Science.gov

Sample records for apurinic sites design

  1. Response of phage T4 polynucleotide kinase toward dinucleotides containing apurinic sites: Design of a sup 32 P-postlabeling assay for apurinic sites in DNA

    SciTech Connect

    Weinfeld, M.; Liuzzi, M.; Paterson, M.C. )

    1990-02-20

    The authors have examined the capacity of bacteriophage T4 polynucleotide kinase to phosphorylate the partially depurinated products of d-ApA, namely d-SpA and d-ApS (where S represents an apurinic deoxyribose group). It was observed that the enzyme acted only on the latter isomer. Since molecules of this type (d-NpS) are the sole apurinic site containing products resulting from the combined digestion of lightly depurinated DNA by snake venom phosphodiesterase and calf alkaline phosphatase they were able to devise a postlabeling assay for these biologically important DNA lesions. The method offers several advantages, including (a) elimination of the need for prelabeled DNA, (b) high (femtomole range) sensitivity, and (c) nearest-neighbor analysis of bases 5{prime} to apurinic/apyrimidinic sites. Using this assay, they obtained a value for the rate of depurination of form I pRSV neo plasmid DNA. The rate of depurination of poly(dA), treated in a similar fashion, was found to be {approximately}1 base per 10{sup 3} nucleotides per hour.

  2. Catalysts of DNA Strand Cleavage at Apurinic/Apyrimidinic Sites.

    PubMed

    Minko, Irina G; Jacobs, Aaron C; de Leon, Arnie R; Gruppi, Francesca; Donley, Nathan; Harris, Thomas M; Rizzo, Carmelo J; McCullough, Amanda K; Lloyd, R Stephen

    2016-01-01

    Apurinic/apyrimidinic (AP) sites are constantly formed in cellular DNA due to instability of the glycosidic bond, particularly at purines and various oxidized, alkylated, or otherwise damaged nucleobases. AP sites are also generated by DNA glycosylases that initiate DNA base excision repair. These lesions represent a significant block to DNA replication and are extremely mutagenic. Some DNA glycosylases possess AP lyase activities that nick the DNA strand at the deoxyribose moiety via a β- or β,δ-elimination reaction. Various amines can incise AP sites via a similar mechanism, but this non-enzymatic cleavage typically requires high reagent concentrations. Herein, we describe a new class of small molecules that function at low micromolar concentrations as both β- and β,δ-elimination catalysts at AP sites. Structure-activity relationships have established several characteristics that appear to be necessary for the formation of an iminium ion intermediate that self-catalyzes the elimination at the deoxyribose ring. PMID:27363485

  3. Catalysts of DNA Strand Cleavage at Apurinic/Apyrimidinic Sites

    PubMed Central

    Minko, Irina G.; Jacobs, Aaron C.; de Leon, Arnie R.; Gruppi, Francesca; Donley, Nathan; Harris, Thomas M.; Rizzo, Carmelo J.; McCullough, Amanda K.; Lloyd, R. Stephen

    2016-01-01

    Apurinic/apyrimidinic (AP) sites are constantly formed in cellular DNA due to instability of the glycosidic bond, particularly at purines and various oxidized, alkylated, or otherwise damaged nucleobases. AP sites are also generated by DNA glycosylases that initiate DNA base excision repair. These lesions represent a significant block to DNA replication and are extremely mutagenic. Some DNA glycosylases possess AP lyase activities that nick the DNA strand at the deoxyribose moiety via a β- or β,δ-elimination reaction. Various amines can incise AP sites via a similar mechanism, but this non-enzymatic cleavage typically requires high reagent concentrations. Herein, we describe a new class of small molecules that function at low micromolar concentrations as both β- and β,δ-elimination catalysts at AP sites. Structure-activity relationships have established several characteristics that appear to be necessary for the formation of an iminium ion intermediate that self-catalyzes the elimination at the deoxyribose ring. PMID:27363485

  4. DNA Apurinic-Apyrimidinic Site Binding And Excision By Endonuclease IV

    SciTech Connect

    Garcin, E.D.; Hosfield, D.J.; Desai, S.A.; Haas, B.J.; Bjoras, M.; Cunningham, R.P.; Tainer, J.A.

    2009-05-18

    Escherichia coli endonuclease IV is an archetype for an abasic or apurinic-apyrimidinic endonuclease superfamily crucial for DNA base excision repair. Here biochemical, mutational and crystallographic characterizations reveal a three-metal ion mechanism for damage binding and incision. The 1.10-{angstrom} resolution DNA-free and the 2.45-{angstrom} resolution DNA-substrate complex structures capture substrate stabilization by Arg37 and reveal a distorted Zn{sub 3}-ligand arrangement that reverts, after catalysis, to an ideal geometry suitable to hold rather than release cleaved DNA product. The 1.45-{angstrom} resolution DNA-product complex structure shows how Tyr72 caps the active site, tunes its dielectric environment and promotes catalysis by Glu261-activated hydroxide, bound to two Zn{sup 2+} ions throughout catalysis. These structural, mutagenesis and biochemical results suggest general requirements for abasic site removal in contrast to features specific to the distinct endonuclease IV alpha-beta triose phosphate isomerase (TIM) barrel and APE1 four-layer alpha-beta folds of the apurinic-apyrimidinic endonuclease families.

  5. Involvement of apurinic sites in the synergistic action of alkylating and intercalating drugs in Escherichia coli.

    PubMed

    Malvy, C; Safraoui, H; Bloch, E; Bertrand, J R

    1988-03-01

    The toxicity of the intercalating compounds 9-aminoellipticine (9AE) and isopropyl-oxazolopyridocarbazole (Ipr-OPC) were studied. The inhibitory effect of non-toxic doses of 9AE, which incises DNA at apurinic (AP) sites, or Ipr-OPC, which does not cleave DNA at AP sites, with non-toxic doses of the alkylating agent dimethylsulphate (DMS) on the growth of Escherichia coli strain AB1157, is additive. The same result has been observed with an exonuclease III mutant which has only 10% of the AP endonuclease activity. However, 9AE or Ipr-OPC display a synergistic toxic effect with a DMS concentration which allows 20% of E. coli AB1157 survival. This synergy is increased for 9AE in the AP endonuclease mutant when compared to the wild-type strain. Under identical conditions 9AE and Ipr-OPC have no synergistic effect on a mutant deficient in the enzymes which generate AP sites. Therefore AP sites are involved in the synergistic toxicity of DMS and the studied intercalating agents. However, the precise role of the interaction of intercalating agents with AP sites, either without cleavage (type 1 compounds) or with cleavage (type 2 compounds), in the observed effect remains an open question. PMID:3284541

  6. Purification and characterization of an endonuclease specific for apurinic sites in DNA from a permanently established mouse plasmacytoma cell line.

    PubMed Central

    Nes, I F

    1980-01-01

    An endonuclease specific for apurinic sites in double stranded DNA has been purified 373-fold from the nuclei of mouse plasmacytoma cells (line MPC-11). The enzyme is free of any detectable amounts of aspecific nucleases. The enzyme does not act on methylated or OsO4-treated DNA. However, high doses of UV-light and gamma-rays render the DNA slightly susceptible to endonucleolytic attack, which is believed to be due to depurination of depyrimidination caused by the treatment. The molecular weight of the enzyme is determined to be 28,000 and its apparent Km of the purified enzyme is calculated to be 2.7 nM apurinic sites. The activity is not absolutely dependent upon the presence of Mg2+ in the assay mixture although metal chelating agents such as sodium citrate and EDTA abolish the activity completely. The nuclease was stimulated by moderate concentrations of potassium chloride optimizing at 50 mM, and higher concentrations inhibiting the activity. The pH optimun for the reaction was 9.5. PMID:6253941

  7. Endonuclease IV cleaves apurinic/apyrimidinic sites in single-stranded DNA and its application for biosensing.

    PubMed

    Kong, Xiang-Juan; Wu, Shuang; Cen, Yao; Chen, Ting-Ting; Yu, Ru-Qin; Chu, Xia

    2016-07-21

    Endonuclease IV (Endo IV), as a DNA repairing enzyme, plays a crucial role in repairing damaged DNA comprising abasic sites to maintain genomic integrity. The cleaving capability of Endo IV to apurinic/apyrimidinic sites (AP) in single-stranded DNA (ssDNA) was demonstrated. It was found that Endo IV has considerably high cleaving activity to AP sites in ssDNA compared with that in double-stranded DNA (dsDNA). The unique feature of Endo IV in cleaving AP sites in ssDNA was further applied to construct a novel dual signal amplified sensing system for highly sensitive enzyme and protein detection by a combination of exonuclease III (Exo III)-aided cyclic amplification reaction and a rolling circle replication (RCR) technique, which showed a good sensing performance with a detection limit of 0.008 U mL(-1) for Endo IV and 2.5 pM for streptavidin. In addition, the developed method had considerably high specificity for Endo IV and streptavidin over other potential interferences. The developed strategy indeed provides a novel platform for protein and enzyme assays and may find a broad spectrum of applications in bioanalysis, disease diagnosis, and drug development. PMID:27186607

  8. Facile Formation of a DNA Adduct of Semicarbazide on Reaction with Apurinic/Apyrimidinic Sites in DNA.

    PubMed

    Wang, Yinan; Chan, Ho Wai; Chan, Wan

    2016-05-16

    Mutagenic semicarbazide (SEM) is a hydrazine-containing food contaminant found in a wide variety of foods. Despite decades of research, the toxicity of SEM remains incompletely understood. In this study, we demonstrate for the first time that SEM reacts rapidly with apurinic/apyrimidinic sites in an endogenous DNA lesion to form covalently bonded DNA adducts in vitro and in bacteria. Specifically, we performed high-performance liquid chromatography with high accuracy and tandem mass spectrometry to characterize the DNA adduct formed by reacting SEM with 2'-deoxyribose and single- and double-stranded oligonucleotides containing abasic sites under physiologically relevant conditions. By analyzing the reaction mixture at different time points, the reaction kinetics of SEM with DNA was also elucidated. Moreover, by using a highly sensitive and selective liquid chromatography-tandem mass spectrometry method, we show that SEM induces the dose-dependent formation of DNA adducts in Escherichia coli. The results from our studies provide the first direct evidence suggesting that SEM may exert genotoxicity by forming covalently bonded DNA adducts. PMID:27058397

  9. Redox Cycling of Catechol Estrogens Generating Apurinic/Apyrimidinic Sites and 8-oxo-Deoxyguanosine via Reactive Oxygen Species Differentiates Equine and Human Estrogens

    PubMed Central

    Wang, Zhican; Chandrasena, Esala R.; Yuan, Yang; Peng, Kuan-wei; van Breemen, Richard B.; Thatcher, Gregory R. J.; Bolton, Judy L.

    2010-01-01

    Metabolic activation of estrogens to catechols and further oxidation to highly reactive o-quinones generates DNA damage including apurinic/apyrimidinic (AP) sites. 4-Hydroxyequilenin (4-OHEN) is the major catechol metabolite of equine estrogens present in estrogen replacement formulations, known to cause DNA strand breaks, oxidized bases, and stable and depurinating adducts. However, the direct formation of AP sites by 4-OHEN has not been characterized. In the present study, the induction of AP sites in vitro by 4-OHEN and the endogenous catechol estrogen metabolite, 4-hydroxyestrone (4-OHE) was examined by an aldehyde reactive probe assay. Both 4-OHEN and 4-OHE can significantly enhance the levels of AP sites in calf thymus DNA in the presence of the redox cycling agents, copper ion and NADPH. The B-ring unsaturated catechol 4-OHEN induced AP sites without added copper, whereas 4-OHE required copper. AP sites were also generated much more rapidly by 4-OHEN. For both catechol estrogens, the levels of AP sites correlated linearly with 8-oxo-dG levels, implying that depuriniation resulted from reactive oxygen species (ROS) rather than depurination of estrogen-DNA adducts. ROS modulators such as catalase which scavenges hydrogen peroxide and a Cu(I) chelator blocked the formation of AP sites. In MCF-7 breast cancer cells, 4-OHEN significantly enhanced the formation of AP sites with added NADH. In contrast, no significant induction of AP sites was detected in 4-OHE-treated cells. The greater redox activity of the equine catechol estrogen produces rapid oxidative DNA damage via ROS, which is enhanced by redox cycling agents and interestingly by NADPH-dependent quinone oxidoreductase (NQO1). PMID:20509668

  10. Rapid photometric detection of thymine residues partially flipped out of double helix as a method for direct scanning of point mutations and apurinic DNA sites.

    PubMed

    Logvina, N A; Yakubovskaya, M G; Dolinnaya, N G

    2011-02-01

    A spectroscopic assay for detection of extrahelical thymine residues in DNA heteroduplexes under their modification by potassium permanganate has been developed. The assay is based on increase in absorbance at 420 nm due to accumulation of thymidine oxidation intermediates and soluble manganese dioxide. The analysis was carried out using a set of 19-bp DNA duplexes containing unpaired thymidines opposite tetrahydrofuranyl derivatives mimicking a widespread DNA damage (apurinic (AP) sites) and a library of 50-bp DNA duplexes containing all types of base mismatches in different surroundings. The relation between the selectivity of unpaired T oxidation and the thermal stability of DNA double helix was investigated. The method described here was shown to discriminate between DNA duplexes with one or two AP sites and to reveal thymine-containing mismatches and all noncanonical base pairs in AT-surroundings. Comparative results of CCM analysis and the rapid photometric assay for mismatch detection are demonstrated for the first time in the same model system. The chemical reactivity of target thymines was shown to correlate with local disturbance of double helix at the mismatch site. As the spectroscopic assay does not require the DNA cleavage reaction and gel electrophoresis, it can be easily automated and used for primary screening of somatic mutations. PMID:21568858

  11. The role of Schizosaccharomyces pombe DNA repair enzymes Apn1p and Uve1p in the base excision repair of apurinic/apyrimidinic sites

    SciTech Connect

    Tanihigashi, Haruna; Yamada, Ayako; Igawa, Emi; Ikeda, Shogo . E-mail: ikeda@dbc.ous.ac.jp

    2006-09-08

    In Schizosaccharomyces pombe the repair of apurinic/apyrimidinic (AP) sites is mainly initiated by AP lyase activity of DNA glycosylase Nth1p. In contrast, the major AP endonuclease Apn2p functions by removing 3'-{alpha},{beta}-unsaturated aldehyde ends induced by Nth1p, rather than by incising the AP sites. S. pombe possesses other minor AP endonuclease activities derived from Apn1p and Uve1p. In this study, we investigated the function of these two enzymes in base excision repair (BER) for methyl methanesulfonate (MMS) damage using the nth1 and apn2 mutants. Deletion of apn1 or uve1 from nth1{delta} cells did not affect sensitivity to MMS. Exogenous expression of Apn1p failed to suppress the MMS sensitivity of nth1{delta} cells. Although Apn1p and Uve1p incised the oligonucleotide containing an AP site analogue, these enzymes could not initiate repair of the AP sites in vivo. Despite this, expression of Apn1p partially restored the MMS sensitivity of apn2{delta} cells, indicating that the enzyme functions as a 3'-phosphodiesterase to remove 3'-blocked ends. Localization of Apn1p in the nucleus and cytoplasm hints at an additional function of the enzyme other than nuclear DNA repair. Heterologous expression of Saccharomyces cerevisiae homologue of Apn1p completely restored the MMS resistance of the nth1{delta} and apn2{delta} cells. This result confirms a difference in the major pathway for processing the AP site between S. pombe and S. cerevisiae cells.

  12. Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair.

    PubMed

    Choi, Yong Jun; Li, Han; Son, Mi Young; Wang, Xiao-Hong; Fornsaglio, Jamie L; Sobol, Robert W; Lee, Moonsook; Vijg, Jan; Imholz, Sandra; Dollé, Martijn E T; van Steeg, Harry; Reiling, Erwin; Hasty, Paul

    2014-01-01

    Ku70 and Ku80 form a heterodimer called Ku that forms a holoenzyme with DNA dependent-protein kinase catalytic subunit (DNA-PKCS) to repair DNA double strand breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. As expected mutating these genes in mice caused a similar DSB repair-defective phenotype. However, ku70(-/-) cells and ku80(-/-) cells also appeared to have a defect in base excision repair (BER). BER corrects base lesions, apurinic/apyrimidinic (AP) sites and single stand breaks (SSBs) utilizing a variety of proteins including glycosylases, AP endonuclease 1 (APE1) and DNA Polymerase β (Pol β). In addition, deleting Ku70 was not equivalent to deleting Ku80 in cells and mice. Therefore, we hypothesized that free Ku70 (not bound to Ku80) and/or free Ku80 (not bound to Ku70) possessed activity that influenced BER. To further test this hypothesis we performed two general sets of experiments. The first set showed that deleting either Ku70 or Ku80 caused an NHEJ-independent defect. We found ku80(-/-) mice had a shorter life span than dna-pkcs(-/-) mice demonstrating a phenotype that was greater than deleting the holoenzyme. We also found Ku70-deletion induced a p53 response that reduced the level of small mutations in the brain suggesting defective BER. We further confirmed that Ku80-deletion impaired BER via a mechanism that was not epistatic to Pol β. The second set of experiments showed that free Ku70 and free Ku80 could influence BER. We observed that deletion of either Ku70 or Ku80, but not both, increased sensitivity of cells to CRT0044876 (CRT), an agent that interferes with APE1. In addition, free Ku70 and free Ku80 bound to AP sites and in the case of Ku70 inhibited APE1 activity. These observations support a novel role for free Ku70 and free Ku80 in altering BER. PMID:24466051

  13. Human Apurinic/Apyrimidinic Endonuclease 1

    PubMed Central

    Li, Mengxia

    2014-01-01

    Abstract Significance: Human apurinic/apyrimidinic endonuclease 1 (APE1, also known as REF-1) was isolated based on its ability to cleave at AP sites in DNA or activate the DNA binding activity of certain transcription factors. We review herein topics related to this multi-functional DNA repair and stress-response protein. Recent Advances: APE1 displays homology to Escherichia coli exonuclease III and is a member of the divalent metal-dependent α/β fold-containing phosphoesterase superfamily of enzymes. APE1 has acquired distinct active site and loop elements that dictate substrate selectivity, and a unique N-terminus which at minimum imparts nuclear targeting and interaction specificity. Additional activities ascribed to APE1 include 3′–5′ exonuclease, 3′-repair diesterase, nucleotide incision repair, damaged or site-specific RNA cleavage, and multiple transcription regulatory roles. Critical Issues: APE1 is essential for mouse embryogenesis and contributes to cell viability in a genetic background-dependent manner. Haploinsufficient APE1+/− mice exhibit reduced survival, increased cancer formation, and cellular/tissue hyper-sensitivity to oxidative stress, supporting the notion that impaired APE1 function associates with disease susceptibility. Although abnormal APE1 expression/localization has been seen in cancer and neuropathologies, and impaired-function variants have been described, a causal link between an APE1 defect and human disease remains elusive. Future Directions: Ongoing efforts aim at delineating the biological role(s) of the different APE1 activities, as well as the regulatory mechanisms for its intra-cellular distribution and participation in diverse molecular pathways. The determination of whether APE1 defects contribute to human disease, particularly pathologies that involve oxidative stress, and whether APE1 small-molecule regulators have clinical utility, is central to future investigations. Antioxid. Redox Signal. 20, 678–707

  14. New oligonucleotide derivatives as unreactive substrate analogues and potential inhibitors of human apurinic/apyrimidinic endonuclease APE1.

    PubMed

    Kuznetsov, Nikita A; Kupryushkin, Maxim S; Abramova, Tatyana V; Kuznetsova, Alexandra A; Miroshnikova, Anastasia D; Stetsenko, Dmitry A; Pyshnyi, Dmitrii V; Fedorova, Olga S

    2016-01-01

    Human apurinic/apyrimidinic endonuclease APE1 is one of the key enzymes of the base excision DNA repair system. The main biological function of APE1 is the hydrolysis of the phosphodiester bond on the 5'-side of an apurinic/apyrimidinic site (AP-site) to give the 5'-phosphate and 3'-hydroxyl group. It has long been known that AP-sites have mutagenic and cytotoxic effects and their accumulation in DNA is a potential hazard to the cell lifecycle. The structural and biochemical studies of APE1 are complicated by its high catalytic activity towards the AP-site and its cyclic or acyclic analogues. This work has focussed on the design, synthesis and analysis of oligonucleotide derivatives as potentially unreactive APE1 substrates. We have shown that the replacement of oxygen atoms in the phosphate group on the 5'-side from the AP-site analogue tetrahydrofuran (F) considerably decreases the rate of enzymatic hydrolysis of modified oligonucleotides. We have calculated that a N3'-P5' phosphoramidate linkage is hydrolysed about 30 times slower than the native phosphodiester bond while phosphorothioate or primary phosphoramidate linkages are cleaved more than three orders of magnitude slower. The value of IC50 of the oligonucleotide duplex containing a primary phosphoramidate linkage is 2.5 × 10(-7) M, which is in accordance with the APE1 association constant of DNA duplexes containing AP-sites. Thus, it is demonstrated that oligonucleotide duplexes with chemical modifications could be used as unreactive substrates and potential competitive inhibitors of APE1. PMID:26548492

  15. SLAC site design aesthetics

    SciTech Connect

    Hall, F.F.

    1985-10-01

    Stanford Linear Accelerator Center (SLAC) is a single mission laboratory dedicated to basic research in high energy particle physics. SLAC site also houses Stanford Synchrotron Radiation Laboratory (SSRL) which is a multi-mission laboratory for research using beams of ultraviolet light and low energy photons as emitted tangentially from SLAC colliding beam facilities. This paper discusses various aspects of SLAC site design aesthetics under the following headings: (1) imposed footprint of SLAC, (2) description of selected site, (3) use of earth cover for radiation and sight screens, (4) use of landscaping for cosmetic purposes, (5) use of exterior paint colors to soften SLAC impact on neighbors, (6) relocation of SLAC main entrance, (7) relocation of SLAC collider arcs and experimental hall, (8) parking lots and storage yards, and (9) land use zoning at SLAC.

  16. Barrier Free Site Design.

    ERIC Educational Resources Information Center

    Dee, Richard K., Ed.

    The booklet provides information for the design and evaluation of a barrier free outdoor environment for handicapped individuals. Section 1 discusses the scope of the study, defines terms, cites pertinent laws and legislation, describes cost/benefit factors, and surveys population statistics. Section 2 considers recommended design details in the…

  17. Instructional Design. [SITE 2001 Section].

    ERIC Educational Resources Information Center

    Boger, Stephanie, Ed.

    This document contains the papers on instructional design from the SITE (Society for Information Technology & Teacher Education) 2001 conference. Topics covered include: an adaptive e-framework for teacher training; assessing the integration of technology into the curriculum; promoting instructional planning; learning and using World Wide Web page…

  18. Instructional Design. [SITE 2002 Section].

    ERIC Educational Resources Information Center

    2002

    This document contains the following papers on instructional design from the SITE (Society for Information Technology & Teacher Education) 2002 conference: "Faculty Guidelines for the Video Development Process" (Ronald J. Abate and Kathleen Benghiat); "Evolution of an Online Graduate Course in Educational Multimedia" (Peter Albion); "PT3…

  19. Teaching Web Site Design: Science or Art?

    ERIC Educational Resources Information Center

    Taylor, Mark John; Salces, Fausto Sainz; Duffy, Sandra Patricia

    2005-01-01

    This paper discusses an approach to teaching web site design to higher education (HE) students that attempts to balance the artistic and scientific aspects of the web site design process. The design of IT systems has traditionally been viewed as a technical activity. However, unlike existing types of IT systems, an organization's web site is…

  20. Suppression of oxidative phosphorylation in mouse embryonic fibroblast cells deficient in apurinic/apyrimidinic endonuclease

    PubMed Central

    Suganya, Rangaswamy; Chakraborty, Anirban; Miriyala, Sumitra; Hazra, Tapas K.; Izumi, Tadahide

    2015-01-01

    The mammalian apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is an essential DNA repair/gene regulatory protein. Decrease of APE1 in cells by inducible shRNA knockdown or by conditional gene knockout caused apoptosis. Here we succeeded in establishing a unique mouse embryonic fibroblast (MEF) line expressing APE1 at a level far lower than those achieved with shRNA knockdown. The cells, named MEFla (MEFlowAPE1), were hypersensitive to methyl methanesulfonate (MMS), and showed little activity for repairing AP-sites and MMS induced DNA damage. While these results were consistent with the essential role of APE1 in repair of AP sites, the MEFla cells grew normally and the basal activation of poly(ADP-ribose) polymerases in MEFla was lower than that in the wild-type MEF (MEFwt), indicating the low DNA damage stress in MEFla under the normal growth condition. Oxidative phosphorylation activity in MEFla was lower than in MEFwt, while the glycolysis rates in MEFla were higher than in MEFwt. In addition, we observed decreased intracellular oxidative stress in MEFla. These results suggest that cells with low APE1 reversibly suppress mitochondrial respiration and thereby reduce DNA damage stress and increases the cell viability. PMID:25645679

  1. Germline variations of apurinic/apyrimidinic endonuclease 1 (APEX1) detected in female breast cancer patients.

    PubMed

    Ali, Kashif; Mahjabeen, Ishrat; Sabir, Maimoona; Baig, Ruqia Mehmood; Zafeer, Maryam; Faheem, Muhammad; Kayani, Mahmood Akhtar

    2014-01-01

    Apurinic/apyrimidinic endonuclease 1 (APEX1) is a multifunctional protein which plays a central role in the BER pathway. APEX1 gene being highly polymorphic in cancer patients and has been indicated to have a contributive role in Apurinic/apyrimidinic (AP) site accumulation in DNA and consequently an increased risk of cancer development. In this case-control study, all exons of the APEX1 gene and its exon/intron boundaries were amplified in 530 breast cancer patients and 395 matched healthy controls and then analyzed by single-stranded conformational polymorphism followed by sequencing. Sequence analysis revealed fourteen heterozygous mutations, seven 5'UTR, one 3 'UTR, two intronic and four missense. Among identified mutations one 5'UTR (rs41561214), one 3'UTR (rs17112002) and one missense mutation (Ser129Arg, Mahjabeen et al., 2013) had already been reported while the remaining eleven mutations. Six novel mutations (g.20923366T>G, g.20923435G>A, g.20923462G>A, g.20923516G>A, 20923539G>A, g.20923529C>T) were observed in 5'UTR region, two (g.20923585T>G, g.20923589T>G) in intron1 and three missense (Glu101Lys, Ala121Pro, Ser123Trp) in exon 4. Frequencues of 5'UTR mutations; g.20923366T>G, g.20923435G>A and 3'UTR (rs17112002) werecalculated as 0.13, 0.1 and 0.1 respectively. Whereas, the frequency of missense mutations Glu101Lys, Ser123Trp and Ser129Arg was calculated as 0.05. A significant association was observed between APEX1 mutations and increased breast cancer by ~9 fold (OR=8.68, 95%CI=2.64 to 28.5) with g.20923435G>A (5'UTR) , ~13 fold (OR= 12.6, 95%CI=3.01 to 53.0) with g.20923539G>A (5'UTR) and~5 fold increase with three missense mutations [Glu101Lys (OR=4.82, 95%CI=1.97 to 11.80), Ser123Trp (OR=4.62, 95%CI=1.7 to 12.19), Ser129Arg (OR=4.86, 95%CI=1.43 to 16.53)]. The incidence of observed mutations was found higher in patients with family history and with early menopause. In conclusion, our study demonstrates a significant association between germ line

  2. GEOSTATISTICAL SAMPLING DESIGNS FOR HAZARDOUS WASTE SITES

    EPA Science Inventory

    This chapter discusses field sampling design for environmental sites and hazardous waste sites with respect to random variable sampling theory, Gy's sampling theory, and geostatistical (kriging) sampling theory. The literature often presents these sampling methods as an adversari...

  3. Redox regulation of apurinic/apyrimidinic endonuclease 1 activity in Long-Evans Cinnamon rats during spontaneous hepatitis.

    PubMed

    Karmahapatra, Soumendra Krishna; Saha, Tapas; Adhikari, Sanjay; Woodrick, Jordan; Roy, Rabindra

    2014-03-01

    The Long-Evans Cinnamon (LEC) rat is an animal model for Wilson's disease. This animal is genetically predisposed to copper accumulation in the liver, increased oxidative stress, accumulation of DNA damage, and the spontaneous development of hepatocellular carcinoma. Thus, this animal model is useful for studying the relationship of endogenous DNA damage to spontaneous carcinogenesis. In this study, we have investigated the apurinic/apyrimidinic endonuclease 1 (APE1)-mediated excision repair of endogenous DNA damage, apurinic/apyrimidinic (AP)-sites, which is highly mutagenic and implicated in human cancer. We found that the activity was reduced in the liver extracts from the acute hepatitis period of LEC rats as compared with extracts from the age-matched Long-Evans Agouti rats. The acute hepatitis period had also a heightened oxidative stress condition as assessed by an increase in oxidized glutathione level and loss of enzyme activity of glyceraldehyde 3-phosphate dehydrogenase, a key redox-sensitive protein in cells. Interestingly, the activity reduction was not due to changes in protein expression but apparently by reversible protein oxidation as the addition of reducing agents to extracts of the liver from acute hepatitis period reactivated APE1 activity and thus, confirmed the oxidation-mediated loss of APE1 activity under increased oxidative stress. These findings show for the first time in an animal model that the repair mechanism of AP-sites is impaired by increased oxidative stress in acute hepatitis via redox regulation which contributed to the increased accumulation of mutagenic AP-sites in liver DNA. PMID:24337968

  4. Characterization and genetic mapping of a mutation affecting apurinic endonuclease activity in Staphylococcus aureus.

    PubMed Central

    Tam, J E; Pattee, P A

    1986-01-01

    Protoplast fusion between the Rec- mutant RN981 (L. Wyman, R. V. Goering, and R. P. Novick, Genetics 76:681-702, 1974) of Staphylococcus aureus NCTC 8325 and a Rec+ NCTC 8325 derivative yielded Rec+ recombinants that exhibited the increased sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine characteristic of RN981. Transformation analyses identified a specific mutation, designated ngr-374, that was responsible not only for N-methyl-N'-nitro-N-nitrosoguanidine sensitivity, but also sensitivity to methyl methanesulfonate, ethyl methanesulfonate, nitrous acid, and UV irradiation. However, ngr-374-carrying recombinants showed no significant increase in their sensitivity to mitomycin C or 4-nitroquinoline 1-oxide and were unaffected in recombination proficiency. In vitro assays showed that ngr-374-carrying strains had lower apurinic/apyrimidinic endonuclease activities than the wild type. The chromosomal locus occupied by ngr-374 was shown to exist in the gene order omega(Chr::Tn551)40-ngr-374-thrB106. PMID:2430940

  5. Mutation in P0, a dual function ribosomal protein/apurinic/apyrimidinic endonuclease, modifies gene expression and position effect variegation in Drosophila.

    PubMed Central

    Frolov, M V; Birchler, J A

    1998-01-01

    In a search for modifiers of gene expression with the white eye color gene as a target, a third chromosomal P-element insertion mutant l(3)01544 has been identified that exhibits a strong pigment increase in a white-apricot background. Molecular analysis shows that the P-element insertion is found in the first intron of the gene surrounding the insertion site. Sequencing both the cDNA and genomic fragments revealed that the identified gene is identical to one encoding ribosomal protein P0/apurinic/apyrimidinic endonuclease. The P-element-induced mutation, l(3)01544, affects the steady-state level of white transcripts and transcripts of some other genes. In addition, l(3)01544 suppresses the variegated phenotypes of In(1)wm4h and In(1)y3P, suggesting a potential involvement of the P0 protein in modifying position effect variegation. The revertant generated by the precise excision of the P element has lost all mutant phenotypes. Recent work revealed that Drosophila ribosomal protein P0 contains an apurinic/apyrimidinic endonuclease activity. Our results suggest that this multifunctional protein is also involved in regulation of gene expression in Drosophila. PMID:9832526

  6. Endonuclease IV Is the major apurinic/apyrimidinic endonuclease in Mycobacterium tuberculosis and is important for protection against oxidative damage.

    PubMed

    Puri, Rupangi Verma; Singh, Nisha; Gupta, Rakesh K; Tyagi, Anil K

    2013-01-01

    During the establishment of an infection, bacterial pathogens encounter oxidative stress resulting in the production of DNA lesions. Majority of these lesions are repaired by base excision repair (BER) pathway. Amongst these, abasic sites are the most frequent lesions in DNA. Class II apurinic/apyrimidinic (AP) endonucleases play a major role in BER of damaged DNA comprising of abasic sites. Mycobacterium tuberculosis, a deadly pathogen, resides in the human macrophages and is continually subjected to oxidative assaults. We have characterized for the first time two AP endonucleases namely Endonuclease IV (End) and Exonuclease III (XthA) that perform distinct functions in M.tuberculosis. We demonstrate that M.tuberculosis End is a typical AP endonuclease while XthA is predominantly a 3'→5' exonuclease. The AP endonuclease activity of End and XthA was stimulated by Mg(2+) and Ca(2+) and displayed a preferential recognition for abasic site paired opposite to a cytosine residue in DNA. Moreover, End exhibited metal ion independent 3'→5' exonuclease activity while in the case of XthA this activity was metal ion dependent. We demonstrate that End is not only a more efficient AP endonuclease than XthA but it also represents the major AP endonuclease activity in M.tuberculosis and plays a crucial role in defense against oxidative stress. PMID:23936515

  7. Characterization of DNA substrate specificities of apurinic/apyrimidinic endonucleases from Mycobacterium tuberculosis.

    PubMed

    Abeldenov, Sailau; Talhaoui, Ibtissam; Zharkov, Dmitry O; Ishchenko, Alexander A; Ramanculov, Erlan; Saparbaev, Murat; Khassenov, Bekbolat

    2015-09-01

    Apurinic/apyrimidinic (AP) endonucleases are key enzymes involved in the repair of abasic sites and DNA strand breaks. Pathogenic bacteria Mycobacterium tuberculosis contains two AP endonucleases: MtbXthA and MtbNfo members of the exonuclease III and endonuclease IV families, which are exemplified by Escherichia coli Xth and Nfo, respectively. It has been shown that both MtbXthA and MtbNfo contain AP endonuclease and 3'→5' exonuclease activities. However, it remains unclear whether these enzymes hold 3'-repair phosphodiesterase and nucleotide incision repair (NIR) activities. Here, we report that both mycobacterial enzymes have 3'-repair phosphodiesterase and 3'-phosphatase, and MtbNfo contains in addition a very weak NIR activity. Interestingly, depending on pH, both enzymes require different concentrations of divalent cations: 0.5mM MnCl2 at pH 7.6 and 10 mM at pH 6.5. MtbXthA requires a low ionic strength and 37 °C, while MtbNfo requires high ionic strength (200 mM KCl) and has a temperature optimum at 60 °C. Point mutation analysis showed that D180 and N182 in MtbXthA and H206 and E129 in MtbNfo are critical for enzymes activities. The steady-state kinetic parameters indicate that MtbXthA removes 3'-blocking sugar-phosphate and 3'-phosphate moieties at DNA strand breaks with an extremely high efficiency (kcat/KM=440 and 1280 μM(-1)∙min(-1), respectively), while MtbNfo exhibits much lower 3'-repair activities (kcat/KM=0.26 and 0.65 μM(-1)∙min(-1), respectively). Surprisingly, both MtbXthA and MtbNfo exhibited very weak AP site cleavage activities, with kinetic parameters 100- and 300-fold lower, respectively, as compared with the results reported previously. Expression of MtbXthA and MtbNfo reduced the sensitivity of AP endonuclease-deficient E. coli xth nfo strain to methylmethanesulfonate and H2O2 to various degrees. Taken together, these data establish the DNA substrate specificity of M. tuberculosis AP endonucleases and suggest their possible role

  8. Lucanthone and its derivative hycanthone inhibit apurinic endonuclease-1 (APE1) by direct protein binding

    SciTech Connect

    Naidu, M.; Naidu, M.; Agarwal, R.; Pena, L.A.; Cunha, L.; Mezei, M.; Shen, M.; Wilson, D.M.; Liu, Y.; Sanchez, Z.; Chaudhary, P.; Wilson, S.H.; Waring, M.J.

    2011-09-15

    Lucanthone and hycanthone are thioxanthenone DNA intercalators used in the 1980s as antitumor agents. Lucanthone is in Phase I clinical trial, whereas hycanthone was pulled out of Phase II trials. Their potential mechanism of action includes DNA intercalation, inhibition of nucleic acid biosyntheses, and inhibition of enzymes like topoisomerases and the dual function base excision repair enzyme apurinic endonuclease 1 (APE1). Lucanthone inhibits the endonuclease activity of APE1, without affecting its redox activity. Our goal was to decipher the precise mechanism of APE1 inhibition as a prerequisite towards development of improved therapeutics that can counteract higher APE1 activity often seen in tumors. The IC{sub 50} values for inhibition of APE1 incision of depurinated plasmid DNA by lucanthone and hycanthone were 5 {mu}M and 80 nM, respectively. The K{sub D} values (affinity constants) for APE1, as determined by BIACORE binding studies, were 89 nM for lucanthone/10 nM for hycanthone. APE1 structures reveal a hydrophobic pocket where hydrophobic small molecules like thioxanthenones can bind, and our modeling studies confirmed such docking. Circular dichroism spectra uncovered change in the helical structure of APE1 in the presence of lucanthone/hycanthone, and notably, this effect was decreased (Phe266Ala or Phe266Cys or Trp280Leu) or abolished (Phe266Ala/Trp280Ala) when hydrophobic site mutants were employed. Reduced inhibition by lucanthone of the diminished endonuclease activity of hydrophobic mutant proteins (as compared to wild type APE1) supports that binding of lucanthone to the hydrophobic pocket dictates APE1 inhibition. The DNA binding capacity of APE1 was marginally inhibited by lucanthone, and not at all by hycanthone, supporting our hypothesis that thioxanthenones inhibit APE1, predominantly, by direct interaction. Finally, lucanthone-induced degradation was drastically reduced in the presence of short and long lived free radical scavengers, e

  9. Effects of mono- and divalent metal ions on DNA binding and catalysis of human apurinic/apyrimidinic endonuclease 1.

    PubMed

    Miroshnikova, Anastasia D; Kuznetsova, Alexandra A; Vorobjev, Yuri N; Kuznetsov, Nikita A; Fedorova, Olga S

    2016-05-26

    Here, we used stopped-flow fluorescence techniques to conduct a comparative kinetic analysis of the conformational transitions in human apurinic/apyrimidinic endonuclease 1 (APE1) and in DNA containing an abasic site in the course of their interaction. Effects of monovalent (K(+)) and divalent (Mg(2+), Mn(2+), Ca(2+), Zn(2+), Cu(2+), and Ni(2+)) metal ions on DNA binding and catalytic stages were studied. It was shown that the first step of substrate binding (corresponding to formation of a primary enzyme-substrate complex) does not depend on the concentration (0.05-5.0 mM) or the nature of divalent metal ions. In contrast, the initial DNA binding efficiency significantly decreased at a high concentration (5-250 mM) of monovalent K(+) ions, indicating the involvement of electrostatic interactions in this stage. It was also shown that Cu(2+) ions abrogated the DNA binding ability of APE1, possibly, due to a strong interaction with DNA bases and the sugar-phosphate backbone. In the case of Ca(2+) ions, the catalytic activity of APE1 was lost completely with retention of binding potential. Thus, the enzymatic activity of APE1 is increased in the order Zn(2+) < Ni(2+) < Mn(2+) < Mg(2+). Circular dichroism spectra and calculation of the contact area between APE1 and DNA reveal that Mg(2+) ions stabilize the protein structure and the enzyme-substrate complex. PMID:27063150

  10. Access to Space Interactive Design Web Site

    NASA Technical Reports Server (NTRS)

    Leon, John; Cutlip, William; Hametz, Mark

    2000-01-01

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

  11. 10 CFR 862.7 - Designation of sites.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Designation of sites. 862.7 Section 862.7 Energy DEPARTMENT OF ENERGY RESTRICTIONS ON AIRCRAFT LANDING AND AIR DELIVERY AT DEPARTMENT OF ENERGY NUCLEAR SITES § 862.7 Designation of sites. (a) DOE shall designate sites covered by this part as deemed...

  12. Conceptual design report for site drainage control

    SciTech Connect

    Hunter, M.R.

    1996-07-01

    The Mound Plant (Mound), located in Miamisburg, Ohio, is a Department of Energy (DOE) development and production facility performing support work for DOE`s weapons and energy-related programs. EG&G Mound Applied Technologies, Inc. (EG&G) is the Operating Contractor (OC) for this Government-Owned, Contractor-Operated (GOCO) facility. The work performed at Mound emphasizes nuclear energy and explosives technology. Mound is currently implementing an Environmental, Safety & Health (ES&H) Upgrades Program designed to protect its employees, the public, and the environment from adverse effects caused by facility activities. The first project of this multiphase program is now in the final stages of construction, and the second project is currently under design. Four additional projects, one of which is presented in this report, are in the conceptual design stage. At Mound, 22 soil zones have become contaminated with radioactive material. These zones cover approximately 20 percent of the total area of developed property at the site. During a storm event, the rainwater washes contaminated soil from these zones into the storm sewer system. These radioactive contaminants may then be discharged along with the stormwater into the Great Miami River via the Miami Erie Canal. This conceptual design report (CDR), Site Drainage Control, the fourth project in the ES&H program, describes a project that will provide improvements and much needed repairs to inadequate and deteriorating portions of the storm drainage system on the developed property. The project also will provide a stormwater retention facility capable of storing the stormwater runoff, from the developed property, resulting from a 100-year storm event. These improvements will permit the effective control and monitoring of stormwater to prevent the spread of radioactive contaminants from contaminated soil zones and will provide a means to collect and contain accidental spills of hazardous substances.

  13. Repository surface design site layout analysis

    SciTech Connect

    Montalvo, H.R.

    1998-02-27

    The purpose of this analysis is to establish the arrangement of the Yucca Mountain Repository surface facilities and features near the North Portal. The analysis updates and expands the North Portal area site layout concept presented in the ACD, including changes to reflect the resizing of the Waste Handling Building (WHB), Waste Treatment Building (WTB), Carrier Preparation Building (CPB), and site parking areas; the addition of the Carrier Washdown Buildings (CWBs); the elimination of the Cask Maintenance Facility (CMF); and the development of a concept for site grading and flood control. The analysis also establishes the layout of the surface features (e.g., roads and utilities) that connect all the repository surface areas (North Portal Operations Area, South Portal Development Operations Area, Emplacement Shaft Surface Operations Area, and Development Shaft Surface Operations Area) and locates an area for a potential lag storage facility. Details of South Portal and shaft layouts will be covered in separate design analyses. The objective of this analysis is to provide a suitable level of design for the Viability Assessment (VA). The analysis was revised to incorporate additional material developed since the issuance of Revision 01. This material includes safeguards and security input, utility system input (size and location of fire water tanks and pump houses, potable water and sanitary sewage rates, size of wastewater evaporation pond, size and location of the utility building, size of the bulk fuel storage tank, and size and location of other exterior process equipment), main electrical substation information, redundancy of water supply and storage for the fire support system, and additional information on the storm water retention pond.

  14. Molecular design of substrate binding sites

    SciTech Connect

    Shelnutt, J.A.; Hobbs, J.D.

    1991-12-31

    Computer-aided molecular design methods were used to tailor binding sites for small substrate molecules, including CO{sub 2} and methane. The goal is to design a cavity, adjacent to a catalytic metal center, into which the substrate will selectively bind through only non-bonding interactions with the groups lining the binding pocket. Porphyrins are used as a basic molecular structure, with various substituents added to construct the binding pocket. The conformations of these highly-substituted porphyrins are predicted using molecular mechanics calculations with a force field that gives accurate predictions for metalloporhyrins. Dynamics and energy-minimization calculations of substrate molecules bound to the cavity indicate high substrate binding affinity. The size, shape and charge-distribution of groups surrounding the cavity provide molecular selectivity. Specifically, calculated binding energies of methane, benzene, dichloromethane, CO{sub 2} and chloroform vary by about 10 kcal/mol for metal octaethyl-tetraphenylporphyrins (OETPPs) with chloroform, dichloromethane, and CO{sub 2} having the lowest. Significantly, a solvent molecule is found in the cavity in the X-ray structures of Co- and CuOETPP crystals obtained from dichloromethane. 5 refs., 3 figs., 3 tabs.

  15. Molecular design of substrate binding sites

    SciTech Connect

    Shelnutt, J.A.; Hobbs, J.D.

    1991-01-01

    Computer-aided molecular design methods were used to tailor binding sites for small substrate molecules, including CO{sub 2} and methane. The goal is to design a cavity, adjacent to a catalytic metal center, into which the substrate will selectively bind through only non-bonding interactions with the groups lining the binding pocket. Porphyrins are used as a basic molecular structure, with various substituents added to construct the binding pocket. The conformations of these highly-substituted porphyrins are predicted using molecular mechanics calculations with a force field that gives accurate predictions for metalloporhyrins. Dynamics and energy-minimization calculations of substrate molecules bound to the cavity indicate high substrate binding affinity. The size, shape and charge-distribution of groups surrounding the cavity provide molecular selectivity. Specifically, calculated binding energies of methane, benzene, dichloromethane, CO{sub 2} and chloroform vary by about 10 kcal/mol for metal octaethyl-tetraphenylporphyrins (OETPPs) with chloroform, dichloromethane, and CO{sub 2} having the lowest. Significantly, a solvent molecule is found in the cavity in the X-ray structures of Co- and CuOETPP crystals obtained from dichloromethane. 5 refs., 3 figs., 3 tabs.

  16. Determination of apurinic/apyrimidinic lesions in DNA with high-performance liquid chromatography and tandem mass spectrometry.

    PubMed

    Roberts, Kenneth P; Sobrino, Justin A; Payton, Julie; Mason, Lavinnia B; Turesky, Robert J

    2006-02-01

    A new method has been developed to accurately measure apurinic and apyrimidinic (AP) DNA damage sites, which are lesions in DNA formed by loss of a nucleobase from oxidative stress or carcinogen adducts. If AP sites are left unrepaired (or if improperly repaired), these sites can lead to DNA mutations that may ultimately result in the formation of cancer. Hence, detection of AP sites may provide a useful indicator of exposure and susceptibility to chemical carcinogens and oxidative stress. AP detection is currently accomplished by immunodetection methods using an aldehyde reactive probe [Nakamura, J., Walker, V. E., Upton, P. B., Chiang, S.-Y., Kow, Y. W., and Swenberg, J. A. (1998) Cancer Res. 58, 222-225; Atamna, H., Cheung, I., and Ames, B. N. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 686-691]; however, these approaches lack the specificity required for unequivocal identification of the AP site. Therefore, we have developed an accurate method based on mass spectrometry detection of AP sites from AP DNA that have been prelabeled with O-4-nitrobenzylhydroxylamine (NBHA). Once labeled and once the excess labeling agent has been removed, enzymatic digestion of DNA to monomeric subunits can be accomplished, followed by isolation and detection with high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Optimization and validation of the experimental procedures and detection limits have been established using a model DNA oligomer (11-mer) containing uracil. Enzymatic removal of uracil with uracil glycosylase generates well-defined AP sites in both single- and double-stranded DNA. The addition of NBHA labels the AP site in the oligomer, creating a labeled 11-mer. HPLC-ESI-MS/MS in the negative ionization mode was used to monitor and confirm binding of NBHA to the AP oligomer. The NBHA-tagged oligomer underwent endo- and exonuclease digestion to the 5'-deoxyribose monophosphate (5'-dRp) level, thereby releasing

  17. Web Site Design Benchmarking within Industry Groups.

    ERIC Educational Resources Information Center

    Kim, Sung-Eon; Shaw, Thomas; Schneider, Helmut

    2003-01-01

    Discussion of electronic commerce focuses on Web site evaluation criteria and applies them to different industry groups in Korea. Defines six categories of Web site evaluation criteria: business function, corporate credibility, contents reliability, Web site attractiveness, systematic structure, and navigation; and discusses differences between…

  18. Conserved structural chemistry for incision activity in structurally non-homologous apurinic/apyrimidinic endonuclease APE1 and endonuclease IV DNA repair enzymes.

    SciTech Connect

    Tsutakawa, Susan E.; Shin, David S.; Mol, Clifford D.; Izum, Tadahide; Arvai, Andrew S.; Mantha, Anil K.; Szczesny, Bartosz; Ivanov, Ivaylo N.; Hosfield, David J.; Maiti, Buddhadev; Pique, Mike E.; Frankel, Kenneth A.; Hitomi, Kenichi; Cunningham, Richard P.; Mitra, Sankar; Tainer, John A.

    2013-03-22

    Non-coding apurinic/apyrimidinic (AP) sites in DNA form spontaneously and as DNA base excision repair intermediates are the most common toxic and mutagenic in vivo DNA lesion. For repair, AP sites must be processed by 5' AP endonucleases in initial stages of base repair. Human APE1 and bacterial Nfo represent the two conserved 5' AP endonuclease families in the biosphere; they both recognize AP sites and incise the phosphodiester backbone 5' to the lesion, yet they lack similar structures and metal ion requirements. Here, we determined and analyzed crystal structures of a 2.4 ? resolution APE1-DNA product complex with Mg(2+) and a 0.92 Nfo with three metal ions. Structural and biochemical comparisons of these two evolutionarily distinct enzymes characterize key APE1 catalytic residues that are potentially functionally similar to Nfo active site components, as further tested and supported by computational analyses. We observe a magnesium-water cluster in the APE1 active site, with only Glu-96 forming the direct protein coordination to the Mg(2+). Despite differences in structure and metal requirements of APE1 and Nfo, comparison of their active site structures surprisingly reveals strong geometric conservation of the catalytic reaction, with APE1 catalytic side chains positioned analogously to Nfo metal positions, suggesting surprising functional equivalence between Nfo metal ions and APE1 residues. The finding that APE1 residues are positioned to substitute for Nfo metal ions is supported by the impact of mutations on activity. Collectively, the results illuminate the activities of residues, metal ions, and active site features for abasic site endonucleases.

  19. Subsystem design package for the on-site monitor at solar heating and cooling sites

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The on-site monitor is a portable device which can be easily connected to a Site Data Acquisition Subsystem to allow readouts of realtime sensor data in voltage or engineering units at instrumented solar heating and cooling sites. The design package consists of the performance specification, performance requirements cross reference, and the acceptance test procedure.

  20. Molecular Recognition of DNA Damage Sites by Apurinic/Apyrimidinic Endonucleases

    SciTech Connect

    Braun, W. A.

    2005-07-28

    The DNA repair/redox factor AP endonuclease 1 (APE1) is a multifunctional protein which is known to to be essential for DNA repair activity in human cells. Structural/functional analyses of the APE activity is thus been an important research field to assess cellular defense mechanisms against ionizing radiation.

  1. Site Characterization Plan (SCP) conceptual design criteria document

    SciTech Connect

    Naiknimbalkar, N.M.

    1986-05-19

    This SCP Conceptual Design Criteria Document was developed to guide engineering effort for Engineering Study No. 10, the supporting document for Chapter 6 of the SCP. The document provides regulatory design guidance, design rationale derived from the Generic Requirements for a Mined Geological Disposal System document, site-specific criteria, and design assumptions. Appendices were added to provide additional information on geology and seals design. 24 figs., 15 tabs.

  2. SCP (Site Characterization Plan) conceptual design criteria document

    SciTech Connect

    Naiknimbalkar, N.M.

    1985-05-01

    This SCP Conceptual Design Criteria Document was developed to guide engineering efforts for Engineering Study No. 10, the supporting document for Chapter 6 of the SCP. The document provides regulatory design guidance, design rationale derived from the Generic Requirements for a Mined Geological Disposal System document, site-specific criteria, and design assumptions. Appendices were added to provide additional information on geology and seals design.

  3. HVDC power transmission electrode siting and design

    SciTech Connect

    Holt, R.J.; Dabkowski, J.; Hauth, R.L.

    1997-04-01

    This research strives to shed light on the feasibility and practicality of using deep earth electrodes to permit their use for extended periods without adverse consequences. This report begins with a review of the fundamentals associated with current conduction in earth, including the various techniques available for measuring the earth`s electrical properties. The sources of existing data are discussed and some specific data for selected regions of the U.S. and Canada are reviewed as examples. Electrode technology and design issues are reviewed and recent experience gained by New England Power and Hydro-Quebec is discussed. The issues associated with direct current flowing in underground pipelines (and other facilities) are described and the present-day mitigation measures are evaluated. Suggestions are made for further R&D in the coordination of cathodic protection systems, an area that has evolved as an empirical, trial- and-error art more than a science.

  4. Design control for the Savannah River Site Consolidated Incineration Facility

    SciTech Connect

    Walker, R.E.; Rider, R.L.

    1991-12-31

    The initiation, development, and control of the design for the Consolidated Incineration Facility at the US Department of Energy Savannah River Site has been, from the inception, a precisely and formally controlled process. A plan was developed and implemented to ensure output properly aligned with approved design criteria and conformed to applicable regulations throughout the design process. The key element of design control was the technical baseline which established the benchmark against which all changes to the design was evaluated. During the conceptual design phase of the project, design criteria were written to reflect the project objectives and functional requirements. Governmental regulations were reviewed to determine permitting and licensing actions required. Hazards assessments were performed to establish design classifications. The resulting design criteria, permitting requirements, and facility classifications were incorporated into the design plan which provided the basis for subsequent design activities. As the project proceeded through the various design phases, design control was maintained according to the design plan. Review of all design products was performed by the project team routinely. Formal independent design reviews were accomplished prior to releasing the design for construction. Alignment between criteria and design output was verified periodically throughout the design process. A formal design change control board was invoked to effect design changes impacting technical baselines. All changes to design initiated following issue for construction also were subject to procedural control.

  5. Design control for the Savannah River Site Consolidated Incineration Facility

    SciTech Connect

    Walker, R.E.; Rider, R.L. )

    1991-01-01

    The initiation, development, and control of the design for the Consolidated Incineration Facility at the US Department of Energy Savannah River Site has been, from the inception, a precisely and formally controlled process. A plan was developed and implemented to ensure output properly aligned with approved design criteria and conformed to applicable regulations throughout the design process. The key element of design control was the technical baseline which established the benchmark against which all changes to the design was evaluated. During the conceptual design phase of the project, design criteria were written to reflect the project objectives and functional requirements. Governmental regulations were reviewed to determine permitting and licensing actions required. Hazards assessments were performed to establish design classifications. The resulting design criteria, permitting requirements, and facility classifications were incorporated into the design plan which provided the basis for subsequent design activities. As the project proceeded through the various design phases, design control was maintained according to the design plan. Review of all design products was performed by the project team routinely. Formal independent design reviews were accomplished prior to releasing the design for construction. Alignment between criteria and design output was verified periodically throughout the design process. A formal design change control board was invoked to effect design changes impacting technical baselines. All changes to design initiated following issue for construction also were subject to procedural control.

  6. Site Analysis--Rudimentary Concept in Residential Design

    ERIC Educational Resources Information Center

    Nystrom, Dennis C.

    1969-01-01

    This article on site analysis is concerned with the external factors affecting the dwelling and surrounding area when planning a residential design. Schematic drawings as well as a list of important data to be considered when planning are included. (GR)

  7. 40 CFR 228.4 - Procedures for designation of sites.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.4 Procedures for designation... permits. Areas where ocean dumping is permitted subject to the specific conditions of individual special... studies for the evaluation and potential selection of dumping sites will be conducted in accordance...

  8. SiteOut: An Online Tool to Design Binding Site-Free DNA Sequences

    PubMed Central

    Scholes, Clarissa; Wunderlich, Zeba; DePace, Angela H.

    2016-01-01

    DNA-binding proteins control many fundamental biological processes such as transcription, recombination and replication. A major goal is to decipher the role that DNA sequence plays in orchestrating the binding and activity of such regulatory proteins. To address this goal, it is useful to rationally design DNA sequences with desired numbers, affinities and arrangements of protein binding sites. However, removing binding sites from DNA is computationally non-trivial since one risks creating new sites in the process of deleting or moving others. Here we present an online binding site removal tool, SiteOut, that enables users to design arbitrary DNA sequences that entirely lack binding sites for factors of interest. SiteOut can also be used to delete sites from a specific sequence, or to introduce site-free spacers between functional sequences without creating new sites at the junctions. In combination with commercial DNA synthesis services, SiteOut provides a powerful and flexible platform for synthetic projects that interrogate regulatory DNA. Here we describe the algorithm and illustrate the ways in which SiteOut can be used; it is publicly available at https://depace.med.harvard.edu/siteout/. PMID:26987123

  9. Diverse Small Molecule Inhibitors of Human Apurinic/Apyrimidinic Endonuclease APE1 Identified from a Screen of a Large Public Collection

    PubMed Central

    Dorjsuren, Dorjbal; Kim, Daemyung; Vyjayanti, Vaddadi N.; Maloney, David J.; Jadhav, Ajit; Wilson, David M.; Simeonov, Anton

    2012-01-01

    The major human apurinic/apyrimidinic endonuclease APE1 plays a pivotal role in the repair of base damage via participation in the DNA base excision repair (BER) pathway. Increased activity of APE1, often observed in tumor cells, is thought to contribute to resistance to various anticancer drugs, whereas down-regulation of APE1 sensitizes cells to DNA damaging agents. Thus, inhibiting APE1 repair endonuclease function in cancer cells is considered a promising strategy to overcome therapeutic agent resistance. Despite ongoing efforts, inhibitors of APE1 with adequate drug-like properties have yet to be discovered. Using a kinetic fluorescence assay, we conducted a fully-automated high-throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR), as well as additional public collections, with each compound tested as a 7-concentration series in a 4 µL reaction volume. Actives identified from the screen were subjected to a panel of confirmatory and counterscreen tests. Several active molecules were identified that inhibited APE1 in two independent assay formats and exhibited potentiation of the genotoxic effect of methyl methanesulfonate with a concomitant increase in AP sites, a hallmark of intracellular APE1 inhibition; a number of these chemotypes could be good starting points for further medicinal chemistry optimization. To our knowledge, this represents the largest-scale HTS to identify inhibitors of APE1, and provides a key first step in the development of novel agents targeting BER for cancer treatment. PMID:23110144

  10. The Effects of Modeled Microgravity on Nucleocytoplasmic Localization of Human Apurinic/Apyrimidinic

    NASA Technical Reports Server (NTRS)

    Gonda, Steve; Jackson, E.B.

    2004-01-01

    Exposure to space radiation and microgravity occurs to humans during space flight. In order to have accurate risk estimations, answering questions to whether increased DNA damage seen during space flight in modified by microgravity are important. Several studies have examined whether intercellular repair of radiation-induced DNA lesions are modified by microgravity. Results from these studies show no modification of the repair processes due to microgravity. However, it is known that in studies not involving radiation that microgravity interferes with normal development. Interestingly, there is no data that attempts to analyze the possible effects of microgravity on the trafficking of DNA repair proteins. In this study, we analyze the effects of modeled microgravity on nucleocytoplasmic shuttling of the human DNA repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1/Ref1) which is involved in base excision repair. We examined nuclear translocation of APE1 using enhanced green fluorescent protein (EGFP) fused to APE1 as a reporter. While APE1 under normal gravity showed normal nuclear localization, APE1 nuclear localization under modeled microgravity was decreased. These results suggest that nucleocytoplasmic translocation of APE1 is modified under modeled microgravity.

  11. Selective inhibition by methoxyamine of the apurinic/apyrimidinic endonuclease activity associated with pyrimidine dimer-DNA glycosylases from Micrococcus luteus and bacteriophage T4

    SciTech Connect

    Liuzzi, M.; Weinfeld, M.; Paterson, M.C.

    1987-06-16

    The UV endonucleases from Micrococcus luteus and bacteriophage T4 possess two catalytic activities specific for the site of cyclobutane pyrimidine dimers in UV-irradiated DNA: a DNA glycosylase that cleaves the 5'-glycosyl bond of the dimerized pyrimidines and an apurinic/apyrimidinic (AP) endonuclease that thereupon incises the phosphodiester bond 3' to the resulting apyrimidinic site. The authors have explored the potential use of methoxyamine, a chemical that reacts at neutral pH with AP sites in DNA, as a selective inhibitor of the AP endonuclease activities residing in the M. luteus and T4 enzymes. The presence of 50 mM methoxyamine during incubation of UV-treated, (/sup 3/H)thymine-labeled poly(dA) x poly(dT) with either enzyme preparation was found to protect completely the irradiated copolymer from endonucleolytic attack at dimer sites, as assayed by yield of acid-soluble radioactivity. In contrast, the dimer-DNA glycosylase activity of each enzyme remained fully functional, as monitored retrospectively by release of free thymine after either photochemical-(5 kJ/m/sup 2/, 254 nm) or photoenzymic- (Escherichia coli photolyase plus visible light) induced reversal of pyrimidine dimers in the UV-damaged substrate. The data demonstrate that the inhibition of the strand-incision reaction arises because of chemical modification of the AP sites and is not due to inactivation of the enzyme by methoxyamine. The results, combined with earlier findings for 5'-acting AP endonucleases, strongly suggest that methoxyamine is a highly specific inhibitor of virtually all AP endonucleases, irrespective of their modes of action, and may therefore prove useful in a wide variety of DNA repair studies.

  12. Directed site exploration for permeable reactive barrier design

    USGS Publications Warehouse

    Lee, J.; Graettinger, A.J.; Moylan, J.; Reeves, H.W.

    2009-01-01

    Permeable reactive barriers (PRBs) are being employed for in situ site remediation of groundwater that is typically flowing under natural gradients. Site characterization is of critical importance to the success of a PRB. A design-specific site exploration approach called quantitatively directed exploration (QDE) is presented. The QDE approach employs three spatially related matrices: (1) covariance of input parameters, (2) sensitivity of model outputs, and (3) covariance of model outputs to identify the most important location to explore based on a specific design. Sampling at the location that most reduces overall site uncertainty produces a higher probability of success of a particular design. The QDE approach is demonstrated on the Kansas City Plant, Kansas City, MO, a case study where a PRB was installed and failed. It is shown that additional quantitatively directed site exploration during the design phase could have prevented the remedial failure that was caused by missing a geologic body having high hydraulic conductivity at the south end of the barrier. The most contributing input parameter approach using head uncertainty clearly indicated where the next sampling should be made toward the high hydraulic conductivity zone. This case study demonstrates the need to include the specific design as well as site characterization uncertainty when choosing the sampling locations. ?? 2008 Elsevier B.V.

  13. Umatilla Satellite and Release Sites Project : Final Conceptual Design Report.

    SciTech Connect

    Montgomery, James M.

    1992-03-01

    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 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.

  14. TWRS privatization Phase I site development design requirements document

    SciTech Connect

    Shord, A.L.

    1997-01-21

    The DOE-RL is pursuing a strategy of hiring private contractors for treatment of Hanford Site tank wastes. This strategy is called privatization and includes design, permitting,construction, operation, and deactivation of facilities for tank waste treatment. The TWRS Privatization Infrastructure Project consists of several sub- projects which will provide key services needed to support the privatization mission. This document identifies the design requirements for the site development sub-project, including construction, power, water, and road modifications. It will be used in development of the project`s conceptual design.

  15. Genetic Polymorphisms of X-ray Repair Cross-Complementing Group 1 and Apurinic/Apyrimidinic Endonuclease-1 in Chronic Obstructive Pulmonary Disease.

    PubMed

    Bardia, Avinash; Vishwakarma, Sandeep Kumar; Reddy, Chandrakala Lakki; Raju, N; Iqbal, Shaik; Sravani, Gallapalli; Lavanya, Narneni; Begum, Nazima; Usma, Naziya; Nallari, Pratibha; Baderuzzaman; Ahmed, Syed Mehmood; Hasan, Asfaq; Khan, Aleem A

    2016-06-01

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous collection of conditions characterized by irreversible expiratory airflow limitation. The disease is interspersed with exacerbations; periods of acute symptomatic, physiological, and functional deterioration. The present study was designed to investigate the role of X-ray cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) polymorphisms and the risk of COPD. Blood samples from 354 unrelated subject (age range 18-60 years; 156 with COPD, 198 healthy controls) were collected. Genomic DNA was isolated and genotyped for XRCC1 Arg399Gln and APE1 Asp148Glu using a confronting two pair primers polymerase chain reaction. GA genotype of XRCC1 gene was found to be predominant in the COPD group compared to controls with 1.86-fold increased risk for COPD (OR 1.86, 95 % CI 1.20-2.88, p = 0.0013). TG genotype of APE1 was found to be predominant in COPD group compared to controls with the difference being statistically significant (OR 1.68, 95 % CI 1.08-2.61, p = 0.0043). The GA haplotype was found to be predominant in COPD than controls with a 2.19-fold significant increase (OR 2.19, 95 % CI 1.46-3.28, p = 0.003). Polymorphism in XRCC1 and APE1 gene is associated with an increased risk of COPD. PMID:27107596

  16. Evolution of the redox function in mammalian apurinic/apyrimidinic endonuclease.

    PubMed

    Georgiadis, M M; Luo, M; Gaur, R K; Delaplane, S; Li, X; Kelley, M R

    2008-08-25

    Human apurinic/apyrimidinic endonuclease (hApe1) encodes two important functional activities: an essential base excision repair (BER) activity and a redox activity that regulates expression of a number of genes through reduction of their transcription factors, AP-1, NFkappaB, HIF-1alpha, CREB, p53 and others. The BER function is highly conserved from prokaryotes (E. coli exonuclease III) to humans (hApe1). Here, we provide evidence supporting a redox function unique to mammalian Apes. An evolutionary analysis of Ape sequences reveals that, of the 7 Cys residues, Cys 93, 99, 208, 296, and 310 are conserved in both mammalian and non-mammalian vertebrate Apes, while Cys 65 is unique to mammalian Apes. In the zebrafish Ape (zApe), selected as the vertebrate sequence most distant from human, the residue equivalent to Cys 65 is Thr 58. The wild-type zApe enzyme was tested for redox activity in both in vitro EMSA and transactivation assays and found to be inactive, similar to C65A hApe1. Substitution of Thr 58 with Cys in zApe, however, resulted in a redox active enzyme, suggesting that a Cys residue in this position is indeed critical for redox function. In order to further probe differences between redox active and inactive enzymes, we have determined the crystal structures of vertebrate redox inactive enzymes, the C65A human Ape1 enzyme and the zApe enzyme at 1.9 and 2.3A, respectively. Our results provide new insights on the redox function and highlight a dramatic gain-of-function activity for Ape1 in mammals not found in non-mammalian vertebrates or lower organisms. PMID:18579163

  17. Induction of apurinic endonuclease 1 overexpression by endoplasmic reticulum stress in hepatoma cells.

    PubMed

    Cheng, Tsung-Lin; Chen, Pin-Shern; Li, Ren-Hao; Yuan, Shyng-Shiou; Su, Ih-Jen; Hung, Jui-Hsiang

    2014-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. Previous studies have noted the induction of endoplasmic reticulum stress or apurinic endonuclease 1 (APE1) expression in many tumors. Therefore, the aim of this study was to investigate the relationship between endoplasmic reticulum (ER stress) and APE1 in hepatocellular carcinoma. Here we investigate the expression of APE1 during ER stress in HepG2 and Huh-7 cell lines. Tunicamycin or brefeldin A, two ER stress inducers, increased APE1 and GRP78, an ER stress marker, expression in HepG2 and Huh-7 cells. Induction of APE1 expression was observed through transcription level in response to ER stress. APE1 nuclear localization during ER stress was determined using immunofluorescence assays in HepG2 cells. Furthermore, expression of Hepatitis B virus pre-S2∆ large mutant surface protein (pre-S2∆), an ER stress-induced protein, also increased GRP78 and APE1 expression in the normal hepatocyte NeHepLxHT cell line. Similarly, tumor samples showed higher expression of APE1 in ER stress-correlated liver cancer tissue in vivo. Our results demonstrate that ER stress and HBV pre-S2∆ increased APE1 expression, which may play an important role in resistance to chemotherapeutic agents or tumor development. Therefore, these data provide an important chemotherapeutic strategy in ER stress and HBV pre-S2∆-associated tumors. PMID:25026174

  18. 40 CFR 228.4 - Procedures for designation of sites.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... 228.4 Section 228.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.4 Procedures for designation... permits. Areas where ocean dumping is permitted subject to the specific conditions of individual...

  19. 40 CFR 228.4 - Procedures for designation of sites.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... 228.4 Section 228.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.4 Procedures for designation... permits. Areas where ocean dumping is permitted subject to the specific conditions of individual...

  20. 40 CFR 228.4 - Procedures for designation of sites.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... 228.4 Section 228.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.4 Procedures for designation... permits. Areas where ocean dumping is permitted subject to the specific conditions of individual...

  1. Designing Site-Based Systems, Deriving a Theory of Practice.

    ERIC Educational Resources Information Center

    Bauer, Scott C.

    1998-01-01

    Reviews five dimensions (focus, scope, structure, process, and capacity) of an organizational design used by 20 New York districts planning for site-based management (SBM) implementation. The confusion surrounding devolution of decision making hinders districts' efforts to effect changes in intermediate variables (job satisfaction and staff…

  2. YqfS from Bacillus subtilis Is a Spore Protein and a New Functional Member of the Type IV Apurinic/Apyrimidinic-Endonuclease Family

    PubMed Central

    Salas-Pacheco, José M.; Urtiz-Estrada, Norma; Martínez-Cadena, Guadalupe; Yasbin, Ronald E.; Pedraza-Reyes, Mario

    2003-01-01

    The enzymatic properties and the physiological function of the type IV apurinic/apyrimidinic (AP)-endonuclease homolog of Bacillus subtilis, encoded by yqfS, a gene specifically expressed in spores, were studied here. To this end, a recombinant YqfS protein containing an N-terminal His6 tag was synthesized in Escherichia coli and purified to homogeneity. An anti-His6-YqfS polyclonal antibody exclusively localized YqfS in cell extracts prepared from B. subtilis spores. The His6-YqfS protein demonstrated enzymatic properties characteristic of the type IV family of DNA repair enzymes, such as AP-endonucleases and 3′-phosphatases. However, the purified protein lacked both 5′-phosphatase and exonuclease III activities. YqfS showed not only a high level of amino acid identity with E. coli Nfo but also a high resistance to inactivation by EDTA, in the presence of DNA containing AP sites (AP-DNA). These results suggest that YqfS possesses a trinuclear Zn center in which the three metal atoms are intimately coordinated by nine conserved basic residues and two water molecules. Electrophoretic mobility shift assays demonstrated that YqfS possesses structural properties that permit it to bind and scan undamaged DNA as well as to strongly interact with AP-DNA. The ability of yqfS to genetically complement the DNA repair deficiency of an E. coli mutant lacking the major AP-endonucleases Nfo and exonuclease III strongly suggests that its product confers protection to cells against the deleterious effects of oxidative promoters and alkylating agents. Thus, we conclude that YqfS of B. subtilis is a spore-specific protein that has structural and enzymatic properties required to participate in the repair of AP sites and 3′ blocking groups of DNA generated during both spore dormancy and germination. PMID:12949090

  3. Apurinic/apyrimidinic endonucleases of Mycobacterium tuberculosis protect against DNA damage but are dispensable for the growth of the pathogen in guinea pigs.

    PubMed

    Puri, Rupangi Verma; Reddy, P Vineel; Tyagi, Anil K

    2014-01-01

    In host cells, Mycobacterium tuberculosis encounters an array of reactive molecules capable of damaging its genome. Non-bulky DNA lesions are the most common damages produced on the exposure of the pathogen to reactive species and base excision repair (BER) pathway is involved in the repair of such damage. During BER, apurinic/apyrimidinic (AP) endonuclease enzymes repair the abasic sites that are generated after spontaneous DNA base loss or by the action of DNA glycosylases, which if left unrepaired lead to inhibition of replication and transcription. However, the role of AP endonucleases in imparting protection against DNA damage and in the growth and pathogenesis of M.tuberculosis has not yet been elucidated. To demonstrate the biological significance of these enzymes in M.tuberculosis, it would be desirable to disrupt the relevant genes and evaluate the resulting mutants for their ability to grow in the host and cause disease. In this study, we have generated M.tuberculosis mutants of the base excision repair (BER) system, disrupted in either one (MtbΔend or MtbΔxthA) or both the AP endonucleases (MtbΔendΔxthA). We demonstrate that these genes are crucial for bacteria to withstand alkylation and oxidative stress in vitro. In addition, the mutant disrupted in both the AP endonucleases (MtbΔendΔxthA) exhibited a significant reduction in its ability to survive inside human macrophages. However, infection of guinea pigs with either MtbΔend or MtbΔxthA or MtbΔendΔxthA resulted in the similar bacillary load and pathological damage in the organs as observed in the case of infection with wild-type M.tuberculosis. The implications of these observations are discussed. PMID:24800740

  4. Rational Design of Antirheumatic Prodrugs Specific for Sites of Inflammation

    PubMed Central

    Onuoha, Shimobi C.; Ferrari, Mathieu; Sblattero, Daniele

    2015-01-01

    Objective Biologic drugs, such as the anti–tumor necrosis factor (anti‐TNF) antibody adalimumab, have represented a breakthrough in the treatment of rheumatoid arthritis. Yet, concerns remain over their lack of efficacy in a sizable proportion of patients and their potential for systemic side effects such as infection. Improved biologic prodrugs specifically targeted to the site of inflammation have the potential to alleviate current concerns surrounding biologic anticytokine therapies. The purpose of this study was to design, construct, and evaluate in vitro and ex vivo the targeting and antiinflammatory capacity of activatable bispecific antibodies. Methods Activatable dual variable domain (aDVD) antibodies were designed and constructed to target intercellular adhesion molecule 1 (ICAM‐1), which is up‐regulated at sites of inflammation, and anti‐TNF antibodies (adalimumab and infliximab). These bispecific molecules included an external arm that targets ICAM‐1 and an internal arm that comprises the therapeutic domain of an anti‐TNF antibody. Both arms were linked to matrix metalloproteinase (MMP)–cleavable linkers. The constructs were tested for their ability to bind and neutralize both in vitro and ex vivo targets. Results Intact aDVD constructs demonstrated significantly reduced binding and anti‐TNF activity in the prodrug formulation as compared to the parent antibodies. Human synovial fluid and physiologic concentrations of MMP enzyme were capable of cleaving the external domain of the antibody, revealing a fully active molecule. Activated antibodies retained the same binding and anti‐TNF inhibitory capacities as the parent molecules. Conclusion The design of a biologic prodrug with enhanced specificity for sites of inflammation (synovium) and reduced specificity for off‐target TNF is described. This construct has the potential to form a platform technology that is capable of enhancing the therapeutic index of drugs for the treatment of

  5. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Rifle, Colorado

    SciTech Connect

    Not Available

    1992-02-01

    This appendix assesses the present conditions and data gathered about the two inactive uranium mill tailings sites near Rifle, Colorado, and the designated disposal site six miles north of Rifle in the area of Estes Gulch. It consolidates available engineering, radiological, geotechnical, hydrological, meteorological, and other information pertinent to the design of the Remedial Action Plan (RAP). The data characterize conditions at the mill, tailings, and disposal site so that the Remedial Action Contractor (RAC) may complete final designs for the remedial actions.

  6. Design and implementation of the site and engineering properties database; Yucca Mountain Site Characterzation Project

    SciTech Connect

    Krebs-Jespersen, M.L.

    1992-02-01

    The Yucca Mountain Site Characterization Project (YMP) is conducting studies to determine whether the Yucca Mountain site in southern Nevada will meet regulatory criteria for a potential mined geologic disposal system for high-level radioactive waste. Data gathered as part of these studies must be compiled and tabulated in a controlled manner for use in design and performance analyses. An integrated data management system has been developed to facilitate this process; this system relies on YMP participants to share in the development of the database and to ensure the integrity of the data. The site and Engineering Properties Database (SEPDB) is unique in that, unlike most databases where one data set is stored for use by one defined user, the SEPDB stores different sets of data which must be structured so that a variety of users can be given access to the information. All individuals responsible for activities supporting the license application should, to the extent possible,work with the same data and the same assumptions. For this reason, it is important that these data sets are readily accessible, comprehensive, and current. The SEPDB contains scientific and engineering data for use in performance assessment and design activities. These data sets currently consist of geologic, hydrologic, and rock properties information from drill holes and field measurements. The users of the SEPDB include engineers and scientists from several government research laboratories (Lawrence Livermore National Laboratory, Los Alamos National Laboratory, and Sandia National Laboratories), the US Geological Survey, and several government contractors. This manuscript describes the detailed requirements, contents, design, and status of the SEPDB, the procedures for submitting data to and/or requesting data from the SEPDB, and a SEPDB data dictionary (Appendix A) for defining the present contents.

  7. Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

    PubMed Central

    Suresh Kumar, M. A.; Peluso, Michael; Chaudhary, Pankaj; Dhawan, Jasbeer; Beheshti, Afshin; Manickam, Krishnan; Thapar, Upasna; Pena, Louis; Natarajan, Mohan; Hlatky, Lynn; Demple, Bruce; Naidu, Mamta

    2015-01-01

    Ionizing radiation causes degeneration of myelin, the insulating sheaths of neuronal axons, leading to neurological impairment. As radiation research on the central nervous system has predominantly focused on neurons, with few studies addressing the role of glial cells, we have focused our present research on identifying the latent effects of single/ fractionated -low dose of low/ high energy radiation on the role of base excision repair protein Apurinic Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells’ differentiation. Apurinic endonuclease-1 is predominantly upregulated in response to oxidative stress by low- energy radiation, and previous studies show significant induction of Apurinic Endonuclease-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of protons cause latent damage to spinal cord architecture while fractionation of HZE (28Si) induce increase in APE1 with single dose, which then decreased with fractionation. The oligodendrocyte progenitor cells differentiation was skewed with increase in immature oligodendrocytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects. PMID:26208353

  8. Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

    SciTech Connect

    Suresh Kumar, M. A.; Peluso, Michael; Chaudhary, Pankaj; Dhawan, Jasbeer; Beheshti, Afshin; Manickam, Krishnan; Thapar, Upasna; Pena, Louis; Natarajan, Mohan; Hlatky, Lynn; Demple, Bruce; Naidu, Mamta

    2015-07-24

    Ionizing radiation causes degeneration of myelin, the insulating sheaths of neuronal axons, leading to neurological impairment. As radiation research on the central nervous system has predominantly focused on neurons, with few studies addressing the role of glial cells, we have focused our present research on identifying the latent effects of single/ fractionated -low dose of low/ high energy radiation on the role of base excision repair protein Apurinic Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells ’ differentiation. Apurinic endonuclease-1 is predominantly upregulated in response to oxidative stress by low- energy radiation, and previous studies show significant induction of Apurinic Endonucle- ase-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of pro- tons cause latent damage to spinal cord architecture while fractionation of HZE (28Si) induce increase in APE1 with single dose, which then decreased with fractionation. In conclusion, the oligoden- drocyte progenitor cells differentiation was skewed with increase in immature oligodendro- cytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects

  9. Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro-Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic Endonuclease 1

    DOE PAGESBeta

    Suresh Kumar, M. A.; Peluso, Michael; Chaudhary, Pankaj; Dhawan, Jasbeer; Beheshti, Afshin; Manickam, Krishnan; Thapar, Upasna; Pena, Louis; Natarajan, Mohan; Hlatky, Lynn; et al

    2015-07-24

    Ionizing radiation causes degeneration of myelin, the insulating sheaths of neuronal axons, leading to neurological impairment. As radiation research on the central nervous system has predominantly focused on neurons, with few studies addressing the role of glial cells, we have focused our present research on identifying the latent effects of single/ fractionated -low dose of low/ high energy radiation on the role of base excision repair protein Apurinic Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells ’ differentiation. Apurinic endonuclease-1 is predominantly upregulated in response to oxidative stress by low- energy radiation, and previous studies show significant induction ofmore » Apurinic Endonucle- ase-1 in neurons and astrocytes. Our studies show for the first time, that fractionation of pro- tons cause latent damage to spinal cord architecture while fractionation of HZE (28Si) induce increase in APE1 with single dose, which then decreased with fractionation. In conclusion, the oligoden- drocyte progenitor cells differentiation was skewed with increase in immature oligodendro- cytes and astrocytes, which likely cause the observed decrease in white matter, increased neuro-inflammation, together leading to the observed significant cognitive defects« less

  10. Savannah River Site reactor hardware design modification study

    SciTech Connect

    Fisher, J.E.

    1990-01-01

    A study was undertaken to assess the merits of proposed design modifications to the Savannah River Site (SRS) reactors. The evaluation was based on the responses calculated by the RELAP5 systems code to double-ended guillotine break loss-of-coolant-accidents (DEGB LOCAs). The three concepts evaluated were (a) elevated plenum inlet piping with a guard vessel and clamshell enclosures, (b) closure of both rotovalves in the affected loop, and (c) closure of the pump suction valve in the affected loop. Each concept included a fast reactor shutdown (to 65% power in 100 ms) and a 2-s ac pump trip. System recovery potential was evaluated for break locations at the pump suction, the pump discharge, and the plenum inlet. The code version used was RELAP5/MOD2.5 version 3d3, a preliminary version of RELAP5/MOD3. The model was a three-dimensional representation of the K-Reactor water plenum and moderator tank. It included explicit representations of all six loops, which were based on the configuration of L-Reactor. A combination of features is recommended to ensure liquid inventory recovery for all break locations. Valve closure design performance for a break location in the short section of piping between the reactor concrete shield and the pump suction valve would benefit from the clamshell enclosing that section of piping. 7 refs., 10 figs., 2 tabs.

  11. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Disposal site design for land disposal. 61.51 Section 61.51 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF... disposal. (a) Disposal site design for near-surface disposal. (1) Site design features must be...

  12. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... disposal. (a) Disposal site design for near-surface disposal. (1) Site design features must be directed... with wastes after disposal. (b) Disposal site design for other than near-surface disposal. ... extent practicable water infiltration, to direct percolating or surface water away from the...

  13. Apurinic/apyrimidinic endonuclease 1 regulates angiogenesis in a transforming growth factor β-dependent manner in human osteosarcoma

    PubMed Central

    Jiang, Xuan; Shan, Jinlu; Dai, Nan; Zhong, Zhaoyang; Qing, Yi; Yang, Yuxing; Zhang, Shiheng; Li, Chongyi; Sui, Jiangdong; Ren, Tao; Li, Mengxia; Wang, Dong

    2015-01-01

    Angiogenesis plays an important role in tumor growth and metastasis and has been reported to be inversely correlated with overall survival of osteosarcoma patients. It has been shown that apurinic/apyrimidinic endonuclease 1 (APE1), a dually functional protein possessing both base excision repair and redox activities, is involved in tumor angiogenesis, although these mechanisms are not fully understood. Our previous study showed that the expression of transforming growth factor β (TGFβ) was significantly reduced in APE1-deficient osteosarcoma cells. Transforming growth factor β promotes cancer metastasis through various mechanisms including immunosuppression, angiogenesis, and invasion. In the current study, we initially revealed that APE1, TGFβ, and microvessel density (MVD) have pairwise correlation in osteosarcoma tissue samples, whereas TGFβ, tumor size, and MVD were inversely related to the prognosis of the cohort. We found that knocking down APE1 in osteosarcoma cells resulted in TGFβ downregulation. In addition, APE1-siRNA led to suppression of angiogenesis in vitro based on HUVECs in Transwell and Matrigel tube formation assays. Reduced secretory protein level of TGFβ of culture medium also resulted in decreased phosphorylation of Smad3 of HUVECs. In a mouse xenograft model, siRNA-mediated silencing of APE1 downregulated TGFβ expression, tumor size, and MVD. Collectively, the current evidence indicates that APE1 regulates angiogenesis in osteosarcoma by controlling the TGFβ pathway, suggesting a novel target for anti-angiogenesis therapy in human osteosarcoma. PMID:26250694

  14. 40 CFR 228.15 - Dumping sites designated on a final basis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Dumping sites designated on a final basis. 228.15 Section 228.15 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.15 Dumping sites designated on a final basis. (a)(1) The...

  15. 40 CFR 228.15 - Dumping sites designated on a final basis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Dumping sites designated on a final basis. 228.15 Section 228.15 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.15 Dumping sites designated on a final basis. (a)(1) The...

  16. 40 CFR 228.15 - Dumping sites designated on a final basis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Dumping sites designated on a final basis. 228.15 Section 228.15 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.15 Dumping sites designated on a final basis. (a)(1) The...

  17. Designing a Marketing Course with Field Site Visits

    ERIC Educational Resources Information Center

    Van Doren, Doris; Corrigan, Hope Bober

    2008-01-01

    A key goal of including field site visits in marketing courses is to give business students increased interaction with industry professionals and community leaders. Site visits give students a concrete idea of how different marketing disciplines work in the business world. Business students gain greater insight into a career in marketing from this…

  18. Hanford Site waste tank farm facilities design reconstitution program plan

    SciTech Connect

    Vollert, F.R.

    1994-09-06

    Throughout the commercial nuclear industry the lack of design reconstitution programs prior to the mid 1980`s has resulted in inadequate documentation to support operating facilities configuration changes or safety evaluations. As a result, many utilities have completed or have ongoing design reconstitution programs and have discovered that without sufficient pre-planning their program can be potentially very expensive and may result in end-products inconsistent with the facility needs or expectations. A design reconstitution program plan is developed here for the Hanford waste tank farms facility as a consequence of the DOE Standard on operational configuration management. This design reconstitution plan provides for the recovery or regeneration of design requirements and basis, the compilation of Design Information Summaries, and a methodology to disposition items open for regeneration that were discovered during the development of Design Information Summaries. Implementation of this plan will culminate in an end-product of about 30 Design Information Summary documents. These documents will be developed to identify tank farms facility design requirements and design bases and thereby capture the technical baselines of the facility. This plan identifies the methodology necessary to systematically recover documents that are sources of design input information, and to evaluate and disposition open items or regeneration items discovered during the development of the Design Information Summaries or during the verification and validation processes. These development activities will be governed and implemented by three procedures and a guide that are to be developed as an outgrowth of this plan.

  19. 40 CFR 228.4 - Procedures for designation of sites.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... for its -disposal. (d) Research Permits. Dumping sites for research permits will be determined by the... research, including that now in progress by the Corps of Engineers. (ii) An environmental impact...

  20. Nuclear depletion of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) is an indicator of energy disruption in neurons

    PubMed Central

    Singh, Shilpee; Englander, Ella W.

    2012-01-01

    Apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) is a multifunctional protein critical for cellular survival. Its involvement in adaptive survival responses includes key roles in redox sensing, transcriptional regulation and repair of DNA damage via the base excision repair (BER) pathway. Ape1 is abundant in most cell types and central in integrating the first BER step catalyzed by different DNA glycosylases. BER is the main process for removal of oxidative DNA lesions in post mitotic brain cells, and after ischemic brain injury preservation of Ape1 coincides with neuronal survival, while its loss has been associated with neuronal death. Here, we report that in cultured primary neurons, diminution of cellular ATP by either oligomycin or H2O2, is accompanied by depletion of nuclear Ape1, while other BER proteins are unaffected and retain their nuclear localization under these conditions. Importantly, while H2O2 induces γH2AX phosphorylation, indicative of chromatin rearrangements in response to DNA damage, oligomycin does not. Furthermore, despite comparable diminution of ATP content, H2O2 and oligomycin differentially affect critical parameters of mitochondrial respiration that ultimately determine cellular ATP content. Taken together, our findings demonstrate that in neurons, nuclear compartmentalization of Ape1 depends on ATP and loss of nuclear Ape1 reflects disruption of neuronal energy homeostasis. Energy crisis is a hallmark of stroke and other ischemic/hypoxic brain injuries. In vivo studies have shown that Ape1 deficit precedes neuronal loss in injured brain regions. Thus, our findings bring to light the possibility that energy failure-induced Ape1 depletion triggers neuronal death in ischemic brain injuries. PMID:22841870

  1. Nuclear depletion of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) is an indicator of energy disruption in neurons.

    PubMed

    Singh, Shilpee; Englander, Ella W

    2012-11-01

    Apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) is a multifunctional protein critical for cellular survival. Its involvement in adaptive survival responses includes key roles in redox sensing, transcriptional regulation, and repair of DNA damage via the base excision repair (BER) pathway. Ape1 is abundant in most cell types and central in integrating the first BER step catalyzed by different DNA glycosylases. BER is the main process for removal of oxidative DNA lesions in postmitotic brain cells, and after ischemic brain injury preservation of Ape1 coincides with neuronal survival, while its loss has been associated with neuronal death. Here, we report that in cultured primary neurons, diminution of cellular ATP by either oligomycin or H(2)O(2) is accompanied by depletion of nuclear Ape1, while other BER proteins are unaffected and retain their nuclear localization under these conditions. Importantly, while H(2)O(2) induces γH2AX phosphorylation, indicative of chromatin rearrangements in response to DNA damage, oligomycin does not. Furthermore, despite comparable diminution of ATP content, H(2)O(2) and oligomycin differentially affect critical parameters of mitochondrial respiration that ultimately determine cellular ATP content. Taken together, our findings demonstrate that in neurons, nuclear compartmentalization of Ape1 depends on ATP and loss of nuclear Ape1 reflects disruption of neuronal energy homeostasis. Energy crisis is a hallmark of stroke and other ischemic/hypoxic brain injuries. In vivo studies have shown that Ape1 deficit precedes neuronal loss in injured brain regions. Thus, our findings bring to light the possibility that energy failure-induced Ape1 depletion triggers neuronal death in ischemic brain injuries. PMID:22841870

  2. Apurinic/Apyrimidinic Endonuclease/Redox Factor-1 (APE1/Ref-1) Redox Function Negatively Regulates NRF2*

    PubMed Central

    Fishel, Melissa L.; Wu, Xue; Devlin, Cecilia M.; Logsdon, Derek P.; Jiang, Yanlin; Luo, Meihua; He, Ying; Yu, Zhangsheng; Tong, Yan; Lipking, Kelsey P.; Maitra, Anirban; Rajeshkumar, N. V.; Scandura, Glenda; Kelley, Mark R.; Ivan, Mircea

    2015-01-01

    Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) (henceforth referred to as Ref-1) is a multifunctional protein that in addition to its base excision DNA repair activity exerts redox control of multiple transcription factors, including nuclear factor κ-light chain enhancer of activated B cells (NF-κB), STAT3, activator protein-1 (AP-1), hypoxia-inducible factor-1 (HIF-1), and tumor protein 53 (p53). In recent years, Ref-1 has emerged as a promising therapeutic target in cancer, particularly in pancreatic ductal carcinoma. Although a significant amount of research has centered on Ref-1, no wide-ranging approach had been performed on the effects of Ref-1 inhibition and transcription factor activity perturbation. Starting with a broader approach, we identified a previously unsuspected effect on the nuclear factor erythroid-related factor 2 (NRF2), a critical regulator of cellular defenses against oxidative stress. Based on genetic and small molecule inhibitor-based methodologies, we demonstrated that repression of Ref-1 potently activates NRF2 and its downstream targets in a dose-dependent fashion, and that the redox, rather than the DNA repair function of Ref-1 is critical for this effect. Intriguingly, our results also indicate that this pathway does not involve reactive oxygen species. The link between Ref-1 and NRF2 appears to be present in all cells tested in vitro, noncancerous and cancerous, including patient-derived tumor samples. In particular, we focused on understanding the implications of the novel interaction between these two pathways in primary pancreatic ductal adenocarcinoma tumor cells and provide the first evidence that this mechanism has implications for overcoming the resistance against experimental drugs targeting Ref-1 activity, with clear translational implications. PMID:25492865

  3. Apurinic/apyrimidinic endonuclease 1, p53, and thioredoxin are linked in control of aging in C. elegans.

    PubMed

    Schlotterer, Andreas; Hamann, Andreas; Kukudov, Georgi; Ibrahim, Youssef; Heckmann, Britta; Bozorgmehr, Farastuk; Pfeiffer, Michael; Hutter, Harald; Stern, David; Du, Xueliang; Brownlee, Michael; Bierhaus, Angelika; Nawroth, Peter; Morcos, Michael

    2010-06-01

    Deletions in mitochondrial DNA (mtDNA) accumulate during aging. Expression of the Caenorhabditis elegans apurinic/apyrimidinic endonuclease 1 (APE1) ortholog exo-3, involved in DNA repair, is reduced by 45% (P < 0.05) during aging of C. elegans. Suppression of exo-3 by treatment with RNAi resulted in a threefold increase in mtDNA deletions (P < 0.05), twofold enhanced generation of reactive oxygen species (ROS) (P < 0.01), distortion of the structural integrity of the nervous system, reduction of head motility by 43% (P < 0.01) and whole animal motility by 38% (P < 0.05). Suppression of exo-3 significantly reduced life span: mean life span decreased from 18.5 +/- 0.4 to 15.4 +/- 0.1 days (P < 0.001) and maximum life span from 25.9 +/- 0.4 to 23.2 +/- 0.1 days (P = 0.001). Additional treatment of exo-3-suppressed animals with a mitochondrial uncoupler decreased ROS levels, reduced neuronal damage, and increased motility and life span. Additional suppression of the C. elegans p53 ortholog cep-1 in exo-3 RNAi-treated animals similarly decreased ROS levels, preserved neuronal integrity, and increased motility and life span. In wild-type animals, suppression of cep-1, involved in downregulation of exo-3, increased expression of exo-3 without a significant effect on ROS levels, preserved neuronal integrity, and increased motility and life span. Suppression of the C. elegans thioredoxin orthologs trx-1 and trx-2, involved in the redox chaperone activity of exo-3, overrides the protective effect of cep-1 RNAi treatment on neuronal integrity, neuronal function, mean and maximum life span. These results show that APE1/EXO-3, p53/CEP-1, and thioredoxin affect each other and that these interactions determine aging as well as neuronal structure and function. PMID:20346071

  4. Energy conserving site design case study: Shenandoah, Georgia. Final report

    SciTech Connect

    Not Available

    1980-01-01

    The case study examines the means by which energy conservation can be achieved at an aggregate community level by using proper planning and analytical techniques for a new town, Shenandoah, Georgia, located twenty-five miles southwest of Atlanta's Hartsfield International Airport. A potentially implementable energy conservation community plan is achieved by a study team examining the land use options, siting characteristics of each building type, alternate infrastructure plans, possible decentralized energy options, and central utility schemes to determine how community energy conservation can be achieved by use of pre-construction planning. The concept for the development of mixed land uses as a passively sited, energy conserving community is based on a plan (Level 1 Plan) that uses the natural site characteristics, maximizes on passive energy siting requirement, and allows flexibility for the changing needs of the developers. The Level 2 Plan is identical with Level 1 plan plus a series of decentraized systems that have been added to the residential units: the single-family detached, the apartments, and the townhouses. Level 3 Plan is similar to the Level 1 Plan except that higher density dwellings have been moved to areas adjacent to central site. The total energy savings for each plan relative to the conventional plan are indicated. (MCW)

  5. ARAC`s site workstation final design and deployment

    SciTech Connect

    Abriam, R.O.; Moore, R.M.

    1994-08-01

    The Atmospheric Release Advisory Capability (ARAC) Center located at Lawrence Livermore National Laboratory, provides real-time estimates of the environmental consequences of accidental releases of radioactivity or other hazardous materials into the atmosphere anywhere in the world. ARAC`s expertise includes integrating a suite of local, regional and global dispersion models into a highly automated system. Since 1979, on-site computers have provided the link between DOE and DOD facilities around the U.S. and the ARAC Center. Beginning in 1993, these facilities have been replacing their personal computers with UNIX workstations running ARAC`s Site Workstation Systems (SWS) software. The SWS consists of a collection of applications that help sites prepare for and respond to incidents involving an atmospheric release. The SWS can be used either as a real-time emergency-response tool or to make historical or hypothetical assessments of releases.

  6. Site-specific design of the super collider in Texas

    SciTech Connect

    Laughton, C.; Nelson, P.P.; Lundin, T.K.

    1990-06-01

    This paper will outline the scope of the Superconducting Super Collider (SSC), underground works and present the current accelerator layout. After a brief overview of the site geotechnical characteristics, emphasis will be placed upon the possibilities for the incorporation of mechanical excavation technology into the construction of the various underground structures. 5 figs.

  7. PERFORMANCE METRICS FOR LANDSCAPE DESIGN: ASSESSING THE SUSTAINABLE SITES INITIATIVE

    EPA Science Inventory

    The research is expected to confirm the efficacy of the SITES program by verifying that projects ranked higher in program have a smaller carbon and water footprint than those that score lower. It is further expected to confirm the appropriate allocation of credits within th...

  8. Restructuring Web Site Design: An Alternative to WebTeams.

    ERIC Educational Resources Information Center

    Davis, Marc; Boyer, Janice

    In July 1997, the University Library at the University of Nebraska at Omaha adopted a new structural model for Web site development--the publishing metaphor. Rather than relying on an individual expert (the Webmaster) or a WebTeam comprised of a few individuals, the model permits everyone in the organization, regardless of position or Web…

  9. Optimising Web Site Designs for People with Learning Disabilities

    ERIC Educational Resources Information Center

    Williams, Peter; Hennig, Christian

    2015-01-01

    Much relevant internet-mediated information is inaccessible to people with learning disabilities because of difficulties in navigating the web. This paper reports on the methods undertaken to determine how information can be optimally presented for this cohort. Qualitative work is outlined where attributes relating to site layout affecting…

  10. 7 CFR Exhibit B to Subpart C of... - Site Development Design Requirements

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Site Development Design Requirements B Exhibit B to... OF AGRICULTURE PROGRAM REGULATIONS CONSTRUCTION AND REPAIR Planning and Performing Site Development Work Pt. 1924, Subpt. C, Exh. B Exhibit B to Subpart C of Part 1924—Site Development...

  11. 7 CFR Exhibit B to Subpart C of... - Site Development Design Requirements

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 12 2013-01-01 2013-01-01 false Site Development Design Requirements B Exhibit B to... OF AGRICULTURE PROGRAM REGULATIONS CONSTRUCTION AND REPAIR Planning and Performing Site Development Work Pt. 1924, Subpt. C, Exh. B Exhibit B to Subpart C of Part 1924—Site Development...

  12. 7 CFR Exhibit B to Subpart C of... - Site Development Design Requirements

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Site Development Design Requirements B Exhibit B to... OF AGRICULTURE PROGRAM REGULATIONS CONSTRUCTION AND REPAIR Planning and Performing Site Development Work Pt. 1924, Subpt. C, Exh. B Exhibit B to Subpart C of Part 1924—Site Development...

  13. 7 CFR Exhibit B to Subpart C of... - Site Development Design Requirements

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Site Development Design Requirements B Exhibit B to... OF AGRICULTURE PROGRAM REGULATIONS CONSTRUCTION AND REPAIR Planning and Performing Site Development Work Pt. 1924, Subpt. C, Exh. B Exhibit B to Subpart C of Part 1924—Site Development...

  14. 78 FR 38672 - Ocean Dumping; Sabine-Neches Waterway (SNWW) Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-27

    ...The EPA is proposing to designate four new Ocean Dredged Material Disposal Site(s) (ODMDS) located offshore of Texas for the disposal of dredged material from the Sabine-Neches Waterway (SNWW), pursuant to the Marine Protection, Research and Sanctuaries Act, as amended (MPRSA). The new sites are needed for the disposal of additional dredged material associated with the SNWW Channel Improvement......

  15. Campus Demonstration Sites for Sustainable Systems and Design: Five "Creation" Stories.

    ERIC Educational Resources Information Center

    Jack, Kathy; Ihara, Dan, Ed.

    This paper provides a summary of the development and management of five campus demonstration sites designed to create harmony with natural systems and meet current student needs without compromising the needs of future generations. Information for each campus includes an overview of the site, project origins, the proposal and design process, the…

  16. 78 FR 37759 - Ocean Dumping; Atchafalaya-West Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ...: Comments. The comment period for the proposed rule and draft EIS published May 21, 2013 (78 FR 29687), is... AGENCY 40 CFR Part 228 Ocean Dumping; Atchafalaya-West Ocean Dredged Material Disposal Site Designation... designate the Atchafalaya-West Ocean Dredged Material Disposal Site pursuant to the draft EIS,...

  17. 24 CFR 3285.103 - Site suitability with design zone maps.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... maps. 3285.103 Section 3285.103 Housing and Urban Development Regulations Relating to Housing and Urban... Considerations § 3285.103 Site suitability with design zone maps. Prior to the initial installation of a new... indicated on the design zone maps provided with the home, are suitable for the site location where the...

  18. 24 CFR 3285.103 - Site suitability with design zone maps.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... maps. 3285.103 Section 3285.103 Housing and Urban Development Regulations Relating to Housing and Urban... Considerations § 3285.103 Site suitability with design zone maps. Prior to the initial installation of a new... indicated on the design zone maps provided with the home, are suitable for the site location where the...

  19. 24 CFR 3285.103 - Site suitability with design zone maps.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... maps. 3285.103 Section 3285.103 Housing and Urban Development Regulations Relating to Housing and Urban... Considerations § 3285.103 Site suitability with design zone maps. Prior to the initial installation of a new... indicated on the design zone maps provided with the home, are suitable for the site location where the...

  20. 24 CFR 3285.103 - Site suitability with design zone maps.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... maps. 3285.103 Section 3285.103 Housing and Urban Development Regulations Relating to Housing and Urban... Considerations § 3285.103 Site suitability with design zone maps. Prior to the initial installation of a new... indicated on the design zone maps provided with the home, are suitable for the site location where the...

  1. Roadmap for Integrating Sustainable Design into Site-Level Operations

    SciTech Connect

    Peterson, Keith L.; Dorsey, Judy A.

    2000-04-19

    Sustainable Design recognizes that products and processes are interdependent with the environmental, economic, and social systems surrounding them and implements measures to prevent an unsustainable compromise to these systems.

  2. Savannah River Site reactor hardware design modification study

    SciTech Connect

    Fisher, J.E.

    1990-03-01

    A study was undertaken to assess the merits of proposed design modifications to the SRS reactors. The evaluation was based on the responses calculated by the RELAP5 systems code to double-ended guillotine break loss-of-coolant-accidents (DEGB LOCAs). The three concepts evaluated were (a) elevated plenum inlet piping with a guard vessel and clamshell enclosures, (b) closure of both rotovalves in the affected loop, and (c) closure of the pump suction valve in the affected loop. Each concept included a fast reactor shutdown (to 65% power in 100 ms) and a 2-s ac pump trip. For the elevated piping design, system recovery was predicted for breaks in the plenum inlet or pump suction piping; response to the pump discharge break location did not show improvement compared to the present system configuration. The rotovalve closure design improved system response to plenum inlet or pump discharge breaks; recovery was not predicted for pump suction breaks. The pump suction valve closure design demonstrated system recovery for all break locations downstream of the valve. A combination of features is recommended to ensure liquid inventory recovery for all break locations. The elevated piping design performance during pump discharge breaks would be improved with addition of a dc pump trip in the affected loop. Valve closure design performance for a break location in the short section of piping between the reactor concrete shield and the pump suction valve would benefit from the clamshell enclosing that section of piping. 12 refs., 10 figs., 2 tabs.

  3. Machine performance and site disturbance in skidding on designated trails

    SciTech Connect

    Olsen, E.D.; Seifert, J.C.W.

    1984-01-01

    Overstorey trees (predominantly western red cedar Thuja plicata) in a stand in Idaho were removed in 1981 using 4 machines and 2 methods: skidding whole trees on undesignated trails; and skidding tree lengths on trails designated in advance. A caterpillar 518 rubber-tyred skidder (RTS) handling whole trees on undesignated trails had the lowest cost and the highest production. An FMC 200 CA torsion-bar track machine (low ground pressure) was the most expensive because of high initial and operating costs, and high incidence of breakdowns. A caterpillar D6D rigid track, medium-horsepower crawler and an international TD-8E rigid track, low-horsepower crawler were intermediate in cost. Output was generally increased when tree lengths were skidded on designated trails. Again the RTS had the lowest cost, and the highest production on haulage distances up to about 900 feet. For longer haulage distances, the D6D hauled more tree-length logs on designated skid trails. For all machine types, 17% of the area of conventionally logged whole tree units and 9% of the units where tree-length logs were skidded on designated trails were calculated to be occupied by roads. Trail designation reduced machine damage to regeneration by about 5%. 3 references.

  4. Synthesis, thermal stability and reactivity towards 9-aminoellipticine of double-stranded oligonucleotides containing a true abasic site.

    PubMed Central

    Bertrand, J R; Vasseur, J J; Rayner, B; Imbach, J L; Paoletti, J; Paoletti, C; Malvy, C

    1989-01-01

    A 13 mers abasic oligonucleotide was synthetized. It was therefore possible to compare thermal stability and reactivity of duplex oligonucleotides either with an apurinic/apyrimidinic site or without any lesion. An important decrease in the melting temperature appeared for duplexes with an abasic site. The chemical reaction of these modified oligonucleotides with the intercalating agent 9-aminoellipticine was studied by gel electrophoresis and by fluorescence. The formation of a Schiff base between 9-aminoellipticine and abasic sites was rapid and complete with duplexes at 11 degrees C. Schiff base related fluorescence and beta-elimination cleavage were more important with the apyrimidinic sites than with the apurinic ones. When compared to previous results obtained with the model d(TprpT) some unexpected behaviours appeared with longer and duplex oligonucleotides. For instance only partial beta-elimination cleavage was observed. It is likely that stacking parameters in the double helix play a great role in the studied reaction. Images PMID:2602153

  5. HYNOL PROCESS ENGINEERING: PROCESS CONFIGURATION, SITE PLAN, AND EQUIPMENT DESIGN

    EPA Science Inventory

    The report describes the design of the hydropyrolysis reactor system of the Hynol process. (NOTE: A bench scale methanol production facility is being constructed to demonstrate the technical feasibility of producing methanol from biomass using the Hynol process. The plant is bein...

  6. The Role of Identity and Culture on Web Site Design

    ERIC Educational Resources Information Center

    Eugene, Wanda; Clark, Kevin

    2009-01-01

    Purpose: The purpose of this paper is to outline an instructional design approach for further development of an African ancestry learning center in order to enhance its educational utility. This is being done in an effort to use technology in transformative ways that extends the practices and opportunities for African Americans.…

  7. Prognostic Significance of Human Apurinic/Apyrimidinic Endonuclease (APE/Ref-1) Expression in Rectal Cancer Treated With Preoperative Radiochemotherapy

    SciTech Connect

    Kim, Jun-Sang; Kim, Jin-Man; Liang, Zhe Long; Jang, Ji Young; Kim, Sup; Huh, Gil Ja; Kim, Ki-Hwan; Cho, Moon-June

    2012-01-01

    Purpose: Human apurinic endonuclease/redox factor 1 (APE/Ref-1) mediates repair of radiation-induced DNA lesions and regulates transcription via redox-based activation. We investigated the predictive and prognostic significance of APE/Ref-1 expression in pretreatment biopsy specimens in locally advanced rectal cancer (LARC) (cT3-T4 or N+). Methods and Materials: APE/Ref-1 expression was analyzed by immunohistochemistry in pretreatment biopsy specimens obtained from 83 patients with LARC. Patients received preoperative radiotherapy of 50.4 Gy in 28 fractions, combined with oral capecitabine and leucovorin chemotherapy, followed by curative surgery. The prognostic significance of various clinicopathologic characteristics, including APE/Ref-1 protein expression, was evaluated. Results: APE/Ref-1 was expressed in 97% of patient samples. Exclusive APE/Ref-1 nuclear staining was observed in 49 of 83 samples (59%), and mixed nuclear and cytoplasmic staining was observed in 31 samples (37%). APE/Ref-1 nuclear expression levels were low in 49 patients (59%) and high in 34 patients (41%). The level of APE/Ref-1 nuclear expression was not a prognostic factor for overall and disease-free survival. Cytoplasmic expression of APE/Ref-1 was a borderline-significant predictive factor for pathologic tumor response (p = 0.08) and a significant prognostic factor for disease-free survival, as shown by univariate analysis (p = 0.037). Multivariate analysis confirmed that cytoplasmic localization of APE/Ref-1 is a significant predictor of disease-free survival (hazard ratio, 0.45; p = 0.046). Conclusions: APE/Ref-1 was expressed in a majority of pretreatment biopsy specimens from patients with LARC. The level of APE/Ref-1 nuclear expression was not a significant predictive and prognostic factor; however, cytoplasmic localization of the protein was negatively associated with disease-free survival. These results indicate that cytoplasmic expression of APE/Ref-1 represents an adverse

  8. 41 CFR 102-76.20 - What issues must Federal agencies consider in providing site planning and landscape design services?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... agencies consider in providing site planning and landscape design services? 102-76.20 Section 102-76.20... What issues must Federal agencies consider in providing site planning and landscape design services? In providing site planning and design services, Federal agencies must— (a) Make the site planning and...

  9. 41 CFR 102-76.20 - What issues must Federal agencies consider in providing site planning and landscape design services?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... agencies consider in providing site planning and landscape design services? 102-76.20 Section 102-76.20... What issues must Federal agencies consider in providing site planning and landscape design services? In providing site planning and design services, Federal agencies must— (a) Make the site planning and...

  10. 41 CFR 102-76.20 - What issues must Federal agencies consider in providing site planning and landscape design services?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... agencies consider in providing site planning and landscape design services? 102-76.20 Section 102-76.20... What issues must Federal agencies consider in providing site planning and landscape design services? In providing site planning and design services, Federal agencies must— (a) Make the site planning and...

  11. 41 CFR 102-76.20 - What issues must Federal agencies consider in providing site planning and landscape design services?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... agencies consider in providing site planning and landscape design services? 102-76.20 Section 102-76.20... What issues must Federal agencies consider in providing site planning and landscape design services? In providing site planning and design services, Federal agencies must— (a) Make the site planning and...

  12. 41 CFR 102-76.20 - What issues must Federal agencies consider in providing site planning and landscape design services?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... agencies consider in providing site planning and landscape design services? 102-76.20 Section 102-76.20... What issues must Federal agencies consider in providing site planning and landscape design services? In providing site planning and design services, Federal agencies must— (a) Make the site planning and...

  13. 78 FR 29687 - Ocean Dumping; Atchafalaya-West Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-21

    ... permits. Pursuant to its voluntary NEPA policy, published at 63 FR 58045 (October 29, 1998), EPA typically... designation through a rulemaking proposal published in the Federal Register (FR), as here. Formal designation... EPA will, wherever feasible, designate ocean dumping sites beyond the edge of the continental...

  14. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Tuba City, Arizona

    SciTech Connect

    Not Available

    1989-08-01

    This Remedial Action Plan (RAP) has been developed to serve a threefold purpose. It presents the series of activities which are proposed by the US Department of Energy (DOE) to accomplish long-term stabilization and control of radioactive materials at the inactive uranium processing site near Tuba City, Arizona. It provides a characterization of the present conditions of the site. It also serves to document the concurrence of the Navajo Nation, the Hopi Tribe, US Bureau of Indian Affairs (BIA), and the US Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by DOE, the Navajo Nation, and the Hopi Tribe, and concurrence by NRC, becomes Appendix B of the Cooperative Agreement. Following the introduction, contents are as follows: Section 2.0 presents the EPA standards, including a discussion of their objectives. Section 3.0 summarizes the present site characteristics and provides a definition of site-specific problems. Section 4.0 is the site design for the proposed action. Section 5.0 summarizes the plan for ensuring environmental, health, and safety protection for the surrounding community and the on-site workers. Section 6.0 presents a detailed listing of the responsibilities of the project participants. Section 7.0 describes the features of the long-term surveillance and maintenance plan. Section 8.0 presents the quality assurance aspects of the project. Section 9.0 documents the ongoing activities to keep the public informed and participating in the project.

  15. Title I conceptual design for Pit 6 landfill closure at Lawrence Livermore National Laboratory Site 300

    SciTech Connect

    MacDonnell, B.A.; Obenauf, K.S.

    1996-08-01

    The objective of this design project is to evaluate and prepare design and construction documents for a closure cover cap for the Pit 6 Landfill located at Lawrence Livermore National Laboratory Site 300. This submittal constitutes the Title I Design (Conceptual Design) for the closure cover of the Pit 6 Landfill. A Title I Design is generally 30 percent of the design effort. Title H Design takes the design to 100 percent complete. Comments and edits to this Title I Design will be addressed in the Title II design submittal. Contents of this report are as follows: project background; design issues and engineering approach; design drawings; calculation packages; construction specifications outline; and construction quality assurance plan outline.

  16. NGA-West 2 GMPE average site coefficients for use in earthquake-resistant design

    USGS Publications Warehouse

    Borcherdt, Roger D.

    2015-01-01

    Site coefficients corresponding to those in tables 11.4–1 and 11.4–2 of Minimum Design Loads for Buildings and Other Structures published by the American Society of Civil Engineers (Standard ASCE/SEI 7-10) are derived from four of the Next Generation Attenuation West2 (NGA-W2) Ground-Motion Prediction Equations (GMPEs). The resulting coefficients are compared with those derived by other researchers and those derived from the NGA-West1 database. The derivation of the NGA-W2 average site coefficients provides a simple procedure to update site coefficients with each update in the Maximum Considered Earthquake Response MCER maps. The simple procedure yields average site coefficients consistent with those derived for site-specific design purposes. The NGA-W2 GMPEs provide simple scale factors to reduce conservatism in current simplified design procedures.

  17. Proteus and the Design of Ligand Binding Sites.

    PubMed

    Polydorides, Savvas; Michael, Eleni; Mignon, David; Druart, Karen; Archontis, Georgios; Simonson, Thomas

    2016-01-01

    This chapter describes the organization and use of Proteus, a multitool computational suite for the optimization of protein and ligand conformations and sequences, and the calculation of pK α shifts and relative binding affinities. The software offers the use of several molecular mechanics force fields and solvent models, including two generalized Born variants, and a large range of scoring functions, which can combine protein stability, ligand affinity, and ligand specificity terms, for positive and negative design. We present in detail the steps for structure preparation, system setup, construction of the interaction energy matrix, protein sequence and structure optimizations, pK α calculations, and ligand titration calculations. We discuss illustrative examples, including the chemical/structural optimization of a complex between the MHC class II protein HLA-DQ8 and the vinculin epitope, and the chemical optimization of the compstatin analog Ac-Val4Trp/His9Ala, which regulates the function of protein C3 of the complement system. PMID:27094287

  18. Comment and response document for the final remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Slick Rock, Colorado. Revision 2

    SciTech Connect

    1996-05-01

    This document for the final remedial action plan and site design has been prepared for US Department of Energy Environmental Restoration Division as part of the Uranium Mill Tailings Remedial Action plan. Comments and responses are included for the site design for stabilization of the inactive uranium mill tailings sites at Slick Rock, Colorado.

  19. Impact of Binding Site Comparisons on Medicinal Chemistry and Rational Molecular Design.

    PubMed

    Ehrt, Christiane; Brinkjost, Tobias; Koch, Oliver

    2016-05-12

    Modern rational drug design not only deals with the search for ligands binding to interesting and promising validated targets but also aims to identify the function and ligands of yet uncharacterized proteins having impact on different diseases. Additionally, it contributes to the design of inhibitors with distinct selectivity patterns and the prediction of possible off-target effects. The identification of similarities between binding sites of various proteins is a useful approach to cope with those challenges. The main scope of this perspective is to describe applications of different protein binding site comparison approaches to outline their applicability and impact on molecular design. The article deals with various substantial application domains and provides some outstanding examples to show how various binding site comparison methods can be applied to promote in silico drug design workflows. In addition, we will also briefly introduce the fundamental principles of different protein binding site comparison methods. PMID:27046190

  20. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Rifle, Colorado

    SciTech Connect

    Not Available

    1990-02-01

    This document has been structured to provide a comprehensive understanding of the remedial action proposed for the Rifle sites. That remedial action consists of removing approximately 4,185,000 cubic yards (cy) of tailings and contaminated materials from their current locations, transporting, and stabilizing the tailings material at the Estes Gulch disposal site, approximately six miles north of Rifle. The tailings and contaminated materials are comprised of approximately 597,000 cy from Old Rifle, 3,232,000 cy from New Rifle, and 322,000 cy from vicinity properties and about 34,000 cy from demolition. The remedial action plan includes specific design requirements for the detailed design and construction of the remedial action. An extensive amount of data and supporting information have been generated for this remedial action and cannot all be incorporated into this document. Pertinent information and data are included with reference given to the supporting documents.

  1. The Role of Virtual Reference in Library Web Site Design: A Qualitative Source for Usage Data

    ERIC Educational Resources Information Center

    Powers, Amanda Clay; Shedd, Julie; Hill, Clay

    2011-01-01

    Gathering qualitative information about usage behavior of library Web sites is a time-consuming process requiring the active participation of patron communities. Libraries that collect virtual reference transcripts, however, hold valuable data regarding how the library Web site is used that could benefit Web designers. An analysis of virtual…

  2. The Path to Graduation: A Model Interactive Web Site Design Supporting Doctoral Students

    ERIC Educational Resources Information Center

    Simmons-Johnson, Nicole

    2012-01-01

    Objective. This 2-phase mixed method study assessed 2nd-year doctoral students' and dissertation students' perceptions of the current Graduate School of Education dissertation support Web site, with implications for designing a model dissertation support Web site. Methods. Phase 1 collected quantitative and qualitative data through an…

  3. Site-specific control of silica mineralization on DNA using a designed peptide.

    PubMed

    Ozaki, Makoto; Nagai, Kazuma; Nishiyama, Hiroto; Tsuruoka, Takaaki; Fujii, Satoshi; Endoh, Tamaki; Imai, Takahito; Tomizaki, Kin-Ya; Usui, Kenji

    2016-03-01

    We developed a site-specific method for precipitating inorganic compounds using organic compounds, DNA, and designed peptides with peptide nucleic acids (PNAs). Such a system for site-specific precipitation represents a powerful tool for use in nanobiochemistry and materials chemistry. PMID:26690695

  4. Cross-site studies "by design:" Experiments and observations that provide new insights

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cross-site comparisons presented in the previous chapters are all conducted after the individual studies are completed. The differences in experimental design in individual studies in a posteriori cross-site studies limit the scope of questions that can be addressed, and the powerfulness and co...

  5. A Checklist for Designing and Evaluating Physical Education Program Web Sites

    ERIC Educational Resources Information Center

    Tucker, Michael; Hill, Grant

    2009-01-01

    Creating a physical education department web site is an excellent way to promote a positive image of the program, because students and parents are able to find important information and improve the lines of communication. A well-designed physical education web site can even encourage students to increase their physical activity levels. Improved…

  6. Sharing Designer and User Perspectives of Web Site Evaluation: A Cross-Campus Collaborative Learning Experience.

    ERIC Educational Resources Information Center

    Collings, Penny; Pearce, Jon

    2002-01-01

    Presents an online collaborative process that facilitates usability evaluation of Web sites. Describes how the system was designed and used by students and staff at two Australian universities and shows that the process provides feedback on Web site usability and the experience of usability evaluation from the perspectives of a user and a…

  7. Design Insights and Inspiration from the Tate: What Museum Web Sites Can Offer Us

    ERIC Educational Resources Information Center

    Riley-Huff, Debra A.

    2009-01-01

    There are many similarities between museums and academic libraries as public service institutions. This article is an examination of museum Web site practices and concepts that might also be transferable to academic library Web sites. It explores the digital manifestations of design and information presentation, user engagement, interactivity, and…

  8. Remedial Action Plan and site conceptual design for stabilization of the inactive uranium mill tailings site at Shiprock, New Mexico

    SciTech Connect

    Hill, T.V.; Morley, J.A. . Uranium Mill Tailings Remedial Action Project Office); Began, E.T. )

    1985-06-01

    This Remedial Action Plan (RAP) has been developed to serve a twofold purpose. It presents the series of activities which are proposed by the Department of Energy (DOE) to effect long-term control of radioactive materials at the inactive uranium processing site located on the Navajo Reservation at Shiprock, New Mexico. It also serves to document the concurrence of both the Navajo Nation and the Nuclear Regulatory Commission (NRC) in the remedial action. This document has been structured to provide a comprehensive understanding of the remedial action proposed for the Shiprock site. Detailed supporting information can be found in appendices and referenced documents. Section 2.0 presents the EPA standards, including a discussion of their objectives. Section 3.0 traces the history of operations at the Shiprock site with a description of the present site characteristics. Section 4.0 provides a definition of site-specific problems, a listing of remedial action alternatives which have been considered, and the action which is being proposed. Section 5.0 presents a summary of the conceptual design for the proposed action which includes objectives, design features, schedule, cost, and implementation methods. Section 6.0 summarizes the plan for ensuring health and safety protection for the surrounding community and the onsite workers. Section 7.0 presents a detailed listing of the responsibilities of the project participants. Section 8.0 describes the quality assurance process that will be used by the RAC during construction. Section 9.0 describes the features of the long-term maintenance and surveillance plan. Section 10.0 documents the on-going activities to keep the public informed and participating in the project. Attached as part of the RAP are five appendices which describe in more detail various aspects of the remedial action.

  9. A usability evaluation exploring the design of American Nurses Association state web sites.

    PubMed

    Alexander, Gregory L; Wakefield, Bonnie J; Anbari, Allison B; Lyons, Vanessa; Prentice, Donna; Shepherd, Marilyn; Strecker, E Bradley; Weston, Marla J

    2014-08-01

    National leaders are calling for opportunities to facilitate the Future of Nursing. Opportunities can be encouraged through state nurses association Web sites, which are part of the American Nurses Association, that are well designed, with appropriate content, and in a language professional nurses understand. The American Nurses Association and constituent state nurses associations provide information about nursing practice, ethics, credentialing, and health on Web sites. We conducted usability evaluations to determine compliance with heuristic and ethical principles for Web site design. We purposefully sampled 27 nursing association Web sites and used 68 heuristic and ethical criteria to perform systematic usability assessments of nurse association Web sites. Web site analysis included seven double experts who were all RNs trained in usability analysis. The extent to which heuristic and ethical criteria were met ranged widely from one state that met 0% of the criteria for "help and documentation" to states that met greater than 92% of criteria for "visibility of system status" and "aesthetic and minimalist design." Suggested improvements are simple yet make an impact on a first-time visitor's impression of the Web site. For example, adding internal navigation and tracking features and providing more details about the application process through help and frequently asked question documentation would facilitate better use. Improved usability will improve effectiveness, efficiency, and consumer satisfaction with these Web sites. PMID:24818790

  10. 10 CFR 433.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Sustainable principles for siting, design and construction. 433.6 Section 433.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS FOR THE DESIGN AND CONSTRUCTION OF NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH-RISE RESIDENTIAL...

  11. 10 CFR 433.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Sustainable principles for siting, design and construction. 433.6 Section 433.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS FOR THE DESIGN AND CONSTRUCTION OF NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH-RISE RESIDENTIAL...

  12. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Rifle, Colorado. Volume 2, Appendices D and E: Final report

    SciTech Connect

    Not Available

    1992-02-01

    This appendix assesses the present conditions and data gathered about the two inactive uranium mill tailings sites near Rifle, Colorado, and the designated disposal site six miles north of Rifle in the area of Estes Gulch. It consolidates available engineering, radiological, geotechnical, hydrological, meteorological, and other information pertinent to the design of the Remedial Action Plan (RAP). The data characterize conditions at the mill, tailings, and disposal site so that the Remedial Action Contractor (RAC) may complete final designs for the remedial actions.

  13. National Ignition Facility subsystem design requirements NIF site improvements SSDR 1.2.1

    SciTech Connect

    Kempel, P.; Hands, J.

    1996-08-19

    This Subsystem Design Requirements (SSDR) document establishes the performance, design, and verification requirements associated with the NIF Project Site at Lawrence Livermore National Laboratory (LLNL) at Livermore, California. It identifies generic design conditions for all NIF Project facilities, including siting requirements associated with natural phenomena, and contains specific requirements for furnishing site-related infrastructure utilities and services to the NIF Project conventional facilities and experimental hardware systems. Three candidate sites were identified as potential locations for the NIF Project. However, LLNL has been identified by DOE as the preferred site because of closely related laser experimentation underway at LLNL, the ability to use existing interrelated infrastructure, and other reasons. Selection of a site other than LLNL will entail the acquisition of site improvements and infrastructure additional to those described in this document. This SSDR addresses only the improvements associated with the NIF Project site located at LLNL, including new work and relocation or demolition of existing facilities that interfere with the construction of new facilities. If the Record of Decision for the PEIS on Stockpile Stewardship and Management were to select another site, this SSDR would be revised to reflect the characteristics of the selected site. Other facilities and infrastructure needed to support operation of the NIF, such as those listed below, are existing and available at the LLNL site, and are not included in this SSDR. Office Building. Target Receiving and Inspection. General Assembly Building. Electro- Mechanical Shop. Warehousing and General Storage. Shipping and Receiving. General Stores. Medical Facilities. Cafeteria services. Service Station and Garage. Fire Station. Security and Badging Services.

  14. Study of seismic design bases and site conditions for nuclear power plants

    SciTech Connect

    Not Available

    1980-04-01

    This report presents the results of an investigation of four topics pertinent to the seismic design of nuclear power plants: Design accelerations by regions of the continental United States; review and compilation of design-basis seismic levels and soil conditions for existing nuclear power plants; regional distribution of shear wave velocity of foundation materials at nuclear power plant sites; and technical review of surface-founded seismic analysis versus embedded approaches.

  15. 75 FR 19311 - Ocean Dumping; Guam Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-14

    ...The EPA is proposing to designate the Guam Deep Ocean Disposal Site (G-DODS) as a permanent ocean dredged material disposal site (ODMDS) located offshore of Guam. Dredging is essential for maintaining safe navigation at port and naval facilities in Apra Harbor and other locations around Guam. Not all dredged materials are suitable for beneficial re-use (e.g., construction materials, landfill......

  16. Aerosol measurements at the Southern Great Plains Site: Design and surface installation

    SciTech Connect

    Leifer, R.; Knuth, R.H.; Guggenheim, S.F.; Albert, B.

    1996-04-01

    To impropve the predictive capabilities of the Atmospheric Radiation Measurements (ARM) program radiation models, measurements of awserosol size distributions, condensation particle concentrations, aerosol scattering coefficients at a number of wavelenghts, and the aerosol absorption coefficients are needed at the Southern Great Plains (SGP) site. Alos, continuous measurements of ozone concnetrations are needed for model validation. The environmental Measuremenr Laboratory (EMK) has the responsibility to establish the surface aerosol measurements program at the SGP site. EML has designed a special sampling manifold.

  17. Are Biophilic-Designed Site Office Buildings Linked to Health Benefits and High Performing Occupants?

    PubMed Central

    Gray, Tonia; Birrell, Carol

    2014-01-01

    This paper discusses the first phase of a longitudinal study underway in Australia to ascertain the broad health benefits of specific types of biophilic design for workers in a building site office. A bespoke site design was formulated to include open plan workspace, natural lighting, ventilation, significant plants, prospect and views, recycled materials and use of non-synthetic materials. Initial data in the first three months was gathered from a series of demographic questions and from interviews and observations of site workers. Preliminary data indicates a strong positive effect from incorporating aspects of biophilic design to boost productivity, ameliorate stress, enhance well-being, foster a collaborative work environment and promote workplace satisfaction, thus contributing towards a high performance workspace. The longitudinal study spanning over two years will track human-plant interactions in a biophilic influenced space, whilst also assessing the concomitant cognitive, social, psychological and physical health benefits for workers. PMID:25431874

  18. Design and control strategy for a hybrid green energy system for mobile telecommunication sites

    NASA Astrophysics Data System (ADS)

    Okundamiya, Michael S.; Emagbetere, Joy O.; Ogujor, Emmanuel A.

    2014-07-01

    The rising energy costs and carbon footprint of operating mobile telecommunication sites in the emerging world have increased research interests in green technology. The intermittent nature of most green energy sources creates the problem of designing the optimum configuration for a given location. This study presents the design analysis and control strategy for a cost effective and reliable operation of the hybrid green energy system (HGES) for GSM base transceiver station (BTS) sites in isolated regions. The design constrains the generation and distribution of power to reliably satisfy the energy demand while ensuring safe operation of the system. The overall process control applies the genetic algorithm-based technique for optimal techno-economic sizing of system's components. The process simulation utilized meteorological data for 3 locations (Abuja, Benin City and Sokoto) with varying climatic conditions in Nigeria. Simulation results presented for green GSM BTS sites are discussed and compared with existing approaches.

  19. Remedial action plan and site design for stabilization of the inactive Uranium Mill Tailings Site at Lowman, Idaho

    SciTech Connect

    Not Available

    1991-09-01

    The DOE proposes to achieve compliance with the proposed EPA groundwater protection standards (Subparts A and B of 40 CFR 192) by meeting the EPA maximum concentration limits (MCLs) or background concentrations for designated hazardous constituents in groundwater in the uppermost aquifer (alluvium/weathered granodiorite) at the point of compliance (POC) at the Lowman disposal site near Lowman, Idaho. The proposed remedial action in conjunction with existing hydrogeological conditions at the Lowman site will ensure sufficient protection of human health and the environment. The DOE has concluded that the EPA groundwater protection standards will be met at the POC because, with the exception of antimony, none of the hazardous constituents that exceed laboratory method detection limits within the radioactive sand pore fluids were above the proposed concentration limits. The DOE has demonstrated that antimony will meet the proposed concentration limits at the POC through attenuation in subsoils beneath the disposal cell and by dilution in groundwater underflow. The Lowman processing site is in compliance with Subpart B of 40 CFR 192 because statistical analyses of groundwater samples indicate no groundwater contamination.

  20. Drift design methodology and preliminary application for the Yucca Mountain Site Characterization Project; Yucca Mountain Site Characterization Project

    SciTech Connect

    Hardy, M.P.; Bauer, S.J.

    1991-12-01

    Excavation stability in an underground nuclear waste repository is required during construction, emplacement, retrieval (if required), and closure phases to ensure worker health and safety, and to prevent development of potential pathways for radionuclide migration in the post-closure period. Stable excavations are developed by appropriate excavation procedures, design of the room shape, design and installation of rock support reinforcement systems, and implementation of appropriate monitoring and maintenance programs. In addition to the loads imposed by the in situ stress field, the repository drifts will be impacted by thermal loads developed after waste emplacement and, periodically, by seismic loads from naturally occurring earthquakes and underground nuclear events. A priori evaluation of stability is required for design of the ground support system, to confirm that the thermal loads are reasonable, and to support the license application process. In this report, a design methodology for assessing drift stability is presented. This is based on site conditions, together with empirical and analytical methods. Analytical numerical methods are emphasized at this time because empirical data are unavailable for excavations in welded tuff either at elevated temperatures or under seismic loads. The analytical methodology incorporates analysis of rock masses that are systematically jointed, randomly jointed, and sparsely jointed. In situ thermal and seismic loads are considered. Methods of evaluating the analytical results and estimating ground support requirements for all the full range of expected ground conditions are outlines. The results of a preliminary application of the methodology using the limited available data are presented. 26 figs., 55 tabs.

  1. Subsystem design package for Mod 2 site data acquisition system: Solar heating and cooling

    NASA Technical Reports Server (NTRS)

    1977-01-01

    The Mod II Site Data Acquisition Subsystem (SDAS) is designed to collect data from sensors located on residential or commercial buildings using a solar heating and/or cooling system. The SDAS takes the data obtained from sensors located on the solar heating and/or cooling system, processes the data into a suitable format, stores the data for a period of time, and provides the capability for both telephone retrieval by the Central Data Processing System (CDPS) and manual retrieval of the data for transfer to the central site. The unit is designed so it will not degrade the operation of the solar heating/cooling system which it is monitoring.

  2. System design package for solar heating and cooling site data acquisition subsystem

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The Site Data Acquisition Subsystem (SDAS) designed to collect data from sensors located on residential or commercial buildings using a solar heating and/or cooling system is described. It takes the data obtained from sensors located on the solar system, processes the data into suitable format, stores the data for a period of time, and provides the capability for either telephone retrieval by the central data processing system or manual retrieval of the data for transfer to a central site. The SDAS is also designed so that it will not degrade the operation of the solar heating/cooling system which it is monitoring.

  3. Compounds designed to fit a site of known structure in human haemoglobin.

    PubMed Central

    Beddell, C R; Goodford, P J; Norrington, F E; Wilkinson, S; Wootton, R

    1976-01-01

    1 The three-dimensional coordinates of the atoms in human haemoglobin are known, and there is a specific site in the deoxygenated form of the protein at which 2,3-diphosphoglycerate (DPG) interacts. 2 Molecular models of this site have been constructed and used to design compounds which should bind to the deoxy conformation and stabilize it. These compounds should therby promote oxygen liberation, as does DPG. 3The compounds so designed were found to promote oxygen liberation. Their relative potencies, as assessed by sigmoidal dose-response curves, are in the predicted sequence. PMID:938794

  4. Design and implementation of an identification system in construction site safety for proactive accident prevention.

    PubMed

    Yang, Huanjia; Chew, David A S; Wu, Weiwei; Zhou, Zhipeng; Li, Qiming

    2012-09-01

    Identifying accident precursors using real-time identity information has great potential to improve safety performance in construction industry, which is still suffering from day to day records of accident fatality and injury. Based on the requirements analysis for identifying precursor and the discussion of enabling technology solutions for acquiring and sharing real-time automatic identification information on construction site, this paper proposes an identification system design for proactive accident prevention to improve construction site safety. Firstly, a case study is conducted to analyze the automatic identification requirements for identifying accident precursors in construction site. Results show that it mainly consists of three aspects, namely access control, training and inspection information and operation authority. The system is then designed to fulfill these requirements based on ZigBee enabled wireless sensor network (WSN), radio frequency identification (RFID) technology and an integrated ZigBee RFID sensor network structure. At the same time, an information database is also designed and implemented, which includes 15 tables, 54 queries and several reports and forms. In the end, a demonstration system based on the proposed system design is developed as a proof of concept prototype. The contributions of this study include the requirement analysis and technical design of a real-time identity information tracking solution for proactive accident prevention on construction sites. The technical solution proposed in this paper has a significant importance in improving safety performance on construction sites. Moreover, this study can serve as a reference design for future system integrations where more functions, such as environment monitoring and location tracking, can be added. PMID:22664682

  5. Anatomy of protein pockets and cavities: measurement of binding site geometry and implications for ligand design.

    PubMed Central

    Liang, J.; Edelsbrunner, H.; Woodward, C.

    1998-01-01

    Identification and size characterization of surface pockets and occluded cavities are initial steps in protein structure-based ligand design. A new program, CAST, for automatically locating and measuring protein pockets and cavities, is based on precise computational geometry methods, including alpha shape and discrete flow theory. CAST identifies and measures pockets and pocket mouth openings, as well as cavities. The program specifies the atoms lining pockets, pocket openings, and buried cavities; the volume and area of pockets and cavities; and the area and circumference of mouth openings. CAST analysis of over 100 proteins has been carried out; proteins examined include a set of 51 monomeric enzyme-ligand structures, several elastase-inhibitor complexes, the FK506 binding protein, 30 HIV-1 protease-inhibitor complexes, and a number of small and large protein inhibitors. Medium-sized globular proteins typically have 10-20 pockets/cavities. Most often, binding sites are pockets with 1-2 mouth openings; much less frequently they are cavities. Ligand binding pockets vary widely in size, most within the range 10(2)-10(3)A3. Statistical analysis reveals that the number of pockets and cavities is correlated with protein size, but there is no correlation between the size of the protein and the size of binding sites. Most frequently, the largest pocket/cavity is the active site, but there are a number of instructive exceptions. Ligand volume and binding site volume are somewhat correlated when binding site volume is < or =700 A3, but the ligand seldom occupies the entire site. Auxiliary pockets near the active site have been suggested as additional binding surface for designed ligands (Mattos C et al., 1994, Nat Struct Biol 1:55-58). Analysis of elastase-inhibitor complexes suggests that CAST can identify ancillary pockets suitable for recruitment in ligand design strategies. Analysis of the FK506 binding protein, and of compounds developed in SAR by NMR (Shuker SB et

  6. 75 FR 54497 - Ocean Dumping; Guam Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-08

    ... Register (FR). Historically, dredged material generated around Guam by the Navy and the Port Authority of... will, wherever feasible, designate ocean dumping sites beyond the edge of the continental shelf and... continental land mass and does not have a continental shelf. In the ] absence of a shelf break,...

  7. 10 CFR 433.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Sustainable principles for siting, design and construction. 433.6 Section 433.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH-RISE RESIDENTIAL BUILDINGS § 433.6 Sustainable...

  8. 10 CFR 433.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Sustainable principles for siting, design and construction. 433.6 Section 433.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH-RISE RESIDENTIAL BUILDINGS § 433.6 Sustainable...

  9. DESIGN AND PERFORMANCE OF SINGLE-WELL TRACER TESTS AT THE MOBILE SITE

    EPA Science Inventory

    Tracer tests are the most reliable field methods for obtaining information describing advection and dispersion in aquifers. The paper describes the design and performance of single-well tracer tests utilizing multilevel observation wells at a field site near Mobile, Alabama. In a...

  10. Beyond the Design and Evaluation of Library Web Sites: An Analysis and Four Case Studies.

    ERIC Educational Resources Information Center

    Shropshire, Sandra

    2003-01-01

    Discusses Web site management, rather than design, as it relates to academic libraries. Reviews library literature as well as literature from other fields and presents results from four case studies that investigated staffing, professional rivalries, governing structure, usability studies, staff tool versus public resource, maintenance, and…

  11. 10 CFR 433.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Sustainable principles for siting, design and construction. 433.6 Section 433.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH-RISE RESIDENTIAL BUILDINGS § 433.6 Sustainable...

  12. Applying the Fundamentals of Librarianship to Technology: Designing and Maintaining Your Library's Web Site.

    ERIC Educational Resources Information Center

    Cooper, Eric A.

    1997-01-01

    Provides guidelines for designing Web sites: identify audience and information needs; make addresses easy to type and remember; consider audience software; keep files short and images to a minimum; categorize information for clarity; use clear contents statements; provide a mix of original documents and others located elsewhere; provide mechanisms…

  13. Understanding and Designing for Interactional Privacy Needs within Social Networking Sites

    ERIC Educational Resources Information Center

    Wisniewski, Pamela J.

    2012-01-01

    "Interpersonal boundary regulation" is a way to optimize social interactions when sharing and connecting through Social Networking Sites (SNSs). The theoretical foundation of much of my research comes from Altman's work on privacy management in the physical world. Altman believed that "we should attempt to design responsive…

  14. Perceptions of Web Site Design Characteristics: A Malaysian/Australian Comparison.

    ERIC Educational Resources Information Center

    Fink, Dieter; Laupase, Ricky

    2000-01-01

    Compares the perceptions of Malaysians and Australians for four Web site design characteristics--atmospherics, news stories, signs, and products and services--as part of the integrated Internet marketing model. Hypothesizes that the predominant culture is not generalized to another culture, discusses validity and reliability, and suggest further…

  15. The Merging of Systems Analysis and Design Principles with Web Site Development: One University's Experience.

    ERIC Educational Resources Information Center

    Kovacs, Paul; Rowell, Dick

    2001-01-01

    Describes the development of a course at Indiana University of Pennsylvania on Web Site theory and design for undergraduate and graduate students. Highlights include the classroom configuration; software; hardware; teaching strategies; and the project-based approach for a course model, including student assessment, student projects, work groups,…

  16. Conceptual design report, TWRS Privatization Phase I, site development and roads, subproject W-505

    SciTech Connect

    Singh, G.

    1997-06-05

    This document includes Conceptual Design Report (CDR) for the site development, construction of new roads and improvements at existing road intersections, habitat mitigation, roadway lighting, and construction power needed for the construction of two Private Contractor (PC) Facilities. Approximately 50 hectare (124 acres) land parcel, east of the Grout Facility, is planned for the PC facilities.

  17. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Sustainable principles for siting, design and construction. 435.6 Section 435.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS FOR NEW FEDERAL LOW-RISE RESIDENTIAL BUILDINGS Mandatory Energy Efficiency Standards for Federal...

  18. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Sustainable principles for siting, design and construction. 435.6 Section 435.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS FOR NEW FEDERAL LOW-RISE RESIDENTIAL BUILDINGS Mandatory Energy Efficiency Standards for Federal...

  19. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Sustainable principles for siting, design and construction. 435.6 Section 435.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS FOR NEW FEDERAL LOW-RISE RESIDENTIAL BUILDINGS Mandatory Energy Efficiency Standards for Federal...

  20. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Sustainable principles for siting, design and construction. 435.6 Section 435.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS FOR NEW FEDERAL LOW-RISE RESIDENTIAL BUILDINGS Mandatory Energy Efficiency Standards for Federal...

  1. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Sustainable principles for siting, design and construction. 435.6 Section 435.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS FOR NEW FEDERAL LOW-RISE RESIDENTIAL BUILDINGS Mandatory Energy Efficiency Standards for Federal...

  2. Leveraging user search behavior to design personalized browsing interfaces for healthcare Web sites.

    PubMed

    Mahoui, Malika; Jones, Josette; Zollinger, Derek; Andersen, Kanitha; Coates, Heather

    2008-01-01

    Understanding and leveraging user search behavior is increasingly becoming a key component towards improving web sites functionality for the health care consumer and provider. In this study we propose to leverage user search behavior to design user-tailored browsing interfaces to better support locating information in healthcare websites at the point-of-need. PMID:18998913

  3. Geohydrologic aspects for siting and design of low-level radioactive-waste disposal

    USGS Publications Warehouse

    Bedinger, M.S.

    1989-01-01

    The objective for siting and design of low-level radioactive-waste repository sites is to isolate the waste from the biosphere until the waste no longer poses an unacceptable hazard as a result of radioactive decay. Low-level radioactive waste commonly is isolated at shallow depths with various engineered features to stabilize the waste and to reduce its dissolution and transport by ground water. The unsaturated zone generally is preferred for isolating the waste. Low-level radioactive waste may need to be isolated for 300 to 500 years. Maintenance and monitoring of the repository site are required by Federal regulations for only the first 100 years. Therefore, geohydrology of the repository site needs to provide natural isolation of the waste for the hazardous period following maintenance of the site. Engineering design of the repository needs to be compatible with the natural geohydrologic conditions at the site. Studies at existing commercial and Federal waste-disposal sites provide information on the problems encountered and the basis for establishing siting guidelines for improved isolation of radioactive waste, engineering design of repository structures, and surveillance needs to assess the effectiveness of the repositories and to provide early warning of problems that may require remedial action. Climate directly affects the hydrology of a site and probably is the most important single factor that affects the suitability of a site for shallow-land burial of low-level radioactive waste. Humid and subhumid regions are not well suited for shallow isolation of low-level radioactive waste in the unsaturated zone; arid regions with zero to small infiltration from precipitation, great depths to the water table, and long flow paths to natural discharge areas are naturally well suited to isolation of the waste. The unsaturated zone is preferred for isolation of low-level radioactive waste. The guiding rationale is to minimize contact of water with the waste and to

  4. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Lowman, Idaho: Attachment 2, Geology report. Final report

    SciTech Connect

    Not Available

    1991-09-01

    Detailed investigations of geologic, geomorphic, and seismic conditions at the Lowman site in central Idaho were conducted by the Technical Assistance Contractor. The purpose of these investigations was basic site characterization and the identification of potential geologic hazards that could affect long-term site stability. Subsequent engineering studies (e.g., analyses of the hydrologic regime and liquefaction potential) use this data . The geomorphic analysis is employed in the design of effective erosion protection. Studies of the regional and local seismotectonic setting, which included a detailed search for possible capable faults within a 65-km (40-mile) radius of the site, provided the basis for estimating seismic design parameters.

  5. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Lowman, Idaho: Attachment 2, Geology report

    SciTech Connect

    Not Available

    1991-09-01

    Detailed investigations of geologic, geomorphic, and seismic conditions at the Lowman site in central Idaho were conducted by the Technical Assistance Contractor. The purpose of these investigations was basic site characterization and the identification of potential geologic hazards that could affect long-term site stability. Subsequent engineering studies (e.g., analyses of the hydrologic regime and liquefaction potential) use this data . The geomorphic analysis is employed in the design of effective erosion protection. Studies of the regional and local seismotectonic setting, which included a detailed search for possible capable faults within a 65-km (40-mile) radius of the site, provided the basis for estimating seismic design parameters.

  6. Remedial action plan and site conceptual design for stabilization of the inactive uranium mill tailings sites at Rifle, Colorado. Appendix D, Final report

    SciTech Connect

    1992-02-01

    This appendix assesses the present conditions and data gathered about the two designated inactive uranium mill tailings sites near Rifle, Colorado, and the proposed disposal site six miles north of Rifle in the area of Estes Gulch. It consolidates available engineering, radiological, geotechnical, hydrological, meteorological, and other information pertinent to the design of the Remedial Action Plan (RAP). The data characterize conditions at the mill, tailings, and disposal site so that the Remedial Action Contractor (RAC) may complete final designs for the remedial actions.

  7. Conceptual Design Report: Nevada Test Site Mixed Waste Disposal Facility Project

    SciTech Connect

    NSTec Environmental Management

    2009-01-31

    Environmental cleanup of contaminated nuclear weapons manufacturing and test sites generates radioactive waste that must be disposed. Site cleanup activities throughout the U.S. Department of Energy (DOE) complex are projected to continue through 2050. Some of this waste is mixed waste (MW), containing both hazardous and radioactive components. In addition, there is a need for MW disposal from other mission activities. The Waste Management Programmatic Environmental Impact Statement Record of Decision designates the Nevada Test Site (NTS) as a regional MW disposal site. The NTS has a facility that is permitted to dispose of onsite- and offsite-generated MW until November 30, 2010. There is not a DOE waste management facility that is currently permitted to dispose of offsite-generated MW after 2010, jeopardizing the DOE environmental cleanup mission and other MW-generating mission-related activities. A mission needs document (CD-0) has been prepared for a newly permitted MW disposal facility at the NTS that would provide the needed capability to support DOE's environmental cleanup mission and other MW-generating mission-related activities. This report presents a conceptual engineering design for a MW facility that is fully compliant with Resource Conservation and Recovery Act (RCRA) and DOE O 435.1, 'Radioactive Waste Management'. The facility, which will be located within the Area 5 Radioactive Waste Management Site (RWMS) at the NTS, will provide an approximately 20,000-cubic yard waste disposal capacity. The facility will be licensed by the Nevada Division of Environmental Protection (NDEP).

  8. Benzene Probes in Molecular Dynamics Simulations Reveal Novel Binding Sites for Ligand Design.

    PubMed

    Tan, Yaw Sing; Reeks, Judith; Brown, Christopher J; Thean, Dawn; Ferrer Gago, Fernando Jose; Yuen, Tsz Ying; Goh, Eunice Tze Leng; Lee, Xue Er Cheryl; Jennings, Claire E; Joseph, Thomas L; Lakshminarayanan, Rajamani; Lane, David P; Noble, Martin E M; Verma, Chandra S

    2016-09-01

    Protein flexibility poses a major challenge in binding site identification. Several computational pocket detection methods that utilize small-molecule probes in molecular dynamics (MD) simulations have been developed to address this issue. Although they have proven hugely successful at reproducing experimental structural data, their ability to predict new binding sites that are yet to be identified and characterized has not been demonstrated. Here, we report the use of benzenes as probe molecules in ligand-mapping MD (LMMD) simulations to predict the existence of two novel binding sites on the surface of the oncoprotein MDM2. One of them was serendipitously confirmed by biophysical assays and X-ray crystallography to be important for the binding of a new family of hydrocarbon stapled peptides that were specifically designed to target the other putative site. These results highlight the predictive power of LMMD and suggest that predictions derived from LMMD simulations can serve as a reliable basis for the identification of novel ligand binding sites in structure-based drug design. PMID:27532490

  9. Design and performance of an automatic regenerating adsorption aerosol dryer for continuous operation at monitoring sites

    NASA Astrophysics Data System (ADS)

    Tuch, T. M.; Haudek, A.; Müller, T.; Nowak, A.; Wex, H.; Wiedensohler, A.

    2009-04-01

    Sizes of aerosol particles depend on the relative humidity of their carrier gas. Most monitoring networks require therefore that the aerosol is dried to a relative humidity below 50% RH to ensure comparability of measurements at different sites. Commercially available aerosol dryers are often not suitable for this purpose at remote monitoring sites. Adsorption dryers need to be regenerated frequently and maintenance-free single column Nafion dryers are not designed for high aerosol flow rates. We therefore developed an automatic regenerating adsorption aerosol dryer with a design flow rate of 1 m3/h. Particle transmission efficiency of this dryer has been determined during a 3 weeks experiment. The lower 50% cut-off was found to be below 3 nm at the design flow rate of the instrument. Measured transmission efficiencies are in good agreement with theoretical calculations. One drier has been successfully deployed in the Amazonas river basin. From this monitoring site, we present data from the first 6 months of measurements (February 2008-August 2008). Apart from one unscheduled service, this dryer did not require any maintenance during this time period. The average relative humidity of the dried aerosol was 27.1+/-7.5% RH compared to an average ambient relative humidity of nearly 80% and temperatures around 30°C. This initial deployment demonstrated that these dryers are well suitable for continuous operation at remote monitoring sites under adverse ambient conditions.

  10. Current plans to characterize the design basis ground motion at the Yucca Mountain, Nevada, site

    SciTech Connect

    Simecka, W.B.; Grant, T.A.; Voegele, M.D.; Cline, K.M.

    1993-09-01

    A site at Yucca Mountain Nevada is currently being studied to assess its suitability as a potential host site for the nation`s first commercial high level waste repository. The DOE has proposed a new methodology for determining design-basis ground motions that uses both deterministic and probabilistic methods. The role of the deterministic approach is primary. It provides the level of detail needed by design engineers in the characterization of ground motions. The probabilistic approach provides a logical structured procedure for integrating the range of possible earthquakes that contribute to the ground motion hazard at the site. In addition, probabilistic methods will be used as needed to provide input for the assessment of long-term repository performance. This paper discusses the local tectonic environment, potential seismic sources and their associated displacements and ground motions. It also discusses the approach to assessing the design basis earthquake for the surface and underground facilities, as well as selected examples of the use of this type of information in design activities.

  11. Oxidative stress alters base excision repair pathway and increases apoptotic response in apurinic/apyrimidinic endonuclease 1/redox factor-1 haploinsufficient mice.

    PubMed

    Unnikrishnan, Archana; Raffoul, Julian J; Patel, Hiral V; Prychitko, Thomas M; Anyangwe, Njwen; Meira, Lisiane B; Friedberg, Errol C; Cabelof, Diane C; Heydari, Ahmad R

    2009-06-01

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is the redox regulator of multiple stress-inducible transcription factors, such as NF-kappaB, and the major 5'-endonuclease in base excision repair (BER). We utilized mice containing a heterozygous gene-targeted deletion of APE1/Ref-1 (Apex(+/-)) to determine the impact of APE1/Ref-1 haploinsufficiency on the processing of oxidative DNA damage induced by 2-nitropropane (2-NP) in the liver tissue of mice. APE1/Ref-1 haploinsufficiency results in a significant decline in NF-kappaB DNA-binding activity in response to oxidative stress in liver. In addition, loss of APE1/Ref-1 increases the apoptotic response to oxidative stress, in which significant increases in GADD45g expression, p53 protein stability, and caspase activity are observed. Oxidative stress displays a differential impact on monofunctional (UNG) and bifunctional (OGG1) DNA glycosylase-initiated BER in the liver of Apex(+/-) mice. APE1/Ref-1 haploinsufficiency results in a significant decline in the repair of oxidized bases (e.g., 8-OHdG), whereas removal of uracil is increased in liver nuclear extracts of mice using an in vitro BER assay. Apex(+/-) mice exposed to 2-NP displayed a significant decline in 3'-OH-containing single-strand breaks and an increase in aldehydic lesions in their liver DNA, suggesting an accumulation of repair intermediates of failed bifunctional DNA glycosylase-initiated BER. PMID:19268524

  12. Apurinic/apyrimidinic endonuclease 1 induced upregulation of fibroblast growth factor 2 and its receptor 3 induces angiogenesis in human osteosarcoma cells.

    PubMed

    Ren, Tao; Qing, Yi; Dai, Nan; Li, Mengxia; Qian, Chengyuan; Yang, Yuxin; Cheng, Yi; Li, Zheng; Zhang, Shiheng; Zhong, Zhaoyang; Wang, Dong

    2014-02-01

    Tumor angiogenesis contributes to inferior prognosis in osteosarcoma. Apurinic/apyrimidinic endonuclease 1 (APE1) and fibroblast growth factor 2 (FGF2) and its receptor 3 (FGFR3) signaling pathway plays an important role in the angiogenic process. In this study we observed that high expression of APE1, FGF2 and FGFR3, and microvessel density are positively correlated with poor prognosis of osteosarcoma patients. Furthermore, the Cox model showed that the tumor size, FGF2 and its receptor 3 (FGFR3), and microvessel density were adverse prognostic factors. Based on our clinical data, and the fact that APE1 is involved in tumor angiogenesis, we hypothesize that it is very likely that APE1 may indirectly promote angiogenesis by upregulating fibroblast FGF2 and FGFR3. Our preliminary data show small interfering RNA-mediated silence of APE1 experiments, which further supports this hypothesis. APE1-small interfering RNA significantly inhibited tumor angiogenesis by downregulating in vitro expression of FGF2 and FGFR3 in human umbilical vein endothelial cells in Matrigel tube formation assay, and further inhibited tumor growth in vivo in a mouse xenograft model. Thus, the proposed APE1-FGF2 and FGFR3 pathway may provide a novel mechanism for regulation of FGF2 and FGFR3 by APE1 in tumor angiogenesis. PMID:24329908

  13. Remedial action and site design for stabilization of the inactive uranium mill tailings sites at Slick Rock, Colorado. Attachment 2, Geology report: Appendix B, Preliminary final

    SciTech Connect

    Not Available

    1994-03-01

    Detailed investigations of geologic, geomorphic, and seismic conditions at the Burro Canyon site were conducted by the US Department of Energy (DOE) as a disposal site for the tailings at two processing sites near the Slick Rock, Colorado, post office. The purposes of these studies are basic site characterization and identification of potential geologic hazards that could affect long-term site stability. Subsequent engineering studies (e.g., analyses of hydrologic and liquefaction hazards) used the data developed in these studies. The geomorphic analysis was employed in the design of effective erosion protection. Studies of the regional and local seismotectonic setting, which included a detailed search for possible capable faults within a 65-km radius of the site, provided the basis for seismic design parameters.

  14. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Mexican Hat, Utah: Appendix D. Final report

    SciTech Connect

    1988-07-01

    This appendix is an assessment of the present conditions of the inactive uranium mill site near Mexican Hat, Utah. It consolidates available engineering, radiological, geotechnical, hydrological, meteorological, and other information pertinent to the design of the Remedial Action Plan. Plan is to characterize the conditions at the mill and tailings site so that the Remedial Action Contractor may complete final designs of the remedial action.

  15. Design and analysis of site-specific single-strand nicking endonucleases for gene correction.

    PubMed

    Metzger, Michael J; Certo, Michael T

    2014-01-01

    Single-strand nicking endonucleases ("nickases") have been shown to induce homology-mediated gene correction with reduced toxicity of DNA double-strand break-producing enzymes, and nickases have been engineered from both homing endonuclease and FokI-based scaffolds. We describe the strategies used to engineer these site-specific nickases as well as the in vitro methods used to confirm their activity and specificity. Additionally, we describe the Traffic Light Reporter system, which uses a flow cytometric assay to simultaneously detect both gene repair and mutagenic nonhomologous end-joining outcomes at a single targeted site in mammalian cells. With these methods, novel nickases can be designed and tested for use in gene correction with novel target sites. PMID:24557907

  16. Guide to radiological accident considerations for siting and design of DOE nonreactor nuclear facilities

    SciTech Connect

    Elder, J.C.; Graf, J.M.; Dewart, J.M.; Buhl, T.E.; Wenzel, W.J.; Walker, L.J.; Stoker, A.K.

    1986-01-01

    This guide was prepared to provide the experienced safety analyst with accident analysis guidance in greater detail than is possible in Department of Energy (DOE) Orders. The guide addresses analysis of postulated serious accidents considered in the siting and selection of major design features of DOE nuclear facilities. Its scope has been limited to radiological accidents at nonreactor nuclear facilities. The analysis steps addressed in the guide lead to evaluation of radiological dose to exposed persons for comparison with siting guideline doses. Other possible consequences considered are environmental contamination, population dose, and public health effects. Choices of models and parameters leading to estimation of source terms, release fractions, reduction and removal factors, dispersion and dose factors are discussed. Although requirements for risk analysis have not been established, risk estimates are finding increased use in siting of major nuclear facilities, and are discussed in the guide. 3 figs., 9 tabs.

  17. Evolution of a designed retro-aldolase leads to complete active site remodeling

    PubMed Central

    Giger, Lars; Caner, Sami; Obexer, Richard; Kast, Peter; Baker, David; Ban, Nenad; Hilvert, Donald

    2013-01-01

    Evolutionary advances are often fueled by unanticipated innovation. Directed evolution of a computationally designed enzyme suggests that dramatic molecular changes can also drive the optimization of primitive protein active sites. The specific activity of an artificial retro-aldolase was boosted >4,400 fold by random mutagenesis and screening, affording catalytic efficiencies approaching those of natural enzymes. However, structural and mechanistic studies reveal that the engineered catalytic apparatus, consisting of a reactive lysine and an ordered water molecule, was unexpectedly abandoned in favor of a new lysine residue in a substrate binding pocket created during the optimization process. Structures of the initial in silico design, a mechanistically promiscuous intermediate, and one of the most evolved variants highlight the importance of loop mobility and supporting functional groups in the emergence of the new catalytic center. Such internal competition between alternative reactive sites may have characterized the early evolution of many natural enzymes. PMID:23748672

  18. A sensitivity analysis of hazardous waste disposal site climatic and soil design parameters using HELP3

    SciTech Connect

    Adelman, D.D.; Stansbury, J.

    1997-12-31

    The Resource Conservation and Recovery Act (RCRA) Subtitle C, Comprehensive Environmental Response, Compensation, And Liability Act (CERCLA), and subsequent amendments have formed a comprehensive framework to deal with hazardous wastes on the national level. Key to this waste management is guidance on design (e.g., cover and bottom leachate control systems) of hazardous waste landfills. The objective of this research was to investigate the sensitivity of leachate volume at hazardous waste disposal sites to climatic, soil cover, and vegetative cover (Leaf Area Index) conditions. The computer model HELP3 which has the capability to simulate double bottom liner systems as called for in hazardous waste disposal sites was used in the analysis. HELP3 was used to model 54 combinations of climatic conditions, disposal site soil surface curve numbers, and leaf area index values to investigate how sensitive disposal site leachate volume was to these three variables. Results showed that leachate volume from the bottom double liner system was not sensitive to these parameters. However, the cover liner system leachate volume was quite sensitive to climatic conditions and less sensitive to Leaf Area Index and curve number values. Since humid locations had considerably more cover liner system leachate volume than and locations, different design standards may be appropriate for humid conditions than for and conditions.

  19. Department of Energy seismic siting and design decisions: Consistent use of probabilistic seismic hazard analysis

    SciTech Connect

    Kimball, J.K.; Chander, H.

    1997-02-01

    The Department of Energy (DOE) requires that all nuclear or non-nuclear facilities shall be designed, constructed and operated so that the public, the workers, and the environment are protected from the adverse impacts of Natural Phenomena Hazards including earthquakes. The design and evaluation of DOE facilities to accommodate earthquakes shall be based on an assessment of the likelihood of future earthquakes occurrences commensurate with a graded approach which depends on the potential risk posed by the DOE facility. DOE has developed Standards for site characterization and hazards assessments to ensure that a consistent use of probabilistic seismic hazard is implemented at each DOE site. The criteria included in the DOE Standards are described, and compared to those criteria being promoted by the staff of the Nuclear Regulatory Commission (NRC) for commercial nuclear reactors. In addition to a general description of the DOE requirements and criteria, the most recent probabilistic seismic hazard results for a number of DOE sites are presented. Based on the work completed to develop the probabilistic seismic hazard results, a summary of important application issues are described with recommendations for future improvements in the development and use of probabilistic seismic hazard criteria for design of DOE facilities.

  20. Design of a permeable reactive barrier in situ remediation system, Vermont site

    SciTech Connect

    Hayes, J.J.; Marcus, D.L.

    1997-12-31

    EMCON designed a Permeable Reactive Barrier (PRB) for a site in Vermont to passively remediate in situ groundwater impacted with chlorinated volatile organic compounds (CVOCs). The PRB was selected over more conventional remediation approaches because it is a potentially low maintenance and long lasting solution for containment of groundwater impacts. Iron media are used as an agent to produce reductive dehalogenation reactions that break down the CVOCs. At the Vermont site, impacted groundwater is found from approximately 1.3 to 4.3 meters (4 to 14 feet) below ground surface in the uppermost aquifer, which is underlain by a silty clay aquitard. These are virtually optimum conditions for the implementation of this kind of technology. Effective design of the PRB required site specific hydrogeologic, geochemical, and geotechnical data, a substantial amount that was already available and some which was collected during the recent Corrective Action Feasibility Investigation (CAFI). Most PRBs have been constructed using sheet pilings to shore excavations backfilled by iron filings. On the Vermont project, continuous trenching is proposed to install HDPE sheeting for the funnel and alternative reactive media may be used in the reactive gates. The Funnel and Gate{trademark} system is being designed to regulate flow velocity through the gate to yield critical contact time between the CVOCs and the reactive media.

  1. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Slick Rock, Colorado. Remedial action selection report, Appendix B

    SciTech Connect

    Not Available

    1993-07-01

    The Slick Rock uranium mill tailings sites are located near the small town of Slick Rock, in San Miguel County, Colorado. There are two designated UMTRA sites at Slick Rock, the Union Carbide (UC) site and the North Continent (NC) site. Both sites are adjacent to the Dolores River. The UC site is approximately 1 mile (mi) [2 kilometers (km)] downstream of the NC site. Contaminated materials cover an estimated 55 acres (ac) [22 hectares (ha)] at the UC site and 12 ac (4.9 ha) at the NC site. The sites contain former mill building concrete foundations, tailings piles, demolition debris, and areas contaminated by windblown and waterborne radioactive materials. The total estimated volume of contaminated materials is approximately 620, 000 cubic yards (yd{sup 3}) [470,000 cubic meters (m{sup 3})]. In addition to the contamination at the two processing site areas, four vicinity properties were contaminated. Contamination associated with the UC and NC sites has leached into groundwater.

  2. 78 FR 939 - Notice of Public Meeting: Designation of an Ocean Dredged Material Disposal Sites (ODMDS) in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-07

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Notice of Public Meeting: Designation of an Ocean Dredged Material Disposal Sites (ODMDS) in... Potential Designation of One or More Ocean Dredged Material Disposal Sites (ODMDS) to Serve the Eastern...

  3. Preclosure performance assessment review of the draft site characterization plan conceptual design report: Technical report

    SciTech Connect

    Waite, D.A.; Gupta, R.; Ludwig, S.B.; Maheras, S.J.; Mayberry, J.J.; Plummer, A.M.; Tarapore, P.S.

    1987-12-01

    This report presents the preclosure performance assessment review (PAR) of the Site Characterization Plan Conceptual Design Report (SCP-CDR). The PAR was performed on the design presented in the SCP-CDR working draft, Revision 1, released in October 1986. After review this working draft became the ''Site Characterization Plan Conceptual Design Report'', Revision 1. There are two distinct objectives of the PAR: (1) to analyze the design presented in the SCP-CDR in terms of offsite and occupational radiological safety, and (2) to test safety assessment methods and tools. This report addresses only the first of the PAR objectives. The PAR analysis consists of assessments of offsite and occupational doses resulting from routine and abnormal repository events. The scope of the analysis is restricted to preclosure operations at the repository. This report addresses (1) the description of repository facilities and operations, (2) the development of radioactive material inventories and radiation dose rates, (3) the development of radioactive material release scenarios and source terms, and (4) the assessment of offsite and occupational radiation dose equivalents. This report contains a summary of the analyses in the above four areas, and analysis details are documented. The results of the assessments are compared with regulatory requirements to determine how the repository performs relative to the requirements. The analyses indicate that the offsite and occupational impacts comply with regulatory requirements. However, based on this preliminary analysis of the draft design document, the occupational impacts exceed the SCP-CDR design objective of 1 rem/year in some areas. 59 refs., 12 figs., 127 tabs.

  4. The Design, Synthesis, and Characterization of Open Sites on Metal Clusters

    NASA Astrophysics Data System (ADS)

    Nigra, Michael Mark

    Coordinatively unsaturated corner and edge atoms have been hypothesized to have the highest activity of sites responsible for many catalytic reactions on a metal surface. Recent studies have validated this hypothesis in varied reaction systems. However, quantification of different types of coordinatively unsaturated sites, and elucidation of their individual catalytic rates has remained a largely unresolved challenge when understanding catalysis on metal surfaces. Yet such structure-function knowledge would be invaluable to the design of more active and selective metal-surface catalysts in the future. I investigated the catalytic contributions of undercoordinated sites such as corner and edge atoms are investigated in a model reaction system using organic ligands bound to the gold nanoparticle surface. The catalyst consisted of 4 nm gold nanoparticles on a metal oxide support, using resazurin to resorufin as a model reaction system. My results demonstrate that in this system, corner atom sites are the most undercoordinated sites, and are over an order of magnitude more active when compared to undercoordinated edge atom sites, while terrace sites remain catalytically inactive for the reduction reaction of resazurin to resorufin. Catalytic activity has been also demonstrated for calixarene-bound gold nanoparticles using the reduction of 4-nitrophenol. With the 4-nitrophenol reduction reaction, a comparative study was undertaken to compare calixarene phosphine and calixarene thiol bound 4 nm gold particles. The results of the study suggested that a leached site was responsible for catalysis and not sites on the original gold nanoparticles. Future experiments with calixarene bound gold clusters could investigate ligand effects in reactions where the active site is not a leached or aggregated gold species, possibly in oxidation reactions, where electron-rich gold is hypothesized to be a good catalyst. The results that emphasize the enhanced catalytic activity of

  5. Final report on the radiological surveys of designated DX firing sites at Los Alamos National Laboratory

    SciTech Connect

    1996-09-09

    CHEMRAD was contracted by Los Alamos National Laboratory to perform USRADS{reg_sign} (UltraSonic Ranging And Data System) radiation scanning surveys at designated DX Sites at the Los Alamos National Laboratory. The primary purpose of these scanning surveys was to identify the presence of Depleted Uranium (D-38) resulting from activities at the DX Firing Sites. This effort was conducted to update the most recent surveys of these areas. This current effort was initiated with site orientation on August 12, 1996. Surveys were completed in the field on September 4, 1996. This Executive Summary briefly presents the major findings of this work. The detail survey results are presented in the balance of this report and are organized by Technical Area and Site number in section 2. This organization is not in chronological order. USRADS and the related survey methods are described in section 3. Quality Control issues are addressed in section 4. Surveys were conducted with an array of radiation detectors either mounted on a backpack frame for man-carried use (Manual mode) or on a tricycle cart (RadCart mode). The array included radiation detectors for gamma and beta surface near surface contamination as well as dose rate at 1 meter above grade. The radiation detectors were interfaced directly to an USRADS 2100 Data Pack.

  6. 2009 Melbourne metropolitan sewerage strategy: a portfolio of decentralised and on-site concept designs.

    PubMed

    Brown, V; Jackson, D W; Khalifé, M

    2010-01-01

    The bulk and retail water companies of the greater Melbourne area are developing the 2009 Metropolitan Sewerage Strategy to provide sustainable sewerage services to 2060. The objective of the strategy is to establish long term principles and near term actions to produce a robust sewage management system for Melbourne. Melbourne's existing sewerage system is largely centralised and discharges to two major treatment plants. Several small satellite treatment plants service local urban areas generally more distant from the centralised system. Decentralised and on-site wastewater systems are options for future sewage management and could play a role in local recycling. A portfolio of 18 on-site and decentralised concept designs was developed, applicable to the full range of urban development types in Melbourne. The concepts can be used in evaluation of metropolitan system configurations as part of future integrated water cycle planning. The options included secondary and tertiary treatment systems incorporating re-use of water for non potable uses, urine separation, black and greywater separation and composting toilets. On-site and cluster treatment systems were analysed. Each option is described by its indicative capital and operating costs, energy use and water and nutrient balances. This paper summarises and compares the portfolio mix of decentralized and on-site options in Melbourne's context. PMID:20705997

  7. Design of potent and selective human cathepsin K inhibitors that span the active site

    PubMed Central

    Thompson, Scott K.; Halbert, Stacie M.; Bossard, Mary J.; Tomaszek, Thaddeus A.; Levy, Mark A.; Zhao, Baoguang; Smith, Ward W.; Abdel-Meguid, Sherin S.; Janson, Cheryl A.; D’Alessio, Karla J.; McQueney, Michael S.; Amegadzie, Bernard Y.; Hanning, Charles R.; DesJarlais, Renee L.; Briand, Jacques; Sarkar, Susanta K.; Huddleston, Michael J.; Ijames, Carl F.; Carr, Steven A.; Garnes, Keith T.; Shu, Art; Heys, J. Richard; Bradbeer, Jeremy; Zembryki, Denise; Lee-Rykaczewski, Liz; James, Ian E.; Lark, Michael W.; Drake, Fred H.; Gowen, Maxine; Gleason, John G.; Veber, Daniel F.

    1997-01-01

    Potent and selective active-site-spanning inhibitors have been designed for cathepsin K, a cysteine protease unique to osteoclasts. They act by mechanisms that involve tight binding intermediates, potentially on a hydrolytic pathway. X-ray crystallographic, MS, NMR spectroscopic, and kinetic studies of the mechanisms of inhibition indicate that different intermediates or transition states are being represented that are dependent on the conditions of measurement and the specific groups flanking the carbonyl in the inhibitor. The species observed crystallographically are most consistent with tetrahedral intermediates that may be close approximations of those that occur during substrate hydrolysis. Initial kinetic studies suggest the possibility of irreversible and reversible active-site modification. Representative inhibitors have demonstrated antiresorptive activity both in vitro and in vivo and therefore are promising leads for therapeutic agents for the treatment of osteoporosis. Expansion of these inhibitor concepts can be envisioned for the many other cysteine proteases implicated for therapeutic intervention. PMID:9405598

  8. Design, Synthesis, and Biological Evaluation of Stable Colchicine Binding Site Tubulin Inhibitors as Potential Anticancer Agents

    PubMed Central

    2015-01-01

    To block the metabolically labile sites of novel tubulin inhibitors targeting the colchicine binding site based on SMART, ABI, and PAT templates, we have designed, synthesized, and biologically tested three focused sets of new derivatives with modifications at the carbonyl linker, the para-position in the C ring of SMART template, and modification of A ring of the PAT template. Structure–activity relationships of these compounds led to the identification of new benzimidazole and imidazo[4,5-c]pyridine-fused ring templates, represented by compounds 4 and 7, respectively, which showed enhanced antitumor activity and substantially improved the metabolic stability in liver microsomes compared to SMART. MOM group replaced TMP C ring and generated a potent analogue 15, which showed comparable potency to the parent SMART compound. Further modification of PAT template yielded another potent analogue 33 with 5-indolyl substituent at A ring. PMID:25122533

  9. Downregulation of the DNA repair enzyme apurinic/apyrimidinic endonuclease 1 stimulates transforming growth factor-β1 production and promotes actin rearrangement.

    PubMed

    Sakai, Yuri; Yamamori, Tohru; Yasui, Hironobu; Inanami, Osamu

    2015-05-22

    The DNA repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1) plays a central role in base excision repair and functions as a reductive activator of various transcription factors. Multiple other functionalities have been ascribed to APE1 in addition to these major functions. A recent study showed that APE1 knockdown upregulated the expression of a set of genes related to extracellular matrix (ECM) production, indicating an additional novel biological role for this enzyme. Based on this finding, we have investigated the effect of APE1 downregulation on ECM-related gene expression and its biological consequences. Endogenous APE1 expression was downregulated in human cervical carcinoma HeLa cells and human lung carcinoma A549 cells using siRNA. When the expression of six ECM-related genes (TGFB1, LAMC1, FN1, COL1A1, COL3A1, and COL4A1) was evaluated, we found that APE1 knockdown upregulated the expression of TGFB1 in both cell lines. APE1 downregulation promoted actin rearrangement, inducing F-actin accumulation in HeLa cells and the dissipation of stress fibers in A549 cells. We also discovered that APE1 knockdown enhanced cellular motility in A549 cells, which was suppressed by the inhibition of transforming growth factor (TGF)-β1 signaling. These results suggested that APE1 controls the organization of actin cytoskeleton through the regulation of TGF-β1 expression, providing novel insights into the biological significance of APE1. PMID:25858321

  10. Early Site Permit Demonstration Program: Guidelines for determining design basis ground motions. Volume 2, Appendices

    SciTech Connect

    Not Available

    1993-03-18

    This report develops and applies a methodology for estimating strong earthquake ground motion. The motivation was to develop a much needed tool for use in developing the seismic requirements for structural designs. An earthquake`s ground motion is a function of the earthquake`s magnitude, and the physical properties of the earth through which the seismic waves travel from the earthquake fault to the site of interest. The emphasis of this study is on ground motion estimation in Eastern North America (east of the Rocky Mountains), with particular emphasis on the Eastern United States and southeastern Canada. Eastern North America is a stable continental region, having sparse earthquake activity with rare occurrences of large earthquakes. While large earthquakes are of interest for assessing seismic hazard, little data exists from the region to empirically quantify their effects. The focus of the report is on the attributes of ground motion in Eastern North America that are of interest for the design of facilities such as nuclear power plants. This document, Volume II, contains Appendices 2, 3, 5, 6, and 7 covering the following topics: Eastern North American Empirical Ground Motion Data; Examination of Variance of Seismographic Network Data; Soil Amplification and Vertical-to-Horizontal Ratios from Analysis of Strong Motion Data From Active Tectonic Regions; Revision and Calibration of Ou and Herrmann Method; Generalized Ray Procedure for Modeling Ground Motion Attenuation; Crustal Models for Velocity Regionalization; Depth Distribution Models; Development of Generic Site Effects Model; Validation and Comparison of One-Dimensional Site Response Methodologies; Plots of Amplification Factors; Assessment of Coupling Between Vertical & Horizontal Motions in Nonlinear Site Response Analysis; and Modeling of Dynamic Soil Properties.

  11. Postclosure performance assessment of the SCP (Site Characterization Plan) conceptual design for horizontal emplacement: Revision 1

    SciTech Connect

    Not Available

    1987-08-01

    This report is a preliminary postclosure performance assessment of the repository design specified in the Site Characterization Plan Conceptual Design Report (SCP-CDR) for horizontal emplacement of high-level nuclear waste. At the time that these analyses were done, horizontal emplacement was the preferred orientation for the waste packages but vertical emplacement is now the reference design. This assessment consists of (1) a review of the regulatory requirements and strategy to demonstrate compliance with these requirements, (2) an analysis of the performance of the total repository system, (3) an analysis of the thermomechanical behavior of the repository, (4) an analysis of brine mobility in the repository, (5) an analysis of the waste package performance, (6) an analysis of the performance of seals, and (7) comments on the sensitivity of the various performance measures to uncertainties in the data and models. These are preliminary analyses and, in most cases, involve bounding calculations of the repository behavior. They have several purposes including (1) assessing how well this conceptual design ''measures up'' against requirements, (2) gaining experience in implementing the performance assessment strategy and tools and thereby learning where improvements are needed, (3) helping to identify needed data, and (4) helping to indicate required design modifications. 26 refs., 40 figs., 20 tabs.

  12. Investigation into the optimal hydrologic design of porous concrete sites using mathematical modeling

    NASA Astrophysics Data System (ADS)

    Syrrakou, C.; Fitch, J.; Eliassen, T.; Ahearn, W.; Pinder, G. F.

    2011-12-01

    Increase in the amount of paved areas as a result of urbanization in modern societies has lead to the need of stormwater best management practices (BMPs). In that direction, porous pavement has been used successfully in regions of warm climate and application in regions of colder climate is an object of ongoing research with encouraging results to date. The significant cost and effort that accompanies the maintenance of porous pavement facilities calls for a design tool that can be used prior construction to facilitate the design process and also post production to evaluate the site's overall performance. Such a tool is a mathematical model which takes into account the different physical processes that can occur in a porous concrete system including recharge from rainfall, runoff from surrounding conventionally paved areas, vertical flow, storage and finally infiltration into the subsurface. In this research a three-dimensional saturated-unsaturated flow and transport model is modified to account for flow through the porous concrete slab and also evaporation. Runoff is accounted by means of a two-dimensional surface flow model which calculates the infiltration into the perimeter porous concrete area. The mathematical model is used to simulate a porous concrete site which operates as a public parking lot facility in Randolph, Vermont. The subgrade soil in the area of interest consists mainly of dense till deposits typically found in New England. Such deposits can result in small infiltration rates. The specific site is unique not only in terms of the underlying geology but also the heavy instrumentation not usually observed in similar sites. The instrumentation includes a number of groundwater wells which are being monitored continuously through a pressure transducer system, temperature probes installed inside the porous concrete and a detailed underdrain system located in the porous concrete's sub-base accumulating infiltrated water. Laboratory research is also

  13. Clustered DNA Lesions Containing 5-Formyluracil and AP Site: Repair via the BER System

    PubMed Central

    Belousova, Ekaterina A.; Vasil'eva, Inna A.; Moor, Nina A.; Zatsepin, Timofey S.; Oretskaya, Tatiana S.; Lavrik, Olga I.

    2013-01-01

    Lesions in the DNA arise under ionizing irradiation conditions or various chemical oxidants as a single damage or as part of a multiply damaged site within 1–2 helical turns (clustered lesion). Here, we explored the repair opportunity of the apurinic/apyrimidinic site (AP site) composed of the clustered lesion with 5-formyluracil (5-foU) by the base excision repair (BER) proteins. We found, that if the AP site is shifted relative to the 5-foU of the opposite strand, it could be repaired primarily via the short-patch BER pathway. In this case, the cleavage efficiency of the AP site-containing DNA strand catalyzed by human apurinic/apyrimidinic endonuclease 1 (hAPE1) decreased under AP site excursion to the 3'-side relative to the lesion in the other DNA strand. DNA synthesis catalyzed by DNA polymerase lambda was more accurate in comparison to the one catalyzed by DNA polymerase beta. If the AP site was located exactly opposite 5-foU it was expected to switch the repair to the long-patch BER pathway. In this situation, human processivity factor hPCNA stimulates the process. PMID:23936307

  14. Recommendations for Advanced Design Mixer Pump Operation in Savannah River Site Tank 18F

    SciTech Connect

    Enderlin, Carl W.; Terrones, Guillermo; Bates, Cameron J.; Hatchell, Brian K.; Adkins, Brannen

    2003-10-30

    This report discusses technical issues and presents recommendations for operating the advanced design mixer pump (ADMP) in Tank 18 at the Savannah River Site (SRS). Also presented are the results obtained from simulated scaled pump-down tests carried out in the 1/4-scale double shell tank (DST) test facility at Pacific Northwest National Laboratory (PNNL). The work was conducted for the DOE Tanks Focus Area (TFA) by the Retrieval Process Development and Enhancement (RPD&E) program. The ability of the Tank 18 retrieval system to mobilize the solid waste and transport it through the retrieval pump, efficiently removing the solids from the tank, are evaluated.

  15. Novel ligands rationally designed for characterizing I2-imidazoline binding sites nature and functions.

    PubMed

    Gentili, Francesco; Cardinaletti, Claudia; Vesprini, Cristian; Ghelfi, Francesca; Farande, Aniket; Giannella, Mario; Piergentili, Alessandro; Quaglia, Wilma; Mattioli, Laura; Perfumi, Marina; Hudson, Alan; Pigini, Maria

    2008-08-28

    The study of two series of 2-aryl-ethylen-imidazolines 3-7 and 8-12 inspired by I2-IBS ligands phenyzoline (1) and diphenyzoline (2), respectively, confirmed the interesting "positive" or "negative" morphine analgesia modulation displayed by their corresponding leads and demonstrated that these effects might be correlated with morphine tolerance and dependence, respectively. By comparative examination of rationally designed compounds, some analogies between binding site cavity of I2-IBS proteins and alpha 2C-adrenoreceptor emerged. PMID:18661965

  16. Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists

    PubMed Central

    Liu, Shenping; Dakin, Leslie A.; Xing, Li; Withka, Jane M.; Sahasrabudhe, Parag V.; Li, Wei; Banker, Mary Ellen; Balbo, Paul; Shanker, Suman; Chrunyk, Boris A.; Guo, Zuojun; Chen, Jinshan M.; Young, Jennifer A.; Bai, Guoyun; Starr, Jeremy T.; Wright, Stephen W.; Bussenius, Joerg; Tan, Sheng; Gopalsamy, Ariamala; Lefker, Bruce A.; Vincent, Fabien; Jones, Lyn H.; Xu, Hua; Hoth, Lise R.; Geoghegan, Kieran F.; Qiu, Xiayang; Bunnage, Mark E.; Thorarensen, Atli

    2016-01-01

    Interleukin-17A (IL-17A) is a principal driver of multiple inflammatory and immune disorders. Antibodies that neutralize IL-17A or its receptor (IL-17RA) deliver efficacy in autoimmune diseases, but no small-molecule IL-17A antagonists have yet progressed into clinical trials. Investigation of a series of linear peptide ligands to IL-17A and characterization of their binding site has enabled the design of novel macrocyclic ligands that are themselves potent IL-17A antagonists. PMID:27527709

  17. Advanced Imaging for Glaucoma Study: Design, Baseline Characteristics, and Inter-Site Comparison

    PubMed Central

    Le, Phuc V.; Zhang, Xinbo; Francis, Brian A.; Varma, Rohit; Greenfield, David S.; Schuman, Joel S.; Loewen, Nils; Huang, David

    2014-01-01

    Purpose To report the baseline characteristics of the participants in the Advanced Imaging for Glaucoma Study. To compare the participating sites for variations among subjects and the performance of imaging instruments. Design Multi-center longitudinal observational cohort study Methods A total of 788 participants (1,329 eyes) were enrolled from three academic referral centers. There were 145 participants (289 eyes) in the normal group, 394 participants (663 eyes) in the glaucoma suspect/preperimetric glaucoma group, and 249 participants (377 eyes) in the perimetric glaucoma group. Participants underwent a full clinical exam, standard automated perimetry, and imaging with time-domain and Fourier-domain optical coherence tomography (OCT), scanning laser polarimetry, and confocal scanning laser ophthalmoscopy. Main Outcome Measures The baseline average, population standard deviation, and repeatability of imaging-derived anatomic variables were reported for each technology and center. Results Compared to the normal participants, glaucoma suspect/preperimetric glaucoma and perimetric glaucoma groups had significantly reduced anatomic measurements. Repeatability of nerve fiber layer thickness was best for Fourier-domain OCT (overall coefficient of variation < 2%), followed by time-domain OCT (coefficient of variation 2-2.9%), scanning laser polarimetry (coefficient of variation 2.6-4.5%), and confocal scanning laser ophthalmoscopy rim area (coefficient of variation 4.2-7.6%). A mixed-effects model showed that the differences between sites was less than 25 percent of the variation within groups and less than the differences between the normal and glaucoma suspect/preperimetric glaucoma group. Conclusions Site-to-site variation was smaller than both the variation within groups and the changes due to glaucoma. Therefore pooling of participants between sites is appropriate. PMID:25447111

  18. Modifications to the remedial action plan and site design for stabilization of the inactive Uranium Mill Tailings Site at Green River, Utah

    SciTech Connect

    Not Available

    1994-09-01

    Modifications to the water resources protection strategy detailed in the remedial action plan for the Green River, Utah, disposal site are presented. The modifications are based on new information, including ground water quality data collected after remedial action was completed and on a revised assessment of disposal cell design features, surface conditions, and site hydrogeology. The modifications will result in compliance with the U.S. EPA proposed ground water standards (52 FR 36000 (1987)).

  19. 75 FR 39523 - Notice of Intent: Designation of an Ocean Dredged Material Disposal Site (ODMDS) Off the Mouth of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-09

    ... policy to prepare a voluntary National Environmental Policy document for all ODMDS designations (63 FR... AGENCY Notice of Intent: Designation of an Ocean Dredged Material Disposal Site (ODMDS) Off the Mouth of... Intent to prepare an Environmental Impact Statement (EIS) for the designation of an ODMDS off the...

  20. Computational design of a red fluorophore ligase for site-specific protein labeling in living cells

    DOE PAGESBeta

    Liu, Daniel S.; Nivon, Lucas G.; Richter, Florian; Goldman, Peter J.; Deerinck, Thomas J.; Yao, Jennifer Z.; Richardson, Douglas; Phipps, William S.; Ye, Anne Z.; Ellisman, Mark H.; et al

    2014-10-13

    In this study, chemical fluorophores offer tremendous size and photophysical advantages over fluorescent proteins but are much more challenging to target to specific cellular proteins. Here, we used Rosetta-based computation to design a fluorophore ligase that accepts the red dye resorufin, starting from Escherichia coli lipoic acid ligase. X-ray crystallography showed that the design closely matched the experimental structure. Resorufin ligase catalyzed the site-specific and covalent attachment of resorufin to various cellular proteins genetically fused to a 13-aa recognition peptide in multiple mammalian cell lines and in primary cultured neurons. We used resorufin ligase to perform superresolution imaging of themore » intermediate filament protein vimentin by stimulated emission depletion and electron microscopies. This work illustrates the power of Rosetta for major redesign of enzyme specificity and introduces a tool for minimally invasive, highly specific imaging of cellular proteins by both conventional and superresolution microscopies.« less

  1. Computational design of a red fluorophore ligase for site-specific protein labeling in living cells

    SciTech Connect

    Liu, Daniel S.; Nivon, Lucas G.; Richter, Florian; Goldman, Peter J.; Deerinck, Thomas J.; Yao, Jennifer Z.; Richardson, Douglas; Phipps, William S.; Ye, Anne Z.; Ellisman, Mark H.; Drennan, Catherine L.; Baker, David; Ting, Alice Y.

    2014-10-13

    In this study, chemical fluorophores offer tremendous size and photophysical advantages over fluorescent proteins but are much more challenging to target to specific cellular proteins. Here, we used Rosetta-based computation to design a fluorophore ligase that accepts the red dye resorufin, starting from Escherichia coli lipoic acid ligase. X-ray crystallography showed that the design closely matched the experimental structure. Resorufin ligase catalyzed the site-specific and covalent attachment of resorufin to various cellular proteins genetically fused to a 13-aa recognition peptide in multiple mammalian cell lines and in primary cultured neurons. We used resorufin ligase to perform superresolution imaging of the intermediate filament protein vimentin by stimulated emission depletion and electron microscopies. This work illustrates the power of Rosetta for major redesign of enzyme specificity and introduces a tool for minimally invasive, highly specific imaging of cellular proteins by both conventional and superresolution microscopies.

  2. Computational design of a red fluorophore ligase for site-specific protein labeling in living cells

    PubMed Central

    Liu, Daniel S.; Nivón, Lucas G.; Richter, Florian; Goldman, Peter J.; Deerinck, Thomas J.; Yao, Jennifer Z.; Richardson, Douglas; Phipps, William S.; Ye, Anne Z.; Ellisman, Mark H.; Drennan, Catherine L.; Baker, David; Ting, Alice Y.

    2014-01-01

    Chemical fluorophores offer tremendous size and photophysical advantages over fluorescent proteins but are much more challenging to target to specific cellular proteins. Here, we used Rosetta-based computation to design a fluorophore ligase that accepts the red dye resorufin, starting from Escherichia coli lipoic acid ligase. X-ray crystallography showed that the design closely matched the experimental structure. Resorufin ligase catalyzed the site-specific and covalent attachment of resorufin to various cellular proteins genetically fused to a 13-aa recognition peptide in multiple mammalian cell lines and in primary cultured neurons. We used resorufin ligase to perform superresolution imaging of the intermediate filament protein vimentin by stimulated emission depletion and electron microscopies. This work illustrates the power of Rosetta for major redesign of enzyme specificity and introduces a tool for minimally invasive, highly specific imaging of cellular proteins by both conventional and superresolution microscopies. PMID:25313043

  3. ZrO2 -Based Alternatives to Conventional Propane Dehydrogenation Catalysts: Active Sites, Design, and Performance.

    PubMed

    Otroshchenko, Tatyana; Sokolov, Sergey; Stoyanova, Mariana; Kondratenko, Vita A; Rodemerck, Uwe; Linke, David; Kondratenko, Evgenii V

    2015-12-21

    Non-oxidative dehydrogenation of propane to propene is an established large-scale process that, however, faces challenges, particularly in catalyst development; these are the toxicity of chromium compounds, high cost of platinum, and catalyst durability. Herein, we describe the design of unconventional catalysts based on bulk materials with a certain defect structure, for example, ZrO2 promoted with other metal oxides. Comprehensive characterization supports the hypothesis that coordinatively unsaturated Zr cations are the active sites for propane dehydrogenation. Their concentration can be adjusted by varying the kind of ZrO2 promoter and/or supporting tiny amounts of hydrogenation-active metal. Accordingly designed Cu(0.05 wt %)/ZrO2 -La2 O3 showed industrially relevant activity and durability over ca. 240 h on stream in a series of 60 dehydrogenation and oxidative regeneration cycles between 550 and 625 °C. PMID:26566072

  4. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Rifle, Colorado

    SciTech Connect

    Not Available

    1990-02-01

    This volume contains appendices D6 through D8 containing laboratory test data: from MK-F investigation, 1987, Old Rifle and New Rifle sites; on bentonite amended radon barrier material; and from MK-F investigation, 1987, riprap tests.

  5. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Attachment 2, Geology report. Revised final report

    SciTech Connect

    Not Available

    1991-12-01

    Detailed investigations of geologic, geomorphic, and seismic conditions at the Bodo Canyon disposal site were conducted. The purpose of these investigations was basic site characterization and identification of potential geologic hazards that could affect long-term site stability. Subsequent engineering studies, such as analyses of hydrologic and liquefaction hazards, used the data developed in these studies. The geomorphic analysis was employed in the design of effective erosion protection. Studies of the regional and local seismotectonic setting, which included a detailed search for possible capable faults within a 65 kilometer radius of the site, provided the basis for seismic design parameters. The scope of work performed included the following: Compilation and analysis of previous published and unpublished geologic literature and maps; Review of historical and instrumental earthquake data; Review of site-specific subsurface geologic data, including lithologic and geophysical logs of exploratory boreholes advanced in the site area; Photogeologic interpretations of existing conventional aerial photographs; and, Ground reconnaissance and mapping of the site region.

  6. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Gunnison, Colorado. Attachment 2, Geology report: Final report

    SciTech Connect

    Not Available

    1992-10-01

    Detailed investigations of geologic, geomorphic, and seismic conditions at the Landfill disposal site were conducted. The purpose of these studies was basic site characterization and identification of potential geologic hazards that could affect long-term site stability. Subsequent engineering studies, such as analyses of hydrologic and liquefaction hazards, used the data developed in these studies. The geomorphic analysis was employed in the design of effective erosion protection. Studies of the regional and local seismotectonic setting, which included a detailed search for possible capable faults within a 65-kilometer (km) (40-mile) radius of the site, provided the basis for seismic design parameters. The scope of work performed included the following: Compilation and analysis of previous published and unpublished geologic literature and maps. Review of historical and instrumental earthquake data. Review of site-specific subsurface geologic data, including lithologic and geophysical logs of exploratory boreholes advanced in the site area. Photogeologic interpretations of existing conventional aerial photographs. Ground reconnaissance and mapping of the site region.

  7. Computational approaches to identifying and characterizing protein binding sites for ligand design.

    PubMed

    Henrich, Stefan; Salo-Ahen, Outi M H; Huang, Bingding; Rippmann, Friedrich F; Cruciani, Gabriele; Wade, Rebecca C

    2010-01-01

    Given the three-dimensional structure of a protein, how can one find the sites where other molecules might bind to it? Do these sites have the properties necessary for high affinity binding? Is this protein a suitable target for drug design? Here, we discuss recent developments in computational methods to address these and related questions. Geometric methods to identify pockets on protein surfaces have been developed over many years but, with new algorithms, their performance is still improving. Simulation methods show promise in accounting for protein conformational variability to identify transient pockets but lack the ease of use of many of the (rigid) shape-based tools. Sequence and structure comparison approaches are benefiting from the constantly increasing size of sequence and structure databases. Energetic methods can aid identification and characterization of binding pockets, and have undergone recent improvements in the treatment of solvation and hydrophobicity. The "druggability" of a binding site is still difficult to predict with an automated procedure. The methodologies available for this purpose range from simple shape and hydrophobicity scores to computationally demanding free energy simulations. PMID:19746440

  8. Design of Hanford Site 4th Generation Multi Function Corrosion Monitoring System

    SciTech Connect

    NORMAN, E.C.

    2000-08-30

    This document describes the design of the fourth-generation corrosion monitoring system scheduled to be installed in DST 241-AN-104 early in fiscal year 2001. A fourth-generation multi-function corrosion monitoring system has been designed for installation into a DST in the 241-AN farm at the Hanford Site in FY 2001. Improvements and upgrades from the third-generation system (installed in 241-AN-105) that have been incorporated into the fourth-generation system include: Addition of a built-in water lance to assist installation of probe into tanks with a hard crust layer at the surface of the waste; and Improvement of the electrode mounting apparatus used to attach the corrosion monitoring electrodes to the stainless steel probe body (new design simplifies probe assembly/wiring). These new features improve on the third-generation design and yield a system that is easier to fabricate and install, provides for a better understanding of the relationship between corrosion and other tank operating parameters, and optimizes the use of the riser that houses the probe in the tank.

  9. CHARACTERIZING THE YUCCA MOUNTAIN SITE FOR DEVELOPING SEISMIC DESIGN GROUND MOTIONS

    SciTech Connect

    S. Upadhyaya, I. Wong, R. Kulkarni, K. Stokoe, M. Dober, W. Silva, and R. Quittmeyer

    2006-02-24

    Yucca Mountain, Nevada is the designated site for the first long-term geologic repository to safely dispose spent nuclear fuel and high-level nuclear waste in the U.S. Yucca Mountain consists of stacked layers of welded and non-welded volcanic tuffs. Site characterization studies are being performed to assess its future performance as a permanent geologic repository. These studies include the characterization of the shear-wave velocity (Vs) structure of the repository block and the surface facilities area. The Vs data are an input in the calculations of ground motions for the preclosure seismic design and for postclosure performance assessment and therefore their accurate estimation is needed. Three techniques have been employed: 24 downhole surveys, 15 suspension seismic logging surveys and 95 spectral-analysis-of-surface-waves (SASW) surveys have been performed to date at the site. The three data sets were compared with one another and with Vs profiles developed from vertical seismic profiling data collected by the Lawrence Berkeley National Laboratory and with Vs profiles developed independently by the University of Nevada, Reno using the refraction microtremor technique. Based on these data, base case Vs profiles have been developed and used in site response analyses. Since the question of adequate sampling arises in site characterization programs and a correlation between geology and Vs would help address this issue, a possible correlation was evaluated. To assess the influence of different factors on velocity, statistical analyses of the Vs data were performed using the method of multi-factor Analysis of Variance (ANOVA). The results of this analysis suggest that the effect of each of three factors, depth, lithologic unit, and spatial location, on velocity is statistically significant. Furthermore, velocity variation with depth is different at different spatial locations: Preliminary results show that the lithologic unit alone explains about 54% and 42% of

  10. Design of a multiplexer to characterize individual optics at a concentrating photovoltaic test site

    NASA Astrophysics Data System (ADS)

    Wilkins, Matthew; Beal, Richard; Haysom, Joan E.; Wheeldon, Jeffrey F.; Mulet, Philippe; Jamieson, Graeme; Youssef, Nashed; Balachandreswaran, Dhan; Fan, Jennifer; Hall, Trevor; Myrskog, Stefan; Hinzer, Karin

    2011-08-01

    An on-sun Concentrating Photovoltaic (CPV) test site with a multiplexed current-voltage measurement capability has been installed at the University of Ottawa. Herein, we present details of the instrumentation, which is designed to provide in-situ I-V measurements of individual solar cells within a functioning, series connected, string. A 4-wire multiplexing system enables current-voltage measurements of individual cells. Where other multi-cell test systems have left cells at open-circuit or connected to a fixed resistor when not selected by the multiplexer, in this system each test cell operates within a string of cells controlled by a maximum power point tracker. This allows us to maintain the test cells at realistic operating conditions for all irradiance conditions. Using the current-voltage data, a range of parameters of interest can be monitored over time, including the solar cell temperature, photovoltaic efficiency and optical efficiency. This information is correlated with time-synchronized spectrometer and pyrheliometer data, allowing automated collection of performance data from several strings of optic/solar cell assemblies. The test site includes two 20m2, dual-axis, ring mounted solar trackers and is being used to test new CPV systems which incorporate novel lightguiding optics designed and manufactured by Morgan Solar Inc.

  11. Remedial Action Plan and site conceptual design for stabilization of the inactive uranium mill tailings site at Spook, Wyoming

    SciTech Connect

    Matthews, M L; Sullivan, M

    1990-04-01

    This Remedial Action Plan (RAP) has been developed to serve a threefold purpose. It presents the series of activities which are proposed by the US Department of Energy (DOE) to accomplish long-term stabilization and control of radioactive materials at an inactive uranium processing site northeast of Casper, Wyoming, and referred to as the Spook site. It provides a characterization of the present conditions at the site and also serves to document the concurrence of the State of Wyoming and the US Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by the DOE and the State of Wyoming, and concurrence by the NRC, becomes Appendix B of the Cooperative Agreement.

  12. 75 FR 22524 - Ocean Dumping; Designation of Ocean Dredged Material Disposal Sites Offshore of the Siuslaw River...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... the Federal Register in 1977 (42 FR 2461), a status superseded by later statutory changes to the MPRSA. Mounding at Site A and concern over the potential for ocean currents to move sediments from Site A back..., EPA published a proposed rule at 75 FR 5708 to designate two new ocean dredged material disposal...

  13. 76 FR 43685 - Designation of an Ocean Dredged Material Disposal Site (ODMDS) in the Gulf of Mexico Off the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... for Voluntary Preparation of National Environmental Policy Act (NEPA) Documents (63 FR 58045), and in... AGENCY Designation of an Ocean Dredged Material Disposal Site (ODMDS) in the Gulf of Mexico Off the Mouth... Act of 1972 (MPRSA), and 40 CFR Part 228 (Criteria for the Management of Disposal Sites for...

  14. Issues and recent advances in optimal experimental design for site investigation (Invited)

    NASA Astrophysics Data System (ADS)

    Nowak, W.

    2013-12-01

    This presentation provides an overview over issues and recent advances in model-based experimental design for site exploration. The addressed issues and advances are (1) how to provide an adequate envelope to prior uncertainty, (2) how to define the information needs in a task-oriented manner, (3) how to measure the expected impact of a data set that it not yet available but only planned to be collected, and (4) how to perform best the optimization of the data collection plan. Among other shortcomings of the state-of-the-art, it is identified that there is a lack of demonstrator studies where exploration schemes based on expert judgment are compared to exploration schemes obtained by optimal experimental design. Such studies will be necessary do address the often voiced concern that experimental design is an academic exercise with little improvement potential over the well- trained gut feeling of field experts. When addressing this concern, a specific focus has to be given to uncertainty in model structure, parameterizations and parameter values, and to related surprises that data often bring about in field studies, but never in synthetic-data based studies. The background of this concern is that, initially, conceptual uncertainty may be so large that surprises are the rule rather than the exception. In such situations, field experts have a large body of experience in handling the surprises, and expert judgment may be good enough compared to meticulous optimization based on a model that is about to be falsified by the incoming data. In order to meet surprises accordingly and adapt to them, there needs to be a sufficient representation of conceptual uncertainty within the models used. Also, it is useless to optimize an entire design under this initial range of uncertainty. Thus, the goal setting of the optimization should include the objective to reduce conceptual uncertainty. A possible way out is to upgrade experimental design theory towards real-time interaction

  15. Houdini: Site and locomotion analysis-driven design of an in-tank mobile cleanup robot

    SciTech Connect

    Schempf, H.

    1995-10-01

    This paper describes design and locomotion analysis efforts to develop a new reconfigurable and collapsible working machine, dubbed Houdini, to remotely clean up hazardous-waste and petroleum storage tanks. The tethered robot system is designed to allow remote entry through man-way openings as small as 0.61 m in diameter, after which it expands its locomotors and opens up its collapsible backhoe/manipulator and plow to subsequently perform waste or material handling operations. The design is optimized to meet stringent site and safety requirements, and represents a viable alternative to (1) the long-reach manipulation systems proposed for hazardous storage tank cleanup, and (2) confined-entry manual cleanup approaches. The system development has been funded to provide waste mobilization and removal solutions for the hazardous waste storage tanks in the Department of Energy (DoE) Fernald and Oak Ridge complexes. Other potential applications areas are the cleanup of heavy-crude petroleum storage tanks. The author has developed a fully operational prototype which is currently undergoing testing.

  16. Remedial Action Plan and Site Design for Stabilization of the Inactive Uranium Mill Tailings Site, Maybell, Colorado. Remedial action selection report: Attachment 2, Geology report, Final

    SciTech Connect

    Not Available

    1994-06-01

    The Maybell uranium mill tailings site is 25 miles (mi) (40 kilometers [km]) west of the town of Craig, Colorado, in Moffat County, in the northwestern part of the state. The unincorporated town of Maybell is 5 road mi (8 km) southwest of the site. The designated site covers approximately 110 acres (ac) (45 hectares [ha]) and consists of a concave-shaped tailings pile and rubble from the demolition of the mill buildings buried in the former mill area. Contaminated materials at the Maybell processing site include the tailings pile, which has an average depth of 20 feet (ft) (6 meters [m]) and contains 2.8 million cubic yards (yd{sup 3}) (2.1 million cubic meters [m{sup 3}]) of tailings. The former mill processing area is on the north side of the site and contains 20,000 yd{sup 3} (15,000 m{sup 3}) of contaminated demolition debris. Off-pile contamination is present and includes areas adjacent to the tailings pile, as well as contamination dispersed by wind and surface water flow. The volume of off-pile contamination to be placed in the disposal cell is 550,000 yd{sup 3} (420,000 m{sup 3}). The total volume of contaminated materials to be disposed of as part of the remedial action is estimated to be 3.37 million yd{sup 3} (2.58 million m{sup 3}). Information presented in this Final Remedial Action Plan (RAP) and referenced in supporting documents represents the current disposal cell design features and ground water compliance strategy proposed by the US Department of Energy (DOE) for the Maybell, Colorado, tailings site. Both the disposal cell design and the ground water compliance strategy have changed from those proposed prior to the preliminary final RAP document as a result of prudent site-specific technical evaluations.

  17. DNA damage processing by human 8-oxoguanine-DNA glycosylase mutants with the occluded active site.

    PubMed

    Lukina, Maria V; Popov, Alexander V; Koval, Vladimir V; Vorobjev, Yuri N; Fedorova, Olga S; Zharkov, Dmitry O

    2013-10-01

    8-Oxoguanine-DNA glycosylase (OGG1) removes premutagenic lesion 8-oxoguanine (8-oxo-G) from DNA and then nicks the nascent abasic (apurinic/apyrimidinic) site by β-elimination. Although the structure of OGG1 bound to damaged DNA is known, the dynamic aspects of 8-oxo-G recognition are not well understood. To comprehend the mechanisms of substrate recognition and processing, we have constructed OGG1 mutants with the active site occluded by replacement of Cys-253, which forms a wall of the base-binding pocket, with bulky leucine or isoleucine. The conformational dynamics of OGG1 mutants were characterized by single-turnover kinetics and stopped-flow kinetics with fluorescent detection. Additionally, the conformational mobility of wild type and the mutant OGG1 substrate complex was assessed using molecular dynamics simulations. Although pocket occlusion distorted the active site and greatly decreased the catalytic activity of OGG1, it did not fully prevent processing of 8-oxo-G and apurinic/apyrimidinic sites. Both mutants were notably stimulated in the presence of free 8-bromoguanine, indicating that this base can bind to the distorted OGG1 and facilitate β-elimination. The results agree with the concept of enzyme plasticity, suggesting that the active site of OGG1 is flexible enough to compensate partially for distortions caused by mutation. PMID:23955443

  18. Catalysis by Design: Well-Defined Single-Site Heterogeneous Catalysts.

    PubMed

    Pelletier, Jérémie D A; Basset, Jean-Marie

    2016-04-19

    Heterogeneous catalysis, a field important industrially and scientifically, is increasingly seeking and refining strategies to render itself more predictable. The main issue is due to the nature and the population of catalytically active sites. Their number is generally low to very low, their "acid strengths" or " redox properties" are not homogeneous, and the material may display related yet inactive sites on the same material. In many heterogeneous catalysts, the discovery of a structure-activity reationship is at best challenging. One possible solution is to generate single-site catalysts in which most, if not all, of the sites are structurally identical. Within this context and using the right tools, the catalyst structure can be designed and well-defined, to reach a molecular understanding. It is then feasible to understand the structure-activity relationship and to develop predictable heterogeneous catalysis. Single-site well-defined heterogeneous catalysts can be prepared using concepts and tools of surface organometallic chemistry (SOMC). This approach operates by reacting organometallic compounds with surfaces of highly divided oxides (or of metal nanoparticles). This strategy has a solid track record to reveal structure-activity relationship to the extent that it is becoming now quite predictable. Almost all elements of the periodical table have been grafted on surfaces of oxides (from simple oxides such as silica or alumina to more sophisticated materials regarding composition or porosity). Considering catalytic hydrocarbon transformations, heterogeneous catalysis outcome may now be predicted based on existing mechanistic proposals and the rules of molecular chemistry (organometallic, organic) associated with some concepts of surface sciences. A thorough characterization of the grafted metal centers must be carried out using tools spanning from molecular organometallic or surface chemistry. By selection of the metal, its ligand set, and the support taken

  19. Molecular docking sites designed for the generation of highly crystalline covalent organic frameworks

    NASA Astrophysics Data System (ADS)

    Ascherl, Laura; Sick, Torben; Margraf, Johannes T.; Lapidus, Saul H.; Calik, Mona; Hettstedt, Christina; Karaghiosoff, Konstantin; Döblinger, Markus; Clark, Timothy; Chapman, Karena W.; Auras, Florian; Bein, Thomas

    2016-04-01

    Covalent organic frameworks (COFs) formed by connecting multidentate organic building blocks through covalent bonds provide a platform for designing multifunctional porous materials with atomic precision. As they are promising materials for applications in optoelectronics, they would benefit from a maximum degree of long-range order within the framework, which has remained a major challenge. We have developed a synthetic concept to allow consecutive COF sheets to lock in position during crystal growth, and thus minimize the occurrence of stacking faults and dislocations. Hereby, the three-dimensional conformation of propeller-shaped molecular building units was used to generate well-defined periodic docking sites, which guided the attachment of successive building blocks that, in turn, promoted long-range order during COF formation. This approach enables us to achieve a very high crystallinity for a series of COFs that comprise tri- and tetradentate central building blocks. We expect this strategy to be transferable to a broad range of customized COFs.

  20. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Slick Rock, Colorado: Remedial Action Selection Report. Preliminary final

    SciTech Connect

    Not Available

    1994-03-01

    This proposed remedial action plan incorporates the results of detailed investigation of geologic, geomorphic, and seismic conditions at the proposed disposal site. The proposed remedial action will consist of relocating the uranium mill tailings, contaminated vicinity property materials, demolition debris, and windblown/waterborne materials to a permanent repository at the proposed Burro Canyon disposal cell. The proposed disposal site will be geomorphically stable. Seismic design parameters were developed for the geotechnical analyses of the proposed cell. Cell stability was analyzed to ensure long-term performance of the disposal cell in meeting design standards, including slope stability, settlement, and liquefaction potential. The proposed cell cover and erosion protection features were also analyzed and designed to protect the RRM (residual radioactive materials) against surface water and wind erosion. The location of the proposed cell precludes the need for permanent drainage or interceptor ditches. Rock to be used on the cell top-, side-, and toeslopes was sized to withstand probable maximum precipitation events.

  1. Design of multiligand inhibitors for the swine flu H1N1 neuraminidase binding site.

    PubMed

    Narayanan, Manoj M; Nair, Chandrasekhar B; Sanjeeva, Shilpa K; Rao, Pv Subba; Pullela, Phani K; Barrow, Colin J

    2013-01-01

    Viral neuraminidase inhibitors such as oseltamivir and zanamivir prevent early virus multiplication by blocking sialic acid cleavage on host cells. These drugs are effective for the treatment of a variety of influenza subtypes, including swine flu (H1N1). The binding site for these drugs is well established and they were designed based on computational docking studies. We show here that some common natural products have moderate inhibitory activity for H1N1 neuraminidase under docking studies. Significantly, docking studies using AutoDock for biligand and triligand forms of these compounds (camphor, menthol, and methyl salicylate linked via methylene bridges) indicate that they may bind in combination with high affinity to the H1N1 neuraminidase active site. These results also indicate that chemically linked biligands and triligands of these natural products could provide a new class of drug leads for the prevention and treatment of influenza. This study also highlights the need for a multiligand docking algorithm to understand better the mode of action of natural products, wherein multiple active ingredients are present. PMID:23983477

  2. Design of multiligand inhibitors for the swine flu H1N1 neuraminidase binding site

    PubMed Central

    Narayanan, Manoj M; Nair, Chandrasekhar B; Sanjeeva, Shilpa K; Rao, PV Subba; Pullela, Phani K; Barrow, Colin J

    2013-01-01

    Viral neuraminidase inhibitors such as oseltamivir and zanamivir prevent early virus multiplication by blocking sialic acid cleavage on host cells. These drugs are effective for the treatment of a variety of influenza subtypes, including swine flu (H1N1). The binding site for these drugs is well established and they were designed based on computational docking studies. We show here that some common natural products have moderate inhibitory activity for H1N1 neuraminidase under docking studies. Significantly, docking studies using AutoDock for biligand and triligand forms of these compounds (camphor, menthol, and methyl salicylate linked via methylene bridges) indicate that they may bind in combination with high affinity to the H1N1 neuraminidase active site. These results also indicate that chemically linked biligands and triligands of these natural products could provide a new class of drug leads for the prevention and treatment of influenza. This study also highlights the need for a multiligand docking algorithm to understand better the mode of action of natural products, wherein multiple active ingredients are present. PMID:23983477

  3. 75 FR 38129 - Freescale Semiconductor, Inc., Hardware/Software Design and Manufacturing A Including On-Site...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ... published in the Federal Register on May 28, 2010 (75 FR 30070). At the request of the State Agency, the... Manufacturing A Including On-Site Leased Workers From TAC Worldwide, GDA Technologies, Inc., Manpower, Ion..., GDA Technologies, Inc., Manpower, Ion Design, Design Solutions, Inc., Veriseo, SilconElite and...

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. Emergence of new red-shifted carbon nanotube photoluminescence based on proximal doped-site design.

    PubMed

    Shiraki, Tomohiro; Shiraishi, Tomonari; Juhász, Gergely; Nakashima, Naotoshi

    2016-01-01

    Single-walled carbon nanotubes (SWNTs) show unique photoluminescence (PL) in the near-infrared (NIR) region. Here we propose a concept based on the proximal modification in local covalent functionalization of SWNTs. Quantum mechanical simulations reveal that the SWNT band gap changes specifically based on the proximal doped-site design. Thus, we synthesize newly-designed bisdiazonium molecules and conduct local fucntionalisation of SWNTs. Consequently, new red-shifted PL (E11(2*)) from the bisdiazonium-modified SWNTs with (6, 5) chirality is recognized around 1250 nm with over ~270 nm Stokes shift from the PL of the pristine SWNTs and the PL wavelengths are shifted depending on the methylene spacer lengths of the modifiers. The present study revealed that SWNT PL modulation is enable by close-proximity-local covalent modification, which is highly important for fundamental understanding of intrinsic SWNT PL properties as well as exciton engineering-based applications including photonic devices and (bio)imaging/sensing. PMID:27345862

  7. Comparison of Permeability and Groutability of Ostur Dam Site Rock Mass for Grout Curtain Design

    NASA Astrophysics Data System (ADS)

    Sadeghiyeh, S. M.; Hashemi, M.; Ajalloeian, R.

    2013-03-01

    The focus of this study is the empirical hydromechanical behaviour of the Ostur dam site rock mass. The area surrounding the dam mostly consists of diorite and andesite, with primary fractures and hydrothermal veins. The hydromechanical behaviour of the rocks was determined using 500 water pressure tests at 5-m intervals. The hydrothermal veins and 2,739 discontinuities were studied and mapped along the dam axis. As a result, it was possible to design an optimum grout curtain for the dam axis. The empirical hydromechanical behaviour of the rock was studied to determine water flow and grout pressurised flow during the field tests that were conducted on two representative A-series grouting operation boreholes (one borehole for each abutment). The secondary permeability index (SPI), Lugeon value (LU), rock quality designation (RQD) and cement take (CT) values are presented and compared in this article. It is concluded that permeability and groutability are mostly controlled by the specifications and characteristics of the veins, especially in shallow areas and lower depths. A procedure is proposed based on a comparison of the trends in the RQD-SPI and LU-CT, and it is suggested that the areas with diverging trends require no treatment and that those with converging trends require heavy treatment. Additional complementary studies that were conducted during the construction stage have validated these results.

  8. Emergence of new red-shifted carbon nanotube photoluminescence based on proximal doped-site design

    NASA Astrophysics Data System (ADS)

    Shiraki, Tomohiro; Shiraishi, Tomonari; Juhász, Gergely; Nakashima, Naotoshi

    2016-06-01

    Single-walled carbon nanotubes (SWNTs) show unique photoluminescence (PL) in the near-infrared (NIR) region. Here we propose a concept based on the proximal modification in local covalent functionalization of SWNTs. Quantum mechanical simulations reveal that the SWNT band gap changes specifically based on the proximal doped-site design. Thus, we synthesize newly-designed bisdiazonium molecules and conduct local fucntionalisation of SWNTs. Consequently, new red-shifted PL (E112*) from the bisdiazonium-modified SWNTs with (6, 5) chirality is recognized around 1250 nm with over ~270 nm Stokes shift from the PL of the pristine SWNTs and the PL wavelengths are shifted depending on the methylene spacer lengths of the modifiers. The present study revealed that SWNT PL modulation is enable by close-proximity-local covalent modification, which is highly important for fundamental understanding of intrinsic SWNT PL properties as well as exciton engineering–based applications including photonic devices and (bio)imaging/sensing.

  9. Emergence of new red-shifted carbon nanotube photoluminescence based on proximal doped-site design

    PubMed Central

    Shiraki, Tomohiro; Shiraishi, Tomonari; Juhász, Gergely; Nakashima, Naotoshi

    2016-01-01

    Single-walled carbon nanotubes (SWNTs) show unique photoluminescence (PL) in the near-infrared (NIR) region. Here we propose a concept based on the proximal modification in local covalent functionalization of SWNTs. Quantum mechanical simulations reveal that the SWNT band gap changes specifically based on the proximal doped-site design. Thus, we synthesize newly-designed bisdiazonium molecules and conduct local fucntionalisation of SWNTs. Consequently, new red-shifted PL (E112*) from the bisdiazonium-modified SWNTs with (6, 5) chirality is recognized around 1250 nm with over ~270 nm Stokes shift from the PL of the pristine SWNTs and the PL wavelengths are shifted depending on the methylene spacer lengths of the modifiers. The present study revealed that SWNT PL modulation is enable by close-proximity-local covalent modification, which is highly important for fundamental understanding of intrinsic SWNT PL properties as well as exciton engineering–based applications including photonic devices and (bio)imaging/sensing. PMID:27345862

  10. Early Site Permit Demonstration Program: Guidelines for determining design basis ground motions. Volume 1

    SciTech Connect

    Not Available

    1993-03-18

    This report develops and applies a methodology for estimating strong earthquake ground motion. The motivation was to develop a much needed tool for use in developing the seismic requirements for structural designs. An earthquake`s ground motion is a function of the earthquake`s magnitude, and the physical properties of the earth through which the seismic waves travel from the earthquake fault to the site of interest. The emphasis of this study is on ground motion estimation in Eastern North America (east of the Rocky Mountains), with particular emphasis on the Eastern United States and southeastern Canada. Eastern North America is a stable continental region, having sparse earthquake activity with rare occurrences of large earthquakes. While large earthquakes are of interest for assessing seismic hazard, little data exists from the region to empirically quantify their effects. Therefore, empirically based approaches that are used for other regions, such as Western North America, are not appropriate for Eastern North America. Moreover, recent advances in science and technology have now made it possible to combine theoretical and empirical methods to develop new procedures and models for estimating ground motion. The focus of the report is on the attributes of ground motion in Eastern North America that are of interest for the design of facilities such as nuclear power plants. Specifically considered are magnitudes M from 5 to 8, distances from 0 to 500 km, and frequencies from 1 to 35 Hz.

  11. Remedial action plan and site conceptual design for stabilization of the inactive uranium mill tailings site at Ambrosia Lake, New Mexico

    SciTech Connect

    Matthews, M.L. . Uranium Mill Tailings Remedial Action Project Office); Mitzelfelt, R. . Environmental Improvement Div.)

    1991-11-01

    This Remedial Action Plan (RAP) has been developed to serve a dual purpose. It presents the series of activities that is proposed by the US Department of Energy (DOE) to stabilize and control radioactive materials at the inactive Phillips/United Nuclear uranium processing site designated as the Ambrosia Lake site in McKinley County, New Mexico. It also serves to document the concurrence of both State of New Mexico and the US Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by the DOE and the state and concurrence by NRC, becomes Appendix B of the Cooperative Agreement.

  12. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Tuba City, Arizona. Text, Appendices A, B, and C: Final report

    SciTech Connect

    Not Available

    1989-08-01

    This Remedial Action Plan (RAP) has been developed to serve a threefold purpose. It presents the series of activities which are proposed by the US Department of Energy (DOE) to accomplish long-term stabilization and control of radioactive materials at the inactive uranium processing site near Tuba City, Arizona. It provides a characterization of the present conditions of the site. It also serves to document the concurrence of the Navajo Nation, the Hopi Tribe, US Bureau of Indian Affairs (BIA), and the US Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by DOE, the Navajo Nation, and the Hopi Tribe, and concurrence by NRC, becomes Appendix B of the Cooperative Agreement. Following the introduction, contents are as follows: Section 2.0 presents the EPA standards, including a discussion of their objectives. Section 3.0 summarizes the present site characteristics and provides a definition of site-specific problems. Section 4.0 is the site design for the proposed action. Section 5.0 summarizes the plan for ensuring environmental, health, and safety protection for the surrounding community and the on-site workers. Section 6.0 presents a detailed listing of the responsibilities of the project participants. Section 7.0 describes the features of the long-term surveillance and maintenance plan. Section 8.0 presents the quality assurance aspects of the project. Section 9.0 documents the ongoing activities to keep the public informed and participating in the project.

  13. Design-Basis Flood Estimation for Site Characterization at Nuclear Power Plants in the United States of America

    SciTech Connect

    Prasad, Rajiv; Hibler, Lyle F.; Coleman, Andre M.; Ward, Duane L.

    2011-11-01

    The purpose of this document is to describe approaches and methods for estimation of the design-basis flood at nuclear power plant sites. Chapter 1 defines the design-basis flood and lists the U.S. Nuclear Regulatory Commission's (NRC) regulations that require estimation of the design-basis flood. For comparison, the design-basis flood estimation methods used by other Federal agencies are also described. A brief discussion of the recommendations of the International Atomic Energy Agency for estimation of the design-basis floods in its member States is also included.

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

    PubMed Central

    2013-01-01

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

  15. Seismic design of circular-section concrete-lined underground openings: Preclosure performance considerations for the Yucca Mountain Site

    SciTech Connect

    Richardson, A.M.; Blejwas, T.E.

    1992-07-01

    Yucca Mountain, the potential site of a repository for high-level radioactive waste, is situated in a region of natural and man-made seismicity. Underground openings excavated at this site must be designed for worker safety in the seismic environment anticipated for the preclosure period. This includes accesses developed for site characterization regardless of the ultimate outcome of the repository siting process. Experience with both civil and mining structures has shown that underground openings are much more resistant to seismic effects than surface structures, and that even severe dynamic strains can usually be accommodated with proper design. This paper discusses the design and performance of lined openings in the seismic environment of the potential site. The types and ranges of possible ground motions (seismic loads) are briefly discussed. Relevant historical records of underground opening performance during seismic loading are reviewed. Simple analytical methods of predicting liner performance under combined in situ, thermal, and seismic loading are presented, and results of calculations are discussed in the context of realistic performance requirements for concrete-lined openings for the preclosure period. Design features that will enhance liner stability and mitigate the impact of the potential seismic load are reviewed. The paper is limited to preclosure performance concerns involving worker safety because present decommissioning plans specify maintaining the option for liner removal at seal locations, thus decoupling liner design from repository postclosure performance issues.

  16. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Mexican Hat, Utah: Appendix E. Final report

    SciTech Connect

    1988-07-01

    This document provides Appendix E of the Remedial Action Plan (RAP) presented in 1988 for the stabilization of the inactive uranium mill tailings at the Mexican Hat, Utah site. The RAP was developed to serve a two- fold purpose. It presents the activities proposed by the Department of Energy (DOE) to accomplish long-term stabilization and control of the residual radioactive materials (RRM) from Monument Valley, Arizona, and Mexican Hat, Utah, at the Mexican Hat disposal site. It also serves to document the concurrence of both the Navajo Nation and the Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by the DOE and the Navajo Nation and concurrence by the NRC, becomes Appendix B of the Cooperative Agreement. The RAP has been structured to provide a comprehensive understanding of the remedial action proposed for the Monument Valley and Mexican Hat sites. It includes specific design and construction requirements for the remedial action.

  17. Site Identification by Ligand Competitive Saturation (SILCS) simulations for fragment-based drug design.

    PubMed

    Faller, Christina E; Raman, E Prabhu; MacKerell, Alexander D; Guvench, Olgun

    2015-01-01

    Fragment-based drug design (FBDD) involves screening low molecular weight molecules ("fragments") that correspond to functional groups found in larger drug-like molecules to determine their binding to target proteins or nucleic acids. Based on the principle of thermodynamic additivity, two fragments that bind nonoverlapping nearby sites on the target can be combined to yield a new molecule whose binding free energy is the sum of those of the fragments. Experimental FBDD approaches, like NMR and X-ray crystallography, have proven very useful but can be expensive in terms of time, materials, and labor. Accordingly, a variety of computational FBDD approaches have been developed that provide different levels of detail and accuracy.The Site Identification by Ligand Competitive Saturation (SILCS) method of computational FBDD uses all-atom explicit-solvent molecular dynamics (MD) simulations to identify fragment binding. The target is "soaked" in an aqueous solution with multiple fragments having different identities. The resulting computational competition assay reveals what small molecule types are most likely to bind which regions of the target. From SILCS simulations, 3D probability maps of fragment binding called "FragMaps" can be produced. Based on the probabilities relative to bulk, SILCS FragMaps can be used to determine "Grid Free Energies (GFEs)," which provide per-atom contributions to fragment binding affinities. For essentially no additional computational overhead relative to the production of the FragMaps, GFEs can be used to compute Ligand Grid Free Energies (LGFEs) for arbitrarily complex molecules, and these LGFEs can be used to rank-order the molecules in accordance with binding affinities. PMID:25709034

  18. Site Identification by Ligand Competitive Saturation (SILCS) Simulations for Fragment-Based Drug Design

    PubMed Central

    Faller, Christina E.; Raman, E. Prabhu; MacKerell, Alexander D.; Guvench, Olgun

    2015-01-01

    Fragment-based drug design (FBDD) involves screening low molecular weight molecules (“fragments”) that correspond to functional groups found in larger drug-like molecules to determine their binding to target proteins or nucleic acids. Based on the principle of thermodynamic additivity, two fragments that bind non-overlapping nearby sites on the target can be combined to yield a new molecule whose binding free energy is the sum of those of the fragments. Experimental FBDD approaches, like NMR and X-ray crystallography, have proven very useful but can be expensive in terms of time, materials, and labor. Accordingly, a variety of computational FBDD approaches have been developed that provide different levels of detail and accuracy. The Site Identification by Ligand Competitive Saturation (SILCS) method of computational FBDD uses all-atom explicit-solvent molecular dynamics (MD) simulations to identify fragment binding. The target is “soaked” in an aqueous solution with multiple fragments having different identities. The resulting computational competition assay reveals what small molecule types are most likely to bind which regions of the target. From SILCS simulations, 3D probability maps of fragment binding called “FragMaps” can be produced. Based on the probabilities relative to bulk, SILCS FragMaps can be used to determine “Grid Free Energies (GFEs),” which provide per-atom contributions to fragment binding affinities. For essentially no additional computational overhead relative to the production of the FragMaps, GFEs can be used to compute Ligand Grid Free Energies (LGFEs) for arbitrarily complex molecules, and these LGFEs can be used to rank-order the molecules in accordance with binding affinities. PMID:25709034

  19. Rational Catalyst Design of Titanium-Silica Materials Aided by Site-Specific Titration Tools

    NASA Astrophysics Data System (ADS)

    Eaton, Todd Robert

    between particle and crystal size, as obtained from XRD. In the course of establishing these relationships we've gained the knowledge of how to control TiO x structure, which enables the design of new and better catalysts. Understanding the synthesis-structure-function relationships allow for the design of a tandem photo/thermocatalytic reaction system for producing and consuming H2O2. By partially overcoating a TiO 2 photocatalyst with a ˜2 nm silica layer we observe a 56-fold rate improvement compared to bare-TiO2 for H2O2 synthesis from the proton-assisted reduction of O2. Addition of metal-SiO2 thermocatalysts (metal=Ti, Nb, or Ta) with sites needed for H2O2 activation creates a tandem system wherein the H2O2 produced in situ is utilized for alkene epoxidation. Compared to a thermocatalytic-only system, the tandem system accelerates epoxidation for cis-cyclooctene(11x faster), styrene(20x) and 1-octene(30x). This approach demonstrates a means for epoxidation with O2 that avoids H2O2 purification and transport, simplifies the total process, provides new opportunities for control by independent H2O2 production and consumption in the same reactor, and enhances rates relative to thermocatalytic-only epoxidation by intimately coupling H2O2 generation and consumption. Critically, establishment of titanium-silica synthesis-structure-function relationships enables the design of new catalysts and systems that are less energy- and material-intensive, leading towards more sustainable chemistry.

  20. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Rifle, Colorado. Volume 1, Text: Appendices A, B, and C: Final report

    SciTech Connect

    Not Available

    1990-02-01

    This document has been structured to provide a comprehensive understanding of the remedial action proposed for the Rifle sites. That remedial action consists of removing approximately 4,185,000 cubic yards (cy) of tailings and contaminated materials from their current locations, transporting, and stabilizing the tailings material at the Estes Gulch disposal site, approximately six miles north of Rifle. The tailings and contaminated materials are comprised of approximately 597,000 cy from Old Rifle, 3,232,000 cy from New Rifle, and 322,000 cy from vicinity properties and about 34,000 cy from demolition. The remedial action plan includes specific design requirements for the detailed design and construction of the remedial action. An extensive amount of data and supporting information have been generated for this remedial action and cannot all be incorporated into this document. Pertinent information and data are included with reference given to the supporting documents.

  1. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Slick Rock, Colorado. Final report

    SciTech Connect

    1996-08-01

    This document contains the page changes for Attachment 3, Ground Water Hydrology Report dated August, 1996 for the Remedial Action Plan and Site Design for Stabilization of the Inactive Uranium Mill Tailings at Slick Rock, Colorado. This portion of Attachment 3 contains the Table of Contents pages i and ii, and pages numbered 3-3 through 3-56 of the Ground Water Hydrology Report. Also included are the cover sheets for Appendix A, B, and C to Attachment 3.

  2. Paleolimnology Web Portal: A Web Site Designed to Increase Paleolimnology Data Availability

    NASA Astrophysics Data System (ADS)

    Eakin, C. M.; Moy, C. M.; Habermann, T.; Gross, W. S.; Keltner, J. M.

    2001-12-01

    Despite widespread use of lacustrine records to interpret paleolimnologic and paleoclimatic change, there is a large gap between the data published in peer-reviewed journals and those submitted for archive and available to other researchers online. A primary goal of the World Data Center (WDC) for paleoclimatology and the International Geosphere-Biosphere Programme (IGBP) - Past Global Changes (PAGES) core programme is to have full and open sharing of all data sets needed for global change studies. To help improve the quantity and quality of data submitted to the WDC for Paleoclimatology, we are developing online data submission and advanced interactive browse and access tools. Our poster presents a new web-site designed to make paleolimnology data more accessible by incorporating web-based data submission forms, a multi-proxy relational database, and interactive mapping tools. The WDC for Paleoclimatology is currently designing intuitive and streamlined web-based submission forms, which will allow investigators to quickly submit their data and metadata on-line. We are also importing all existing data and metadata in our archives into a multiproxy relational database that will allow users to quickly query and retrieve paleolimnological data, as well as display the data in various formats. Furthermore, we are implementing two Paleolimnology mapping tools that will allow users to search, display, and query data in a geographical format. The first tool, WebMapper, uses a Java applet to draw maps and display metadata. This will be supplemented by a plotting tool that will provide basic plotting functions to allow users to examine data before downloading them. The second mapping tool, ArcIMS, allows users to overlay paleoclimatic data with various GIS data sets in addition to providing basic spatial analysis functions. We believe that these new web-based features will encourage more extensive data sharing and submission, making paleolimnological data more available and

  3. Wind load comparison for the ASCE standard 7 and the Hanford site design criteria

    SciTech Connect

    Giller, R.A., Westinghouse Hanford

    1996-07-16

    This document provides calculations and discussions to compare Hanford Site wind load criteria with the current national standard for wind loads (ASCE 7, 1995). Site criteria uses the 1988 edition ASCE 7.

  4. Pilot-scale demonstration of surfactant-enhanced PCE solubilization at the Bachman Road site. 1. Site characterization and test design.

    PubMed

    Abriola, Linda M; Drummond, Chad D; Hahn, Ernest J; Hayes, Kim F; Kibbey, Tohren C G; Lemke, Lawrence D; Pennell, Kurt D; Petrovskis, Erik A; Ramsburg, C Andrew; Rathfelder, Klaus M

    2005-03-15

    A pilot-scale demonstration of surfactant-enhanced aquifer remediation (SEAR) was conducted to recover dense nonaqueous phase liquid (DNAPL) tetrachloroethene (PCE) from a sandy glacial outwash aquifer underlying a former dry cleaning facility at the Bachman Road site in Oscoda, MI. Part one of this two-part paper describes site characterization efforts and a comprehensive approach to SEAR test design, effectively integrating laboratory and modeling studies. Aquifer coring and drive point sampling suggested the presence of PCE-DNAPL in a zone beneath an occupied building. A narrow PCE plume emanating from the vicinity of this building discharges into Lake Huron. The shallow unconfined aquifer, characterized by relatively homogeneous fine-medium sand deposits, an underlying clay layer, and the absence of significant PCE transformation products, was judged suitable for the demonstration of SEAR. Tween 80 was selected for application based upon its favorable solubilization performance in batch and two-dimensional sand tank treatability studies, biodegradation potential, and regulatory acceptance. Three-dimensional flow and transport models were employed to develop a robust design for surfactant delivery and recovery. Physical and fiscal constraints led to an unusual hydraulic design, in which surfactant was flushed across the regional groundwater gradient, facilitating the delivery of concentrations of Tween 80 exceeding 1% (wt) throughout the treatment zone. The potential influence of small-scale heterogeneity on PCE-DNAPL distribution and SEAR performance was assessed through numerical simulations incorporating geostatistical permeability fields based upon available core data. For the examined conditions simulated PCE recoveries ranged from 94to 99%. The effluent treatment system design consisted of low-profile air strippers coupled with carbon adsorption to trap off-gas PCE and discharge of treated aqueous effluent to a local wastewater treatment plant. The

  5. Design, construction, and performance of a single geomembrane liner system at a residual waste disposal site in western Pennsylvania

    SciTech Connect

    Khilji, K.H.; Gould, S.E.; Hamel, T.W.; Thomas, W.B.

    1997-11-01

    This paper examines the effectiveness of a single geomembrane-lined deep valley coal ash/coal mine refuse disposal site to maintain ground-water quality after 10 years of operation. The site occupies over 81 hectares (ha) [200 acres (ac)] in western Pennsylvania. The effectiveness of the liner system was evaluated based on an assessment of the site`s ground-water quality. The liner system was designed in 1983. Selection of geosynthetics and drainage materials, interface shear values, and construction control methods were based on laboratory testing, field investigations, slope stability analyses, and construction load analyses. Diligent construction quality control was applied during all aspects of site development. To examine the site`s ground-water quality, the ground-water monitoring network was sampled approximately once every six weeks for one year. Results of statistical analyses show that the liner system is effectively separating disposal site leachate from ground water and that the site is not degrading ground water.

  6. Designing an in-flight airborne calibration site using experience from vicarious radiometric satellite calibration

    NASA Astrophysics Data System (ADS)

    Livens, Stefan; Debruyn, Walter; Sterckx, Sindy; Reusen, Ils

    2011-11-01

    Laboratory calibration of electro-optical sensors is preferably complemented by regular in-flight verification. This checks whether the lab calibration parameters remain valid or recalibration is necessary. In-flight verification can be achieved by vicarious calibration using in-flight measurements of calibration targets. We intend to identify and design a set of suitable radiometric calibration targets. For this, we borrow from expertise gained with the PROBA-V satellite calibration system, which uses multiple vicarious methods relying on diverse natural on-ground targets. Besides reflectance based calibration using ground measurements, the PROBA-V calibration methods are unproven for use in airborne calibration. The selected targets should be suitable for the calibration of both multispectral and hyperspectral imagers. We start from general requirements for radiometric targets and investigate their applicability to airborne calibration. From this we identify two possible sets of natural calibration sites in Belgium. One set, located in the Campine region, contains small water bodies and sandy lakesides. Another set is located in the Westhoek region near the Belgian coast. It offers better suitable water bodies, as well as sandy areas, grass fields and dark targets. Airborne calibration lends itself to the use of smaller artifical targets. We propose to complement the natural targets with a portable target consisting of agricultural nets with different densities. The definition of sets of calibration targets, both natural and artificial can facilitate the investigation of the usability of vicarious targets and method for inflight radiometric verification.

  7. Geotechnical, Hydrogeologic and Vegetation Data Package for 200-UW-1 Waste Site Engineered Surface Barrier Design

    SciTech Connect

    Ward, Andy L.

    2007-11-26

    Fluor Hanford (FH) is designing and assessing the performance of engineered barriers for final closure of 200-UW-1 waste sites. Engineered barriers must minimize the intrusion and water, plants and animals into the underlying waste to provide protection for human health and the environment. The Pacific Northwest National Laboratory (PNNL) developed Subsurface Transport Over Multiple Phases (STOMP) simulator is being used to optimize the performance of candidate barriers. Simulating barrier performance involves computation of mass and energy transfer within a soil-atmosphere-vegetation continuum and requires a variety of input parameters, some of which are more readily available than others. Required input includes parameter values for the geotechnical, physical, hydraulic, and thermal properties of the materials comprising the barrier and the structural fill on which it will be constructed as well as parameters to allow simulation of plant effects. This report provides a data package of the required parameters as well as the technical basis, rationale and methodology used to obtain the parameter values.

  8. Hydrolysis of phosphodiesters by diiron complexes: design of nonequivalent iron sites in purple acid phosphatase models.

    PubMed

    Verge, François; Lebrun, Colette; Fontecave, Marc; Ménage, Stéphane

    2003-01-27

    New mu-oxo-diferric complexes have been designed for hydrolysis of phosphodiesters. To mimic the diiron active site of purple acid phosphatase, a combinatorial method has been used to select complexes containing two distinct iron coordination spheres. The introduction of a bidentate ligand, a substituted phenanthroline (L) into complex 1, [Fe2O(bipy)4(OH2)2](NO3)4, generates in solution the complex [Fe2O(bipy)3(L)(OH2)2](NO3)4 as shown by ESI/MS and 1H NMR studies. The latter complex was found to be 20-fold more active than complex 1. On the basis of kinetic studies, we demonstrated that the complex [Fe2O(bipy)3(L)(OH)(OH2)](NO3)3 was the active species and the reaction proceeded through the formation of a ternary complex in which one iron binds a hydroxide and the second, the substrate. At nonsaturating concentrations of the substrate, the increased activity with increased methyl substituents in L was due to an increased affinity of the complex for the substrate. The activity of [Fe2O(bipy)3(33'44'Me2-Phen)(OH2)2](NO3)4 [33'44'Me2Phen = 3,3',4,4'-dimethyl-1,10-phenanthroline] was found to be comparable to that reported for Co(III) or Ce(IV) complexes. PMID:12693232

  9. Conceptual design study. Standard Floating Nuclear Power Plant on inshore site and Modified Floating Nuclear Power plant on upriver site

    NASA Astrophysics Data System (ADS)

    1982-02-01

    Both plants/designs are technically feasible. Both compare favorably with conventional nuclear plants with respect to licensability, quality of construction, reliability of operation, and safety. Both offer considerable reductions in construction schedule over conventional nuclear plants. It was estimated that if project durations were reduced by three years the cost of a 1100 MWe nuclear unit could be decreased by $260 million to $450 million. The allowance for funds during construction (AFDC) was estimated to be $929 million for a 1260 MWe nuclear plant with a commercial operation date in 1992. Reducing the schedule from 12 to 9 years, a reduction of 25%, implies a savings in AFDC alone of approximately $230 million. .DLN : Killed, superseded by N85-21597 NASA patent

  10. Site Selection for the European ELT: working package included in the European FP6 ``ELT design study'' contract

    NASA Astrophysics Data System (ADS)

    Muñoz-Tuñón, C.; Sarazin, M.; Vernin, J.

    2007-10-01

    The site selection for the future European Large Telescope (E-ELT) is a key issue within the European proposal funded by the European Union (EU), within the ``ELT design study'' proposal. The organization, working scheme and baseline frameworks are reviewed. For the definition of the working package WP12000 ``Site Characterization'', important use has been done of previous work in the definition of techniques and tools for the study of the atmosphere above observing sites. We have also taken advantage of the number of data already available which have naturally defined a ranking among the known places which have also been taken as a base line for pre-selecting the candidate sites. The work will last 4 years, it started in 2005 and is organized in subtasks, working packages WP, whose main objectives are the following: WP12100: to characterize two top astronomical sites (ORM and North-Paranal) and to explore three other alternatives (Macon in Argentina, Izaña in Spain and Aklim in Morocco) suitable to install an ELT under the best conditions (Dome C is been currently under investigation, and no particular effort will be put in this site, but rather its atmospheric properties will be compared to the above mentioned sites). WP12200 is dedicated to design, build and operate a set of standard equipment in all the sites and to perform long term campaign. WP12300 will investigate wavefront properties over large baselines (50-100 m) corresponding to the size of the future ELT, as well as the fine characterization of the optical turbulence within the boundary layer. A similar plan is being carried out by the Thirty Meter Telescope (TMT) site selection team. For the sake of saving resources (budget and people), the TMT preselected sites (all in the American Continent) are not included in our European study.

  11. Site study plan for Exploratory shaft facilities design foundation boreholes (shaft surface facility foundation borings), Deaf Smith County Site, Texas: Surface-based geotechnical field program: Preliminary draft

    SciTech Connect

    Not Available

    1987-12-01

    This site study plan describes the Exploratory Shaft Facilities (ESF) Design Foundation Boreholes field activities to be conducted during early stages of Site Characterization at the Deaf Smith County, Texas, site. The field program has been designed to provide data useful in addressing information/data needs resulting from federal/state/local regulations, and repository program requirements. Approximately 50 foundation boreholes will be drilled within the ESP location to provide data necessary for design of the ESF and to satisfy applicable shaft permitting requirements. Soils and subsurface rock will be sampled as the foundation boreholes are advanced. Soil samples or rock core will be taken through the Blackwater Draw and Ogallala Formations and the Dockum Group. Hydrologic testing will be performed in boreholes that penetrates the water table. In-situ elastic properties will be determined from both the soil strata and rock units along the length of the boreholes. Field methods/tests are chosen that provide the best or only means of obtaining the required data. The Salt Repository Project (SRP) Networks specify the schedule under which the program will operate. Drilling will not begin until after site ground water baseline conditions have been established. The Technical Field Services Contractor is responsible for conducting the field program of drilling and testing. Samples and data will be handled and reported in accordance with established SRP procedures. A quality assurance program will be utilized to assure that activities affecting quality are performed correctly and that the appropriate documentation is maintained. 25 refs., 10 figs., 6 tabs.

  12. A terrain-based paired-site sampling design to assess biodiversity losses from eastern hemlock decline

    USGS Publications Warehouse

    Young, J.A.; Smith, D.R.; Snyder, C.D.; Lemarie, D.P.

    2002-01-01

    Biodiversity surveys are often hampered by the inability to control extraneous sources of variability introduced into comparisons of populations across a heterogenous landscape. If not specifically accounted for a priori, this noise can weaken comparisons between sites, and can make it difficult to draw inferences about specific ecological processes. We developed a terrain-based, paired-site sampling design to analyze differences in aquatic biodiversity between streams draining eastern hemlock (Tsuga canadensis) forests, and those draining mixed hardwood forests in Delaware Water Gap National Recreation Area (USA). The goal of this design was to minimize variance due to terrain influences on stream communities, while representing the range of hemlock dominated stream environments present in the park. We used geographic information systems (GIS) and cluster analysis to define and partition hemlock dominated streams into terrain types based on topographic variables and stream order. We computed similarity of forest stands within terrain types and used this information to pair hemlock-dominated streams with hardwood counterparts prior to sampling. We evaluated the effectiveness of the design through power analysis and found that power to detect differences in aquatic invertebrate taxa richness was highest when sites were paired and terrain type was included as a factor in the analysis. Precision of the estimated difference in mean richness was nearly doubled using the terrain-based, paired site design in comparison to other evaluated designs. Use of this method allowed us to sample stream communities representative of park-wide forest conditions while effectively controlling for landscape variability.

  13. Site specific cleavage of thetaX-174 replicative form DNA after modification by N-acetoxy-N-2-acetylaminofluorene

    SciTech Connect

    Bases, R.; Mendez, F.; Mendez, L.

    1983-01-01

    Three kinds of structural disturbances were found in an 88 base pair (bp) fragment of thetaX-174 DNA after exposure to N-acetoxy-N-2-acetylaminofluorene (N-Aco-AAF). Frequent strand scissions at two specific guanine sites on the 5' /sup 32/P-end-labeled fragment were identified by base sequence analysis. Scissions at these two sites were induced at neutral pH and they were not increased by treatment with apurinic endonuclease. They are an immediate consequence of N-Aco-AAF action and are not primarily apurinic sites. Alkali treatment with 1 M piperidine at 90/sup 0/C induced strand scissions at every guanine, demonstrating adduct slices, depurination and strand scissions. Adducted DNA was sensitive to single-strand specific nuclease digestion, suggesting unwound DNA. These studies indicate the prediliction of N-Aco-AAF for certain DNA sites and they suggest three kinds of DNA modifications which can be expected after adduction by this carcinogen. Some of the sites may be premutational carcinogen-induced DNA structural modifications.

  14. X-ray crystallographic analyses of symmetrical allosteric effectors of hemoglobin: compounds designed to link primary and secondary binding sites.

    PubMed

    Safo, Martin K; Boyiri, Telih; Burnett, James C; Danso-Danquah, Richmond; Moure, Carmen M; Joshi, Gajanan S; Abraham, Donald J

    2002-04-01

    The rational design and X-ray crystallographic analyses of two symmetrical allosteric effectors of hemoglobin (Hb) are reported. Compound design was directed by the previously solved co-crystal structure of one of the most potent allosteric effectors of Hb, 2-[4-[(3,5-dichlorophenylcarbamoyl)-methyl]-phenoxy]-2-methylpropionic acid (RSR4), which revealed two distinct binding sites for this compound in the Hb central water cavity. The primary binding site has been observed for all compounds of this structural class, which stabilize deoxy Hb by engaging in inter-dimer contacts with three of the four protein subunits. Interactions at the secondary binding site of RSR4 occur primarily between the beta(1) and beta(2) subunits and serve to further constrain the deoxy state. Based on these observations, it was hypothesized that compounds with the ability to simultaneously span and link both of these sites would possess increased potency, but at a lower molar concentration than RSR4. Two symmetrical compounds were designed and synthesized based on this hypothesis. The symmetrical effector approach was taken to minimize the number of compound orientations needed to successfully bind at either of the distinct allosteric sites. X-ray crystallographic analyses of these two effectors in complex with Hb revealed that they successfully spanned the RSR4 primary and secondary binding sites. However, the designed compounds interacted with the secondary binding site in such a way that intra-dimer, as opposed to inter-dimer, interactions were generated. In agreement with these observations, in vitro evaluation of the symmetrical effectors in Hb solution indicated that neither compound possessed the potency of RSR4. A detailed analysis of symmetrical effector-Hb contacts and comparisons with the binding contacts of RSR4 are discussed. PMID:11914488

  15. Design report for the interim waste containment facility at the Niagara Falls Storage Site. [Surplus Facilities Management Program

    SciTech Connect

    Not Available

    1986-05-01

    Low-level radioactive residues from pitchblende processing and thorium- and radium-contaminated sand, soil, and building rubble are presently stored at the Niagara Falls Storage Site (NFSS) in Lewiston, New York. These residues and wastes derive from past NFSS operations and from similar operations at other sites in the United States conducted during the 1940s by the Manhattan Engineer District (MED) and subsequently by the Atomic Energy Commission (AEC). The US Department of Energy (DOE), successor to MED/AEC, is conducting remedial action at the NFSS under two programs: on-site work under the Surplus Facilities Managemnt Program and off-site cleanup of vicinity properties under the Formerly Utilized Sites Remedial Action Program. On-site remedial action consists of consolidating the residues and wastes within a designated waste containment area and constructing a waste containment facility to prevent contaminant migration. The service life of the system is 25 to 50 years. Near-term remedial action construction activities will not jeopardize or preclude implementation of any other remedial action alternative at a later date. Should DOE decide to extend the service life of the system, the waste containment area would be upgraded to provide a minimum service life of 200 years. This report describes the design for the containment system. Pertinent information on site geology and hydrology and on regional seismicity and meteorology is also provided. Engineering calculations and validated computer modeling studies based on site-specific and conservative parameters confirm the adequacy of the design for its intended purposes of waste containment and environmental protection.

  16. Automated Site-Directed Drug Design: The Formation of Molecular Templates in Primary Structure Generation

    NASA Astrophysics Data System (ADS)

    Lewis, R. A.; Dean, P. M.

    1989-03-01

    In this paper the spacer skeleton concept is used to produce molecular graphs of putative ligands for binding sites. The skeletons are transformed into molecular templates within the constraints of the accessible surface of the ligand-binding site. A distance-matrix method is used to compare ligand points with vertices of the spacer skeleton through a permutation of all possible correspondences. A tolerance parameter is used to screen for poor matches. As a result. a small number of matched vertices and ligand points are produced. These are fitted into the site by a constrained optimization routine using an analytical function. Ligand points fall within the site and are optimally positioned adjacent to the corresponding site points, other vertices of the spacer skeleton lying beneath the accessible surface of the site are clipped off. A molecular template is thereby formed with its vertices linked to the ligand points. The final step is to verify that the bonding integrity of the skeleton remains. The computational methods outlined in this paper have been tested at two binding sites the pteridine binding site in dihydrofolate reductase and the amidinophenylpyruvate site of trypsin. Molecular graphs for both sites were generated automatically, they showed strong similarity to those of the natural ligands.

  17. LEAD (Pb) IN BIOTA AND PERCEPTIONS OF Pb EXPOSURE AT A RECENTLY DESIGNATED SUPERFUND BEACH SITE IN NEW JERSEY

    PubMed Central

    Burger, Joanna; Gochfeld, Michael; Jeitner, Christian; Donio, Mark; Pittfield, Taryn

    2014-01-01

    The Raritan Bay Slag Site (New Jersey) was designated a Superfund site in 2009 because the seawall, jetties, and sediment contained lead (Pb). Our objective was to compare Pb and mercury (Hg) levels in biota and public perceptions of exposure at the Superfund and reference sites. Samples (algae, invertebrates, fish) were collected from the Raritan Bay Slag Site and reference sites and analyzed for Pb and Hg. Waterfront users were interviewed using a standard questionnaire. Levels of Pb in aquatic organisms were compared to ecological and human health safety standards. Lead levels were related to location, trophic level, and mobility. Lead levels in biota were highest at the western side of the West Jetty. Mean Pb levels were highest for algae (Fucus = 53,600 ± 6990 ng/g = ppb [wet weight], Ulva = 23,900 ± 2430 ppb), intermediate for grass shrimp (7270 ± 1300 ppb, 11,600 ± 3340 ppb), and lowest for fish (Atlantic silversides 218 ± 44 ppb). Within species, Pb levels varied significantly across the sampling sites. Lead levels in algae, sometimes ingested by individuals, were sufficiently high to exceed human safety levels. Mercury levels did not differ between the Superfund and reference sites. Despite the fence and warnings, people (1) used the Superfund and reference sites similarly, (2) had similar fish consumption rates, and (3) were not concerned about Pb, although most individuals knew the metal was present. The fish sampled posed no apparent risk for human consumers, but the algae did. PMID:22409490

  18. Lead (Pb) in biota and perceptions of Pb exposure at a recently designated Superfund beach site in New Jersey.

    PubMed

    Burger, Joanna; Gochfeld, Michael; Jeitner, Christian; Donio, Mark; Pittfield, Taryn

    2012-01-01

    The Raritan Bay Slag Site (New Jersey) was designated a Superfund site in 2009 because the seawall, jetties, and sediment contained lead (Pb). Our objective was to compare Pb and mercury (Hg) levels in biota and public perceptions of exposure at the Superfund and reference sites. Samples (algae, invertebrates, fish) were collected from the Raritan Bay Slag Site and reference sites and analyzed for Pb and Hg. Waterfront users were interviewed using a standard questionnaire. Levels of Pb in aquatic organisms were compared to ecological and human health safety standards. Lead levels were related to location, trophic level, and mobility. Lead levels in biota were highest at the western side of the West Jetty. Mean Pb levels were highest for algae (Fucus = 53,600 ± 6990 ng/g = ppb [wet weight], Ulva = 23,900 ± 2430 ppb), intermediate for grass shrimp (7270 ± 1300 ppb, 11,600 ± 3340 ppb), and lowest for fish (Atlantic silversides 218 ± 44 ppb). Within species, Pb levels varied significantly across the sampling sites. Lead levels in algae, sometimes ingested by individuals, were sufficiently high to exceed human safety levels. Mercury levels did not differ between the Superfund and reference sites. Despite the fence and warnings, people (1) used the Superfund and reference sites similarly, (2) had similar fish consumption rates, and (3) were not concerned about Pb, although most individuals knew the metal was present. The fish sampled posed no apparent risk for human consumers, but the algae did. PMID:22409490

  19. Modification No. 2 to the remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Green River, Utah: Final

    SciTech Connect

    1996-11-01

    Portions of the final Remedial Action Plan (RAP) for the Green River site, Volumes 1 and 2, Appendix B of the Cooperative Agreement No. DE-FC04-81AL16257, March 1991 (DOE, 1991) have been modified. The changes to the RAP are designated as RAP Modification No. 2. These changes have been placed in a three-ring binder that will supplement the original RAP (DOE, 1991), and include the following: addendum to the Executive Summary; Section 3.5 (Ground Water part of the Site Characterization Summary); Section 4.0 (Site Design); Section5.0 (Water Resources Protection Strategy Summary); Appendix D.5 (Ground Water Hydrology); and Appendix E (Ground Water Protection Strategy). In addition to these revisions, there have been editorial changes that clarify the text, but do not change the meaning. Also, certain sections of the document, which are included in the submittal for ease of review and continuity, have been updated to reflect the final ground water protection standards and the current UMTRA Project format and content of RAPs.

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

    SciTech Connect

    Not Available

    1991-12-01

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

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

    SciTech Connect

    Not Available

    1991-12-01

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

  2. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Falls City, Texas. [Uranium Mill Tailings Remedial Action (UMTRA) Project

    SciTech Connect

    Chernoff, A.R. . Uranium Mill Tailings Remedial Action Project Office); Lacker, D.K. . Bureau of Radiation Control)

    1992-09-01

    The uranium processing site near Falls City, Texas, was one of 24 inactive uranium mill sites designated to be remediated by the US Department of Energy (DOE) under Title I of the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA). The UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE's remedial action plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the US Environmental Protection Agency (EPA). The RAP, which includes this summary remedial action selection report (RAS), serves a two-fold purpose. First, it describes the activities proposed by the DOE to accomplish long-term stabilization and control of the residual radioactive materials at the inactive uranium processing site near Falls City, Texas. Second, this document and the remainder of the RAP, upon concurrence and execution by the DOE, the State of Texas, and the NRC, becomes Appendix B of the Cooperative Agreement between the DOE and the State of Texas.

  3. Remedial action plan and site design for stabilization of the inactive uranium processing site at Naturita, Colorado. Remedial action selection report, Attachment 2, Geology report: Preliminary final

    SciTech Connect

    Not Available

    1993-08-01

    The uranium processing site near Naturita, Colorado, is one of 24 inactive uranium mill sites designated to be cleaned up by the US Department of Energy (DOE) under the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA), Public Law 95-604. Part of the UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE`s remedial action plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the US Environmental Protection Agency (EPA). Included in the RAP is this Remedial Action Selection Report (RAS), which serves two purposes. First, it describes the activities that are proposed by the DOE to accomplish remediation and long-term stabilization and control of the radioactive materials at the inactive uranium processing site near Naturita, Colorado. Second, this document and the rest of the RAP, upon concurrence and execution by the DOE, the state of Colorado, and the NRC, become Appendix B of the cooperative agreement between the DOE and the State of Colorado.

  4. Multiple-site replacement analogs of glucagon. A molecular basis for antagonist design.

    PubMed

    Unson, C G; Wu, C R; Fitzpatrick, K J; Merrifield, R B

    1994-04-29

    Extensive structure activity analysis has allowed us to identify specific residues in the glucagon sequence that are responsible for either receptor recognition or signal transduction. For instance, we have demonstrated that aspartic acid 9 and histidine 1 are essential for activation, and that an ionic interaction between the negative carboxylate and the protonated imidazole may contribute to the activation reaction at the molecular level. In the absence of the carboxylic group at position 9, aspartic 21 or aspartic 15 might furnish distal electrostatic effects to maintain partial agonism. Further investigation established that each of the 4 serine residues in the hormone play distinct roles. Serine 8 provides an important determinant of binding. Whereas neither serines 2, 11, nor 16 are required for receptor recognition. We have shown that serine 16 is essential for signal transduction and thus have identified it to be the third residue in glucagon to participate in a putative catalytic triad together with aspartic 9 and histidine 1, in the transduction of the glucagon response. In this work, we utilized insights into the functional significance of particular residues in the peptide appropriated from our structure-function assignments, as the basis of a molecular approach for the design of active-site directed antagonists of glucagon. The importance as well as the accuracy of our findings are confirmed by the synthesis of a series of improved glucagon antagonists based on replacements at positions 1, 9, 11, 16, and 21. The inhibition index, (I/A)50, of our best antagonist des-His1-[Nle9-Ala11-Ala16]glucagon amide, has been improved 10-fold over the previous best glucagon inhibitor. PMID:8175663

  5. Assessment, approval, design and construction of a facility on a Superfund site in 36 months

    SciTech Connect

    Drag, D.J.; Webb, C.K.; Luenenborg, G.W.

    1996-11-01

    The Union Pacific Resources Corporation (UPRC) owned and operated a 600-acre crude oil production field in Wilmington, California. UPRC granted a lease to the TCL Corporation in 1951 for the disposal of oil and gas drilling field wastes. In the 1950s and 1960s, waste materials consisting of oil-free rotary mud, as well as rotary mud containing oil and crude oil tank bottoms were accepted at the site. Site testing and record investigations have shown that some other wastes, inconsistent with those permitted by the agreement between UPRC and TCL, were also disposed of at the site. Soil samples collected from the site in 1981 showed moderately high levels of metals in the soils at the site. In 1983, the site was included on the California State Superfund list of hazardous waste contaminated sites. In 1988, UPRC signed a Consent order Agreement with the Department of Toxic Substance Control (DTSC) whereby UPRC agreed to investigate a 31-acre area of the Study Area and develop a Remedial Action Plan (RAP) with DTSC oversight. The Port of Long Beach (POLB) is assuming the responsibility for implementing subsequent investigative and remedial activities at the portions of the site which they have since purchased from UPRC. The overall project objective was to investigate a 31-acre parcel within the Study Area (TCL site), develop a RAP, remediate the oil sump soils, and develop the parcel as an automobile distribution facility to be used by Toyota Motor Sales (TMS).

  6. Development of in-structure design spectra for dome mounted equipment on underground waste storage tanks at the Hanford Site

    SciTech Connect

    Julyk, L.J.

    1995-09-01

    In-structure response spectra for dome mounted equipment on underground waste storage tanks at the Hanford Site are developed on the basis of recent soil-structure-interaction analyses. Recommended design spectra are provided for various locations on the tank dome.

  7. 77 FR 67399 - Hewlett-Packard Company, Design Delivery Organization (DDO), Including On-Site Leased Workers...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF LABOR Employment and Training Administration Hewlett-Packard Company, Design Delivery Organization (DDO), Including On-Site Leased Workers From Manpower, Synova Inc., and Pinnacle Technical Resources, Corvallis, OR; Hewlett-Packard Company, Ink Jet & Web...

  8. User-Interface Design Characteristics of Fortune 500 B2C E-Commerce Sites and Industry Differences

    ERIC Educational Resources Information Center

    Zhao, Jensen J.; Truell, Allen D.; Alexander, Melody W.

    2006-01-01

    This study examined the user-interface design characteristics of 107 Fortune 500 B2C e-commerce Web sites and industry differences. Data were collected from corporate homepages, B2C product/service pages, B2C interactive shopping pages, as well as customer satisfaction of 321 online shoppers. The findings indicate that (a) to attract online…

  9. 41 CFR 102-76.55 - What sustainable development principles must Federal agencies apply to the siting, design, and...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and Construction Sustainable Development § 102-76.55 What sustainable development principles must... Acquisition,” Federal agencies must apply sustainable development principles to the siting, design, and... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false What...

  10. 41 CFR 102-76.55 - What sustainable development principles must Federal agencies apply to the siting, design, and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... and Construction Sustainable Development § 102-76.55 What sustainable development principles must... Acquisition,” Federal agencies must apply sustainable development principles to the siting, design, and... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What...

  11. 41 CFR 102-76.55 - What sustainable development principles must Federal agencies apply to the siting, design, and...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and Construction Sustainable Development § 102-76.55 What sustainable development principles must... Acquisition,” Federal agencies must apply sustainable development principles to the siting, design, and... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false What...

  12. 41 CFR 102-76.55 - What sustainable development principles must Federal agencies apply to the siting, design, and...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... and Construction Sustainable Development § 102-76.55 What sustainable development principles must... Acquisition,” Federal agencies must apply sustainable development principles to the siting, design, and... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false What...

  13. 41 CFR 102-76.55 - What sustainable development principles must Federal agencies apply to the siting, design, and...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What sustainable development principles must Federal agencies apply to the siting, design, and construction of new facilities? 102-76.55 Section 102-76.55 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL...

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

    ERIC Educational Resources Information Center

    Odell, John H.

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

  15. Site characterization plan: Conceptual design report: Volume 4, Appendices F-O: Nevada Nuclear Waste Storage Investigations Project

    SciTech Connect

    MacDougall, H R; Scully, L W; Tillerson, J R

    1987-09-01

    The site for the prospective repository is located at Yucca Mountain in southwestern Nevada, and the waste emplacement area will be constructed in the underlying volcanic tuffs. The target horizon for waste emplacement is a sloping bed of densely welded tuff more than 650 ft below the surface and typically more than 600 ft above the water table. The conceptual design described in this report is unique among repository designs in that it uses ramps in addition to shafts to gain access to the underground facility, the emplacement horizon is located above the water table, and it is possible that 300- to 400-ft-long horizontal waste emplacement boreholes will be used. This report summarizes the design bases, design and performance criteria, and the design analyses performed. The current status of meeting the preclosure performance objectives for licensing and of resolving the repository design and preclosure issues is presented. The repository design presented in this report will be expanded and refined during the advanced conceptual design, the license application design, and the final procurement and construction design phases. Volume 4 contains Appendices F to O.

  16. [Rapid site-directed mutagenesis on full-length plasmid DNA by using designed restriction enzyme assisted mutagenesis].

    PubMed

    Zhang, Baozhong; Ran, Duoliang; Zhang, Xin; An, Xiaoping; Shan, Yunzhu; Zhou, Yusen; Tong, Yigang

    2009-02-01

    To use the designed restriction enzyme assisted mutagenesis technique to perform rapid site-directed mutagenesis on double-stranded plasmid DNA. The target amino acid sequence was reversely translated into DNA sequences with degenerate codons, resulting in large amount of silently mutated sequences containing various restriction endonucleases (REs). Certain mutated sequence with an appropriate RE was selected as the target DNA sequence for designing mutation primers. The full-length plasmid DNA was amplified with high-fidelity Phusion DNA polymerase and the amplified product was 5' phosphorylated by T4 polynucleotide kinase and then self-ligated. After transformation into an E. coli host the transformants were rapidly screened by cutting with the designed RE. With this strategy we successfully performed the site-directed mutagenesis on an 8 kb plasmid pcDNA3.1-pIgR and recovered the wild-type amino acid sequence of human polymeric immunoglobulin receptor (pIgR). A novel site-directed mutagenesis strategy based on DREAM was developed which exploited RE as a rapid screening measure. The highly efficient, high-fidelity Phusion DNA polymerase was applied to ensure the efficient and faithful amplification of the full-length sequence of a plasmid of up to 8 kb. This rapid mutagenesis strategy avoids using any commercial site-directed mutagenesis kits, special host strains or isotopes. PMID:19459340

  17. Trends in Culturally Relevant Interface Design Features for Latino Web Site Users

    ERIC Educational Resources Information Center

    Sachau, Lori L.; Hutchinson, Susan R.

    2012-01-01

    There is a lack of published research on designing Web-based instruction for the adult U.S. Latino population. Instructional designers need guidance on how to design culturally relevant learning environments for this audience, particularly for Latino people from Mexican heritage. The authors used content analysis to investigate the extent to which…

  18. 24 CFR 3285.103 - Site suitability with design zone maps.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... is to be installed. The design zone maps are those identified in part 3280 of this chapter. (a) Wind zone. Manufactured homes must not be installed in a wind zone that exceeds the design wind loads for which the home has been designed, as evidenced by the wind zone indicated on the home's data plate...

  19. Remedial action plan and site design for stabilization of the inactive Uranium Mill Tailings Site at Lowman, Idaho. Attachment 4, Water resources protection strategy: Final report

    SciTech Connect

    Not Available

    1991-09-01

    The DOE proposes to achieve compliance with the proposed EPA groundwater protection standards (Subparts A and B of 40 CFR 192) by meeting the EPA maximum concentration limits (MCLs) or background concentrations for designated hazardous constituents in groundwater in the uppermost aquifer (alluvium/weathered granodiorite) at the point of compliance (POC) at the Lowman disposal site near Lowman, Idaho. The proposed remedial action in conjunction with existing hydrogeological conditions at the Lowman site will ensure sufficient protection of human health and the environment. The DOE has concluded that the EPA groundwater protection standards will be met at the POC because, with the exception of antimony, none of the hazardous constituents that exceed laboratory method detection limits within the radioactive sand pore fluids were above the proposed concentration limits. The DOE has demonstrated that antimony will meet the proposed concentration limits at the POC through attenuation in subsoils beneath the disposal cell and by dilution in groundwater underflow. The Lowman processing site is in compliance with Subpart B of 40 CFR 192 because statistical analyses of groundwater samples indicate no groundwater contamination.

  20. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Mexican Hat, Utah: Text, Appendices A--C. Final report

    SciTech Connect

    1988-07-01

    This Remedial Action Plan (RAP) has been developed to serve a two- fold purpose. It presents the activities proposed by the Department of Energy (DOE) to accomplish long-term stabilization and control of the residual radioactive materials (RRM) from Monument Valley Arizona, and Mexican Hat, Utah, at the Mexican Hat disposal site. It also serves to document the concurrence of both the Navajo Nation and the Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by DOE and the Navajo Nation and concurrence by the NRC, becomes Appendix B of the Cooperative Agreement. This document has been structured to provide a comprehensive understanding of the remedial action proposed for the Monument Valley and Mexican Hat sites. It includes specific design and construction requirements for the remedial action. Pertinent information and data are included with reference given to the supporting documents. Appendices A,B, and C are provided as part of this document. Appendix A presents regulatory compliance issues, Appendix B provides details of the engineering design, and Appendix C presents the radiological support plan.

  1. 40 CFR 228.15 - Dumping sites designated on a final basis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... practicable alternatives (as defined in 40 CFR 227.16(b)) to open-water disposal in Long Island Sound and that...) Restrictions: See 40 CFR 228.15(b)(4)(vi). (c) Region I Final Other Wastes Sites. (1) No final sites. (2) (d... as to reduce impacts within the PRA to acceptable levels in accordance with 40 CFR 228.11(c). Use...

  2. 40 CFR 228.15 - Dumping sites designated on a final basis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... practicable alternatives (as defined in 40 CFR 227.16(b)) to open-water disposal in Long Island Sound and that...) Restrictions: See 40 CFR 228.15(b)(4)(vi). (c) Region I Final Other Wastes Sites. (1) No final sites. (2) (d... as to reduce impacts within the PRA to acceptable levels in accordance with 40 CFR 228.11(c). Use...

  3. Development of Site-Specific Soil Design Basis Earthquake (DBE) Parameters for the Integrated Waste Treatment Unit (IWTU)

    SciTech Connect

    Payne, Suzette

    2008-08-01

    Horizontal and vertical PC 3 (2,500 yr) Soil Design Basis Earthquake (DBE) 5% damped spectra, corresponding time histories, and strain-compatible soil properties were developed for the Integrated Waste Treatment Unit (IWTU). The IWTU is located at the Idaho Nuclear Technology and Engineering Center (INTEC) at the Idaho National Laboratory (INL). Mean and 84th percentile horizontal DBE spectra derived from site-specific site response analyses were evaluated for the IWTU. The horizontal and vertical PC 3 (2,500 yr) Soil DBE 5% damped spectra at the 84th percentile were selected for Soil Structure Interaction (SSI) analyses at IWTU. The site response analyses were performed consistent with applicable Department of Energy (DOE) Standards, recommended guidance of the Nuclear Regulatory Commission (NRC), American Society of Civil Engineers (ASCE) Standards, and recommendations of the Blue Ribbon Panel (BRP) and Defense Nuclear Facilities Safety Board (DNFSB).

  4. Bifunctional chelating agent for the design and development of site specific radiopharmaceuticals and biomolecule conjugation strategy

    DOEpatents

    Katti, Kattesh V.; Prabhu, Kandikere R.; Gali, Hariprasad; Pillarsetty, Nagavara Kishore; Volkert, Wynn A.

    2003-10-21

    There is provided a method of labeling a biomolecule with a transition metal or radiometal in a site specific manner to produce a diagnostic or therapeutic pharmaceutical compound by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radio metal or a transition metal, and covalently linking the resulting metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. Also provided is a method of synthesizing the --PR.sub.2 containing biomolecules by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radiometal or a transition metal, and covalently linking the resulting radio metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. There is provided a therapeutic or diagnostic agent comprising a --PR.sub.2 containing biomolecule.

  5. Environmental design criteria for the 1/3 scale OTEC cold water pipe at-sea test site off Honolulu, Hawaii

    NASA Astrophysics Data System (ADS)

    1983-01-01

    In order to expedite development of the design of the 1/3 scale At-Sea Test CWP/Platform/Mooring System, environmental design criteria data at the proposed At-Sea Test site evaluated from available historic data is provided. An evaluation of the available data to date is described. It is expected that as the design develops actual site specific observation will be obtained to verify these critical design criteria.

  6. Sampling design and procedures for fixed surface-water sites in the Georgia-Florida coastal plain study unit, 1993

    USGS Publications Warehouse

    Hatzell, H.H.; Oaksford, E.T.; Asbury, C.E.

    1995-01-01

    The implementation of design guidelines for the National Water-Quality Assessment (NAWQA) Program has resulted in the development of new sampling procedures and the modification of existing procedures commonly used in the Water Resources Division of the U.S. Geological Survey. The Georgia-Florida Coastal Plain (GAFL) study unit began the intensive data collection phase of the program in October 1992. This report documents the implementation of the NAWQA guidelines by describing the sampling design and procedures for collecting surface-water samples in the GAFL study unit in 1993. This documentation is provided for agencies that use water-quality data and for future study units that will be entering the intensive phase of data collection. The sampling design is intended to account for large- and small-scale spatial variations, and temporal variations in water quality for the study area. Nine fixed sites were selected in drainage basins of different sizes and different land-use characteristics located in different land-resource provinces. Each of the nine fixed sites was sampled regularly for a combination of six constituent groups composed of physical and chemical constituents: field measurements, major ions and metals, nutrients, organic carbon, pesticides, and suspended sediments. Some sites were also sampled during high-flow conditions and storm events. Discussion of the sampling procedure is divided into three phases: sample collection, sample splitting, and sample processing. A cone splitter was used to split water samples for the analysis of the sampling constituent groups except organic carbon from approximately nine liters of stream water collected at four fixed sites that were sampled intensively. An example of the sample splitting schemes designed to provide the sample volumes required for each sample constituent group is described in detail. Information about onsite sample processing has been organized into a flowchart that describes a pathway for each of

  7. 78 FR 73097 - Ocean Dumping; Sabine-Neches Waterway (SNWW) Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-05

    ... Federal Register (FR) April 4, 2011 (Vol. 76, Nos. 43). That document is available for public inspection.... Pursuant to its voluntary NEPA policy, published at 63 FR 58045 (October 29, 1998), EPA typically relies on... designation through a rulemaking process published in the Federal Register (FR). Formal designation of...

  8. Teaching E-Commerce Web Page Evaluation and Design: A Pilot Study Using Tourism Destination Sites

    ERIC Educational Resources Information Center

    Susser, Bernard; Ariga, Taeko

    2006-01-01

    This study explores a teaching method for improving business students' skills in e-commerce page evaluation and making Web design majors aware of business content issues through cooperative learning. Two groups of female students at a Japanese university studying either tourism or Web page design were assigned tasks that required cooperation to…

  9. Software Design for Wireless Sensor-based Site-specific Irrigation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In-field sensor-based site-specific irrigation management is of benefit to producers for efficient water management. Integration of the decision making process with the controls is a viable option for determining when and where to irrigate, and how much water to apply. This research presents the des...

  10. Impact of habitat variability on biological assessments at hazardous waste sites -- design and data interpretation considerations

    SciTech Connect

    Henry, R.

    1994-12-31

    Biological assessment methods that use aquatic macroinvertebrate communities to assess environmental impacts have been developed and used at hazardous waste sites. Shifts in community structure and function typically are attributed to the availability and toxicity of a contaminant, and information of this nature may be incorporated into remedial decisions. However, chemical stressors are often associated with habitat characteristics that may result in or contribute to an observed biological response. An ecological assessment focusing on benthic macroinvertebrates was conducted in a third order stream adjacent to a hazardous waste site. Habitat variability throughout the study area complicated the selection of sampling locations and equipment, and threatened to obscure potential ecological impairment associated with contaminants. For example, a 540 hectare impoundment exists approximately 100 meters upstream of the site which affects water quality, nutrient availability, and hydrology. Furthermore, portions of the stream adjacent to and immediately downstream of the site consist of a series of small, interconnecting braids that form the central core of a riparian wetland hydrosystem. Finally, historic and current riparian landaus includes mining, industrial, commercial, residential, and forested areas. Several reference areas, replicate and multihabitat samples, and careful habitat analysis were used to discriminate between habitat and contaminant effects. Although contaminants were detected in the stream, results of the macroinvertebrate survey and habitat analysis suggest that shifts in community structure and function were driven by habitat characteristics and that contaminants were not biologically available or present in toxic concentrations.

  11. Design, development and evaluation of a tree planting-site-specific fumigant applicator

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of this research was to use recent advances in the global positioning system (GPS) and computer technology to apply just the right amount of fumigant where it is most needed (i.e., tree-planting-site-specific application) to decrease the incidence of replant disease, and achieve the environ...

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

    ERIC Educational Resources Information Center

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

    2016-01-01

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

  13. Computational design of an endo-1,4-β-xylanase ligand binding site

    PubMed Central

    Morin, Andrew; Kaufmann, Kristian W.; Fortenberry, Carie; Harp, Joel M.; Mizoue, Laura S.; Meiler, Jens

    2011-01-01

    The field of computational protein design has experienced important recent success. However, the de novo computational design of high-affinity protein–ligand interfaces is still largely an open challenge. Using the Rosetta program, we attempted the in silico design of a high-affinity protein interface to a small peptide ligand. We chose the thermophilic endo-1,4-β-xylanase from Nonomuraea flexuosa as the protein scaffold on which to perform our designs. Over the course of the study, 12 proteins derived from this scaffold were produced and assayed for binding to the target ligand. Unfortunately, none of the designed proteins displayed evidence of high-affinity binding. Structural characterization of four designed proteins revealed that although the predicted structure of the protein model was highly accurate, this structural accuracy did not translate into accurate prediction of binding affinity. Crystallographic analyses indicate that the lack of binding affinity is possibly due to unaccounted for protein dynamics in the ‘thumb’ region of our design scaffold intrinsic to the family 11 β-xylanase fold. Further computational analysis revealed two specific, single amino acid substitutions responsible for an observed change in backbone conformation, and decreased dynamic stability of the catalytic cleft. These findings offer new insight into the dynamic and structural determinants of the β-xylanase proteins. PMID:21349882

  14. Computational design of an endo-1,4-[beta]-xylanase ligand binding site

    SciTech Connect

    Morin, Andrew; Kaufmann, Kristian W.; Fortenberry, Carie; Harp, Joel M.; Mizoue, Laura S.; Meiler, Jens

    2012-09-05

    The field of computational protein design has experienced important recent success. However, the de novo computational design of high-affinity protein-ligand interfaces is still largely an open challenge. Using the Rosetta program, we attempted the in silico design of a high-affinity protein interface to a small peptide ligand. We chose the thermophilic endo-1,4-{beta}-xylanase from Nonomuraea flexuosa as the protein scaffold on which to perform our designs. Over the course of the study, 12 proteins derived from this scaffold were produced and assayed for binding to the target ligand. Unfortunately, none of the designed proteins displayed evidence of high-affinity binding. Structural characterization of four designed proteins revealed that although the predicted structure of the protein model was highly accurate, this structural accuracy did not translate into accurate prediction of binding affinity. Crystallographic analyses indicate that the lack of binding affinity is possibly due to unaccounted for protein dynamics in the 'thumb' region of our design scaffold intrinsic to the family 11 {beta}-xylanase fold. Further computational analysis revealed two specific, single amino acid substitutions responsible for an observed change in backbone conformation, and decreased dynamic stability of the catalytic cleft. These findings offer new insight into the dynamic and structural determinants of the {beta}-xylanase proteins.

  15. "Less Clicking, More Watching": Results from the User-Centered Design of a Multi-Institutional Web Site for Art and Culture.

    ERIC Educational Resources Information Center

    Vergo, John; Karat, Clare-Marie; Karat, John; Pinhanez, Claudio; Arora, Renee; Cofino, Thomas; Riecken, Doug; Podlaseck, Mark

    This paper summarizes a 10-month long research project conducted at the IBM T.J. Watson Research Center aimed at developing the design concept of a multi-institutional art and culture web site. The work followed a user-centered design (UCD) approach, where interaction with prototypes and feedback from potential users of the web site were sought…

  16. Environmental monitoring at designed geopressured-geothermal well sites, Louisiana and Texas

    SciTech Connect

    Not Available

    1990-01-01

    This document covers the activities of monitoring environmental aspects at designated geothermal wells in Texas and Louisiana during the second quarter of 1990 by the Louisiana Geological Survey, Louisiana State University under contract with US DOE. 1 fig. (FSD)

  17. Issues in Designing and Implementing a Spanish-Language Multi-Site Clinical Trial

    PubMed Central

    Suarez-Morales, Lourdes; Matthews, Julie; Martino, Steve; Ball, Samuel A.; Rosa, Carmen; Farentinos, Christine; Szapocznik, José; Carroll, Kathleen M.

    2013-01-01

    To address at least in part health disparities in Hispanic populations, the NIDA Clinical Trials Network implemented the first multi-site randomized clinical trial of substance abuse treatment conducted entirely in Spanish. This trial was intended to evaluate the effectiveness of Motivational Enhancement Therapy in a diverse population of Hispanics. In the conduct of this trial, several barriers to the successful implementation of a Spanish-language multi-site trial had to be addressed, including the appropriate translation of assessment instruments, shortage of appropriately trained Spanish-speaking clinical staff, and barriers to recruitment and retention of this population. To encourage similar research, strategies are described that were developed by the study team to meet these challenges. PMID:17612825

  18. A quantitative method for groundwater surveillance monitoring network design at the Hanford Site

    SciTech Connect

    Meyer, P.D.

    1993-12-01

    As part of the Environmental Surveillance Program at the Hanford Site, mandated by the US Department of Energy, hundreds of groundwater wells are sampled each year, with each sample typically analyzed for a variety of constituents. The groundwater sampling program must satisfy several broad objectives. These objectives include an integrated assessment of the condition of groundwater and the identification and quantification of existing, emerging, or potential groundwater problems. Several quantitative network desip objectives are proposed and a mathematical optimization model is developed from these objectives. The model attempts to find minimum cost network alternatives that maximize the amount of information generated by the network. Information is measured both by the rats of change with respect to time of the contaminant concentration and the uncertainty in contaminant concentration. In an application to tritium monitoring at the Hanford Site, both information measures were derived from historical data using time series analysis.

  19. Environmental Aspects of Two Volatile Organic Compound Groundwater Treatment Designs at the Rocky Flats Site - 13135

    SciTech Connect

    Michalski, Casey C.; DiSalvo, Rick; Boylan, John

    2013-07-01

    DOE's Rocky Flats Site in Colorado is a former nuclear weapons production facility that began operations in the early 1950's. Because of releases of hazardous substances to the environment, the federally owned property and adjacent offsite areas were placed on the CERCLA National Priorities List in 1989. The final remedy was selected in 2006. Engineered components of the remedy include four groundwater treatment systems that were installed before closure as CERCLA-accelerated actions. Two of the systems, the Mound Site Plume Treatment System and the East Trenches Plume Treatment System, remove low levels of volatile organic compounds using zero-valent iron media, thereby reducing the loading of volatile organic compounds in surface water resulting from the groundwater pathway. However, the zero-valent iron treatment does not reliably reduce all volatile organic compounds to consistently meet water quality goals. While adding additional zero-valent iron media capacity could improve volatile organic compound removal capability, installation of a solar powered air-stripper has proven an effective treatment optimization in further reducing volatile organic compound concentrations. A comparison of the air stripper to the alternative of adding additional zero-valent iron capacity to improve Mound Site Plume Treatment System and East Trenches Plume Treatment System treatment based on several key sustainable remediation aspects indicates the air stripper is also more 'environmentally friendly'. These key aspects include air pollutant emissions, water quality, waste management, transportation, and costs. (authors)

  20. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Gunnison, Colorado. Attachment 5, Supplemental radiological data: Final report

    SciTech Connect

    Not Available

    1992-10-01

    Diffusion coefficients for radon gas in earthen materials are required to design suitable radon-barrier covers for uranium tailings impoundments and other materials that emit radon gas. Many early measurements of radon diffusion coefficients relied on the differences in steady-state radon fluxes measured from radon source before and after installation of a cover layer of the material being tested. More recent measurements have utilized the small-sample transient (SST) technique for greater control on moistures and densities of the test soils, greater measurement precision, and reduced testing time and costs. Several of the project sites for the US Department of Energy`s Uranium Mill Tailings Remedial Action (UMTRA) Program contain radiologically contaminated subsurface material composed predominantly of cobbles, gravels andsands. Since remedial action designs require radon diffusion coefficients for the source materials as well as the cover materials, these cobbly and gravelly materials also must be tested. This report contains the following information: a description of the test materials used and the methods developed to conduct the SST radon diffusion measurements on cobbly soils; the protocol for conducting radon diffusion tests oncobbly soils; the results of measurements on the test samples; and modifications to the FITS computer code for analyzing the time-dependent radon diffusion data.

  1. Engineered materials characterization report for the Yucca Mountain Site Characterization Project. Volume 2, Design data

    SciTech Connect

    Konynenburg, R.A.; McCright, R.D.; Roy, A.K.; Jones, D.A.

    1995-08-01

    This is Volume 2 of the Engineered Materials Characterization Report which presents the design data for candidate materials needed in fabricating different components for both large and medium multi-purpose canister (MPC) disposal containers, waste packages for containing uncanistered spent fuel (UCF), and defense high-level waste (HLW) glass disposal containers. The UCF waste package consists of a disposal container with a basket therein. It is assumed that the waste packages will incorporate all-metallic multibarrier disposal containers to accommodate medium and large MPCs, ULCF, and HLW glass canisters. Unless otherwise specified, the disposal container designs incorporate an outer corrosion-allowance metal barrier over an inner corrosion-resistant metal barrier. The corrosion-allowance barrier, which will be thicker than the inner corrosion-resistant barrier, is designed to undergo corrosion-induced degradation at a very low rate, thus providing the inner barrier protection from the near-field environment for a prolonged service period.

  2. Remedial Action Plan and Site Design for stabilization of the inactive Uranium Mill Tailings sites at Slick Rock, Colorado: Appendix C to Attachment 3, Calculations. Final

    SciTech Connect

    1995-09-01

    This volume contains calculations for: Slick Rock processing sites background ground water quality; Slick Rock processing sites lysimeter water quality; Slick Rock processing sites on-site and downgradient ground water quality; Slick Rock disposal site background water quality; Burro Canyon disposal site, Slick Rock, Colorado, average hydraulic gradients and average liner ground water velocities in the upper, middle, and lower sandstone units of the Burro Canyon formation; Slick Rock--Burro Canyon disposal site, Burro Canyon pumping and slug tests--analyses; water balance and surface contours--Burro Canyon disposal cell; and analytical calculation of drawdown in a hypothetical well completed in the upper sandstone unit of the Burro Canyon formation.

  3. Remedial action and site design for stabilization of the inactive uranium mill tailings sites at Slick Rock, Colorado. Attachment 3, Groundwater hydrology report

    SciTech Connect

    Not Available

    1993-07-01

    The US Environmental Protection Agency (EPA) has established health and environmental protection regulations to correct and prevent groundwater contamination resulting from processing activities at inactive uranium milling sites (EPA, 1987). According to the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 1978 Public Law (PL) 95-604 (PL 95-604), the US Department of Energy (DOE) is responsible for assessing the inactive uranium processing sites. The DOE has determined that for Slick Rock, this assessment shall include hydrogeologic site characterization for two separate uranium processing sites, the Union Carbide (UC) site and the North Continent (NC) site, and for the proposed Burro Canyon disposal site.

  4. Seismic design spectra 200 West and East Areas DOE Hanford Site, Washington

    SciTech Connect

    Tallman, A.M.

    1995-12-31

    This document presents equal hazard response spectra for the W236A project for the 200 East and West new high-level waste tanks. The hazard level is based upon WHC-SD-W236A-TI-002, Probabilistic Seismic Hazard Analysis, DOE Hanford Site, Washington. Spectral acceleration amplification is plotted with frequency (Hz) for horizontal and vertical motion and attached to this report. The vertical amplification is based upon the preliminary draft revision of Standard ASCE 4-86. The vertical spectral acceleration is equal to the horizontal at frequencies above 3.3Hz because of near-field, less than 15 km, sources.

  5. 7 CFR Exhibit B to Subpart C of... - Site Development Design Requirements

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... entrances. 2. Cul-de-sacs. Cul-de-sac streets shall have a turn-around with an outside roadway diameter of at least 80 feet, and a right-of-way diameter of at least 100 feet. 3. Intersection Angle. Streets... other public right-of-way) shall have an inside diameter based on design analysis but not less than...

  6. Design and operation of a low-level solid-waste disposal site at Los Alamos

    NASA Astrophysics Data System (ADS)

    Balo, K. A.; Wilson, N. E.; Warren, J. L.

    Approximately 185000 cu m of low level and transuranic radioactive solid waste, were disposed of by onsite shallow land burial. Procedures and facilities were designed and evaluated in the areas of waste acceptance, treatment and storage, disposal, traffic control, and support systems. The methodologies assuring the proper management and disposal of radioactive solid waste are summarized.

  7. Making Creative Spaces: The Art and Design Classroom as a Site of Performativity

    ERIC Educational Resources Information Center

    Wild, Carol

    2011-01-01

    Rather than taking a transformational role in schools, new art and design teachers quickly become subject to "school art" orthodoxy. Theories of subjectivity and the development of professional identity within communities of practice can feel far removed from the classroom. This article seeks to make clearer the processes by which teacher identity…

  8. The Design and Implementation of Aircraft Maintenance On-site Control System

    NASA Astrophysics Data System (ADS)

    Zhou, Guilin; Zhang, Huawei

    Based on the desire of aircraft maintenance, combined with the situation in work, this paper present the design and implementation of aircraft maintenance system based dot Net. For a partial page refresh object, AJAX is used through the system. New technology is used in a creative way and will promote innovation and transformation of the business.

  9. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... extent practicable water infiltration, to direct percolating or surface water away from the disposed... must direct surface water drainage away from disposal units at velocities and gradients which will not... be designed to minimize to the extent practicable the contact of water with waste during storage,...

  10. Discovery of novel STAT3 small molecule inhibitors via in silico site-directed fragment-based drug design.

    PubMed

    Yu, Wenying; Xiao, Hui; Lin, Jiayuh; Li, Chenglong

    2013-06-13

    Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been validated as an attractive therapeutic target for cancer therapy. To stop both STAT3 activation and dimerization, a viable strategy is to design inhibitors blocking its SH2 domain phosphotyrosine binding site that is responsible for both actions. A new fragment-based drug design (FBDD) strategy, in silico site-directed FBDD, was applied in this study. A designed novel compound, 5,8-dioxo-6-(pyridin-3-ylamino)-5,8-dihydronaphthalene-1-sulfonamide (LY5), was confirmed to bind to STAT3 SH2 by fluorescence polarization assay. In addition, four out of the five chosen compounds have IC50 values lower than 5 μM for the U2OS cancer cells. 8 (LY5) has an IC50 range in 0.5-1.4 μM in various cancer cell lines. 8 also suppresses tumor growth in an in vivo mouse model. This study has demonstrated the utility of this approach and could be used to other drug targets in general. PMID:23651330

  11. A designed DNA binding motif that recognizes extended sites and spans two adjacent major grooves†

    PubMed Central

    Rodríguez, Jéssica; Mosquera, Jesús; García-Fandiño, Rebeca; Vázquez, M. Eugenio; Mascareñas, José L.

    2016-01-01

    We report the rational design of a DNA-binding peptide construct composed of the DNA-contacting regions of two transcription factors (GCN4 and GAGA) linked through an AT-hook DNA anchor. The resulting chimera, which represents a new, non-natural DNA binding motif, binds with high affinity and selectivity to a long composite sequence of 13 base pairs (TCAT-AATT-GAGAG). PMID:27252825

  12. A Pilot Study of the Interface Design of Cross-Cultural Web Sites through Usability Testing of Multilanguage Web Sites and Determining the Preferences of Taiwanese and American Users

    ERIC Educational Resources Information Center

    Ku, David Tawei; Chang, Chia-Chi

    2014-01-01

    By conducting usability testing on a multilanguage Web site, this study analyzed the cultural differences between Taiwanese and American users in the performance of assigned tasks. To provide feasible insight into cross-cultural Web site design, Microsoft Office Online (MOO) that supports both traditional Chinese and English and contains an almost…

  13. Elucidating the design principles of photosynthetic electron-transfer proteins by site-directed spin labeling EPR spectroscopy.

    PubMed

    Ishara Silva, K; Jagannathan, Bharat; Golbeck, John H; Lakshmi, K V

    2016-05-01

    Site-directed spin labeling electron paramagnetic resonance (SDSL EPR) spectroscopy is a powerful tool to determine solvent accessibility, side-chain dynamics, and inter-spin distances at specific sites in biological macromolecules. This information provides important insights into the structure and dynamics of both natural and designed proteins and protein complexes. Here, we discuss the application of SDSL EPR spectroscopy in probing the charge-transfer cofactors in photosynthetic reaction centers (RC) such as photosystem I (PSI) and the bacterial reaction center (bRC). Photosynthetic RCs are large multi-subunit proteins (molecular weight≥300 kDa) that perform light-driven charge transfer reactions in photosynthesis. These reactions are carried out by cofactors that are paramagnetic in one of their oxidation states. This renders the RCs unsuitable for conventional nuclear magnetic resonance spectroscopy investigations. However, the presence of native paramagnetic centers and the ability to covalently attach site-directed spin labels in RCs makes them ideally suited for the application of SDSL EPR spectroscopy. The paramagnetic centers serve as probes of conformational changes, dynamics of subunit assembly, and the relative motion of cofactors and peptide subunits. In this review, we describe novel applications of SDSL EPR spectroscopy for elucidating the effects of local structure and dynamics on the electron-transfer cofactors of photosynthetic RCs. Because SDSL EPR Spectroscopy is uniquely suited to provide dynamic information on protein motion, it is a particularly useful method in the engineering and analysis of designed electron transfer proteins and protein networks. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. PMID:26334844

  14. Design, technology, and science: Sites for learning, resistance, and social reproduction in urban schools

    NASA Astrophysics Data System (ADS)

    Seiler, Gale; Tobin, Kenneth; Sokolic, Joseph

    2001-09-01

    The teaching of science through activities that emphasize design and technology has been advocated as a vehicle for accomplishing science for all students. This study was situated in an inner7-city neighborhood school populated mainly by African American students from life worlds characterized by poverty. The article explores the discourse and practices of students and three coteachers as a curriculum was enacted to provide opportunities for students to learn about the physics of motion through designing, building, and testing a model car. Some students participated in ways that led to their building viable model cars and interacting with one another in ways that suggest design and technological competence. However, there also was evidence of resistance from students who participated sporadically and refused to cooperate with teachers as they endeavored to structure the environment in ways that would lead to a deeper understanding of science. Analysis of in-class interactions reveals an untapped potential for the emergence of a sciencelike discourse and diverse outcomes. Among the challenges explored in this article is a struggle for respect that permeates the students' lives on the street and bleeds into the classroom environment. Whereas teachers enacted the curriculum as if learning was the chief goal for students, it is apparent that students used the class opportunistically to maintain and earn the respect of peers.

  15. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Lowman, Idaho: Remedial action selection report for the Lowman UMTRA project site, Idaho. Final report

    SciTech Connect

    Matthews, M.L.; Nagel, J.

    1991-09-01

    The inactive uranium mill tailings site near Lowman, Idaho, was designated as one of 24 abandoned uranium tailings sites to be remediated by the US Department of Energy (DOE) under the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA). The UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE`s remedial action plan and certify that the remedial action complies with the standards promulgated by the US Environmental Protection Agency (EPA). The remedial action plan (RAP), which includes this remedial action selection report (RAS), has been developed to serve a two-fold purpose. First, it describes the activities that are proposed by the DOE to accomplish long-term stabilization and control of residual radioactive materials at the inactive uranium processing site near Lowman, Idaho. Second, this document and the remainder of the RAP, upon concurrence and execution by the DOE, the State of Idaho, and the NRC, becomes Appendix B of the Cooperative Agreement (No. DE-FC04-85AL20535) between the DOE and the State of Idaho.

  16. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Lowman, Idaho: Remedial action selection report for the Lowman UMTRA project site, Idaho

    SciTech Connect

    Matthews, M.L. . Uranium Mill Tailings Remedial Action Project Office); Nagel, J. . Div. of Environmental Quality)

    1991-09-01

    The inactive uranium mill tailings site near Lowman, Idaho, was designated as one of 24 abandoned uranium tailings sites to be remediated by the US Department of Energy (DOE) under the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA). The UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE's remedial action plan and certify that the remedial action complies with the standards promulgated by the US Environmental Protection Agency (EPA). The remedial action plan (RAP), which includes this remedial action selection report (RAS), has been developed to serve a two-fold purpose. First, it describes the activities that are proposed by the DOE to accomplish long-term stabilization and control of residual radioactive materials at the inactive uranium processing site near Lowman, Idaho. Second, this document and the remainder of the RAP, upon concurrence and execution by the DOE, the State of Idaho, and the NRC, becomes Appendix B of the Cooperative Agreement (No. DE-FC04-85AL20535) between the DOE and the State of Idaho.

  17. Remedial action plan and site design for stabilization of the Inactive Uranium Mill Tailings Site, Maybell, Colorado. Final report, Appendixes to attachment 3

    SciTech Connect

    Not Available

    1994-06-01

    This document contains supporting appendices to attachment 3 for the remedial action and site stabilization plan for Maybell, Colorado UMTRA site. Appendix A includes the Hydrological Services Calculations and Appendix B contains Ground Water Quality by Location data.

  18. Design and field-scale implementation of an "on site" bioremediation treatment in PAH-polluted soil.

    PubMed

    Pelaez, A I; Lores, I; Sotres, A; Mendez-Garcia, C; Fernandez-Velarde, C; Santos, J A; Gallego, J L R; Sanchez, J

    2013-10-01

    An "on site" bioremediation program was designed and implemented in soil polluted with polycyclic aromatic hydrocarbons (PAHs), especially naphthalene. We began by characterizing the soil's physical and chemical properties. A microbiological screening corroborated the presence of microorganisms capable of metabolizing PAHs. We then analyzed the viability of bioremediation by developing laboratory microcosms and pilot scale studies, to optimize the costs and time associated with remediation. The treatment assays were based on different types of biostimulants, such as a slow or fast-release fertilizer, combined with commercial surfactants. Once the feasibility of the biostimulation was confirmed, a real-scale bioremediation program was undertaken in 900 m(3) of contaminated soil. The three-step design reduced PAH contamination by 94.4% at the end of treatment (161 days). The decrease in pollutants was concomitant with the selection of autochthonous bacteria capable of degrading PAHs, with Bacillus and Pseudomonas the most abundant genera. PMID:23867700

  19. REVIEW REPORT: BUILDING C-400 THERMAL TREATMENT 90 PERCENT REMEDIAL DESIGN REPORT AND SITE INVESTIGATION, PGDP, PADUCAH, KENTUCKY

    SciTech Connect

    Looney, B; Jed Costanza, J; Eva Davis, E; Joe Rossabi, J; Lloyd Stewart, L; Hans Stroo, H

    2007-08-15

    On 9 April 2007, the U.S. Department of Energy (DOE) Headquarters, Office of Soil and Groundwater Remediation (EM-22) initiated an Independent Technical Review (ITR) of the 90% Remedial Design Report (RDR) and Site Investigation (RDSI) for thermal treatment of trichloroethylene (TCE) in the soil and groundwater in the vicinity of Building C-400 at the Paducah Gaseous Diffusion Plant (PGDP). The general ITR goals were to assess the technical adequacy of the 90% RDSI and provide recommendations sufficient for DOE to determine if modifications are warranted pertaining to the design, schedule, or cost of implementing the proposed design. The ultimate goal of the effort was to assist the DOE Paducah/Portsmouth Project Office (PPPO) and their contractor team in ''removing'' the TCE source zone located near the C-400 Building. This report provides the ITR findings and recommendations and supporting evaluations as needed to facilitate use of the recommendations. The ITR team supports the remedial action objective (RAO) at C-400 to reduce the TCE source area via subsurface Electrical Resistance Heating (ERH). Further, the ITR team commends PPPO, their contractor team, regulators, and stakeholders for the significant efforts taken in preparing the 90% RDR. To maximize TCE removal at the target source area, several themes emerge from the review which the ITR team believes should be considered and addressed before implementing the thermal treatment. These themes include the need for: (1) Accurate and site-specific models as the basis to verify the ERH design for full-scale implementation for this challenging hydrogeologic setting; (2) Flexible project implementation and operation to allow the project team to respond to observations and data collected during construction and operation; (3) Defensible performance metrics and monitoring, appropriate for ERH, to ensure sufficient and efficient clean-up; and (4) Comprehensive (creative and diverse) contingencies to address the

  20. Rational design of carbon nitride photocatalysts by identification of cyanamide defects as catalytically relevant sites

    NASA Astrophysics Data System (ADS)

    Lau, Vincent Wing-Hei; Moudrakovski, Igor; Botari, Tiago; Weinberger, Simon; Mesch, Maria B.; Duppel, Viola; Senker, Jürgen; Blum, Volker; Lotsch, Bettina V.

    2016-07-01

    The heptazine-based polymer melon (also known as graphitic carbon nitride, g-C3N4) is a promising photocatalyst for hydrogen evolution. Nonetheless, attempts to improve its inherently low activity are rarely based on rational approaches because of a lack of fundamental understanding of its mechanistic operation. Here we employ molecular heptazine-based model catalysts to identify the cyanamide moiety as a photocatalytically relevant `defect'. We exploit this knowledge for the rational design of a carbon nitride polymer populated with cyanamide groups, yielding a material with 12 and 16 times the hydrogen evolution rate and apparent quantum efficiency (400 nm), respectively, compared with the unmodified melon. Computational modelling and material characterization suggest that this moiety improves coordination (and, in turn, charge transfer kinetics) to the platinum co-catalyst and enhances the separation of the photogenerated charge carriers. The demonstrated knowledge transfer for rational catalyst design presented here provides the conceptual framework for engineering high-performance heptazine-based photocatalysts.

  1. Rational design of carbon nitride photocatalysts by identification of cyanamide defects as catalytically relevant sites

    PubMed Central

    Lau, Vincent Wing-hei; Moudrakovski, Igor; Botari, Tiago; Weinberger, Simon; Mesch, Maria B.; Duppel, Viola; Senker, Jürgen; Blum, Volker; Lotsch, Bettina V.

    2016-01-01

    The heptazine-based polymer melon (also known as graphitic carbon nitride, g-C3N4) is a promising photocatalyst for hydrogen evolution. Nonetheless, attempts to improve its inherently low activity are rarely based on rational approaches because of a lack of fundamental understanding of its mechanistic operation. Here we employ molecular heptazine-based model catalysts to identify the cyanamide moiety as a photocatalytically relevant ‘defect'. We exploit this knowledge for the rational design of a carbon nitride polymer populated with cyanamide groups, yielding a material with 12 and 16 times the hydrogen evolution rate and apparent quantum efficiency (400 nm), respectively, compared with the unmodified melon. Computational modelling and material characterization suggest that this moiety improves coordination (and, in turn, charge transfer kinetics) to the platinum co-catalyst and enhances the separation of the photogenerated charge carriers. The demonstrated knowledge transfer for rational catalyst design presented here provides the conceptual framework for engineering high-performance heptazine-based photocatalysts. PMID:27387536

  2. Rational design of carbon nitride photocatalysts by identification of cyanamide defects as catalytically relevant sites.

    PubMed

    Lau, Vincent Wing-Hei; Moudrakovski, Igor; Botari, Tiago; Weinberger, Simon; Mesch, Maria B; Duppel, Viola; Senker, Jürgen; Blum, Volker; Lotsch, Bettina V

    2016-01-01

    The heptazine-based polymer melon (also known as graphitic carbon nitride, g-C3N4) is a promising photocatalyst for hydrogen evolution. Nonetheless, attempts to improve its inherently low activity are rarely based on rational approaches because of a lack of fundamental understanding of its mechanistic operation. Here we employ molecular heptazine-based model catalysts to identify the cyanamide moiety as a photocatalytically relevant 'defect'. We exploit this knowledge for the rational design of a carbon nitride polymer populated with cyanamide groups, yielding a material with 12 and 16 times the hydrogen evolution rate and apparent quantum efficiency (400 nm), respectively, compared with the unmodified melon. Computational modelling and material characterization suggest that this moiety improves coordination (and, in turn, charge transfer kinetics) to the platinum co-catalyst and enhances the separation of the photogenerated charge carriers. The demonstrated knowledge transfer for rational catalyst design presented here provides the conceptual framework for engineering high-performance heptazine-based photocatalysts. PMID:27387536

  3. CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites

    PubMed Central

    Naito, Yuki; Hino, Kimihiro; Bono, Hidemasa; Ui-Tei, Kumiko

    2015-01-01

    Summary: CRISPRdirect is a simple and functional web server for selecting rational CRISPR/Cas targets from an input sequence. The CRISPR/Cas system is a promising technique for genome engineering which allows target-specific cleavage of genomic DNA guided by Cas9 nuclease in complex with a guide RNA (gRNA), that complementarily binds to a ∼20 nt targeted sequence. The target sequence requirements are twofold. First, the 5′-NGG protospacer adjacent motif (PAM) sequence must be located adjacent to the target sequence. Second, the target sequence should be specific within the entire genome in order to avoid off-target editing. CRISPRdirect enables users to easily select rational target sequences with minimized off-target sites by performing exhaustive searches against genomic sequences. The server currently incorporates the genomic sequences of human, mouse, rat, marmoset, pig, chicken, frog, zebrafish, Ciona, fruit fly, silkworm, Caenorhabditis elegans, Arabidopsis, rice, Sorghum and budding yeast. Availability: Freely available at http://crispr.dbcls.jp/. Contact: y-naito@dbcls.rois.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25414360

  4. Design of a Soil Cutting Resistance Sensor for Application in Site-Specific Tillage

    PubMed Central

    Agüera, Juan; Carballido, Jacob; Gil, Jesús; Gliever, Chris J.; Perez-Ruiz, Manuel

    2013-01-01

    One objective of precision agriculture is to provide accurate information about soil and crop properties to optimize the management of agricultural inputs to meet site-specific needs. This paper describes the development of a sensor equipped with RTK-GPS technology that continuously and efficiently measures soil cutting resistance at various depths while traversing the field. Laboratory and preliminary field tests verified the accuracy of this prototype soil strength sensor. The data obtained using a hand-operated soil cone penetrometer was used to evaluate this field soil compaction depth profile sensor. To date, this sensor has only been tested in one field under one gravimetric water content condition. This field test revealed that the relationships between the soil strength profile sensor (SSPS) cutting force and soil cone index values are assumed to be quadratic for the various depths considered: 0–10, 10–20 and 20–30 cm (r2 = 0.58, 0.45 and 0.54, respectively). Soil resistance contour maps illustrated its practical value. The developed sensor provides accurate, timely and affordable information on soil properties to optimize resources and improve agricultural economy. PMID:23666127

  5. Rational design of an on-site volume reduction system for source-separated urine.

    PubMed

    Pahore, Muhammad Masoom; Ito, Ryusei; Funamizu, Naoyuki

    2010-04-01

    Human urine contains nitrogen, phosphorus and potassium, which can be applied as fertilizer in agriculture, replacing commercial fertilizer. However, owing to the low nutrient content of the urine, huge quantities must be transported to farmland to meet the nutrient demand of crops. This highly increases the transportation cost for the farmers. To address the transportation issue, a new on-site volume reduction system was tested at the laboratory scale based on water evaporation from vertical gauze sheets. A mathematical water transport model was proposed to evaluate the performance of the system. The mass transfer coefficient and the resistance of water flow through the sheet in the water transport model were obtained from the experiments. The results agreed with the simulated data, thereby confirming the proposed model. The model was then applied to the dry climate of southern Pakistan, having an air temperature of 30-40 degrees C and air humidity of 20-40%, for an 80% volume reduction of 10 L urine per day, which corresponds to a family of 10 members (average for a household in Pakistan). The findings revealed that the estimated size of the vertical sheet is 440-2060 cm2, which is only a small area for setting up the system at a household level. PMID:20450114

  6. Application of an integrated real time investigation to expedite the acquisition of pre-design data at a Superfund site

    SciTech Connect

    Gelb, S.B.; Fitzpatrick, R.; Koller, D.

    1995-12-31

    At a Superfund Site in EPA Region 2, McLaren/Hart implemented its Integrated Real-Time Approach (IRTA), with EPA approval, to obtain pre-design data in support of the pump and treat remedy required by the ROD. The flexibility of the IRTA program allowed the lateral extent of a dissolved VOC plume in the shallow aquifer to be delineated, and resulted in the identification of previously unknown contaminated source areas. The IRTA approach employed a multi-disciplinary field team consisting of a hydrogeologists functioning as the Field Team Manager, an on-site chemist and sampling technicians. Rapid sample collection was achieved with a variety of equipment operated by McLaren/Hart`s Field Services Division. Samples were analyzed on-site by the McLaren/Hart Mobile laboratory. Analytical data were reviewed and evaluated by the field team as the information was generated, allowing informed selection of subsequent sampling locations. Groundwater samples were initially collected from areas known to be contaminated, and then proceeded outward until the lateral extent of the VOC plume had been defined. Soil samples were then collected from areas where the groundwater displayed the highest VOC concentrations. As such, the versatility of IRTA allowed for cost-effective groundwater plume delineation and source area identification.

  7. Two- and Three-Electron Oxidation of Single-Site Vanadium Centers at Surfaces by Ligand Design.

    PubMed

    Skomski, Daniel; Tempas, Christopher D; Cook, Brian J; Polezhaev, Alexander V; Smith, Kevin A; Caulton, Kenneth G; Tait, Steven L

    2015-06-24

    Rational, systematic tuning of single-site metal centers on surfaces offers a new approach to increase selectivity in heterogeneous catalysis reactions. Although such metal centers of uniform oxidation states have been achieved, the ability to control their oxidation states through the use of carefully designed ligands had not been shown. To this end, tetrazine ligands functionalized by two pyridinyl or pyrimidinyl substituents were deposited, along with vanadium metal, on the Au(100) surface. The greater oxidizing power of the bis-pyrimidinyltetrazine facilitates the on-surface redox formation of V(3+), compared to V(2+) when paired with the bis-pyridinyltetrazine, as determined by X-ray photoelectron spectroscopy. This demonstrates the ability to control metal oxidation states in surface coordination architectures by altering the redox properties of organic ligands. The metal-ligand complexes take the form of one-dimensional polymeric chains, resolved by scanning tunneling microscopy. The chain structures in the first layer are very uniform and are based on the same quasi-square-planar coordination geometry around single-site V with either ligand. Formation of a different, dimer structure is observed in the early stages of the second layer formation. These systems offer new opportunities in controlling the oxidation state of single-site transition metal atoms at a surface for new advances in heterogeneous catalysts. PMID:26029790

  8. Lessons learned from the preclosure performance assessment review of the Fluor Technology, Inc. , draft site characterization plan conceptual design report

    SciTech Connect

    Mayberry, J.J.

    1987-06-09

    This report presents the lessons learned from the preclosure performance assessment review (PAR) of the Draft Site Characterization Plan---Conceptual Design Report (SCP-CDR). The PAR analyzes the operations of the waste handling facilities as presented in the SCP-CDR against appropriate regulatory and design criteria. The PAR applies to the design presented in a working draft released in April, 1986. We will analyze the design presented in the SCP-CDR, the other is to test safety assessment methods and tools. This report addresses only the second of these objectives. The PAR analysis consists of assessments of offsite and occupational doses resulting from routine and accidental events during preclosure operations at the repository. The activities related to the PAR are divided into subject areas. These areas include (1) the description of repository facilities and operations, (2) the development of radioactive material inventories and radiation dose rates, (3) the development of radioactive material-release scenarios and source terms, (4) the assessment of offsite dose equivalents, and (5) the assessment of occupational radiation dose equivalents. This report contains a summary of the analyses in these fives areas and lists those preclosure analyses not performed as part of the PAR. Chapters detail the strengths and weaknesses of each analysis and include recommendations for improving the analyses. 15 refs., 1 fig., 1 tab.

  9. The effect of nitrogen loading on on-site system design: a model for determining land application area size.

    PubMed

    McCardell, A; Davison, L; Edwards, A

    2005-01-01

    Designers of on-site wastewater management systems have six opportunities to remove pollutants of concern from the aqueous waste stream before it reaches ground or surface waters. These opportunities occur at source, at point of collection (primary treatment), secondary treatment, tertiary treatment, land application and buffers. This paper presents a computer based model for the sizing of on-site system land application areas applicable to the Lismore area in Northern New South Wales, a region of high rainfall. Inputs to the model include daily climatic data, soil type, number of people loading the system and size of housing allotment. Constraints include allowable phosphorus export, nitrogen export and hydraulic percolation. In the Lismore area nitrogen is the nutrient of most concern. In areas close to environmentally sensitive waterways, and in dense developments, the allowable annual nitrogen export becomes the main factor determining the land application area size. The model offers system designers the opportunity to test various combinations of nitrogen attenuation strategies (source control, secondary treatment) in order to create a solution which offers an acceptable nitrogen export rate while meeting the client's household and financial needs. The model runs on an Excel spreadsheet and has been developed by Lismore City Council. PMID:16104429

  10. Design of the primary pre-TRMM and TRMM ground truth site

    NASA Technical Reports Server (NTRS)

    Garstang, Michael

    1988-01-01

    The primary objective of the Tropical Rain Measuring Mission (TRMM) were to: integrate the rain gage measurements with radar measurements of rainfall using the KSFC/Patrick digitized radar and associated rainfall network; delineate the major rain bearing systems over Florida using the Weather Service reported radar/rainfall distributions; combine the integrated measurements with the delineated rain bearing systems; use the results of the combined measurements and delineated rain bearing systems to represent patterns of rainfall which actually exist and contribute significantly to the rainfall to test sampling strategies and based on the results of these analyses decide upon the ground truth network; and complete the design begun in Phase 1 of a multi-scale (space and time) surface observing precipitation network centered upon KSFC. Work accomplished and in progress is discussed.

  11. Compressed air energy storage: preliminary design and site development program in an aquifer. Final draft, Task 1: establish facility design criteria and utility benefits

    SciTech Connect

    1980-10-01

    Compressed air energy storage (CAES) has been identified as one of the principal new energy storage technologies worthy of further research and development. The CAES system stores mechanical energy in the form of compressed air during off-peak hours, using power supplied by a large, high-efficiency baseload power plant. At times of high electrical demand, the compressed air is drawn from storage and is heated in a combustor by the burning of fuel oil, after which the air is expanded in a turbine. In this manner, essentially all of the turbine output can be applied to the generation of electricity, unlike a conventional gas turbine which expends approximately two-thirds of the turbine shaft power in driving the air compressor. The separation of the compression and generation modes in the CAES system results in increased net generation and greater premium fuel economy. The use of CAES systems to meet the utilities' high electrical demand requirements is particularly attractive in view of the reduced availability of premium fuels such as oil and natural gas. This volume documents the Task 1 work performed in establishing facility design criteria for a CAES system with aquifer storage. Information is included on: determination of initial design bases; preliminary analysis of the CAES system; development of data for site-specific analysis of the CAES system; detailed analysis of the CAES system for three selected heat cycles; CAES power plant design; and an economic analysis of CAES.

  12. Designing for selectivity: weak interactions and the competition for reactive sites on gold catalysts.

    PubMed

    Siler, C G F; Madix, R J; Friend, C M

    2016-07-01

    A major challenge in heterogeneous catalysis is controlling reaction selectivity, especially in complex environments. When more than one species is present in the gas mixture, the competition for binding sites on the surface of a catalyst is an important factor in determining reaction selectivity and activity. We establish an experimental hierarchy for the binding of a series of reaction intermediates on Au(111) and demonstrate that this hierarchy accounts for reaction selectivity on both the single crystal surface and under operating catalytic conditions at atmospheric pressure using a nanoporous Au catalyst. A partial set of measurements of relative binding has been measured by others on other catalyst materials, including Ag, Pd and metal oxide surfaces; a comparison demonstrates the generality of this concept and identifies differences in the trends. Theoretical calculations for a subset of reactants on Au(111) show that weak van der Waals interactions are key to predicting the hierarchy of binding strengths for alkoxides bound to Au(111). This hierarchy is key to the control of the selectivity for partial oxidation of alcohols to esters on both Au surfaces and under working catalytic conditions using nanoporous gold. The selectivity depends on the competition for active sites among key intermediates. New results probing the effect of fluorine substitution are also presented to extend the relation of reaction selectivity to the hierarchy of binding. Motivated by an interest in synthetic manipulation of fluorinated organics, we specifically investigated the influence of the -CF3 group on alcohol reactivity and selectivity. 2,2,2-Trifluoroethanol couples on O-covered Au(111) to yield CF3CH2O-C([double bond, length as m-dash]O)(CF3), but in the presence of methanol or ethanol it preferentially forms the respective 2,2,2-trifluoroethoxy-esters. The ester is not the dominant product in any of these cases, though, indicating that the rate of β-H elimination from

  13. Energy conserving site design: Greenbrier case study, Chesapeake, Virginia. Final report

    SciTech Connect

    Not Available

    1980-04-01

    A specific case study of project planning for energy conservation for a major planned unit development at the 3000-acre Greenbrier development site in Chesapeake, Virginia, is summarized. The research suggests that very considerable reductions in energy conservation can be achieved within the confines of private-sector land development and residential construction with increased incremental costs of $200.00 to $3150.00 per dwelling unit. It is hypothesized that energy consumption at Greenbrier can be reduced by one-half with an average annual savings of 21,275 kWh per residential unit, using state-of-the-art technology with careful planning and control. This represents an annual savings $750.00 per unit at the current utility rate of 3.5 cents per kWh. These savings can be achieved through reduction in heating and cooling loads and application of more-efficient heating and cooling of the remaining loads. The reduction in loads are achieved by redesign of the land plan to include a higher percentage of south-facing lots, use of vegetation to modify microclimate, decreases in air infiltration, the use of 2 x 6 framing, better insulation, and the use of an insulated slab-on-grade foundation. Further energy savings can be expected by increased efficiencies in mechanical systems used for space heating and cooling and domestic hot water. When applied to the single-family portion of Greenbrier, containing 541 dwelling units, these options reduce the total end-use energy consumption 54.7%. This reduction represents an annual savings of $432,800.00 for an initial capital investment of $1.7 million.

  14. Use of Ground Penetrating Radar for Site Investigation of Low-Volume Roadways and Design Recommendations

    NASA Astrophysics Data System (ADS)

    Scullion, T.; Saarenketo, T.

    2002-07-01

    This report will present several case studies describing the use of ground penetrating radar (GPR) technology for site investigations. Two types of GPR will be described-the air-launched and ground-coupled systems. The use of air-launched radar is well established within the Texas Department of Transportation (TxDOT). The limitation of this technology is its depth of penetration. While providing very useful information on the surface and base layers, it provides little information on the sub-grade soils. The use of low-frequency ground-coupled radar systems will provide little useful near-surface information but it can provide data on sub-grade properties and how they vary along a project. Combining both radar types can potentially provide a comprehensive subsurface investigative tool for both new pavement construction and for major pavement rehabilitation projects. In this report a brief description will be provided of the different systems together with the software used to process the GPR signals. Air-launched data are processed with the COLORMAP system developed by the Texas Transportation Institute. The ground-coupled data are processed using the Road Doctor system developed by Roadscanners, Inc. of Finland. The case studies presented were collected on actual TxDOT evaluation projects mainly in the Bryan District. They range from near-surface applications where the goal was to identify changes in pavement structure which were not available in construction records to identifying the areas beneath the pavement subsidence associated with strip mining activities.

  15. "Intelligent design" of a 3D reflection survey for the SAFOD drill-hole site

    NASA Astrophysics Data System (ADS)

    Alvarez, G.; Hole, J. A.; Klemperer, S. L.; Biondi, B.; Imhof, M.

    2003-12-01

    SAFOD seeks to better understand the earthquake process by drilling though the San Andreas fault (SAF) to sample an earthquake in situ. To capitalize fully on the opportunities presented by the 1D drill-hole into a complex fault zone we must characterize the surrounding 3D geology at a scale commensurate with the drilling observations, to provide the structural context to extrapolate 1D drilling results along the fault plane and into the surrounding 3D volume. Excellent active-2D and passive-3D seismic observations completed and underway lack the detailed 3D resolution required. Only an industry-quality 3D reflection survey can provide c. 25 m subsurface sample-spacing horizontally and vertically. A 3D reflection survey will provide subsurface structural and stratigraphic control at the 100-m level, mapping major geologic units, structural boundaries, and subsurface relationships between the many faults that make up the SAF fault system. A principal objective should be a reflection-image (horizon-slice through the 3D volume) of the near-vertical fault plane(s) to show variations in physical properties around the drill-hole. Without a 3D reflection image of the fault zone, we risk interpreting drilled anomalies as ubiquitous properties of the fault, or risk missing important anomalies altogether. Such a survey cannot be properly costed or technically designed without major planning. "Intelligent survey design" can minimize source and receiver effort without compromising data-quality at the fault target. Such optimization can in principal reduce the cost of a 3D seismic survey by a factor of two or three, utilizing the known surface logistic constraints, partially-known sub-surface velocity field, and the suite of scientific targets at SAFOD. Our methodology poses the selection of the survey parameters as an optimization process that allows the parameters to vary spatially in response to changes in the subsurface. The acquisition geometry is locally optimized for

  16. Designating Earth's Moon as a United Nations World Heritage Site - Permanently Protected from Commercial or Military Uses

    NASA Astrophysics Data System (ADS)

    Steiner, R. G.

    2002-01-01

    This paper proposes that Earth's Moon, in its entirety, be designated a United Nations World Heritage Site (WHS), permanently protected from any and all commercial or military utilization and reserved exclusively for scientific and aesthetic purposes. The paper discusses: 1) the extraordinary importance of the Moon for science, culture, and religion - past, present and future; 2) the history of proposals to exploit the Moon for commercial and military purposes and the shortcomings of this colonial, exploitation paradigm; and 3) the necessity, policy mechanisms, and political dynamics of designating the Moon as a World Heritage Site, permanently protected from commercial and/or military uses. The first part of the paper discusses the extraordinary importance of the Moon as it exists today - as a scientific laboratory, a source of beauty and inspiration throughout human evolution, a source for artistic expression, and as an object that is considered sacred by many cultures. Next, the paper traces the history of specific proposals for the exploitation of the Moon for commercial and/or military purposes - including plans by the U.S. Air Force in 1959 to detonate a nuclear explosion on the Moon, proposals to strip-mine the lunar regolith for helium-3 and rocket-fuel hydrogen; construction of solar power plants to transmit energy to Earth, and proposals to use the lunar surface as a billboard upon which to project commercial advertisements visible from Earth. The profound ethical, legal, and scientific shortcomings of this exploitation paradigm are described as an emerging Extraterrestrial Manifest Destiny that we have a collective obligation to challenge and constrain. The paper proposes that space exploration be infused with an ethical commitment to compassion, reverence, conservation, and non-interference to abiotic and biotic systems alike; as opposed to the expansion and extraterrestrial imposition of the colonization, exploitation, domination, and despoliation

  17. Improving the Applicability of Tomographic GPR for Crosshole Site Characterization Through Data Acquisition Design

    NASA Astrophysics Data System (ADS)

    Flaxman, A. O.; Hou, Z.

    2008-12-01

    Tomographic ground penetrating radar (GPR) traveltime data has been widely used for hydrologic parameter estimation in the shallow subsurface. However, hydrogeological information extracted from tomographic GPR data is subject to great uncertainty because of the nonlinear and non-unique relationships between hydrogeological and geophysical attributes, and the spatial heterogeneity of these attributes. Such uncertainty relies heavily on the data acquisition parameters. Good data acquisition can make the hydrogeological parameter estimation problems less ill-posed. However, few efforts have been made to evaluate the impacts of different data acquisition parameters (soil type, borehole geometry, antenna locations and spacing, soil saturation conditions, etc.) on the borehole radar responses. The inaccuracy of geophysical forward models also increases the level of uncertainty in parameter estimation. Here we adopt a finite-difference method that solves the Eikonal equation to obtain accurate radar travel times, by taking all possible wave paths into account through a local traveltime computation algorithm. In this study, we treat the data acquisition parameters as random variables which are characterized by their probabilistic density distributions. Through stochastic sampling approach, we generate multiple fields with different data acquisition parameters; then the eikonal solver method is used to compute the corresponding GPR responses; and finally, we use a Bayesian inverse approach to estimate hydrogeological parameters for different field conditions. In this way, the impact of data acquisition parameters on the applicability of the borehole radar data can be systematically evaluated. Therefore, this study provides useful information on borehole radar data acquisition design.

  18. Fragment-Based Design of Ligands Targeting a Novel Site on the Integrase Enzyme of Human Immunodeficiency Virus;#8197;1

    SciTech Connect

    Wielens, Jerome; Headey, Stephen J.; Deadman, John J.; Rhodes, David I.; Parker, Michael W.; Chalmers, David K.; Scanlon, Martin J.

    2011-08-17

    Fragment-based screening has been used to identify a novel ligand binding site on HIV-1 integrase. Crystal structures of fragments bound at this site (shown) have been used to design elaborated second-generation compounds that bind with higher affinity and good ligand efficiency.

  19. Learning to Design and Implement Educational Web Sites within Pre-Service Training: A Project-Based Learning Environment and Its Impact on Student Teachers

    ERIC Educational Resources Information Center

    Papastergiou, Marina

    2005-01-01

    This paper reports on a project-based learning (PBL) environment targeted towards introducing student teachers to the design and development of educational web sites. The participants were 46 student teachers who constructed 16 web sites for primary school. A survey of their views, before and after the projects, and an evaluation of the web sites…

  20. Learning to Design and Implement Educational Web Sites within Pre-Service Training: a Project-Based Learning Environment and its Impact on Student Teachers

    ERIC Educational Resources Information Center

    Papastergiou, Marina

    2005-01-01

    This paper reports on a project-based learning (PBL) environment targeted towards introducing student teachers to the design and development of educational web sites. The participants were 46 student teachers who constructed 16 web sites for primary school. A survey of their views, before and after the projects, and an evaluation of the web sites…

  1. Annual survival estimation of migratory songbirds confounded by incomplete breeding site-fidelity: Study designs that may help

    USGS Publications Warehouse

    Marshall, M.R.; Diefenbach, D.R.; Wood, L.A.; Cooper, R.J.

    2004-01-01

    Many species of bird exhibit varying degrees of site-fidelity to the previous year's territory or breeding area, a phenomenon we refer to as incomplete breeding site-fidelity. If the territory they occupy is located beyond the bounds of the study area or search area (i.e., they have emigrated from the study area), the bird will go undetected and is therefore indistinguishable from dead individuals in capture-mark-recapture studies. Differential emigration rates confound inferences regarding differences in survival between sexes and among species if apparent survival rates are used as estimates of true survival. Moreover, the bias introduced by using apparent survival rates for true survival rates can have profound effects on the predictions of population persistence through time, source/sink dynamics, and other aspects of life-history theory. We investigated four study design and analysis approaches that result in apparent survival estimates that are closer to true survival estimates. Our motivation for this research stemmed from a multi-year capture-recapture study of Prothonotary Warblers (Protonotaria citrea) on multiple study plots within a larger landscape of suitable breeding habitat where substantial inter-annual movements of marked individuals among neighboring study plots was documented. We wished to quantify the effects of this type of movement on annual survival estimation. The first two study designs we investigated involved marking birds in a core area and resighting them in the core as well as an area surrounding the core. For the first of these two designs, we demonstrated that as the resighting area surrounding the core gets progressively larger, and more "emigrants" are resighted, apparent survival estimates begin to approximate true survival rates (bias < 0.01). However, given observed inter-annual movements of birds, it is likely to be logistically impractical to resight birds on sufficiently large surrounding areas to minimize bias. Therefore

  2. HotSpot Wizard 2.0: automated design of site-specific mutations and smart libraries in protein engineering

    PubMed Central

    Bendl, Jaroslav; Stourac, Jan; Sebestova, Eva; Vavra, Ondrej; Musil, Milos; Brezovsky, Jan; Damborsky, Jiri

    2016-01-01

    HotSpot Wizard 2.0 is a web server for automated identification of hot spots and design of smart libraries for engineering proteins’ stability, catalytic activity, substrate specificity and enantioselectivity. The server integrates sequence, structural and evolutionary information obtained from 3 databases and 20 computational tools. Users are guided through the processes of selecting hot spots using four different protein engineering strategies and optimizing the resulting library's size by narrowing down a set of substitutions at individual randomized positions. The only required input is a query protein structure. The results of the calculations are mapped onto the protein's structure and visualized with a JSmol applet. HotSpot Wizard lists annotated residues suitable for mutagenesis and can automatically design appropriate codons for each implemented strategy. Overall, HotSpot Wizard provides comprehensive annotations of protein structures and assists protein engineers with the rational design of site-specific mutations and focused libraries. It is freely available at http://loschmidt.chemi.muni.cz/hotspotwizard. PMID:27174934

  3. HotSpot Wizard 2.0: automated design of site-specific mutations and smart libraries in protein engineering.

    PubMed

    Bendl, Jaroslav; Stourac, Jan; Sebestova, Eva; Vavra, Ondrej; Musil, Milos; Brezovsky, Jan; Damborsky, Jiri

    2016-07-01

    HotSpot Wizard 2.0 is a web server for automated identification of hot spots and design of smart libraries for engineering proteins' stability, catalytic activity, substrate specificity and enantioselectivity. The server integrates sequence, structural and evolutionary information obtained from 3 databases and 20 computational tools. Users are guided through the processes of selecting hot spots using four different protein engineering strategies and optimizing the resulting library's size by narrowing down a set of substitutions at individual randomized positions. The only required input is a query protein structure. The results of the calculations are mapped onto the protein's structure and visualized with a JSmol applet. HotSpot Wizard lists annotated residues suitable for mutagenesis and can automatically design appropriate codons for each implemented strategy. Overall, HotSpot Wizard provides comprehensive annotations of protein structures and assists protein engineers with the rational design of site-specific mutations and focused libraries. It is freely available at http://loschmidt.chemi.muni.cz/hotspotwizard. PMID:27174934

  4. A novel approach for determination of fundamental physical transport processes in natural channel design restoration sites with river steering structures

    NASA Astrophysics Data System (ADS)

    Robinson, J.; Endreny, T. A.; Becker, J. F.; Kroll, C.

    2012-12-01

    River restoration projects in the United States are frequently proposed and constructed with the intention of improving water quality, yet relatively little evidence exists regarding the success of these efforts. Many projects use an approach known as natural channel design (NCD), and include river steering structures. Prior assessment of water quality improvements within NCD sites has involved hydrologic retention modeling using a non-reactive tracer, with the goal of separately identifying hyporheic and surface transient storage (STS). A comparative approach involving NCD and non-NCD sites used by the authors yielded mixed results: although physically-based assessments of STS profiles in many NCD sites support larger STS zones than non-NCD sites, these differences are not apparent when examining common transient storage metrics. Inverse modeling within nine NCD sites reveals additional obstacles, including generation of spurious lateral inflow/outflow values, limited detection of hyporheic processes due to strong surface transient storage, shear and Taylor dispersion, and divergent temporal patterns of solute flux over channel cross sections bounding structures. To overcome the obstacles encountered with 1D inverse modeling, data is presented from a new approach used in NCD reaches. This approach involves deriving a mass flux signature via pairing velocity and channel geometry with multiple electrical conductivity (EC) loggers deployed laterally at control cross sections (CCS). These CCS bound sub-reach segments (15 total across four NCD reaches) that include river steering structures and intermediate geomorphic features. Velocity and geometry measurements yield discharge values surrounding each EC logger which are used to weight a composite mass flux breakthrough curve above, within, and below each segment. Composite mass flux signatures reflect exchange processes that are not fully integrated laterally immediately below structures, and can be analyzed via

  5. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Slick Rock, Colorado. Attachment 3, Ground water hydrology report: Preliminary final

    SciTech Connect

    Not Available

    1994-03-04

    The US Environmental Protection Agency (EPA) has established health and environmental protection regulations to correct and prevent ground water contamination resulting from processing activities at inactive uranium milling sites (52 FR 36000 (1987)). According to the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 1978, 42 USC {section}7901 et seq., the US Department of Energy (DOE) is responsible for assessing the inactive uranium processing sites. The DOE has determined that for Slick Rock, this assessment shall include hydrogeologic site characterization for two separate uranium processing sites, the Union Carbide (UC) site and the North Continent (NC) site, and for the proposed Burro Canyon disposal site. The water resources protection strategy that describes how the proposed action will comply with the EPA ground water protection standards is presented in Attachment 4. The following site characterization activities are discussed in this attachment: Characterization of the hydrogeologic environment, including hydrostratigraphy, ground water occurrence, aquifer parameters, and areas of recharge and discharge. Characterization of existing ground water quality by comparison with background water quality and the maximum concentration limits (MCL) of the proposed EPA ground water protection standards. Definition of physical and chemical characteristics of the potential contaminant source, including concentration and leachability of the source in relation to migration in ground water and hydraulically connected surface water. Description of local water resources, including current and future use, availability, and alternative supplies.

  6. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Slick Rock, Colorado: Appendix A to Attachment 3, tables; Preliminary final

    SciTech Connect

    1994-03-01

    This appendix contains the supporting tables for the remedial action plan for uranium mill tailings sites at Slick Rock, CO. The tables contain monitoring well information, background groundwater quality data, regulated constituent summaries, tailings pore fluid sample analyses, and other data for each of the sites studied.

  7. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Lakeview, Oregon: Volume 3, Attachments A and B to Appendix F

    SciTech Connect

    Not Available

    1992-07-01

    Volume three contains attachments A and B for appendix F, compliance strategy for the proposed EPA groundwater standards. Attachment A has water quality data by location for the Lakeview processing site and Collins Ranch disposal site (1984 though 1991). Attachment B consists of water quality statistics data and water quality data by location (1984 through 1988).

  8. Rational design of a protein that binds integrin αvβ3 outside the ligand binding site

    PubMed Central

    Turaga, Ravi Chakra; Yin, Lu; Yang, Jenny J.; Lee, Hsiauwei; Ivanov, Ivaylo; Yan, Chunli; Yang, Hua; Grossniklaus, Hans E.; Wang, Siming; Ma, Cheng; Sun, Li; Liu, Zhi-Ren

    2016-01-01

    Integrin αvβ3 expression is altered in various diseases and has been proposed as a drug target. Here we use a rational design approach to develop a therapeutic protein, which we call ProAgio, that binds to integrin αvβ3 outside the classical ligand-binding site. We show ProAgio induces apoptosis of integrin αvβ3-expressing cells by recruiting and activating caspase 8 to the cytoplasmic domain of integrin αvβ3. ProAgio also has anti-angiogenic activity and strongly inhibits growth of tumour xenografts, but does not affect the established vasculature. Toxicity analyses demonstrate that ProAgio is not toxic to mice. Our study reports a new integrin-targeting agent with a unique mechanism of action, and provides a template for the development of integrin-targeting therapeutics. PMID:27241473

  9. Rational design of a protein that binds integrin αvβ3 outside the ligand binding site.

    PubMed

    Turaga, Ravi Chakra; Yin, Lu; Yang, Jenny J; Lee, Hsiauwei; Ivanov, Ivaylo; Yan, Chunli; Yang, Hua; Grossniklaus, Hans E; Wang, Siming; Ma, Cheng; Sun, Li; Liu, Zhi-Ren

    2016-01-01

    Integrin αvβ3 expression is altered in various diseases and has been proposed as a drug target. Here we use a rational design approach to develop a therapeutic protein, which we call ProAgio, that binds to integrin αvβ3 outside the classical ligand-binding site. We show ProAgio induces apoptosis of integrin αvβ3-expressing cells by recruiting and activating caspase 8 to the cytoplasmic domain of integrin αvβ3. ProAgio also has anti-angiogenic activity and strongly inhibits growth of tumour xenografts, but does not affect the established vasculature. Toxicity analyses demonstrate that ProAgio is not toxic to mice. Our study reports a new integrin-targeting agent with a unique mechanism of action, and provides a template for the development of integrin-targeting therapeutics. PMID:27241473

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Design, synthesis and antiviral activity of entry inhibitors that target the CD4-binding site of HIV-1

    PubMed Central

    Curreli, Francesca; Choudhury, Spreeha; Pyatkin, Ilya; Zagorodnikov, Victor P.; Bulay, Anna Khulianova; Altieri, Andrea; Kwon, Young Do; Kwong, Peter D.; Debnath, Asim K.

    2012-01-01

    The CD4 binding site on HIV-1 gp120 has been validated as a drug target to prevent HIV-1 entry to cells. Previously, we identified two small molecule inhibitors consisting of a 2,2,6,6-tetramethylpiperidine ring linked by an oxalamide to a p-halide-substituted phenyl group, which target this site, specifically, a cavity termed “Phe43 cavity”. Here we use synthetic chemistry, functional assessment and structure-based analysis to explore variants of each region of these inhibitors for improved antiviral properties. Alterations of the phenyl group and of the oxalamide linker indicated that these regions were close to optimal in the original lead compounds. Design of a series of compounds, where the tetramethylpiperidine ring was replaced with new scaffolds, lead to improved antiviral activity. These new scaffolds provide insight into the surface chemistry at the entrance of the cavity and offer additional opportunities by which to optimize further these potential-next-generation therapeutics and microbicides against HIV-1. PMID:22524483

  12. On the Proper Estimation of the Confidence Interval for the Design Formula of Blast-Induced Vibrations with Site Records

    NASA Astrophysics Data System (ADS)

    Yan, W. M.; Yuen, Ka-Veng

    2015-01-01

    Blast-induced ground vibration has received much engineering and public attention. The vibration is often represented by the peak particle velocity (PPV) and the empirical approach is employed to describe the relationship between the PPV and the scaled distance. Different statistical methods are often used to obtain the confidence level of the prediction. With a known scaled distance, the amount of explosives in a planned blast can then be determined by a blast engineer when the PPV limit and the confidence level of the vibration magnitude are specified. This paper shows that these current approaches do not incorporate the posterior uncertainty of the fitting coefficients. In order to resolve this problem, a Bayesian method is proposed to derive the site-specific fitting coefficients based on a small amount of data collected at an early stage of a blasting project. More importantly, uncertainty of both the fitting coefficients and the design formula can be quantified. Data collected from a site formation project in Hong Kong is used to illustrate the performance of the proposed method. It is shown that the proposed method resolves the underestimation problem in one of the conventional approaches. The proposed approach can be easily conducted using spreadsheet calculation without the need for any additional tools, so it will be particularly welcome by practicing engineers.

  13. sgRNAcas9: A Software Package for Designing CRISPR sgRNA and Evaluating Potential Off-Target Cleavage Sites

    PubMed Central

    Xie, Shengsong; Shen, Bin; Zhang, Chaobao; Huang, Xingxu; Zhang, Yonglian

    2014-01-01

    Although the CRISPR/Cas9/sgRNA system efficiently cleaves intracellular DNA at desired target sites, major concerns remain on potential “off-target” cleavage that may occur throughout the whole genome. In order to improve CRISPR-Cas9 specificity for targeted genome editing and transcriptional control, we describe a bioinformatics tool “sgRNAcas9”, which is a software package developed for fast design of CRISPR sgRNA with minimized off-target effects. This package consists of programs to perform a search for CRISPR target sites (protospacers) with user-defined parameters, predict genome-wide Cas9 potential off-target cleavage sites (POT), classify the POT into three categories, batch-design oligonucleotides for constructing 20-nt (nucleotides) or truncated sgRNA expression vectors, extract desired length nucleotide sequences flanking the on- or off-target cleavage sites for designing PCR primer pairs to validate the mutations by T7E1 cleavage assay. Importantly, by identifying potential off-target sites in silico, the sgRNAcas9 allows the selection of more specific target sites and aids the identification of bona fide off-target sites, significantly facilitating the design of sgRNA for genome editing applications. sgRNAcas9 software package is publicly available at BiooTools website (www.biootools.com) under the terms of the GNU General Public License. PMID:24956386

  14. Comment and response document on the final remedial action plan and site design for stabilization of the inactive Uranium Mill Tailings Site at Lakeview, Oregon

    SciTech Connect

    Not Available

    1991-10-01

    This report contains comments provided by the Oregon Department of Energy and responses to these comments on the final remedial action plan for the inactive uranium mill tailings site at Lakeview, Oregon.

  15. Remedial action and site design for stabilization of the inactive uranium mill tailings sites at Slick Rock, Colorado. Attachment 2, Geology report

    SciTech Connect

    Not Available

    1993-07-01

    This report presents geologic considerations that are pertinent to the Remedial Action Plan for Slick Rock mill tailings. Topics covered include regional geology, site geology, geologic stability, and geologic suitability.

  16. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Attachment 3, Groundwater hydrology report. Revised final report

    SciTech Connect

    Not Available

    1991-12-01

    The US Environmental Protection Agency (EPA) has established health and environmental protection regulations to correct and prevent groundwater contamination resulting from processing activities at inactive uranium milling sites. According to the Uranium Mill Tailings Radiation Control Act of 1978, (UMTRCA) the US Department of Energy (DOE) is responsible for assessing the inactive uranium processing sites. The DOE has determined this assessment shall include information on hydrogeologic site characterization. The water resources protection strategy that describes how the proposed action will comply with the EPA groundwater protection standards is presented in Attachment 4. Site characterization activities discussed in this section include: Characterization of the hydrogeologic environment; characterization of existing groundwater quality; definition of physical and chemical characteristics of the potential contaminant source; and description of local water resources.

  17. Osmotically regulated floating asymmetric membrane capsule for controlled site-specific delivery of ranitidine hydrochloride: optimization by central composite design.

    PubMed

    Chauhan, Manvendra S; Kumar, Anil; Pathak, Kamla

    2012-12-01

    A nondisintegrating, floating asymmetric membrane capsule (FAMC) was developed to achieve site-specific osmotic flow of a highly water-soluble drug, ranitidine hydrochloride (RHCl), in a controlled manner. Solubility suppression of RHCl was achieved by the common ion effect, using optimized coated sodium chloride as a formulation component. The capsular wall of FAMC was prepared by the phase inversion process wherein the polymeric membrane was precipitated on glass pins by dipping them in a solution of cellulose acetate followed by quenching. Central composite design was utilized to investigate the influence of independent variables, namely, level(s) of membrane former, pore former, and osmogen, on percent cumulative drug release (response). The release mechanism of RHCl through FAMC was confirmed as osmotic pumping. The asymmetry of the membrane was characterized by scanning electron microscopy that revealed a dense nonporous outer region of membrane supported by an inner porous region. Differential scanning calorimetry indicated no incompatibility between the drug and excipients. In vitro drug release in three biorelevant media, pH 2.5 (low fed), pH 4.5 (intermediate fed), and pH 6.5 (high fed), demonstrated pH-independent release of RHCl (P > 0.05). Floating ability for 12 h of the optimized FAMC9 was visually examined during the in vitro release studies that showed maximal drug release with zero-order kinetics (r (2) = 0.9991). Thus, a novel osmotically regulated floating capsular system was developed for site-specific delivery of RHCl. PMID:23104305

  18. Site-Directed Mutagenesis of a Hyperthermophilic Endoglucanase Cel12B from Thermotoga maritima Based on Rational Design

    PubMed Central

    Zhang, Jinfeng; Shi, Hao; Xu, Linyu; Zhu, Xiaoyan; Li, Xiangqian

    2015-01-01

    To meet the demand for the application of high activity and thermostable cellulases in the production of new-generation bioethanol from nongrain-cellulose sources, a hyperthermostable β-1,4-endoglucase Cel12B from Thermotoga maritima was selected for further modification by gene site-directed mutagenesis method in the present study, based on homology modeling and rational design. As a result, two recombinant enzymes showed significant improvement in enzyme activity by 77% and 87%, respectively, higher than the parental enzyme TmCel12B. Furthermore, the two mutants could retain 80% and 90.5% of their initial activity after incubation at 80°C for 8 h, while only 45% for 5 h to TmCel12B. The Km and Vmax of the two recombinant enzymes were 1.97±0.05 mM, 4.23±0.15 μmol·mg-1·min-1 of TmCel12B-E225H-K207G-D37V, and 2.97±0.12 mM, 3.15±0.21 μmol·mg-1·min-1 of TmCel12B-E225H-K207G, respectively, when using CMC-Na as the substrate. The roles of the mutation sites were also analyzed and evaluated in terms of electron density, hydrophobicity of the modeled protein structures. The recombinant enzymes may be used in the hydrolysis of cellulose at higher temperature in the future. It was concluded that the gene mutagenesis approach of a certain active residues may effectively improve the performance of cellulases for the industrial applications and contribute to the study the thermostable mechanism of thermophilic enzymes. PMID:26218520

  19. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Gunnison, Colorado. Attachment 4, Water resources protection strategy: Final report

    SciTech Connect

    Not Available

    1992-10-01

    To achieve compliance with the proposed US Environmental Protection Agency (EPA) groundwater protection standards the US Department of Energy (DOE) proposes to meet background concentrations or the EPA maximum concentration limits (MCLS) for hazardous constituents in groundwater in the uppermost aquifer at the point of compliance (POC) at the Gunnison Uranium Mill Tailings Remedial Action (UMTRA) Project disposal site near Gunnison, Colorado. The proposed remedial action will ensure protection of human health and the environment. A summary of the principal features of the water resources protection strategy for the Gunnison disposal site is included in this report.

  20. Theoretical and experimental design of site-specific applicators and heating protocols for interstitial ultrasound thermal therapy

    NASA Astrophysics Data System (ADS)

    Tyreus, Per Daniel; Nau, William H.; Wu, Alex; Diederich, Chris J.

    2003-06-01

    Theoretical and experimental approaches were used to develop and evaluate site-specific designs of internally cooled direct coupled (ICDC) and catheter-cooled (CC) ultrasound applicators for thermal coagulation of disease in the prostate, liver, brain, and uterus. The diameter of an interstitial applicator can influence its clinical practicality and effectiveness as well as application site. One purpose of this study was to determine whether the use of larger ultrasound transducers and the inherent increase in applicator size could be justified by potentially producing larger lesion diameters. A second purpose was to explore how the response of tissue acoustic attenuation to heating effects lesion size and preferred applicator configuration. Four applicator configurations and sizes were studied using ex vivo tissue experiments in liver and beef and using acoustic and biothermal simulations. Transmission attenuation measurements showed a 6 to 8 fold increase in baseline tissue attenution inside interstitial ultrasound lesions. Formation of these high attenuation zones in lesions reduced potential lesion size. Larger applicators produced lesions with radial penetration depths superior to their smaller counterparts at power levels in the 20-40W /cm range. The higher cooling rates along the outer surface of the larger diameter applicators due to their greater surface area was a dominant factor in increasing lesion size. The higher cooling rates pushed the maximum temperature farther from the applicator surface and reduced the formation of high acoustic attenuation tissue zones. Acoustic and biothermal simulations matched the experimental data well and were applied to model these applicators within sites of clinical interest such as prostate, uterine fibroid, brain, and normal liver. Lesions of 3.9 to 4.7cm diameter were predicted for moderately perfused tissues such as prostate and fibroid and 2.8 to 3.2cm for highly perfused tissues such as normal liver. Feedback

  1. Trans-complementation by human apurinic endonuclease (Ape) of hypersensitivity to DNA damage and spontaneous mutator phenotype in apn1-yeast.

    PubMed Central

    Wilson, D M; Bennett, R A; Marquis, J C; Ansari, P; Demple, B

    1995-01-01

    Abasic (AP) sites in DNA are potentially lethal and mutagenic. 'Class II' AP endonucleases initiate the repair of these and other DNA lesions. In yeast, the predominant enzyme of this type is Apn1, and its elimination sensitizes the cells to killing by simple alkylating agents or oxidants, and raises the rate of spontaneous mutation. We investigated the ability of the major human class II AP endonuclease, Ape, which is structurally unrelated to Apn1, to replace the yeast enzyme in vivo. Confocal immunomicroscopy studies indicate that approximately 25% of the Ape expressed in yeast is present in the nucleus. High-level Ape expression corresponding to approximately 7000 molecules per nucleus, equal to the normal Apn1 copy number, restored resistance to methyl methanesulfonate to near wild-type levels in Apn1-deficient (apn1-) yeast. Ape expression in apn1- yeast provided little protection against H2O2 challenges, consistent with the weak 3'-repair diesterase activity of the human enzyme. Ape expression at approximately 2000 molecules per nucleus reduced the spontaneous mutation rate of apn1- yeast to that seen for wild-type cells. Because Ape has a powerful AP endonuclease but weak 3'-diesterase activity, these findings indicate that endogenously generated AP sites can drive spontaneous mutagenesis. Images PMID:8559661

  2. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Gunnison, Colorado. Appendix A to Attachment 3, Tables: Final report

    SciTech Connect

    Not Available

    1992-10-01

    This volume contains the following tables: monitoring well information; static ground water levels; background ground water quality data by parameter; 1984 lysimeter tailings pore water quality by parameter; lysimeter tailings pore fluid quality data by parameter; and on site/downgradient ground water quality data by parameter.

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

    USGS Publications Warehouse

    Scott, J.C.

    1990-01-01

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

  4. Thermal calculations for the design, construction, operation, and evaluation of the Spent Fuel Test - Climax, Nevada Test Site

    SciTech Connect

    Montan, D.N.; Patrick, W.C.

    1981-09-30

    The Spent Fuel Test-Climax (SFT-C) is a test of retrievable deep geologic storage of commercially generated spent nuclear reactor fuel in granitic rock. Eleven spent fuel assemblies, together with six electrical simulators and 20 guard heaters, are emplaced 420 m below the surface in the Climax granite at the US Department of Energy Nevada Test Site. On June 2, 1978 LLNL secured funding for the SFT-C, and completed spent fuel emplacement May 28, 1980. This report documents a series of thermal calculations that were performed in support of the SFT-C. Early calculations employed analytical solutions to address such design and construction issues as drift layout and emplacement hole spacings. Operational aspects of the test required more detailed numerical solutions dealing with ventilation and guard-heater power levels. The final set of calculations presented here provides temperature histories throughout the test facility for evaluation of the response of the SFT-C and for comparison of calculations with acquired data. This final set of calculations employs the as-built test geometry and best-available material properties.

  5. Probabilistic Seismic Hazard Characterization and Design Parameters for the Sites of the Nuclear Power Plants of Ukraine

    SciTech Connect

    Savy, J.B.; Foxall, W.

    2000-01-26

    The U.S. Department of Energy (US DOE), under the auspices of the International Nuclear Safety Program (INSP) is supporting in-depth safety assessments (ISA) of nuclear power plants in Eastern Europe and the former Soviet Union for the purpose of evaluating the safety and upgrades necessary to the stock of nuclear power plants in Ukraine. For this purpose the Hazards Mitigation Center at Lawrence Livermore National Laboratory (LLNL) has been asked to assess the seismic hazard and design parameters at the sites of the nuclear power plants in Ukraine. The probabilistic seismic hazard (PSH) estimates were updated using the latest available data and knowledge from LLNL, the U.S. Geological Survey, and other relevant recent studies from several consulting companies. Special attention was given to account for the local seismicity, the deep focused earthquakes of the Vrancea zone, in Romania, the region around Crimea and for the system of potentially active faults associated with the Pripyat Dniepro Donnetts rift. Aleatory (random) uncertainty was estimated from the available data and the epistemic (knowledge) uncertainty was estimated by considering the existing models in the literature and the interpretations of a small group of experts elicited during a workshop conducted in Kiev, Ukraine, on February 2-4, 1999.

  6. Design of an Optimal Microseismic Monitoring Network: Synthetic Study for the Kimberlina CO2 Storage Demonstration Site

    NASA Astrophysics Data System (ADS)

    Huang, L.; Chen, T.; Lin, Y.; Foxall, W.; Hutchings, L. J.; Bachmann, C. E.; Daley, T. M.

    2014-12-01

    As part of the U.S. DOE initiative, National Risk Assessment Partnership (NRAP) to develop quantitative risk assessment methodologies for carbon capture, utilization and storage (CCUS), we explore the design of an optimal microseismic monitoring network using synthetic earthquake data for the Kimberlina CCUS pilot site in California. The overpressure field calculated by fluid flow modeling within a reservoir confined by two fault zones in the vicinity of the Kimberlina injection well is input to induced earthquake simulations carried out using the code RSQSim (Dieterich and Richards-Dinger, Seismol. Res. Let., 2012). Velocity and attenuation structures developed using geological data for the reservoir overburden and underburden are used for numerical wave propagation modeling to calculate surface ground motion time series produced by the simulated microseismic events. We then invert the time series data using a fat-ray double-difference tomography method to locate the events, and compare the results with the known locations. The tomography method is applied to time series calculated for different surface recording network configurations to study the resulting variations in event locations uncertainties, and to assess an optimal network for cost-effective, long-term monitoring for CCUS.

  7. State of the art design: A closure system for the largest hazardous waste landfill at the Savannah River Site

    SciTech Connect

    Bartlett, S.F.; Serrato, M.G.; McMullin, S.R.

    1992-12-31

    This paper discusses the cover system proposed for a 55-acre, hazardous waste closure of the sanitary landfill at the Savannah River Site, near Aiken, South Carolina. The proposed cover system has been designed to accommodate a significant amount of post-closure settlement while maintaining a permeability of 1 {times} 10{sup {minus}7} cm/s or less throughout its 30-year, regulatory lifetime. A composite cover consisting of a geomembrane (GM) underlain by a geosynthetic clay liner (GCL) was selected because of its extremely low permeability, ability to elongate without tearing, and capacity to ``self-heal`` if punctured. These characteristics will enable the cover system to accommodate differential settlement without cracking or tearing, this providing long-term protection with minimal maintenance. Also, to improve the ability of the cover system to span voids that may develop in the underlying waste, a geogrid has been included in the foundation layer. A gas vent layer has been included to allow for the safe collection and venting of landfill gases.

  8. State of the art design: A closure system for the largest hazardous waste landfill at the Savannah River Site

    SciTech Connect

    Bartlett, S.F.; Serrato, M.G.; McMullin, S.R.

    1992-01-01

    This paper discusses the cover system proposed for a 55-acre, hazardous waste closure of the sanitary landfill at the Savannah River Site, near Aiken, South Carolina. The proposed cover system has been designed to accommodate a significant amount of post-closure settlement while maintaining a permeability of 1 [times] 10[sup [minus]7] cm/s or less throughout its 30-year, regulatory lifetime. A composite cover consisting of a geomembrane (GM) underlain by a geosynthetic clay liner (GCL) was selected because of its extremely low permeability, ability to elongate without tearing, and capacity to self-heal'' if punctured. These characteristics will enable the cover system to accommodate differential settlement without cracking or tearing, this providing long-term protection with minimal maintenance. Also, to improve the ability of the cover system to span voids that may develop in the underlying waste, a geogrid has been included in the foundation layer. A gas vent layer has been included to allow for the safe collection and venting of landfill gases.

  9. Exploration of the Active Site of Neuronal Nitric Oxide Synthase by the Design and Synthesis of Pyrrolidinomethyl 2-Aminopyridine Derivatives

    PubMed Central

    Ji, Haitao; Delker, Silvia L.; Li, Huiying; Martásek, Pavel; Roman, Linda J.; Poulos, Thomas L.; Silverman, Richard B.

    2010-01-01

    Neuronal nitric oxide synthase (nNOS) represents an important therapeutic target for the prevention of brain injury and the treatment of various neurodegenerative disorders. A series of trans substituted amino pyrrolidinomethyl 2-aminopyridine derivatives (8–34) was designed and synthesized. A structure-activity relationship analysis led to the discovery of low nanomolar nNOS inhibitors [(±)-32 and (±)-34] with more than 1000-fold selectivity for nNOS over eNOS. Four enantiomerically pure isomers of 3′-[2″-(3‴-fluorophenethylamino)ethoxy]pyrrolidin-4′-yl}methyl}-4-methylpyridin-2-amine (4) also were synthesized. It was found that (3′R, 4′R)-4 can induce enzyme elasticity to generate a new “hot spot” for ligand binding. The inhibitor adopts a unique binding mode, the same as that observed for (3′R, 4′R)-3′-[2″-(3‴-fluorophenethylamino)ethylamino]pyrrolidin-4′-yl}methyl}-4-methylpyridin-2-amine ((3′R, 4′R)-3) (J. Am. Chem. Soc. 2010, 132(15), 5437–5442). On the basis of structure-activity relationships of 8–34 and different binding conformations of the cis and trans isomers of 3 and 4, critical structural requirements of the NOS active site for ligand binding are revealed. PMID:20958055

  10. Design wind speeds for high hazard, moderate hazard, important/low hazard and general use facilities at the Savannah River Site

    SciTech Connect

    King, H.H.

    1989-09-11

    The design wind speeds for High Hazard, Moderate Hazard, Important/Low Hazard and General Use facilities at the Savannah River Site are developed below using the procedures and site-specific hazards model required by DOE Order 6430.1A. These are less than the previously required Design Wind Speeds and are: (1) High Hazard (Maximum Resistance) Facility, 185 mph; (2) Moderate Hazard (High Resistance) Facility, 37 mph; (3) Important/Low Hazard (Intermediate) Facility, 83 mph; and, (4) General Use (Standard) Facility, 78 mph.

  11. Estimating site occupancy rates for aquatic plants using spatial sub-sampling designs when detection probabilities are less than one

    USGS Publications Warehouse

    Nielson, Ryan M.; Gray, Brian R.; McDonald, Lyman L.; Heglund, Patricia J.

    2011-01-01

    Estimation of site occupancy rates when detection probabilities are <1 is well established in wildlife science. Data from multiple visits to a sample of sites are used to estimate detection probabilities and the proportion of sites occupied by focal species. In this article we describe how site occupancy methods can be applied to estimate occupancy rates of plants and other sessile organisms. We illustrate this approach and the pitfalls of ignoring incomplete detection using spatial data for 2 aquatic vascular plants collected under the Upper Mississippi River's Long Term Resource Monitoring Program (LTRMP). Site occupancy models considered include: a naïve model that ignores incomplete detection, a simple site occupancy model assuming a constant occupancy rate and a constant probability of detection across sites, several models that allow site occupancy rates and probabilities of detection to vary with habitat characteristics, and mixture models that allow for unexplained variation in detection probabilities. We used information theoretic methods to rank competing models and bootstrapping to evaluate the goodness-of-fit of the final models. Results of our analysis confirm that ignoring incomplete detection can result in biased estimates of occupancy rates. Estimates of site occupancy rates for 2 aquatic plant species were 19–36% higher compared to naive estimates that ignored probabilities of detection <1. Simulations indicate that final models have little bias when 50 or more sites are sampled, and little gains in precision could be expected for sample sizes >300. We recommend applying site occupancy methods for monitoring presence of aquatic species.

  12. Mycobacterium tuberculosis class II apurinic/apyrimidinic-endonuclease/3'-5' exonuclease III exhibits DNA regulated modes of interaction with the sliding DNA β-clamp.

    PubMed

    Khanam, Taran; Rai, Niyati; Ramachandran, Ravishankar

    2015-10-01

    The class-II AP-endonuclease (XthA) acts on abasic sites of damaged DNA in bacterial base excision repair. We identified that the sliding DNA β-clamp forms in vivo and in vitro complexes with XthA in Mycobacterium tuberculosis. A novel 239 QLRFPKK245 motif in the DNA-binding domain of XthA was found to be important for the interactions. Likewise, the peptide binding-groove (PBG) and the C-terminal of β-clamp located on different domains interact with XthA. The β-clamp-XthA complex can be disrupted by clamp binding peptides and also by a specific bacterial clamp inhibitor that binds at the PBG. We also identified that β-clamp stimulates the activities of XthA primarily by increasing its affinity for the substrate and its processivity. Additionally, loading of the β-clamp onto DNA is required for activity stimulation. A reduction in XthA activity stimulation was observed in the presence of β-clamp binding peptides supporting that direct interactions between the proteins are necessary to cause stimulation. Finally, we found that in the absence of DNA, the PBG located on the second domain of the β-clamp is important for interactions with XthA, while the C-terminal domain predominantly mediates functional interactions in the substrate's presence. PMID:26103519

  13. Functional and Mechanistic Analyses of Biomimetic Aminoacyl Transfer Reactions in de novo Designed Coiled Coil Peptides via Rational Active Site Engineering

    PubMed Central

    Leman, Luke J.; Weinberger, Dana A.; Huang, Zheng-Zheng; Wilcoxen, Keith M.; Ghadiri, M. Reza

    2008-01-01

    Ribosomes and nonribosomal peptide synthetases (NRPSs) carry out instructed peptide synthesis through a series of directed intermodular aminoacyl transfer reactions. We recently reported the design of coiled-coil assemblies that could functionally mimic the elementary aminoacyl loading and intermodular aminoacyl transfer steps of NRPSs. These peptides were designed initially to accelerate aminoacyl transfer mainly through catalysis by approximation by closely juxtaposing four active site moieties, two each from adjacent noncovalently-associated helical modules. In our designs peptide self-assembly positions a cysteine residue that is used to covalently capture substrates from solution via transthiolesterification (substrate loading step to generate the aminoacyl donor site) adjacent to an aminoacyl acceptor site provided by a covalently tethered amino acid or modeled by the ε-amine of an active site lysine. However, through systematic functional analyses of 48 rationally designed peptide sequences, we have now determined that the substrate loading and intermodular aminoacyl transfer steps can be significantly influenced (up to ~103-fold) by engineering changes in the active site microenvironment through amino acid substitutions and variations in the inter-residue distances and geometry. Mechanistic studies based on 15N-NMR and kinetic analysis further indicate that certain active site constellations furnish an unexpectedly large pKa depression (1.5 pH units) of the aminoacyl-acceptor moiety, helping to explain the observed high rates of aminoacyl transfer in those constructs. Taken together, our studies demonstrate the feasibility of engineering efficient de novo peptide sequences possessing active sites and functions reminiscent of those in natural enzymes. PMID:17302417

  14. The future through the past: The use of analog sites for design criteria and long-term performance assessment of evapotranspiration landfill covers.

    SciTech Connect

    David Shafer; Julianne Miller; Susan Edwards; Stuart Rawlinson

    2001-10-18

    There is growing support for using evapotranspiration (ET) covers for closure of low-level waste (LLW) and other types of waste disposal sites, particularly in the lower latitude arid regions of the western United States. For the Nevada Test Site (NTS), monolayer ET covers is the baseline technology for closure of LLW and mixed LLW cells. To better predict the long-term performance of monolayer ET covers, as well as to identify design criteria that will potentially improve their performance, the properties of, and processes occurring on, analog sites for ET covers on the NTS are being studied. Four analog sites on the NTS have been selected to predict performance of ET covers over a 1,000-year compliance period. Two are relatively recently disturbed sites (within the last 50 years) and have been selected for the evaluation of processes and changes on ET covers for the early period of post-institutional controls when cover maintenance would be discontinued. Two other sites, late to mid-Holocene in age, are intended as analogs for the end (1,000 years or more) of the compliance period. The late to mid-Holocene surfaces are both abandoned alluvial/colluvial deposits, dated by thermoluminescence analysis. The history of the early post-institutional control analog sites is being evaluated by an archaeologist to help determine when the sites were last disturbed or modified and the mode of disturbance, to help set baseline conditions. Similar to the other ''landforms,'' ET covers will evolve over time because of pedogenic, biotic, and climatic processes. Properties of analog sites that could affect ET water-balance performance will be evaluated to help understand ET cover performance over time. Results of analog site work and resultant modifications to design, monitoring and maintenance of ET covers on the NTS will be compared with results of a similar study being done at Sandia National Laboratories (SNL), where ET cover closures are planned as well. The comparison will

  15. Remedial action plan and site conceptual design for stabilization of the inactive uranium mill tailings site at Ambrosia Lake, New Mexico. Volume 1, Text, Appendices A, B, and C: Final report

    SciTech Connect

    Matthews, M.L.; Mitzelfelt, R.

    1991-11-01

    This Remedial Action Plan (RAP) has been developed to serve a dual purpose. It presents the series of activities that is proposed by the US Department of Energy (DOE) to stabilize and control radioactive materials at the inactive Phillips/United Nuclear uranium processing site designated as the Ambrosia Lake site in McKinley County, New Mexico. It also serves to document the concurrence of both State of New Mexico and the US Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by the DOE and the state and concurrence by NRC, becomes Appendix B of the Cooperative Agreement.

  16. A thick homogeneous vegetated cover design proves cost - and schedule-effective for the reclamation of uranium mills sites near Spokane, Washington

    SciTech Connect

    Blacklaw, J.; Robertson, G.; Stoffel, D.; Ahmad, J.; Fordham, E.

    1997-08-01

    The Washington State Department of Health (WDOH) has licensed two medium sized uranium mills with tailings impoundments covering 28 and 40 hectares (70 and 100 acres), respectively, The uranium mill licensees have submitted closure and reclamation plans to the state, and site-specific conditions have determined the closure design features, Conventional uranium mill cover designs usually incorporate an overall cap of one to three meters, which includes a low-permeability clay barrier layer. A technical evaluation of several uranium mill facilities that used this design was published in the fall of 1994 and reported that unexpected vegetation root damage had occurred in the low-permeability clay (or bentonite amended) barrier layers. The technical report suggested that the low-permeability design feature at some sites could be compromised within a very short time and the regulatory goal of 1,000 years performance might not be achieved. In October 1994, WDOH sponsored a technical forum meeting to consider design alternatives to address these reliability concerns. Representatives from the federal government, nuclear industry, licensees, engineering firms, and state regulatory agencies attended the workshop. Risk factors considered in the evaluation of the uranium mill reclamation plans include: (1) radon gas emanation through the cover (the air pathway), and (2) migration of hazardous and/or radioactive constituents (the groundwater pathway). Additional design considerations include site structural stability, longevity of 1,000 years, and no active (ongoing) maintenance. 9 refs.

  17. Assessment of the applicability of a "toolbox" designed for microbially assisted phytoremediation: the case study at Ingurtosu mining site (Italy).

    PubMed

    Sprocati, Anna Rosa; Alisi, Chiara; Pinto, Valentina; Montereali, Maria Rita; Marconi, Paola; Tasso, Flavia; Turnau, Katarzyna; De Giudici, Giovanni; Goralska, Katarzyna; Bevilacqua, Marta; Marini, Federico; Cremisini, Carlo

    2014-01-01

    The paper describes the fieldwork at the Italian test site of the abandoned mine of sphalerite and galena in Ingurtosu (Sardinia), with the aim to assess the applicability of a "toolbox" to establish the optimized techniques for remediation of soils contaminated by mining activities. A preliminary characterization-including (hydro)geochemistry, heavy metal concentration and their mobility in soil, bioprospecting for microbiology and botany-provided a data set for the development of a toolbox to deliver a microbially assisted phytoremediation process. Euphorbia pithyusa was selected as an endemic pioneer plant to be associated with a bacterial consortium, established with ten selected native strains, including metal-tolerant bacteria and producers of plant growth factors. The toolbox was firstly assessed in a greenhouse pot experiment. A positive effect of bacterial inoculum on E. pithyusa germination and total plant survival was observed. E. pithyusa showed to be a well-performing metallophyte species, and only inoculated soil retained a microbial activity with a high functional diversity, expanding metabolic affinity also towards root exudates. These results supported the decision to proceed with a field trial, investigating different treatments used singly or in combination: bioaugmentation with bacterial consortia, mycorrhizal fungi and a commercial mineral amendment. Microbial activity in soil, plant physiological parameters and heavy metal content in plants and in soil were monitored. Five months after the beginning, an early assessment of the toolbox under field conditions was carried out. Despite the cold season (October-March), results suggested the following: (1) the field setup as well as the experimental design proved to be effective; (2) plant survival was satisfactory; (3) soil quality was increased and bioaugmentation improved microbial activity, expanding the metabolic competences towards plant interaction (root exudates); and (4) multivariate

  18. The Rational Design of Specific Peptide Inhibitor against p38α MAPK at Allosteric-Site: A Therapeutic Modality for HNSCC

    PubMed Central

    Gill, Kamaldeep; Nigam, Lokesh; Singh, Ratnakar; Kumar, Suresh; Subbarao, Naidu; Chauhan, Shyam Singh; Dey, Sharmistha

    2014-01-01

    p38α is a significant target for drug designing against cancer. The overproduction of p38α MAPK promotes tumorigenesis in head and neck squamous cell carcinoma (HNSCC). The ATP binding and an allosteric site referred as DFG are the key sites of the p38α mitogen activated protein kinase (MAPK) exploited for the design of inhibitors. This study demonstrated design of peptide inhibitor on the basis of allosteric site using Glide molecular docking software and the biochemical analysis of the best modeled peptide. The best fitted tetrapeptide (FWCS) in the allosteric site inhibited the pure recombinant and serum p38α of HNSCC patients by 74 and 72%, respectively. The potency of the peptide was demonstrated by its IC50 (4.6 nM) and KD (3.41×10−10 M) values, determined by ELISA and by surface plasmon resonance (SPR) technology, respectively. The cell viability of oral cancer i.e. KB cell line was reduced in dose dependent manner by 60 and 97% by the treatment of peptide and the IC50 was 600 and 210 µM after 24 and 72 h incubation, respectively. Our result provides an insight for the development of a proficient small peptide as a promising anticancer agent targeting DFG site of p38α kinase. PMID:24983631

  19. Site characterization plan conceptual design report for a high-level nuclear waste repository in salt, vertical emplacement mode: Volume 1

    SciTech Connect

    Not Available

    1987-12-01

    This Conceptual Design Report describes the conceptual design of a high-level nuclear waste repository in salt at a proposed site in Deaf Smith County, Texas. Waste receipt, processing, packing, and other surface facility operations are described. Operations in the shafts underground are described, including waste hoisting, transfer, and vertical emplacement. This report specifically addresses the vertical emplacement mode, the reference design for the repository. Waste retrieval capability is described. The report includes a description of the layout of the surface, shafts, and underground. Major equipment items are identified. The report includes plans for decommissioning and sealing of the facility. The report discusses how the repository will satisfy performance objectives. Chapters are included on basis for design, design analyses, and data requirements for completion of future design efforts. 105 figs., 52 tabs.

  20. A Strategy and Case Study Example for Designing and Implementing Environmental Long-Term Monitoring at Legacy Management Sites

    SciTech Connect

    Earl D. Mattson; Roelof J. Versteeg; Mark Ankeny; Gail Heath; Alex Richardson

    2004-04-01

    Environmental monitoring objectives of site owners, regulators, consultants, and scientists typically share the common elements of (1) cost management, (2) risk management, and (3) information management (Figure 1). Many site owners focus on minimizing monitoring costs while regulators typically focus on risk and regulatory compliance. Scientists and consultants typically provide information management in the form of spreadsheets with extracted information provided in reports to other users. This common piecemeal approach upon individual focus on elements of the monitoring objectives, rather than the common objective of minimizing cost and risk using site information, results in missed opportunities for cost savings, environmental protection, and improved understanding of site performance.

  1. The Design and Implementation of an Intergenerational Program at a Private Long-Term Healthcare Facility with On-Site Childcare.

    ERIC Educational Resources Information Center

    Rosenberg, Marcia Kasper

    A practicum project addressed the problem of separation of generations. An intergenerational program was designed to provide elders at a long-term care facility and children at the on-site daycare center with opportunities to interact with one another for the social and emotional betterment of both groups. Participants in the program included 17…

  2. SU-D-213-05: Design, Evaluation and First Applications of a Off-Site State-Of-The-Art 3D Dosimetry System

    SciTech Connect

    Malcolm, J; Mein, S; McNiven, A; Letourneau, D; Oldham, M

    2015-06-15

    Purpose: To design, construct and commission a prototype in-house three dimensional (3D) dose verification system for stereotatic body radiotherapy (SBRT) verification at an off-site partner institution. To investigate the potential of this system to achieve sufficient performance (1mm resolution, 3% noise, within 3% of true dose reading) for SBRT verification. Methods: The system was designed utilizing a parallel ray geometry instigated by precision telecentric lenses and an LED 630nm light source. Using a radiochromic dosimeter, a 3D dosimetric comparison with our gold-standard system and treatment planning software (Eclipse) was done for a four-field box treatment, under gamma passing criteria of 3%/3mm/10% dose threshold. Post off-site installation, deviations in the system’s dose readout performance was assessed by rescanning the four-field box irradiated dosimeter and using line-profiles to compare on-site and off-site mean and noise levels in four distinct dose regions. As a final step, an end-to-end test of the system was completed at the off-site location, including CT-simulation, irradiation of the dosimeter and a 3D dosimetric comparison of the planned (Pinnacle{sup 3}) to delivered dose for a spinal SBRT treatment(12 Gy per fraction). Results: The noise level in the high and medium dose regions of the four field box treatment was relatively 5% pre and post installation. This reflects the reduction in positional uncertainty through the new design. This At 1mm dose voxels, the gamma pass rates(3%,3mm) for our in-house gold standard system and the off-site system were comparable at 95.8% and 93.2% respectively. Conclusion: This work will describe the end-to-end process and results of designing, installing, and commissioning a state-of-the-art 3D dosimetry system created for verification of advanced radiation treatments including spinal radiosurgery.

  3. Remedial action plan and site design for stabilization of the inactive uranium processing site at Naturita, Colorado. Appendix A of Attachment 3: Calculations, Final

    SciTech Connect

    Not Available

    1994-03-01

    This report contains calculations for: hydraulic gradients for Alluvial Aquifer and Salt Wash Aquifer; slug test analysis to determine hydraulic conductivity for Alluvial Aquifer and Salt Wash Aquifer; average linear groundwater velocity for Alluvial Aquifer and Salt Wash Aquifer; statistical analysis of the extent of existing groundwater contamination; hydraulic gradients for Dakota/Burro Canyon Formation and Salt Wash Aquifer; slug test analysis to determine hydraulic conductivity for Dakota/Burro Canyon Formation and Perched Salt Wash Aquifer; determination of hydraulic conductivity of the Dakota/Burro Canyon Formation from Packer Tests; average linear groundwater velocity for Dakota/Burro Canyon and Salt Wash Aquifer; chemical and mineralogical characterization of core samples from the Dry Flats Disposal Site; and demonstration of low groundwater yield from Uppermost Aquifer.

  4. 75 FR 5708 - Ocean Dumping; Designation of Ocean Dredged Material Disposal Sites Offshore of the Siuslaw River...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-04

    ... the Federal Register in 1977 (42 FR 2461), a status superseded by later statutory changes to the MPRSA. Mounding at Site A and concern over the potential for ocean currents to move sediments from Site A back... Procedures for Voluntary Preparation of NEPA Documents,'' (Voluntary NEPA Policy), 63 FR 58045, (October...

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

    ERIC Educational Resources Information Center

    Kouri, Christopher

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

  6. Ground motions associated with the design basis earthquake at the Savannah River Site, South Carolina, based on a deterministic approach

    SciTech Connect

    Youngs, R.R.; Coppersmith, K.J.; Stephenson, D.E.; Silva, W.

    1991-12-31

    Ground motion assessments are presented for evaluation of the seismic safety of K-Reactor at the Savannah River Site. Two earthquake sources are identified as the most significant to seismic hazard at the site, a M 7.5 earthquake occurring in Charleston, South Carolina, and a M 5 event occurring in the site vicinity. These events control the low frequency and high frequency portions of the spectrum, respectively. Three major issues were identified in the assessment of ground motions for the Savannah River site; specification of the appropriate stress drop for the Charleston source earthquake, specification of the appropriate levels of soil damping at large depths for site response analyses, and the appropriateness of western US recordings for specification of ground motions in the eastern US.

  7. Ground motions associated with the design basis earthquake at the Savannah River Site, South Carolina, based on a deterministic approach

    SciTech Connect

    Youngs, R.R.; Coppersmith, K.J. ); Stephenson, D.E. ); Silva, W. )

    1991-01-01

    Ground motion assessments are presented for evaluation of the seismic safety of K-Reactor at the Savannah River Site. Two earthquake sources are identified as the most significant to seismic hazard at the site, a M 7.5 earthquake occurring in Charleston, South Carolina, and a M 5 event occurring in the site vicinity. These events control the low frequency and high frequency portions of the spectrum, respectively. Three major issues were identified in the assessment of ground motions for the Savannah River site; specification of the appropriate stress drop for the Charleston source earthquake, specification of the appropriate levels of soil damping at large depths for site response analyses, and the appropriateness of western US recordings for specification of ground motions in the eastern US.

  8. Environmental design criteria for the 1/3 scale OTEC (Ocean Thermal Energy Conversion) cold water pipe At-Sea Test Site off Honolulu, Hawaii

    SciTech Connect

    Not Available

    1982-01-01

    A fully instrumented At-Sea Test of a 1/3 scale OTEC cold water pipe (CWP) will be carried out. The future prototype for this 1/3 scale model is envisioned to be the OTEC Pilot Plant design in the 10 to 40 megawatt-electric size range with an estimated CWP diameter of about 30 ft and an overall vertical length of about 3000 ft. Thus the 1/3 scale CWP consists of a pipe about 10 ft in diameter and 1000 ft long. The selected At-Sea Test site is located at 21/sup 0/15.5'N latitude and 157/sup 0/54.6'W longitude off Honolulu, Hawaii. In order to expedite development of the design of the 1/3 scale At-Sea Test CWP/Platform/Mooring System the report provides environmental design criteria data at the proposed At-Sea Test site evaluated from available historic data.

  9. Areal power density: A preliminary examination of underground heat transfer in a potential Yucca Mountain repository and recommendations for thermal design approaches; Yucca Mountain Site Characterization Project

    SciTech Connect

    Hertel, E.S. Jr.; Ryder, E.E.

    1991-11-01

    The design of the potential Yucca Mountain repository is subject to many thermal goals related to the compliance of the site with federal regulations. This report summarizes a series of sensitivity studies that determined the expected temperatures near the potential repository. These sensitivity studies were used to establish an efficient loading scheme for the spent fuel canisters and a maximum areal power density based strictly on thermal goals. Given the current knowledge of the site, a design-basis areal power density of 80 kW/acre can be justified based on thermal goals only. Further analyses to investigate the impacts of this design-basis APD on mechanical and operational aspects of the potential repository must be undertaken before a final decision is made.

  10. Remedial action plan and site design for stabilization of the inactive uranium processing site at Naturita, Colorado. Remedial Action Selection Report, Appendix B of Attachment 2: Geology report, Final

    SciTech Connect

    Not Available

    1994-03-01

    The uranium processing site near Naturita, Colorado, is one of 24 inactive uranium mill sites designated to be cleaned up by the US Department of Energy (DOE) under the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA), 42 USC {section} 7901 et seq. Part of the UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE`s remedial action plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the US Environmental Protection Agency (EPA). Included in the RAP is this Remedial Action Selection Report (RAS), which describes the proposed remedial action for the Naturita site. An extensive amount of data and supporting information has been generated and evaluated for this remedial action. These data and supporting information are not incorporated into this single document but are included or referenced in the supporting documents. The RAP consists of this RAS and four supporting documents or attachments. This Attachment 2, Geology Report describes the details of geologic, geomorphic, and seismic conditions at the Dry Flats disposal site.

  11. A method for distance determination in proteins using a designed metal ion binding site and site-directed spin labeling: evaluation with T4 lysozyme.

    PubMed Central

    Voss, J; Salwiński, L; Kaback, H R; Hubbell, W L

    1995-01-01

    The use of molecular genetics to introduce both a metal ion binding site and a nitroxide spin label into the same protein opens the use of paramagnetic metalnitroxyl interactions to estimate intramolecular distances in a wide variety of proteins. In this report, a His-Xaa3-His metal ion binding motif was introduced at the N terminus of the long interdomain helix of T4 lysozyme (Lys-65 --> His/Gln-69 --> His) of three mutants, each containing a single nitroxide-labeled cysteine residue at position 71, 76, or 80. The results show that Cu(II)-induced relaxation effects on the nitroxide can be quantitatively analyzed in terms of interspin distance in the range of 10-25 A using Redfield theory, as first suggested by Leigh [Leigh, J.S. (1970) J. Chem. Phys. 52, 2608-2612]. Of particular interest is the observation that distances can be determined both under rigid lattice conditions in frozen solution and in the presence of motion of the spins at room temperature under physiological conditions. The method should be particularly attractive for investigating structure in membrane proteins that are difficult to crystallize. In the accompanying paper, the technique is applied to a polytopic membrane protein, lactose permease. Images Fig. 1 PMID:8618888

  12. A Team-Based Process for Designing Comprehensive, Integrated, Three-Tiered (CI3T) Models of Prevention: How Does My School-Site Leadership Team Design a CI3T Model?

    ERIC Educational Resources Information Center

    Lane, Kathleen Lynne; Oakes, Wendy Peia; Jenkins, Abbie; Menzies, Holly Mariah; Kalberg, Jemma Robertson

    2014-01-01

    Comprehensive, integrated, three-tiered models are context specific and developed by school-site teams according to the core values held by the school community. In this article, the authors provide a step-by-step, team-based process for designing comprehensive, integrated, three-tiered models of prevention that integrate academic, behavioral, and…

  13. Design and Synthesis of Photoaffinity Labeling Ligands of the l-Prolyl-l-leucyl-glycinmide Binding Site Involved in the Allosteric Modulation of the Dopamine Receptor

    PubMed Central

    Fisher, Abigail; Mann, Amandeep; Verma, Vaneeta; Thomas, Nancy; Mishra, Ram K.; Johnson, Rodney L.

    2008-01-01

    Pro-Leu-Gly-NH2 (PLG), in addition to its endocrine effects, possesses the ability to modulate dopamine D2 receptors within the CNS. However, the precise binding site of PLG is unknown. Potential photoaffinity labeling ligands of the PLG binding site were designed as tools to be used in the identification of the macromolecule that possesses this binding site. Six different photoaffinity labeling ligands were designed and synthesized based upon γ-lactam PLG peptidomimetic 1. The 4-azido-benzoyl and 4-azido-2-hydroxy-benzoyl photoaffinity labeling moieties were placed at opposite ends of PLG peptidomimetic 1 to generate a series of ligands that potentially could be used to map the PLG binding site. All of the compounds that were synthesized possessed activity comparable to or better than PLG in enhancing [3H]N-propylnorapomorphine agonist binding to dopamine receptors. Photoaffinity ligands that were cross-linked to the receptor preparation produced a modulatory effect that was either comparable to or greater than the increase in agonist binding produced by the respective ligands that were not cross-linked to the dopamine receptor. The results indicate that these photoaffinity labeling agents are binding at the same site as PLG and PLG peptidomimetic 1. PMID:16392815

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

    PubMed Central

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

    2014-01-01

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

  15. The Future Through the Past: The Use of Analog Sites for Design Criteria and Long Term Performance Assessment of Evapotranspiration Landfill Covers

    SciTech Connect

    Shafer, D. S.; Miller, J. J.; Young, M. H.; Edwards, S. C.; Rawlinson, S. E.

    2002-02-26

    There is growing support for using evapotranspiration (ET) covers for closure of low-level waste (LLW) and other types of waste disposal sites, particularly in the lower latitude arid regions of the western United States. At the Nevada Test Site (NTS), monolayer ET covers are the baseline technology for closure of LLW and mixed LLW cells. To better predict the long-term performance of monolayer ET covers, as well as to identify design criteria that will potentially improve their performance, the properties of, and processes occurring on, analog sites for ET covers on the NTS are being studied. The project is funded through the Subsurface Contaminants Focus Area of the U.S. Department of Energy. Four analog sites on the NTS have been selected to predict performance of ET covers over a 1,000-year compliance period. Two sites are relatively recently disturbed (within the last 50 years) and have been selected to evaluate processes and changes on ET covers for the early period after active cover maintenance is discontinued. Two other sites, late to mid-Holocene in age, are intended as analogs for the end of the compliance period (1,000 years or more); both surfaces are abandoned alluvial/colluvial deposits. The history of the early post-institutional control analog sites are being evaluated by an archaeologist to help determine when the sites were last disturbed or modified, and the mode of disturbance to help set baseline conditions. Similar to other ''landforms,'' ET covers will evolve over time because of pedogenic, biotic, and climatic processes. Properties of analog sites that could affect ET water balance performance will be evaluated to help understand ET cover performance over time.

  16. Base excision repair enzymes protect abasic sites in duplex DNA from interstrand cross-links.

    PubMed

    Admiraal, Suzanne J; O'Brien, Patrick J

    2015-03-10

    Hydrolysis of the N-glycosyl bond between a nucleobase and deoxyribose leaves an abasic site within duplex DNA. The abasic site can react with exocyclic amines of nucleobases on the complementary strand to form interstrand DNA-DNA cross-links (ICLs). We find that several enzymes from the base excision repair (BER) pathway protect an abasic site on one strand of a DNA duplex from cross-linking with an amine on the opposing strand. Human alkyladenine DNA glycosylase (AAG) and Escherichia coli 3-methyladenine DNA glycosylase II (AlkA) accomplish this by binding tightly to the abasic site and sequestering it. AAG protects an abasic site opposite T, the product of its canonical glycosylase reaction, by a factor of ∼10-fold, as estimated from its inhibition of the reaction of an exogenous amine with the damaged DNA. Human apurinic/apyrimidinic site endonuclease 1 and E. coli endonuclease III both decrease the amount of ICL at equilibrium by generating a single-strand DNA nick at the abasic position as it is liberated from the cross-link. The reversibility of the reaction between amines and abasic sites allows BER enzymes to counter the potentially disruptive effects of this type of cross-link on DNA transactions. PMID:25679877

  17. 45 CFR 670.29 - Designation of Antarctic Specially Protected Areas, Specially Managed Areas and Historic Sites...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... of the moraine separating this point from the glacier and bearing an inscription. HSM 46All of the.... HSM 68Site of depot at Hells Gate Moraine, Inexpressible Island, Terra Nova Bay. HSM 69Message post...

  18. 45 CFR 670.29 - Designation of Antarctic Specially Protected Areas, Specially Managed Areas and Historic Sites...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... of the moraine separating this point from the glacier and bearing an inscription. HSM 46All of the.... HSM 68Site of depot at Hells Gate Moraine, Inexpressible Island, Terra Nova Bay. HSM 69Message post...

  19. 45 CFR 670.29 - Designation of Antarctic Specially Protected Areas, Specially Managed Areas and Historic Sites...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... of the moraine separating this point from the glacier and bearing an inscription. HSM 46All of the.... HSM 68Site of depot at Hells Gate Moraine, Inexpressible Island, Terra Nova Bay. HSM 69Message post...

  20. A design study for the isolation of the 281-3H retention basin at the Savannah River Site using the viscous liquid barrier technology

    SciTech Connect

    Moridis, G.J.; Persoff, P.; Apps, J.; James, A.; Oldenburg, C.; McGrath, A.; Myer, L.; Pellerin, L.; Pruess, K.

    1996-11-01

    This report is a description of the design study for a pilot-scale field demonstration of the Viscous Liquid Barrier (VLB) technology, a new subsurface containment technology for waste isolation using a new generation of barrier liquids. The demonstration site was Retention Basin 281-3H, a shallow catchment basin at the Savannah River Site, which is contaminated mainly by radionuclides ({sup 137}Cs, {sup 90}Sr, and {sup 238}Pu). The goals of the field demonstration were (a) to demonstrate the ability to create a continuous subsurface barrier in order to isolate the contaminants, and (b) to demonstrate the continuity, performance, and integrity of the barrier. The site was characterized, and preliminary hydraulic conductivity data were obtained from core samples. Based on the site characteristics and the functional requirements, a conceptual model was developed, the barrier specifications were defined, and lance injection was selected as the emplacement method. The injection strategy for the subsurface conditions at the site was determined using numerical simulations. An appropriate variant of Colloidal Silica (CS) was selected as the barrier liquid based on its relative insensitivity to interactions with the site soils, and the formulation for optimum site performance was determined. A barrier verification strategy, including hydraulic, pneumatic, tracer, and geophysical methods, was developed. A lance water injection test was conducted in order to obtain representative estimates of the hydraulic conductivity and its distribution for the design of the barrier emplacement. The water injection test demonstrated the lack of permeable zones for CS injection, and a decision not to proceed with the barrier emplacement was reached.

  1. Selective Targeting of the TPX2 Site of Importin-α Using Fragment-Based Ligand Design.

    PubMed

    Holvey, Rhian S; Valkov, Eugene; Neal, David; Stewart, Murray; Abell, Chris

    2015-07-01

    Protein-protein interactions are difficult therapeutic targets, and inhibiting pathologically relevant interactions without disrupting other essential ones presents an additional challenge. Herein we report how this might be achieved for the potential anticancer target, the TPX2-importin-α interaction. Importin-α is a nuclear transport protein that regulates the spindle assembly protein TPX2. It has two binding sites--major and minor-to which partners bind. Most nuclear transport cargoes use the major site, whereas TPX2 binds principally to the minor site. Fragment-based approaches were used to identify small molecules that bind importin-α, and crystallographic studies identified a lead series that was observed to bind specifically to the minor site, representing the first ligands specific for this site. Structure-guided synthesis informed the elaboration of these fragments to explore the source of ligand selectivity between the minor and major sites. These ligands are starting points for the development of inhibitors of this protein-protein interaction. PMID:25899172

  2. VS30 – A site-characterization parameter for use in building Codes, simplified earthquake resistant design, GMPEs, and ShakeMaps

    USGS Publications Warehouse

    Borcherdt, Roger D.

    2012-01-01

    VS30, defined as the average seismic shear-wave velocity from the surface to a depth of 30 meters, has found wide-spread use as a parameter to characterize site response for simplified earthquake resistant design as implemented in building codes worldwide. VS30 , as initially introduced by the author for the US 1994 NEHRP Building Code, provides unambiguous definitions of site classes and site coefficients for site-dependent response spectra based on correlations derived from extensive borehole logging and comparative ground-motion measurement programs in California. Subsequent use of VS30 for development of strong ground motion prediction equations (GMPEs) and measurement of extensive sets of VS borehole data have confirmed the previous empirical correlations and established correlations of SVS30 with VSZ at other depths. These correlations provide closed form expressions to predict S30 V at a large number of additional sites and further justify S30 V as a parameter to characterize site response for simplified building codes, GMPEs, ShakeMap, and seismic hazard mapping.

  3. The Use of Analog Sites for Designing and Evaluating Long Term Performance of Evapotranspiration Covers in the Northern Mojave Desert, USA

    NASA Astrophysics Data System (ADS)

    Shafer, D. S.

    2001-12-01

    Support is growing for using evapotranspiration (ET) covers for closing low-level waste (LLW) and other types of waste disposal sites, particularly in the lower latitude arid regions of the western United States. ET covers are planned at the Nevada Test Site (NTS) for closure of LLW shallow land burial waste cells. To better predict the long-term performance of ET covers, and to identify design criteria that will potentially improve their performance, the hydrologic and ecological processes occurring on analog surfaces for ET covers are being studied. Four analog sites on the NTS have been selected to study performance of ET covers over a 1000-year compliance period. Two are relatively recently disturbed sites (less than 40 years ago) and have been selected to evaluate processes and changes on covers for the early period of post-institutional controls when the waste cell covers will no longer be maintained. The histories of these control sites were evaluated by an archeologist to help determine the mode and timing of site disturbance to understand baseline conditions. Two other sites, late to mid-Holocene in age, are intended as analogs for the end of the compliance period for LLW closure (>1000 years). Both are abandoned alluvial/colluvial deposits, dated by thermoluminscence analysis. Observations to date on the younger analog sites suggest that bioturbation by small mammals begins immediately after site abandonment and may alter surface properties that effect the hydrologic performance and vegetation succession of the cover system. Bioturbation has resulted in local mounds of larger surface clasts, which are favorable sites for the establishment of native shrubs. Vegetation density and diversity decrease away from these mounds. While infiltration is expected to be greater in the vicinity of these shrubs because of their co-occurrence with bioturbated surface soils, ET potential may also be greater because of deeper root penetration. However, the bioturbation

  4. 76 FR 26720 - Notice of Intent: Designation of an Expanded Ocean Dredged Material Disposal Site (ODMDS) off...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-09

    ... Environmental Policy Document for all ODMDS designations (63 FR 58045, October 1998). For Further Information... is based on capacity computer modeling results. Alternatives: The following proposed...

  5. Design of a hairpin polyamide, ZT65B, for targeting the inverted CCAAT box (ICB) site in the multidrug resistant (MDR1) gene.

    PubMed

    Buchmueller, Karen L; Taherbhai, Zarmeen; Howard, Cameron M; Bailey, Suzanna L; Nguyen, Binh; O'Hare, Caroline; Hochhauser, Daniel; Hartley, John A; Wilson, W David; Lee, Moses

    2005-12-01

    A novel hairpin polyamide, ZT65B, containing a 3-methylpicolinate moiety was designed to target the inverted CCAAT box (ICB) of the human multidrug resistance 1 gene (MDR1) promoter. Binding of nuclear factor-Y (NF-Y) to the ICB site upregulates MDR1 gene expression and is, therefore, a good target for anticancer therapeutic agents. However, it is important to distinguish amongst different promoter ICB sites so that only specific genes will be affected. All ICB sites have the same sequence but they differ in the sequence of the flanking base pairs, which can be exploited in the design of sequence-specific polyamides. To test this hypothesis, ten ICB-containing DNA hairpins were designed with different flanking base pairs; the sequences ICBa and ICBb were similar to the 3'-ICB site of MDR1 (TGGCT). Thermal-denaturation studies showed that ZT65B effectively targeted ICBa and ICBb (DeltaTM=6.5 and 7.0 degrees C) in preference to the other DNA hairpins (<3.5 degrees C), with the exception of ICBc (5.0 degrees C). DNase I-footprinting assays were carried out with the topoisomerase IIalpha-promoter sequence, which contains five ICB sites; of these, ICB1 and ICB5 are similar to the ICB site of MDR1. ZT65B was found to selectively bind ICB1 and ICB5; footprints were not observed with ICB2, ICB3, or ICB4. A strong, positive induced ligand band at 325 nm in CD studies confirmed that ZT65B binds in the DNA minor groove. The selectivity of ZT65B binding to hairpins that contained the MDR1 ICB site compared to one that did not (ICBd) was confirmed by surface-plasmon studies, and equilibrium constants of 5x10(6)-1x10(7) and 4.6x10(5) M-1 were obtained with ICB1, ICB5,and ICB2 respectively. ZT65B and the previously published JH37 (J. A. Henry, et al. Biochemistry 2004, 43, 12 249-12 257) serve as prototypes for the design of novel polyamides. These can be used to specifically target the subset of ubiquitous gene elements known as ICBs, and thereby affect the expression of one or

  6. P-SAMS: a web site for plant artificial microRNA and synthetic trans-acting small interfering RNA design

    PubMed Central

    Fahlgren, Noah; Hill, Steven T.; Carrington, James C.; Carbonell, Alberto

    2016-01-01

    Summary: The Plant Small RNA Maker Site (P-SAMS) is a web tool for the simple and automated design of artificial miRNAs (amiRNAs) and synthetic trans-acting small interfering RNAs (syn-tasiRNAs) for efficient and specific targeted gene silencing in plants. P-SAMS includes two applications, P-SAMS amiRNA Designer and P-SAMS syn-tasiRNA Designer. The navigation through both applications is wizard-assisted, and the job runtime is relatively short. Both applications output the sequence of designed small RNA(s), and the sequence of the two oligonucleotides required for cloning into ‘B/c’ compatible vectors. Availability and implementation: The P-SAMS website is available at http://p-sams.carringtonlab.org. Contact: acarbonell@ibmcp.upv.es or nfahlgren@danforthcenter.org PMID:26382195

  7. Application of Frequency of Detection Methods in Design and Optimization of the INL Site Ambient Air Monitoring Network

    SciTech Connect

    Rood, Arthur S.; Sondrup, A. Jeffrey

    2015-11-01

    This report presents an evaluation of a hypothetical INL Site monitoring network and the existing INL air monitoring network using frequency of detection methods. The hypothetical network was designed to address the requirement in 40 CFR Part 61, Subpart H (2006) that “emissions of radionuclides to ambient air from U.S. DOE facilities shall not exceed those amounts that would cause any member of the public to receive in any year an effective dose equivalent exceeding 10 mrem/year.” To meet the requirement for monitoring only, “radionuclide releases that would result in an effective dose of 10% of the standard shall be readily detectable and distinguishable from background.” Thus, the hypothetical network consists of air samplers placed at residence locations that surround INL and at other locations where onsite livestock grazing takes place. Two exposure scenarios were used in this evaluation: a resident scenario and a shepherd/rancher scenario. The resident was assumed to be continuously present at their residence while the shepherd/rancher was assumed to be present 24-hours at a fixed location on the grazing allotment. Important radionuclides were identified from annual INL radionuclide National Emission Standards for Hazardous Pollutants reports. Important radionuclides were defined as those that potentially contribute 1% or greater to the annual total dose at the radionuclide National Emission Standards for Hazardous Pollutants maximally exposed individual location and include H-3, Am-241, Pu-238, Pu 239, Cs-137, Sr-90, and I-131. For this evaluation, the network performance objective was set at achieving a frequency of detection greater than or equal to 95%. Results indicated that the hypothetical network for the resident scenario met all performance objectives for H-3 and I-131 and most performance objectives for Cs-137 and Sr-90. However, all actinides failed to meet the performance objectives for most sources. The shepherd/rancher scenario showed

  8. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Falls City, Texas. Remedial action selection report: Attachment 2, Geology report; Attachment 3, Groundwater hydrology report; Attachment 4, Water resources protection strategy: Final report

    SciTech Connect

    Chernoff, A.R.; Lacker, D.K.

    1992-09-01

    The uranium processing site near Falls City, Texas, was one of 24 inactive uranium mill sites designated to be remediated by the US Department of Energy (DOE) under Title I of the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA). The UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE`s remedial action plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the US Environmental Protection Agency (EPA). The RAP, which includes this summary remedial action selection report (RAS), serves a two-fold purpose. First, it describes the activities proposed by the DOE to accomplish long-term stabilization and control of the residual radioactive materials at the inactive uranium processing site near Falls City, Texas. Second, this document and the remainder of the RAP, upon concurrence and execution by the DOE, the State of Texas, and the NRC, becomes Appendix B of the Cooperative Agreement between the DOE and the State of Texas.

  9. X-ray structure of the ternary MTX·NADPH complex of the anthrax dihydrofolate reductase: A pharmacophore for dual-site inhibitor design

    SciTech Connect

    Bennett, Brad C.; Wan, Qun; Ahmad, Md Faiz; Langan, Paul; Dealwis, Chris G.

    2009-11-18

    For reasons of bioterrorism and drug resistance, it is imperative to identify and develop new molecular points of intervention against anthrax. Dihydrofolate reductase (DHFR) is a highly conserved enzyme and an established target in a number of species for a variety of chemotherapeutic programs. Recently, the crystal structure of B. anthracis DHFR (baDHFR) in complex with methotrexate (MTX) was determined and, based on the structure, proposals were made for drug design strategies directed against the substrate binding site. However, little is gleaned about the binding site for NADPH, the cofactor responsible for hydride transfer in the catalytic mechanism. In the present study, X-ray crystallography at 100 K was used to determine the structure of baDHFR in complex with MTX and NADPH. Although the NADPH binding mode is nearly identical to that seen in other DHFR ternary complex structures, the adenine moiety adopts an off-plane tilt of nearly 90 deg. and this orientation is stabilized by hydrogen bonds to functionally conserved Arg residues. A comparison of the binding site, focusing on this region, between baDHFR and the human enzyme is discussed, with an aim at designing species-selective therapeutics. Indeed, the ternary model, refined to 2.3{angstrom} resolution, provides an accurate template for testing the feasibility of identifying dual-site inhibitors, compounds that target both the substrate and cofactor binding site. With the ternary model in hand, using in silico methods, several compounds were identified which could potentially form key bonding contacts in the substrate and cofactor binding sites. Ultimately, two structurally distinct compounds were verified that inhibit baDHFR at low {mu}M concentrations. The apparent K{sub d} for one of these, (2-(3-(2-(hydroxyimino)-2-(pyridine-4-yl)-6,7-dimethylquinoxalin-2-yl)-1-(pyridine-4-yl)ethanone oxime), was measured by fluorescence spectroscopy to be 5.3 {mu}M.

  10. X-ray structure of the ternary MTX•NADPH complex of the anthrax dihydrofolate reductase: a pharmacophore for dual-site inhibitor design

    PubMed Central

    Bennett, Brad C.; Wan, Qun; Ahmad, Md Faiz; Dealwis, Chris G.

    2009-01-01

    For reasons of bioterrorism and drug resistance, it is imperative to identify and develop new molecular points of intervention against anthrax. Dihydrofolate reductase (DHFR) is a highly conserved enzyme and an established target in a number of species for a variety of chemotherapeutic programs. Recently, the crystal structure of B. anthracis DHFR (baDHFR) in complex with methotrexate (MTX) was determined and, based on the structure, proposals were made for drug design strategies directed against the substrate binding site. However, little is gleaned about the binding site for NADPH, the cofactor responsible for hydride transfer in the catalytic mechanism. In the present study, X-ray crystallography at 100 K was used to determine the structure of baDHFR in complex with MTX and NADPH. Although the NADPH binding mode is nearly identical to that seen in other DHFR ternary complex structures, the adenine moiety adopts an off-plane tilt of nearly 90° and this orientation is stabilized by hydrogen bonds to functionally conserved Arg residues. A comparison of the binding site, focusing on this region, between baDHFR and the human enzyme is discussed, with an aim at designing species-selective therapeutics. Indeed, the ternary model, refined to 2.3Å resolution, provides an accurate template for testing the feasibility of identifying dual-site inhibitors, compounds that target both the substrate and cofactor binding site. With the ternary model in hand, using in silico methods, several compounds were identified which could potentially form key bonding contacts in the substrate and cofactor binding sites. Ultimately, two structurally distinct compounds were verified that inhibit baDHFR at low μM concentrations. The apparent Kd for one of these, (2-(3-(2-(hydroxyimino)-2-(pyridine-4-yl)-6,7-dimethylquinoxalin-2-yl)-1-(pyridine-4-yl)ethanone oxime), was measured by fluorescence spectroscopy to be 5.3 μM. PMID:19374017

  11. A Grounded Theory Approach to Examining Design and Usability Guidelines for Four-Year Tribal College Web Sites

    ERIC Educational Resources Information Center

    Broberg, Loretta L.

    2011-01-01

    With the increasing awareness of design and usability issues in regards to websites, in this case tribal college websites, there is an increasing desire to have a set of guidelines to assist in determining design and usability for academic websites. Though there is an overwhelming amount of information available to researchers in this subject area…

  12. 45 CFR 670.29 - Designation of Antarctic Specially Protected Areas, Specially Managed Areas and Historic Sites...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION CONSERVATION OF ANTARCTIC ANIMALS AND... descriptions of the sites and complete management plans can be obtained from the National Science Foundation, Office of Polar Programs, National Science Foundation, Room 755, 4201 Wilson Boulevard,...

  13. 45 CFR 670.29 - Designation of Antarctic Specially Protected Areas, Specially Managed Areas and Historic Sites...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION CONSERVATION OF ANTARCTIC ANIMALS AND... descriptions of the sites and complete management plans can be obtained from the National Science Foundation, Office of Polar Programs, National Science Foundation, Room 755, 4201 Wilson Boulevard,...

  14. Digital mapping of the Mars Pathfinder landing site: Design, acquisition, and derivation of cartographic products for science applications

    USGS Publications Warehouse

    Gaddis, L.R.; Kirk, R.L.; Johnson, J. R.; Soderblom, L.A.; Ward, A.W.; Barrett, J.; Becker, K.; Decker, T.; Blue, J.; Cook, D.; Eliason, E.; Hare, T.; Howington-Kraus, E.; Isbell, C.; Lee, E.M.; Redding, B.; Sucharski, R.; Sucharski, T.; Smith, P.H.; Britt, D.T.

    1999-01-01

    The Imager for Mars Pathfinder (IMP) acquired more than 16,000 images and provided panoramic views of the surface of Mars at the Mars Pathfinder landing site in Ares Vallis. This paper describes the stereoscopic, multispectral IMP imaging sequences and focuses on their use for digital mapping of the landing site and for deriving cartographic products to support science applications of these data. Two-dimensional cartographic processing of IMP data, as performed via techniques and specialized software developed for ISIS (the U.S.Geological Survey image processing software package), is emphasized. Cartographic processing of IMP data includes ingestion, radiometric correction, establishment of geometric control, coregistration of multiple bands, reprojection, and mosaicking. Photogrammetric processing, an integral part of this cartographic work which utilizes the three-dimensional character of the IMP data, supplements standard processing with geometric control and topographic information [Kirk et al., this issue]. Both cartographic and photogrammetric processing are required for producing seamless image mosaics and for coregistering the multispectral IMP data. Final, controlled IMP cartographic products include spectral cubes, panoramic (360?? azimuthal coverage) and planimetric (top view) maps, and topographic data, to be archived on four CD-ROM volumes. Uncontrolled and semicontrolled versions of these products were used to support geologic characterization of the landing site during the nominal and extended missions. Controlled products have allowed determination of the topography of the landing site and environs out to ???60 m, and these data have been used to unravel the history of large- and small-scale geologic processes which shaped the observed landing site. We conclude by summarizing several lessons learned from cartographic processing of IMP data. Copyright 1999 by the American Geophysical Union.

  15. Digital mapping of the Mars Pathfinder landing site: Design, acquisition, and derivation of cartographic products for science applications

    NASA Astrophysics Data System (ADS)

    Gaddis, L. R.; Kirk, R. L.; Johnson, J. R.; Soderblom, L. A.; Ward, A. W.; Barrett, J.; Becker, K.; Becker, T.; Blue, J.; Cook, D.; Eliason, E.; Hare, T.; Howington-Kraus, E.; Isbell, C.; Lee, E. M.; Redding, B.; Sucharski, R.; Sucharski, T.; Smith, P. H.; Britt, D. T.

    1999-04-01

    The Imager for Mars Pathfinder (IMP) acquired more than 16,000 images and provided panoramic views of the surface of Mars at the Mars Pathfinder landing site in Ares Vallis. This paper describes the stereoscopic, multispectral IMP imaging sequences and focuses on their use for digital mapping of the landing site and for deriving cartographic products to support science applications of these data. Two-dimensional cartographic processing of IMP data, as performed via techniques and specialized software developed for ISIS (the U.S. Geological Survey image processing software package), is emphasized. Cartographic processing of IMP data includes ingestion, radiometric correction, establishment of geometric control, coregistration of multiple bands, reprojection, and mosaicking. Photogrammetric processing, an integral part of this cartographic work which utilizes the three-dimensional character of the IMP data, supplements standard processing with geometric control and topographic information [Kirk et al., this issue]. Both cartographic and photogrammetric processing are required for producing seamless image mosaics and for coregistering the multispectral IMP data. Final, controlled IMP cartographic products include spectral cubes, panoramic (360° azimuthal coverage) and planimetric (top view) maps, and topographic data, to be archived on four CD-ROM volumes. Uncontrolled and semicontrolled versions of these products were used to support geologic characterization of the landing site during the nominal and extended missions. Controlled products have allowed determination of the topography of the landing site and environs out to ~60 m, and these data have been used to unravel the history of large- and small-scale geologic processes which shaped the observed landing site. We conclude by summarizing several lessons learned from cartographic processing of IMP data.

  16. Do Cross-circle Designs, the Mayan World Tree, Chitto Tustenuggee's, and Miami's Tequesta, Sites have Analogs in Brazil as they have in Peru, Europe, and Africa?

    NASA Astrophysics Data System (ADS)

    Ataide, Jade; Mc Leod, Roger; Mc Leod, David

    2007-04-01

    Florida's Miami Tequesta site conveys information about potential tornadoes, hurricanes, and even earthquakes. It is visually analogous to cross-circle designs, like other equivalent sites we have located, as in Maine, New Hampshire, in Medicine Wheels, and elsewhere. We focus on the detectable effects of time-and-place dependent electromagnetic signals. Non-technologic societies, and individuals, still find and use them, even today, especially in places like Cuzco, Peru. Modes of detection involve senses, such as sensitive, observant eyesight, and electromagnetically induced nerve signals interpreted as tinnitus, as traditionally indicated by ``Kokopelli's'' flute-playing, ``pins and needles,'' or even odor sensations. Recorded events show that youthful children are sometimes involved, as by Pacal's Classic-Mayan-era son, who became Kan Balum, Serpent Jaguar. Our intent is to check whether similar signals can be technologically identified in Brazil and New England. Site information investigated by us seems to be driven by the electromagnetic field. Enigmatic Brazilian locations should be technologically investigated with site correlations to other possible analogs, such as Florida's Chitto Tustenuggee site at Miramar. To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2007.NES07.C2.6

  17. A Structural Study of Norovirus 3C Protease Specificity: Binding of a Designed Active Site-Directed Peptide Inhibitor†

    PubMed Central

    2010-01-01

    Noroviruses are the major cause of human epidemic nonbacterial gastroenteritis. Viral replication requires a 3C cysteine protease that cleaves a 200 kDa viral polyprotein into its constituent functional proteins. Here we describe the X-ray structure of the Southampton norovirus 3C protease (SV3CP) bound to an active site-directed peptide inhibitor (MAPI) which has been refined at 1.7 Å resolution. The inhibitor, acetyl-Glu-Phe-Gln-Leu-Gln-X, which is based on the most rapidly cleaved recognition sequence in the 200 kDa polyprotein substrate, reacts covalently through its propenyl ethyl ester group (X) with the active site nucleophile, Cys 139. The structure permits, for the first time, the identification of substrate recognition and binding groups in a noroviral 3C protease and thus provides important new information for the development of antiviral prophylactics. PMID:21128685

  18. Effect of rotor configuration on guyed tower and foundation designs and estimated costs for intermediate site horizontal axis wind turbines

    NASA Technical Reports Server (NTRS)

    Frederick, G. R.; Winemiller, J. R.; Savino, J. M.

    1982-01-01

    Three designs of a guyed cylindrical tower and its foundation for an intermediate size horizontal axis wind turbine generator are discussed. The primary difference in the three designs is the configuration of the rotor. Two configurations are two-blade rotors with teetering hubs - one with full span pitchable blades, the other with fixed pitch blades. The third configuration is a three-bladed rotor with a rigid hub and fixed pitch blades. In all configurations the diameter of the rotor is 38 meters and the axis of rotation is 30.4 meters above grade, and the power output is 200 kW and 400 kW. For each configuration the design is based upon for the most severe loading condition either operating wind or hurricane conditions. The diameter of the tower is selected to be 1.5 meters (since it was determined that this would provide sufficient space for access ladders within the tower) with guy rods attached at 10.7 meters above grade. Completing a design requires selecting the required thicknesses of the various cylindrical segments, the number and diameter of the guy rods, the number and size of soil anchors, and the size of the central foundation. The lower natural frequencies of vibration are determined for each design to ensure that operation near resonance does not occur. Finally, a cost estimate is prepared for each design. A preliminary design and cost estimate of a cantilever tower (cylindrical and not guyed) and its foundation is also presented for each of the three configurations.

  19. SITE QUARTERLY REPORT HIGHLIGHTS (SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION (SITE) PROGRAM)

    EPA Science Inventory

    The SITE Quarterly Report Highlights were designed to keep readers and stakeholders informed of recent developments in the SITE program. Pertinent items listed in the Highlights include (1) schedules for planned SITE Demonstrations, (2) SITE solicitation updates, (3) new developm...

  20. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Rifle, Colorado: Final report. Volume 4, Addenda D1--D5 to Appendix D

    SciTech Connect

    Allen, James W.

    1990-02-01

    This radiologic characterization of tho two inactive uranium millsites at Rifle, Colorado, was conducted by Bendix Field Engineering Corporation (Bendix) for the US Department of Energy (DOE), Grand Junction Projects Office, in accord with a Statement of Work prepared by the DOE Uranium Mill Tailings Remedial Action (UMTRA) Project Technical Assistance Contractor, Jacobs Engineering Group, Inc. (Jacobs). The purpose of this project is to define the extent of radioactive contamination at the Rifle sites that exceeds US Environmental Protection Agency, (EPA) standards for UMTRA sites. The data presented in this report are required for characterization of the areas adjacent to the tailings piles and for the subsequent design of cleanup activities. An orientation visit to the study area was conducted on 31 July--1 August 1984, in conjunction with Jacobs, to determine the approximate extent of contaminated area surrounding tho piles. During that visit, survey control points were located and baselines were defined from which survey grids would later be established; drilling requirements were assessed; and radiologic and geochemical data were collected for use in planning the radiologic fieldwork. The information gained from this visit was used by Jacobs, with cooperation by Bendix, to determine the scope of work required for the radiologic characterization of the Rifle sites. Fieldwork at Rifle was conducted from 1 October through 16 November 1984.

  1. Design and construction of deinococcus radiodurans for biodegradation of organic toxins at radioactive DOE waste sites. 1998 annual progress report

    SciTech Connect

    Daly, M.J.; Wackett, L.P.; Minton, K.W.

    1998-06-01

    'A 1992 survey of DOE waste sites indicates that about 32% of soils and 45% of groundwaters at these sites contain radionuclides and metals plus an organic toxin class. The most commonly reported combinations of these hazardous compounds being radionuclides and metals (e.g., U, Pu, Cs, Pb, Cr, As) plus chlorinated hydrocarbons (e.g., trichloroethylene), fuel hydrocarbons (e.g., toluene), or polychlorinated biphenyls (e.g., Arochlor 1248). These wastes are some of the most hazardous pollutants and pose an increasing risk to human health as they leach into the environment. The objective of this research is to develop novel organisms, that are highly resistant to radiation and the toxic effects of metals and radionuclides, for in-situ bioremediation of organic toxins. Few organisms exist that are able to remediate such environmental organic pollutants, and among those that can, the bacteria belonging to the genus Pseudomonas are the most characterized. Unfortunately, these bacteria are very radiation sensitive. For example, Pseudomonas spp. is even more sensitive than Escherichia coli and, thus, is not suitable as a bioremediation host in environments subjected to radiation. By contrast, D. radiodurans, a natural soil bacterium, is the most radiation resistant organism yet discovered; it is several thousand times more resistant to ionizing radiation than Pseudomonas. The sophisticated gene transfer and expression systems the authors have developed for D. radiodurans over the last eight years make this organism an ideal candidate for high-level expression of genes that degrade organic toxins, in radioactive environments. The authors ultimate aim is to develop organisms and approaches that will be useful for remediating the large variety of toxic organic compounds found in DOE waste sites that are too radioactive to support other bioremediation organisms. This report summarizes work after the first 6 months of a 3-year project.'

  2. Design of a three-dimensional site-scale model for the unsaturated zone at Yucca Mountain, Nevada

    SciTech Connect

    Wittwer, C.S.; Bodvarsson, G.S.; Chornack, M.P.; Flint, A.L.; Lewis, B.D.; Spengler, R.W.; Flint, L.E.; Rautman, C.A.

    1992-01-01

    A three-dimensional model of moisture flow within the unsaturated zone at Yucca Mountain is being developed. This site-scale model covers an area of about 30 km{sup 2} and is bounded by major faults to the east and west. A detailed numerical grid has been developed based on location of boreholes, different infiltration zones, hydrogeological units and their outcrops, major faults, and water level data. Different maps, such as contour maps and isopachs maps, are presented for the different infiltration zones, and for the base of the Tiva Canyon, the Paintbrush, and the Topopah Spring hydrogeological units.

  3. Design of a three-dimensional site scale model for the unsaturated zone at Yucca Mountain, Nevada

    SciTech Connect

    Wittwer, C.S.; Bodvarsson, G.S.; Chornack, M.P.; Flint, A.L.; Lewis, B.D.; Spengler, R.W.; Flint, L.E.; Rautman, C.A.

    1992-10-01

    This paper discusses a three-dimensional model of moisture flow within the unsaturated zone at Yucca Mountain which is being developed. The site-scale model covers an area of about 30 km{sup 2} and is bounded by major faults to the east and west. A detailed numerical grid has been developed based on locations of boreholes, different infiltration zones, hydrogeological units and their outcrops, major faults, and water level data. Different maps, such as contour maps and isopachs maps, are presented for the different infiltration zones, and for the base of the Tiva Canyon, the Paintbrush, and the Topopah Spring hydrogeological units.

  4. Design

    ERIC Educational Resources Information Center

    Buchanan, Richard; Cross, Nigel; Durling, David; Nelson, Harold; Owen, Charles; Valtonen, Anna; Boling, Elizabeth; Gibbons, Andrew; Visscher-Voerman, Irene

    2013-01-01

    Scholars representing the field of design were asked to identify what they considered to be the most exciting and imaginative work currently being done in their field, as well as how that work might change our understanding. The scholars included Richard Buchanan, Nigel Cross, David Durling, Harold Nelson, Charles Owen, and Anna Valtonen. Scholars…

  5. Designing a Site to Embed and to Interact with Wolfram Alpha Widgets in Math and Sciences Courses

    ERIC Educational Resources Information Center

    Cepeda, Francisco Javier Delgado; Acosta, Ruben Dario Santiago

    2014-01-01

    This paper reports design and implementation outcomes at middle development advance of an educative program based on use and construction of widgets on Wolfram Alpha platform at higher education level for engineering and sciences areas. Widgets were based on Physics and Mathematics curricula under Project Oriented Learning and Blended Learning…

  6. Hybrid Placemaking in the Library: Designing Digital Technology to Enhance Users' On-Site Experience

    ERIC Educational Resources Information Center

    Bilandzic, Mark; Johnson, Daniel

    2013-01-01

    This paper presents research findings and design strategies that illustrate how digital technology can be applied as a tool for "hybrid" placemaking in ways that would not be possible in purely digital or physical spaces. Digital technology has revolutionised the way people learn and gather new information. This trend has challenged the…

  7. 77 FR 63312 - Notice of Intent: Designation of an Ocean Dredged Material Disposal Site (ODMDS) in Eastern Long...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-16

    ... Island Sound; Connecticut, New York, and Rhode Island AGENCY: Environmental Protection Agency (EPA... Island Sound region (Connecticut, New York, and Rhode Island). SUMMARY: EPA is authorized to designate... the analyses that were conducted for the 2005 Long Island Sound Environmental Impact Statement...

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

    ERIC Educational Resources Information Center

    New York City Dept. of City Planning, NY.

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

  9. 77 FR 77076 - Notice of Intent: Designation of an Expanded Ocean Dredged Material Disposal Site (ODMDS) off...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-31

    ... Charleston, South Carolina AGENCY: U.S. Environmental Protection Agency (EPA) Region 4. ACTION: Notice of... From the Federal Register Online via the Government Publishing Office ] ENVIRONMENTAL PROTECTION... prepare a National Environmental Policy Document for all ODMDS designations (63 FR 58045, October...

  10. Design of an interpolyelectrolyte gastroretentive matrix for the site-specific zero-order delivery of levodopa in Parkinson's disease.

    PubMed

    Ngwuluka, Ndidi C; Choonara, Yahya E; Modi, Girish; du Toit, Lisa C; Kumar, Pradeep; Ndesendo, Valence M K; Pillay, Viness

    2013-06-01

    This study focused on developing a gastroretentive drug delivery system employing a triple-mechanism interpolyelectrolyte complex (IPEC) matrix comprising high density, swelling, and bioadhesiveness for the enhanced site-specific zero-order delivery of levodopa in Parkinson's disease. An IPEC was synthesized and directly compressed into a levodopa-loaded matrix employing pharmaceutical technology and evaluated with respect to its physicochemical and physicomechanical properties and in vitro drug release. The IPEC-based matrix displayed superior mechanical properties in terms of matrix hardness (34-39 N/mm) and matrix resilience (44-47%) when different normality's of solvent and blending ratios were employed. Fourier transform infrared spectroscopy confirmed the formation of the IPEC. The formulations exhibited pH and density dependence with desirable gastro-adhesion with Peak Force of Adhesion ranging between 0.15 and 0.21 N/mm, densities from 1.43 to 1.54 g/cm(3) and swellability values of 177-234%. The IPEC-based gastroretentive matrix was capable of providing site-specific levodopa release with zero-order kinetics corroborated by detailed mathematical and molecular modeling studies. Overall, results from this study have shown that the IPEC-based matrix has the potential to improve the absorption and subsequent bioavailability of narrow absorption window drugs, such as levodopa with constant and sustained drug delivery. PMID:23494468

  11. Design, synthesis, crystal structure and magnetic properties of novel osmium-based B-site ordered double perovskites

    NASA Astrophysics Data System (ADS)

    Russell, David D.

    Transition metal oxides (TMOs) with face centered cubic arrangement of magnetic ions are composed of triangular sub-lattices. When antiferromagnetic (AFM) interactions of the same strengths between all three pathways in triangular settings are in place, spin constraints cannot be fulfilled simultaneously and the system undergoes geometric magnetic frustration (GMF). The purpose of the work presented in this thesis is to better understand the criteria for a system to undergo GMF. To achieve this, the novel B-site ordered double perovskites Ca2ScOsO6 and Ca2.2Mg0.8 OsO6 were synthesized in polycrystalline form utilizing the conventional solid-state method. The crystal structure of these compounds were characterized through X-ray diffraction, and magnetic properties were explored through magnetic susceptibility measurements. Employing the spin-dimer analysis method, relative magnetic exchange interactions were calculated and modeled. These novel osmium-based B-site ordered double perovskites were then compared to isostructural compounds to study the effects of the osmium oxidation state on crystal structure and the exhibited properties.

  12. Structure of the endonuclease IV homologue from Thermotoga maritima in the presence of active-site divalent metal ions

    SciTech Connect

    Tomanicek, Stephen J.; Hughes, Ronny C.; Ng, Joseph D.; Coates, Leighton

    2010-10-05

    The most frequent lesion in DNA is at apurinic/apyrimidinic (AP) sites resulting from DNA-base losses. These AP-site lesions can stall DNA replication and lead to genome instability if left unrepaired. The AP endonucleases are an important class of enzymes that are involved in the repair of AP-site intermediates during damage-general DNA base-excision repair pathways. These enzymes hydrolytically cleave the 5{prime}-phosphodiester bond at an AP site to generate a free 3{prime}-hydroxyl group and a 5{prime}-terminal sugar phosphate using their AP nuclease activity. Specifically, Thermotoga maritima endonuclease IV is a member of the second conserved AP endonuclease family that includes Escherichia coli endonuclease IV, which is the archetype of the AP endonuclease superfamily. In order to more fully characterize the AP endonuclease family of enzymes, two X-ray crystal structures of the T. maritima endonuclease IV homologue were determined in the presence of divalent metal ions bound in the active-site region. These structures of the T. maritima endonuclease IV homologue further revealed the use of the TIM-barrel fold and the trinuclear metal binding site as important highly conserved structural elements that are involved in DNA-binding and AP-site repair processes in the AP endonuclease superfamily.

  13. Conceptual designs for waste packages for horizontal or vertical emplacement in a repository in salt for reference in the site characterization plan

    SciTech Connect

    Not Available

    1987-06-01

    This report includes the options of horizontal and vertical emplacement, the addition of a phased repository, an additional waste form (intact spent fuel), revised geotechnical data appropriate for the Deaf Smith County site, new corrosion data for the container, and new repository design data. The waste package consists of waste form and canister within a thick-walled, low-carbon steel container surrounded by packing. The container is a hollow cylinder with a flat head welded to each end. The design concepts for the waste container or vertical and horizontal emplacement are identical. This report discusses the results of analyses of aspects of the reference waste package concept needing changes because of new data and information believed applicable to the Deaf Smith County site. Included are waste package conceptual designs or (1) the reference defense high-level waste form from the Savannah River Plant; (2) intact spent fuel with our pressurized-water-reactor or nine boiling-water-reactor assemblies per package for emplacement during Phase 1 of repository operation; and (3) spent fuel which has been disassembled and consolidated into a segmented cylindrical canister with rods from either 12 pressurized-water-reactor or 30 boiling-water-reactor assemblies per package for emplacement during Phase 2. 30 refs., 61 figs., 30 tabs.

  14. Design and synthesis of fused bicyclic inhibitors targeting the L5 loop site of centromere-associated protein E.

    PubMed

    Hirayama, Takaharu; Okaniwa, Masanori; Banno, Hiroshi; Kakei, Hiroyuki; Ohashi, Akihiro; Ohori, Momoko; Nambu, Tadahiro; Iwai, Kenichi; Kawamoto, Tomohiro; Yokota, Akihiro; Miyamoto, Maki; Ishikawa, Tomoyasu

    2016-09-01

    Centromere-associated protein-E (CENP-E) is a mitotic kinesin which plays roles in cell division, and is regarded as a promising therapeutic target for the next generation of anti-mitotic agents. We designed novel fused bicyclic CENP-E inhibitors starting from previous reported dihydrobenzofuran derivative (S)-(+)-1. Our design concept was to adjust the electron density distribution on the benzene ring of the dihydrobenzofuran moiety to increase the positive charge for targeting the negatively charged L5 loop of CENP-E, using predictions from electrostatic potential map (EPM) analysis. For the efficient synthesis of our 2,3-dihydro-1-benzothiophene 1,1-dioxide derivatives, a new synthetic method was developed. As a result, we discovered 6-cyano-7-trifluoromethyl-2,3-dihydro-1-benzothiophene 1,1-dioxide derivative (+)-5d (Compound A) as a potent CENP-E inhibitor with promising potential for in vivo activity. In this Letter, we discuss the design and synthetic strategy used in the discovery of (+)-5d and structure-activity relationships for its analogs possessing various fused bicyclic L5 binding moieties. PMID:27476141

  15. Rapid Deployment Drilling System for on-site inspections under a Comprehensive Test Ban Preliminary Engineering Design

    SciTech Connect

    Maurer, W.C.; Deskins, W.G.; McDonald, W.J.; Cohen, J.H.; Heuze, F.E.; Butler, M.W.

    1996-09-01

    While not a new drilling technology, coiled-tubing (CT) drilling continues to undergo rapid development and expansion, with new equipment, tools and procedures developed almost daily. This project was undertaken to: analyze available technological options for a Rapid Deployment Drilling System (RDDS) CT drilling system: recommend specific technologies that best match the requirements for the RDDS; and highlight any areas where adequate technological solutions are not currently available. Postshot drilling is a well established technique at the Nevada Test Site (NTS). Drilling provides essential data on the results of underground tests including obtaining samples for the shot zone, information on cavity size, chimney dimensions, effects of the event on surrounding material, and distribution of radioactivity.

  16. Active Site and Loop 4 Movements with Human Glycolate Oxidase: Implications for Substrate Specificity and Drug Design

    SciTech Connect

    Murray,M.; Holmes, R.; Lowther, W.

    2008-01-01

    Human glycolate oxidase (GO) catalyzes the FMN-dependent oxidation of glycolate to glyoxylate and glyoxylate to oxalate, a key metabolite in kidney stone formation. We report herein the structures of recombinant GO complexed with sulfate, glyoxylate, and an inhibitor, 4-carboxy-5-dodecylsulfanyl-1, 2,3-triazole (CDST), determined by X-ray crystallography. In contrast to most {alpha}-hydroxy acid oxidases including spinach glycolate oxidase, a loop region, known as loop 4, is completely visible when the GO active site contains a small ligand. The lack of electron density for this loop in the GO-CDST complex, which mimics a large substrate, suggests that a disordered to ordered transition may occur with the binding of substrates. The conformational flexibility of Trp110 appears to be responsible for enabling GO to react with a-hydroxy acids of various chain lengths. Moreover, the movement of Trp110 disrupts a hydrogen-bonding network between Trp110, Leu191, Tyr134, and Tyr208. This loss of interactions is the first indication that active site movements are directly linked to changes in the conformation of loop 4. The kinetic parameters for the oxidation of glycolate, glyoxylate, and 2-hydroxy octanoate indicate that the oxidation of glycolate to glyoxylate is the primary reaction catalyzed by GO, while the oxidation of glyoxylate to oxalate is most likely not relevant under normal conditions. However, drugs that exploit the unique structural features of GO may ultimately prove to be useful for decreasing glycolate and glyoxylate levels in primary hyperoxaluria type 1 patients who have the inability to convert peroxisomal glyoxylate to glycine.

  17. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Attachment 6, Supplemental standard for Durango processing site. Revised final report

    SciTech Connect

    Not Available

    1991-12-01

    Excavation control to the 15 pCi/g radium-226 (Ra-226) standard at certain areas along the Animas River on the Durango Site would require extensive engineering and construction support. Elevated Ra-226 concentrations have been encountered immediately adjacent to the river at depths in excess of 7 feet below the present river stage. Decontamination to such depths to ensure compliance with the EPA standards will, in our opinion, become unreasonable. This work does not appear to be in keeping with the intent of the standards. Because the principal reason for radium removal is reduction of radon daughter concentrations (RDC) in homes to be built onsite, and because radon produced at depth will be attenuated in clean fill cover before entering such homes, it is appropriate to calculate the depth of excavation needed under a home to reduce RDC to acceptable levels. Potential impact was assessed through radon emanation estimation, using the RAECOM computer model. Elevated Ra-226 concentrations were encountered during final radium excavation of the flood plain below the large tailings pile, adjacent to the slag area. Data from 7 test pits excavated across the area were analyzed to provide an estimate of the Ra-226 concentration profile. Results are given in this report.

  18. miR-Synth: a computational resource for the design of multi-site multi-target synthetic miRNAs

    PubMed Central

    Laganà, Alessandro; Acunzo, Mario; Romano, Giulia; Pulvirenti, Alfredo; Veneziano, Dario; Cascione, Luciano; Giugno, Rosalba; Gasparini, Pierluigi; Shasha, Dennis; Ferro, Alfredo; Croce, Carlo Maria

    2014-01-01

    RNAi is a powerful tool for the regulation of gene expression. It is widely and successfully employed in functional studies and is now emerging as a promising therapeutic approach. Several RNAi-based clinical trials suggest encouraging results in the treatment of a variety of diseases, including cancer. Here we present miR-Synth, a computational resource for the design of synthetic microRNAs able to target multiple genes in multiple sites. The proposed strategy constitutes a valid alternative to the use of siRNA, allowing the employment of a fewer number of molecules for the inhibition of multiple targets. This may represent a great advantage in designing therapies for diseases caused by crucial cellular pathways altered by multiple dysregulated genes. The system has been successfully validated on two of the most prominent genes associated to lung cancer, c-MET and Epidermal Growth Factor Receptor (EGFR). (See http://microrna.osumc.edu/mir-synth). PMID:24627222

  19. High-Affinity Self-Reactive Human Antibodies by Design and Selection: Targeting the Integrin Ligand Binding Site

    NASA Astrophysics Data System (ADS)

    Barbas, Carlos F., III; Languino, Lucia R.; Smith, Jeffrey W.

    1993-11-01

    A strategy for the design and selection of human antibodies that bind receptors is described. We have demonstrated the validity of the approach by producing semisynthetic human antibodies that bind integrins α_vβ_3 and αIIbβ_3 with high affinity (10-10 M). The selected antibodies mimic the integrins' natural ligands as demonstrated by their ability to compete with these ligands and Arg-Gly-Asp (RGD)-containing peptides for binding to the integrins. Furthermore, the antibodies bind in a cation-dependent fashion and are functional in cell adhesion assays. Antibodies that are high-affinity inhibitors of cell adhesion receptors should be of use in assessing receptor function and dissecting mechanisms of adhesion. Semisynthetic human antibodies that target integrins are potential therapeutic agents for the treatment of a number of diseases including thrombosis and metastasis. Furthermore, antibodies that are optimized to bind by a single complementarity determining region may be important lead compounds for the design of small molecule pharmaceuticals.

  20. Remedial Action Plan and Site Design for Stabilization of the Inactive Uranium Mill Tailings Sites at Slick Rock, Colorado: Appendix B to Attachment 3, Lithologic logs and monitor well construction information. Final report

    SciTech Connect

    1995-09-01

    This volume contains lithology logs and monitor well construction information for: NC processing site; UC processing site; and Burro Canyon disposal site. This information pertains to the ground water hydrology investigations which is attachment 3 of this series of reports.

  1. Geological and Geotechnical Site Investigation for the Design of a CO2 Rich Flue Gas Direct Injection and Storage Facility

    SciTech Connect

    Metz, Paul; Bolz, Patricia

    2013-03-25

    With international efforts to limit anthropogenic carbon in the atmosphere, various CO{sub 2} sequestration methods have been studied by various facilities worldwide. Basalt rock in general has been referred to as potential host material for mineral carbonation by various authors, without much regard for compositional variations due to depositional environment, subsequent metamorphism, or hydrothermal alteration. Since mineral carbonation relies on the presence of certain magnesium, calcium, or iron silicates, it is necessary to study the texture, mineralogy, petrology, and geochemistry of specific basalts before implying potential for mineral carbonation. The development of a methodology for the characterization of basalts with respect to their susceptibility for mineral carbonation is proposed to be developed as part of this research. The methodology will be developed based on whole rock data, petrography and microprobe analyses for samples from the Caledonia Mine in Michigan, which is the site for a proposed small-scale demonstration project on mineral carbonation in basalt. Samples from the Keweenaw Peninsula will be used to determine general compositional trends using whole rock data and petrography. Basalts in the Keweenaw Peninsula have been subjected to zeolite and prehnite-pumpellyite facies metamorphism with concurrent native copper deposition. Alteration was likely due to the circulation of CO{sub 2}-rich fluids at slightly elevated temperatures and pressures, which is the process that is attempted to be duplicated by mineral carbonation.

  2. Rational design, biophysical and biological characterization of site-specific antibody-tubulysin conjugates with improved stability, efficacy and pharmacokinetics.

    PubMed

    Thompson, Pamela; Fleming, Ryan; Bezabeh, Binyam; Huang, Fengying; Mao, Shenlan; Chen, Cui; Harper, Jay; Zhong, Haihong; Gao, Xizhe; Yu, Xiang-Qing; Hinrichs, Mary Jane; Reed, Molly; Kamal, Adeela; Strout, Patrick; Cho, Song; Woods, Rob; Hollingsworth, Robert E; Dixit, Rakesh; Wu, Herren; Gao, Changshou; Dimasi, Nazzareno

    2016-08-28

    Antibody-drug conjugates (ADCs) are among the most promising empowered biologics for cancer treatment. ADCs are commonly prepared by chemical conjugation of small molecule cytotoxic anti-cancer drugs to antibodies through either lysine side chains or cysteine thiols generated by the reduction of interchain disulfide bonds. Both methods yield heterogeneous conjugates with complex biophysical properties and suboptimal serum stability, efficacy, and pharmacokinetics. To limit the complexity of cysteine-based ADCs, we have engineered and characterized in vitro and in vivo antibody cysteine variants that allow precise control of both site of conjugation and drug load per antibody molecule. We demonstrate that the chemically-defined cysteine-engineered antibody-tubulysin conjugates have improved ex vivo and in vivo stability, efficacy, and pharmacokinetics when compared to conventional cysteine-based ADCs with similar drug-to-antibody ratios. In addition, to limit the non-target FcγRs mediated uptake of the ADCs by cells of the innate immune system, which may result in off-target toxicities, the ADCs have been engineered to lack Fc-receptor binding. The strategies described herein are broadly applicable to any full-length IgG or Fc-based ADC and have been incorporated into an ADC that is in phase I clinical development. PMID:27327768

  3. Laparoendoscopic Single-Site Surgery for Benign Urologic Disease with a Homemade Single Port Device: Design and Tips for Beginners

    PubMed Central

    Lee, Joo Yong; Kang, Dong Hyuk; Chung, Jae Hoon; Jo, Jung Ki

    2012-01-01

    Purpose A single surgeon skilled in conventional laparoscopic surgery used laparoendoscopic single-site surgery (LESS) to treat benign urological diseases. This study reports our surgical results and introduces a simple technique with tips based on our experience. Materials and Methods LESS surgery was performed on 116 patients by use of a homemade single-port device composed of an Alexis wound retractor and a powder-free surgical glove. Cases were 44 varicocelectomies (including 8 bilateral cases), 38 renal cyst marsupializations (including 3 bilateral cases), 26 ureterolithotomies (with 1 concomitant ureterolithotomy and contralateral renal cyst marsupialization), 4 prostatic enucleations, and 4 bladder rupture repairs. The mean patient age was 44.43±16.46 years (range, 11 to 76 years), and the male-to-female ratio was 87:29. Results In one ureterolithotomy case, LESS was converted to conventional laparoscopic surgery. The mean operative time was 87.03±45.03 minutes, the estimated blood loss was 61.90 ml (range, 0 to 2,000 ml), and the mean hospital stay was 3.03±2.12 days. Two patients underwent single-port transvesical enucleation of the prostate (STEP) requiring patient-controlled anesthesia. No patients developed major complications, and all patients were satisfied, with 75.86% expressing a high degree of satisfaction. Conclusions We report successful treatment outcomes for LESS in 116 cases of benign urological disease. Our findings suggest that LESS can replace conventional laparoscopy. PMID:22468211

  4. Modification to the Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Mexican Hat, Utah: Volume 1, Text, Attachments 1--6. Final report

    SciTech Connect

    1989-01-01

    This document provides the modifications to the 1988 Remedial Action Plan (RAP) of the contaminated materials at the Monument Valley, Arizona, and Mexican Hat, Utah. The text detailing the modifications and attachments 1 through 6 are provided with this document. The RAP was developed to serve a two-fold purpose. It presents the activities proposed by the Department of Energy (DOE) to accomplish long-term stabilization and control of the residual radioactive materials (RRM) from Monument Valley, Arizona, and Mexican Hat, Utah, at the Mexican Hat disposal site. It also serves to document the concurrence of both the Navajo Nation and the Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by DOE and the Navajo Nation and concurrence by the NRC, becomes Appendix B of the Cooperative Agreement. This document has been structured to provide a comprehensive understanding of the remedial action proposed for the Monument Valley and Mexican Hat sites. It includes specific design and construction requirements for the remedial action. Pertinent information and data are included with reference given to the supporting documents.

  5. Groundwater contamination from waste management sites: The interaction between risk-based engineering design and regulatory policy: 1. Methodology

    NASA Astrophysics Data System (ADS)

    Massmann, Joel; Freeze, R. Allan

    1987-02-01

    This paper puts in place a risk-cost-benefit analysis for waste management facilities that explicitly recognizes the adversarial relationship that exists in a regulated market economy between the owner/operator of a waste management facility and the government regulatory agency under whose terms the facility must be licensed. The risk-cost-benefit analysis is set up from the perspective of the owner/operator. It can be used directly by the owner/operator to assess alternative design strategies. It can also be used by the regulatory agency to assess alternative regulatory policy, but only in an indirect manner, by examining the response of an owner/operator to the stimuli of various policies. The objective function is couched in terms of a discounted stream of benefits, costs, and risks over an engineering time horizon. Benefits are in the form of revenues for services provided; costs are those of construction and operation of the facility. Risk is defined as the cost associated with the probability of failure, with failure defined as the occurrence of a groundwater contamination event that violates the licensing requirements established for the facility. Failure requires a breach of the containment structure and contaminant migration through the hydrogeological environment to a compliance surface. The probability of failure can be estimated on the basis of reliability theory for the breach of containment and with a Monte-Carlo finite-element simulation for the advective contaminant transport. In the hydrogeological environment the hydraulic conductivity values are defined stochastically. The probability of failure is reduced by the presence of a monitoring network operated by the owner/operator and located between the source and the regulatory compliance surface. The level of reduction in the probability of failure depends on the probability of detection of the monitoring network, which can be calculated from the stochastic contaminant transport simulations. While

  6. Design and installation of deep multilevel piezometer nests in Columbia River basalts at the Hanford Site, Washington. [Measurement of head in different rock zones sealed from each other

    SciTech Connect

    Jackson, R.L.; Veatch, M.D.

    1985-04-01

    The Basalt Waste Isolation Project (BWIP) was established in 1976 as part of the National Waste Terminal Storage Program, now the Office of Civilian Radioactive Waste Management. The BWIP objective is to assess the suitability of basalt as a repository medium for the long-term storage of commercial high-level radioactive waste. As part of the hydrogeologic characterization activities, BWIP designed and installed multilevel piezometer nests at three borehole cluster sites within and adjacent to the 18-square-mile reference repository location. These borehole cluster sites will provide multilevel piezometric baseline data across the reference repository location prior to, during, and after drilling a large-diameter exploratory shaft. They will also be used to monitor future hydraulic stress tests on a large scale. Three series of piezometer nests (A-, C-, and D-series) were installed at three borehole cluster sites in nine hydrogeologic units from a depth of about 500 to 3700 feet within the Columbia River Basalt Group. These multilevel monitoring zones are isolated from each other and the next overlying hydrogeologic unit by high-density cement seals. The A-series piezometer nests monitor two shallow sedimentary units. The C-series piezometer nests monitor basalt flow tops in the six deepest zones. The D-series piezometer monitors an intermediate sedimentary unit. Each piezometer tube was developed by air-lift pumping to complete the installtion prior to installing downhole pressure transducers. 23 refs., 10 figs., 1 tab.

  7. Design, synthesis, and evaluation of 7H-thiazolo-[3,2-b]-1,2,4-triazin-7-one derivatives as dual binding site acetylcholinesterase inhibitors.

    PubMed

    Liu, Sijie; Shang, Ruofeng; Shi, Lanxiang; Zhou, Ran; He, Jingyu; Wan, David Chi-Cheong

    2014-08-01

    New dual binding site acetylcholinesterase (AChE) inhibitors have been designed and synthesized as a new drug candidate for the treatment of Alzheimer's disease (AD) through the binding to both catalytic and peripheral sites of the enzyme. Therefore, a series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives 6a-j were synthesized and investigated for their ability to inhibit the activity of human AChE (hAChE) in comparison with huperzine-A. All the compounds were found to inhibit AChE activity, especially compounds 6c and 6i with the inhibition value of 76.10% and 77.82%, respectively. The molecular docking study indicated that they were nicely accommodated by AChE. The molecular docking study revealed that 6c and 6i possessed a more optimal binding conformation than 6a and can perfectly fit into the active and peripheral site of hAChE, and consequently exhibited highly improved inhibitor potency to hAChE. PMID:24890706

  8. Molecular insights of protein contour recognition with ligand pharmacophoric sites through combinatorial library design and MD simulation in validating HTLV-1 PR inhibitors.

    PubMed

    Selvaraj, Chandrabose; Omer, Ankur; Singh, Poonam; Singh, Sanjeev Kumar

    2015-01-01

    Retroviruses HIV-1 and HTLV-1 are chiefly considered to be the most dangerous pathogens in Homo sapiens. These two viruses have structurally unique protease (PR) enzymes, which are having common function of its replication mechanism. Though HIV PR drugs failed to inhibit HTLV-1 infections, they emphatically emphasise the need for designing new lead compounds against HTLV-1 PR. Therefore, we tried to understand the binding level interactions through the charge environment present in both ligand and protein active sites. The domino effect illustrates that libraries of purvalanol-A are attuned to fill allosteric binding site of HTLV-1 PR through molecular recognition and shows proper binding of ligand pharmacophoric features in receptor contours. Our screening evaluates seven compounds from purvalanol-A libraries, and these compounds' pharmacophore searches for an appropriate place in the binding site and it places well according to respective receptor contour surfaces. Thus our result provides a platform for the progress of more effective compounds, which are better in free energy calculation, molecular docking, ADME and molecular dynamics studies. Finally, this research provided novel chemical scaffolds for HTLV-1 drug discovery. PMID:25335799

  9. 4-Acyl Pyrrole Derivatives Yield Novel Vectors for Designing Inhibitors of the Acetyl-Lysine Recognition Site of BRD4(1).

    PubMed

    Hügle, Martin; Lucas, Xavier; Weitzel, Gerhard; Ostrovskyi, Dmytro; Breit, Bernhard; Gerhardt, Stefan; Einsle, Oliver; Günther, Stefan; Wohlwend, Daniel

    2016-02-25

    Several human diseases, including cancer, show altered signaling pathways resulting from changes in the activity levels of epigenetic modulators. In the past few years, small-molecule inhibitors against specific modulators, including the bromodomain and extra-terminal (BET) bromodomain family of acetylation readers, have shown early promise in the treatment of the genetically defined midline carcinoma and hematopoietic malignancies. We have recently developed a novel potent inhibitor of BET proteins, 1 (XD14[ Angew. Chem., Int. Ed. 2013, 52, 14055]), which exerts a strong inhibitory potential on the proliferation of specific leukemia cell lines. In the study presented here, we designed analogues of 1 to study the potential of substitutions on the 4-acyl pyrrole backbone to occupy additional sites within the substrate recognition site of BRD4(1). The compounds were profiled using ITC, DSF, and X-ray crystallography. We could introduce several substitutions that address previously untargeted areas of the substrate recognition site. This work may substantially contribute to the development of therapeutics with increased target specificity against BRD4-related malignancies. PMID:26731611

  10. Design and performance of a Nafion dryer for continuous operation at CO2 and CH4 air monitoring sites

    NASA Astrophysics Data System (ADS)

    Welp, L. R.; Keeling, R. F.; Weiss, R. F.; Paplawsky, W.; Heckman, S.

    2012-08-01

    In preparation for the routine deployment of the Earth Networks greenhouse gas monitoring network, we have designed and tested a simple method for drying ambient air to below 0.2% mole fraction H2O using a Nafion dryer. The inlet was designed for use with a Picarro model G2301 cavity ring down spectrometer (CRDS) CO2/CH4/H2O analyzer. The analyzer measures water vapor mixing ratio at the same frequency as CO2 and CH4 and then corrects for the dilution and peak broadening effects of H2O on the CO2 and CH4 mixing ratios. This analyzer is remarkably stable and performs well on water vapor correction tests, but there is potentially an added benefit of reducing the dependence on the H2O correction for long term field measurement programs. Substantially lowering the amount of H2O in the sample can reduce uncertainties in the applied H2O corrections by an order of magnitude or more, and eliminate the need to determine an instrument-specific H2O correction factor and to verify its stability over time. Our Nafion drying inlet system takes advantage of the extra capacity of the analyzer pump to redirect 30% of the dry gas exiting the Nafion to the outer shell side of the dryer and has no consumables. We tested the Nafion dryer against a cryotrap (-95 °C) method for removing H2O and found that it does not significantly alter the CO2 and CH4 dry mixing ratios of the sample gas. Systematic differences between the drying methods were at the level of 0.05 ppm in CO2 and 0.1 ppb in CH4 for the wet-air tests, well within the WMO compatibility guidelines.

  11. Site-preferential design of itinerant ferromagnetic borides: experimental and theoretical investigation of MRh6B3 (M = Fe, Co).

    PubMed

    Misse, Patrick R N; Gillessen, Michael; Fokwa, Boniface P T

    2011-10-17

    Single-phase polycrystalline samples of the compounds MRh(6)B(3) (M = Fe, Co) as well as single crystals of CoRh(6)B(3) have been synthesized by arc-melting the elements under a purified argon atmosphere in a water-cooled copper crucible. The characterization of the new phases was achieved by using single-crystal and powder X-ray diffraction as well as EDX measurements. The two phases are isotypic and crystallize in the hexagonal Th(7)Fe(3) structure type (space group P6(3)mc, no. 186, Z = 2). In this structure, the magnetically active atoms (Fe, Co) are preferentially found on only one of the three available rhodium sites, and together with rhodium they build a three-dimensional network of interconnected (Rh/M)(3) triangles. Magnetic properties investigations show that both phases order ferromagnetically below Curie temperatures of 240 K (for FeRh(6)B(3)) and 150 K (for CoRh(6)B(3)). First-principles DFT calculations correctly reproduce not only the lattice parameters but also the ground state magnetic ordering in the two phases. These calculations also show that the long-range magnetic ordering in both phases occurs via indirect ferromagnetic coupling between the iron atoms mediated by rhodium. This magnetic structural model also predicts the saturation magnetizations to be 4.02 μ(B) for FeRh(6)B(3) (3.60 μ(B) found experimentally) and 2.75 μ(B) for CoRh(6)B(3). Furthermore, both phases are predicted to be metallic conductors as expected for these intermetallic borides. PMID:21905755

  12. Design and Methods of a Multi-Site, Multi-Behavioral Treatment Trial for Menopausal Symptoms: The MsFLASH Experience

    PubMed Central

    Sternfeld, Barbara; LaCroix, Andrea; Caan, Bette J.; Dunn, Andrea L.; Newton, Katherine M.; Reed, Susan D.; Guthrie, Katherine A; Booth-LaForce, Cathryn; Sherman, Karen J; Cohen, Lee; Freeman, Marlene P.; Carpenter, Janet S.; Hunt, Julie R.; Roberts, Melanie; Ensrud, Kristine E.

    2013-01-01

    Background Behavioral strategies are recommended for menopausal symptoms, but little evidence exists regarding efficacy. Purpose Describe design and methodology of a randomized controlled 3 by 2 factorial trial of yoga, exercise and omega-3 fatty acids. Methods Women from three geographic areas with a weekly average of ≥14 hot flashes/night sweats, who met exclusion/inclusion criteria, were randomized to 12 weeks of: 1) yoga classes and daily home practice; 2) supervised, facility-based aerobic exercise training; or 3) usual activity. Women in each arm were further randomized to either omega-3 supplement or placebo. Standardized training, on-going monitoring, and site visits were adopted to ensure consistency across sites and fidelity to the intervention. Participant adherence to the intervention protocol was monitored continuously, and retention was actively encouraged by staff. Information on adverse events was systematically collected. Results Of 7,377 women who responded to mass mailings, 355 (4.8%) were randomized; mean age was 54.7 (sd=3.7), 26.2% were African American, 81.7% were post-menopausal, and mean baseline frequency of daily hot flashes/night sweats was 7.6 (sd=3.8). Adherence of ≥ 80% was 59% for yoga, 77% for exercise training, and 80% for study pills. Final week 12 data were collected from 95.2% Conclusions Conducting a multi-site, multi-behavioral randomized trial for menopausal symptoms is challenging but feasible. Benefits included cost-effective study design, centralized recruitment, and methodologic standardization. PMID:23462342

  13. Designing Surface Monitoring Meshes for Geologic Carbon Capture and Storage Sites: Accurate Emissions Accounting for an Essential 2°C Mitigation Technology

    NASA Astrophysics Data System (ADS)

    Augustin, C. M.; Swart, P. K.; Broad, K.

    2014-12-01

    Geologic carbon capture and storage (CCS) is a feasible solution to the international greenhouse gas (GHG) emissions problem and it has recently been called a "vital" mitigation tool by the International Energy Agency. However, there exists uncertainty concerning the terminal fate of stored carbon dioxide (CO2.) In this regard, reliable monitoring, verification and accounting (MVA) technologies are essential for making CCS publicly acceptable. Chiefly, MVA addresses safety and environmental concerns by providing a warning system to prevent or alleviate CO2 leakages. A secondary purpose of MVA technologies is to prove compliance with CO2 reduction standards through inventory verification. A key MVA tool for tracking CO2 leakages is surface (atmospheric) monitoring. Demonstrating its value, industry actors feel an impetus to invest in surface monitoring as a low-risk, high-value technology to mitigate liability in cases of potential leakages. Despite how necessary this tool is, to date, all surface monitoring mesh designs and best practices have been proposed locally, without discussion of standardization or optimization on a regional, national or international level. We identify the fundamental problem of surface monitoring mesh design as locating the monitoring sites to record CO2 levels over the designated geographic area at lowest cost with maximum impact. We approach this problem from both an operations research (OR) perspective and atmospheric dispersion perspective. From an OR perspective, we approach mesh design using multiobjective optimization models - we specify the relative placement of candidate sites, observation time interval, and optimality criteria. In the second approach, we model CO2 leakage scenarios to test the effectiveness of proposed mesh design from the first approach. We use atmospheric dispersion modeling softwares AERMOD and SCREEN3 - both tools developed by the United States Environmental Protection Agency and codified into law - for

  14. Perioperative oxygen fraction – effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial

    PubMed Central

    Meyhoff, Christian S; Wetterslev, Jørn; Jorgensen, Lars N; Henneberg, Steen W; Simonsen, Inger; Pulawska, Therese; Walker, Line R; Skovgaard, Nina; Heltø, Kim; Gocht-Jensen, Peter; Carlsson, Palle S; Rask, Henrik; Karim, Sharaf; Carlsen, Charlotte G; Jensen, Frank S; Rasmussen, Lars S

    2008-01-01

    Background A high perioperative inspiratory oxygen fraction may reduce the risk of surgical site infections, as bacterial eradication by neutrophils depends on wound oxygen tension. Two trials have shown that a high perioperative inspiratory oxygen fraction (FiO2 = 0.80) significantly reduced risk of surgical site infections after elective colorectal surgery, but a third trial was stopped early because the frequency of surgical site infections was more than doubled in the group receiving FiO2 = 0.80. It has not been settled if a high inspiratory oxygen fraction increases the risk of pulmonary complications, such as atelectasis, pneumonia and respiratory failure. The aim of our trial is to assess the potential benefits and harms of a high perioperative oxygen fraction in patients undergoing abdominal surgery. Methods and design The PROXI-Trial is a randomized, patient- and assessor blinded trial of perioperative supplemental oxygen in 1400 patients undergoing acute or elective laparotomy in 14 Danish hospitals. Patients are randomized to receive either 80% oxygen (FiO2 = 0.80) or 30% oxygen (FiO2 = 0.30) during surgery and for the first 2 postoperative hours. The primary outcome is surgical site infection within 14 days. The secondary outcomes are: atelectasis, pneumonia, respiratory failure, re-operation, mortality, duration of postoperative hospitalization, and admission to intensive care unit. The sample size allows detection of a 33% relative risk reduction in the primary outcome with 80% power. Discussion This trial assesses benefits and harms of a high inspiratory oxygen fraction, and the trial may be generalizable to a general surgical population undergoing laparotomy. Trial registration ClinicalTrials.gov identifier: NCT00364741. PMID:18945347

  15. The Use of Genetic Algorithms as an Inverse Technique to Guide the Design and Implementation of Research at a Test Site in Shelby County, Tennessee

    NASA Astrophysics Data System (ADS)

    Gentry, R. W.

    2002-12-01

    The Shelby Farms test site in Shelby County, Tennessee is being developed to better understand recharge hydraulics to the Memphis aquifer in areas where leakage through an overlying aquitard occurs. The site is unique in that it demonstrates many opportunities for interdisciplinary research regarding environmental tracers, anthropogenic impacts and inverse modeling. The objective of the research funding the development of the test site is to better understand the groundwater hydrology and hydraulics between a shallow alluvial aquifer and the Memphis aquifer given an area of leakage, defined as an aquitard window. The site is situated in an area on the boundary of a highly developed urban area and is currently being used by an agricultural research agency and a local recreational park authority. Also, an abandoned landfill is situated to the immediate south of the window location. Previous research by the USGS determined the location of the aquitard window subsequent to the landfill closure. Inverse modeling using a genetic algorithm approach has identified the likely extents of the area of the window given an interaquifer accretion rate. These results, coupled with additional fieldwork, have been used to guide the direction of the field studies and the overall design of the research project. This additional work has encompassed the drilling of additional monitoring wells in nested groups by rotasonic drilling methods. The core collected during the drilling will provide additional constraints to the physics of the problem that may provide additional help in redefining the conceptual model. The problem is non-unique with respect to the leakage area and accretion rate and further research is being performed to provide some idea of the advective flow paths using a combination of tritium and 3He analyses and geochemistry. The outcomes of the research will result in a set of benchmark data and physical infrastructure that can be used to evaluate other environmental

  16. Design and performance of a Nafion dryer for continuous operation at CO2 and CH4 air monitoring sites

    NASA Astrophysics Data System (ADS)

    Welp, L. R.; Keeling, R. F.; Weiss, R. F.; Paplawsky, W.; Heckman, S.

    2013-05-01

    In preparation for routine deployment in a network of greenhouse gas monitoring stations, we have designed and tested a simple method for drying ambient air to near or below 0.2% (2000 ppm) mole fraction H2O using a Nafion dryer. The inlet system was designed for use with cavity ring-down spectrometer (CRDS) analyzers such as the Picarro model G2301 that measure H2O in addition to their principal analytes, in this case CO2 and CH4. These analyzers report dry-gas mixing ratios without drying the sample by measuring H2O mixing ratio at the same frequency as the main analytes, and then correcting for the dilution and peak broadening effects of H2O on the mixing ratios of the other analytes measured in moist air. However, it is difficult to accurately validate the water vapor correction in the field. By substantially lowering the amount of H2O in the sample, uncertainties in the applied water vapor corrections can be reduced by an order of magnitude or more, thus eliminating the need to determine instrument-specific water vapor correction coefficients and to verify the stability over time. Our Nafion drying inlet system takes advantage of the extra capacity of the analyzer pump to redirect 30% of the dry gas exiting the Nafion to the outer shell side of the dryer and has no consumables. We tested the Nafion dryer against a cryotrap (-97 °C) method for removing H2O and found that in wet-air tests, the Nafion reduces the CO2 dry-gas mixing ratios of the sample gas by as much as 0.1 ± 0.01 ppm due to leakage across the membrane. The effect on CH4 was smaller and varied within ± 0.2 ppb, with an approximate uncertainty of 0.1 ppb. The Nafion-induced CO2 bias is partially offset by sending the dry reference gases through the Nafion dryer as well. The residual bias due to the impact of moisture differences between sample and reference gas on the permeation through the Nafion was approximately -0.05 ppm for CO2 and varied within ± 0.2 ppb for CH4. The uncertainty of this

  17. USDA-ARS Southeast Watershed Laboratory at Tifton, GA:Index Site Design for the Suwannee Basin

    NASA Astrophysics Data System (ADS)

    Bosch, D.; Strickland, T.; Sheridan, J.; Lowrance, R.; Truman, C.; Hubbard, R.; Potter, T.; Wauchope, D.; Vellidis, G.; Thomas, D.

    2001-12-01

    The Southeast Watershed Hydrology Research Center (SEWHRC) was established in 1966 by order of the U.S. Senate "to identify and characterize those elements that control the flow of water from watersheds in the southeast". A 129 sq.mi. area within the headwaters of Little River Watershed (LRW) in central south Georgia was instrumented to provide data for evaluating and characterizing Coastal Plain hydrologic processes and for development and testing of prediction methodologies for use in ungaged watersheds in regions of low topographic relief. Pesticide analytical capabilities were added in 1976, and inorganic chemistry and sediment transport research were expanded. In 1980, the Center was renamed as the Southeast Watershed Research Laboratory (SEWRL), and laboratories were constructed for nutrient analysis and soil physics. A pesticide analysis laboratory was constructed in 1987. In the early 1990s, a hydraulics laboratory was established for sediment and chemical transport studies, and research on riparian buffers was expanded. The SEWRL research program continues to focus on hydrologic and environmental concerns. Major components of the program are hydrology, pesticides behavior, buffer systems, animal waste management, erosion, remote sensing of watershed condition, and relationships between site-specific agricultural management (BMPs) and small-to-large watershed response. SEWRL's program will be expanded over the next five years to include two additional watersheds comparable in size and instrumentation to the LRW; nesting the LRW within the full Little River drainage and subsequently...all three watersheds within the full Suwannee Basin; and mapping and quantifying irrigation water removals within the Suwannee Basin. We will instrument the three intensive study watersheds and the full Suwannee Basin to provide real-time characterization of precipitation, soil moisture, hydrologic flow, and water quality at a range of spatial and temporal scales. We will

  18. Compressed air energy storage: preliminary design and site development program in an aquifer. Final draft, Task 2: Volume 2 of 3. Characterize and explore potential sites and prepare research and development plan

    SciTech Connect

    1980-12-01

    The characteristics of sites in Indiana and Illinois which are being investigated as potential sites for compressed air energy storage power plants are documented. These characteristics include geological considerations, economic factors, and environmental considerations. Extensive data are presented for 14 specific sites and a relative rating on the desirability of each site is derived. (LCL)

  19. Processing of abasic site damaged lesions by APE1 enzyme on DNA adsorbed over normal and organomodified clay.

    PubMed

    Kumari, Bhavini; Banerjee, Shib Shankar; Singh, Vandana; Das, Prolay; Bhowmick, Anil K

    2014-10-01

    The efficiency of the apurinic/apyrimidinic endonuclease (APE1) DNA repair enzyme in the processing of abasic site DNA damage lesions at precise location in DNA oligomer duplexes that are adsorbed on clay surfaces was evaluated. Three different forms of clay namely montmorillonite, quaternary ammonium salt modified montmorillonite and its boiled counterpart i.e. partially devoid of organic moiety were used for a comparative study of adsorption, desorption and DNA repair efficiency on their surfaces. The interaction between the DNA and the clay was analysed by X-ray diffraction, Atomic force microscopy, UV-Vis spectroscopy and Infrared spectroscopy. The abasic site cleavage efficiency of APE1 enzyme was quantitatively evaluated by polyacrylamide gel electrophoresis. Apart from the difference in the DNA adsorption or desorption capacity of the various forms of clay, substantial variation in the repair efficiency of abasic sites initiated by the APE1 enzyme on the clay surfaces was observed. The incision efficiency of APE1 enzyme at abasic sites was found to be greatly diminished, when the DNA was adsorbed over organomodified montmorillonite. The reduced repair activity indicates an important role of the pendant surfactant groups on the clay surfaces in directing APE1 mediated cleavage of abasic site DNA damage lesions. PMID:25048946

  20. Design, synthesis and evaluation of rivastigmine and curcumin hybrids as site-activated multitarget-directed ligands for Alzheimer's disease therapy.

    PubMed

    Li, Yujie; Peng, Peng; Tang, Li; Hu, Yunzhen; Hu, Yongzhou; Sheng, Rong

    2014-09-01

    A series of novel 2-methoxy-phenyl dimethyl-carbamate derivatives were designed, synthesized and evaluated as site-activated MTDLs based on rivastigmine and curcumin. Most of them exhibited good to excellent AChE and BuChE inhibitory activities with sub-micromolar IC50 values. Among all the compounds, 6a demonstrated the most potent AChE inhibition with IC50 value of 0.097μM, which is about 20-fold than that of rivastigmine. In addition, the three selected compounds 5a, 6a and 6e demonstrated inhibitory activity against Aβ self-aggregation similar to cucurmin in TEM assay, which is obviously different from the weak activity of rivastigmine. Moreover, the hydrolysate of 6a (compound 7) also showed potent ABTS(+) scavenging and moderate copper ion chelating activity in vitro. PMID:25082512

  1. Binding of 3,4,5,6-Tetrahydroxyazepanes to the Acid-[beta]-glucosidase Active Site: Implications for Pharmacological Chaperone Design for Gaucher Disease

    SciTech Connect

    Orwig, Susan D.; Tan, Yun Lei; Grimster, Neil P.; Yu, Zhanqian; Powers, Evan T.; Kelly, Jeffery W.; Lieberman, Raquel L.

    2013-03-07

    Pharmacologic chaperoning is a therapeutic strategy being developed to improve the cellular folding and trafficking defects associated with Gaucher disease, a lysosomal storage disorder caused by point mutations in the gene encoding acid-{beta}-glucosidase (GCase). In this approach, small molecules bind to and stabilize mutant folded or nearly folded GCase in the endoplasmic reticulum (ER), increasing the concentration of folded, functional GCase trafficked to the lysosome where the mutant enzyme can hydrolyze the accumulated substrate. To date, the pharmacologic chaperone (PC) candidates that have been investigated largely have been active site-directed inhibitors of GCase, usually containing five- or six-membered rings, such as modified azasugars. Here we show that a seven-membered, nitrogen-containing heterocycle (3,4,5,6-tetrahydroxyazepane) scaffold is also promising for generating PCs for GCase. Crystal structures reveal that the core azepane stabilizes GCase in a variation of its proposed active conformation, whereas binding of an analogue with an N-linked hydroxyethyl tail stabilizes GCase in a conformation in which the active site is covered, also utilizing a loop conformation not seen previously. Although both compounds preferentially stabilize GCase to thermal denaturation at pH 7.4, reflective of the pH in the ER, only the core azepane, which is a mid-micromolar competitive inhibitor, elicits a modest increase in enzyme activity for the neuronopathic G202R and the non-neuronopathic N370S mutant GCase in an intact cell assay. Our results emphasize the importance of the conformational variability of the GCase active site in the design of competitive inhibitors as PCs for Gaucher disease.

  2. Binding of 3,4,5,6-tetrahydroxyazepanes to the acid-β-glucosidase active site: implications for pharmacological chaperone design for Gaucher disease†

    PubMed Central

    Orwig, Susan. D.; Tan, Yun Lei; Grimster, Neil P.; Yu, Zhanqian; Powers, Evan; Kelly, Jeffery W.; Lieberman, Raquel L.

    2011-01-01

    Pharmacological chaperoning is a therapeutic strategy being developed to restore cellular folding and trafficking defects associated with Gaucher disease, a lysosomal storage disorder caused by point mutations in the gene encoding for acid- β-glucosidase (GCase). In this approach, small molecules bind to and stabilize mutant GCase in the endoplasmic reticulum (ER), increasing the concentration of folded, functional GCase trafficked to the lysosome where the mutant enzyme can hydrolyze accumulated substrate. To date, pharmacologic chaperone (PC) candidates investigated have largely been active-site-directed inhibitors of GCase, usually containing five- or six-membered rings, such as modified azasugars. Here we show that a seven-membered, nitrogen-containing heterocycle (3,4,5,6-tetrahydroxyazepane) scaffold is also promising for generating PCs for GCase. Crystal structures reveal that the core azepane stabilizes GCase in a variation of its proposed active conformation, whereas binding of an analog with an N-linked hydroxyethyl tail stabilizes a conformation of GCase in which the active site is covered, also utilizing a loop conformation not seen previously. Although both compounds preferentially stabilize GCase to thermal denaturation at pH 7.4, reflective of the pH in the ER, only the core azepane, which is a micromolar competitive inhibitor, elicits a modest increase in enzyme activity for the neuronopathic G202R- and the non-neuronopathic N370S- mutant GCase in an intact cell assay. Our results emphasize the importance of the conformational variability of the GCase active site in the design of competitive inhibitors as PCs for Gaucher disease. PMID:22047104

  3. Design, Synthesis, and Biological Evaluation of 1-Methyl-1,4-dihydroindeno[1,2-c]pyrazole Analogues as Potential Anticancer Agents Targeting Tubulin Colchicine Binding Site.

    PubMed

    Liu, Yan-Na; Wang, Jing-Jing; Ji, Ya-Ting; Zhao, Guo-Dong; Tang, Long-Qian; Zhang, Cheng-Mei; Guo, Xiu-Li; Liu, Zhao-Peng

    2016-06-01

    By targeting a new binding region at the interface between αβ-tubulin heterodimers at the colchicine binding site, we designed a series of 7-substituted 1-methyl-1,4-dihydroindeno[1,2-c]pyrazoles as potential tubulin polymerization inhibitors. Among the compounds synthesized, 2-(6-ethoxy-3-(3-ethoxyphenylamino)-1-methyl-1,4-dihydroindeno[1,2-c]pyrazol-7-yloxy)acetamide 6a and 2-(6-ethoxy-3-(3-ethoxyphenylamino)-1-methyl-1,4-dihydroindeno[1,2-c]pyrazol-7-yloxy)-N-hydroxyacetamide 6n showed noteworthy low nanomolar potency against HepG2, Hela, PC3, and MCF-7 cancer cell lines. In mechanism studies, 6a inhibited tubulin polymerization and disorganized microtubule in A549 cells by binding to tubulin colchicine binding site. 6a arrested A549 cells in G2/M phase that was related to the alterations in the expression of cyclin B1 and p-cdc2. 6a induced A549 cells apoptosis through the activation of caspase-3 and PARP. In addition, 6a inhibited capillary tube formation in a concentration-dependent manner. In nonsmall cell lung cancer xenografts mouse model, 6a suppressed tumor growth by 59.1% at a dose of 50 mg/kg (ip) without obvious toxicity, indicating its in vivo potential as anticancer agent. PMID:27172319

  4. White paper on the proposed design, development, and implementation of a monitored retrievable storage module and the siting criteria for spent nuclear fuel

    SciTech Connect

    Villarreal, B.; Knobeloch, D.

    1996-01-01

    Congress enacted the Nuclear Waste Policy (NWP) Act in 1982 as comprehensive legislation for the DOE to locate, build, and operate repositories to permanently dispose of spent nuclear fuel and other high-level wastes. In 1987, Congress amended the NWP Act and authorized the DOE to site, construct, and operate one Monitored Retrievable Storage (MRS) facility. The MRS facility was planned as a means to enhance the flexibility and reliability of the overall waste management system. This white paper presents a broad prospectus of the scientific and regulatory capabilities at Los Alamos National Laboratory and outlines the methodology to design and implement an MRS test module. This proposed module will incorporate the flexibility to store all types of spent nuclear fuel above or below ground level and will be fully monitored for the residence time of the spent fuel in the MRS module. The purpose of this test module is to define the parameters necessary to build a simple and economical MRS system. Demonstration of the proposed MRS test module will be important because it will form the basis for an integrated MRS site model.

  5. High-Resolution Monitoring of CO2 Injection with Permanent Electrodes: A 5-Year Retrospect from the Ketzin Site and Design Recommendations for Future Projects

    NASA Astrophysics Data System (ADS)

    Wagner, F. M.; Bergmann, P.; Labitzke, T.; Schmidt-Hattenberger, C.; Guenther, T.; Maurer, H.

    2014-12-01

    Reliable and cost-efficient reservoir surveillance techniques play an important role in the context of geological carbon dioxide storage. Electrical methods are particularly suited to image the displacement of highly conductive formation fluids by a more resistive CO2 plume. At the Ketzin site close to Berlin, Germany, a permanent installation of 45 ring-shaped stainless steel electrodes distributed in an injection well and two observation wells is in operation since the start of injection in June 2008. The depth of the installation intervals in the three wells ranges from 590 m to 735 m. Based on our practical experience after more than five years of injection (until August 2013), we draw conclusions with regard to the usefulness and versatility of such an electrode array as well as associated challenges under the aspect of technical longevity. With regard to future installations, we present an experimental design approach to estimate optimum electrode locations along the borehole trajectories with the objective to maximize the resolution within a prescribed target horizon. Our results show that a sparse but well-conceived set of electrodes with a refinement of the electrode spacing in the target region can provide a large portion of the information content offered by very dense electrode layouts. Using Ketzin as a case study for realistic CO2 plume migration, we compare the optimized layout to the existing equidistant installation at Ketzin with a focus on the offered resolution and the inversion performance. The presented results can assist practitioners in the design of reliable and cost-efficient monitoring systems for future underground storage sites.

  6. Reservoir High's TE Site Wins Web Site of the Month

    ERIC Educational Resources Information Center

    Tech Directions, 2008

    2008-01-01

    This article features "Mr. Rhine's Technology Education Web Site," a winner of the Web Site of the Month. This Web site was designed by Luke Rhine, a teacher at the Reservoir High School in Fulton, Maryland. Rhine's Web site offers course descriptions and syllabuses, class calendars, lectures and presentations, design briefs and other course…

  7. Designing Allosteric Regulators of Thrombin. Exosite 2 Features Multiple Sub-Sites That Can Be Targeted By Sulfated Small Molecules for Inducing Inhibition

    PubMed Central

    Sidhu, Preetpal Singh; Abdel Aziz, May H.; Sarkar, Aurijit; Mehta, Akul Y.; Zhou, Qibing; Desai, Umesh R.

    2013-01-01

    We recently designed a group of novel exosite 2-directed, sulfated, small, allosteric inhibitors of thrombin. To develop more potent inhibitors, monosulfated benzofuran tri- and tetrameric homologs of the parent designed dimers were synthesized in 7–8 steps and found to exhibit a wide range of potencies. Among these, trimer 9a was found to be nearly 10-fold more potent than the first generation molecules. Michaelis-Menten studies indicated an allosteric mechanism of inhibition. Competitive studies using a hirudin peptide (exosite 1 ligand) and, unfractionated heparin, heparin octasaccharide and γ′-fibrinogen peptide (exosite 2 ligands), demonstrated exosite 2 recognition in a manner different from the parent dimers. Alanine scanning mutagenesis of 12 Arg/Lys residues of exosite 2 revealed a defect in 9a potency for Arg233Ala thrombin only confirming the major difference in site of recognition between the two structurally related sulfated benzofurans. The results suggest that multiple avenues are available within exosite 2 for inducing thrombin inhibition. PMID:23718540

  8. Discovery of Cyclic Acylguanidines as Highly Potent and Selective β-Site Amyloid Cleaving Enzyme (BACE) Inhibitors: Part I–Inhibitor Design and Validation

    SciTech Connect

    Zhu, Zhaoning; Sun, Zhong-Yue; Ye, Yuanzan; Voigt, Johannes; Strickland, Corey; Smith, Elizabeth M.; Cumming, Jared; Wang, Lingyan; Wong, Jesse; Wang, Yu-Sen; Wyss, Daniel F.; Chen, Xia; Kuvelkar, Reshma; Kennedy, Matthew E.; Favreau, Leonard; Parker, Eric; McKittrick, Brian A.; Stamford, Andrew; Czarniecki, Michael; Greenlee, William; Hunter, John C.

    2013-11-20

    A number of novel amidine containing heterocycles were designed to reproduce the unique interaction pattern, revealed by X-ray crystallography, between the BACE-1 catalytic diad and a weak NMR screening hit, with special attention paid to maintaining the appropriate basicity and limiting the number of H-bonding donors of these scaffolds. The iminohydantoin cores were examined first and found to interact with the catalytic diad in one of two binding modes (A and B), each with the iminohydantoin core flipped 180° in relation to the other. The amidine structural motif within each core forms a bidentate interaction with a different aspartic acid of the catalytic diad. Both modes reproduced a highly conserved interaction pattern between the inhibitors and the catalytic aspartates. Potent iminohydantoin BACE-1 inhibitors have been obtained, validating the molecular design as aspartyl protease catalytic site inhibitors. Brain penetrant small molecule BACE inhibitors with high ligand efficiencies have been discovered, enabling multiple strategies for further development of these inhibitors into highly potent, selective and in vivo efficacious BACE inhibitors.

  9. Discovery of Cyclic Acylguanidines as Highly Potent and Selective β-Site Amyloid Cleaving Enzyme (BACE) Inhibitors: Part I-Inhibitor Design and Validation

    SciTech Connect

    Zhu, Zhaoning; Sun, Zhong-Yue; Ye, Yuanzan; Voigt, Johannes; Strickland, Corey; Smith, Elizabeth M; Cumming, Jared; Wang, Lingyan; Wong, Jesse; Wang, Yu-Sen; Wyss, Daniel F; Chen, Xia; Kuvelkar, Reshma; Kennedy, Matthew E; Favreau, Leonard; Parker, Eric; McKittrick, Brian A; Stamford, Andrew; Czarniecki, Michael; Greenlee, William; Hunter, John C

    2010-10-18

    A number of novel amidine containing heterocycles were designed to reproduce the unique interaction pattern, revealed by X-ray crystallography, between the BACE-1 catalytic diad and a weak NMR screening hit (3), with special attention paid to maintaining the appropriate basicity and limiting the number of H-bonding donors of these scaffolds. The iminohydantoin cores (10 and 23) were examined first and found to interact with the catalytic diad in one of two binding modes (A and B), each with the iminohydantoin core flipped 180º in relation to the other. The amidine structural motif within each core forms a bidentate interaction with a different aspartic acid of the catalytic diad. Both modes reproduced a highly conserved interaction pattern between the inhibitors and the catalytic aspartates, as revealed by 3. Potent iminohydantoin BACE-1 inhibitors have been obtained, validating the molecular design as aspartyl protease catalytic site inhibitors. Brain penetrant small molecule BACE inhibitors with high ligand efficiencies have been discovered, enabling multiple strategies for further development of these inhibitors into highly potent, selective and in vivo efficacious BACE inhibitors.

  10. Design Support of an Above Cap-rock Early Detection Monitoring System using Simulated Leakage Scenarios at the FutureGen2.0 Site

    SciTech Connect

    Williams, Mark D.; USA, Richland Washington; Vermuel, Vince R.; USA, Richland Washington; Oostrom, Mart; USA, Richland Washington; Porse, Sean L.; USA, Richland Washington; Thorne, Paul D.; USA, Richland Washington; Szecsody, Jim E.; USA, Richland Washington; Horner, Jake A.; USA, Richland Washington; Gilmore, Tyler J.; USA, Richland Washington

    2014-12-31

    The FutureGen 2.0 Project will design and build a first-of-its-kind, near-zero emissions coal-fueled power plant with carbon capture and storage (CCS). To assess storage site performance and meet the regulatory requirements of the Class VI Underground Injection Control (UIC) Program for CO2 Geologic Sequestration, the FutureGen 2.0 project will implement a suite of monitoring technologies designed to evaluate CO2 mass balance and detect any unforeseen loss in CO2 containment. The monitoring program will include direct monitoring of the reservoir, and early-leak-detection monitoring directly above the primary confining zone. This preliminary modeling study described here focuses on hypothetical leakage scenarios into the first permeable unit above the primary confining zone (Ironton Sandstone) and is used to support assessment of early-leak detection capabilities. Future updates of the model will be used to assess potential impacts on the lowermost underground source of drinking water (Saint Peter Sandstone) for a range of theoretical leakage scenarios. This preliminary modeling evaluation considers both pressure response and geochemical signals in the overlying Ironton Sandstone. This model is independent of the FutureGen 2.0 reservoir model in that it does not simulate caprock discontinuities, faults, or failure scenarios. Instead this modeling effort is based on theoretical, volumetric-rate based leakage scenarios. The scenarios include leakage of 1% of the total injected CO2 mass, but spread out over different time periods (20, 100, and 500 years) with each case yielding a different mass flux (i.e., smaller mass fluxes for longer duration leakage cases]. A brine leakage scenario using a volumetric leakage similar to the 20 year 1% CO2 case was also considered. A framework for the comparison of the various cases was developed based on the exceedance of selected pressure and geochemical thresholds at different

  11. Design Support of an Above Cap-rock Early Detection Monitoring System using Simulated Leakage Scenarios at the FutureGen2.0 Site

    DOE PAGESBeta

    Williams, Mark D.; USA, Richland Washington; Vermuel, Vince R.; USA, Richland Washington; Oostrom, Mart; USA, Richland Washington; Porse, Sean L.; USA, Richland Washington; Thorne, Paul D.; USA, Richland Washington; et al

    2014-12-31

    The FutureGen 2.0 Project will design and build a first-of-its-kind, near-zero emissions coal-fueled power plant with carbon capture and storage (CCS). To assess storage site performance and meet the regulatory requirements of the Class VI Underground Injection Control (UIC) Program for CO2 Geologic Sequestration, the FutureGen 2.0 project will implement a suite of monitoring technologies designed to evaluate CO2 mass balance and detect any unforeseen loss in CO2 containment. The monitoring program will include direct monitoring of the reservoir, and early-leak-detection monitoring directly above the primary confining zone. This preliminary modeling study described here focuses on hypothetical leakage scenarios intomore » the first permeable unit above the primary confining zone (Ironton Sandstone) and is used to support assessment of early-leak detection capabilities. Future updates of the model will be used to assess potential impacts on the lowermost underground source of drinking water (Saint Peter Sandstone) for a range of theoretical leakage scenarios. This preliminary modeling evaluation considers both pressure response and geochemical signals in the overlying Ironton Sandstone. This model is independent of the FutureGen 2.0 reservoir model in that it does not simulate caprock discontinuities, faults, or failure scenarios. Instead this modeling effort is based on theoretical, volumetric-rate based leakage scenarios. The scenarios include leakage of 1% of the total injected CO2 mass, but spread out over different time periods (20, 100, and 500 years) with each case yielding a different mass flux (i.e., smaller mass fluxes for longer duration leakage cases]. A brine leakage scenario using a volumetric leakage similar to the 20 year 1% CO2 case was also considered. A framework for the comparison of the various cases was developed based on the exceedance of selected pressure and geochemical thresholds at different distances from the point of leakage and at

  12. Conceptual Design of a Simplified Skid-Mounted Caustic-Side Solvent Extraction Process for Removal of Cesium from Savannah Rive Site High-Level Waste

    SciTech Connect

    Birdwell, JR.J.F.

    2004-05-12

    This report presents the results of a conceptual design of a solvent extraction process for the selective removal of {sup 137}Cs from high-level radioactive waste currently stored in underground tanks at the U.S. Department of Energy's Savannah River Site (SRS). This study establishes the need for and feasibility of deploying a simplified version of the Caustic-Side Solvent Extraction (CSSX) process; cost/benefit ratios ranging from 33 to 55 strongly support the considered deployment. Based on projected compositions, 18 million gallons of dissolved salt cake waste has been identified as having {sup 137}Cs concentrations that are substantially lower than the worst-case design basis for the CSSX system that is to be deployed as part of the Salt Waste Processing Facility (SWPF) but that does not meet the waste acceptance criteria for immobilization as grout in the Saltstone Manufacturing and Disposal Facility at SRS. Absent deployment of an alternative cesium removal process, this material will require treatment in the SWPF CSSX system, even though the cesium decontamination factor required is far less than that provided by that system. A conceptual design of a CSSX processing system designed for rapid deployment and having reduced cesium decontamination factor capability has been performed. The proposed accelerated-deployment CSSX system (CSSX-A) has been designed to have a processing rate of 3 million gallons per year, assuming 90% availability. At a more conservative availability of 75% (reflecting the novelty of the process), the annual processing capacity is 2.5 million gallons. The primary component of the process is a 20-stage cascade of centrifugal solvent extraction contactors. The decontamination and concentration factors are 40 and 15, respectively. The solvent, scrub, strip, and wash solutions are to have the same compositions as those planned for the SWPF CSSX system. As in the SWPF CSSX system, the solvent and scrub flow rates are equal. The system is

  13. The W's of Web Design.

    ERIC Educational Resources Information Center

    Finnegan, John; Griffin, Jeffrey A.

    2000-01-01

    Focuses on the pre-design questions that a Web site designer and client need to address. Discusses the why, who, what, where, and when phases of the Web site design process. Includes a Web Site Development Form to guide site designs through the first two stages of Web site development: specification and design. (AEF)

  14. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Tuba City, Arizona: Phase 2, Construction, Subcontract documents: Appendix E, final report. [Uranium Mill Tailings Remedial Action (UMTRA) Project

    SciTech Connect

    Not Available

    1989-08-01

    This appendix discusses Phase II construction and subcontract documents uranium mill site near Tuba City, Arizona. It contains the bid schedule, special conditions, specifications, and subcontract drawings.

  15. NeSL-1, an ancient lineage of site-specific non-LTR retrotransposons from Caenorhabditis elegans.

    PubMed Central

    Malik, H S; Eickbush, T H

    2000-01-01

    Phylogenetic analyses of non-LTR retrotransposons suggest that all elements can be divided into 11 lineages. The 3 oldest lineages show target site specificity for unique locations in the genome and encode an endonuclease with an active site similar to certain restriction enzymes. The more "modern" non-LTR lineages possess an apurinic endonuclease-like domain and generally lack site specificity. The genome sequence of Caenorhabditis elegans reveals the presence of a non-LTR retrotransposon that resembles the older elements, in that it contains a single open reading frame with a carboxyl-terminal restriction-like endonuclease domain. Located near the N-terminal end of the ORF is a cysteine protease domain not found in any other non-LTR element. The N2 strain of C. elegans appears to contain only one full-length and several 5' truncated copies of this element. The elements specifically insert in the Spliced leader-1 genes; hence the element has been named NeSL-1 (Nematode Spliced Leader-1). Phylogenetic analysis confirms that NeSL-1 branches very early in the non-LTR lineage and that it represents a 12th lineage of non-LTR elements. The target specificity of NeSL-1 for the spliced leader exons and the similarity of its structure to that of R2 elements leads to a simple model for its expression and retrotransposition. PMID:10628980

  16. A novel electrophoretic technique designed to modify the ratio of magnesium isotopes inside the creatine kinase active sites. A preliminary report.

    PubMed

    Kouznetsov, Dmitri A; Arkhangelsky, Stanislav E; Berdieva, Alana G; Khasigov, Peter Z; Orlova, Marina A

    2004-09-01

    A simple and efficient preparative electrophoretic technique has been proposed to obtain a modified creatine kinase (CK, E.C.2.7.3.2) molecule with an increased content of 25Mg in the active site. A key point of the method is the special design of a 0.9 x 12.0 cm column for ascendent electrophoresis, packed consecutively, from the bottom to the top, with layers of 30 % PAAG (polyacrylamide grade), 25Mg2+ -containing 7.5 % PAAG, enzyme-binding ADP Sepharose and 2.2 % agarose gels, based on different tris-glycine and tris-HCl separation buffer systems. The isotope substitution process was a result of simultaneous desorption of enzyme from ADP Sepharose and electrically directed extensive flow of 25Mg2+ cations through the porous gel matrix. Greater than 8-fold 25Mg enrichment, i.e. a 10.2-86.3 % increase of 25Mg contribution to total enzyme magnesium, has been reached. The modified 25Mg-rich CK samples manifest higher (2.4-fold increase) values of specific catalytic activity when compared with intact (control) ones. PMID:15370286

  17. Design and Baseline Findings of a Multi-site Non-randomized Evaluation of the Effect of a Health Programme on Microfinance Clients in India

    PubMed Central

    Saha, Somen

    2014-01-01

    Microfinance is the provision of financial services for the poor. Health program through microfinance has the potential to address several access barriers to health. We report the design and baseline findings of a multi-site non-randomized evaluation of the effect of a health program on the members of two microfinance organizations from Karnataka and Gujarat states of India. Villages identified for roll-out of health services with microfinance were pair-matched with microfinance only villages. A quantitative survey at inception and twelve months post health intervention compare the primary outcome (incidence of childhood diarrhea), and secondary outcome (place of last delivery, toilet at home, and out-of-pocket expenditure on treatment). At baseline, the intervention and comparison communities were similar except for out-of-pocket expenditure on health. Low reported use of toilet at home indicates the areas are heading towards a sanitation crisis. This should be an area of program priority for the microfinance organizations. While respondents primarily rely on their savings for meeting treatment expenditure, borrowing from friends, relatives, and money-lenders remains other important source of meeting treatment expenditure in the community. Programs need to prioritize steps to ensure awareness about national health insurance schemes, entitlement to increase service utilization, and developing additional health financing safety nets for financing outpatient care, that are responsible for majority of health-debt. Finally we discuss implications of such programs for national policy makers. PMID:24373263

  18. Two ScFv antibody libraries derived from identical VL-VH framework with different binding site designs display distinct binding profiles.

    PubMed

    Huovinen, Tuomas; Syrjänpää, Markku; Sanmark, Hanna; Brockmann, Eeva-Christine; Azhayev, Alex; Wang, Qi; Vehniäinen, Markus; Lamminmäki, Urpo

    2013-10-01

    In directed evolution experiments, a single randomization scheme of an antibody gene does not provide optimal diversity for recognition of all sizes of antigens. In this study, we have expanded the recognition potential of our universal library, termed ScFvP, with a second distinct diversification scheme. In the second library, termed ScFvM, diversity was designed closer to the center of the antigen binding site in the same antibody framework as earlier. Also, the CDR-H3 loop structures were redesigned to be shorter, 5-12 aa and mostly without the canonical salt bridge between Arg106H and Asp116H to increase the flexibility of the loop and to allow more space in the center of the paratope for binding smaller targets. Antibodies were selected from the two libraries against various antigens separately and as a mixture. The origin and characteristics of the retrieved antibodies indicate that complementary diversity results in complementary functionality widening the spectrum of targets amenable for selection. PMID:23966567

  19. Design and construction of a silver(I)-loaded cellulose-based wound dressing: trackable and sustained release of silver for controlled therapeutic delivery to wound sites.

    PubMed

    deBoer, T R; Chakraborty, I; Mascharak, P K

    2015-10-01

    Although application of silver nitrate and silver sulfadiazine have been shown to be effective in thwarting infections at burn sites, optimization of the delivery of bioactive silver (Ag(+)) remains as an obstacle due to rapid precipitation and/or insolubility of the silver sources. To circumvent these shortcomings, we have designed a silver(I) complex [Ag(ImD)2]ClO4 (ImD = dansyl imidazole) that effectively increases the bioavailability of Ag(+) and exhibits MIC values of 2.3 and 4.7 μg/mL against E. coli and S. aureus, respectively. This fluorescent silver complex has been incorporated within a robust hydrogel derived from carboxymethyl cellulose that allows slow release of silver. A complete occlusive dressing has finally been constructed with the Ag(ImD)CMC (1% Ag loaded) pad sealed between a sterile mesh gauze (as bottom layer) and a rayon-based surgical tape (as the top layer). Such construction has afforded a dressing that displays sustained delivery of silver onto a skin and soft tissue infection model and causes effective eradication of bacterial loads within 24 h. The transfer of the bioactive silver complex is readily visualized by the observed fluorescence that overlays precisely with the kill zone. The latter feature introduces a unique feature of therapeutic trackability to this silver-donating occlusive dressing. PMID:26411439

  20. Numerical study on criteria for design and operation of water curtain system in underground oil storage cavern using site descriptive fracture networks

    NASA Astrophysics Data System (ADS)

    Moon, Jiwon; Yeo, In Wook

    2013-04-01

    Underground unlined caverns have been constructed in fractured rocks to stockpile oil and petroleum products, where they are hydraulically contained by natural groundwater pressure. However, for the case that natural groundwater pressure is not maintained at the required level, water curtain boreholes, through which water is injected, are often constructed above the cavern as engineering barrier to secure water pressure enough to overwhelm the operational pressure of the cavern. For secure containment of oil and petroleum products inside the cavern, it is essential to keep water pressure around the cavern higher than operational pressure of the cavern using either natural groundwater pressure or engineering barrier. In the Republic of Korea, a number of underground stockpile bases are being operated by Korea National Oil Corporation (KNOC) and private companies, most of which have water curtain system. The criterion that KNOC adopts for water curtain system design and operation such as the vertical distance from the cavern and operational injection rate is based on the Åberg hypothesis that the vertical hydraulic gradient should be larger than one. The criterion has been used for maintaining oil storage cavern without its thorough review. In this study, systematic numerical works have been done for reviewing the Åberg criterion. As groundwater predominantly takes places through fractures in underground caverns, discrete fracture modeling approach is essential for this study. Fracture data, obtained from boreholes drilled at the stage of site investigation at the Yeosu stockpile base in Korea, were statistically analyzed in terms of orientation and intensity, which were used to generate the site descriptive three dimensional fracture networks. Then, groundwater flow modeling has been carried out for the fracture networks. Constant head boundaries were applied along the circumference of the cavern and water curtain boreholes. Main flow channel and hydraulic

  1. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Rifle, Colorado. Volume 5, Addenda D6--D8 to Appendix D: Final report

    SciTech Connect

    Not Available

    1990-02-01

    This volume contains appendices D6 through D8 containing laboratory test data: from MK-F investigation, 1987, Old Rifle and New Rifle sites; on bentonite amended radon barrier material; and from MK-F investigation, 1987, riprap tests.

  2. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Gunnison, Colorado: Remedial action selection report. [Uranium Mill Tailings Remedial Action (UMTRA) Project

    SciTech Connect

    Not Available

    1992-10-01

    The Gunnison uranium mill tailings site is just south of the city limits of Gunnison, Colorado, in the south-central part of the state. The entire site covers 61 acres in the valley of the Gunnison River and Tomichi Creek. Contaminated materials at the Gunnison processing site include the tailings pile, covering about 35 acres to an average depth of nine feet and containing 459,000 cubic yards. Ore storage areas and the former mill processing area cover about 20 acres on the south side of the site. The volume of contaminated materials to be disposed of as part of the remedial action is estimated to be 718,900 cubic yards. An interim action was approved by the US Department of Energy to eliminate existing safety hazards to the Gunnison community. These actions, started in September 1991, included demolition of mill buildings and related processing facilities, excavation of two underground storage tanks, removal of asbestos and other hazardous materials from buildings, storage of those materials in a secured area on the site, and improvements of site security.

  3. Remedial Action Plan and Site design for stabilization of the inactive Uranium Mill Tailings sites at Slick Rock, Colorado: Revision 1. Remedial action selection report, Attachment 2, geology report, Attachment 3, ground water hydrology report, Attachment 4, water resources protection strategy. Final

    SciTech Connect

    1995-09-01

    The Slick Rock uranium mill tailings sites are located near the small community of Slick Rock, in San Miguel County, Colorado. There are two designated Uranium Mill Tailings Remedial Action (UMTRA) Project sites at Slick Rock: the Union Carbide site and the North Continent site. Both sites are adjacent to the Dolores River. The sites contain former mill building concrete foundations, tailings piles, demolition debris, and areas contaminated by windblown and waterborne radioactive materials. The total estimated volume of contaminated materials is approximately 621,000 cubic yards (475,000 cubic meters). In addition to the contamination at the two processing site areas, 13 vicinity properties were contaminated. Contamination associated with the UC and NC sites has leached into ground water. Pursuant to the requirements of the Uranium Mill Tailings Radiation Control Act (UMTRCA) (42 USC {section}7901 et seq.), the proposed remedial action plan (RAP) will satisfy the final US Environmental Protection Agency (EPA) standards in 40 CFR Part 192 (60 FR 2854) for cleanup, stabilization, and control of the residual radioactive material (RRM) (tailings and other contaminated materials) at the disposal site at Burro Canyon. The requirements for control of the RRM (Subpart A) will be satisfied by the construction of an engineered disposal cell. The proposed remedial action will consist of relocating the uranium mill tailings, contaminated vicinity property materials, demolition debris, and windblown/weaterborne materials to a permanent repository at the Burro Canyon disposal site. The site is approximately 5 road mi (8 km) northeast of the mill sites on land recently transferred to the DOE by the Bureau of Land Management.

  4. Elongation Factor Tu Prevents Misediting of Gly-tRNA(Gly) Caused by the Design Behind the Chiral Proofreading Site of D-Aminoacyl-tRNA Deacylase

    PubMed Central

    Routh, Satya Brata; Ahmad, Sadeem; Suma, Katta; Kumar, Mantu; Kuncha, Santosh Kumar; Yadav, Kranthikumar; Kruparani, Shobha P; Sankaranarayanan, Rajan

    2016-01-01

    D-aminoacyl-tRNA deacylase (DTD) removes D-amino acids mischarged on tRNAs and is thus implicated in enforcing homochirality in proteins. Previously, we proposed that selective capture of D-aminoacyl-tRNA by DTD’s invariant, cross-subunit Gly-cisPro motif forms the mechanistic basis for its enantioselectivity. We now show, using nuclear magnetic resonance (NMR) spectroscopy-based binding studies followed by biochemical assays with both bacterial and eukaryotic systems, that DTD effectively misedits Gly-tRNAGly. High-resolution crystal structure reveals that the architecture of DTD’s chiral proofreading site is completely porous to achiral glycine. Hence, L-chiral rejection is the only design principle on which DTD functions, unlike other chiral-specific enzymes such as D-amino acid oxidases, which are specific for D-enantiomers. Competition assays with elongation factor thermo unstable (EF-Tu) and DTD demonstrate that EF-Tu precludes Gly-tRNAGly misediting at normal cellular concentrations. However, even slightly higher DTD levels overcome this protection conferred by EF-Tu, thus resulting in significant depletion of Gly-tRNAGly. Our in vitro observations are substantiated by cell-based studies in Escherichia coli that show that overexpression of DTD causes cellular toxicity, which is largely rescued upon glycine supplementation. Furthermore, we provide direct evidence that DTD is an RNA-based catalyst, since it uses only the terminal 2′-OH of tRNA for catalysis without the involvement of protein side chains. The study therefore provides a unique paradigm of enzyme action for substrate selection/specificity by DTD, and thus explains the underlying cause of DTD’s activity on Gly-tRNAGly. It also gives a molecular and functional basis for the necessity and the observed tight regulation of DTD levels, thereby preventing cellular toxicity due to misediting. PMID:27224426

  5. Elongation Factor Tu Prevents Misediting of Gly-tRNA(Gly) Caused by the Design Behind the Chiral Proofreading Site of D-Aminoacyl-tRNA Deacylase.

    PubMed

    Routh, Satya Brata; Pawar, Komal Ishwar; Ahmad, Sadeem; Singh, Swati; Suma, Katta; Kumar, Mantu; Kuncha, Santosh Kumar; Yadav, Kranthikumar; Kruparani, Shobha P; Sankaranarayanan, Rajan

    2016-05-01

    D-aminoacyl-tRNA deacylase (DTD) removes D-amino acids mischarged on tRNAs and is thus implicated in enforcing homochirality in proteins. Previously, we proposed that selective capture of D-aminoacyl-tRNA by DTD's invariant, cross-subunit Gly-cisPro motif forms the mechanistic basis for its enantioselectivity. We now show, using nuclear magnetic resonance (NMR) spectroscopy-based binding studies followed by biochemical assays with both bacterial and eukaryotic systems, that DTD effectively misedits Gly-tRNAGly. High-resolution crystal structure reveals that the architecture of DTD's chiral proofreading site is completely porous to achiral glycine. Hence, L-chiral rejection is the only design principle on which DTD functions, unlike other chiral-specific enzymes such as D-amino acid oxidases, which are specific for D-enantiomers. Competition assays with elongation factor thermo unstable (EF-Tu) and DTD demonstrate that EF-Tu precludes Gly-tRNAGly misediting at normal cellular concentrations. However, even slightly higher DTD levels overcome this protection conferred by EF-Tu, thus resulting in significant depletion of Gly-tRNAGly. Our in vitro observations are substantiated by cell-based studies in Escherichia coli that show that overexpression of DTD causes cellular toxicity, which is largely rescued upon glycine supplementation. Furthermore, we provide direct evidence that DTD is an RNA-based catalyst, since it uses only the terminal 2'-OH of tRNA for catalysis without the involvement of protein side chains. The study therefore provides a unique paradigm of enzyme action for substrate selection/specificity by DTD, and thus explains the underlying cause of DTD's activity on Gly-tRNAGly. It also gives a molecular and functional basis for the necessity and the observed tight regulation of DTD levels, thereby preventing cellular toxicity due to misediting. PMID:27224426

  6. Experimental design for the formulation and optimization of novel cross-linked oilispheres developed for in vitro site-specific release of Mentha piperita oil.

    PubMed

    Sibanda, Wilbert; Pillay, Viness; Danckwerts, Michael P; Viljoen, Alvaro M; van Vuuren, Sandy; Khan, Riaz A

    2004-03-12

    A Plackett-Burman design was employed to develop and optimize a novel crosslinked calcium-aluminum-alginate-pectinate oilisphere complex as a potential system for the in vitro site-specific release of Mentha piperita, an essential oil used for the treatment of irritable bowel syndrome. The physicochemical and textural properties (dependent variables) of this complex were found to be highly sensitive to changes in the concentration of the polymers (0%-1.5% wt/vol), crosslinkers (0%-4% wt/vol), and crosslinking reaction times (0.5-6 hours) (independent variables). Particle size analysis indicated both unimodal and bimodal populations with the highest frequency of 2 mm oilispheres. Oil encapsulation ranged from 6 to 35 mg/100 mg oilispheres. Gravimetric changes of the crosslinked matrix indicated significant ion sequestration and loss in an exponential manner, while matrix erosion followed Higuchi's cube root law. Among the various measured responses, the total fracture energy was the most suitable optimization objective (R2 = 0.88, Durbin-Watson Index = 1.21%, Coefficient of Variation (CV) = 33.21%). The Lagrangian technique produced no significant differences (P > .05) between the experimental and predicted total fracture energy values (0.0150 vs 0.0107 J). Artificial Neural Networks, as an alternative predictive tool of the total fracture energy, was highly accurate (final mean square error of optimal network epoch approximately 0.02). Fused-coated optimized oilispheres produced a 4-hour lag phase followed by zero-order kinetics (n > 0.99), whereby analysis of release data indicated that diffusion (Fickian constant k1 = 0.74 vs relaxation constant k2 = 0.02) was the predominant release mechanism. PMID:15198539

  7. Remedial action plan and site design for stabilization of the inactive Uranium Mill Tailing site Maybell, Colorado. Attachment 3, ground water hydrology report, Attachment 4, water resources protection strategy. Final report

    SciTech Connect

    Not Available

    1994-06-01

    The U.S. Environmental Protection Agency (EPA) has established health and environmental regulations to correct and prevent ground water contamination resulting from former uranium processing activities at inactive uranium processing sites (40 CFR Part 192 (1993)) (52 FR 36000 (1978)). According to the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 1978 (42 USC {section} 7901 et seq.), the U.S. Department of Energy (DOE) is responsible for assessing the inactive uranium processing sites. The DOE has decided that each assessment will include information on hydrogeologic site characterization. The water resources protection strategy that describes the proposed action compliance with the EPA ground water protection standards is presented in Attachment 4, Water Resources Protection Strategy. Site characterization activities discussed in this section include the following: (1) Definition of the hydrogeologic characteristics of the environment, including hydrostratigraphy, aquifer parameters, areas of aquifer recharge and discharge, potentiometric surfaces, and ground water velocities. (2) Definition of background ground water quality and comparison with proposed EPA ground water protection standards. (3) Evaluation of the physical and chemical characteristics of the contaminant source and/or residual radioactive materials. (4) Definition of existing ground water contamination by comparison with the EPA ground water protection standards. (5) Description of the geochemical processes that affect the migration of the source contaminants at the processing site. (6) Description of water resource use, including availability, current and future use and value, and alternate water supplies.

  8. Ground water protection strategy for the Uranium Mill Tailings Site at Green River, Utah. Final, Revision 2, Version 5: Appendix E to the remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Green River, Utah

    SciTech Connect

    1995-09-01

    The purpose of this appendix is to provide a ground water protection strategy for the Uranium Mill Tailings Remedial Action (UMTRA) Project disposal site at Green River, Utah. Compliance with the US Environmental Protection Agency (EPA) ground water protection standards will be achieved by applying supplemental standards (40 CFR {section} 192.22(a); 60 FR 2854) based on the limited use ground water present in the uppermost aquifer that is associated with widespread natural ambient contamination (40 CFR {section} 192.11(e); 60 FR 2854). The strategy is based on new information, including ground water quality data collected after remedial action was completed, and on a revised assessment of disposal cell design features, surface conditions, and site hydrogeology. The strategy will result in compliance with Subparts A and C of the EPA final ground water protection standards (60 FR 2854). The document contains sufficient information to support the proposed ground water protection strategy, with monitor well information and ground water quality data included as a supplement. Additional information is available in the final remedial action plan (RAP) (DOE, 1991a), the final completion report (DOE, 1991b), and the long-term surveillance plan (LTSP) (DOE, 1994a).

  9. Commercial Web Site Links.

    ERIC Educational Resources Information Center

    Thelwall, Mike

    2001-01-01

    Discusses business use of the Web and related search engine design issues as well as research on general and academic links before reporting on a survey of the links published by a collection of business Web sites. Results indicate around 66% of Web sites do carry external links, most of which are targeted at a specific purpose, but about 17%…

  10. Directed modification of the Aspergillus usamii β-mannanase to improve its substrate affinity by in silico design and site-directed mutagenesis.

    PubMed

    Li, Jianfang; Wei, Xihuan; Tang, Cunduo; Wang, Junqing; Zhao, Mei; Pang, Qingfeng; Wu, Minchen

    2014-04-01

    β-Mannanases (EC 3.2.1.78) can catalyze the cleavage of internal β-1,4-D-mannosidic linkages of mannan backbones, and they have found applications in food, feed, pulp and paper, oil, pharmaceutical and textile industries. Suitable amino acid substitution can promote access to the substrate-binding groove and maintain the substrate therein, which probably improves the substrate affinity and, thus, increases catalytic efficiency of the enzyme. In this study, to improve the substrate affinity of AuMan5A, a glycoside hydrolase (GH) family 5 β-mannanase from Aspergillus usamii, had its directed modification conducted by in silico design, and followed by site-directed mutagenesis. The mutant genes, Auman5A (Y111F) and Auman5A (Y115F), were constructed by megaprimer PCR, respectively. Then, Auman5A and its mutant genes were expressed in Pichia pastoris GS115 successfully. The specific activities of purified recombinant β-mannanases (reAuMan5A, reAuMan5A(Y111F) and reAuMan5A(Y115F)) towards locust bean gum were 152.5, 199.6 and 218.9 U mg(-1), respectively. The two mutants were found to be similar to reAuMan5A regarding temperature and pH characteristics. Nevertheless, the K m values of reAuMan5A(Y111F) and reAuMan5A(Y115F), towards guar gum, decreased to 2.95 ± 0.22 and 2.39 ± 0.33 mg ml(-1) from 4.49 ± 0.07 mg ml(-1) of reAuMan5A, which would make reAuMan5A(Y111F) and reAuMan5A(Y115F) promising candidates for industrial processes. Structural analysis showed that the two mutants increased their affinity by decreasing the steric conflicts with those more complicated substrates. The results suggested that subtle conformational modification in the substrate-binding groove could substantially alter the substrate affinity of AuMan5A. This study laid a solid foundation for the directed modification of substrate affinities of β-mannanases and other enzymes. PMID:24493565

  11. Microchannel Reactor System Design & Demonstration For On-Site H2O2 Production by Controlled H2/O2 Reaction

    SciTech Connect

    Adeniyi Lawal

    2008-12-09

    We successfully demonstrated an innovative hydrogen peroxide (H2O2) production concept which involved the development of flame- and explosion-resistant microchannel reactor system for energy efficient, cost-saving, on-site H2O2 production. We designed, fabricated, evaluated, and optimized a laboratory-scale microchannel reactor system for controlled direct combination of H2 and O2 in all proportions including explosive regime, at a low pressure and a low temperature to produce about 1.5 wt% H2O2 as proposed. In the second phase of the program, as a prelude to full-scale commercialization, we demonstrated our H2O2 production approach by ‘numbering up’ the channels in a multi-channel microreactor-based pilot plant to produce 1 kg/h of H2O2 at 1.5 wt% as demanded by end-users of the developed technology. To our knowledge, we are the first group to accomplish this significant milestone. We identified the reaction pathways that comprise the process, and implemented rigorous mechanistic kinetic studies to obtain the kinetics of the three main dominant reactions. We are not aware of any such comprehensive kinetic studies for the direct combination process, either in a microreactor or any other reactor system. We showed that the mass transfer parameter in our microreactor system is several orders of magnitude higher than what obtains in the macroreactor, attesting to the superior performance of microreactor. A one-dimensional reactor model incorporating the kinetics information enabled us to clarify certain important aspects of the chemistry of the direct combination process as detailed in section 5 of this report. Also, through mathematical modeling and simulation using sophisticated and robust commercial software packages, we were able to elucidate the hydrodynamics of the complex multiphase flows that take place in the microchannel. In conjunction with the kinetics information, we were able to validate the experimental data. If fully implemented across the whole

  12. Making It Work for Everyone: HTML5 and CSS Level 3 for Responsive, Accessible Design on Your Library's Web Site

    ERIC Educational Resources Information Center

    Baker, Stewart C.

    2014-01-01

    This article argues that accessibility and universality are essential to good Web design. A brief review of library science literature sets the issue of Web accessibility in context. The bulk of the article explains the design philosophies of progressive enhancement and responsive Web design, and summarizes recent updates to WCAG 2.0, HTML5, CSS…

  13. Site Development Planning Handbook

    SciTech Connect

    1981-01-01

    The Handbook provides facility managers and site planners at DOE organizations responsible for planning site developments and facilities utilization a step-by-step planning checklist to ensure that planners at each site are focusing on Department-wide goals and objectives. It begins with a brief discussion of a site development-by-objectives program design to promote, recognize, and implement opportunities for improvements in site utilization through planning. Additional information is included on: assembling existing data, plans, programs, and procedures; establishing realistic objectives; identifying site problems, opportunities; and development needs; determining priorities among development needs; developing short and long-range plans; choosing the right development solutions and meeting minimum legal site restrictions; presenting the plan; implementing elements of the plan; monitoring and reporting plan status; and modifying development program plans. (MCW)

  14. Site-directed mutagenesis of the human DNA repair enzyme HAP1: identification of residues important for AP endonuclease and RNase H activity.

    PubMed

    Barzilay, G; Walker, L J; Robson, C N; Hickson, I D

    1995-05-11

    HAP1 protein, the major apurinic/apyrimidinic (AP) endonuclease in human cells, is a member of a homologous family of multifunctional DNA repair enzymes including the Escherichia coli exonuclease III and Drosophila Rrp1 proteins. The most extensively characterised member of this family, exonuclease III, exhibits both DNA- and RNA-specific nuclease activities. Here, we show that the RNase H activity characteristic of exonuclease III has been conserved in the human homologue, although the products resulting from RNA cleavage are dissimilar. To identify residues important for enzymatic activity, five mutant HAP1 proteins containing single amino acid substitutions were purified and analysed in vitro. The substitutions were made at sites of conserved amino acids and targeted either acidic or histidine residues because of their known participation in the active sites of hydrolytic nucleases. One of the mutant proteins (replacement of Asp-219 by alanine) showed a markedly reduced enzymatic activity, consistent with a greatly diminished capacity to bind DNA and RNA. In contrast, replacement of Asp-90, Asp-308 or Glu-96 by alanine led to a reduction in enzymatic activity without significantly compromising nucleic acid binding. Replacement of His-255 by alanine led to only a very small reduction in enzymatic activity. Our data are consistent with the presence of a single catalytic active site for the DNA- and RNA-specific nuclease activities of the HAP1 protein. PMID:7784208

  15. Lessons Learned from the 200 West Pump and Treatment Facility Construction Project at the US DOE Hanford Site - A Leadership for Energy and Environmental Design (LEED) Gold-Certified Facility

    SciTech Connect

    Dorr, Kent A.; Ostrom, Michael J.; Freeman-Pollard, Jhivaun R.

    2013-01-11

    CH2M Hill Plateau Remediation Company (CHPRC) designed, constructed, commissioned, and began operation of the largest groundwater pump and treatment facility in the U.S. Department of Energy’s (DOE) nationwide complex. This one-of-a-kind groundwater pump and treatment facility, located at the Hanford Nuclear Reservation Site (Hanford Site) in Washington State, was built to an accelerated schedule with American Recovery and Reinvestment Act (ARRA) funds. There were many contractual, technical, configuration management, quality, safety, and Leadership in Energy and Environmental Design (LEED) challenges associated with the design, procurement, construction, and commissioning of this $95 million, 52,000 ft groundwater pump and treatment facility to meet DOE’s mission objective of treating contaminated groundwater at the Hanford Site with a new facility by June 28, 2012. The project team’s successful integration of the project’s core values and green energy technology throughout design, procurement, construction, and start-up of this complex, first-of-its-kind Bio Process facility resulted in successful achievement of DOE’s mission objective, as well as attainment of LEED GOLD certification, which makes this Bio Process facility the first non-administrative building in the DOE Office of Environmental Management complex to earn such an award.

  16. Lessons Learned From The 200 West Pump And Treatment Facility Construction Project At The US DOE Hanford Site - A Leadership For Energy And Environmental Design (LEED) Gold-Certified Facility

    SciTech Connect

    Dorr, Kent A.; Ostrom, Michael J.; Freeman-Pollard, Jhivaun R.

    2012-11-14

    CH2M Hill Plateau Remediation Company (CHPRC) designed, constructed, commissioned, and began operation of the largest groundwater pump and treatment facility in the U.S. Department of Energy's (DOE) nationwide complex. This one-of-a-kind groundwater pump and treatment facility, located at the Hanford Nuclear Reservation Site (Hanford Site) in Washington State, was built in an accelerated manner with American Recovery and Reinvestment Act (ARRA) funds and has attained Leadership in Energy and Environmental Design (LEED) GOLD certification, which makes it the first non-administrative building in the DOE Office of Environmental Management complex to earn such an award. There were many contractual, technical, configuration management, quality, safety, and LEED challenges associated with the design, procurement, construction, and commissioning of this $95 million, 52,000 ft groundwater pump and treatment facility. This paper will present the Project and LEED accomplishments, as well as Lessons Learned by CHPRC when additional ARRA funds were used to accelerate design, procurement, construction, and commissioning of the 200 West Groundwater Pump and Treatment (2W P&T) Facility to meet DOE's mission of treating contaminated groundwater at the Hanford Site with a new facility by June 28, 2012.

  17. Lessons Learned from the 200 West Pump and Treatment Facility Construction Project at the US DOE Hanford Site - A Leadership for Energy and Environmental Design (LEED) Gold-Certified Facility - 13113

    SciTech Connect

    Dorr, Kent A.; Freeman-Pollard, Jhivaun R.; Ostrom, Michael J.

    2013-07-01

    CH2M Hill Plateau Remediation Company (CHPRC) designed, constructed, commissioned, and began operation of the largest groundwater pump and treatment facility in the U.S. Department of Energy's (DOE) nationwide complex. This one-of-a-kind groundwater pump and treatment facility, located at the Hanford Nuclear Reservation Site (Hanford Site) in Washington State, was built to an accelerated schedule with American Recovery and Reinvestment Act (ARRA) funds. There were many contractual, technical, configuration management, quality, safety, and Leadership in Energy and Environmental Design (LEED) challenges associated with the design, procurement, construction, and commissioning of this $95 million, 52,000 ft groundwater pump and treatment facility to meet DOE's mission objective of treating contaminated groundwater at the Hanford Site with a new facility by June 28, 2012. The project team's successful integration of the project's core values and green energy technology throughout design, procurement, construction, and start-up of this complex, first-of-its-kind Bio Process facility resulted in successful achievement of DOE's mission objective, as well as attainment of LEED GOLD certification (Figure 1), which makes this Bio Process facility the first non-administrative building in the DOE Office of Environmental Management complex to earn such an award. (authors)

  18. Radioactive Waste Evaporation: Current Methodologies Employed for the Development, Design, and Operation of Waste Evaporators at the Savannah River Site and Hanford Waste Treatment Plant

    SciTech Connect

    Calloway, T.B.

    2003-09-11

    Evaporation of High level and Low Activity (HLW and LAW) radioactive wastes for the purposes of radionuclide separation and volume reduction has been conducted at the Savannah River and Hanford Sites for more than forty years. Additionally, the Savannah River Site (SRS) has used evaporators in preparing HLW for immobilization into a borosilicate glass matrix. This paper will discuss the methodologies, results, and achievements of the SRTC evaporator development program that was conducted in support of the SRS and Hanford WTP evaporator processes. The cross pollination and application of waste treatment technologies and methods between the Savannah River and Hanford Sites will be highlighted. The cross pollination of technologies and methods is expected to benefit the Department of Energy's Mission Acceleration efforts by reducing the overall cost and time for the development of the baseline waste treatment processes.

  19. Science. [SITE 2002 Section].

    ERIC Educational Resources Information Center

    Roach, Linda Easley, Ed.

    This document contains the following papers on science from the SITE (Society for Information Technology & Teacher Education) 2002 conference: (1) "Color & Light: Design and Evaluation of a Multimedia-Case for Elementary Teacher-Education" (Peter Blijleven and Ellen van den Berg); (2) "Standards-Based Design of Technology-Integrated Science…

  20. Modifications to the Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Green River, Utah. [Uranium Mill Tailings Remedial Action (UMTRA) Project

    SciTech Connect

    Not Available

    1991-10-01

    This modification to the Green River Final Remedial Action Plan (FRAP) represents the changes made to the document in accordance with a joint agreement between the US Department of Energy (DOE) and the US Nuclear Regulatory Commission (NRC) outlined in a letter dated August 7, 1991. As specified in this letter, methylene chloride will no longer be analyzed in groundwater samples collected from on-site monitor wells. All references to methylene chloride sampling have been deleted from the FRAP, as indicated by the pages in Section 2.0 of this document.