, Ronny [Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Antwerp (Belgium); Kestemont, Patrick [Research Unit in Organismal Biology (URBO), University of Namur (FUNDP), Namur (Belgium); De Coen, Wim [Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Antwerp (Belgium); European Chemicals Agency (ECHA), Helsinki (Finland)

2010-09-15

In vitro estrogenicity screens are believed to provide a first prioritization step in hazard characterization of endocrine disrupting chemicals. When applied to complex environmental matrices or mixture samples, they have been indicated valuable in estimating the overall estrogen-mimicking load. In this study, the performance of an adapted format of the classical E-screen or MCF-7 cell proliferation assay was profoundly evaluated to rank pure compounds as well as influents and effluents of sewage treatment plants (STPs) according to estrogenic activity. In this adapted format, flow cytometric cell cycle analysis was used to allow evaluation of the MCF-7 cell proliferative effects after only 24 h of exposure. With an average EC{sub 50} value of 2 pM and CV of 22%, this assay appears as a sensitive and reproducible system for evaluation of estrogenic activity. Moreover, estrogenic responses of 17 pure compounds corresponded well, qualitatively and quantitatively, with other in vitro and in vivo estrogenicity screens, such as the classical E-screen (R{sup 2} = 0.98), the estrogen receptor (ER) binding (R{sup 2} = 0.84) and the ER transcription activation assay (R{sup 2} = 0.87). To evaluate the applicability of this assay for complex samples, influents and effluents of 10 STPs covering different treatment processes, were compared and ranked according to estrogenic removal efficiencies. Activated sludge treatment with phosphorus and nitrogen removal appeared most effective in eliminating estrogenic activity, followed by activated sludge, lagoon and filter bed. This is well in agreement with previous findings based on chemical analysis or biological activity screens. Moreover, ER blocking experiments indicated that cell proliferative responses were mainly ER mediated, illustrating that the complexity of the end point, cell proliferation, compared to other ER screens, does not hamper the interpretation of the results. Therefore, this study, among other E-screen studies

Performance of the flow cytometric E-screen assay in screening estrogenicity of pure compounds and environmental samples

International Nuclear Information System (INIS)

Vanparys, Caroline; Depiereux, Sophie; Nadzialek, Stephanie; Robbens, Johan; Blust, Ronny; Kestemont, Patrick; De Coen, Wim

2010-01-01

In vitro estrogenicity screens are believed to provide a first prioritization step in hazard characterization of endocrine disrupting chemicals. When applied to complex environmental matrices or mixture samples, they have been indicated valuable in estimating the overall estrogen-mimicking load. In this study, the performance of an adapted format of the classical E-screen or MCF-7 cell proliferation assay was profoundly evaluated to rank pure compounds as well as influents and effluents of sewage treatment plants (STPs) according to estrogenic activity. In this adapted format, flow cytometric cell cycle analysis was used to allow evaluation of the MCF-7 cell proliferative effects after only 24 h of exposure. With an average EC 50 value of 2 pM and CV of 22%, this assay appears as a sensitive and reproducible system for evaluation of estrogenic activity. Moreover, estrogenic responses of 17 pure compounds corresponded well, qualitatively and quantitatively, with other in vitro and in vivo estrogenicity screens, such as the classical E-screen (R 2 = 0.98), the estrogen receptor (ER) binding (R 2 = 0.84) and the ER transcription activation assay (R 2 = 0.87). To evaluate the applicability of this assay for complex samples, influents and effluents of 10 STPs covering different treatment processes, were compared and ranked according to estrogenic removal efficiencies. Activated sludge treatment with phosphorus and nitrogen removal appeared most effective in eliminating estrogenic activity, followed by activated sludge, lagoon and filter bed. This is well in agreement with previous findings based on chemical analysis or biological activity screens. Moreover, ER blocking experiments indicated that cell proliferative responses were mainly ER mediated, illustrating that the complexity of the end point, cell proliferation, compared to other ER screens, does not hamper the interpretation of the results. Therefore, this study, among other E-screen studies, supports the use of

Using the emergency department as a screening site for high blood pressure. A method for improving hypertension detection and appropriate referral.

Science.gov (United States)

Mamon, J; Green, L; Levine, D M; Gibson, G; Gurley, H T

1987-08-01

This study describes the development and testing of a high blood pressure protocol for use in emergency departments (ED) to enhance detection of those patients appropriate for subsequent referral. The protocol involves two serial blood pressure measurements and a patient interview to determine: 1) previous history of high blood pressure (HBP), 2) treatment in past year for HBP, and 3) usual source of medical care. The accuracy of patient reporting was validated by comparison with the patients' hospital record (reflecting outpatient and inpatient visits). Results indicate that these self-reports have high levels of sensitivity (range 90-100%) and specificity (range 79-96%). Use of the additional patient information increased the sensitivity of the screening protocol in identifying when and where a patient should be referred. Use of this methodology indicates that the protocol is a simple and effective method for HBP screening. The findings also suggest that the ED is an ideal site for screening the "hard-to-reach" hypertensive population.

Assertions of Japanese Websites for and Against Cancer Screening: a Text Mining Analysis

Science.gov (United States)

Okuhara, Tsuyoshi; Ishikawa, Hirono; Okada, Masahumi; Kato, Mio; Kiuchi, Takahiro

2017-04-01

Background: Cancer screening rates are lower in Japan than in Western countries such as the United States and the United Kingdom. While health professionals publish pro-cancer-screening messages online to encourage proactive seeking for screening, anti-screening activists use the same medium to warn readers against following guidelines. Contents of pro- and anti-cancer-screening sites may contribute to readers’ acceptance of one or the other position. We aimed to use a text-mining method to examine frequently appearing contents on sites for and against cancer screening. Methods: We conducted online searches in December 2016 using two major search engines in Japan (Google Japan and Yahoo! Japan). Targeted websites were classified as “pro”, “anti”, or “neutral” depending on their claims, with the author(s) classified as “health professional”, “mass media”, or “layperson”. Text-mining analyses were conducted, and statistical analysis was performed using the chi-square test. Results: Of the 169 websites analyzed, the top-three most frequently appearing content topics in pro sites were reducing mortality via cancer screening, benefits of early detection, and recommendations for obtaining detailed examination. The top three most frequent in anti-sites were harm from radiation exposure, non-efficacy of cancer screening, and lack of necessity of early detection. Anti-sites also frequently referred to a well-known Japanese radiologist, Makoto Kondo, who rejects the standard forms of cancer care. Conclusion: Our findings should enable authors of pro-cancer-screening sites to write to counter misleading anti-cancer-screening messages and facilitate dissemination of accurate information. Creative Commons Attribution License

Comparison of field screening techniques with fuel-contaminated soils

International Nuclear Information System (INIS)

Klopp, C.; Turriff, D.

1995-01-01

This paper presents the results of a comparison of four field screening techniques. Field screenings, is an important part of conducting cost-effective and comprehensive site investigations. Regulators limit the use of field screening in lieu of laboratory analyses, in part, because there is little information on the accuracy and precision of field screening techniques. The results here represent a step forward towards a better understanding of the accuracy and practicality of field screening methods. The authors hope that the role of field screening in site investigation will increase as this type of information becomes more available. Innovative techniques for homogenizing soils were used to allow simultaneous analysis of hydrocarbon contaminated soils using field GCs, immunoassays, ''jar headspace'' and ''Lab in a Bag.'' The results shown here illustrate the variability of field screening results and the importance of good method development and operator competency. Certainly more work in this area is needed to truly characterize field screening techniques

The global security perspective on the effects of executive cognitive function on complex behavioral screening intervention and HIV/AIDS.

Science.gov (United States)

Kim, Suk-Hee

2010-11-01

The purpose of this quantitative study is to understand the global security perspective on the effects of executive cognitive function (ECF) on Complex Behavioral Screening Intervention and HIV/AIDS. The HIV/AIDS pandemic is as much a social, political, economic, and cultural problem as a biomedical one. HIV/AIDS is associated centrally with the collapse not just of communities and families but potentially of states, with some of the largest public health interventions ever and enormous questions about governance, a huge population of orphans, and deep questions about intergenerational relations and cultural transmission. This study also is to develop a screening instrument that improves quality of life for individuals with executive cognitive impairments and behavior problems in our communities and the global society.

Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer’s-Associated Aβ Oligomers

Science.gov (United States)

Wilcox, Kyle C.; Marunde, Matthew R.; Das, Aditi; Velasco, Pauline T.; Kuhns, Benjamin D.; Marty, Michael T.; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G.; Klein, William L.

2015-01-01

Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer’s dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs). This method gives a soluble membrane protein library (SMPL)—a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer’s model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can facilitate drug

AMMOS: A Software Platform to Assist in silico Screening

Directory of Open Access Journals (Sweden)

Lagorce D.

2009-12-01

Full Text Available Three software packages based on the common platform of AMMOS (Automated Molecular Mechanics Optimization tool for in silico Screening for assisting virtual ligand screening purposes have been recently developed. DG-AMMOS allows generation of 3D conformations of small molecules using distance geometry and molecular mechanics optimization. AMMOS_SmallMol is a package for structural refinement of compound collections that can be used prior to docking experiments. AMMOS_ProtLig is a package for energy minimization of protein-ligand complexes. It performs an automatic procedure for molecular mechanics minimization at different levels of flexibility - from rigid to fully flexible structures of both the ligand and the receptor. The packages have been tested on small molecules with a high structural diversity and proteins binding sites of completely different geometries and physicochemical properties. The platform is developed as an open source software and can be used in a broad range of in silico drug design studies.

Cone penetrometer testing and discrete-depth groundwater sampling techniques: A cost-effective method of site characterization in a multiple-aquifer setting

International Nuclear Information System (INIS)

Zemo, D.A.; Pierce, Y.G.; Gallinatti, J.D.

1992-01-01

Cone penetrometer testing (CPT), combined with discrete-depth groundwater sampling methods, can reduce significantly the time and expense required to characterize large sites that have multiple aquifers. Results from the screening site characterization can be used to design and install a cost-effective monitoring well network. At a site in northern California, it was necessary to characterize the stratigraphy and the distribution of volatile organic compounds (VOCs) to a depth of 80 feet within a 1/2 mile-by-1/4-mile residential and commercial area in a complex alluvial fan setting. To expedite site characterization, a five-week field screening program was implemented that consisted of a shallow groundwater survey, CPT soundings, and discrete-depth groundwater sampling. Based on continuous lithologic information provided by the CPT soundings, four coarse-grained water-yielding sedimentary packages were identified. Eighty-three discrete-depth groundwater samples were collected using shallow groundwater survey techniques, the BAT Enviroprobe, or the QED HydroPunch 1, depending on subsurface conditions. A 20-well monitoring network was designed and installed to monitor critical points within each sedimentary package. Understanding the vertical VOC distribution and concentrations produced substantial cost savings by minimizing the number of permanent monitoring wells and reducing the number of costly conductor casings to be installed. Significant long-term cost savings will result from reduced sampling costs. Where total VOC concentrations exceeded 20 φg/l in the screening samples, a good correlation was found between the discrete-depth screening data and data from monitoring wells. Using a screening program to characterize the site before installing monitoring wells resulted in an estimated 50-percent reduction in costs for site characterization, 65-percent reduction in time for site characterization, and 50-percent reduction in long-term monitoring costs

Screening diagnostic program breast cancer

International Nuclear Information System (INIS)

Portnoj, L.M.; Zhakova, I.I.; Budnikova, N.V.; Rukhlyadko, E.D.

1995-01-01

The authors propose their screening program for detection of breast cancer. It includes the entire complex of present-day screening diagnostic methods, starting from an original system for the formation of groups at risk of breast cancer and completed by the direct diagnostic model of detection of the condition, oriented at a differentiated approach to the use of mammographic techniques. The proposed organizational and methodologic screening measures are both economic and diagnostically effective, thus meeting the principal requirements to screening programs. Screening of 8541 risk-groups patients helped detect 867 nodular formations, 244 of which were cancer and 623 benign formations. 8 refs., 3 figs.,

The low molecular weight protein PsaI stabilizes the light-harvesting complex II docking site of photosystem I

DEFF Research Database (Denmark)

Plöchinger, Magdalena; Torabi, Salar; Rantala, Marjaana

2016-01-01

PsaI represents one of three low molecular weight peptides of PSI. Targeted inactivation of the plastid PsaI gene in Nicotiana tabacum has no measurable effect on photosynthetic electron transport around PSI or on accumulation of proteins involved in photosynthesis. Instead, the lack of Psa......I destabilizes the association of PsaL and PsaH to PSI, both forming the light-harvesting complex (LHC)II docking site of PSI. These alterations at the LHCII binding site surprisingly did not prevent state transition but led to an increased incidence of PSI-LHCII complexes, coinciding with an elevated...

Changes in Cerebral Hemodynamics during Complex Motor Learning by Character Entry into Touch-Screen Terminals.

Directory of Open Access Journals (Sweden)

Akira Sagari

Full Text Available Studies of cerebral hemodynamics during motor learning have mostly focused on neurorehabilitation interventions and their effectiveness. However, only a few imaging studies of motor learning and the underlying complex cognitive processes have been performed.We measured cerebral hemodynamics using near-infrared spectroscopy (NIRS in relation to acquisition patterns of motor skills in healthy subjects using character entry into a touch-screen terminal. Twenty healthy, right-handed subjects who had no previous experience with character entry using a touch-screen terminal participated in this study. They were asked to enter the characters of a randomly formed Japanese syllabary into the touch-screen terminal. All subjects performed the task with their right thumb for 15 s alternating with 25 s of rest for 30 repetitions. Performance was calculated by subtracting the number of incorrect answers from the number of correct answers, and gains in motor skills were evaluated according to the changes in performance across cycles. Behavioral and oxygenated hemoglobin concentration changes across task cycles were analyzed using Spearman's rank correlations.Performance correlated positively with task cycle, thus confirming motor learning. Hemodynamic activation over the left sensorimotor cortex (SMC showed a positive correlation with task cycle, whereas activations over the right prefrontal cortex (PFC and supplementary motor area (SMA showed negative correlations.We suggest that increases in finger momentum with motor learning are reflected in the activity of the left SMC. We further speculate that the right PFC and SMA were activated during the early phases of motor learning, and that this activity was attenuated with learning progress.

Screening the DNA interaction ability and antimicrobial activity of a few novel bioactive complexes tethering N-((2-aminophenyl)(phenyl)methylene)-4-nitroaniline

Energy Technology Data Exchange (ETDEWEB)

Muniyandi, Vellaichamy; Raman, Natarajan, E-mail: ramchem1964@gmail.com

2016-11-01

Few novel transition metal complexes having N-((2-aminophenyl)(phenyl)methylene)-4-nitroaniline were synthesized and characterized by elemental analyses, IR, {sup 1}H and {sup 13}C NMR, electronic, EPR and mass spectra, conductivity and magnetic susceptibility measurements. All the metal complexes adopted square planar geometrical arrangements. The DNA-binding properties of the metal(II) complexes have been investigated by electronic absorption, fluorescence, CD spectra, cyclic voltammetry, differential pulse voltammogram and viscosity measurements. The results obtained indicate that these complexes bind to DNA via an intercalation binding mode. DNA cleavage activities indicate that the metal complexes exhibit greater activity than the ligand. The antimicrobial screening reveals that all the metal complexes exhibit better activity than the free ligand. - Highlights: • The newly synthesized mixed-ligand metal complexes act as persistent intercalators. • These mixed-ligand metal complexes display better chemical nuclease activity. • They exhibit potential antimicrobial activity. • Novel DNA targeting metal complexes are synthesized.

Absence of Non-histone Protein Complexes at Natural Chromosomal Pause Sites Results in Reduced Replication Pausing in Aging Yeast Cells

Directory of Open Access Journals (Sweden)

Marleny Cabral

2016-11-01

Full Text Available There is substantial evidence that genomic instability increases during aging. Replication pausing (and stalling at difficult-to-replicate chromosomal sites may induce genomic instability. Interestingly, in aging yeast cells, we observed reduced replication pausing at various natural replication pause sites (RPSs in ribosomal DNA (rDNA and non-rDNA locations (e.g., silent replication origins and tRNA genes. The reduced pausing occurs independent of the DNA helicase Rrm3p, which facilitates replication past these non-histone protein-complex-bound RPSs, and is independent of the deacetylase Sir2p. Conditions of caloric restriction (CR, which extend life span, also cause reduced replication pausing at the 5S rDNA and at tRNA genes. In aged and CR cells, the RPSs are less occupied by their specific non-histone protein complexes (e.g., the preinitiation complex TFIIIC, likely because members of these complexes have primarily cytosolic localization. These conditions may lead to reduced replication pausing and may lower replication stress at these sites during aging.

Experimental Seismic Event-screening Criteria at the Prototype International Data Center

Science.gov (United States)

Fisk, M. D.; Jepsen, D.; Murphy, J. R.

- Experimental seismic event-screening capabilities are described, based on the difference of body-and surface-wave magnitudes (denoted as Ms:mb) and event depth. These capabilities have been implemented and tested at the prototype International Data Center (PIDC), based on recommendations by the IDC Technical Experts on Event Screening in June 1998. Screening scores are presented that indicate numerically the degree to which an event meets, or does not meet, the Ms:mb and depth screening criteria. Seismic events are also categorized as onshore, offshore, or mixed, based on their 90% location error ellipses and an onshore/offshore grid with five-minute resolution, although this analysis is not used at this time to screen out events.Results are presented of applications to almost 42,000 events with mb>=3.5 in the PIDC Standard Event Bulletin (SEB) and to 121 underground nuclear explosions (UNE's) at the U.S. Nevada Test Site (NTS), the Semipalatinsk and Novaya Zemlya test sites in the Former Soviet Union, the Lop Nor test site in China, and the Indian, Pakistan, and French Polynesian test sites. The screening criteria appear to be quite conservative. None of the known UNE's are screened out, while about 41 percent of the presumed earthquakes in the SEB with mb>=3.5 are screened out. UNE's at the Lop Nor, Indian, and Pakistan test sites on 8 June 1996, 11 May 1998, and 28 May 1998, respectively, have among the lowest Ms:mb scores of all events in the SEB.To assess the validity of the depth screening results, comparisons are presented of SEB depth solutions to those in other bulletins that are presumed to be reliable and independent. Using over 1600 events, the comparisons indicate that the SEB depth confidence intervals are consistent with or shallower than over 99.8 percent of the corresponding depth estimates in the other bulletins. Concluding remarks are provided regarding the performance of the experimental event-screening criteria, and plans for future

Fungal community structure under goat willows (Salix caprea L.) growing at metal polluted site: the potential of screening in a model phytostabilisation study

Science.gov (United States)

Marjana Regvar; Matevz Likar; Andrej Piltaver; Nives Kugonic; Jane E. Smith

2010-01-01

Goat willow (Salix caprea L.) was selected in a previous vegetation screening study as a potential candidate for the later-stage phytostabilisation efforts at a heavily metal polluted site in Slovenia. The aims of this study were to identify the fungi colonising roots of S. caprea along the gradient of vegetation succession and...

Screening and assessment of solidification/stabilization amendments suitable for soils of lead-acid battery contaminated site.

Science.gov (United States)

Zhang, Zhuo; Guo, Guanlin; Teng, Yanguo; Wang, Jinsheng; Rhee, Jae Seong; Wang, Sen; Li, Fasheng

2015-05-15

Lead exposure via ingestion of soil and dust generally occurs at lead-acid battery manufacturing and recycling sites. Screening solidification/stabilization (S/S) amendments suitable for lead contaminated soil in an abandoned lead-acid battery factory site was conducted based on its chemical forms and environmental risks. Twelve amendments were used to immobilize the Pb in soil and assess the solidification/stabilization efficiency by toxicity leaching tests. The results indicated that three amendments, KH₂PO₄ (KP), KH₂PO₄:oyster shell power=1:1 (by mass ratio; SPP), and KH₂PO₄:sintered magnesia=1:1 (by mass ratio; KPM) had higher remediation efficiencies that led to a 92% reduction in leachable Pb with the addition of 5% amendments, while the acid soluble fraction of Pb (AS-Pb) decreased by 41-46% and the residual fraction (RS-Pb) increased by 16-25%. The S/S costs of the three selected amendments KP, SPP, and KPM could be controlled to $22.3 per ton of soil when the Pb concentration in soil ranged from 2000 to 3000 mg/kg. The results of this study demonstrated that KP, SPP, and KPM can effectively decrease bioavailability of Pb. These findings could provide basis for decision-making of S/S remediation of lead-acid battery contaminated sites. Copyright © 2015 Elsevier B.V. All rights reserved.

Using a Full Complex Site Transfer Function to Estimate Strong Ground Motion in Port-au-Prince (Haiti).

Science.gov (United States)

ST Fleur, S.; Courboulex, F.; Bertrand, E.; Mercier De Lepinay, B. F.; Hough, S. E.; Boisson, D.; Momplaisir, R.

2017-12-01

To assess the possible impact of a future earthquake in the urban area of Port-au-Prince (Haiti), we have implemented a simulation approach for complex ground motions produced by an earthquake. To this end, we have integrated local site effect in the prediction of strong ground motions in Port-au-Prince using the complex transfer functions method, which takes into account amplitude changes as well as phase changes. This technique is particularly suitable for basins where a conventional 1D digital approach proves inadequate, as is the case in Port-au-Prince. To do this, we use the results of the Standard Spectral Ratio (SSR) approach of St Fleur et al. (2016) to estimate the amplitude of the response of the site to a nearby rock site. Then, we determine the phase difference between sites, interpreted as changes in the phase of the signal related to local site conditions, using the signals of the 2010 earthquake aftershocks records. Finally, the accelerogram of the simulated earthquake is obtain using the technique of the inverse Fourier transform. The results of this study showed that the strongest soil motions are expected in neighborhoods of downtown Port-au-Prince and adjacent hills. In addition, this simulation method by complex transfer functions was validated by comparison with recorded actual data. Our simulated response spectra reproduce very well both the amplitude and the shape of the response spectra of recorded earthquakes. This new approach allowed to reproduce the lengthening of the signal that could be generated by surface waves at certain stations in the city of Port-au-Prince. However, two points of vigilance must be considered: (1) a good signal-to-noise ratio is necessary to obtain a robust estimate of the site-reference phase shift (ratio at least equal to 10); (2) unless the amplitude and phase changes are measured on strong motion records, this technique does not take non-linear effects into account.

Acceptability of Cervical Cancer Screening in Rural Mozambique

Science.gov (United States)

Audet, Carolyn M.; Matos, Carla Silva; Blevins, Meridith; Cardoso, Aventina; Moon, Troy D.; Sidat, Mohsin

2012-01-01

In Zambezia province, Mozambique, cervical cancer (CC) screening was introduced to rural communities in 2010. Our study sought to determine whether women would accept screening via pelvic examination and visual inspection with acetic acid (VIA) at two clinical sites near the onset of a new CC screening program. A cross-sectional descriptive study…

Receptor-ligand binding sites and virtual screening.

Science.gov (United States)

Hattotuwagama, Channa K; Davies, Matthew N; Flower, Darren R

2006-01-01

Within the pharmaceutical industry, the ultimate source of continuing profitability is the unremitting process of drug discovery. To be profitable, drugs must be marketable: legally novel, safe and relatively free of side effects, efficacious, and ideally inexpensive to produce. While drug discovery was once typified by a haphazard and empirical process, it is now increasingly driven by both knowledge of the receptor-mediated basis of disease and how drug molecules interact with receptors and the wider physiome. Medicinal chemistry postulates that to understand a congeneric ligand series, or set thereof, is to understand the nature and requirements of a ligand binding site. Likewise, structural molecular biology posits that to understand a binding site is to understand the nature of ligands bound therein. Reality sits somewhere between these extremes, yet subsumes them both. Complementary to rules of ligand design, arising through decades of medicinal chemistry, structural biology and computational chemistry are able to elucidate the nature of binding site-ligand interactions, facilitating, at both pragmatic and conceptual levels, the drug discovery process.

Exquisite Modulation of the Active Site of Methanocaldococcus jannaschii Adenylosuccinate Synthetase in Forward Reaction Complexes.

Science.gov (United States)

Karnawat, Vishakha; Mehrotra, Sonali; Balaram, Hemalatha; Puranik, Mrinalini

2016-05-03

In enzymes that conduct complex reactions involving several substrates and chemical transformations, the active site must reorganize at each step to complement the transition state of that chemical step. Adenylosuccinate synthetase (ADSS) utilizes a molecule each of guanosine 5'-monophosphate (GTP) and aspartate to convert inosine 5'-monophosphate (IMP) into succinyl adenosine 5'-monophosphate (sAMP) through several kinetic intermediates. Here we followed catalysis by ADSS through high-resolution vibrational spectral fingerprints of each substrate and intermediate involved in the forward reaction. Vibrational spectra show differential ligand distortion at each step of catalysis, and band positions of substrates are influenced by binding of cosubstrates. We found that the bound IMP is distorted toward its N1-deprotonated form even in the absence of any other ligands. Several specific interactions between GTP and active-site amino acid residues result in large Raman shifts and contribute substantially to intrinsic binding energy. When both IMP and GTP are simultaneously bound to ADSS, IMP is converted into an intermediate 6-phosphoryl inosine 5'-monophosphate (6-pIMP). The 6-pIMP·ADSS complex was found to be stable upon binding of the third ligand, hadacidin (HDA), an analogue of l-aspartate. We find that in the absence of HDA, 6-pIMP is quickly released from ADSS, is unstable in solution, and converts back into IMP. HDA allosterically stabilizes ADSS through local conformational rearrangements. We captured this complex and determined the spectra and structure of 6-pIMP in its enzyme-bound state. These results provide important insights into the exquisite tuning of active-site interactions with changing substrate at each kinetic step of catalysis.

Observations concerning the quinol oxidation site of the cytochrome bc{sub 1} complex

Energy Technology Data Exchange (ETDEWEB)

Berry, Edward A.; Huang, Li-Shar

2003-09-07

A direct hydrogen bond between ubiquinone/quinol bound at the QO site and a cluster-ligand histidine of the iron-sulfur protein (ISP) is described as a major determining factor explaining much experimental data on position of the ISP ectodomain, EPR lineshape and midpoint potential of the iron-sulfur cluster, and the mechanism of the bifurcated electron transfer from ubiquinol to the high and low potential chains of the bc1 complex.

Central interstate low-level radioactive waste compact region site exclusionary screening study. Phase I. Final report

International Nuclear Information System (INIS)

1985-06-01

The Low-Level Radioactive Waste Policy Act of 1980 assigns to the states the responsibility for disposal of the low-level radioactive waste generated within their boundaries. It also provides for regional compacts among states to address their needs on a broader basis and permits restriction of the use of regional disposal facilities after January 1, 1986, to generators of low-level waste within the region. Each state, either individually or as a member of a compact, must therefore consider the establishment of a low-level radioactive waste disposal facility within its borders. The states of Arkansas, Kansas, Louisiana, Nebraska, and Oklahoma adopted the Central Interstate Low-Level Waste Compact (CILLWC) and legislation was submitted to Congress for consent in June of 1983 legislation is being reintroduced in the 99th Congress. In August of 1984, the CILLWC selected and contracted Dames and Moore to conduct a Phase I-Site Suitability Screening Study for a low-level radioactive waste disposal facility in the five-state region. This report presents the results of the Phase I Screening Study. Dames and Moore reported to the Technical Advisory Committee (TAC) of the CILLWC which provided guidance and comment on work progress and direction

Surfactant screening of diesel-contaminated soil

International Nuclear Information System (INIS)

Peters, R.W.; Montemagno, C.D.; Shem, L.; Lewis, B.-A.

1992-01-01

At one installation in California, approximately 60,000 gal of No. 2 diesel fuel leaked into the subsurface environment, resulting in contamination at depths from 6 to 34 m below the surface. Argonne National Laboratory was contracted to perform treatability studies for site remediation. This paper summarizes a surfactant screening/surfactant flooding research program in which 22 surfactants were screened for their effectiveness in mobilizing the organics from the contaminated soil prior to bioremediation. Anionic surfactants resulted in the greatest degree of diesel mobilization. The most promising surfactants will be employed on contaminated soil samples obtained from the site

Dynamics of translocation and substrate binding in individual complexes formed with active site mutants of {phi}29 DNA polymerase.

Science.gov (United States)

Dahl, Joseph M; Wang, Hongyun; Lázaro, José M; Salas, Margarita; Lieberman, Kate R

2014-03-07

The Φ29 DNA polymerase (DNAP) is a processive B-family replicative DNAP. Fluctuations between the pre-translocation and post-translocation states can be quantified from ionic current traces, when individual Φ29 DNAP-DNA complexes are held atop a nanopore in an electric field. Based upon crystal structures of the Φ29 DNAP-DNA binary complex and the Φ29 DNAP-DNA-dNTP ternary complex, residues Tyr-226 and Tyr-390 in the polymerase active site were implicated in the structural basis of translocation. Here, we have examined the dynamics of translocation and substrate binding in complexes formed with the Y226F and Y390F mutants. The Y226F mutation diminished the forward and reverse rates of translocation, increased the affinity for dNTP in the post-translocation state by decreasing the dNTP dissociation rate, and increased the affinity for pyrophosphate in the pre-translocation state. The Y390F mutation significantly decreased the affinity for dNTP in the post-translocation state by decreasing the association rate ∼2-fold and increasing the dissociation rate ∼10-fold, implicating this as a mechanism by which this mutation impedes DNA synthesis. The Y390F dissociation rate increase is suppressed when complexes are examined in the presence of Mn(2+) rather than Mg(2+). The same effects of the Y226F or Y390F mutations were observed in the background of the D12A/D66A mutations, located in the exonuclease active site, ∼30 Å from the polymerase active site. Although translocation rates were unaffected in the D12A/D66A mutant, these exonuclease site mutations caused a decrease in the dNTP dissociation rate, suggesting that they perturb Φ29 DNAP interdomain architecture.

Remedial investigation and feasibility study for the Lawrence Livermore National Laboratory Site 300 Pit 7 Complex

Energy Technology Data Exchange (ETDEWEB)

Taffet, M.J. (Lawrence Livermore National Lab., CA (USA)); Oberdorfer, J.A. (San Jose State Univ., CA (USA)); McIlvride, W.A. (Weiss Associates, Oakland, CA (USA))

1989-10-01

This report summarizes the results and conclusions of the investigation of tritium and other compounds in ground water in the vicinity of landfills at the Lawrence Livermore National Laboratory (LLNL) Site 300 Pit 7 Complex. 91 refs., 110 figs., 43 tabs.

The Cu2+-nitrilotriacetic acid complex improves loading of α-helical double histidine site for precise distance measurements by pulsed ESR

Science.gov (United States)

Ghosh, Shreya; Lawless, Matthew J.; Rule, Gordon S.; Saxena, Sunil

2018-01-01

Site-directed spin labeling using two strategically placed natural histidine residues allows for the rigid attachment of paramagnetic Cu2+. This double histidine (dHis) motif enables extremely precise, narrow distance distributions resolved by Cu2+-based pulsed ESR. Furthermore, the distance measurements are easily relatable to the protein backbone-structure. The Cu2+ ion has, till now, been introduced as a complex with the chelating agent iminodiacetic acid (IDA) to prevent unspecific binding. Recently, this method was found to have two limiting concerns that include poor selectivity towards α-helices and incomplete Cu2+-IDA complexation. Herein, we introduce an alternative method of dHis-Cu2+ loading using the nitrilotriacetic acid (NTA)-Cu2+ complex. We find that the Cu2+-NTA complex shows a four-fold increase in selectivity toward α-helical dHis sites. Furthermore, we show that 100% Cu2+-NTA complexation is achievable, enabling precise dHis loading and resulting in no free Cu2+ in solution. We analyze the optimum dHis loading conditions using both continuous wave and pulsed ESR. We implement these findings to show increased sensitivity of the Double Electron-Electron Resonance (DEER) experiment in two different protein systems. The DEER signal is increased within the immunoglobulin binding domain of protein G (called GB1). We measure distances between a dHis site on an α-helix and dHis site either on a mid-strand or a non-hydrogen bonded edge-strand β-sheet. Finally, the DEER signal is increased twofold within two α-helix dHis sites in the enzymatic dimer glutathione S-transferase exemplifying the enhanced α-helical selectivity of Cu2+-NTA.

Sorption of trivalent lanthanides and actinides onto montmorillonite: Macroscopic, thermodynamic and structural evidence for ternary hydroxo and carbonato surface complexes on multiple sorption sites.

Science.gov (United States)

Fernandes, M Marques; Scheinost, A C; Baeyens, B

2016-08-01

The credibility of long-term safety assessments of radioactive waste repositories may be greatly enhanced by a molecular level understanding of the sorption processes onto individual minerals present in the near- and far-fields. In this study we couple macroscopic sorption experiments to surface complexation modelling and spectroscopic investigations, including extended X-ray absorption fine structure (EXAFS) and time-resolved laser fluorescence spectroscopies (TRLFS), to elucidate the uptake mechanism of trivalent lanthanides and actinides (Ln/An(III)) by montmorillonite in the absence and presence of dissolved carbonate. Based on the experimental sorption isotherms for the carbonate-free system, the previously developed 2 site protolysis non electrostatic surface complexation and cation exchange (2SPNE SC/CE) model needed to be complemented with an additional surface complexation reaction onto weak sites. The fitting of sorption isotherms in the presence of carbonate required refinement of the previously published model by reducing the strong site capacity and by adding the formation of Ln/An(III)-carbonato complexes both on strong and weak sites. EXAFS spectra of selected Am samples and TRLFS spectra of selected Cm samples corroborate the model assumptions by showing the existence of different surface complexation sites and evidencing the formation of Ln/An(III) carbonate surface complexes. In the absence of carbonate and at low loadings, Ln/An(III) form strong inner-sphere complexes through binding to three Al(O,OH)6 octahedra, most likely by occupying vacant sites in the octahedral layers of montmorillonite, which are exposed on {010} and {110} edge faces. At higher loadings, Ln/An(III) binds to only one Al octahedron, forming a weaker, edge-sharing surface complex. In the presence of carbonate, we identified a ternary mono- or dicarbonato Ln/An(III) complex binding directly to one Al(O,OH)6 octahedron, revealing that type-A ternary complexes form with the one

Chemical dechlorination of pesticides at a superfund site in Region II

International Nuclear Information System (INIS)

Pendergrass, S.; Prince, J.

1991-01-01

Selecting technologies for cleaning up hazardous waste sites is a complex task, due in part to the rapidly changing nature of the state-of-the-art in technology. There is strong support for use of innovative technologies as specified in Section 121(b) of CERCLA. However, use of an innovative technology requires overcoming a variety of challenges. These challenges include: Screening potentially appropriate technologies, including innovative technologies, and selecting one or more potential innovative technologies for which preliminary results are promising; however, site-specific data are needed prior to technology evaluation. Evaluating the effectiveness of the proposed technology for the site through the use of treatability studies. Gaining acceptance for the innovative technology, which may employ new or unfamiliar concepts. Determining optimal design and operating parameters for full-scale remediation. This paper discusses the technology evaluation process and how that process supported the selection of an innovative technology for the Myers Property site, a Superfund site in Region II. A case study is presented showing how technology screening and laboratory treatability studies were used to evaluate an innovative technology (chemical dechlorination), which was selected as the technology for remediation of soils and sediments contaminated with pesticides at this environmentally sensitive site in New Jersey. The remedy selected by the U.S. EPA for this site designates chemical dechlorination as the selected technology, but does not specify any particular vendor or process. Rather, the remedy sets forth technology performance standards and recommends certain design tasks which may be used to select a particular chemical process. This paper discusses he of these design tasks as they might apply to innovative technologies, using chemical dechlorination as a model

Photoreactivity of biologically active compounds. VII. Interaction of antimalarial drugs with melanin in vitro as part of phototoxicity screening.

Science.gov (United States)

Kristensen, S; Orsteen, A L; Sande, S A; Tønnesen, H H

1994-10-01

The drugs commonly used in the treatment of malaria are photochemically unstable. Several of these compounds accumulate in melanin-rich tissues and cause toxic reactions which may be light induced. As part of the screening of the photochemical properties and phototoxic capabilities of antimalarials, the in vitro interaction of eight antimalarials with melanin was studied. The dissociation constant for the drug-melanin complex and the relative number of binding sites on melanin were estimated for six of the drugs using a curve-fitting program. The reaction rate for the formation of the melanin-drug complex was determined, and the complexes were further characterized by zeta potential measurements.

Region-to-area screening methodology for the Crystalline Repository Project

International Nuclear Information System (INIS)

1985-04-01

The purpose of this document is to describe the Crystalline Repository Project's (CRP) process for region-to-area screening of exposed and near-surface crystalline rock bodies in the three regions of the conterminous United States where crystalline rock is being evaluated as a potential host for the second nuclear waste repository (i.e., in the North Central, Northeastern, and Southeastern Regions). This document indicates how the US Department of Energy's (DOE) General Guidelines for the Recommendation of Sites for Nuclear Waste Repositories (10 CFR 960) were used to select and apply factors and variables for the region-to-area screening, explains how these factors and variable are to be applied in the region-to-area screening, and indicates how this methodology relates to the decision process leading to the selection of candidate areas. A brief general discussion of the screening process from the national survey through area screening and site recommendation is presented. This discussion sets the scene for detailed discussions which follow concerning the region-to-area screening process, the guidance provided by the DOE Siting Guidelines for establishing disqualifying factors and variables for screening, and application of the disqualifying factors and variables in the screening process. This document is complementary to the regional geologic and environmental characterization reports to be issued in the summer of 1985 as final documents. These reports will contain the geologic and environmental data base that will be used in conjunction with the methodology to conduct region-to-area screening

Site selection of a dual purpose nuclear power plant in Saudi Arabia

International Nuclear Information System (INIS)

Hussein, F.M.; Obeid, M.A.; El-Malahy, K.S.

1987-01-01

Selecting a nuclear power plant site for power production and water desalination is a very complex problem, especially in countries with moderate technology. Many interrelated factors affect the process, and professional judgments by various experts are involved. Four sites, all located on the West Coast of Saudi Arabia along the Red Sea, were chosen as potential sites for building such a plant. (All sites were in either the northern or southern section of the coast; the central part was excluded for pilgrims' safety.) The East Coast was completely eliminated in the initial screening process due to its strategic location, the existence of oil fields and refineries, and its proximity to other Arabian (Persian) Gulf countries (to minimize radioactive releases to these countries in case of an accident). A computer code based on Saaty's eigenvalue technique and developed in a previous study was used in this analysis. Twenty-one main criteria were considered, and the sites were ranked to determine which was most desirable. Site 4 was found to be most suitable, followed by site 3

Estimating HAPs and radionuclide emissions from a laboratory complex at a nuclear processing site

International Nuclear Information System (INIS)

Paul, R.A.; Faugl, T.

1993-01-01

A unique methodology was developed for conducting an air emission inventory (AEI) at a DOE nuclear processing facility. This methodology involved the use of computer-assisted design (CAD) drawings to document emission points, computerized process drawings to document industrial processes leading to emissions, and a computerized data base of AEI forms to document emission estimates and related process data. A detailed air emissions inventory for operating years 1985--1991 was recently implemented for the entire site using this methodology. One industrial area at the DOE Site is comprised of laboratory facilities that provide direct support to the nuclear reactor and recovery operations, developmental studies to support reactor and separation operations, and developmental studies to support waste handling and storage. The majority of the functions are conducted in a single large building complex wherein bench scale and pilot scale experiments are carried out involving radionuclides, hazardous air pollutants (HAP), and other chemicals reportable under the Clean Air Act Amendments (CAAA) and Superfund Amendments and Re-authorization Act (SARA) Title 111. The results of the inventory showed that HAP and radionuclide emissions from the laboratory complex were relatively minor

Strategic planning model for achieving stakeholder involvement in environmental at DOE weapons complex sites

International Nuclear Information System (INIS)

Weber, G.

1994-01-01

Within today's reality a public manager often needs to develop cooperative relationships among a number of individual, program, and organizational stakeholders to accomplish particular projects, programs, or policies. A DOE site manager charged with accomplishing environmental restoration and conversion at former weapons production sites is no exception. Important reasons for this include the technical and political complexity of the clean-up problem; limits on the funding, authority, and other resources available to DOE; authority, responsibilities, and interests of other stakeholders; and the ever present potential for conflict among stakeholders, and power of any one to hinder, if not halt, the clean-up process if conflicts aren't managed and cooperative relationships established and maintained

ESI-MS study on non-covalent bond complex of rhFKBP12 and new neurogrowth promoter

Institute of Scientific and Technical Information of China (English)

WANG; Hongxia; (王红霞); ZHANG; Xuemin; (张学敏); YANG; Songcheng; (杨松成); XIAO; Junhai; (肖军海); NIE; Aihua; (聂爱华); ZHAO; Liqin; (赵丽琴); LI; Song; (李松)

2003-01-01

An ESI-MS method for studying the non-covalent bond complex of rhFKBP12 with its nonimmunosuppressive ligands was developed. The method was used to screen out three compounds capable of binding to rhFKBP12 non-covalently from 52 compounds. By competing binding experiment, the binding site and the relative binding strength of these three compounds 000107, 000308 and A2B12 with rhFKBP12 were measured. All of them have the same binding site as FK506 does. X-ray crystalline diffraction experiment of non-covalent bond complex of 000107, 000308 with rhFKBP12 by Tsinghua University showed the same results. Among them 000308 has good effect on stimulating neurite to grow in chicken sensory neuronal cultures.

Mobile Screens: The Visual Regime of Navigation

NARCIS (Netherlands)

Verhoeff, N.

2012-01-01

In this book on screen media, space, and mobility I compare synchronically, as well as diachronically, diverse and variegated screen media - their technologies and practices – as sites for virtual mobility and navigation. Mobility as a central trope can be found on the multiple levels that are

Insulator protein Su(Hw) recruits SAGA and Brahma complexes and constitutes part of Origin Recognition Complex-binding sites in the Drosophila genome

Science.gov (United States)

Vorobyeva, Nadezhda E.; Mazina, Marina U.; Golovnin, Anton K.; Kopytova, Daria V.; Gurskiy, Dmitriy Y.; Nabirochkina, Elena N.; Georgieva, Sofia G.; Georgiev, Pavel G.; Krasnov, Aleksey N.

2013-01-01

Despite increasing data on the properties of replication origins, molecular mechanisms underlying origin recognition complex (ORC) positioning in the genome are still poorly understood. The Su(Hw) protein accounts for the activity of best-studied Drosophila insulators. Here, we show that Su(Hw) recruits the histone acetyltransferase complex SAGA and chromatin remodeler Brahma to Su(Hw)-dependent insulators, which gives rise to regions with low nucleosome density and creates conditions for ORC binding. Depletion in Su(Hw) leads to a dramatic drop in the levels of SAGA, Brahma and ORC subunits and a significant increase in nucleosome density on Su(Hw)-dependent insulators, whereas artificial Su(Hw) recruitment itself is sufficient for subsequent SAGA, Brahma and ORC binding. In contrast to the majority of replication origins that associate with promoters of active genes, Su(Hw)-binding sites constitute a small proportion (6%) of ORC-binding sites that are localized preferentially in transcriptionally inactive chromatin regions termed BLACK and BLUE chromatin. We suggest that the key determinants of ORC positioning in the genome are DNA-binding proteins that constitute different DNA regulatory elements, including insulators, promoters and enhancers. Su(Hw) is the first example of such a protein. PMID:23609538

Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery.

Science.gov (United States)

Pérot, Stéphanie; Sperandio, Olivier; Miteva, Maria A; Camproux, Anne-Claude; Villoutreix, Bruno O

2010-08-01

Detection, comparison and analyses of binding pockets are pivotal to structure-based drug design endeavors, from hit identification, screening of exosites and de-orphanization of protein functions to the anticipation of specific and non-specific binding to off- and anti-targets. Here, we analyze protein-ligand complexes and discuss methods that assist binding site identification, prediction of druggability and binding site comparison. The full potential of pockets is yet to be harnessed, and we envision that better understanding of the pocket space will have far-reaching implications in the field of drug discovery, such as the design of pocket-specific compound libraries and scoring functions.

Site-specific Probabilistic Analysis of DCGLs Using RESRAD Code

Energy Technology Data Exchange (ETDEWEB)

Kim, Jeongju; Yoon, Suk Bon; Sohn, Wook [KHNP CRI, Daejeon (Korea, Republic of)

2016-10-15

In general, DCGLs can be conservative (screening DCGL) if they do not take into account site specific factors. Use of such conservative DCGLs can lead to additional remediation that would not be required if the effort was made to develop site-specific DCGLs. Therefore, the objective of this work is to provide an example on the use of the RESRAD 6.0 probabilistic (site-specific) dose analysis to compare with the screening DCGL. Site release regulations state that a site will be considered acceptable for unrestricted use if the residual radioactivity that is distinguishable from background radiation results in a Total Effective Dose Equivalent (TEDE) to an average member of the critical group of less than the site release criteria, for example 0.25 mSv per year in U.S. Utilities use computer dose modeling codes to establish an acceptable level of contamination, the derived concentration guideline level (DCGL) that will meet this regulatory limit. Since the DCGL value is the principal measure of residual radioactivity, it is critical to understand the technical basis of these dose modeling codes. The objective this work was to provide example on nuclear power plant decommissioning dose analysis in a probabilistic analysis framework. The focus was on the demonstration of regulatory compliance for surface soil contamination using the RESRAD 6.0 code. Both the screening and site-specific probabilistic dose analysis methodologies were examined. Example analyses performed with the screening probabilistic dose analysis confirmed the conservatism of the NRC screening values and indicated the effectiveness of probabilistic dose analysis in reducing the conservatism in DCGL derivation.

Crystal structure of an affinity-matured prolactin complexed to its dimerized receptor reveals the topology of hormone binding site 2

DEFF Research Database (Denmark)

Broutin, Isabelle; Jomain, Jean-Baptiste; Tallet, Estelle

2010-01-01

We report the first crystal structure of a 1:2 hormone.receptor complex that involves prolactin (PRL) as the ligand, at 3.8-A resolution. Stable ternary complexes were obtained by generating affinity-matured PRL variants harboring an N-terminal tail from ovine placental lactogen, a closely relate...... and prostate cancer.......We report the first crystal structure of a 1:2 hormone.receptor complex that involves prolactin (PRL) as the ligand, at 3.8-A resolution. Stable ternary complexes were obtained by generating affinity-matured PRL variants harboring an N-terminal tail from ovine placental lactogen, a closely related...... PRL receptor (PRLR) ligand. This structure allows one to draw up an exhaustive inventory of the residues involved at the PRL.PRLR site 2 interface, consistent with all previously reported site-directed mutagenesis data. We propose, with this description, an interaction model involving three structural...

Multiple complex odontomas and subsequent occurrence of an ossifying fibroma at the same site as the removed odontoma

Directory of Open Access Journals (Sweden)

Kou Matsuo

2013-06-01

Full Text Available We report a rare case of multiple complex odontomas and the subsequent occurrence of an ossifying fibroma at the same site as one of the removed odontomas. A 3-year-old Japanese boy presented three complex odontomas at the unerupted deciduous first and second molars and permanent first molar on the left side of the mandible. The two odontomas at the deciduous teeth were immediately extirpated, and, after 2 years of follow-up, the odontoma at the unerupted permanent first molar was removed. At the age of 7 years, a small odontoma surrounding the deciduous second molar emerged as a recurrence. When the patient was 9 years old, an ossifying fibroma occurred near the apex of the first premolar, i.e., the site where one of the original odontomas existed. Furthermore, a small radiopaque mass over the crown of the unerupted permanent second molar was observed at the age of 10 years; this mass was probably an additional fourth complex odontoma. This is not only a rare case report of ossifying fibroma associated with multiple complex odontomas but also a valuable time course observation of the development of such odontogenic tumors.

FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2.

Directory of Open Access Journals (Sweden)

Maria Castella

2015-10-01

Full Text Available The Fanconi anemia (FA-BRCA pathway mediates repair of DNA interstrand crosslinks. The FA core complex, a multi-subunit ubiquitin ligase, participates in the detection of DNA lesions and monoubiquitinates two downstream FA proteins, FANCD2 and FANCI (or the ID complex. However, the regulation of the FA core complex itself is poorly understood. Here we show that the FA core complex proteins are recruited to sites of DNA damage and form nuclear foci in S and G2 phases of the cell cycle. ATR kinase activity, an intact FA core complex and FANCM-FAAP24 were crucial for this recruitment. Surprisingly, FANCI, but not its partner FANCD2, was needed for efficient FA core complex foci formation. Monoubiquitination or ATR-dependent phosphorylation of FANCI were not required for the FA core complex recruitment, but FANCI deubiquitination by USP1 was. Additionally, BRCA1 was required for efficient FA core complex foci formation. These findings indicate that FANCI functions upstream of FA core complex recruitment independently of FANCD2, and alter the current view of the FA-BRCA pathway.

A real-time view of the TAR:Tat:P-TEFb complex at HIV-1 transcription sites

Directory of Open Access Journals (Sweden)

Knezevich Anna

2007-05-01

Full Text Available Abstract HIV-1 transcription is tightly regulated: silent in long-term latency and highly active in acutely-infected cells. Transcription is activated by the viral protein Tat, which recruits the elongation factor P-TEFb by binding the TAR sequence present in nascent HIV-1 RNAs. In this study, we analyzed the dynamic of the TAR:Tat:P-TEFb complex in living cells, by performing FRAP experiments at HIV-1 transcription sites. Our results indicate that a large fraction of Tat present at these sites is recruited by Cyclin T1. We found that in the presence of Tat, Cdk9 remained bound to nascent HIV-1 RNAs for 71s. In contrast, when transcription was activated by PMA/ionomycin, in the absence of Tat, Cdk9 turned-over rapidly and resided on the HIV-1 promoter for only 11s. Thus, the mechanism of trans-activation determines the residency time of P-TEFb at the HIV-1 gene, possibly explaining why Tat is such a potent transcriptional activator. In addition, we observed that Tat occupied HIV-1 transcription sites for 55s, suggesting that the TAR:Tat:P-TEFb complex dissociates from the polymerase following transcription initiation, and undergoes subsequent cycles of association/dissociation.

An Approximate Reasoning-Based Method for Screening High-Level-Waste Tanks for Flammable Gas

International Nuclear Information System (INIS)

Eisenhawer, Stephen W.; Bott, Terry F.; Smith, Ronald E.

2000-01-01

The in situ retention of flammable gas produced by radiolysis and thermal decomposition in high-level waste can pose a safety problem if the gases are released episodically into the dome space of a storage tank. Screening efforts at the Hanford site have been directed at identifying tanks in which this situation could exist. Problems encountered in screening motivated an effort to develop an improved screening methodology. Approximate reasoning (AR) is a formalism designed to emulate the kinds of complex judgments made by subject matter experts. It uses inductive logic structures to build a sequence of forward-chaining inferences about a subject. Approximate-reasoning models incorporate natural language expressions known as linguistic variables to represent evidence. The use of fuzzy sets to represent these variables mathematically makes it practical to evaluate quantitative and qualitative information consistently. In a pilot study to investigate the utility of AR for flammable gas screening, the effort to implement such a model was found to be acceptable, and computational requirements were found to be reasonable. The preliminary results showed that important judgments about the validity of observational data and the predictive power of models could be made. These results give new insights into the problems observed in previous screening efforts

An approximate reasoning-based method for screening high-level-waste tanks for flammable gas

International Nuclear Information System (INIS)

Eisenhawer, S.W.; Bott, T.F.; Smith, R.E.

2000-01-01

The in situ retention of flammable gas produced by radiolysis and thermal decomposition in high-level waste can pose a safety problem if the gases are released episodically into the dome space of a storage tank. Screening efforts at the Hanford site have been directed at identifying tanks in which this situation could exist. Problems encountered in screening motivated an effort to develop and improved screening methodology. Approximate reasoning (AR) is a formalism designed to emulate the kinds of complex judgments made by subject matter experts. It uses inductive logic structures to build a sequence of forward-chaining inferences about a subject. Approximate-reasoning models incorporate natural language expressions known as linguistic variables to represent evidence. The use of fuzzy sets to represent these variables mathematically makes it practical to evaluate quantitative and qualitative information consistently. In a pilot study to investigate the utility of AR for flammable gas screening, the effort to implement such a model was found to be acceptable, and computational requirements were found to be reasonable. The preliminary results showed that important judgments about the validity of observational data and the predictive power of models could be made. These results give new insights into the problems observed in previous screening efforts

An approximate reasoning-based method for screening high-level-waste tanks for flammable gas

Energy Technology Data Exchange (ETDEWEB)

Eisenhawer, S.W.; Bott, T.F.; Smith, R.E.

2000-06-01

The in situ retention of flammable gas produced by radiolysis and thermal decomposition in high-level waste can pose a safety problem if the gases are released episodically into the dome space of a storage tank. Screening efforts at the Hanford site have been directed at identifying tanks in which this situation could exist. Problems encountered in screening motivated an effort to develop and improved screening methodology. Approximate reasoning (AR) is a formalism designed to emulate the kinds of complex judgments made by subject matter experts. It uses inductive logic structures to build a sequence of forward-chaining inferences about a subject. Approximate-reasoning models incorporate natural language expressions known as linguistic variables to represent evidence. The use of fuzzy sets to represent these variables mathematically makes it practical to evaluate quantitative and qualitative information consistently. In a pilot study to investigate the utility of AR for flammable gas screening, the effort to implement such a model was found to be acceptable, and computational requirements were found to be reasonable. The preliminary results showed that important judgments about the validity of observational data and the predictive power of models could be made. These results give new insights into the problems observed in previous screening efforts.

Combining pharmacophore fingerprints and PLS-discriminant analysis for virtual screening and SAR elucidation

DEFF Research Database (Denmark)

Askjær, Sune; Langgård, Morten

2008-01-01

The criterion of success for the initial stages of a ligand-based drug-discovery project is dual. First, a set of suitable lead compounds has to be identified. Second, a level of a preliminary structure-activity relationship (SAR) of the identified ligands has to be established in order to guide ...... by the protein-binding site known from X-ray complexes. The result of this analysis assists in explaining the efficiency of 2D pharmacophore fingerprints as descriptors in virtual screening....... the lead optimization toward a final drug candidate. This paper presents a combined approach to solving these two problems of ligand-based virtual screening and elucidation of SAR based on interplay between pharmacophore fingerprints and interpretation of PLS-discriminant analysis (PLS-DA) models....... The virtual screening capability of the PLS-DA method is compared to group fusion maximum similarity searching in a test using four graph-based pharmacophore fingerprints over a range of 10 diverse targets. The PLS-DA method was generally found to do better than the Smax method. The GpiDAPH3 and PCH...

Use of activity-based probes to develop high throughput screening assays that can be performed in complex cell extracts.

Directory of Open Access Journals (Sweden)

Edgar Deu

2010-08-01

Full Text Available High throughput screening (HTS is one of the primary tools used to identify novel enzyme inhibitors. However, its applicability is generally restricted to targets that can either be expressed recombinantly or purified in large quantities.Here, we described a method to use activity-based probes (ABPs to identify substrates that are sufficiently selective to allow HTS in complex biological samples. Because ABPs label their target enzymes through the formation of a permanent covalent bond, we can correlate labeling of target enzymes in a complex mixture with inhibition of turnover of a substrate in that same mixture. Thus, substrate specificity can be determined and substrates with sufficiently high selectivity for HTS can be identified. In this study, we demonstrate this method by using an ABP for dipeptidyl aminopeptidases to identify (Pro-Arg2-Rhodamine as a specific substrate for DPAP1 in Plasmodium falciparum lysates and Cathepsin C in rat liver extracts. We then used this substrate to develop highly sensitive HTS assays (Z'>0.8 that are suitable for use in screening large collections of small molecules (i.e >300,000 for inhibitors of these proteases. Finally, we demonstrate that it is possible to use broad-spectrum ABPs to identify target-specific substrates.We believe that this approach will have value for many enzymatic systems where access to large amounts of active enzyme is problematic.

Screening level dose assessment of aquatic biota downstream of the Marcoule nuclear complex in southern France.

Science.gov (United States)

St-Pierre, S; Chambers, D B; Lowe, L M; Bontoux, J G

1999-09-01

Aquatic biota in the Rhone River downstream of the Marcoule nuclear complex in France are exposed to natural sources of radiation and to radioactivity released from the Marcoule complex. A simple conservative screening level model was used to estimate the range of concentrations in aquatic media (water, sediments, and aquatic organisms) of both artificial and natural radionuclides and the consequent absorbed (whole body) dose rates for aquatic organisms. Five categories of aquatic organisms were studied, namely, submerged aquatic plants (phanerogam), non-bottom-feeding fish, bottom-feeding fish, mollusca, and fish-eating birds. The analysis was based on the radionuclide concentrations reported in four consecutive annual radioecological monitoring reports published by French agencies with nuclear regulatory responsibilities. The results of this assessment were used to determine, qualitatively, the magnitude of any potential health impacts on each of the five categories of aquatic organisms studied. The range of dose rate estimates ranged over three orders of magnitude, with maximum dose rates estimated to be in the order of 1 to 10 microGy h(-1). These maximum dose rates are a factor 40 or more below the international guideline intended to ensure the protection of aquatic populations (about 400 microGy h(-1)), and a factor ten or more below the level which may trigger the need for a more detailed evaluation of potential ecological consequences to the exposed populations (about 100 microGy h(-1)). As a result, chronic levels of radioactivity, artificial and natural, measured in aquatic media downstream of Marcoule are unlikely to result in adverse health impacts on the categories and species of aquatic organisms studied. Thus, based on the screening level analysis discussed in this paper, a more detailed evaluation of the dose rates does not appear to be warranted.

Environmental assessment: Solid waste retrieval complex, enhanced radioactive and mixed waste storage facility, infrastructure upgrades, and central waste support complex, Hanford Site, Richland, Washington

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-09-01

The U.S. Department of Energy (DOE) needs to take action to: retrieve transuranic (TRU) waste because interim storage waste containers have exceeded their 20-year design life and could fail causing a radioactive release to the environment provide storage capacity for retrieved and newly generated TRU, Greater-than-Category 3 (GTC3), and mixed waste before treatment and/or shipment to the Waste Isolation Pilot Project (WIPP); and upgrade the infrastructure network in the 200 West Area to enhance operational efficiencies and reduce the cost of operating the Solid Waste Operations Complex. This proposed action would initiate the retrieval activities (Retrieval) from Trench 4C-T04 in the 200 West Area including the construction of support facilities necessary to carry out the retrieval operations. In addition, the proposed action includes the construction and operation of a facility (Enhanced Radioactive Mixed Waste Storage Facility) in the 200 West Area to store newly generated and the retrieved waste while it awaits shipment to a final disposal site. Also, Infrastructure Upgrades and a Central Waste Support Complex are necessary to support the Hanford Site`s centralized waste management area in the 200 West Area. The proposed action also includes mitigation for the loss of priority shrub-steppe habitat resulting from construction. The estimated total cost of the proposed action is $66 million.

The DNA relaxation activity and covalent complex accumulation of Mycobacterium tuberculosis topoisomerase I can be assayed in Escherichia coli: application for identification of potential FRET-dye labeling sites

Directory of Open Access Journals (Sweden)

Abrenica Maria V

2010-09-01

Full Text Available Abstract Background Mycobacterium tuberculosis topoisomerase I (MtTOP1 and Escherichia coli topoisomerase I have highly homologous transesterification domains, but the two enzymes have distinctly different C-terminal domains. To investigate the structure-function of MtTOP1 and to target its activity for development of new TB therapy, it is desirable to have a rapid genetic assay for its catalytic activity, and potential bactericidal consequence from accumulation of its covalent complex. Results We show that plasmid-encoded recombinant MtTOP1 can complement the temperature sensitive topA function of E. coli strain AS17. Moreover, expression of MtTOP1-G116 S enzyme with the TOPRIM mutation that inhibits DNA religation results in SOS induction and loss of viability in E. coli. The absence of cysteine residues in the MtTOP1 enzyme makes it an attractive system for introduction of potentially informative chemical or spectroscopic probes at specific positions via cysteine mutagenesis. Such probes could be useful for development of high throughput screening (HTS assays. We employed the AS17 complementation system to screen for sites in MtTOP1 that can tolerate cysteine substitution without loss of complementation function. These cysteine substitution mutants were confirmed to have retained the relaxation activity. One such mutant of MtTOP1 was utilized for fluorescence probe incorporation and fluorescence resonance energy transfer measurement with fluorophore-labeled oligonucleotide substrate. Conclusions The DNA relaxation and cleavage complex accumulation of M. tuberculosis topoisomerase I can be measured with genetic assays in E. coli, facilitating rapid analysis of its activities, and discovery of new TB therapy targeting this essential enzyme.

Site characterization studies in the NWTS program

International Nuclear Information System (INIS)

Shipler, D.; Evans, G.

1980-01-01

The US Department of Energy (DOE) has the responsibility to identify sites and construct and operate facilities for the storage or isolation of spent fuel and/or reprocessing radioactive wastes from commercial nuclear power plants. The National Waste Terminal Storage (NWTS) Program has been initiated by the DOE to develop the technology and demonstrate the feasibility of burial and isolation of high level radioactive waste in deep geologic formations. The NTWS Program plan which sets forth the criteria, procedures, and other considerations required to characterize and select a site in a comprehensive stepwise manner is discussed. The plan is not specific to any given geologic medium but serves as a guide for site selection in any geohydrologic system deemed appropriate for consideration for a deep geologic repository. The plan will be used by all NWTS Project Offices in the conduct of their site characterization program. The plan will be updated, as warranted, to reflect technology development, National policies, rulemakings by regulatory agencies, and other changing political, social, and institutional considerations. Site characterization begins with the identification of regions believed to have suitable geologic, hydrologic, and environmental characteristics for repository siting. This is followed by an iterative process of data collection and analysis to identify areas and locations which appear most suitable for further investigations. In addition, screening studies of the DOE's nuclear complexes has led to the selection of the Nevada Test Site and the Hanford Site for further characterization studies. The site characterization process results in a number of candidate sites from which a site will be selected and proposed to the NRC for licensing

Lys and Arg in UBI: A specific site for a stable Tc-99m complex?

International Nuclear Information System (INIS)

Melendez-Alafort, Laura; Ramirez, Flor de Maria; Ferro-Flores, Guillermina; Murphy, Consuelo Arteaga de; Pedraza-Lopez, Martha; Hnatowich, Donald J.

2003-01-01

The aim of this study was to help establish if ubiquicidin peptide 29-41 fragment (UBI) contains a specific site for 99m Tc labeling by a new direct method under alkaline conditions. Since this peptide does not have cysteine residues, it is possible that neighboring arginine and lysine in the peptide amino acid sequence (Thr-Gly-Arg-Ala-Lys-Arg-Arg-Met-Gln-Tyr-Asn-Arg-Arg) could be a specific coordination site to form a stable 99m Tc-UBI complex. Following direct labeling, the in vitro stability of 99m Tc-UBI was compared to UBI radiolabeled by one indirect method using HYNIC/tricine and HYNIC/tricine/EDDA. Radiochemical purity of 99m Tc-UBI averaged 97% compared to 88% for 99m Tc-HYNIC-UBI/tricine and 98% for 99m Tc-HYNIC-UBI/tricine/EDDA. Both 99m Tc-HYNIC-UBI (tricine or EDDA) and 99m Tc-UBI showed stability in human serum and solutions of cysteine. 99m Tc-UBI radiochemical purity 24 h after dilution in 0.9% NaCl was greater than 90% at pH 9 and greater than 95% at pH 6.5. Under one set of experimental conditions, in vitro binding to bacteria of 99m Tc-UBI was 35% and identical to that of 99m Tc-HYNIC-UBI/tricine and 99m Tc-HYNIC-UBI/tricine/EDDA at 32% and 31% respectively. The biodistribution of 99m Tc-UBI in mice showed a rapid renal clearance. To help identify the site(s) of 99m Tc binding following direct labeling, molecular mechanics and quantum-mechanical calculations were performed which showed that the amine groups of Arg 7 and Lys are the most probable site. The calculations show that these groups can form a square pyramid with two water molecules for the Tc cation (dxysp 3 ). It will be necessary to isolate and characterize the 99 Tc(V)(O)-UBI . (H 2 O) n complex to confirm these results

Prevention of the wind migration of Semipalatinsk test site contaminated topsoil by inter-polymer complexes

International Nuclear Information System (INIS)

Kudaibergenov, S.E.

2010-01-01

Full text: It is well known that Semipalatinsk Test Site has been contaminated by radionuclides mainly as a result of atmospheric, aboveground and underground intensive nuclear tests during more than 40 years. Survey of residual radioactivity in the soil at ten Semipalatinsk Test Site areas showed that a great number of Plutonium-239, 240, Strontium-90 and Cesium-137 are concentrated in the depth of soil layer 0-8 cm. The residual radioactivity within the Semipalatinsk Test Site is tightly bound to the topsoil as a result of extreme heating and melting of the soils during the tests. The maximal amount of radionuclides is accumulated on the fine soil particles having 0.1-1.0 mm size. Wind erosion is responsible for suspension of contaminated soil particles in the air and further spreading of contamination far away. For instance, dust particles of diameter 0,05-0,1 mm are dropped within a couple of kilometers of the erosion site, while particles of about 0.005-0.01 mm diameter can move hundreds and thousands of kilometers. According to the results of the Institute of Radiation Safety and Ecology, Kazakhstan, in “Degelen” massive, where the intensive nuclear tests were carried out, the concentration of radionuclides in air increases for Sr-90 up to 5 times, for Pu-239,240 up to 100-250 times during the elevation of thin dust from the ground surface. In this connection agglomeration of thin dust containing radionuclides is of primary importance to protect the population from inhalation of re-suspended dust. Inter-polymer complexes are water-insoluble, moisture and gas permeable substances that form a “cobweb” on the surface of soil particles and consequently leading to formation of protective crust. Inter-polymer complexes enhance the intrusion of water into the soil, resulting in increased soil moisture to promote seed germination and plant growth. Inter-polymer complexes are also able to accumulate radionuclides via inclusion of metal ions into the Inter

Molecular characterization of a complex site-specific radiation-induced DNA double-strand break

International Nuclear Information System (INIS)

Datta, K.; Dizdaroglu, M.; Jaruga, P.; Neumann, R.D.; Winters, T.A.

2003-01-01

Radiation lethality is a function of radiation-induced DNA double-strand breaks (DSB). Current models propose the lethality of a DSB to be a function of its structural complexity. We present here for the first time a map of damage associated with a site-specific double-strand break produced by decay of 125 I in a plasmid bound by a 125 I-labeled triplex forming oligonucleotide ( 125 I-TFO). The E. coli DNA repair enzymes, endonuclease IV (endo IV), endonuclease III (endo III), and formamidopyrimidine-DNA glycosylase (Fpg), which recognize AP sites, and pyrimidine and purine base damage respectively, were used as probes in this study. 125 I-TFO bound plasmid was incubated with and without DMSO at -80 deg C for 1 month. No significant difference in DSB yield was observed under these conditions. A 32 base pair fragment from the upstream side of the decay site was isolated by restriction digestion and enzymatically probed to identify damage sites. Endo IV treatment of the 5'-end labeled upper strand indicated clustering of AP sites within 3 bases downstream and 7 bases upstream of the targeted base. Also, repeated experiments consistently detected an AP site 4 bases upstream of the 125 Itarget base. This was further supported by complementary results with the 3'-end labeled upper strand. Endo IV analysis of the lower strand also shows clustering of AP sites near the DSB end. Endo III and Fpg probing demonstrated that base damage is also clustered near the targeted break site. DSBs produced in the absence of DMSO displayed a different pattern of enzyme sensitive damage than those produced in the presence of DMSO. Identification of specific base damage types within the restriction fragment containing the DSB end was achieved with GC/MS. Base damage consisted of 8-hydroguanine, 8-hydroxyadenine, and 5-hydroxycytosine. These lesions were observed at relative yields of 8-hydroguanine and 5-hydroxycytosine to 8-hydroxyadenine of 7.4:1 and 4.7:1, respectively, in the absence

Screening for renal insufficiency following ESUR (European Society of Urogenital Radiology) guidelines with on-site creatinine measurements in an outpatient setting

International Nuclear Information System (INIS)

Ledermann, H.P.; Mengiardi, B.; Schmid, A.; Froehlich, J.M.

2010-01-01

To report the results and implications for workflow following introduction of ESUR guidelines to screen for potential renal insufficiency (RI) in private practice with on-site creatinine measurements. A total of 1,766 consecutive outpatients scheduled for contrast-enhanced CT (CECT) completed the ESUR questionnaire enquiring about kidney disease, renal surgery, proteinuria, diabetes mellitus, hypertension, gout or use of nephrotoxic drugs. Patients with positive risk factors underwent on-site creatinine measurement and calculation of estimated glomerular filtration rate (eGFR). Attending radiologists adapted subsequent imaging depending on renal function and presence of risk factors. One or more ESUR risk factors were present in 796 (45.1%) patients, including hypertension (37.7%), nephrotoxic medication (21.3%), diabetes mellitus (8.0%), proteinuria (3.9%), renal disease (4.1%), gout (3.1%) and renal surgery (2.6%). Pre-procedural creatinine measurements revealed severe RI (eGFR -1 1.73 m -2 ) in 10 (1.3%) and moderate RI (eGFR 30-59 ml min -1 1.73 m -2 ) in 106 (13.8%). Imaging work-up was adapted in 132 (16.6%) as follows: reduction of contrast material dose (n = 85), CT without contrast (n = 40), changeover to MRI (n = 3) or scintigraphy (n = 4). Screening for RI following ESUR guidelines requires creatinine measurements in nearly half of outpatients scheduled for CECT and reveals moderate to severe renal impairment in 6.6%. (orig.)

Dual binding mode of the nascent polypeptide-associated complex reveals a novel universal adapter site on the ribosome.

Science.gov (United States)

Pech, Markus; Spreter, Thomas; Beckmann, Roland; Beatrix, Birgitta

2010-06-18

Nascent polypeptide-associated complex (NAC) was identified in eukaryotes as the first cytosolic factor that contacts the nascent polypeptide chain emerging from the ribosome. NAC is present as a homodimer in archaea and as a highly conserved heterodimer in eukaryotes. Mutations in NAC cause severe embryonically lethal phenotypes in mice, Drosophila melanogaster, and Caenorhabditis elegans. In the yeast Saccharomyces cerevisiae NAC is quantitatively associated with ribosomes. Here we show that NAC contacts several ribosomal proteins. The N terminus of betaNAC, however, specifically contacts near the tunnel exit ribosomal protein Rpl31, which is unique to eukaryotes and archaea. Moreover, the first 23 amino acids of betaNAC are sufficient to direct an otherwise non-associated protein to the ribosome. In contrast, alphaNAC (Egd2p) contacts Rpl17, the direct neighbor of Rpl31 at the ribosomal tunnel exit site. Rpl31 was also recently identified as a contact site for the SRP receptor and the ribosome-associated complex. Furthermore, in Escherichia coli peptide deformylase (PDF) interacts with the corresponding surface area on the eubacterial ribosome. In addition to the previously identified universal adapter site represented by Rpl25/Rpl35, we therefore refer to Rpl31/Rpl17 as a novel universal docking site for ribosome-associated factors on the eukaryotic ribosome.

A dynamic simulation model of the Savannah River Site high level waste complex

International Nuclear Information System (INIS)

Gregory, M.V.; Aull, J.E.; Dimenna, R.A.

1994-01-01

A detailed, dynamic simulation entire high level radioactive waste complex at the Savannah River Site has been developed using SPEEDUP(tm) software. The model represents mass transfer, evaporation, precipitation, sludge washing, effluent treatment, and vitrification unit operation processes through the solution of 7800 coupled differential and algebraic equations. Twenty-seven discrete chemical constituents are tracked through the unit operations. The simultaneous simultaneous simulation of concurrent batch and continuous processes is achieved by several novel, customized SPEEDUP(tm) algorithms. Due to the model's computational burden, a high-end work station is required: simulation of a years operation of the complex requires approximately three CPU hours on an IBM RS/6000 Model 590 processor. The model will be used to develop optimal high level waste (HLW) processing strategies over a thirty year time horizon. It will be employed to better understand the dynamic inter-relationships between different HLW unit operations, and to suggest strategies that will maximize available working tank space during the early years of operation and minimize overall waste processing cost over the long-term history of the complex. Model validation runs are currently underway with comparisons against actual plant operating data providing an excellent match

Internet-Based Cervical Cancer Screening Program

National Research Council Canada - National Science Library

Wilbur, David C; Crothers, Barbara A; Eichhorn, John H; Ro, Min S; Gelfand, Jeffrey A

2008-01-01

This project explores the combination of computerized automated primary screening of cervical cytology specimens in remote sites with interpretation of device-selected images transmitted via the Internet...

Internet-Based Cervical Cytology Screening System

National Research Council Canada - National Science Library

Wilbur, David C; Crothers, Barbara A; Eichhorn, John H; Ro, Min S; Gelfand, Jeffrey A

2007-01-01

This project explores the combination of computerized automated primary screening of cervical cytology specimens in remote sites with interpretation of device-selected images transmitted via the Internet...

Internet-Based Cervical Cytology Screening Program

National Research Council Canada - National Science Library

Wilbur, David C; Crothers, Barbara A; Eichhorn, John H; Ro, Min S; Gelfand, Jeffrey A

2006-01-01

This project explores the combination of computerized automated primary screening of cervical cytology specimens in remote sites with interpretation of device-selected images transmitted via the Internet...

TRANSIT: model for providing generic transportation input for preliminary siting analysis

International Nuclear Information System (INIS)

McNair, G.W.; Cashwell, J.W.

1985-02-01

To assist the US Department of Energy's efforts in potential facility site screening in the nuclear waste management program, a computerized model, TRANSIT, is being developed. Utilizing existing data on the location and inventory characteristics of spent nuclear fuel at reactor sites, TRANSIT derives isopleths of transportation mileage, costs, risks and fleet requirements for shipments to storage sites and/or repository sites. This technique provides a graphic, first-order method for use by the Department in future site screening efforts. 2 refs

Site characterization design and techniques used at the Southern Shipbuilding Corporation site

International Nuclear Information System (INIS)

Mueller, J.P.; Geraghty, C.A.; Moore, G.W.; Mullins, J.R.

1995-01-01

The Southern Shipbuilding Corporation (SSC) site is an inactive barge/ship manufacturing and repair facility situated on approximately 54 acres in Slidell, St. Tammany Parish, Louisiana. Two unlined surface impoundments (North and South impoundments) are situated on the northwest portion of the site and are surrounded on three sides by Bayou Bonfouca. These impoundments are the sources of carcinogenic polynuclear aromatic hydrocarbon (CPAH) contamination at the site. Inadequate containment has resulted in the release of impoundment wastes into the bayou. To evaluate potential response alternatives for the site, an Engineering Evaluation/Cost Analysis (EE/CA) field investigation was conducted from July through October 1994. A two phase sampling approach was used in combination with innovative and traditional sampling techniques, field screening technologies, and exploitation of the visual characteristics of the waste to determine the extent of waste migration with limited off-site laboratory confirmation. A skid-mounted mobile drilling unit, secured to a specialized sampling platform designed for multiple applications, was used for collection of sediment cores from the bayou as well as tarry sludge cores from the impoundments. Field screening of core samples was accomplished on site using an organic vapor analyzer and a total petroleum hydrocarbon (TPH) field analyzer. Pollutants of concern include metals, cyanide, dioxin, and organic compounds. This paper presents details on the sampling design and characterization techniques used to accomplish the EE/CA field investigation

Alternative approaches to improve site investigations

International Nuclear Information System (INIS)

Beach, R.B.; Silka, L.R.

1992-01-01

Common complaints about standard investigations at hazardous waste sites include high costs and long time frames. Investigations at military bases as part of the installation restoration program or base closures suffer additionally from nonuniformity of approach and results and redundancy of work effort conducted by multiple environmental contractors. The problems of high costs and long time frames can be minimized by the consistent use of alternative sampling methods (such as soil gas surveys) and the utilization of analytical screening procedures at both on-site and off-site laboratories. Acceptable data quality is maintained by several procedures. Incorporation of quality control measures (10 % frequency), such as matrix spikes and duplicates, into the alternative analytical techniques allows assessment of the data quality relative to predetermined data quality objectives (DQOs). Confirmation of the screening results (10% frequency) using standard US EPA methods, such as the contract laboratory program (CLP) statement of work (SOW), allows an additional evaluation of the data accuracy. Depending on the investigative objectives, knowledge based computer systems (expert systems,) could be used to improve uniformity of site evaluations. Several case histories will be presented demonstrating how soil gas surveys, screening analyses and standard analyses can be utilized to give increased site information in a reduced time frame and at a cost savings of 30 to 40%. One case history illustrates a screening technique developed by the author for polynuclear aromatics (semi-volatile organic compounds) that can be conducted at a cost savings of 90% relative to a standard US EPA method. A comparison of the phased investigative approach to one using an integrated field team is presented for fuel spill or UST areas

A peripheral artery disease screening study in Puerto Rico.

Science.gov (United States)

Delgado-Osorio, Héctor; Franqui-Rivera, Hilton; García-Palmieri, Mario R; Díaz-Santana, Mary V; Alvarez, Mario

2011-01-01

Peripheral artery disease (PAD) of the lower extremities is frequently underdiagnosed and undertreated. The results of screening for PAD in adults attending outpatient clinics at different sites in Puerto Rico from 2007 to 2010 are presented. A total of 33 outpatients screening clinics were conducted at different sites throughout the Island. Following the ACC/AHA Guideline recommendations, asymptomatic patients who qualified were screened for PAD using the ankle-brachial index (ABI). An ABI diabetes mellitus, and dyslipidemia are known key factors in development of PAD. Practicing physicians must be aware of the importance of an early diagnosis of PAD, particularly in the asymptomatic patient, so as to institute preventive and management measures.

A summary of ecological investigations at the burial ground complex, Savannah River Site - 1994

Energy Technology Data Exchange (ETDEWEB)

Friday, G.P.; Hartman, G.D.; Mackey, H.E. Jr.; Riley, R.S.; Roach, J.L.; Specht, W.L.; Westbury, H.M.; Wike, L.D.

1994-11-01

This report summarizes the results of three ecological investigations that were conducted in 1994 at the Burial Ground Complex (BGC) at the Savannah River Site (SRS). The three topics of study included remote sensing, aquatic toxicity testing, and qualitative surveys of herpetofauna and small mammals. Interim reports from each investigation are included in the appendices (A, B, and C). The objectives of the remote sensing effort were to compile historical aerial photography of the BGC and to develop a land use/cover map of the complex using recent aerial imagery. The goal of the aquatic toxicity testing was to determine if surface waters were toxic to aquatic biota whereas the objectives of the vertebrate surveys were to identify the species diversity and relative abundances of amphibians, reptiles, and small mammals inhabiting the study area.

A summary of ecological investigations at the burial ground complex, Savannah River Site - 1994

International Nuclear Information System (INIS)

Friday, G.P.; Hartman, G.D.; Mackey, H.E. Jr.; Riley, R.S.; Roach, J.L.; Specht, W.L.; Westbury, H.M.; Wike, L.D.

1994-11-01

This report summarizes the results of three ecological investigations that were conducted in 1994 at the Burial Ground Complex (BGC) at the Savannah River Site (SRS). The three topics of study included remote sensing, aquatic toxicity testing, and qualitative surveys of herpetofauna and small mammals. Interim reports from each investigation are included in the appendices (A, B, and C). The objectives of the remote sensing effort were to compile historical aerial photography of the BGC and to develop a land use/cover map of the complex using recent aerial imagery. The goal of the aquatic toxicity testing was to determine if surface waters were toxic to aquatic biota whereas the objectives of the vertebrate surveys were to identify the species diversity and relative abundances of amphibians, reptiles, and small mammals inhabiting the study area

Methodology for selecting low-level radioactive waste disposal sites with application to the Oak Ridge Reservation

International Nuclear Information System (INIS)

Lee, D.W.; Ketelle, R.H.

1984-01-01

A methodology was developed to select an environmentally acceptable site for low-level radioactive waste disposal for a predetermined region of interest using prescribed site suitability requirements. The methodology provides a defensible means for identifying candidate areas within the region, candidate sites within the areas, and an environmentally preferred site from the candidate sites. This is accomplished in site screening and site characterization stages. The site screening stage relies on reconnaissance data to identify a preferred site. The site characterization stage relies on a detailed site investigation to determine site acceptability. The methodology was applied to the US Department of Energy Oak Ridge Reservation through the site screening stage. 6 references, 3 figures, 7 tables

EPA RE-Powering Mapper: Alternative Energy Potential at Cleanup Sites

Science.gov (United States)

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management??s (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

Exploiting PubChem for Virtual Screening.

Science.gov (United States)

Xie, Xiang-Qun

2010-12-01

IMPORTANCE OF THE FIELD: PubChem is a public molecular information repository, a scientific showcase of the NIH Roadmap Initiative. The PubChem database holds over 27 million records of unique chemical structures of compounds (CID) derived from nearly 70 million substance depositions (SID), and contains more than 449,000 bioassay records with over thousands of in vitro biochemical and cell-based screening bioassays established, with targeting more than 7000 proteins and genes linking to over 1.8 million of substances. AREAS COVERED IN THIS REVIEW: This review builds on recent PubChem-related computational chemistry research reported by other authors while providing readers with an overview of the PubChem database, focusing on its increasing role in cheminformatics, virtual screening and toxicity prediction modeling. WHAT THE READER WILL GAIN: These publicly available datasets in PubChem provide great opportunities for scientists to perform cheminformatics and virtual screening research for computer-aided drug design. However, the high volume and complexity of the datasets, in particular the bioassay-associated false positives/negatives and highly imbalanced datasets in PubChem, also creates major challenges. Several approaches regarding the modeling of PubChem datasets and development of virtual screening models for bioactivity and toxicity predictions are also reviewed. TAKE HOME MESSAGE: Novel data-mining cheminformatics tools and virtual screening algorithms are being developed and used to retrieve, annotate and analyze the large-scale and highly complex PubChem biological screening data for drug design.

Scarce information about breast cancer screening: An Italian websites analysis.

Science.gov (United States)

Attena, Francesco; Cancellieri, Mariagrazia; Pelullo, Concetta Paola

2016-12-01

Although the public should have complete and correct information about risk/benefit ratio of breast cancer screening, public knowledge appears generally scarce and oriented to overestimate benefits, with little awareness of possible disadvantages of the screening.We evaluated any document specifically addressed to the general female public and posted on internet by Italian public health services. The presence of false positive, false positive after biopsy, false negative, interval cancer, overdiagnosis, lead-time bias, exposure to irradiation, and mortality reduction was analyzed.Of the 255 websites consulted, 136 (53.3%) had sites addressed to the female public. The most commonly reported information points were the false-positive (30.8% of sites) and radiation exposure (29.4%) rates. Only 11 documents mentioned overdiagnosis, 2 mentioned risk of false positive with biopsy, and only 1 mentioned lead-time bias. Moreover, only 15 sites (11.0%) reported quantitative data for any risk variables.Most documents about breast cancer screening published on the web for the female public contained little or no information about risk/benefit ratio and were biased in favor of screening.

Automated tool for virtual screening and pharmacology-based pathway prediction and analysis

Directory of Open Access Journals (Sweden)

Sugandh Kumar

2017-10-01

Full Text Available The virtual screening is an effective tool for the lead identification in drug discovery. However, there are limited numbers of crystal structures available as compared to the number of biological sequences which makes (Structure Based Drug Discovery SBDD a difficult choice. The current tool is an attempt to automate the protein structure modelling and automatic virtual screening followed by pharmacology-based prediction and analysis. Starting from sequence(s, this tool automates protein structure modelling, binding site identification, automated docking, ligand preparation, post docking analysis and identification of hits in the biological pathways that can be modulated by a group of ligands. This automation helps in the characterization of ligands selectivity and action of ligands on a complex biological molecular network as well as on individual receptor. The judicial combination of the ligands binding different receptors can be used to inhibit selective biological pathways in a disease. This tool also allows the user to systemically investigate network-dependent effects of a drug or drug candidate.

Localization of the AP-3 adaptor complex defines a novel endosomal exit site for lysosomal membrane proteins

NARCIS (Netherlands)

Peden, A.A.; Oorschot, V.; Hesser, B.A.; Austin, C.D.; Scheller, R.H.; Klumperman, J.

2004-01-01

The adaptor protein (AP) 3 adaptor complex has been implicated in the transport of lysosomal membrane proteins, but its precise site of action has remained controversial. Here, we show by immuno-electron microscopy that AP-3 is associated with budding profiles evolving from a tubular endosomal

Screening Phosphorylation Site Mutations in Yeast Acetyl-CoA Carboxylase Using Malonyl-CoA Sensor to Improve Malonyl-CoA-Derived Product.

Science.gov (United States)

Chen, Xiaoxu; Yang, Xiaoyu; Shen, Yu; Hou, Jin; Bao, Xiaoming

2018-01-01

Malonyl-coenzyme A (malonyl-CoA) is a critical precursor for the biosynthesis of a variety of biochemicals. It is synthesized by the catalysis of acetyl-CoA carboxylase (Acc1p), which was demonstrated to be deactivated by the phosphorylation of Snf1 protein kinase in yeast. In this study, we designed a synthetic malonyl-CoA biosensor and used it to screen phosphorylation site mutations of Acc1p in Saccharomyces cerevisiae . Thirteen phosphorylation sites were mutated, and a combination of three site mutations in Acc1p, S686A, S659A, and S1157A, was found to increase malonyl-CoA availability. ACC1 S686AS659AS1157A expression also improved the production of 3-hydroxypropionic acid, a malonyl-CoA-derived chemical, compared to both wild type and the previously reported ACC1 S659AS1157A mutation. This mutation will also be beneficial for other malonyl-CoA-derived products.

Screening criteria for siting waste management facilities: Regional Management Plan

International Nuclear Information System (INIS)

1986-01-01

The Midwest Interstate Low-Level Radioactive Waste Commission (Midwest Compact) seeks to define and place into operation a system for low-level waste management that will protect the public health and safety and the environment from the time the waste leaves its point of origin. Once the system is defined it will be necessary to find suitable sites for the components of that waste management system. The procedure for siting waste management facilities that have been chosen by the compact is one in which a host state is chosen for each facility. The host state is then given the freedom to select the site. Sites will be needed of low-level waste disposal facilities. Depending on the nature of the waste management system chosen by the host state, sites may also be needed for regional waste treatment facilities, such as compactors or incinerators. This report provides example criteria for use in selecting sites for low-level radioactive waste treatment and disposal facilities. 14 refs

Phosphorylation site on yeast pyruvate dehydrogenase complex

International Nuclear Information System (INIS)

Uhlinger, D.J.

1986-01-01

The pyruvate dehydrogenase complex was purified to homogeneity from baker's yeast (Saccharomyces cerevisiae). Yeast cells were disrupted in a Manton-Gaulin laboratory homogenizer. The pyruvate dehydrogenase complex was purified by fractionation with polyethylene glycol, isoelectric precipitation, ultracentrifugation and chromatography on hydroxylapatite. Final purification of the yeast pyruvate dehydrogenase complex was achieved by cation-exchange high pressure liquid chromatography (HPLC). No endogenous pyruvate dehydrogenase kinase activity was detected during the purification. However, the yeast pyruvate dehydrogenase complex was phosphorylated and inactivated with purified pyruvate dehydrogenase kinase from bovine kidney. Tryptic digestion of the 32 P-labeled complex yielded a single phosphopeptide which was purified to homogeniety. The tryptic digest was subjected to chromatography on a C-18 reverse phase HPLC column with a linear gradient of acetonitrile. Radioactive fractions were pooled, concentrated, and subjected to anion-exchange HPLC. The column was developed with a linear gradient of ammonium acetate. Final purification of the phosphopeptide was achieved by chromatography on a C-18 reverse phase HPLC column developed with a linear gradient of acetonitrile. The amino acid sequence of the homogeneous peptide was determined by manual modified Edman degradation

Hazardous Waste Landfill Siting using GIS Technique and Analytical Hierarchy Process

Directory of Open Access Journals (Sweden)

Ozeair Abessi

2010-07-01

Full Text Available Disposal of large amount of generated hazardous waste in power plants, has always received communities' and authori¬ties attentions. In this paper using site screening method and Analytical Hierarchy Process (AHP a sophisticated approach for siting hazardous waste landfill in large areas is presented. This approach demonstrates how the evaluation criteria such as physical, socio-economical, technical, environmental and their regulatory sub criteria can be introduced into an over layer technique to screen some limited appropriate zones in the area. Then, in order to find the optimal site amongst the primary screened site utilizing a Multiple Criteria Decision Making (MCDM method for hierarchy computations of the process is recommended. Using the introduced method an accurate siting procedure for environmental planning of the landfills in an area would be enabled. In the study this approach was utilized for disposal of hazardous wastes of Shahid Rajaee thermal power plant located in Qazvin province west central part of Iran. As a result of this study 10 suitable zones were screened in the area at first, then using analytical hierarchy process a site near the power plant were chosen as the optimal site for landfilling of the hazardous wastes in Qazvin province.

Quantifying and visualizing site performance in clinical trials.

Science.gov (United States)

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

2018-03-01

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

The screening effects of the screened exchange hybrid functional in surface systems: A case study on the CO/Pt(111) problem

Energy Technology Data Exchange (ETDEWEB)

Li, H., E-mail: li-huanglong@mail.tsinghua.edu.cn [Department of Precision Instrument, Tsinghua University, Beijing, 100084 (China); Gillen, R. [Institut für Festkörperphysik. Technische Universität Berlin. Hardenbergstr. 36, 10623 Berlin (Germany); Robertson, J., E-mail: jr214@cam.ac.uk [Engineering Department, University of Cambridge, Cambridge CB2 1PZ (United Kingdom)

2016-06-15

The screened exchange (sX) hybrid functional has been widely used in computational material science. Although it has widely been studied in bulk systems, less is known about its functional behavior in surface systems which are crucial to many technologies such as materials synthesis and nano-electronic devices. Assessing the screening dependent functional behaviors in the surface systems is therefore important for its application in such systems. In this work, we investigate the screening effects of the sX in CO adsorption on Pt(111) surface. The differences between the sX and Heyd-Scuseria-Ernzerhof (HSE06) hybrid functionals, and the effects of screening parameters are studied. The screening has two effects: first, the HOMO-LUMO gap is screening dependent. This affects the site preference most significantly. In this work, atop adsorption of CO/Pt(111) is predicted by the hybrid functionals with screened exchange potential. The sX(1.44) gives the largest HOMO-LUMO gap for the isolated CO molecule. The adsorption energy difference between the atop and fcc site is also the largest by the sX(1.44) which is explained by the reduced metal d states to the CO 2π* state back-donation, with stronger effect for the fcc adsorption than for the atop adsorption; second, the adsorption energy is screening dependent. This can be seen by comparing the sX(2.38) and HSE06 which have different screening strengths. They show similar surface band structures for the CO adsorption but different adsorption energies, which is explained by the stronger CO 5σ state to the metal d states donation or the effectively screened Pauli repulsion. This work underlines the screening strength as a main difference between sX and HSE06, as well as an important hybrid functional parameter for surface calculation.

Screening concepts for the isolation of biosurfactant producing microorganisms.

Science.gov (United States)

Walter, Vanessa; Syldatk, Christoph; Hausmann, Rudolf

2010-01-01

This chapter gives an overview of current methods for the isolation of biosurfactant producing microbes. The common screening methods for biosurfactants are presented. Sampling and isolation of bacteria are the basis for screening of biosurfactant producing microbes. Hydrocarbon-contaminated sites are the most promising for the isolation of biosurfactant producing microbes, but many strains have also been isolated from undisturbed sites. In subsequent steps the isolates have to be characterized in order to identify the strains which are interesting for a further investigation. Several techniques have been developed for identifying biosurfactant producing strains. Most of them are directly based on the surface or interfacial activity of the culture supernatant. Apart from that, some screening methods explore the hydrophobicity of the cell surface. This trait also gives an indication on biosurfactant production. In recent years automation and miniaturization have led to the development of high throughput methods for screening. High throughput screening (HTS) for analyzing large amounts of potential candidates or whole culture collections is reflected in the end. However, no new principals have been introduced by HTS methods.

Site identification presentation: Basalt Waste Isolation Project

International Nuclear Information System (INIS)

1979-11-01

The final step in the site identification process for the Basalt Waste Isolation Project is described. The candidate sites are identified. The site identification methodology is presented. The general objectives which must be met in selecting the final site are listed. Considerations used in the screening process are also listed. Summary tables of the guidelines used are included

Screened Coulomb interactions in metallic alloys. I. Universal screening in the atomic-sphere approximation

DEFF Research Database (Denmark)

Ruban, Andrei; Skriver, Hans Lomholt

2002-01-01

We have used the locally self-consistent Green's-function (LSGF) method in supercell calculations to establish the distribution of the net charges assigned to the atomic spheres of the alloy components in metallic alloys with different compositions and degrees of order. This allows us to determine......-site local interaction zone. We demonstrate that the basic mechanism that governs the charge distribution is the screening of the net charges of the alloy components that makes the direct Coulomb interactions short ranged. In the atomic-sphere approximation, this screening appears to be almost independent...

Crystal structure of CotA laccase complexed with 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) at a novel binding site

International Nuclear Information System (INIS)

Liu, Zhongchuan; Xie, Tian; Zhong, Qiuping; Wang, Ganggang

2016-01-01

The crystal structure of CotA complexed with 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) in a hole motif has been solved; this novel binding site could be a potential structure-based target for protein engineering of CotA laccase. The CotA laccase from Bacillus subtilis is an abundant component of the spore outer coat and has been characterized as a typical laccase. The crystal structure of CotA complexed with 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) in a hole motif has been solved. The novel binding site was about 26 Å away from the T1 binding pocket. Comparison with known structures of other laccases revealed that the hole is a specific feature of CotA. The key residues Arg476 and Ser360 were directly bound to ABTS. Site-directed mutagenesis studies revealed that the residues Arg146, Arg429 and Arg476, which are located at the bottom of the novel binding site, are essential for the oxidation of ABTS and syringaldazine. Specially, a Thr480Phe variant was identified to be almost 3.5 times more specific for ABTS than for syringaldazine compared with the wild type. These results suggest this novel binding site for ABTS could be a potential target for protein engineering of CotA laccases

Crystal structure of CotA laccase complexed with 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) at a novel binding site

Energy Technology Data Exchange (ETDEWEB)

Liu, Zhongchuan; Xie, Tian [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, People’s Republic of (China); Key Laboratory of Environmental Microbiology of Sichuan Province, Chengdu 610041, People’s Republic of (China); Zhong, Qiuping [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, People’s Republic of (China); Key Laboratory of Environmental Microbiology of Sichuan Province, Chengdu 610041, People’s Republic of (China); University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of (China); Wang, Ganggang, E-mail: wanggg@cib.ac.cn [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, People’s Republic of (China); Key Laboratory of Environmental Microbiology of Sichuan Province, Chengdu 610041, People’s Republic of (China)

2016-03-24

The crystal structure of CotA complexed with 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) in a hole motif has been solved; this novel binding site could be a potential structure-based target for protein engineering of CotA laccase. The CotA laccase from Bacillus subtilis is an abundant component of the spore outer coat and has been characterized as a typical laccase. The crystal structure of CotA complexed with 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) in a hole motif has been solved. The novel binding site was about 26 Å away from the T1 binding pocket. Comparison with known structures of other laccases revealed that the hole is a specific feature of CotA. The key residues Arg476 and Ser360 were directly bound to ABTS. Site-directed mutagenesis studies revealed that the residues Arg146, Arg429 and Arg476, which are located at the bottom of the novel binding site, are essential for the oxidation of ABTS and syringaldazine. Specially, a Thr480Phe variant was identified to be almost 3.5 times more specific for ABTS than for syringaldazine compared with the wild type. These results suggest this novel binding site for ABTS could be a potential target for protein engineering of CotA laccases.

Screening for renal insufficiency following ESUR (European Society of Urogenital Radiology) guidelines with on-site creatinine measurements in an outpatient setting

Energy Technology Data Exchange (ETDEWEB)

Ledermann, H.P.; Mengiardi, B.; Schmid, A. [IMAMED Radiologie Nordwest, Basel (Switzerland); Froehlich, J.M. [Guerbet AG, Medical Affairs, Zurich (Switzerland); University of Bern, Radiology Department, Bern (Switzerland)

2010-08-15

To report the results and implications for workflow following introduction of ESUR guidelines to screen for potential renal insufficiency (RI) in private practice with on-site creatinine measurements. A total of 1,766 consecutive outpatients scheduled for contrast-enhanced CT (CECT) completed the ESUR questionnaire enquiring about kidney disease, renal surgery, proteinuria, diabetes mellitus, hypertension, gout or use of nephrotoxic drugs. Patients with positive risk factors underwent on-site creatinine measurement and calculation of estimated glomerular filtration rate (eGFR). Attending radiologists adapted subsequent imaging depending on renal function and presence of risk factors. One or more ESUR risk factors were present in 796 (45.1%) patients, including hypertension (37.7%), nephrotoxic medication (21.3%), diabetes mellitus (8.0%), proteinuria (3.9%), renal disease (4.1%), gout (3.1%) and renal surgery (2.6%). Pre-procedural creatinine measurements revealed severe RI (eGFR < 30 ml min{sup -1} 1.73 m{sup -2}) in 10 (1.3%) and moderate RI (eGFR 30-59 ml min{sup -1} 1.73 m{sup -2}) in 106 (13.8%). Imaging work-up was adapted in 132 (16.6%) as follows: reduction of contrast material dose (n = 85), CT without contrast (n = 40), changeover to MRI (n = 3) or scintigraphy (n = 4). Screening for RI following ESUR guidelines requires creatinine measurements in nearly half of outpatients scheduled for CECT and reveals moderate to severe renal impairment in 6.6%. (orig.)

Site characterization report for the Basalt Waste Isolation Project

International Nuclear Information System (INIS)

1982-11-01

This Site Characterization Report documents the results of the site screening process, the preliminary site characterization data, the technical issues that need to be addressed, and the plans for resolving these issues

Conformational coupling between receptor and kinase binding sites through a conserved salt bridge in a signaling complex scaffold protein.

Directory of Open Access Journals (Sweden)

Davi R Ortega

Full Text Available Bacterial chemotaxis is one of the best studied signal transduction pathways. CheW is a scaffold protein that mediates the association of the chemoreceptors and the CheA kinase in a ternary signaling complex. The effects of replacing conserved Arg62 of CheW with other residues suggested that the scaffold protein plays a more complex role than simply binding its partner proteins. Although R62A CheW had essentially the same affinity for chemoreceptors and CheA, cells expressing the mutant protein are impaired in chemotaxis. Using a combination of molecular dynamics simulations (MD, NMR spectroscopy, and circular dichroism (CD, we addressed the role of Arg62. Here we show that Arg62 forms a salt bridge with another highly conserved residue, Glu38. Although this interaction is unimportant for overall protein stability, it is essential to maintain the correct alignment of the chemoreceptor and kinase binding sites of CheW. Computational and experimental data suggest that the role of the salt bridge in maintaining the alignment of the two partner binding sites is fundamental to the function of the signaling complex but not to its assembly. We conclude that a key feature of CheW is to maintain the specific geometry between the two interaction sites required for its function as a scaffold.

A tiered analytical protocol for the characterization of heavy oil residues at petroleum-contaminated hazardous waste sites

International Nuclear Information System (INIS)

Pollard, S.J.T.; Kenefick, S.L.; Hrudey, S.E.; Fuhr, B.J.; Holloway, L.R.; Rawluk, M.

1994-01-01

The analysis of hydrocarbon-contaminated soils from abandoned refinery sites in Alberta, Canada is used to illustrate a tiered analytical approach to the characterization of complex hydrocarbon wastes. Soil extracts isolated from heavy oil- and creosote-contaminated sites were characterized by thin layer chromatography with flame ionization detection (TLC-FID), ultraviolet fluorescence, simulated distillation (GC-SIMDIS) and chemical ionization GC-MS analysis. The combined screening and detailed analytical methods provided information essential to remedial technology selection including the extent of contamination, the class composition of soil extracts, the distillation profile of component classes and the distribution of individual class components within various waste fractions. Residual contamination was characteristic of heavy, degraded oils, consistent with documented site operations and length of hydrocarbon exposure at the soil surface

Safety assessment document for the environmental test complex (Building 834) at Site 300

International Nuclear Information System (INIS)

Odell, B.N.; Pfeifer, H.E.

1981-01-01

A safety assessment was performed to determine if accidents occurring at the 834 Complex at Site 300 could present undue hazards to the general public, personnel at Site 300, or have an adverse effect on the environment. The credible accidents that might have an effect on these facilities or have off-site consequences were considered. These were earthquake, extreme wind (including missiles), lightning, flood, criticality, high explosive (HE) detonation that disperses uranium and beryllium, spontaneous oxidation of plutonium, explosions due to finely divided particles, and a fire. Seismic and extreme wind (including missiles) analyses indicate that the buildings are basically sound. (However, there are a few recommendations to further enhance the structural integrity of these facilities). Additional lightning protection for these facilities is being installed. These buildings are located high above the dry creek bed so that a flood is improbable. A criticality or a high explosive detonation involving plutonium is very remote since the radioactive materials are encased and plutonium and HE are not permitted concurrently in the same area at Site 300. (The exceptions to this policy are that explosive actuating devices are sometimes located in assemblies containing fissile materials. However, a planned or accidental actuation will not effect the safe containment of the fissile material within the assembly). Even though the possibility of an HE explosion involving uranium and beryllium is remote, the off-site lung doses were calculated and found to be below the accepted standards. It was determined that a fire was unlikely due to the low fire loading and the absence of ignition sources. It was also determined that the consequences of any accidents were reduced by the remote location of these facilities, their design, and by administrative controls

Instant, Visual, and Instrument-Free Method for On-Site Screening of GTS 40-3-2 Soybean Based on Body-Heat Triggered Recombinase Polymerase Amplification.

Science.gov (United States)

Wang, Rui; Zhang, Fang; Wang, Liu; Qian, Wenjuan; Qian, Cheng; Wu, Jian; Ying, Yibin

2017-04-18

On-site monitoring the plantation of genetically modified (GM) crops is of critical importance in agriculture industry throughout the world. In this paper, a simple, visual and instrument-free method for instant on-site detection of GTS 40-3-2 soybean has been developed. It is based on body-heat recombinase polymerase amplification (RPA) and followed with naked-eye detection via fluorescent DNA dye. Combining with extremely simplified sample preparation, the whole detection process can be accomplished within 10 min and the fluorescent results can be photographed by an accompanied smart phone. Results demonstrated a 100% detection rate for screening of practical GTS 40-3-2 soybean samples by 20 volunteers under different ambient temperatures. This method is not only suitable for on-site detection of GM crops but also demonstrates great potential to be applied in other fields.

Synthesis, spectroscopic characterization, biological screenings, DNA binding study and POM analyses of transition metal carboxylates

Science.gov (United States)

Uddin, Noor; Sirajuddin, Muhammad; Uddin, Nizam; Tariq, Muhammad; Ullah, Hameed; Ali, Saqib; Tirmizi, Syed Ahmed; Khan, Abdur Rehman

2015-04-01

This article contains the synthesis of a novel carboxylic acid derivative, its transition metal complexes and evaluation of biological applications. Six carboxylate complexes of transition metals, Zn(II) and Hg(II), have been successfully synthesized and characterized by FT-IR and NMR (1H, 13C). The ligand, HL, (4-[(2,6-Diethylphenyl)amino]-4-oxobutanoic acid) was also characterized by single crystal X-ray analysis. The complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date show the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than that of the free ligand. The ligand and its complexes were screened for antifungal and antileishmanial activities. The results showed that the ligand and its complexes are active with few exceptions. UV-visible spectroscopy and viscometry results reveal that the ligand and its complexes interact with the DNA via intercalative mode of interaction. A new and efficient strategy to identify the pharmacophores and anti-pharmacophores sites in carboxylate derivatives for the antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.

Application of new technologies for characterization of Hanford Site high-level waste

International Nuclear Information System (INIS)

Winters, W.I.

1998-01-01

To support remediation of Hanford Site high-level radioactive waste tanks, new chemical and physical measurement technologies must be developed and deployed. This is a major task of the Chemistry Analysis Technology Support (CATS) group of the Hanford Corporation. New measurement methods are required for efficient and economical resolution of tank waste safety, waste retrieval, and disposal issues. These development and deployment activities are performed in cooperation with Waste Management Federal Services of Hanford, Inc. This paper provides an overview of current analytical technologies in progress. The high-level waste at the Hanford Site is chemically complex because of the numerous processes used in past nuclear fuel reprocessing there, and a variety of technologies is required for effective characterization. Programmatic and laboratory operational needs drive the selection of new technologies for characterizing Hanford Site high-level waste, and these technologies are developed for deployment in laboratories, hot cells or in the field. New physical methods, such as the propagating reactive systems screening tool (PRSST) to measure the potential for self-propagating reactions in stored wastes, are being implemented. Technology for sampling and measuring gases trapped within the waste matrix is being used to evaluate flammability hazards associated with gas releases from stored wastes. Application of new inductively coupled plasma and laser ablation mass spectrometry systems at the Hanford Site's 222-S Laboratory will be described. A Raman spectroscopy probe mounted in a cone penetrometer to measure oxyanions in wastes or soils will be described. The Hanford Site has used large volumes of organic complexants and acids in processing waste, and capillary zone electrophoresis (CZE) methods have been developed for determining several of the major organic components in complex waste tank matrices. The principles involved, system installation, and results from

Distributed Idea Screening in Stage–gate Development Processes

DEFF Research Database (Denmark)

Onarheim, Balder; Christensen, Bo T.

2012-01-01

This paper investigates the gate screening of ideas in engineering design, by examination of the validity of employee voting schemes and biases associated with such voting. After conducting an employee-driven innovation project at a major producer of disposable medical equipment, 99 ideas had...... to be screened for further development. Inspired by the concept of ‘wisdom of the crowd’, all ideas were individually rated by a broad selection of employees, and the ratings were used to investigate two biases in employee voting: visual complexity and endowment effect/ownership of ideas. The visual complexity...

Construction of CRISPR Libraries for Functional Screening.

Science.gov (United States)

Carstens, Carsten P; Felts, Katherine A; Johns, Sarah E

2018-01-01

Identification of gene function has been aided by the ability to generate targeted gene knockouts or transcriptional repression using the CRISPR/CAS9 system. Using pooled libraries of guide RNA expression vectors that direct CAS9 to a specific genomic site allows identification of genes that are either enriched or depleted in response to a selection scheme, thus linking the affected gene to the chosen phenotype. The quality of the data generated by the screening is dependent on the quality of the guide RNA delivery library with regards to error rates and especially evenness of distribution of the guides. Here, we describe a method for constructing complex plasmid libraries based on pooled designed oligomers with high representation and tight distributions. The procedure allows construction of plasmid libraries of >60,000 members with a 95th/5th percentile ratio of less than 3.5.

Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site.

Science.gov (United States)

Handing, Katarzyna B; Shabalin, Ivan G; Szlachta, Karol; Majorek, Karolina A; Minor, Wladek

2016-03-01

Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1Å. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in human serum albumin (HSA), and suggest that binding of cetirizine to HSA will be similar. In support of that hypothesis, we show that the dissociation constants for cetirizine binding to CBS2 in ESA and HSA are identical using tryptophan fluorescence quenching. Presence of lysine and arginine residues that have been previously reported to undergo nonenzymatic glycosylation in CBS1 and CBS2 suggests that cetirizine transport in patients with diabetes could be altered. A review of all available SA structures from the PDB shows that in addition to the novel drug binding site we present here (CBS1), there are two pockets on SA capable of binding drugs that do not overlap with fatty acid binding sites and have not been discussed in published reviews. Copyright © 2016 Elsevier Ltd. All rights reserved.

Surfactant screening of diesel-contaminated soil

International Nuclear Information System (INIS)

Peters, R.W.; Shem, L.; Montemagno, C.D.; Lewis, B.

1991-01-01

At one installation, approximately 60,000 gal of No. 2 diesel fuel leaked into the subsurface environment, with contamination at depths of 6 to 34 m below the surface. Argonne National Laboratory was contracted to perform treatability studies for site remediation. The treatability studies focused on four separate phases: (1) leachability studies on the various contaminated soil borings, (2) air stripping studies, (3) bioremediation studies, and (4) surfactant screening/surfactant flooding studies. This paper summarizes the fourth phase of the research program in which 21 surfactants were screened for possible use to mobilize the organics from the contaminated soil prior to bioremediation. Anionic surfactants resulted in the greatest degree of diesel mobilization. The most promising surfactants will be employed on actual contaminated soil samples obtained from the site

Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening

Energy Technology Data Exchange (ETDEWEB)

Begley, Darren W.; Davies, Douglas R.; Hartley, Robert C.; Hewitt, Stephen N.; Rychel, Amanda L.; Myler, Peter J.; Van Voorhis, Wesley C.; Staker, Bart L.; Stewart, Lance J. (Emerald)

2014-10-02

Glutaric acidemia type 1 is an inherited metabolic disorder which can cause macrocephaly, muscular rigidity, spastic paralysis and other progressive movement disorders in humans. The defects in glutaryl-CoA dehydrogenase (GCDH) associated with this disease are thought to increase holoenzyme instability and reduce cofactor binding. Here, the first structural analysis of a GCDH enzyme in the absence of the cofactor flavin adenine dinucleotide (FAD) is reported. The apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the FAD-binding pocket relative to the ternary complex of the highly homologous human GCDH. After conducting a fragment-based screen, four small molecules were identified which bind to GCDH from B. pseudomallei. Complex structures were determined for these fragments, which cause backbone and side-chain perturbations to key active-site residues. Structural insights from this investigation highlight differences from apo GCDH and the utility of small-molecular fragments as chemical probes for capturing alternative conformational states of preformed protein crystals.

Structural studies of Ca2+-ATPase ligand and regulatory complexes

DEFF Research Database (Denmark)

Drachmann, Nikolaj Düring

2015-01-01

, the surrounding membrane itself has a huge influence on SERCA structure and function. Changes in the membrane thickness can alter the activity of the ATPase significantly, and even cause changes in the stoichiometry of ion transport. Structural studies on SERCA in the presence of four different phosphatidyl...... choline lipids with different aliphatic chain length and saturation show three specific lipid binding sites. The four different lipids analysed bind to the same binding sites with varying degrees of disorder. The study contributes to understanding the complex interplay between the surrounding membrane...... to explore the possibilities for an efficient screening of ligand-bound SERCA structures, serial femtosecond crystallography experiments of microcrystals of SERCA1a in the Ca2+ bound state and in a vanadate stabilised E2 state was conducted. A structure obtained at 2.8 Å maximum resolution of the proof...

Small Molecule Screen for Candidate Antimalarials Targeting Plasmodium Kinesin-5*

Science.gov (United States)

Liu, Liqiong; Richard, Jessica; Kim, Sunyoung; Wojcik, Edward J.

2014-01-01

Plasmodium falciparum and vivax are responsible for the majority of malaria infections worldwide, resulting in over a million deaths annually. Malaria parasites now show measured resistance to all currently utilized drugs. Novel antimalarial drugs are urgently needed. The Plasmodium Kinesin-5 mechanoenzyme is a suitable “next generation” target. Discovered via small molecule screen experiments, the human Kinesin-5 has multiple allosteric sites that are “druggable.” One site in particular, unique in its sequence divergence across all homologs in the superfamily and even within the same family, exhibits exquisite drug specificity. We propose that Plasmodium Kinesin-5 shares this allosteric site and likewise can be targeted to uncover inhibitors with high specificity. To test this idea, we performed a screen for inhibitors selective for Plasmodium Kinesin-5 ATPase activity in parallel with human Kinesin-5. Our screen of nearly 2000 compounds successfully identified compounds that selectively inhibit both P. vivax and falciparum Kinesin-5 motor domains but, as anticipated, do not impact human Kinesin-5 activity. Of note is a candidate drug that did not biochemically compete with the ATP substrate for the conserved active site or disrupt the microtubule-binding site. Together, our experiments identified MMV666693 as a selective allosteric inhibitor of Plasmodium Kinesin-5; this is the first identified protein target for the Medicines of Malaria Venture validated collection of parasite proliferation inhibitors. This work demonstrates that chemical screens against human kinesins are adaptable to homologs in disease organisms and, as such, extendable to strategies to combat infectious disease. PMID:24737313

Uptake and Predictors of Anal Cancer Screening in Men Who Have Sex With Men

Science.gov (United States)

D'Souza, Gypsyamber; Rajan, Shirani D.; Bhatia, Rohini; Cranston, Ross D.; Plankey, Michael W.; Silvestre, Anthony; Ostrow, David G.; Wiley, Dorothy; Shah, Nisha; Brewer, Noel T.

2013-01-01

Objectives. We investigated attitudes about and acceptance of anal Papanicolaou (Pap) screening among men who have sex with men (MSM). Methods. Free anal Pap screening (cytology) was offered to 1742 MSM in the Multicenter AIDS Cohort Study, who reported history of, attitudes about, and experience with screening. We explored predictors of declining screening with multivariate logistic regression. Results. A history of anal Pap screening was uncommon among non–HIV-infected MSM, but more common among HIV-infected MSM (10% vs 39%; P < .001). Most participants expressed moderate or strong interest in screening (86%), no anxiety about screening (66%), and a strong belief in the utility of screening (65%). Acceptance of screening during this study was high (85%) across all 4 US sites. Among those screened, most reported it was “not a big deal” or “not as bad as expected,” and 3% reported that it was “scary.” Declining to have screening was associated with Black race, anxiety about screening, and low interest, but not age or HIV status. Conclusions. This study demonstrated high acceptance of anal Pap screening among both HIV-infected and non–HIV-infected MSM across 4 US sites. PMID:23865658

Results of screening activities in salt states prior to the enactment of the Nationall Waste Policy Act

International Nuclear Information System (INIS)

Carbiener, W.A.

1983-01-01

The identification of potential sites for a nuclear waste repository through screening procedures in the salt states is a well-established, deliberate process. This screening process has made it possible to carry out detailed studies of many of the most promising potential sites, and general studies of all the sites, in anticipation of the siting guidelines specified in the Nuclear Waste Policy Act. The screening work completed prior to the passage of the Act allowed the Secretary of Energy to identify seven salt sites as potentially acceptable under the provisions of Section 116(a) of the Act. These sites were formally identified by letters from Secretary Hodel to the states of Texas, Utah, Mississippi, and Louisiana on February 2, 1983. The potentially acceptable salt sites were in Deaf Smith and Swisher Counties in Texas; Davis and Lavender Canyons in the Gibson Dome location in Utah; Richton and Cypress Creek Domes in Mississippi; and Vacherie Dome in Louisiana. Further screening will include comparison of each potentially acceptable site against disqualification factors and selection of a preferred site in each of the three geohydrologic settings from those remaining, in accordance with the siting guidelines. These steps will be documented in statutory Environmental Assessments prepared for each site to be nominated for detailed characterization. 9 references

Calcium-manganese oxides as structural and functional models for active site in oxygen evolving complex in photosystem II: lessons from simple models.

Science.gov (United States)

Najafpour, Mohammad Mahdi

2011-01-01

The oxygen evolving complex in photosystem II which induces the oxidation of water to dioxygen in plants, algae and certain bacteria contains a cluster of one calcium and four manganese ions. It serves as a model to split water by sunlight. Reports on the mechanism and structure of photosystem II provide a more detailed architecture of the oxygen evolving complex and the surrounding amino acids. One challenge in this field is the development of artificial model compounds to study oxygen evolution reaction outside the complicated environment of the enzyme. Calcium-manganese oxides as structural and functional models for the active site of photosystem II are explained and reviewed in this paper. Because of related structures of these calcium-manganese oxides and the catalytic centers of active site of the oxygen evolving complex of photosystem II, the study may help to understand more about mechanism of oxygen evolution by the oxygen evolving complex of photosystem II. Copyright © 2010 Elsevier B.V. All rights reserved.

Structure and properties of silver sulfate complexes derived from dipyridyl methylthio ligands with secondary donor site

Energy Technology Data Exchange (ETDEWEB)

Chen, Wen-Hua; Yan, Hao-Jie; Chen, Hui; Liu, Rui-Heng; Li, Ai-Min; Wang, Guo [Beijing Key Laboratory for Optical Materials and Photonic Devices, Department of Chemistry, Capital Normal University, Beijing 100048 (China); Wan, Chong-Qing, E-mail: wancq@cnu.edu.cn [Beijing Key Laboratory for Optical Materials and Photonic Devices, Department of Chemistry, Capital Normal University, Beijing 100048 (China); State Key Laboratory of Structural Chemistry in China, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China)

2017-06-15

Dipyridyl sulphide ligands 4-(pyridin-4-ylmethylthio)pyridine (abbreviated as L1) and 3-(pyridin-4-ylmethylthio)pyridine (abbreviated as L2) have been designed and used as μ-{sub N},{sub N}-bridging linkages to construct coordination polymers with free –S–CH{sub 2}– groups as secondary donor sites. By use solvent control method, coordination polymers ([Ag{sub 3}SO{sub 4}(L1){sub 3}](Cl)·4.5H{sub 2}O){sub ∞}(1), ([Ag{sub 2}SO{sub 4}(L1){sub 2}]·6H{sub 2}O·2CH{sub 3}OH){sub ∞}(2), ([Ag{sub 2}SO{sub 4}(L2){sub 2}]·H{sub 2}O){sub ∞}(3) and ([Ag{sub 4}(SO{sub 4}){sub 2}(L2){sub 4}]·5H{sub 2}O){sub ∞}(4) with different architectures were obtained. Complexes 1, 3 and 4 feature 1D channel with different sizes and structures. Complex 1 exhibits guest exchange by THF and 1,4-dioxane, and Hg{sup 2+} sorption ability from solution due to its relative larger channel and available bonding sites of –S– exposed to the channel region. All complexes have been characterized through single-crystal and powder X-ray diffraction (PXRD), FT-IR spectra, X-ray photoelectron spectroscopy (XPS), elemental and thermogravimetric analyses. The guest exchange and Hg{sup 2+} sorption were monitored and identified, and the structure-property relationship of coordination polymers 1–4 are discussed. - Graphical abstract: Coordination polymers of silver(I) sulfate with secondary donor sites are shown guest exchange property and Hg{sup 2+} absorb ability from solution. This work provides a new method to construct functional materials with potential application. - Highlights: • New example of constructing functional coordination polymer with secondary donor methylthio group. • Guest exchange and interesting Hg(II) absorb ability from solution are investigated. • New method to construct functional materials with potential application.

Genome-wide identification and characterization of Notch transcription complex-binding sequence paired sites in leukemia cells

Science.gov (United States)

Severson, Eric; Arnett, Kelly L.; Wang, Hongfang; Zang, Chongzhi; Taing, Len; Liu, Hudan; Pear, Warren S.; Liu, X. Shirley; Blacklow, Stephen C.; Aster, Jon C.

2018-01-01

Notch transcription complexes (NTCs) drive target gene expression by binding to two distinct types of genomic response elements, NTC monomer-binding sites and sequence-paired sites (SPSs) that bind NTC dimers. SPSs are conserved and are linked to the Notch-responsiveness of a few genes, but their overall contribution to Notch-dependent gene regulation is unknown. To address this issue, we determined the DNA sequence requirements for NTC dimerization using a fluorescence resonance energy transfer (FRET) assay, and applied insights from these in vitro studies to Notch-“addicted” leukemia cells. We find that SPSs contribute to the regulation of approximately a third of direct Notch target genes. While originally described in promoters, SPSs are present mainly in long-range enhancers, including an enhancer containing a newly described SPS that regulates HES5. Our work provides a general method for identifying sequence-paired sites in genome-wide data sets and highlights the widespread role of NTC dimerization in Notch-transformed leukemia cells. PMID:28465412

Complexes of Escherichia coli adenylate kinase and nucleotides: 1H NMR studies of the nucleotide sites in solution

International Nuclear Information System (INIS)

Vetter, I.R.; Reinstein, J.; Roesch, P.

1990-01-01

One- and two-dimensional nuclear magnetic resonance (NMR) studies, in particular substrate-protein nuclear Overhauser effect (NOESY) measurements, as well as nucleotide and P 1 ,P 5 -bis-(5'-adenosyl) pentaphosphate (AP 5 A) titrations and studies of the temperature-dependent unfolding of the tertiary structure of Escherichia coli adenylate kinase (AK EC ) were performed. These experiments and comparison with the same type of experiments performed with the porcine enzyme led them to the following conclusions: (1) at pH 8 and concentrations of approximately 2.5-3 mM, AK EC is partially unfolded at 318 K; (2) ATP·Mg 2+ binds to the ATP site with a dissociation constant of approximately 40 μM under the assumption that ATP binds to one nucleotide site only; (3) AP 5 A·Mg 2+ binds to both nucleotide sites and thus simulates the active complex; (4) the ATP·Mg 2+ adenine in the AK EC ·AP 5 A·Mg 2+ complex is located close to His 134 and Phe 19 ; (5) the AK EC G-loop with bound ATP·Mg 2+ is structurally highly homologous to the loop region in the oncogene product p21 with bound GTP·Mg 2+

Biological Evaluations of an Off-Stream Channel, Horizontal Flat-Plate Fish Screen-The Farmers Screen

Science.gov (United States)

Mesa, Matthew G.; Rose, Brien P.; Copeland, Elizabeth S.

2010-01-01

Screens are commonly installed at water diversion sites to reduce entrainment of fish. Recently, the Farmers Irrigation District in Hood River, Oregon, developed a new flat-plate screen design that offers passive operation and may result in reduced operation and installation costs to irrigators. To evaluate the performance (its biological effect on fish) of this type of screen, two size classes of juvenile coho salmon (Oncorhynchus kistuch) were released over a small version of this screen in the field-the Herman Creek screen. The performance of the screen was evaluated over a range of inflow [0.02 to 0.42 m3/s (cubic meters per second)] and diversion flows (0.02 to 0.34 m3/s) at different weir wall heights. The mean approach velocities for the screen ranged from 0 to 5 cm/s (centimeters per second) and mean sweeping velocities ranged from 36 to 178 cm/s. Water depths over the screen surface ranged from 1 to 25 centimeters and were directly related to weir wall height and inflow. Passage of juvenile coho salmon over the screen under a variety of hydraulic conditions did not severely injure them or cause delayed mortality. For all fish, the mean percentage of body surface area that was injured after passage over the screen ranged from about 0.4 to 3.0%. This occurred even though many fish contacted the screen surface during passage. No fish were observed becoming impinged on the screen surface (greater than 1 second contact with the screen). When operated within its design criteria (diversion flows of about 0.28 m3/s), the screen provided safe and effective downstream passage of juvenile salmonids under a variety of hydraulic conditions. However, we do not recommend operating the screen at inflows less than 0.14 m3/s (5 ft3/s) because water depth can get quite shallow and the screen can completely dewater, particularly at very low flows.

SPATIALLY-EXPLICIT BAT IMPACT SCREENING TOOL FOR WIND TURBINE SITING

Energy Technology Data Exchange (ETDEWEB)

Versar, Inc.; Exponent, Inc.

2013-10-28

As the U.S. seeks to increase energy production from renewable energy sources, development of wind power resources continues to grow. One of the most important ecological issues restricting wind energy development, especially the siting of wind turbines, is the potential adverse effect on bats. High levels of bat fatality have been recorded at a number of wind energy facilities, especially in the eastern United States. The U.S. Department of Energy contracted with Versar, Inc., and Exponent to develop a spatially-explicit site screening tool to evaluate the mortality of bats resulting from interactions (collisions or barotrauma) with wind turbines. The resulting Bat Vulnerability Assessment Tool (BVAT) presented in this report integrates spatial information about turbine locations, bat habitat features, and bat behavior as it relates to possible interactions with turbines. A model demonstration was conducted that focuses on two bat species, the eastern red bat (Lasiurus borealis) and the Indiana bat (Myotis sodalis). The eastern red bat is a relatively common tree-roosting species that ranges broadly during migration in the Eastern U.S., whereas the Indiana bat is regional species that migrates between a summer range and cave hibernacula. Moreover, Indiana bats are listed as endangered, and so the impacts to this species are of particular interest. The model demonstration used conditions at the Mountaineer Wind Energy Center (MWEC), which consists of 44 wind turbines arranged in a linear array near Thomas, West Virginia (Tucker County), to illustrate model functions and not to represent actual or potential impacts of the facility. The turbines at MWEC are erected on the ridge of Backbone Mountain with a nacelle height of 70 meters and a collision area of 72 meters (blade height) or 4,071 meters square. The habitat surrounding the turbines is an Appalachian mixed mesophytic forest. Model sensitivity runs showed that bat mortality in the model was most sensitive to

Screening specifications for Gulf Coast salt domes

International Nuclear Information System (INIS)

Brunton, G.D.; Laughon, R.B.; McClain, W.C.

1978-01-01

A reconnaissance survey of the salt domes of Mississippi, Louisiana, and east Texas is being planned to identify study areas for potential sites for radioactive waste disposal. Preliminary screening specifications were derived for each of the geological evaluation criteria by application of the significant factors that will have an impact on the reconnaissance survey. The procedure for the derivation of each screening specification is discussed. The screening specifications are the official OWI values to be used for the first-cut acceptance for salt dome study areas along the Gulf Coast. The derivation of the screening specifications is illustrated by (1) a statement of the geological evaluation criterion, (2) a discussion of the pertinent factors affecting the criterion, and (3) the evaluation of the value of the specification

Identification and removal of low-complexity sites in allele-specific analysis of ChIP-seq data.

Science.gov (United States)

Waszak, Sebastian M; Kilpinen, Helena; Gschwind, Andreas R; Orioli, Andrea; Raghav, Sunil K; Witwicki, Robert M; Migliavacca, Eugenia; Yurovsky, Alisa; Lappalainen, Tuuli; Hernandez, Nouria; Reymond, Alexandre; Dermitzakis, Emmanouil T; Deplancke, Bart

2014-01-15

High-throughput sequencing technologies enable the genome-wide analysis of the impact of genetic variation on molecular phenotypes at unprecedented resolution. However, although powerful, these technologies can also introduce unexpected artifacts. We investigated the impact of library amplification bias on the identification of allele-specific (AS) molecular events from high-throughput sequencing data derived from chromatin immunoprecipitation assays (ChIP-seq). Putative AS DNA binding activity for RNA polymerase II was determined using ChIP-seq data derived from lymphoblastoid cell lines of two parent-daughter trios. We found that, at high-sequencing depth, many significant AS binding sites suffered from an amplification bias, as evidenced by a larger number of clonal reads representing one of the two alleles. To alleviate this bias, we devised an amplification bias detection strategy, which filters out sites with low read complexity and sites featuring a significant excess of clonal reads. This method will be useful for AS analyses involving ChIP-seq and other functional sequencing assays. The R package abs filter for library clonality simulations and detection of amplification-biased sites is available from http://updepla1srv1.epfl.ch/waszaks/absfilter

Environmental impact assessment screening tool

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-05-01

An environmental assessment and impact planning software, SCREENER, was tested at a pilot project at the Cameco site (Port Hope). SCREENER was used to screen the impacts of a new construction project in accordance with the process and reporting requirements laid out in the Canadian Environmental Assessment Act. The software test concentrated on the activities that are directly involved with the structure construction and site preparation activities. In addition, a two and one half day training course was given to three AECB staff using the test case as a hands on example. The conclusion of this project is that an automated tool such as SCREENER (or Calyx, the new generation of environmental assessment tools from ESSA Software Ltd.), will help the AECB to standardize the approach to environmental assessment, assist in project planning, and save resources in the screening process. The new approach could allow to allocate AECB limited resources to the detailed assessments required for maximum impact activities. 2 figs. 7 refs.

Environmental impact assessment screening tool

International Nuclear Information System (INIS)

1995-05-01

An environmental assessment and impact planning software, SCREENER, was tested at a pilot project at the Cameco site (Port Hope). SCREENER was used to screen the impacts of a new construction project in accordance with the process and reporting requirements laid out in the Canadian Environmental Assessment Act. The software test concentrated on the activities that are directly involved with the structure construction and site preparation activities. In addition, a two and one half day training course was given to three AECB staff using the test case as a hands on example. The conclusion of this project is that an automated tool such as SCREENER (or Calyx, the new generation of environmental assessment tools from ESSA Software Ltd.), will help the AECB to standardize the approach to environmental assessment, assist in project planning, and save resources in the screening process. The new approach could allow to allocate AECB limited resources to the detailed assessments required for maximum impact activities

Evaluating cost and resource use associated with pulse oximetry screening for critical congenital heart disease: Empiric estimates and sources of variation.

Science.gov (United States)

Reeder, Matthew R; Kim, Jaewhan; Nance, Amy; Krikov, Sergey; Feldkamp, Marcia L; Randall, Harper; Botto, Lorenzo D

2015-11-01

Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry is being implemented in the United States and internationally; however, few data are available on the associated in-hospital costs and use of resources. Time and motion study in well-baby nurseries at two large urban hospitals in Utah using different approaches to pulse oximetry screening. Two observers recorded the time for each screening step together with provider and equipment characteristics. Structured questionnaire provided additional information on labor and equipment costs. Fifty-three CCHD screens were observed. At site A (n = 22), screening was mostly done by medical assistants (95%) using disposable probes (100%); at site B (n = 31), screening was mostly performed by certified nursing assistants (90%) using reusable probes (90%). Considering only first screens (n = 53), the median screen time was 8.6 min (range: 3.2-23.2), with no significant difference between sites. The overall cost ($ in 2014) of screening per baby was $24.52 at site A and $2.60 at site B. Nearly all the variation in cost (90%) was due to the cost of disposable probes; labor costs were similar between sites. CCHD screening by means of pulse oximetry is reasonably fast for most babies, leading to relative small labor costs with little variation by provider type. The main driver of costs is equipment: in a high throughput setting, reusable probes are currently associated with considerable cost saving compared with disposable probes. As programs expand to universal screening, improved and cheaper technologies could lead to considerable economies of scale. © 2015 Wiley Periodicals, Inc.

Easier operation and similar power of 10 g monofilament test for screening diabetic peripheral neuropathy.

Science.gov (United States)

Zhang, Qi; Yi, Na; Liu, Siying; Zheng, Hangping; Qiao, Xiaona; Xiong, Qian; Liu, Xiaoxia; Zhang, Shuo; Wen, Jie; Ye, Hongying; Zhou, Linuo; Li, Yiming; Hu, Renming; Lu, Bin

2018-01-01

Objective The 10 g Semmes-Weinstein monofilament evaluation (SWME) of 4 sites on each foot is recommended for distal symmetric polyneuropathy screening and diagnosis. A similar method has been proposed to diagnose 'high-risk' (for ulceration) feet, using 3 sites per foot. This study compared the effectiveness of SWME for testing 3, 4 and 10 sites per foot to identify patients with diabetic neuropathy. Methods We included 3497 subjects in a SWME of 10 sites; records from the 10-site SWME were used for a SWME of 3 and 4 sites. Neuropathy symptom scores and neuropathy deficit scores were evaluated to identify patients with diabetic peripheral neuropathy. Results The sensitivities of the 10 g SWME for 3, 4 and 10 sites were 17.8%, 19.0% and 22.4%, respectively. The Kappa coefficients for the SWME tests of 3, 4 and 10 sites were high (range: 0.78-0.93). Conclusions There were no significant differences in the effectiveness of 3-, 4- and 10-site SWME testing for diabetic peripheral neuropathy screening. SWME testing of 3 sites on each foot may be sufficient to screen for diabetic neuropathy.

Mammography screening. Benefits, harms, and informed choice.

Science.gov (United States)

Jørgensen, Karsten Juhl

2013-04-01

The rationale for breast cancer screening with mammography is deceptively simple: catch it early and reduce mortality from the disease and the need for mastectomies. But breast cancer is a complex problem, and complex problems rarely have simple solutions. Breast screening brings forward the time of diagnosis only slightly compared to the lifetime of a tumour, and screen-detected tumours have a size where metastases are possible. A key question is if screening can prevent metastases, and if the screen-detected tumours are small enough to allow breast conserving surgery rather than mastectomy. A mortality reduction can never justify a medical intervention in its own right, but must be weighed against the harms. Overdiagnosis is the most important harm of breast screening, but has gained wider recognition only in recent years. Screening leads to the detection and treatment of breast cancers that would otherwise never have been detected because they grow very slowly or not at all and would not have been detected in the woman's lifetime in the absence of screening. Screening therefore turns women into cancer patients unnecessarily, with life-long physical and psychological harms. The debate about the justification of breast screening is therefore not a simple question of whether screening reduces breast cancer mortality. This dissertation quantifies the primary benefits and harms of screening mammography. Denmark has an unscreened "control group" because only two geographical regions offered screening over a long time-period, which is unique in an international context. This was used to study breast cancer mortality, overdiagnosis, and the use of mastectomies. Also, a systematic review of overdiagnosis in five other countries allowed us to show that about half of the screen-detected breast cancers are overdiagnosed. An effect on breast cancer mortality is doubtful in today's setting, and overdiagnosis causes an increase in the use of mastectomies. These findings are

Nuclear Energy Center Site Survey, 1975. Executive summary

International Nuclear Information System (INIS)

1976-01-01

The Nuclear Energy Center Site Survey is a study of a potential alternative siting approach for nuclear power and fuel-cycle facilities, an approach that would cluster sizable groups of such facilities on a relatively small number of sites. The largest aggregation of reactors on a single site being planned today is four, and this quad is assumed (for comparative study purposes) to be the typical dispersed site by the year 2000. Three basic types of nuclear energy centers are considered: power-plant centers, consisting of 10 to 40 nuclear electric generating units of 1200-megawatt electric capacity each; fuel-cycle centers, consisting of fuel reprocessing plants, mixed-oxide fuel fabrication facilities, and radioactive waste management facilities; and combined centers, containing both power plants and fuel-cycle facilities. The results of the general site-location screening efforts are shown on a United States map that shows the locations of large areas identified as likely to contain suitable candidate sites for power NECs, on the basis of four coarse screening criteria: water resources, seismic activity, population density, and statutory excluded lands

On-site customization of silicone stents: towards optimal palliation of complex airway conditions.

Science.gov (United States)

Breen, David P; Dutau, Hervé

2009-01-01

Stents may be indicated as treatment of benign and malignant conditions of the central airways. Occasionally, aberrant and/or distorted airways secondary to therapy or surgery may preclude the use of commercially manufactured stents. The customization of stents is well described for nonpulmonary diseases, but to date there are only limited data in the literature on prosthesis customization for airway disease. To review all the different techniques and indications of on-site silicone stent customizations and their related complications. A retrospective study was undertaken to identify all patients who underwent treatment with a silicone stent which was customized on site by the physician. The study included subjects treated during an 8-year period. Forty-nine on-site customizations were performed in 43 patients (34 males, mean age 63 +/- 5.2 years). Stent customization was performed in 5.4% of the cases. Stent customization was performed for malignant and benign disease in 35 (81.3%) and 8 (18.7%) cases, respectively. In all cases, the stent deployed successfully and performed well while in situ. Stent manipulation did not increase complications. Customization of airway stents by the physician can lead to successful stenting of difficult airway lesions with a good short-term safety profile. Standard commercially available stents may have resulted in suboptimal management of complex airway pathologies. A prospective study is warranted to further investigate the safety profile and complications associated with stent customization. Copyright 2009 S. Karger AG, Basel.

A genome-wide map of hyper-edited RNA reveals numerous new sites

Science.gov (United States)

Porath, Hagit T.; Carmi, Shai; Levanon, Erez Y.

2014-01-01

Adenosine-to-inosine editing is one of the most frequent post-transcriptional modifications, manifested as A-to-G mismatches when comparing RNA sequences with their source DNA. Recently, a number of RNA-seq data sets have been screened for the presence of A-to-G editing, and hundreds of thousands of editing sites identified. Here we show that existing screens missed the majority of sites by ignoring reads with excessive (‘hyper’) editing that do not easily align to the genome. We show that careful alignment and examination of the unmapped reads in RNA-seq studies reveal numerous new sites, usually many more than originally discovered, and in precisely those regions that are most heavily edited. Specifically, we discover 327,096 new editing sites in the heavily studied Illumina Human BodyMap data and more than double the number of detected sites in several published screens. We also identify thousands of new sites in mouse, rat, opossum and fly. Our results establish that hyper-editing events account for the majority of editing sites. PMID:25158696

Establishment and Application of a High Throughput Screening System Targeting the Interaction between HCV Internal Ribosome Entry Site and Human Eukaryotic Translation Initiation Factor 3

Directory of Open Access Journals (Sweden)

Yuying Zhu

2017-05-01

Full Text Available Viruses are intracellular obligate parasites and the host cellular machinery is usually recruited for their replication. Human eukaryotic translation initiation factor 3 (eIF3 could be directly recruited by the hepatitis C virus (HCV internal ribosome entry site (IRES to promote the translation of viral proteins. In this study, we establish a fluorescence polarization (FP based high throughput screening (HTS system targeting the interaction between HCV IRES and eIF3. By screening a total of 894 compounds with this HTS system, two compounds (Mucl39526 and NP39 are found to disturb the interaction between HCV IRES and eIF3. And these two compounds are further demonstrated to inhibit the HCV IRES-dependent translation in vitro. Thus, this HTS system is functional to screen the potential HCV replication inhibitors targeting human eIF3, which is helpful to overcome the problem of viral resistance. Surprisingly, one compound HP-3, a kind of oxytocin antagonist, is discovered to significantly enhance the interaction between HCV IRES and eIF3 by this HTS system. HP-3 is demonstrated to directly interact with HCV IRES and promote the HCV IRES-dependent translation both in vitro and in vivo, which strongly suggests that HP-3 has potentials to promote HCV replication. Therefore, this HTS system is also useful to screen the potential HCV replication enhancers, which is meaningful for understanding the viral replication and screening novel antiviral drugs. To our knowledge, this is the first HTS system targeting the interaction between eIF3 and HCV IRES, which could be applied to screen both potential HCV replication inhibitors and enhancers.

Hazard screening application guide. Safety Analysis Report Update Program

Energy Technology Data Exchange (ETDEWEB)

None

1992-06-01

The basic purpose of hazard screening is to group precesses, facilities, and proposed modifications according to the magnitude of their hazards so as to determine the need for and extent of follow on safety analysis. A hazard is defined as a material, energy source, or operation that has the potential to cause injury or illness in human beings. The purpose of this document is to give guidance and provide standard methods for performing hazard screening. Hazard screening is applied to new and existing facilities and processes as well as to proposed modifications to existing facilities and processes. The hazard screening process evaluates an identified hazards in terms of the effects on people, both on-site and off-site. The process uses bounding analyses with no credit given for mitigation of an accident with the exception of certain containers meeting DOT specifications. The process is restricted to human safety issues only. Environmental effects are addressed by the environmental program. Interfaces with environmental organizations will be established in order to share information.

Assessing the efficacy of cancer screening

Directory of Open Access Journals (Sweden)

Gemma Jacklyn

2017-07-01

Full Text Available Background: Population-based cancer screening has been established for several types of cancer in Australia and internationally. Screening may perform differently in practice from randomised controlled trials, which makes evaluating programs complex. Materials and methods: We discuss how to assess the evidence of benefits and harms of cancer screening, including the main biases that can mislead clinicians and policy makers (such as volunteer, lead-time, length-time and overdiagnosis bias. We also discuss ways in which communication of risks can inform or mislead the community. Results: The evaluation of cancer screening programs should involve balancing the benefits and harms. When considering the overall worth of an intervention and allocation of scarce health resources, decisions should focus on the net benefits and be informed by systematic reviews. Communication of screening outcomes can be misleading. Many messages highlight the benefits while downplaying the harms, and often use relative risks and 5-year survival to persuade people to screen rather than support informed choice. Lessons learned: An evidence based approach is essential when evaluating and communicating the benefits and harms of cancer screening, to minimise misleading biases and the reliance on intuition.

Site characterization plan: Gulf Coast salt domes

International Nuclear Information System (INIS)

1983-12-01

The National Waste Terminal Storage (NWTS) program of the US Department of Energy (DOE) is responsible for developing technology and providing facilities for safe, environmentally acceptable, permanent disposal of high-level nuclear waste. The Office of Nuclear Waste Isolation has been intensively investigating Gulf Coast Salt Dome Basin salt domes and bedded salt in Texas and Utah since 1978. In the Gulf Coast, the application of screening criteria in the region phase led to selection of eight domes for further study in the location phase. Further screening in the area phase identified four domes for more intensive study in the location phase: Oakwood Dome, Texas; Vacherie Dome, Louisiana; and Richton Dome and Cypress Creek Dome, Mississippi. For each dome, this Site Characterization Plan identifies specific hydrologic, geologic, tectonic, geochemical, and environmental key issues that are related to the DOE/NWTS screening criteria or affect the feasibility of constructing an exploratory shaft. The Site Characterization Plan outlines studies need to: (1) resolve issues sufficiently to allow one or more salt domes to be selected and compared to bedded salt sites in order to determine a prime salt site for an exploratory shaft; (2) conduct issue-related studies to provide a higher level of confidence that the preferred salt dome site is viable for construction of an exploratory shaft; and (3) provide a vehicle for state input to issues. Extensive references, 7 figures, 20 tables

Failure and Redemption of Multifilter Rotating Shadowband Radiometer (MFRSR/Normal Incidence Multifilter Radiometer (NIMFR Cloud Screening: Contrasting Algorithm Performance at Atmospheric Radiation Measurement (ARM North Slope of Alaska (NSA and Southern Great Plains (SGP Sites

Directory of Open Access Journals (Sweden)

James Barnard

2013-09-01

Full Text Available Well-known cloud-screening algorithms, which are designed to remove cloud-contaminated aerosol optical depths (AOD from Multifilter Rotating Shadowband Radiometer (MFRSR and Normal Incidence Multifilter Radiometer (NIMFR measurements, have exhibited excellent performance at many middle-to-low latitude sites around world. However, they may occasionally fail under challenging observational conditions, such as when the sun is low (near the horizon and when optically thin clouds with small spatial inhomogeneity occur. Such conditions have been observed quite frequently at the high-latitude Atmospheric Radiation Measurement (ARM North Slope of Alaska (NSA sites. A slightly modified cloud-screening version of the standard algorithm is proposed here with a focus on the ARM-supported MFRSR and NIMFR data. The modified version uses approximately the same techniques as the standard algorithm, but it additionally examines the magnitude of the slant-path line of sight transmittance and eliminates points when the observed magnitude is below a specified threshold. Substantial improvement of the multi-year (1999–2012 aerosol product (AOD and its Angstrom exponent is shown for the NSA sites when the modified version is applied. Moreover, this version reproduces the AOD product at the ARM Southern Great Plains (SGP site, which was originally generated by the standard cloud-screening algorithms. The proposed minor modification is easy to implement and its application to existing and future cloud-screening algorithms can be particularly beneficial for challenging observational conditions.

A Simple Surface-Enhanced Raman Spectroscopic Method for on-Site Screening of Tetracycline Residue in Whole Milk

Directory of Open Access Journals (Sweden)

Sagar Dhakal

2018-02-01

Full Text Available Therapeutic and subtherapeutic use of veterinary drugs has increased the risk of residue contamination in animal food products. Antibiotics such as tetracycline are used for mastitis treatment of lactating cows. Milk expressed from treated cows before the withdrawal period has elapsed may contain tetracycline residue. This study developed a simple surface-enhanced Raman spectroscopic (SERS method for on-site screening of tetracycline residue in milk and water. Six batches of silver colloid nanoparticles were prepared for surface enhancement measurement. Milk-tetracycline and water-tetracycline solutions were prepared at seven concentration levels (1000, 500, 100, 10, 1, 0.1, and 0.01 ppm and spiked with silver colloid nanoparticles. A 785 nm Raman spectroscopic system was used for spectral measurement. Tetracycline vibrational modes were observed at 1285, 1317 and 1632 cm−1 in water-tetracycline solutions and 1322 and 1621 cm−1 (shifted from 1317 and 1632 cm−1, respectively in milk-tetracycline solutions. Tetracycline residue concentration as low as 0.01 ppm was detected in both the solutions. The peak intensities at 1285 and 1322 cm−1 were used to estimate the tetracycline concentrations in water and milk with correlation coefficients of 0.92 for water and 0.88 for milk. Results indicate that this SERS method is a potential tool that can be used on-site at field production for qualitative and quantitative detection of tetracycline residues.

A Simple Surface-Enhanced Raman Spectroscopic Method for on-Site Screening of Tetracycline Residue in Whole Milk.

Science.gov (United States)

Dhakal, Sagar; Chao, Kuanglin; Huang, Qing; Kim, Moon; Schmidt, Walter; Qin, Jianwei; Broadhurst, C Leigh

2018-02-01

Therapeutic and subtherapeutic use of veterinary drugs has increased the risk of residue contamination in animal food products. Antibiotics such as tetracycline are used for mastitis treatment of lactating cows. Milk expressed from treated cows before the withdrawal period has elapsed may contain tetracycline residue. This study developed a simple surface-enhanced Raman spectroscopic (SERS) method for on-site screening of tetracycline residue in milk and water. Six batches of silver colloid nanoparticles were prepared for surface enhancement measurement. Milk-tetracycline and water-tetracycline solutions were prepared at seven concentration levels (1000, 500, 100, 10, 1, 0.1, and 0.01 ppm) and spiked with silver colloid nanoparticles. A 785 nm Raman spectroscopic system was used for spectral measurement. Tetracycline vibrational modes were observed at 1285, 1317 and 1632 cm -1 in water-tetracycline solutions and 1322 and 1621 cm -1 (shifted from 1317 and 1632 cm -1 , respectively) in milk-tetracycline solutions. Tetracycline residue concentration as low as 0.01 ppm was detected in both the solutions. The peak intensities at 1285 and 1322 cm -1 were used to estimate the tetracycline concentrations in water and milk with correlation coefficients of 0.92 for water and 0.88 for milk. Results indicate that this SERS method is a potential tool that can be used on-site at field production for qualitative and quantitative detection of tetracycline residues.

How to Commission, Operate and Maintain a Large Future Accelerator Complex From Far Remote Sites

International Nuclear Information System (INIS)

Phinney, Nan

2001-01-01

A study on future large accelerators [1] has considered a facility, which is designed, built and operated by a worldwide collaboration of equal partner institutions, and which is remote from most of these institutions. The full range of operation was considered including commissioning, machine development, maintenance, trouble shooting and repair. Experience from existing accelerators confirms that most of these activities are already performed remotely. The large high-energy physics experiments and astronomy projects, already involve international collaborations of distant institutions. Based on this experience, the prospects for a machine operated remotely from far sites are encouraging. Experts from each laboratory would remain at their home institution but continue to participate in the operation of the machine after construction. Experts are required to be on site only during initial commissioning and for particularly difficult problems. Repairs require an on-site non-expert maintenance crew. Most of the interventions can be made without an expert and many of the rest resolved with remote assistance. There appears to be no technical obstacle to controlling an accelerator from a distance. The major challenge is to solve the complex management and communication problems

How to Commission, Operate and Maintain a Large Future Accelerator Complex From Far Remote Sites

Energy Technology Data Exchange (ETDEWEB)

Phinney, Nan

2001-12-07

A study on future large accelerators [1] has considered a facility, which is designed, built and operated by a worldwide collaboration of equal partner institutions, and which is remote from most of these institutions. The full range of operation was considered including commissioning, machine development, maintenance, troubleshooting and repair. Experience from existing accelerators confirms that most of these activities are already performed 'remotely'. The large high-energy physics experiments and astronomy projects, already involve international collaborations of distant institutions. Based on this experience, the prospects for a machine operated remotely from far sites are encouraging. Experts from each laboratory would remain at their home institution but continue to participate in the operation of the machine after construction. Experts are required to be on site only during initial commissioning and for particularly difficult problems. Repairs require an on-site non-expert maintenance crew. Most of the interventions can be made without an expert and many of the rest resolved with remote assistance. There appears to be no technical obstacle to controlling an accelerator from a distance. The major challenge is to solve the complex management and communication problems.

The potential of P1 site alterations in peptidomimetic protease inhibitors as suggested by virtual screening and explored by the use of C-C-coupling reagents.

Science.gov (United States)

Weik, Steffen; Luksch, Torsten; Evers, Andreas; Böttcher, Jark; Sotriffer, Christoph A; Hasilik, Andrej; Löffler, Hans-Gerhard; Klebe, Gerhard; Rademann, Jörg

2006-04-01

A synthetic concept is presented that allows the construction of peptide isostere libraries through polymer-supported C-acylation reactions. A phosphorane linker reagent is used as a carbanion equivalent; by employing MSNT as a coupling reagent, the C-acylation can be conducted without racemization. Diastereoselective reduction was effected with L-selectride. The reagent linker allows the preparation of a norstatine library with full variation of the isosteric positions including the P1 side chain that addresses the protease S1 pocket. Therefore, the concept was employed to investigate the P1 site specificity of peptide isostere inhibitors systematically. The S1 pocket of several aspartic proteases including plasmepsin II and cathepsin D was modeled and docked with approximately 500 amino acid side chains. Inspired by this virtual screen, a P1 site mutation library was designed, synthesized, and screened against three aspartic proteases (plasmepsin II, HIV protease, and cathepsin D). The potency of norstatine inhibitors was found to depend strongly on the P1 substituent. Large, hydrophobic residues such as biphenyl, 4-bromophenyl, and 4-nitrophenyl enhanced the inhibitory activity (IC50) by up to 70-fold against plasmepsin II. In addition, P1 variation introduced significant selectivity, as up to 9-fold greater activity was found against plasmepsin II relative to human cathepsin D. The active P1 site residues did not fit into the crystal structure; however, molecular dynamics simulation suggested a possible alternative binding mode.

Infirmity and injury complexity are risk factors for surgical-site infection after operative fracture care.

Science.gov (United States)

Bachoura, Abdo; Guitton, Thierry G; Smith, R Malcolm; Vrahas, Mark S; Zurakowski, David; Ring, David

2011-09-01

Orthopaedic surgical-site infections prolong hospital stays, double rehospitalization rates, and increase healthcare costs. Additionally, patients with orthopaedic surgical-site infections (SSI) have substantially greater physical limitations and reductions in their health-related quality of life. However, the risk factors for SSI after operative fracture care are unclear. We determined the incidence and quantified modifiable and nonmodifiable risk factors for SSIs in patients with orthopaedic trauma undergoing surgery. We retrospectively indentified, from our prospective trauma database and billing records, 1611 patients who underwent 1783 trauma-related procedures between 2006 and 2008. Medical records were reviewed and demographics, surgery-specific data, and whether the patients had an SSI were recorded. We determined which if any variables predicted SSI. Six factors independently predicted SSI: (1) the use of a drain, OR 2.3, 95% CI (1.3-3.8); (2) number of operations OR 3.4, 95% CI (2.0-6.0); (3) diabetes, OR 2.1, 95% CI (1.2-3.8); (4) congestive heart failure (CHF), OR 2.8, 95% CI (1.3-6.5); (5) site of injury tibial shaft/plateau, OR 2.3, 95% CI (1.3-4.2); and (6) site of injury, elbow, OR 2.2, 95% CI (1.1-4.7). The risk factors for SSIs after skeletal trauma are most strongly determined by nonmodifiable factors: patient infirmity (diabetes and heart failure) and injury complexity (site of injury, number of operations, use of a drain). Level II, prognostic study. See the Guideline for Authors for a complete description of levels of evidence.

Depression Screening at a Community Health Fair: Descriptives and Treatment Linkage.

Science.gov (United States)

Opperman, Kiel J; Hanson, Devin M; Toro, Paul A

2017-08-01

Health fairs are a cost-efficient platform for dissemination of preventive services to vulnerable populations. Effectiveness of depression screenings and associated treatment linkage via community health fairs warrants investigation. This study offers the first examination of a depression screening at a community health fair in 261 adult men (18-87years). The PHQ-9 was administered via interview by graduate students and on-site psychiatric nurses were available for a brief consultation for those interested. Over a quarter of participants screened positive for at least moderate depressive symptomatology. Of those who screened positive, 35.8% met with an on-site psychiatric nurse for a consultation. At six-month follow-up, none of the participants given a referral made an appointment at the community mental health agency. This suggests the importance of providing on-site clinician consultations at health fairs and the need for a more coordinated system to schedule future appointments while at the event. Community health fairs reach vulnerable populations, such as those who are uninsured and who have not spoken with a professional about mental health concerns. By conducting depression screening and providing onsite access to a mental health consultation at community health fairs, participants are better able to identify their depressive symptoms and are introduced to ways to treat depression. Copyright © 2017 Elsevier Inc. All rights reserved.

Site-selective electroless nickel plating on patterned thin films of macromolecular metal complexes.

Science.gov (United States)

Kimura, Mutsumi; Yamagiwa, Hiroki; Asakawa, Daisuke; Noguchi, Makoto; Kurashina, Tadashi; Fukawa, Tadashi; Shirai, Hirofusa

2010-12-01

We demonstrate a simple route to depositing nickel layer patterns using photocross-linked polymer thin films containing palladium catalysts, which can be used as adhesive interlayers for fabrication of nickel patterns on glass and plastic substrates. Electroless nickel patterns can be obtained in three steps: (i) the pattern formation of partially quaterized poly(vinyl pyridine) by UV irradiation, (ii) the formation of macromolecular metal complex with palladium, and (iii) the nickel metallization using electroless plating bath. Metallization is site-selective and allows for a high resolution. And the resulting nickel layered structure shows good adhesion with glass and plastic substrates. The direct patterning of metallic layers onto insulating substrates indicates a great potential for fabricating micro/nano devices.

Simultaneous screening of four epidermal growth factor receptor antagonists from Curcuma longa via cell membrane chromatography online coupled with HPLC-MS.

Science.gov (United States)

Sun, Meng; Ma, Wei-na; Guo, Ying; Hu, Zhi-gang; He, Lang-chong

2013-07-01

The epidermal growth factor receptors (EGFRs) are significant targets for screening active compounds. In this work, an analytical method was established for rapid screening, separation, and identification of EGFRs antagonists from Curcuma longa. Human embryonic kidney 293 cells with a steadily high expression of EGFRs were used to prepare the cell membrane stationary phase in a cell membrane chromatography model for screening active compounds. Separation and identification of the retention chromatographic peaks was achieved by HPLC-MS. The active sites, docking extents and inhibitory effects of the active compounds were also demonstrated. The screening result found that ar-turmerone, curcumin, demethoxycurcumin, and bisdemethoxycurcumin from Curcuma longa could be active components in a similar manner to gefitinib. Biological trials showed that all of four compounds can inhibit EGFRs protein secretion and cell growth in a dose-dependent manner, and downregulate the phosphorylation of EGFRs. This analytical method demonstrated fast and effective characteristics for screening, separation and identification of the active compounds from a complex system and should be useful for drug discovery with natural medicinal herbs. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Site characterization techniques used in environmental remediation activities

International Nuclear Information System (INIS)

Kostelnik, K.M.

2000-01-01

As a result of decades of nuclear energy research, weapons production, as well as ongoing operations, a significant amount of radioactive contamination has occurred throughout the United States Department of Energy (DOE) complex. DOE facility are in the process of assessing and potentially remediating various sites according to the regulations imposed by a Federal Facility Agreement and Consent order (FFA/CO) between DOE, the state in which the facility is located, and the U.S. Environmental Protection Agency (EPA). In support of these active site remediation efforts, the DOE has devoted considerable resources towards the development of innovative site characterization techniques that support environmental restoration activities. These resources and efforts have focused on various aspects of this complex problem. Research and technology development conducted at the Idaho National Engineering and Environmental Laboratory (INEEL) has resulted in the ability and state-of-the-art equipment required to obtain real-time, densely spaced, in situ characterization data (i.e. detection, speciation, and location) of various radionuclides and contaminants. The Remedial Action Monitoring System (RAMS), developed by the INEEL, consists of enhanced sensor technology, measurement modeling and interpretation techniques, and a suite of deployment platforms which can be interchanged to directly support remedial cleanup and site verification operations. In situ characterization techniques have advanced to the point where they are being actively deployed in support of remedial operations. The INEEL has deployed its system at various DOE and international sites. The deployment of in situ characterization systems during environmental restoration operations has shown that this approach results in several significant benefits versus conventional sampling techniques. A flexible characterization system permits rapid modification to satisfy physical site conditions, available site resources

Ligand screening by saturation-transfer difference (STD) NMR spectroscopy.

Energy Technology Data Exchange (ETDEWEB)

Krishnan, V V

2005-04-26

NMR based methods to screen for high-affinity ligands have become an indispensable tool for designing rationalized drugs, as these offer a combination of good experimental design of the screening process and data interpretation methods, which together provide unprecedented information on the complex nature of protein-ligand interactions. These methods rely on measuring direct changes in the spectral parameters, that are often simpler than the complex experimental procedures used to study structure and dynamics of proteins. The goal of this review article is to provide the basic details of NMR based ligand-screening methods, with particular focus on the saturation transfer difference (STD) experiment. In addition, we provide an overview of other NMR experimental methods and a practical guide on how to go about designing and implementing them.

Behavioral economics: "nudging" underserved populations to be screened for cancer.

Science.gov (United States)

Purnell, Jason Q; Thompson, Tess; Kreuter, Matthew W; McBride, Timothy D

2015-01-15

Persistent disparities in cancer screening by race/ethnicity and socioeconomic status require innovative prevention tools and techniques. Behavioral economics provides tools to potentially reduce disparities by informing strategies and systems to increase prevention of breast, cervical, and colorectal cancers. With an emphasis on the predictable, but sometimes flawed, mental shortcuts (heuristics) people use to make decisions, behavioral economics offers insights that practitioners can use to enhance evidence-based cancer screening interventions that rely on judgments about the probability of developing and detecting cancer, decisions about competing screening options, and the optimal presentation of complex choices (choice architecture). In the area of judgment, we describe ways practitioners can use the availability and representativeness of heuristics and the tendency toward unrealistic optimism to increase perceptions of risk and highlight benefits of screening. We describe how several behavioral economic principles involved in decision-making can influence screening attitudes, including how framing and context effects can be manipulated to highlight personally salient features of cancer screening tests. Finally, we offer suggestions about ways practitioners can apply principles related to choice architecture to health care systems in which cancer screening takes place. These recommendations include the use of incentives to increase screening, introduction of default options, appropriate feedback throughout the decision-making and behavior completion process, and clear presentation of complex choices, particularly in the context of colorectal cancer screening. We conclude by noting gaps in knowledge and propose future research questions to guide this promising area of research and practice.

Quality of prostate cancer screening information on the websites of nationally recognized cancer centers and health organizations.

Science.gov (United States)

Manole, Bogdan-Alexandru; Wakefield, Daniel V; Dove, Austin P; Dulaney, Caleb R; Marcrom, Samuel R; Schwartz, David L; Farmer, Michael R

2017-12-24

The purpose of this study was to survey the accessibility and quality of prostate-specific antigen (PSA) screening information from National Cancer Institute (NCI) cancer center and public health organization Web sites. We surveyed the December 1, 2016, version of all 63 NCI-designated cancer center public Web sites and 5 major online clearinghouses from allied public/private organizations (cancer.gov, cancer.org, PCF.org, USPSTF.org, and CDC.gov). Web sites were analyzed according to a 50-item list of validated health care information quality measures. Web sites were graded by 2 blinded reviewers. Interrater agreement was confirmed by Cohen kappa coefficient. Ninety percent of Web sites addressed PSA screening. Cancer center sites covered 45% of topics surveyed, whereas organization Web sites addressed 70%. All organizational Web pages addressed the possibility of false-positive screening results; 41% of cancer center Web pages did not. Forty percent of cancer center Web pages also did not discuss next steps if a PSA test was positive. Only 6% of cancer center Web pages were rated by our reviewers as "superior" (eg, addressing >75% of the surveyed topics) versus 20% of organizational Web pages. Interrater agreement between our reviewers was high (kappa coefficient = 0.602). NCI-designated cancer center Web sites publish lower quality public information about PSA screening than sites run by major allied organizations. Nonetheless, information and communication deficiencies were observed across all surveyed sites. In an age of increasing patient consumerism, prospective prostate cancer patients would benefit from improved online PSA screening information from provider and advocacy organizations. Validated cancer patient Web educational standards remain an important, understudied priority. Copyright © 2018. Published by Elsevier Inc.

Study of the nucleotide binding site of the yeast Schizosaccharomyces pombe plasma membrane H+-ATPase using formycin triphosphate-terbium complex

International Nuclear Information System (INIS)

Ronjat, M.; Lacapere, J.J.; Dufour, J.P.; Dupont, Y.

1987-01-01

The plasma membrane of yeasts contains an H+-ATPase similar to the other cation transport ATPases of eukaryotic organisms. This enzyme has been purified and shows H+ transport in reconstituted vesicles. In the presence of Mg2+, formycin triphosphate (FTP) is hydrolyzed by the H+-ATPase and supports H+ transport. When combined with terbium ion, FTP (Tb-FTP) and ATP (Tb-ATP) are no longer hydrolyzed. Competition between Mg-ATP and Tb-FTP for ATP hydrolysis indicates that terbium-associated nucleotides bind to the catalytic site of the H+-ATPase. The fluorescent properties of the Tb-FTP complex were used to study the active site of the H+-ATPase. Fluorescence of Tb-FTP is greatly enhanced upon binding into the nucleotide site of H+-ATPase with a dissociation constant of 1 microM. Tb-ATP, Tb-ADP, and Tb-ITP are competitive inhibitors of Tb-FTP binding with Ki = 4.5, 5.0, and 6.0 microM, respectively. Binding of Tb-FTP is observed only in the presence of an excess of Tb3+ with an activation constant Ka = 25 microM for Tb3+. Analysis of the data reveals that the sites for Tb-FTP and Tb3+ binding are independent entities. In standard conditions these sites would be occupied by Mg-ATP and Mg2+, respectively. These findings suggest an important regulatory role of divalent cations on the activity of H+-ATPase. Replacement of H 2 O by D 2 O in the medium suggests the existence of two types of nucleotide binding sites differing by the hydration state of the Tb3+ ion in the bound Tb-FTP complex

Environmental assessment: Solid waste retrieval complex, enhanced radioactive and mixed waste storage facility, infrastructure upgrades, and central waste support complex, Hanford Site, Richland, Washington

International Nuclear Information System (INIS)

1995-09-01

The U.S. Department of Energy (DOE) needs to take action to: retrieve transuranic (TRU) waste because interim storage waste containers have exceeded their 20-year design life and could fail causing a radioactive release to the environment provide storage capacity for retrieved and newly generated TRU, Greater-than-Category 3 (GTC3), and mixed waste before treatment and/or shipment to the Waste Isolation Pilot Project (WIPP); and upgrade the infrastructure network in the 200 West Area to enhance operational efficiencies and reduce the cost of operating the Solid Waste Operations Complex. This proposed action would initiate the retrieval activities (Retrieval) from Trench 4C-T04 in the 200 West Area including the construction of support facilities necessary to carry out the retrieval operations. In addition, the proposed action includes the construction and operation of a facility (Enhanced Radioactive Mixed Waste Storage Facility) in the 200 West Area to store newly generated and the retrieved waste while it awaits shipment to a final disposal site. Also, Infrastructure Upgrades and a Central Waste Support Complex are necessary to support the Hanford Site's centralized waste management area in the 200 West Area. The proposed action also includes mitigation for the loss of priority shrub-steppe habitat resulting from construction. The estimated total cost of the proposed action is $66 million

Comparison between dispersed nuclear power plants and a nuclear energy center at a hypothetical site on Kentucky Lake, Tennessee. Vol. IV. A site selection methodology

International Nuclear Information System (INIS)

Rosemarin, C.S.; Yaffee, S.L.

1976-09-01

A methodology has been developed for selecting suitable sites for development as nuclear energy centers. First, the forty-eight contiguous states were screened on the basis of four variables: (1) seismic stability; (2) distance from projected population centers; (3) adequate water supply; and (4) noninterference with scenic and reserved lands. After location of a surrogate area in north central Tennessee, further screening was performed using 22 variables to find a suitable 75-sq-mile surrogate site within this 1500-sq-mile area. A computer method for screening the surrogate area is presented, and the use of the data for the 22 variables is illustrated

Nuclear Energy Center Site Survey, 1975. Part V. Resource availability and site screening

International Nuclear Information System (INIS)

1976-01-01

Resource requirements for nuclear energy centers are discussed and the large land areas which meet these requirements and may contain potential sites for a nuclear energy center (NEC) are identified. Maps of the areas are included that identify seismic zones, river flow rates, and population density

Relativity, nuclear polarizability, and screening in sub-Coulomb elastic scattering

International Nuclear Information System (INIS)

Lynch, W.G.; Tsang, M.B.; Bhang, H.C.; Cramer, J.G.; Puigh, R.J.

Elastic scattering of p-shell nuclear projectiles from 208 Pb has been examined for deviations from Rutherford scattering. Four effects can be important: atomic screening, vacuum polarization, nuclear polarizability and a relativistic effect of dynamical origin. The presence of atomic screening, nuclear polarizability and the relativistic effect was observed thus constituting the first measurement of this relativistic effect using complex nuclei and the first measurement of this relativistic effect using complex nuclei and the first measurement of nuclear polarizability in an external Coulomb field

Molecular screening in galactosemia

Energy Technology Data Exchange (ETDEWEB)

Elsas, L.J.; Singh, R.; Fernhoff, P.M. [Emory Univ., Atlanta, GA (United States)] [and others

1994-09-01

Classical galactosemia (G/G) is caused by the absence of galactose-1-phosphate uridyl transferase (GALT) activity while the Duarte allele produces partial impairment and a specific biochemical phenotype. Cloning and sequencing of the human GALT gene has enabled the identification of prevalent mutations for both Classical and Duarte alleles. The G allele is caused by a Q188R codon mutation in exon 6 in 70% of a Caucasian population while the D allele is caused by an N134D codon mutation in exon 10. Since the Q188R sequence creates a new Hpa II site and the N314D sequence creates a new Sin I site, it is relatively easy to screen for both mutations by multiplex PCR and restriction digest. Here we describe a method for detection of new mutations producing impaired GALT. Patient DNAs are subjected to SSCP (single strand conformational polymorphism) analysis of their 11 GALT exons. Direct sequencing of the exons targeted by SSCP has revealed many codon changes: IVSC 956 (a splice acceptor site loss), S135L, V151A, E203K, A320T, and Y323D. Two of these codon changes, V151A and S135L, have been confirmed as mutations by finding impaired GALT activity in a yeast expression system. We conclude that molecular screening of GALT DNA will clarify the structural biology of GALT and the pathophysiology of galactosemia.

Increasing chlamydia screening tests in general practice: a modified Zelen prospective Cluster Randomised Controlled Trial evaluating a complex intervention based on the Theory of Planned Behaviour.

Science.gov (United States)

McNulty, Cliodna A M; Hogan, Angela H; Ricketts, Ellie J; Wallace, Louise; Oliver, Isabel; Campbell, Rona; Kalwij, Sebastian; O'Connell, Elaine; Charlett, Andre

2014-05-01

To determine if a structured complex intervention increases opportunistic chlamydia screening testing of patients aged 15-24 years attending English general practitioner (GP) practices. A prospective, Cluster Randomised Controlled Trial with a modified Zelen design involving 160 practices in South West England in 2010. The intervention was based on the Theory of Planned Behaviour (TPB). It comprised of practice-based education with up to two additional contacts to increase the importance of screening to GP staff and their confidence to offer tests through skill development (including videos). Practical resources (targets, posters, invitation cards, computer reminders, newsletters including feedback) aimed to actively influence social cognitions of staff, increasing their testing intention. Data from 76 intervention and 81 control practices were analysed. In intervention practices, chlamydia screening test rates were 2.43/100 15-24-year-olds registered preintervention, 4.34 during intervention and 3.46 postintervention; controls testing rates were 2.61/100 registered patients prior intervention, 3.0 during intervention and 2.82 postintervention. During the intervention period, testing in intervention practices was 1.76 times as great (CI 1.24 to 2.48) as controls; this persisted for 9 months postintervention (1.57 times as great, CI 1.27 to 2.30). Chlamydia infections detected increased in intervention practices from 2.1/1000 registered 15-24-year-olds prior intervention to 2.5 during the intervention compared with 2.0 and 2.3/1000 in controls (Estimated Rate Ratio intervention versus controls 1.4 (CI 1.01 to 1.93). This complex intervention doubled chlamydia screening tests in fully engaged practices. The modified Zelen design gave realistic measures of practice full engagement (63%) and efficacy of this educational intervention in general practice; it should be used more often. The trial was registered on the UK Clinical Research Network Study Portfolio database

Umatilla Satellite and Release Sites Project : Final Siting Report.

Energy Technology Data Exchange (ETDEWEB)

Montgomery, James M.

1992-04-01

This report presents the results of site analysis for the Umatilla Satellite and Release Sites Project. The purpose of this project is to provide engineering services for the siting and conceptual design of satellite and release facilities for the Umatilla Basin hatchery program. The Umatilla Basin hatchery program consists of artificial production facilities for salmon and steelhead to enhance production in the Umatilla River as defined in the Umatilla master plan approved in 1989 by the Northwest Power Planning Council. Facilities identified in the master plan include adult salmon broodstock holding and spawning facilities, facilities for recovery, acclimation, and/or extended rearing of salmon juveniles, and development of river sites for release of hatchery salmon and steelhead. The historic and current distribution of fall chinook, summer chinook, and coho salmon and steelhead trout was summarized for the Umatilla River basin. Current and future production and release objectives were reviewed. Twenty seven sites were evaluated for the potential and development of facilities. Engineering and environmental attributes of the sites were evaluated and compared to facility requirements for water and space. Site screening was conducted to identify the sites with the most potential for facility development. Alternative sites were selected for conceptual design of each facility type. A proposed program for adult holding facilities, final rearing/acclimation, and direct release facilities was developed.

Architecture of the 99 bp DNA-six-protein regulatory complex of the lambda att site.

Science.gov (United States)

Sun, Xingmin; Mierke, Dale F; Biswas, Tapan; Lee, Sang Yeol; Landy, Arthur; Radman-Livaja, Marta

2006-11-17

The highly directional and tightly regulated recombination reaction used to site-specifically excise the bacteriophage lambda chromosome out of its E. coli host chromosome requires the binding of six sequence-specific proteins to a 99 bp segment of the phage att site. To gain structural insights into this recombination pathway, we measured 27 FRET distances between eight points on the 99 bp regulatory DNA bound with all six proteins. Triangulation of these distances using a metric matrix distance-geometry algorithm provided coordinates for these eight points. The resulting path for the protein-bound regulatory DNA, which fits well with the genetics, biochemistry, and X-ray crystal structures describing the individual proteins and their interactions with DNA, provides a new structural perspective into the molecular mechanism and regulation of the recombination reaction and illustrates a design by which different families of higher-order complexes can be assembled from different numbers and combinations of the same few proteins.

2016 Annual Industrial Wastewater Reuse Report for the Idaho National Laboratory Site's Materials and Fuels Complex Industrial Waste Ditch and Industrial Waste Pond

International Nuclear Information System (INIS)

Cafferty, Kara Grace

2017-01-01

This report describes conditions, as required by the state of Idaho Industrial Wastewater Reuse Permit (WRU-I-0160-01, Modification 1, formerly LA 000160 01), for the wastewater reuse site at the Idaho National Laboratory Site's Materials and Fuels Complex Industrial Waste Ditch and Industrial Waste Pond from November 1, 2015, through October 31, 2016.

Complex evaluation of ecology situation and soil productivity of Semipalatinsk nuclear test site, perspectives of use

International Nuclear Information System (INIS)

Lebed', L.; Ptiskaya, L.; Lyashenko; Pisak, R.

1996-01-01

Objective of the Project. The goal of the project is complex evaluation of environmental resources at the former Semipalatinsk Test Site and perspectives of their cultivation with taking into account radioactive pollution. Scope of Activities. The following main works at the territory of the former Semipalatinsk Test Site: - estimate of climate, climatic resources and their changes; - organization and realization of complex visual and tool-making air survey (geo botanical, utter satellite spectrometric, radiometric); - reception and computer treatment of space information; - organization and realization of surface expedition field works (radiometric measurements and geo botanical observations); - realization of laboratory analysis for exposure of radio nucleus content in soil, plant and water; - treatment of materials of geo botanical survey, construction of plant and soil maps; - treatment of materials of aero spectrometric and space survey, calculation of vegetation cover productivity, drawing up of computer maps; - assessment of desert and steppe zone vegetation dynamic under artificial and climate impact.Expected Results. The following main investigation results will be obtained first for the territory of Semipalatinsk Test Site and area around it. 1. Objective modern characteristics of radioactive land pollution. Distribution of radio nucleus in soil and vegetation cover. 2. Modern characteristics climatic resources assessment under possible climate change. 3. New maps of vegetation and soil cover, biological and feed productivity of the lands of the polygon at the scale 1:100 000 -1:1 500 000 taking into account climatic resources of the region. 4. Dynamics of desert and steppe zone vegetation assessment under radiation impact and possible climate change. 5. Features of vegetation restoration under constant radiation influence. 6. Basis of perspectives of land cultivation in the Semipalatinsk polygon area and recommendation on rehabilitation soil and

Comparative analysis of pharmacophore screening tools.

NARCIS (Netherlands)

Sanders, M.P.A.; Barbosa, A.J.; Zarzycka, B.; Nicolaes, G.A.; Klomp, J.P.G.; Vlieg, J. de; Rio, A. Del

2012-01-01

The pharmacophore concept is of central importance in computer-aided drug design (CADD) mainly because of its successful application in medicinal chemistry and, in particular, high-throughput virtual screening (HTVS). The simplicity of the pharmacophore definition enables the complexity of molecular

Genetic screens to identify new Notch pathway mutants in Drosophila.

Science.gov (United States)

Giagtzoglou, Nikolaos

2014-01-01

Notch signaling controls a wide range of developmental processes, including proliferation, apoptosis, and cell fate specification during both development and adult tissue homeostasis. The functional versatility of the Notch signaling pathway is tightly linked with the complexity of its regulation in different cellular contexts. To unravel the complexity of Notch signaling, it is important to identify the different components of the Notch signaling pathway. A powerful strategy to accomplish this task is based on genetic screens. Given that the developmental context of signaling is important, these screens should be customized to specific cell populations or tissues. Here, I describe how to perform F1 clonal forward genetic screens in Drosophila to identify novel components of the Notch signaling pathway. These screens combine a classical EMS (ethyl methanesulfonate) chemical mutagenesis protocol along with clonal analysis via FRT-mediated mitotic recombination. These F1 clonal screens allow rapid phenotypic screening within clones of mutant cells induced at specific developmental stages and in tissues of interest, bypassing the pleiotropic effects of isolated mutations. More importantly, since EMS mutations have been notoriously difficult to map to specific genes in the past, I briefly discuss mapping methods that allow rapid identification of the causative mutations.

Scanning mutagenesis of the amino acid sequences flanking phosphorylation site 1 of the mitochondrial pyruvate dehydrogenase complex

Directory of Open Access Journals (Sweden)

Nagib eAhsan

2012-07-01

Full Text Available The mitochondrial pyruvate dehydrogenase complex is regulated by reversible seryl-phosphorylation of the E1α subunit by a dedicated, intrinsic kinase. The phospho-complex is reactivated when dephosphorylated by an intrinsic PP2C-type protein phosphatase. Both the position of the phosphorylated Ser-residue and the sequences of the flanking amino acids are highly conserved. We have used the synthetic peptide-based kinase client assay plus recombinant pyruvate dehydrogenase E1α and E1α-kinase to perform scanning mutagenesis of the residues flanking the site of phosphorylation. Consistent with the results from phylogenetic analysis of the flanking sequences, the direct peptide-based kinase assays tolerated very few changes. Even conservative changes such as Leu, Ile, or Val for Met, or Glu for Asp, gave very marked reductions in phosphorylation. Overall the results indicate that regulation of the mitochondrial pyruvate dehydrogenase complex by reversible phosphorylation is an extreme example of multiple, interdependent instances of co-evolution.

City and County Solar PV Training Program, Module 2: Screening and Identifying PV Projects

Energy Technology Data Exchange (ETDEWEB)

Elgqvist, Emma M [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

2018-04-09

When screening and identifying PV projects, cities and counties should understand the different factors that impact the technical and economic potential of a PV project, the steps of the PV screening process, and how to use REopt Lite to screen a site for PV and storage project potential.

An Effective Community?Academic Partnership to Extend the Reach of Screenings for Fall Risk

OpenAIRE

Schrodt, Lori A.; Garbe, Kathie C.; Chaplin, Rebecca; Busby-Whitehead, Jan; Shubert, Tiffany E.

2013-01-01

Older adults should be screened for fall risk annually. Community providers (people without formal medical training who work with older adults in senior centers or aging services) may be a viable group to expand the reach of screenings. Our community–academic partnership developed a program to increase and assess fall risk screenings by community providers. Community sites hosted training workshops and screening events. Community screenings were well attended and received by providers and old...

Volunteers Oriented Interface Design for the Remote Navigation of Rescue Robots at Large-Scale Disaster Sites

Science.gov (United States)

Yang, Zhixiao; Ito, Kazuyuki; Saijo, Kazuhiko; Hirotsune, Kazuyuki; Gofuku, Akio; Matsuno, Fumitoshi

This paper aims at constructing an efficient interface being similar to those widely used in human daily life, to fulfill the need of many volunteer rescuers operating rescue robots at large-scale disaster sites. The developed system includes a force feedback steering wheel interface and an artificial neural network (ANN) based mouse-screen interface. The former consists of a force feedback steering control and a six monitors’ wall. It provides a manual operation like driving cars to navigate a rescue robot. The latter consists of a mouse and a camera’s view displayed in a monitor. It provides a semi-autonomous operation by mouse clicking to navigate a rescue robot. Results of experiments show that a novice volunteer can skillfully navigate a tank rescue robot through both interfaces after 20 to 30 minutes of learning their operation respectively. The steering wheel interface has high navigating speed in open areas, without restriction of terrains and surface conditions of a disaster site. The mouse-screen interface is good at exact navigation in complex structures, while bringing little tension to operators. The two interfaces are designed to switch into each other at any time to provide a combined efficient navigation method.

Virtual Screening of Peptide and Peptidomimetic Fragments Targeted to Inhibit Bacterial Dithiol Oxidase DsbA.

Directory of Open Access Journals (Sweden)

Wilko Duprez

Full Text Available Antibacterial drugs with novel scaffolds and new mechanisms of action are desperately needed to address the growing problem of antibiotic resistance. The periplasmic oxidative folding system in Gram-negative bacteria represents a possible target for anti-virulence antibacterials. By targeting virulence rather than viability, development of resistance and side effects (through killing host native microbiota might be minimized. Here, we undertook the design of peptidomimetic inhibitors targeting the interaction between the two key enzymes of oxidative folding, DsbA and DsbB, with the ultimate goal of preventing virulence factor assembly. Structures of DsbB--or peptides--complexed with DsbA revealed key interactions with the DsbA active site cysteine, and with a hydrophobic groove adjacent to the active site. The present work aimed to discover peptidomimetics that target the hydrophobic groove to generate non-covalent DsbA inhibitors. The previously reported structure of a Proteus mirabilis DsbA active site cysteine mutant, in a non-covalent complex with the heptapeptide PWATCDS, was used as an in silico template for virtual screening of a peptidomimetic fragment library. The highest scoring fragment compound and nine derivatives were synthesized and evaluated for DsbA binding and inhibition. These experiments discovered peptidomimetic fragments with inhibitory activity at millimolar concentrations. Although only weakly potent relative to larger covalent peptide inhibitors that interact through the active site cysteine, these fragments offer new opportunities as templates to build non-covalent inhibitors. The results suggest that non-covalent peptidomimetics may need to interact with sites beyond the hydrophobic groove in order to produce potent DsbA inhibitors.

Field screening procedures for determining the presence of volatile organic compounds in soil

International Nuclear Information System (INIS)

Crockett, A.B.; DeHaan, M.S.

1991-01-01

Many field screening procedures have been used to detect the presence of volatile organic compounds (VOC) in soils but almost none have been documented and verified. Users of these procedures have not really known whether their objectives in screening were met. A reliable VOC screening procedure could significantly reduce the number of samples currently being submitted to laboratories, thereby reducing costs and improving site characterization. The Environmental Protection Agency's Environmental Monitoring Systems Laboratory in Las Vegas (EMSL-LV) has therefore sponsored a research effort to evaluate and improve headspace methods for screening soils for VOC in the field. The research involved comparing several extraction procedures using soils from actual waste sites, and determining the agitation and mixing necessary to achieve equilibrium. Headspace was analyzed using a relatively simple portable gas chromatograph with a short column. The results were variable and show that several procedures should be attempted and the results evaluated before selecting a screening procedure. 10 refs., 6 tabs

A Xylenol Orange-Based Screening Assay for the Substrate Specificity of Flavin-Dependent para-Phenol Oxidases

Directory of Open Access Journals (Sweden)

Tom A. Ewing

2018-01-01

Full Text Available Vanillyl alcohol oxidase (VAO and eugenol oxidase (EUGO are flavin-dependent enzymes that catalyse the oxidation of para-substituted phenols. This makes them potentially interesting biocatalysts for the conversion of lignin-derived aromatic monomers to value-added compounds. To facilitate their biocatalytic exploitation, it is important to develop methods by which variants of the enzymes can be rapidly screened for increased activity towards substrates of interest. Here, we present the development of a screening assay for the substrate specificity of para-phenol oxidases based on the detection of hydrogen peroxide using the ferric-xylenol orange complex method. The assay was used to screen the activity of VAO and EUGO towards a set of twenty-four potential substrates. This led to the identification of 4-cyclopentylphenol as a new substrate of VAO and EUGO and 4-cyclohexylphenol as a new substrate of VAO. Screening of a small library of VAO and EUGO active-site variants for alterations in their substrate specificity led to the identification of a VAO variant (T457Q with increased activity towards vanillyl alcohol (4-hydroxy-3-methoxybenzyl alcohol and a EUGO variant (V436I with increased activity towards chavicol (4-allylphenol and 4-cyclopentylphenol. This assay provides a quick and efficient method to screen the substrate specificity of para-phenol oxidases, facilitating the enzyme engineering of known para-phenol oxidases and the evaluation of the substrate specificity of novel para-phenol oxidases.

A Xylenol Orange-Based Screening Assay for the Substrate Specificity of Flavin-Dependent para-Phenol Oxidases.

Science.gov (United States)

Ewing, Tom A; van Noord, Aster; Paul, Caroline E; van Berkel, Willem J H

2018-01-14

Vanillyl alcohol oxidase (VAO) and eugenol oxidase (EUGO) are flavin-dependent enzymes that catalyse the oxidation of para -substituted phenols. This makes them potentially interesting biocatalysts for the conversion of lignin-derived aromatic monomers to value-added compounds. To facilitate their biocatalytic exploitation, it is important to develop methods by which variants of the enzymes can be rapidly screened for increased activity towards substrates of interest. Here, we present the development of a screening assay for the substrate specificity of para -phenol oxidases based on the detection of hydrogen peroxide using the ferric-xylenol orange complex method. The assay was used to screen the activity of VAO and EUGO towards a set of twenty-four potential substrates. This led to the identification of 4-cyclopentylphenol as a new substrate of VAO and EUGO and 4-cyclohexylphenol as a new substrate of VAO. Screening of a small library of VAO and EUGO active-site variants for alterations in their substrate specificity led to the identification of a VAO variant (T457Q) with increased activity towards vanillyl alcohol (4-hydroxy-3-methoxybenzyl alcohol) and a EUGO variant (V436I) with increased activity towards chavicol (4-allylphenol) and 4-cyclopentylphenol. This assay provides a quick and efficient method to screen the substrate specificity of para -phenol oxidases, facilitating the enzyme engineering of known para- phenol oxidases and the evaluation of the substrate specificity of novel para -phenol oxidases.

Design of Screens for Sand Control of Wells

Directory of Open Access Journals (Sweden)

Ján Pinka

2006-04-01

Full Text Available Drilling, completion, production, and reservoir engineers, supervisors, foremen, superintendents, service company personnel, technologists and anyone involved with recommending, selecting, designing or on-site performance of well completions or workovers where sand production is, or may become, a serious problem will benefit from this course. Less sand influx can be expected in a horizontal well than in a vertical well. If horizontal holes in weak formation sands can be successfully gravel packed, the result could be significantly higher well productivity than with a liner, screen or pre-packed screen alone. The article covers innovative screens for sand control used in oil and gas industry from the world leaders in total completion. The type of screen (wire wrapped, reinforced, pre-packed, ect. should also be chosen with due consideration to running-in condition (curve radius, compression when the screens are pushed along the drain hole, etc..

The Novel Language-Systematic Aphasia Screening SAPS: Screening-Based Therapy in Combination with Computerised Home Training

Science.gov (United States)

Krzok, Franziska; Rieger, Verena; Niemann, Katharina; Nobis-Bosch, Ruth; Radermacher, Irmgard; Huber, Walter; Willmes, Klaus; Abel, Stefanie

2018-01-01

Background: SAPS--'Sprachsystematisches Aphasiescreening'--is a novel language-systematic aphasia screening developed for the German language, which already had been positively evaluated. It offers a fast assessment of modality-specific psycholinguistic components at different levels of complexity and the derivation of impairment-based treatment…

An Automated Algorithm to Screen Massive Training Samples for a Global Impervious Surface Classification

Science.gov (United States)

Tan, Bin; Brown de Colstoun, Eric; Wolfe, Robert E.; Tilton, James C.; Huang, Chengquan; Smith, Sarah E.

2012-01-01

An algorithm is developed to automatically screen the outliers from massive training samples for Global Land Survey - Imperviousness Mapping Project (GLS-IMP). GLS-IMP is to produce a global 30 m spatial resolution impervious cover data set for years 2000 and 2010 based on the Landsat Global Land Survey (GLS) data set. This unprecedented high resolution impervious cover data set is not only significant to the urbanization studies but also desired by the global carbon, hydrology, and energy balance researches. A supervised classification method, regression tree, is applied in this project. A set of accurate training samples is the key to the supervised classifications. Here we developed the global scale training samples from 1 m or so resolution fine resolution satellite data (Quickbird and Worldview2), and then aggregate the fine resolution impervious cover map to 30 m resolution. In order to improve the classification accuracy, the training samples should be screened before used to train the regression tree. It is impossible to manually screen 30 m resolution training samples collected globally. For example, in Europe only, there are 174 training sites. The size of the sites ranges from 4.5 km by 4.5 km to 8.1 km by 3.6 km. The amount training samples are over six millions. Therefore, we develop this automated statistic based algorithm to screen the training samples in two levels: site and scene level. At the site level, all the training samples are divided to 10 groups according to the percentage of the impervious surface within a sample pixel. The samples following in each 10% forms one group. For each group, both univariate and multivariate outliers are detected and removed. Then the screen process escalates to the scene level. A similar screen process but with a looser threshold is applied on the scene level considering the possible variance due to the site difference. We do not perform the screen process across the scenes because the scenes might vary due to

High-throughput fragment screening by affinity LC-MS.

Science.gov (United States)

Duong-Thi, Minh-Dao; Bergström, Maria; Fex, Tomas; Isaksson, Roland; Ohlson, Sten

2013-02-01

Fragment screening, an emerging approach for hit finding in drug discovery, has recently been proven effective by its first approved drug, vemurafenib, for cancer treatment. Techniques such as nuclear magnetic resonance, surface plasmon resonance, and isothemal titration calorimetry, with their own pros and cons, have been employed for screening fragment libraries. As an alternative approach, screening based on high-performance liquid chromatography separation has been developed. In this work, we present weak affinity LC/MS as a method to screen fragments under high-throughput conditions. Affinity-based capillary columns with immobilized thrombin were used to screen a collection of 590 compounds from a fragment library. The collection was divided into 11 mixtures (each containing 35 to 65 fragments) and screened by MS detection. The primary screening was performed in 3500 fragments per day). Thirty hits were defined, which subsequently entered a secondary screening using an active site-blocked thrombin column for confirmation of specificity. One hit showed selective binding to thrombin with an estimated dissociation constant (K (D)) in the 0.1 mM range. This study shows that affinity LC/MS is characterized by high throughput, ease of operation, and low consumption of target and fragments, and therefore it promises to be a valuable method for fragment screening.

Qualitative vs. quantitative data: Controls on the accuracy of PID field screening in petroleum contamination assessment applications

International Nuclear Information System (INIS)

Luessen, M.J.; Allex, M.K.; Holzel, F.R.

1995-01-01

The use of photoionization detectors (PIDs) for field screening of soils for volatile organic contaminants has become a standard industry practice. PID screening data is generally utilized as a qualitative basis for selection of samples for laboratory analysis to quantify concentrations of specific contaminants of concern. Both qualitative field screening data and quantitative laboratory analytical data were reviewed for more than 100 hydrogeologic assessment sites in Ohio to evaluate controls on the effectiveness of field screening data. Assessment data evaluated was limited to sites at which the suspected contaminant source was a gasoline underground storage tanks system. In each case, a 10.0 eV (or greater) PID calibrated for benzene was used to screen soils which were analyzed for benzene, toluene, ethylbenzene and xylene (BTEX) by SW 846 method 8020. Controls on field screening which were evaluated for each site included (1) soil classification, (2) soil moisture, (3) weather conditions, (4) background levels, (5) equipment quality, (6) screening methodology, and (7) laboratory QA/QC. Statistical data analysis predictably indicated a general overestimate of total BTEX levels based on field screening (gasoline is approximately 25 weight percent BTEX). However, data locally indicated cases of both significant (i.e., more than an order of magnitude difference) over- and under-estimation of actual BTEX concentrations (i.e., quantitative laboratory data) by field screening data

Siting Study for the Remote-Handled Low-Level Waste Disposal Project

Energy Technology Data Exchange (ETDEWEB)

Lisa Harvego; Joan Connolly; Lance Peterson; Brennon Orr; Bob Starr

2010-10-01

The U.S. Department of Energy has identified a mission need for continued disposal capacity for remote-handled low-level waste (LLW) generated at the Idaho National Laboratory (INL). An alternatives analysis that was conducted to evaluate strategies to achieve this mission need identified two broad options for disposal of INL generated remote-handled LLW: (1) offsite disposal and (2) onsite disposal. The purpose of this study is to identify candidate sites or locations within INL boundaries for the alternative of an onsite remote handled LLW disposal facility and recommend the highest-ranked locations for consideration in the National Environmental Policy Act process. The study implements an evaluation based on consideration of five key elements: (1) regulations, (2) key assumptions, (3) conceptual design, (4) facility performance, and (5) previous INL siting study criteria, and uses a five-step process to identify, screen, evaluate, score, and rank 34 separate sites located across INL. The result of the evaluation is identification of two recommended alternative locations for siting an onsite remote-handled LLW disposal facility. The two alternative locations that best meet the evaluation criteria are (1) near the Advanced Test Reactor Complex and (2) west of the Idaho Comprehensive Environmental Response, Compensation, and Liability Act Disposal Facility.

Constitutive properties of salt from four sites

International Nuclear Information System (INIS)

Pfeifle, T.W.; Mellegard, K.D.; Senseny, P.E.

1983-04-01

Results are presented from laboratory strength and creep tests performed on salt specimens from the Richton dome in Mississippi, the Vacherie dome in Louisiana, the Permian basin in Texas, and the Paradox basin in Utah. The constitutive properties obtained are the elastic moduli and the failure envelope at 24 0 C and parameter values for the baseline creep law. Some additional data are presented to indicate how the elastic moduli and strength change with temperature. The constitutive properties given in this report and subsequent numerical simulations will serve as input to the screening of site locations for a nuclear-waste repository. The matrix of tests performed is the minimum effort required to obtain these constitutive properties. Comparison of results with those obtained for sites that have been characterized in greater detail suggests that the constitutive parameter values obtained are adequate for site-screening activity

Washington Phase II Fish Diversion Screen Evaluations in the Yakima River Basin, 2004-2005 Annual Report.

Energy Technology Data Exchange (ETDEWEB)

Vucelick, Jessica; McMichael, Geoffrey; Chamness, Mickie [Pacific Northwest National Laboratory

2006-02-01

In 2004, the Pacific Northwest National Laboratory (PNNL) evaluated 25 Phase II fish screen sites in the Yakima River Basin as part of a multi-year project for the Bonneville Power Administration on the effectiveness of fish screening devices. PNNL collected data to determine whether velocities in front of the screens and in the bypasses met the National Oceanic and Atmospheric Administration Fisheries (NOAA Fisheries, formerly the National Marine Fisheries Service (NMFS)) criteria to promote safe and timely fish passage. In addition, PNNL conducted underwater video surveys to evaluate the environmental and operational conditions of the screen sites with respect to fish passage. Based on evaluations in 2004, PNNL concluded that: (1) In general, water velocity conditions at the screen sites met fish passage criteria set by NOAA Fisheries. (2) Conditions at most facilities would be expected to provide for safe juvenile fish passage. (3) Automated cleaning brushes generally functioned properly; chains and other moving parts were typically well-greased and operative. (4) Removal of sediment buildup and accumulated leafy and woody debris could be improved at some sites. (5) Conditions at some facilities indicate that operation and/or maintenance should be modified to improve passage conditions for juvenile fish. For example, Taylor has had problems meeting bypass flow and submergence operating criteria since the main river channel shifted away from the site 2 years ago, and Fruitvale consistently has had problems meeting bypass flow criteria when the water is low. (6) Continued problems at Gleed point to design flaws. This site should be considered for redesign or replacement.

Retinal Imaging Techniques for Diabetic Retinopathy Screening

Science.gov (United States)

Goh, James Kang Hao; Cheung, Carol Y.; Sim, Shaun Sebastian; Tan, Pok Chien; Tan, Gavin Siew Wei; Wong, Tien Yin

2016-01-01

Due to the increasing prevalence of diabetes mellitus, demand for diabetic retinopathy (DR) screening platforms is steeply increasing. Early detection and treatment of DR are key public health interventions that can greatly reduce the likelihood of vision loss. Current DR screening programs typically employ retinal fundus photography, which relies on skilled readers for manual DR assessment. However, this is labor-intensive and suffers from inconsistency across sites. Hence, there has been a recent proliferation of automated retinal image analysis software that may potentially alleviate this burden cost-effectively. Furthermore, current screening programs based on 2-dimensional fundus photography do not effectively screen for diabetic macular edema (DME). Optical coherence tomography is becoming increasingly recognized as the reference standard for DME assessment and can potentially provide a cost-effective solution for improving DME detection in large-scale DR screening programs. Current screening techniques are also unable to image the peripheral retina and require pharmacological pupil dilation; ultra-widefield imaging and confocal scanning laser ophthalmoscopy, which address these drawbacks, possess great potential. In this review, we summarize the current DR screening methods using various retinal imaging techniques, and also outline future possibilities. Advances in retinal imaging techniques can potentially transform the management of patients with diabetes, providing savings in health care costs and resources. PMID:26830491

iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan.

Science.gov (United States)

Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

2011-06-01

The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan

Science.gov (United States)

Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

2011-06-01

The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

Developments in SPR Fragment Screening.

Science.gov (United States)

Chavanieu, Alain; Pugnière, Martine

2016-01-01

Fragment-based approaches have played an increasing role alongside high-throughput screening in drug discovery for 15 years. The label-free biosensor technology based on surface plasmon resonance (SPR) is now sensitive and informative enough to serve during primary screens and validation steps. In this review, the authors discuss the role of SPR in fragment screening. After a brief description of the underlying principles of the technique and main device developments, they evaluate the advantages and adaptations of SPR for fragment-based drug discovery. SPR can also be applied to challenging targets such as membrane receptors and enzymes. The high-level of immobilization of the protein target and its stability are key points for a relevant screening that can be optimized using oriented immobilized proteins and regenerable sensors. Furthermore, to decrease the rate of false negatives, a selectivity test may be performed in parallel on the main target bearing the binding site mutated or blocked with a low-off-rate ligand. Fragment-based drug design, integrated in a rational workflow led by SPR, will thus have a predominant role for the next wave of drug discovery which could be greatly enhanced by new improvements in SPR devices.

The site selection process

International Nuclear Information System (INIS)

Kittel, J.H.

1989-01-01

One of the most arduous tasks associated with the management of radioactive wastes is the siting of new disposal facilities. Experience has shown that the performance of the disposal facility during and after disposal operations is critically dependent on the characteristics of the site itself. The site selection process consists of defining needs and objectives, identifying geographic regions of interest, screening and selecting candidate sites, collecting data on the candidate sites, and finally selecting the preferred site. Before the site selection procedures can be implemented, however, a formal legal system must be in place that defines broad objectives and, most importantly, clearly establishes responsibilities and accompanying authorities for the decision-making steps in the procedure. Site selection authorities should make every effort to develop trust and credibility with the public, local officials, and the news media. The responsibilities of supporting agencies must also be spelled out. Finally, a stable funding arrangement must be established so that activities such as data collection can proceed without interruption. Several examples, both international and within the US, are given

Self-collected cervicovaginal sampling for site-of-care primary HPV-based cervical cancer screening: a pilot study in a rural underserved Greek population.

Science.gov (United States)

Chatzistamatiou, Kimon; Chatzaki, Εkaterini; Constantinidis, Τheocharis; Nena, Evangelia; Tsertanidou, Athena; Agorastos, Theodoros

2017-11-01

In the present pilot study, the feasibility of a site-of-care cervicovaginal self-sampling methodology for HPV-based screening was tested in 346 women residing in underserved rural areas of Northern Greece. These women provided self-collected cervicovaginal sample along with a study questionnaire. Following molecular testing, using the cobas ® HPV Test, Roche ® , HPV positive women, were referred to colposcopy and upon abnormal findings, to biopsy and treatment. Participation rate was 100%. Regular pap-test examination was reported for 17.1%. Among hrHPV testing, 11.9% were positive and colposcopy/biopsy revealed 2 CIN3 cases. Non-compliance was the most prevalent reason for no previous attendance. Most women reported non-difficulty and non-discomfort in self-sampling (77.6% and 82.4%, respectively). They would choose self-sampling over clinician-sampling (86.2%), and should self-sampling being available, they would test themselves more regularly (92.3%). In conclusion, self-sampling is feasible and well-accepted for HPV-based screening, and could increase population coverage in underserved areas, helping towards successful prevention.

Polyhomologation based on in situ generated Boron-thexyl-silaboracyclic initiating sites: a novel strategy towards the synthesis of polyethylene-based complex architectures

KAUST Repository

Zhang, Zhen; Zhang, Hefeng; Gnanou, Yves; Hadjichristidis, Nikolaos

2015-01-01

A novel strategy, based on the in situ generated Boron-thexyl-silaboracyclic initiating sites for the polyhomologation of dimethylsulfoxonium methylide, has been developed for the synthesis of complex polyethylene-based architectures. As examples

Directional R-Loop Formation by the CRISPR-Cas Surveillance Complex Cascade Provides Efficient Off-Target Site Rejection

Directory of Open Access Journals (Sweden)

Marius Rutkauskas

2015-03-01

Full Text Available CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against foreign nucleic acids. In type I CRISPR-Cas systems, invading DNA is detected by a large ribonucleoprotein surveillance complex called Cascade. The crRNA component of Cascade is used to recognize target sites in foreign DNA (protospacers by formation of an R-loop driven by base-pairing complementarity. Using single-molecule supercoiling experiments with near base-pair resolution, we probe here the mechanism of R-loop formation and detect short-lived R-loop intermediates on off-target sites bearing single mismatches. We show that R-loops propagate directionally starting from the protospacer-adjacent motif (PAM. Upon reaching a mismatch, R-loop propagation stalls and collapses in a length-dependent manner. This unambiguously demonstrates that directional zipping of the R-loop accomplishes efficient target recognition by rapidly rejecting binding to off-target sites with PAM-proximal mutations. R-loops that reach the protospacer end become locked to license DNA degradation by the auxiliary Cas3 nuclease/helicase without further target verification.

Automated microscopy for high-content RNAi screening

Science.gov (United States)

2010-01-01

Fluorescence microscopy is one of the most powerful tools to investigate complex cellular processes such as cell division, cell motility, or intracellular trafficking. The availability of RNA interference (RNAi) technology and automated microscopy has opened the possibility to perform cellular imaging in functional genomics and other large-scale applications. Although imaging often dramatically increases the content of a screening assay, it poses new challenges to achieve accurate quantitative annotation and therefore needs to be carefully adjusted to the specific needs of individual screening applications. In this review, we discuss principles of assay design, large-scale RNAi, microscope automation, and computational data analysis. We highlight strategies for imaging-based RNAi screening adapted to different library and assay designs. PMID:20176920

In silico structure-based drug screening of novel antimycobacterial pharmacophores by DOCK-GOLD tandem screening

Directory of Open Access Journals (Sweden)

Junichi Taira

2017-01-01

Full Text Available Background: Enzymes responsible for cell wall development in Mycobacterium tuberculosis are considered as potential targets of anti-tuberculosis (TB agents. Mycobacterial cyclopropane mycolic acid synthase 1 (CmaA1 is essential for mycobacterial survival because of its critical role in synthesizing mycolic acids. Materials and Methods: We screened compounds that were capable of interacting with the mycobacterial CmaA1 active site using a virtual compound library with an in silico structure-based drug screening (SBDS. Following the selection of such compounds, their antimycobacterial activity was examined. Results: With the in silico SBDS, for which we also used DOCK-GOLD programs and screening methods that utilized the structural similarity between the selected active compounds, we identified two compounds with potent inhibitory effects on mycobacterial growth. The antimycobacterial effect of the compounds was comparable to that of isoniazid, which is used as a first-line anti-TB drug. Conclusion: The compounds identified through SBDS were expected to be a novel class of anti-TB pharmacophores.

Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

Directory of Open Access Journals (Sweden)

Aman C. Kaushik

2018-02-01

Full Text Available GPR142 (G protein receptor 142 is a novel orphan GPCR (G protein coupled receptor belonging to “Class A” of GPCR family and expressed in β cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling, and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

Science.gov (United States)

Kaushik, Aman C.; Kumar, Sanjay; Wei, Dong Q.; Sahi, Shakti

2018-02-01

GPR142 (G protein receptor 142) is a novel orphan GPCR (G protein coupled receptor) belonging to ‘Class A’ of GPCR family and expressed in beta cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

Molecular dynamics simulations and in silico peptide ligand screening of the Elk-1 ETS domain

Directory of Open Access Journals (Sweden)

Hussain Abrar

2011-11-01

Full Text Available Abstract Background The Elk-1 transcription factor is a member of a group of proteins called ternary complex factors, which serve as a paradigm for gene regulation in response to extracellular signals. Its deregulation has been linked to multiple human diseases including the development of tumours. The work herein aims to inform the design of potential peptidomimetic compounds that can inhibit the formation of the Elk-1 dimer, which is key to Elk-1 stability. We have conducted molecular dynamics simulations of the Elk-1 ETS domain followed by virtual screening. Results We show the ETS dimerisation site undergoes conformational reorganisation at the α1β1 loop. Through exhaustive screening of di- and tri-peptide libraries against a collection of ETS domain conformations representing the dynamics of the loop, we identified a series of potential binders for the Elk-1 dimer interface. The di-peptides showed no particular preference toward the binding site; however, the tri-peptides made specific interactions with residues: Glu17, Gln18 and Arg49 that are pivotal to the dimer interface. Conclusions We have shown molecular dynamics simulations can be combined with virtual peptide screening to obtain an exhaustive docking protocol that incorporates dynamic fluctuations in a receptor. Based on our findings, we suggest experimental binding studies to be performed on the 12 SILE ranked tri-peptides as possible compounds for the design of inhibitors of Elk-1 dimerisation. It would also be reasonable to consider the score-ranked tri-peptides as a comparative test to establish whether peptide size is a determinant factor of binding to the ETS domain.

Re-Inversion of Surface Electrical Resistivity Tomography Data from the Hanford Site B-Complex

Energy Technology Data Exchange (ETDEWEB)

Johnson, Timothy C.; Wellman, Dawn M.

2013-05-01

This report documents the three-dimensional (3D) inversion results of surface electrical resistivity tomography (ERT) data collected over the Hanford Site B-Complex. The data were collected in order to image the subsurface distribution of electrically conductive vadose zone contamination resulting from both planned releases of contamination into subsurface infiltration galleries (cribs, trenches, and tile fields), as well as unplanned releases from the B, BX, and BY tank farms and/or associated facilities. Electrically conductive contaminants are those which increase the ionic strength of pore fluids compared to native conditions, which comprise most types of solutes released into the subsurface B-Complex. The ERT data were collected and originally inverted as described in detail in report RPP-34690 Rev 0., 2007, which readers should refer to for a detailed description of data collection and waste disposal history. Although the ERT imaging results presented in that report successfully delineated the footprint of vadose zone contamination in areas outside of the tank farms, imaging resolution was not optimized due to the inability of available inversion codes to optimally process the massive ERT data set collected at the site. Recognizing these limitations and the potential for enhanced ERT characterization and time-lapse imaging at contaminated sites, a joint effort was initiated in 2007 by the U.S. Department of Energy – Office of Science (DOE-SC), with later support by the Office of Environmental Management (DOE-EM), and the U.S. Department of Defense (DOD), to develop a high-performance distributed memory parallel 3D ERT inversion code capable of optimally processing large ERT data sets. The culmination of this effort was the development of E4D (Johnson et al., 2010,2012) In 2012, under the Deep Vadose Zone Applied Field Research Initiative (DVZ-AFRI), the U.S. Department of Energy – Richland Operations Office (DOE-RL) and CH2M Hill Plateau Remediation

The flora and fauna of a proposed wind turbine site near Royal Road, Prince Edward County, Ontario : preliminary screening of the natural environment

Energy Technology Data Exchange (ETDEWEB)

Holder, M.; Leggett, A. [Jacques Whitford Environment Ltd., Markham, ON (Canada)

2002-07-15

Calgary based Vision Quest Windelectric has been given zoning approval to install a 22 MW windfarm in Ontario's Prince Edward County. Following a preliminary screening to determine the effect of the windfarm on the natural environment, the Royal Road Windfarm will be developed in stages with up to 32 turbines. Jacques Whitford Environment Ltd. conducted an environmental study which showed that an exploratory wind turbine in the area is not likely to cause major adverse impacts on local fauna and flora. The proposed location of the wind turbine is not in an important bird area (IBA). An IBA is defined as a site providing essential habitat for one of more species of breeding or non-breeding birds. In 1999, Vision Quest initiated a program to examine bird interactions with wind turbines in southern Alberta. It was shown that most species choose flight paths to avoid turbines. The Royal Road site hosts rare alvars which are naturally open landscapes found in shallow soils on flat limestones. The alvars are subject to seasonal drought and flooding and have specific types of vegetation and animals. Since the exploratory wind turbine will be placed outside the IBA area, its impact on birds will be minimized, and it will have minimal effect on migrant, breeding and wintering birds. It was recommended that monitoring take place at the site during the first year of operation. It is also presumed that the wind turbine will not have any impact on mammals, reptiles and amphibians, or insects. However, it was recommended that more information be gathered on bat movement in the area. If placed appropriately, the wind turbine is not expected to impact on rare plants. It was emphasized that in the past, Vision Quest Windelectric has conducted environmental screening activities, and has acted on recommendations to place wind turbines in locations where environmental impact will be minimized. 26 refs., 5 tabs., 2 figs., 2 appendices.

Environmental site description for a Uranium Atomic Vapor Laser Isotope Separation (U-AVLIS) production plant at the Paducah Gaseous Diffusion Plant site

International Nuclear Information System (INIS)

Marmer, G.J.; Dunn, C.P.; Moeller, K.L.; Pfingston, J.M.; Policastro, A.J.; Yuen, C.R.; Cleland, J.H.

1991-09-01

Uranium enrichment in the United States has utilized a diffusion process to preferentially enrich the U-235 isotope in the uranium product. The U-AVLIS process is based on electrostatic extraction of photoionized U-235 atoms from an atomic vapor stream created by electron-beam vaporization of uranium metal alloy. The U-235 atoms are ionized when precisely tuned laser light -- of appropriate power, spectral, and temporal characteristics -- illuminates the uranium vapor and selectively photoionizes the U-235 isotope. A programmatic document for use in screening DOE site to locate a U-AVLIS production plant was developed and implemented in two parts. The first part consisted of a series of screening analyses, based on exclusionary and other criteria, that identified a reasonable number of candidate sites. These sites were subjected to a more rigorous and detailed comparative analysis for the purpose of developing a short list of reasonable alternative sites for later environmental examination. This environmental site description (ESD) provides a detailed description of the PGDP site and vicinity suitable for use in an environmental impact statement (EIS). The report is based on existing literature, data collected at the site, and information collected by Argonne National Laboratory (ANL) staff during a site visit. 65 refs., 15 tabs

Environmental site description for a Uranium Atomic Vapor Laser Isotope Separation (U-AVLIS) production plant at the Paducah Gaseous Diffusion Plant site

Energy Technology Data Exchange (ETDEWEB)

Marmer, G.J.; Dunn, C.P.; Moeller, K.L.; Pfingston, J.M.; Policastro, A.J.; Yuen, C.R.; Cleland, J.H. (ed.)

1991-09-01

Uranium enrichment in the United States has utilized a diffusion process to preferentially enrich the U-235 isotope in the uranium product. The U-AVLIS process is based on electrostatic extraction of photoionized U-235 atoms from an atomic vapor stream created by electron-beam vaporization of uranium metal alloy. The U-235 atoms are ionized when precisely tuned laser light -- of appropriate power, spectral, and temporal characteristics -- illuminates the uranium vapor and selectively photoionizes the U-235 isotope. A programmatic document for use in screening DOE site to locate a U-AVLIS production plant was developed and implemented in two parts. The first part consisted of a series of screening analyses, based on exclusionary and other criteria, that identified a reasonable number of candidate sites. These sites were subjected to a more rigorous and detailed comparative analysis for the purpose of developing a short list of reasonable alternative sites for later environmental examination. This environmental site description (ESD) provides a detailed description of the PGDP site and vicinity suitable for use in an environmental impact statement (EIS). The report is based on existing literature, data collected at the site, and information collected by Argonne National Laboratory (ANL) staff during a site visit. 65 refs., 15 tabs.

Smartphone Use for Cervical Cancer Screening in Low-Resource Countries: A Pilot Study Conducted in Madagascar.

Directory of Open Access Journals (Sweden)

Rosa Catarino

Full Text Available Visual inspection of the cervix after application of 5% acetic acid (VIA is a screening technique for cervical cancer used widely in low and middle-income countries (LMIC. To improve VIA screening performance, digital images after acid acetic application (D-VIA are taken. The aim of this study was to evaluate the use of a smartphone for on- and off-site D-VIA diagnosis.Women aged 30-65 years, living in the city of Ambanja, Madagascar, were recruited through a cervical cancer screening campaign. Each performed a human papillomavirus (HPV self-sample as a primary screen. Women testing positive for HPV were referred for VIA followed by D-VIA, cervical biopsy and endocervical curettage according to routine protocol. In addition, the same day, the D-VIA was emailed to a tertiary care center for immediate assessment. Results were scored as either D-VIA normal or D-VIA abnormal, requiring immediate therapy or referral to a tertiary center. Each of the three off-site physicians were blinded to the result reported by the one on-site physician and each gave their individual assessment followed by a consensus diagnosis. Statistical analyses were conducted using STATA software.Of the 332 women recruited, 137 (41.2% were HPV-positive and recalled for VIA triage; compliance with this invitation was 69.3% (n = 95. Cervical intraepithelial neoplasia was detected in 17.7% and 21.7% of digital images by on-site and off-site physicians, respectively. The on-site physician had a sensitivity of 66.7% (95%CI: 30.0-90.3 and a specificity of 85.7% (95%CI: 76.7-91.6; the off-site physician consensus sensitivity was 66.7% (95%CI: 30.0-90.3 with a specificity of 82.3% (95%CI: 72.4-89.1.This pilot study supports the use of telemedicine for off-site diagnosis of cervical intraepithelial neoplasia, with diagnostic performance similar to those achieved on-site. Further studies need to determine if smartphones can improve cervical cancer screening efficiency in LMIC.

Framework for DOE mixed low-level waste disposal: Site fact sheets

Energy Technology Data Exchange (ETDEWEB)

Gruebel, M.M.; Waters, R.D.; Hospelhorn, M.B.; Chu, M.S.Y. [eds.

1994-11-01

The Department of Energy (DOE) is required to prepare and submit Site Treatment Plans (STPS) pursuant to the Federal Facility Compliance Act (FFCAct). Although the FFCAct does not require that disposal be addressed in the STPS, the DOE and the States recognize that treatment of mixed low-level waste will result in residues that will require disposal in either low-level waste or mixed low-level waste disposal facilities. As a result, the DOE is working with the States to define and develop a process for evaluating disposal-site suitability in concert with the FFCAct and development of the STPS. Forty-nine potential disposal sites were screened; preliminary screening criteria reduced the number of sites for consideration to twenty-six. The DOE then prepared fact sheets for the remaining sites. These fact sheets provided additional site-specific information for understanding the strengths and weaknesses of the twenty-six sites as potential disposal sites. The information also provided the basis for discussion among affected States and the DOE in recommending sites for more detailed evaluation.

Behavioral Economics: “Nudging” Underserved Populations to Be Screened for Cancer

Science.gov (United States)

Thompson, Tess; Kreuter, Matthew W.; McBride, Timothy D.

2015-01-01

Persistent disparities in cancer screening by race/ethnicity and socioeconomic status require innovative prevention tools and techniques. Behavioral economics provides tools to potentially reduce disparities by informing strategies and systems to increase prevention of breast, cervical, and colorectal cancers. With an emphasis on the predictable, but sometimes flawed, mental shortcuts (heuristics) people use to make decisions, behavioral economics offers insights that practitioners can use to enhance evidence-based cancer screening interventions that rely on judgments about the probability of developing and detecting cancer, decisions about competing screening options, and the optimal presentation of complex choices (choice architecture). In the area of judgment, we describe ways practitioners can use the availability and representativeness of heuristics and the tendency toward unrealistic optimism to increase perceptions of risk and highlight benefits of screening. We describe how several behavioral economic principles involved in decision-making can influence screening attitudes, including how framing and context effects can be manipulated to highlight personally salient features of cancer screening tests. Finally, we offer suggestions about ways practitioners can apply principles related to choice architecture to health care systems in which cancer screening takes place. These recommendations include the use of incentives to increase screening, introduction of default options, appropriate feedback throughout the decision-making and behavior completion process, and clear presentation of complex choices, particularly in the context of colorectal cancer screening. We conclude by noting gaps in knowledge and propose future research questions to guide this promising area of research and practice. PMID:25590600

screening of pleurotus ostreatus and gleophylum sepiarium strains ...

African Journals Online (AJOL)

USER

sawdust dump-site were screened for protease enzyme production. High yields of protease ... glass spreader, sterilized by dipping in 95% ethanol and flaming. .... because higher temperatures led to a sharp decrease in activity. The result is ...

Defining the origins of electron transfer at screen-printed graphene-like and graphite electrodes: MoO2 nanowire fabrication on edge plane sites reveals electrochemical insights.

Science.gov (United States)

Rowley-Neale, Samuel J; Brownson, Dale A C; Banks, Craig E

2016-08-18

Molybdenum (di)oxide (MoO2) nanowires are fabricated onto graphene-like and graphite screen-printed electrodes (SPEs) for the first time, revealing crucial insights into the electrochemical properties of carbon/graphitic based materials. Distinctive patterns observed in the electrochemical process of nanowire decoration show that electron transfer occurs predominantly on edge plane sites when utilising SPEs fabricated/comprised of graphitic materials. Nanowire fabrication along the edge plane sites (and on edge plane like-sites/defects) of graphene/graphite is confirmed with Cyclic Voltammetry, Scanning Electron Microscopy (SEM) and Raman Spectroscopy. Comparison of the heterogeneous electron transfer (HET) rate constants (k°) at unmodified and nanowire coated SPEs show a reduction in the electrochemical reactivity of SPEs when the edge plane sites are effectively blocked/coated with MoO2. Throughout the process, the basal plane sites of the graphene/graphite electrodes remain relatively uncovered; except when the available edge plane sites have been utilised, in which case MoO2 deposition grows from the edge sites covering the entire surface of the electrode. This work clearly illustrates the distinct electron transfer properties of edge and basal plane sites on graphitic materials, indicating favourable electrochemical reactivity at the edge planes in contrast to limited reactivity at the basal plane sites. In addition to providing fundamental insights into the electron transfer properties of graphite and graphene-like SPEs, the reported simple, scalable, and cost effective formation of unique and intriguing MoO2 nanowires realised herein is of significant interest for use in both academic and commercial applications.

A Multi-Center Diabetes Eye Screening Study in Community Settings: Study Design and Methodology.

Science.gov (United States)

Murchison, Ann P; Friedman, David S; Gower, Emily W; Haller, Julia A; Lam, Byron L; Lee, David J; McGwin, Gerald; Owsley, Cynthia; Saaddine, Jinan; Insight Study Group

2016-01-01

Diabetes is the leading cause of new cases of blindness among adults aged 20-74 years within the United States. The Innovative Network for Sight Research group (INSIGHT) designed the Diabetic Eye Screening Study (DESS) to examine the feasibility and short-term effectiveness of non-mydriatic diabetic retinopathy (DR) screening for adults with diabetes in community-based settings. Study enrollment began in December 2011 at four sites: an internal medicine clinic at a county hospital in Birmingham, Alabama; a Federally-qualified community healthcare center in Miami-Dade County, Florida; a university-affiliated outpatient pharmacy in Philadelphia, Pennsylvania; and a medical home in Winston-Salem, North Carolina. People 18 years or older with previously diagnosed diabetes were offered free DR screening using non-mydriatic retinal photography that was preceded by a brief questionnaire addressing demographic information and previous eye care use. Visual acuity was also measured for each eye. Images were evaluated at a telemedicine reading center by trained evaluators using the National Health System DR grading classification. Participants and their physicians were sent screening report results and telephoned for a follow-up survey 3 months post-screening to determine whether participants had sought follow-up comprehensive eye care and their experiences with the screening process. Target enrollment at each site was a minimum of 500 persons. Three of the four sites met this enrollment goal. The INSIGHT/DESS is intended to establish the feasibility and short-term effectiveness of DR screening using non-mydriatic retinal photography in persons with diabetes who seek services in community-based clinic and pharmacy settings.

New Reactor Siting in Finland, Hanhikivi Site in Pyhaejoki - STUK preliminary safety assessment

International Nuclear Information System (INIS)

Nevalainen, Janne

2013-01-01

STUK has performed a preliminary assessment of the Decision-in-Principle on the Fennovoima application. A variety of factors must be considered in the selection of a site, including effects of the site on the plant design and the effects of the plant on the site environment. These include external hazards, both natural and human-induced. Since this is a new site, an extensive siting process is followed, that can include an EIA. A site survey is performed to identify candidate sites, after investigating a large region and rejecting unsuitable sites. The remaining sites are then screened and compared on the basis of safety and other considerations to select one or more preferred sites. Natural hazards include geology, seismology, hydrology and meteorology. Offshore ice will be a particular hazard for this plant, since the site is on average only 1.5 m above sea level. The design basis earthquake corresponds to a return frequency of 100,000 years, with 50 % confidence. The existing sites in southern Finland used a design peak ground acceleration of 0.1 g with the ground response spectrum maximum at 10 Hz. The candidate sites in northern Finland will require a peak ground acceleration of 0.2 g with the ground response spectrum maximum at 25 Hz

The surface chemistry of divalent metal carbonate minerals; a critical assessment of surface charge and potential data using the charge distribution multi-site ion complexation model

NARCIS (Netherlands)

Wolthers, M.; Charlet, L.; Van Cappellen, P.

2008-01-01

The Charge Distribution MUltiSite Ion Complexation or CD–MUSIC modeling approach is used to describe the chemical structure of carbonate mineralaqueous solution interfaces. The new model extends existing surface complexation models of carbonate minerals, by including atomic scale information on

Method for screening prevention and control measures and technologies based on groundwater pollution intensity assessment

Energy Technology Data Exchange (ETDEWEB)

Li, Juan, E-mail: lijuan@craes.org.cn [College of Water Sciences, Beijing Normal University, Beijing 100875 (China); Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Yang, Yang [College of Environment, Beijing Normal University, Beijing 100875 (China); Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Huan, Huan; Li, Mingxiao [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Xi, Beidou, E-mail: xibd413@yeah.net [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Lanzhou Jiaotong University, Lanzhou 730070 (China); Lv, Ningqing [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China); Wu, Yi [Guizhou Academy of Environmental Science and Designing, Guizhou 550000 (China); Xie, Yiwen, E-mail: qin3201@126.com [School of Chemical and Environmental Engineering, Dongguan University of Technology, Dongguan, 523808 (China); Li, Xiang; Yang, Jinjin [Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Beijing, 100012 (China)

2016-05-01

This paper presents a system for determining the evaluation and gradation indices of groundwater pollution intensity (GPI). Considering the characteristics of the vadose zone and pollution sources, the system decides which anti-seepage measures should be implemented at the contaminated site. The pollution sources hazards (PSH) and groundwater intrinsic vulnerability (GIV) are graded by the revised Nemerow Pollution Index and an improved DRTAS model, respectively. GPI is evaluated and graded by a double-sided multi-factor coupling model, which is constructed by the matrix method. The contaminated sites are categorized as prior, ordinary, or common sites. From the GPI results, we develop guiding principles for preventing and removing pollution sources, procedural interruption and remediation, and end treatment and monitoring. Thus, we can select appropriate prevention and control technologies (PCT). To screen the technological schemes and optimize the traditional analytical hierarchy process (AHP), we adopt the technique for order preference by the similarity to ideal solution (TOPSIS) method. Our GPI approach and PCT screening are applied to three types of pollution sites: the refuse dump of a rare earth mine development project (a potential pollution source), a chromium slag dump, and a landfill (existing pollution sources). These three sites are identified as ordinary, prior, and ordinary sites, respectively. The anti-seepage materials at the refuse dump should perform as effectively as a 1.5-m-thick clay bed. The chromium slag dump should be preferentially treated by soil flushing and in situ chemical remediation. The landfill should be treated by natural attenuation technology. The proposed PCT screening approach was compared with conventional screening methods results at the three sites and proved feasible and effective. The proposed method can provide technical support for the monitoring and management of groundwater pollution in China. - Highlights: • An

Method for screening prevention and control measures and technologies based on groundwater pollution intensity assessment

International Nuclear Information System (INIS)

Li, Juan; Yang, Yang; Huan, Huan; Li, Mingxiao; Xi, Beidou; Lv, Ningqing; Wu, Yi; Xie, Yiwen; Li, Xiang; Yang, Jinjin

2016-01-01

This paper presents a system for determining the evaluation and gradation indices of groundwater pollution intensity (GPI). Considering the characteristics of the vadose zone and pollution sources, the system decides which anti-seepage measures should be implemented at the contaminated site. The pollution sources hazards (PSH) and groundwater intrinsic vulnerability (GIV) are graded by the revised Nemerow Pollution Index and an improved DRTAS model, respectively. GPI is evaluated and graded by a double-sided multi-factor coupling model, which is constructed by the matrix method. The contaminated sites are categorized as prior, ordinary, or common sites. From the GPI results, we develop guiding principles for preventing and removing pollution sources, procedural interruption and remediation, and end treatment and monitoring. Thus, we can select appropriate prevention and control technologies (PCT). To screen the technological schemes and optimize the traditional analytical hierarchy process (AHP), we adopt the technique for order preference by the similarity to ideal solution (TOPSIS) method. Our GPI approach and PCT screening are applied to three types of pollution sites: the refuse dump of a rare earth mine development project (a potential pollution source), a chromium slag dump, and a landfill (existing pollution sources). These three sites are identified as ordinary, prior, and ordinary sites, respectively. The anti-seepage materials at the refuse dump should perform as effectively as a 1.5-m-thick clay bed. The chromium slag dump should be preferentially treated by soil flushing and in situ chemical remediation. The landfill should be treated by natural attenuation technology. The proposed PCT screening approach was compared with conventional screening methods results at the three sites and proved feasible and effective. The proposed method can provide technical support for the monitoring and management of groundwater pollution in China. - Highlights: • An

EIA screening and nature protection in Denmark.

Science.gov (United States)

Christensen, Per; Kørnøv, Lone

2011-04-01

The number of environmental impact assessment (EIA) screenings in Denmark has increased dramatically since 2000. This is a consequence of increased pig production as well as the concentration of production on larger farms. In the same period, EIA rules have developed primarily due to an increased focus on the protection of groundwater and Natura 2000 sites. In particular, the implementation of Natura 2000 in Danish legislation has increased the demands on many farms. In its rulings on appealed cases, the Nature Protection Board of Appeal has strengthened its demands, and this is mirrored in screening practices. In this paper, the demands formulated in the guidelines of local authorities were analysed in order to investigate how the protection of groundwater, coastal waters, lakes and Natura 2000 sites develops through EIA screening. It is concluded that the level of protection has improved, and that the main cause for this is not EIA regulations as such, but the positive role which the implementation of the Natura 2000 objectives has played in this development. However, it was also found that the formulation of demands varies greatly between the counties, thus often resulting in ambiguity and leaving room for quite different practices in different counties. Copyright © 2010 Elsevier Ltd. All rights reserved.

International technology catalogue: Foreign technologies to support the environmental restoration and waste management needs of the DOE complex

International Nuclear Information System (INIS)

Matalucci, R.V.

1995-07-01

This document represents a summary of 27 foreign-based environmental restoration and waste management technologies that have been screened and technically evaluated for application to the cleanup problems of the Department of Energy (DOE) nuclear weapons complex. The evaluation of these technologies was initiated in 1992 and completed in 1995 under the DOE's International Technology Coordination Program of the Office of Technology Development. A methodology was developed for conducting a country-by-country survey of several regions of the world where specific environmental technology capabilities and market potential were investigated. The countries that were selected from a rank-ordering process for the survey included: then West Germany, the Netherlands, France, Japan, Taiwan, the Czech and Slovak Republics, and the Former Soviet Union. The notably innovative foreign technologies included in this document were screened initially from a list of several hundred, and then evaluated based on criteria that examined for level of maturity, suitability to the DOE needs, and for potential cost effective application at a DOE site. Each of the selected foreign technologies that were evaluated in this effort for DOE application were subsequently matched with site-specific environmental problem units across the DOE complex using the Technology Needs Assessment CROSSWALK Report. For ease of tracking these technologies to site problem units, and to facilitate their input into the DOE EnviroTRADE Information System, they were categorized into the following three areas: (1) characterization, monitoring and sensors, (2) waste treatment and separations, and (3) waste containment. Technical data profiles regarding these technologies include title and description, performance information, development status, key regulatory considerations, intellectual property rights, institute and contact personnel, and references

Structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase in complex with the feedback inhibitor CoA reveals only one active-site conformation

Energy Technology Data Exchange (ETDEWEB)

Wubben, T.; Mesecar, A.D. (Purdue); (UIC)

2014-10-02

Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway, reversibly transferring an adenylyl group from ATP to 4'-phosphopantetheine to form dephosphocoenzyme A (dPCoA). To complement recent biochemical and structural studies on Mycobacterium tuberculosis PPAT (MtPPAT) and to provide further insight into the feedback regulation of MtPPAT by CoA, the X-ray crystal structure of the MtPPAT enzyme in complex with CoA was determined to 2.11 {angstrom} resolution. Unlike previous X-ray crystal structures of PPAT-CoA complexes from other bacteria, which showed two distinct CoA conformations bound to the active site, only one conformation of CoA is observed in the MtPPAT-CoA complex.

Facilitating Site Specific and Citizens Advisory Boards: Running Effective Meetings that Involve Complex Technical Issues

International Nuclear Information System (INIS)

Freeman, J.

2009-01-01

the Board with a different level of knowledge and interest? A facilitator need not be a scientist or an engineer, but he or she must be proactive in learning the site issues, responsive to concerns about meeting content that is too technical or not technical enough, and resilient when working with individuals for whom the goals of the Board are not necessarily their own. When an SSAB or a CAB is working together purposively with ground rules understood and respect given to each Board member, a facilitator is free to develop effective processes to help Board participants and the members of the public focus on the content and substance of their work together. What are the processes that confront the challenge of ensuring that SSAB and CAB members understand complex technical cleanup issues? How can a facilitator be effective in working with members of the public so that their input is as valuable as possible while balanced with the goals of the Board? This paper will explore the unique environments of this nation's SSABs and CABs; discuss the nature of issues that come before the Boards; examine the make-up of the Boards regarding their potential for understanding complex technical issues and discuss facilitation techniques that provide structure while encouraging participation, interactive work on the tasks at hand, and satisfaction. (authors)

Waste Tank Safety Screening Module: An aspect of Hanford Site tank waste characterization

International Nuclear Information System (INIS)

Hill, J.G.; Wood, T.W.; Babad, H.; Redus, K.S.

1994-01-01

Forty-five (45) of the 149 Hanford single-shell tanks have been designated as Watch-List tanks for one or more high-priority safety issues, which include significant concentrations of organic materials, ferrocyanide salts, potential generation of flammable gases, high heat generation, criticality, and noxious vapor generation. While limited waste characterization data have been acquired on these wastes under the original Tri-Party Agreement, to date all of the tank-by-tank assessments involved in these safety issue designations have been based on historical data rather than waste on data. In response to guidance from the Defense Nuclear Facilities Safety Board (DNFSB finding 93-05) and related direction from the US Department of Energy (DOE), Westinghouse Hanford Company, assisted by Pacific Northwest Laboratory, designed a measurements-based screening program to screen all single-shell tanks for all of these issues. This program, designated the Tank Safety Screening Module (TSSM), consists of a regime of core, supernatant, and auger samples and associated analytical measurements intended to make first-order discriminations of the safety status on a tank-by-tank basis. The TSSM combines limited tank sampling and analysis with monitoring and tank history to provide an enhanced measurement-based categorization of the tanks relative to the safety issues. This program will be implemented beginning in fiscal year (FY) 1994 and supplemented by more detailed characterization studies designed to support safety issue resolution

Site characterization report for the basalt waste isolation project. Volume III

International Nuclear Information System (INIS)

1982-11-01

The reference location for a repository in basalt for the terminal storage of nuclear wastes on the Hanford Site and the candidate horizons within this reference repository location have been identified and the preliminary characterization work in support of the site screening process has been completed. Fifteen technical questions regarding the qualification of the site were identified to be addressed during the detailed site characterization phase of the US Department of Energy-National Waste Terminal Storage Program site selection process. Resolution of these questions will be provided in the final site characterization progress report, currently planned to be issued in 1987, and in the safety analysis report to be submitted with the License Application. The additional information needed to resolve these questions and the plans for obtaining the information have been identified. This Site Characterization Report documents the results of the site screening process, the preliminary site characterization data, the technical issues that need to be addressed, and the plans for resolving these issues. Volume 3 contains chapters 13 through 19: site issues and plans; geoengineering and repository design issues and plans; waste package and site geochemistry issues and plans; performance-assessment issues and plans; site characterization program; quality assurance; and identification of alternate sites

Computer simulations of discharges from a lignite power plant complex

International Nuclear Information System (INIS)

Koukouliou, V.; Horyna, J.; Perez-Sanchez, D.

2008-01-01

This paper describes work carried out within the IAEA EMRAS program NORM working group to test the predictions of three computer models against measured radionuclide concentrations resulting from discharges from a lignite power plant complex. This complex consists of two power plants with a total of five discharge stacks, situated approximately 2-5 kilometres from a city of approximately 10,000 inhabitants. Monthly measurements of mean wind speed and direction, dust loading, and 238 U activities in fallout samples, as well as mean annual values of 232 Th activity in the nearest city sampling sites were available for the study. The models used in the study were Pc-CREAM (a detailed impact assessment model), and COMPLY and CROM (screening models). In applying the models to this scenario it was noted that the meteorological data provided was not ideal for testing, and that a number of assumptions had to be made, particularly for the simpler models. However, taking the gaps and uncertainties in the data into account, the model predictions from PC-CREAM were generally in good agreement with the measured data, and the results from different models were also generally consistent with each other. However, the COMPLY predictions were generally lower than those from PC-CREAM. This is of concern, as the aim of a screening model (COMPLY) is to provide conservative estimates of contaminant concentrations. Further investigation of this problem is required. The general implications of the results for further model development are discussed. (author)

Post-translational modifications near the quinone binding site of mammalian complex I.

Science.gov (United States)

Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

2013-08-23

Complex I (NADH:ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 44 protein subunits with one arm buried in the inner membrane of the mitochondrion and the orthogonal arm protruding about 100 Å into the matrix. The protruding arm contains the binding sites for NADH, the primary acceptor of electrons flavin mononucleotide (FMN), and a chain of seven iron-sulfur clusters that carries the electrons one at a time from FMN to a coenzyme Q molecule bound in the vicinity of the junction between the two arms. In the structure of the closely related bacterial enzyme from Thermus thermophilus, the quinone is thought to bind in a tunnel that spans the interface between the two arms, with the quinone head group close to the terminal iron-sulfur cluster, N2. The tail of the bound quinone is thought to extend from the tunnel into the lipid bilayer. In the mammalian enzyme, it is likely that this tunnel involves three of the subunits of the complex, ND1, PSST, and the 49-kDa subunit. An arginine residue in the 49-kDa subunit is symmetrically dimethylated on the ω-N(G) and ω-N(G') nitrogen atoms of the guanidino group and is likely to be close to cluster N2 and to influence its properties. Another arginine residue in the PSST subunit is hydroxylated and probably lies near to the quinone. Both modifications are conserved in mammalian enzymes, and the former is additionally conserved in Pichia pastoris and Paracoccus denitrificans, suggesting that they are functionally significant.

Accessibility and screening uptake rates for gestational diabetes mellitus in Ireland.

LENUS (Irish Health Repository)

Cullinan, John

2012-03-01

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy and is associated with a range of maternal and neonatal complications and conditions. Given increasing levels of prevalence worldwide, there are growing calls for the implementation of screening practices to identify and treat positive GDM cases. This paper uses a unique dataset to investigate the role of healthcare centre accessibility on the decision to attend for screening, employing geographic information systems, econometric and simulation techniques. We focus on the extent to which \\'travel distance to screening hospital site\\' impacts upon the individual\\'s screen uptake decision, whether significant geographic inequalities exist in relation to accessibility to screening, and the likely impact on uptake rates of providing screening services at a local level via primary care. Our findings have important implications for the provision of GDM screening services.

Artificial intelligence for breast cancer screening: Opportunity or hype?

Science.gov (United States)

Houssami, Nehmat; Lee, Christoph I; Buist, Diana S M; Tao, Dacheng

2017-12-01

Interpretation of mammography for breast cancer (BC) screening can confer a mortality benefit through early BC detection, can miss a cancer that is present or fast growing, or can result in false-positives. Efforts to improve screening outcomes have mostly focused on intensifying imaging practices (double instead of single-reading, more frequent screens, or supplemental imaging) that may add substantial resource expenditures and harms associated with population screening. Less attention has been given to making mammography screening practice 'smarter' or more efficient. Artificial intelligence (AI) is capable of advanced learning using large complex datasets and has the potential to perform tasks such as image interpretation. With both highly-specific capabilities, and also possible un-intended (and poorly understood) consequences, this viewpoint considers the promise and current reality of AI in BC detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Readiness for Implementation of Lung Cancer Screening. A National Survey of Veterans Affairs Pulmonologists.

Science.gov (United States)

Tukey, Melissa H; Clark, Jack A; Bolton, Rendelle; Kelley, Michael J; Slatore, Christopher G; Au, David H; Wiener, Renda Soylemez

2016-10-01

To mitigate the potential harms of screening, professional societies recommend that lung cancer screening be conducted in multidisciplinary programs with the capacity to provide comprehensive care, from screening through pulmonary nodule evaluation to treatment of screen-detected cancers. The degree to which this standard can be met at the national level is unknown. To assess the readiness of clinical facilities in a national healthcare system for implementation of comprehensive lung cancer screening programs, as compared with the ideal described in policy recommendations. This was a cross-sectional, self-administered survey of staff pulmonologists in pulmonary outpatient clinics in Veterans Health Administration facilities. The facility-level response rate was 84.1% (106 of 126 facilities with pulmonary clinics); 88.7% of facilities showed favorable provider perceptions of the evidence for lung cancer screening, and 73.6% of facilities had a favorable provider-perceived local context for screening implementation. All elements of the policy-recommended infrastructure for comprehensive screening programs were present in 36 of 106 facilities (34.0%); the most common deficiencies were the lack of on-site positron emission tomography scanners or radiation oncology services. Overall, 26.5% of Veterans Health Administration facilities were ideally prepared for lung cancer screening implementation (44.1% if the policy recommendations for on-site positron emission tomography scanners and radiation oncology services were waived). Many facilities may be less than ideally positioned for the implementation of comprehensive lung cancer screening programs. To ensure safe, effective screening, hospitals may need to invest resources or coordinate care with facilities that can offer comprehensive care for screening through downstream evaluation and treatment of screen-detected cancers.

Study of site layout in the Rokkasho site

International Nuclear Information System (INIS)

Sato, Kazuyoshi; Tamura, Kousaku; Yagenji, Akira; Sekiya, Shigeki; Takahashi, Hideo; Neyatani, Yuzuru; Uehara, Masaharu; Motohashi, Keiichi; Hashimoto, Masayoshi; Ogino, Shunji; Nagamatsu, Nobuhide

2006-03-01

The Final Design Report (FDR) of the International Thermonuclear Experimental Reactor (ITER) was published on July 2001 as a summary of the Engineering Design Activity (EDA). After the EDA, site dependent design has been investigated for the invitation of ITER toward Rokkasho Site (Iyasakadai area) in Aomori prefecture. This report describes the results of site layout of major buildings and structures of ITER in the Rokkasho-Site. The data of the ground near the site and the results of site dependent design in Japan were applied to this study. Through this study, the most appropriate site layout has been constructed with satisfaction of following conditions. (1) Bedrock level at the tokamak complex building is relatively high and it can be reduced the cost of excavation and foundation work. (2) Total amount of excavation soil for site preparation is minimized and the flexibility of the layout is ensured with flat ground level. (3) Accessibility of human and equipments, reduction of noise and vibration to the environment can be obtained. Total length of ducts and piping between buildings in site is minimized. (author)

SITE-2, Power Plant Siting, Cost, Environment, Seismic and Meteorological Effects

International Nuclear Information System (INIS)

Frigerio, N.A.; Habegger, L.J.; King, R.F.; Hoover, L.J.; Clark, N.A.; Cobian, J.M.

1977-01-01

1 - Description of problem or function: SITE2 is designed to (1) screen candidate energy facility sites or areas within an electric utility region, based on the region's physical and socioeconomic attributes, the planned facility's characteristics, and impact assessments, and (2) evaluate the cumulative regional impacts associated with alternate energy supply options and inter-regional energy import/export practices, specifically, comparison of different energy technologies and their regional distribution in clustered or dispersed patterns. 2 - Method of solution: The SITE2 methodology is based on the quantification of three major site-related vectors. A cost vector is determined which identifies site-specific costs, such as transmission costs, cooling costs as related to water availability, and costs of specific controls needed to protect the surrounding environment. An impact vector is also computed for each potential site, using models of health and environmental impacts incurred in areas adjacent to the site. Finally, a site attribute vector is developed which reflects such characteristics as population, seismic conditions, meteorology, land use, and local ecological systems. This vector can be used to eliminate certain sites because of their inability to satisfy specific constraints. These three vectors can be displayed as density maps and combined in a simple overlay approach, similar to that developed by I. L. McHarg in reference 2, to identify candidate sites. Alternatively, the vector elements can be computationally combined into a weighted sum to obtain quantitative indicators of site suitability

SITE-2, Power Plant Siting, Cost, Environment, Seismic and Meteorological Effects

Energy Technology Data Exchange (ETDEWEB)

Frigerio, N A [Environmental Impact Studies, Argonne National Laboratory 9700 South Cass Avenue, Argonne, Illinois 60439 (United States); Habegger, L J; King, R F; Hoover, L J [Energy and Environmental Systems Division, Argonne National Laboratory 9700 South Cass Avenue, Argonne, Illinois 60439 (United States); Clark, N A [Applied Mathematics Division, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439 (United States); Cobian, J M [Northwestern University, Evanston, Illinois 60201 (United States)

1977-08-01

1 - Description of problem or function: SITE2 is designed to (1) screen candidate energy facility sites or areas within an electric utility region, based on the region's physical and socioeconomic attributes, the planned facility's characteristics, and impact assessments, and (2) evaluate the cumulative regional impacts associated with alternate energy supply options and inter-regional energy import/export practices, specifically, comparison of different energy technologies and their regional distribution in clustered or dispersed patterns. 2 - Method of solution: The SITE2 methodology is based on the quantification of three major site-related vectors. A cost vector is determined which identifies site-specific costs, such as transmission costs, cooling costs as related to water availability, and costs of specific controls needed to protect the surrounding environment. An impact vector is also computed for each potential site, using models of health and environmental impacts incurred in areas adjacent to the site. Finally, a site attribute vector is developed which reflects such characteristics as population, seismic conditions, meteorology, land use, and local ecological systems. This vector can be used to eliminate certain sites because of their inability to satisfy specific constraints. These three vectors can be displayed as density maps and combined in a simple overlay approach, similar to that developed by I. L. McHarg in reference 2, to identify candidate sites. Alternatively, the vector elements can be computationally combined into a weighted sum to obtain quantitative indicators of site suitability.

Characteristics and suitability of waste dump sites in Owerri, Nigeria ...

African Journals Online (AJOL)

A five point criteria screening of the three major waste dumpsites in Owerri Municipality was identified, and a ranking procedure adopted to determine the suitability or otherwise of the dumpsites. The sites were screened and ranked hydro-geologically and geo-technically in order of suitable, moderately suitable, and not ...

Report of early site suitability evaluation of the potential repository site at Yucca Mountain, Nevada; Yucca Mountain Site Characterization Project

Energy Technology Data Exchange (ETDEWEB)

Younker, J.L.; Andrews, W.B.; Fasano, G.A.; Herrington, C.C.; Mattson, S.R.; Murray, R.C. [Science Applications International Corp., Las Vegas, NV (United States); Ballou, L.B.; Revelli, M.A. [Lawrence Livermore National Lab., CA (United States); Ducharme, A.R.; Shephard, L.E. [Sandia National Labs., Albuquerque, NM (United States); Dudley, W.W.; Hoxie, D.T. [Geological Survey, Denver, CO (United States); Herbst, R.J.; Patera, E.A. [Los Alamos National Lab., NM (United States); Judd, B.R. [Decision Analysis Co., Portola Valley, CA (United States); Docka, J.A.; Rickertsen, L.D. [Weston Technical Associates, Washington, DC (United States)

1992-01-01

This study evaluated the technical suitability of Yucca Mountain, Nevada, as a potential site for a mined geologic repository for the permanent disposal of radioactive waste. The evaluation was conducted primarily to determine early in the site characterization program if there are any features or conditions at the site that indicate it is unsuitable for repository development. A secondary purpose was to determine the status of knowledge in the major technical areas that affect the suitability of the site. This early site suitability evaluation (ESSE) was conducted by a team of technical personnel at the request of the Associate Director of the US Department of Energy (DOE) Office of Geologic Disposal, a unit within the DOE`s Office of Civilian Radioactive Waste Management. The Yucca Mountain site has been the subject of such evaluations for over a decade. In 1983, the site was evaluated as part of a screening process to identify potentially acceptable sites. The site was evaluated in greater detail and found suitable for site characterization as part of the Environmental Assessment (EA) (DOE, 1986) required by the Nuclear Waste Policy Act of 1982 (NWPA). Additional site data were compiled during the preparation of the Site Characterization Plan (SCP) (DOE, 1988a). This early site suitability evaluation has considered information that was used in preparing both-documents, along with recent information obtained since the EA and SCP were published. This body of information is referred to in this report as ``current information`` or ``available evidence.``

Characterization of a viral phosphoprotein binding site on the surface of the respiratory syncytial nucleoprotein.

Science.gov (United States)

Galloux, Marie; Tarus, Bogdan; Blazevic, Ilfad; Fix, Jenna; Duquerroy, Stéphane; Eléouët, Jean-François

2012-08-01

The human respiratory syncytial virus (HRSV) genome is composed of a negative-sense single-stranded RNA that is tightly associated with the nucleoprotein (N). This ribonucleoprotein (RNP) complex is the template for replication and transcription by the viral RNA-dependent RNA polymerase. RNP recognition by the viral polymerase involves a specific interaction between the C-terminal domain of the phosphoprotein (P) (P(CTD)) and N. However, the P binding region on N remains to be identified. In this study, glutathione S-transferase (GST) pulldown assays were used to identify the N-terminal core domain of HRSV N (N(NTD)) as a P binding domain. A biochemical characterization of the P(CTD) and molecular modeling of the N(NTD) allowed us to define four potential candidate pockets on N (pocket I [PI] to PIV) as hydrophobic sites surrounded by positively charged regions, which could constitute sites complementary to the P(CTD) interaction domain. The role of selected amino acids in the recognition of the N-RNA complex by P was first screened for by site-directed mutagenesis using a polymerase activity assay, based on an HRSV minigenome containing a luciferase reporter gene. When changed to Ala, most of the residues of PI were found to be critical for viral RNA synthesis, with the R132A mutant having the strongest effect. These mutations also reduced or abolished in vitro and in vivo P-N interactions, as determined by GST pulldown and immunoprecipitation experiments. The pocket formed by these residues is critical for P binding to the N-RNA complex, is specific for pneumovirus N proteins, and is clearly distinct from the P binding sites identified so far for other nonsegmented negative-strand viruses.

Synthesis, spectroscopic characterization, electrochemistry and biological evaluation of some metal (II) complexes with ONO donor ligand containing benzo[b]thiophene and coumarin moieties

Science.gov (United States)

Mahendra Raj, K.; Mruthyunjayaswamy, B. H. M.

2014-09-01

Schiff base ligand 3-chloro-N‧-((7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)methylene)benzo[b]thiophene-2-carbohydrazide and its Cu(II), Co(II), Ni(II) and Zn(II) complexes were synthesized, characterized by elemental analysis and various physico-chemical techniques like, IR, 1H NMR, ESI-mass, UV-Visible, thermogravimetry - differential thermal analysis, magnetic measurements and molar conductance. Spectral analysis indicates octahedral geometry for all the complexes. Cu(II) complex have 1:1 stoichiometry of the type [M(L)(Cl)(H2O)2], whereas Co(II), Ni(II) and Zn(II) complexes have 1:2 stoichiometric ratio of the type [M(L)2]. The bonding sites are the oxygen atom of amide carbonyl, nitrogen of azomethine function and phenolic oxygen of the Schiff base ligand via deprotonation. The thermogravimetry - differential thermal analysis studies gave evidence for the presence of coordinated water molecules in the composition of Cu(II) complex which was further supported by IR measurements. All the complexes were investigated for their electrochemical activity, but only the Cu(II) complex showed the redox property. In order to evaluate the effect of antimicrobial potency of metal ions upon chelation, ligand and its metal complexes along with their respective metal chlorides were screened for their antibacterial and antifungal activities by minimum inhibitory concentration (MIC) method. The results showed that the metal complexes were found to be more active than free ligand. Ligand and its complexes were screened for free radical scavenging activity by DPPH method and DNA cleavage activity using Calf-thymus DNA (Cat. No-105850).

A stable isotope approach for source apportionment of chlorinated ethene plumes at a complex multi-contamination events urban site

Science.gov (United States)

Nijenhuis, Ivonne; Schmidt, Marie; Pellegatti, Eleonora; Paramatti, Enrico; Richnow, Hans Hermann; Gargini, Alessandro