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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. Maintenance of DNA and repair of Apurinic sites.

    PubMed

    Verly, W G

    1975-01-01

    Escherichia coli cells contain an enzyme which hydrolyzes a phosphodiester bond near each apurinic site in double-stranded DNA. This endonuclease is specific for apurinic sites; it has no effect on normal DNA, and its action on alkylated DNA is restricted to apurinic sites. In vitro incubation with the endonuclease for apurinic sites, DNA polymerase I, and ligase permits repair of DNA containing apurinic sites. The endonuclease for apurinic sites might thus play a role in cell survival after a treatment with alkylating agents; as DNA spontaneously loses purines, the enzyme might also play a role in the maintance of a normal DNA in every cell. Indeed, an endonuclease for apurinic sites has been found not only in bacteria but also in animal and plant cells; it is very active in thermophilic bacteria.

  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. Excision of apurinic sites from DNA with enzymes isolated from rat-liver chromatin.

    PubMed

    Goffin, C; Verly, W G

    1982-10-01

    Apurinic sites were excised from phi X174 RF DNA with two enzymes isolated from rat liver chromatin: an apurinic/apyrimidinic endodeoxyribonuclease and a 5'-3'-exonuclease; the resulting gap was filled with DNA polymerase beta also prepared from rat liver chromatin and the repair was fully terminated with T4 ligase.

  5. Design of a New Fluorescent Oligonucleotide-Based Assay for a Highly Specific Real-Time Detection of Apurinic/Apyrimidinic Site Cleavage by Tyrosyl-DNA Phosphodiesterase 1.

    PubMed

    Lebedeva, Natalia A; Anarbaev, Rashid O; Kupryushkin, Maxim S; Rechkunova, Nadejda I; Pyshnyi, Dmitrii V; Stetsenko, Dmitry A; Lavrik, Olga I

    2015-10-21

    Tyrosyl-DNA phosphodiesterase 1 (Tdp1) promotes catalytic scission of a phosphodiester bond between the 3'-end of DNA and the hydroxyl group of a tyrosine residue, as well as cleaving off a variety of other 3'-terminal phosphate-linked DNA substituents. We have shown recently that Tdp1 can initiate an apurinic/apyrimidinic (AP) site repair pathway that is independent from the one mediated by AP endonuclease 1 (APE1). Until recently, there was no method available of tracking the AP-site cleaving activity of Tdp1 by real-time fluorescence assay. In the present study we demonstrate a highly specific real-time detection of the AP-site cleaving activity of Tdp1 which allows one to distinguish it from the activity of APE1 by using a short hairpin oligonucleotide with a 1,12-dodecanediol loop, a 5'-fluorophore, and a 3'-quencher. Specific phosphodiesterase activity of Tdp1, which is usually able to remove quencher from the 3'-end of DNA, was suppressed in our approach by introducing a noncleavable phosphate group mimic between the 3'-end and the quencher. As a nondigestible 3'-phosphate analogue, we have used a new uncharged tetramethyl phosphoryl guanidine (Tmg) group, which is resistant to 3'-phosphodiesterase cleavage.

  6. Relating aromatic hydrocarbon-induced DNA adducts and c-H-ras mutations in mouse skin papillomas: the role of apurinic sites.

    PubMed Central

    Chakravarti, D; Pelling, J C; Cavalieri, E L; Rogan, E G

    1995-01-01

    Mouse skin tumors contain activated c-H-ras oncogenes, often caused by point mutations at codons 12 and 13 in exon 1 and codons 59 and 61 in exon 2. Mutagenesis by the noncoding apurinic sites can produce G-->T and A-->T transversions by DNA misreplication with more frequent insertion of deoxyadenosine opposite the apurinic site. Papillomas were induced in mouse skin by several aromatic hydrocarbons, and mutations in the c-H-ras gene were determined to elucidate the relationship among DNA adducts, apurinic sites, and ras oncogene mutations. Dibenzo[a,l]pyrene (DB[a,l]P), DB[a,l]P-11,12-dihydrodiol, anti-DB[a,l]P-11,12-diol-13,14-epoxide, DB[a,l]P-8,9-dihydrodiol, 7,12-dimethylbenz[a]anthracene (DMBA), and 1,2,3,4-tetrahydro-DMBA consistently induced a CAA-->CTA mutation in codon 61 of the c-H-ras oncogene. Benzo[a]pyrene induced a GGC-->GTC mutation in codon 13 in 54% of tumors and a CAA-->CTA mutation in codon 61 in 15%. The pattern of mutations induced by each hydrocarbon correlated with its profile of DNA adducts. For example, both DB[a,l]P and DMBA primarily form DNA adducts at the N-3 and/or N-7 of deoxyadenosine that are lost from the DNA by depurination, generating apurinic sites. Thus, these results support the hypothesis that misreplication of unrepaired apurinic sites generated by loss of hydrocarbon-DNA adducts is responsible for transforming mutations leading to papillomas in mouse skin. PMID:7479797

  7. Transient-state kinetics of apurinic/apyrimidinic (AP) endonuclease 1 acting on an authentic AP site and commonly used substrate analogs: the effect of diverse metal ions and base mismatches.

    PubMed

    Schermerhorn, Kelly M; Delaney, Sarah

    2013-10-29

    Apurinic/apyrimidinic endonuclease 1 (APE1) is an Mg²⁺-dependent enzyme responsible for incising the DNA backbone 5' to an apurinic/apyrimidinic (AP) site. Here, we use rapid quench flow (RQF) techniques to provide a comprehensive kinetic analysis of the strand-incision activity (k(chemistry)) of APE1 acting on an authentic AP site along with two widely used analogs, a reduced AP site and a tetrahydrofuran (THF) site. In the presence of biologically relevant Mg²⁺, APE1 incises all three substrates at a rate faster than the resolution of the RQF, ≥700 s⁻¹. To obtain quantitative values of k(chemistry) and to facilitate a comparison of the authentic substrate versus the substrate analogs, we replaced Mg²⁺ with Mn²⁺ or Ni²⁺ or introduced a mismatch 5' to the lesion site. Both strategies were sufficient to slow k(chemistry) and resulted in rates within the resolution of the RQF. In all cases where quantitative rates were obtained, k(chemistry) for the reduced AP site is indistinguishable from the authentic AP site. Notably, there is a small decrease, ~1.5-fold, in k(chemistry) for the THF site relative to the authentic AP site. These results highlight a role in strand incision for the C1' oxygen of the AP site and warrant consideration when designing experiments using substrate analogs.

  8. High-resolution crystal structures reveal plasticity in the metal binding site of apurinic/apyrimidinic endonuclease I.

    PubMed

    He, Hongzhen; Chen, Qiujia; Georgiadis, Millie M

    2014-10-21

    Apurinic/apyrimidinic endonuclease I (APE1) is an essential base excision repair enzyme that catalyzes a Mg²⁺-dependent reaction in which the phosphodiester backbone is cleaved 5' of an abasic site in duplex DNA. This reaction has been proposed to involve either one or two metal ions bound to the active site. In the present study, we report crystal structures of Mg²⁺, Mn²⁺, and apo-APE1 determined at 1.4, 2.2, and 1.65 Å, respectively, representing two of the highest resolution structures yet reported for APE1. In our structures, a single well-ordered Mn²⁺ ion was observed coordinated by D70 and E96; the Mg²⁺ site exhibited disorder modeled as two closely positioned sites coordinated by D70 and E96 or E96 alone. Direct metal binding analysis of wild-type, D70A, and E96A APE1, as assessed by differential scanning fluorimetry, indicated a role for D70 and E96 in binding of Mg²⁺ or Mn²⁺ to APE1. Consistent with the disorder exhibited by Mg²⁺ bound to the active site, two different conformations of E96 were observed coordinated to Mg²⁺. A third conformation for E96 in the apo structure is similar to that observed in the APE1-DNA-Mg²⁺ complex structure. Thus, binding of Mg²⁺ in three different positions within the active site of APE1 in these crystal structures corresponds directly with three different conformations of E96. Taken together, our results are consistent with the initial capture of metal by D70 and E96 and repositioning of Mg²⁺ facilitated by the structural plasticity of E96 in the active site.

  9. Interaction of Nucleotide Excision Repair Protein XPC-RAD23B with DNA Containing Benzo[a]pyrene-Derived Adduct and Apurinic/Apyrimidinic Site within a Cluster.

    PubMed

    Starostenko, L V; Maltseva, E A; Lebedeva, N A; Pestryakov, P E; Lavrik, O I; Rechkunova, N I

    2016-03-01

    The combined action of reactive metabolites of benzo[a]pyrene (B[a]P) and oxidative stress can lead to cluster-type DNA damage that includes both a bulky lesion and an apurinic/apyrimidinic (AP) site, which are repaired by the nucleotide and base excision repair mechanisms - NER and BER, respectively. Interaction of NER protein XPC-RAD23B providing primary damage recognition with DNA duplexes containing a B[a]P-derived residue linked to the exocyclic amino group of a guanine (BPDE-N(2)-dG) in the central position of one strand and AP site in different positions of the other strand was analyzed. It was found that XPC-RAD23B crosslinks to DNA containing (+)-trans-BPDE-N(2)-dG more effectively than to DNA containing cis-isomer, independently of the AP site position in the opposite strand; protein affinity to DNA containing one of the BPDE-N(2)-dG isomers depends on the AP site position in the opposite strand. The influence of XPC-RAD23B on hydrolysis of an AP site clustered with BPDE-N(2)-dG catalyzed by the apurinic/apyrimidinic endonuclease 1 (APE1) was examined. XPC-RAD23B was shown to stimulate the endonuclease and inhibit the 3'-5' exonuclease activity of APE1. These data demonstrate the possibility of cooperation of two proteins belonging to different DNA repair systems in the repair of cluster-type DNA damage.

  10. Human Apurinic/Apyrimidinic Endonuclease (APE1) Is Acetylated at DNA Damage Sites in Chromatin, and Acetylation Modulates Its DNA Repair Activity

    PubMed Central

    Roychoudhury, Shrabasti; Nath, Somsubhra; Song, Heyu; Hegde, Muralidhar L.; Bellot, Larry J.; Mantha, Anil K.; Sengupta, Shiladitya; Ray, Sutapa; Natarajan, Amarnath

    2016-01-01

    ABSTRACT Apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in the genome, inhibit transcription and block replication. The primary enzyme that repairs AP sites in mammalian cells is the AP endonuclease (APE1), which functions through the base excision repair (BER) pathway. Although the mechanism by which APE1 repairs AP sites in vitro has been extensively investigated, it is largely unknown how APE1 repairs AP sites in cells. Here, we show that APE1 is acetylated (AcAPE1) after binding to the AP sites in chromatin and that AcAPE1 is exclusively present on chromatin throughout the cell cycle. Positive charges of acetylable lysine residues in the N-terminal domain of APE1 are essential for chromatin association. Acetylation-mediated neutralization of the positive charges of the lysine residues in the N-terminal domain of APE1 induces a conformational change; this in turn enhances the AP endonuclease activity of APE1. In the absence of APE1 acetylation, cells accumulated AP sites in the genome and showed higher sensitivity to DNA-damaging agents. Thus, mammalian cells, unlike Saccharomyces cerevisiae or Escherichia coli cells, require acetylation of APE1 for the efficient repair of AP sites and base damage in the genome. Our study reveals that APE1 acetylation is an integral part of the BER pathway for maintaining genomic integrity. PMID:27994014

  11. Apurinic/apyrimidinic (AP) site recognition by the 5'-dRP/AP lyase in poly(ADP-ribose) polymerase-1 (PARP-1).

    PubMed

    Khodyreva, S N; Prasad, R; Ilina, E S; Sukhanova, M V; Kutuzov, M M; Liu, Y; Hou, E W; Wilson, S H; Lavrik, O I

    2010-12-21

    The capacity of human poly(ADP-ribose) polymerase-1 (PARP-1) to interact with intact apurinic/apyrimidinic (AP) sites in DNA has been demonstrated. In cell extracts, sodium borohydride reduction of the PARP-1/AP site DNA complex resulted in covalent cross-linking of PARP-1 to DNA; the identity of cross-linked PARP-1 was confirmed by mass spectrometry. Using purified human PARP-1, the specificity of PARP-1 binding to AP site-containing DNA was confirmed in competition binding experiments. PARP-1 was only weakly activated to conduct poly(ADP-ribose) synthesis upon binding to AP site-containing DNA, but was strongly activated for poly(ADP-ribose) synthesis upon strand incision by AP endonuclease 1 (APE1). By virtue of its binding to AP sites, PARP-1 could be poised for its role in base excision repair, pending DNA strand incision by APE1 or the 5'-dRP/AP lyase activity in PARP-1.

  12. 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

  13. Efficacy of puffer fish (Takifugu rubripes) sauce in reducing hydroxyl radical damage to DNA assessed using the apurinic/apyrimidinic site method.

    PubMed

    Harada, Kazuki; Makino, Yoshio; Yamauchi, Tomio; Fukuda, Nami; Tamaru, Miki; Okubo, Yasue; Maeda, Toshimichi; Fukuda, Yutaka; Shiba, Tsuneo

    2007-09-01

    Apurinic/apyrimidinic (AP) sites are frequently observed DNA lesions when cells are exposed to hydroxyl radicals. We developed a new method for measurement of the antioxidative activity of foods using the occurrence frequency of AP sites on DNA. Combined with the electron spin resonance (ESR) method as a standard method, we examined whether fish and soy sauces including puffer fish [Takifugu rubripes (Temminck et Schlegel)] sauce could protect DNA from damage caused by hydroxyl radicals. The results showed that the ratios of DNA protection by puffer fish sauce, salmon fish sauce, sandfish fish sauce (Shottsuru), colorless soy sauce, squid fish sauce (Ishiru), dark color soy sauce and light color soy sauce were 68.9, 67.0, 60.1, 49.7, 34.1, 28.2 and -4.4%, respectively. Puffer, salmon, and sandfish fish sauces showed high ratios of DNA protection against hydroxyl radicals. On the other hand, IC(50) values of hydroxyl radical scavenging of the puffer, salmon, sandfish, squid fish sauces and colorless, dark and light color soy sauces were 0.20, 0.09, 4.16, 0.26% and 0.28, 0.14 and 0.18%, respectively. Though the puffer fish sauce exhibited the highest level of DNA protection among the examined samples and a high hydroxyl radical scavenging capability, a correlation between the radical scavenging capability and DNA protection against hydroxyl radicals among the examined fish and soy sauces was not found.

  14. Quantitation of DNA and hemoglobin adducts and apurinic/apyrimidinic sites in tissues of F344 rats exposed to propylene oxide by inhalation.

    PubMed

    Ríos-Blanco, M N; Faller, T H; Nakamura, J; Kessler, W; Kreuzer, P E; Ranasinghe, A; Filser, J G; Swenberg, J A

    2000-11-01

    Propylene oxide (PO) is a relatively weak mutagen that induces nasal tumor formation in rats during long-term inhalation studies at high exposures (> or =300 p.p.m.), concentrations that also cause cytotoxicity and increases in cell proliferation. Direct alkylation of DNA by PO leads mainly to the formation of N:7-(2-hydroxypropyl)guanine (7-HPG). In this study, the accumulation of 7-HPG in tissues of male F344 rats exposed to 500 p. p.m. PO (6 h/day, 5 days/week for 4 weeks) by the inhalation route was measured by gas chromatography-high resolution mass spectrometry (GC-HRMS). In animals killed up to 7 h following the end of the last exposure the levels of 7-HPG (pmol/micromol guanine) in nasal respiratory tissue, nasal olfactory tissue, lung, spleen, liver and testis DNA were 606.2 +/- 53.0, 297.5 +/- 56.5, 69.8 +/- 3.8, 43.0 +/- 3.8, 27.5 +/- 2.4 and 14.2 +/- 0.7, respectively. The amounts of 7-HPG in the same tissues of animals killed 3 days after cessation of exposure were 393.3 +/- 57.0, 222.7 +/- 29.5, 51.5 +/- 1.2, 26.7 +/- 1.0, 18.0 +/- 2.6 and 10.4 +/- 0.1. A comparable rate of disappearance of 7-HPG was found among all tissues. DNA from lymphocytes pooled from four rats killed at the end of the last exposure was found to have 39.6 pmol adduct/micromol guanine. Quantitation of DNA apurinic/apyrimidinic sites, potentially formed after adduct loss by chemical depurination or DNA repair, showed no difference between tissues from control and exposed rats. The level of N:-(2-hydroxypropyl)valine in hemoglobin of exposed rats was also determined using a modified Edman degradation method followed by GC-HRMS analysis. The value obtained was 90.2 +/- 10.3 pmol/mg globin. These data demonstrate that nasal respiratory tissue, which is the target tissue for carcinogenesis, has a much greater level of alkylation of DNA than non-target tissues.

  15. Effects of ethylene oxide and ethylene inhalation on DNA adducts, apurinic/apyrimidinic sites and expression of base excision DNA repair genes in rat brain, spleen, and liver.

    PubMed

    Rusyn, Ivan; Asakura, Shoji; Li, Yutai; Kosyk, Oksana; Koc, Hasan; Nakamura, Jun; Upton, Patricia B; Swenberg, James A

    2005-09-28

    Ethylene oxide (EO) is an important industrial chemical that is classified as a known human carcinogen (IARC, Group 1). It is also a metabolite of ethylene (ET), a compound that is ubiquitous in the environment and is the most used petrochemical. ET has not produced evidence of cancer in laboratory animals and is "not classifiable as to its carcinogenicity to humans" (IARC, Group 3). The mechanism of carcinogenicity of EO is not well characterized, but is thought to involve the formation of DNA adducts. EO is mutagenic in a variety of in vitro and in vivo systems, whereas ET is not. Apurinic/apyrimidinic sites (AP) that result from chemical or glycosylase-mediated depurination of EO-induced DNA adducts could be an additional mechanism leading to mutations and chromosomal aberrations. This study tested the hypothesis that EO exposure results in the accumulation of AP sites and induces changes in expression of genes for base excision DNA repair (BER). Male Fisher 344 rats were exposed to EO (100 ppm) or ET (40 or 3000 ppm) by inhalation for 1, 3 or 20 days (6h/day, 5 days a week). Animals were sacrificed 2h after exposure for 1, 3 or 20 days as well as 6, 24 and 72 h after a single-day exposure. Experiments were performed with tissues from brain and spleen, target sites for EO-induced carcinogenesis, and liver, a non-target organ. Exposure to EO resulted in time-dependent increases in N7-(2-hydroxyethyl)guanine (7-HEG) in brain, spleen, and liver and N7-(2-hydroxyethyl)valine (7-HEVal) in globin. Ethylene exposure also induced 7-HEG and 7-HEVal, but the numbers of adducts were much lower. No increase in the number of aldehydic DNA lesions, an indicator of AP sites, was detected in any of the tissues between controls and EO-, or ET-exposed animals, regardless of the duration or strength of exposure. EO exposure led to a 3-7-fold decrease in expression of 3-methyladenine-DNA glycosylase (Mpg) in brain and spleen in rats exposed to EO for 1 day. Expression of 8

  16. Physical association of the 2,6-diamino-4-hydroxy-5N-formamidopyrimidine-DNA glycosylase of Escherichia coli and an activity nicking DNA at apurinic/apyrimidinic sites.

    PubMed Central

    O'Connor, T R; Laval, J

    1989-01-01

    The 2,6-diamino-4-hydroxy-5N-formamidopyrimidine (Fapy)-DNA glycosylase of Escherichia coli, which is coded for by the fpg gene, excises purine bases with ring-opened imidazoles. In addition to the DNA glycosylase activity, we report that the Fapy-DNA glycosylase of E. coli has an associated activity, resistant to EDTA, that nicks DNA at apurinic/apyrimidinic (AP) sites. The levels of Fapy-DNA glycosylase and AP-nicking activity were parallel in crude lysates of E. coli HB101 harboring different plasmids constructed from the fpg gene. The fpg gene is different from the xth, nth, and nfo genes of E. coli, whose gene products also cleave DNA at AP sites. The Fapy-DNA glycosylase was purified to electrophoretic homogeneity. During this purification, the Fapy-DNA glycosylase copurified with an AP-nicking activity using chromatographic separations based on ion-exchange, molecular weight exclusion, and hydrophobicity. The cleavage at AP sites by the Fapy-DNA glycosylase left a 5'-phosphomonoester nucleotide at one terminus. In addition, DNA containing reduced AP sites was not nicked by the Fapy-DNA glycosylase. These data suggest that the mechanism of cleavage involved beta elimination. Therefore, this activity of the Fapy-DNA glycosylase nicking DNA at AP sites should be referred to as an AP lyase. The 3' terminus did not prime nick-translation by E. coli DNA polymerase I. However, the 3' terminus becomes a substrate for nick-translation if first allowed to react with calf intestine phosphatase or the E. coli exonuclease III. These data suggest that the repair of the Fapy lesion at least to some extent results in the formation of both 5'- and 3'-phosphomonoester nucleotides and the release of the deoxyribose. Images PMID:2664776

  17. 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

  18. 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.

  19. Site specific synthesis and polymerase bypass of oligonucleotides containing a 6-hydroxy-3,5,6,7-tetrahydro-9H-imidazo[1,2-a]purin-9-one base, an intermediate in the formation of 1,N2-etheno-2'-deoxyguanosine.

    PubMed

    Goodenough, Angela K; Kozekov, Ivan D; Zang, Hong; Choi, Jeong-Yun; Guengerich, F Peter; Harris, Thomas M; Rizzo, Carmelo J

    2005-11-01

    The reaction of DNA with certain bis-electrophiles such as chlorooxirane and chloroacetaldehyde produces etheno adducts. These lesions are highly miscoding, and some of the chemical agents that produce them have been shown to be carcinogenic in laboratory animals and in humans. An intermediate in the formation of 1,N2-ethenoguanine is 6-hydroxy-3,5,6,7-tetrahydro-9H-imidazo[1,2-a]purin-9-one (6-hydroxyethanoguanine), which undergoes conversion to the etheno adduct. The chemical properties and miscoding potential of the hydroxyethano adduct have not been previously studied. A synthesis of the hydroxyethano-adducted nucleoside was developed, and it was site specifically incorporated into oligonucleotides. This adduct had a half-life of between 24 and 48 h at neutral pH and 25 degrees C at the nucleoside and oligonucleotide levels. The miscoding potential of the hydroxyethano adduct was examined by primer extension reactions with the DNA polymerases Dpo4 and pol T7-, and the results were compared to the corresponding etheno-adducted oligonucleotide. Dpo4 preferentially incorporated dATP opposite the hydroxyethano adduct and dGTP opposite the etheno adduct; pol T7- preferentially incorporated dATP opposite the etheno adduct while dGTP and dATP were incorporated opposite the hydroxyethano adduct with nearly equal catalytic efficiencies. Collectively, these results indicate that the hydroxyethano adduct has a sufficient lifetime and miscoding properties to contribute to the mutagenic spectrum of chlorooxirane and related genotoxic species.

  20. 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…

  1. 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…

  2. Publicity through Better Web Site Design.

    ERIC Educational Resources Information Center

    Guenther, Kim

    1999-01-01

    Describes how to design Web sites that will reach the most people possible. Discusses publicity; Web search engine sites; adopting Web development standards; using metatags to effectively index a site; Web site addresses and naming conventions; writing for the Web; mass submissions; subject area knowledge; making Web rings; and additional ideas to…

  3. 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...

  4. 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

  5. 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

  6. Human apurinic/apyrimidinic endonuclease 1 (APE1) has 3' RNA phosphatase and 3' exoribonuclease activities.

    PubMed

    Chohan, Manbir; Mackedenski, Sebastian; Li, Wai-Ming; Lee, Chow H

    2015-01-30

    Apurinic/apyrimidinic endonuclease 1 (APE1) is the predominant mammalian enzyme in DNA base excision repair pathway that cleaves the DNA backbone immediately 5' to abasic sites. In addition to its abasic endonuclease activity, APE1 has 3' phosphatase and 3'-5' exonuclease activities against DNA. We recently identified APE1 as an endoribonuclease that preferentially cleaves at UA, UG, and CA sites in single-stranded regions of RNAs and can regulate c-myc mRNA level and half-life in cells. APE1 can also endonucleolytically cleave abasic single-stranded RNA. Here, we show for the first time that the human APE1 has 3' RNA phosphatase and 3' exoribonuclease activities. Using three distinct RNA substrates, we show that APE1, but not RNase A, can remove the phosphoryl group from the 3' end of RNA decay products. Studies using various site-directed APE1 mutant proteins (H309N, H309S, D283N, N68A, D210N, Y171F, D308A, F266A, and D70A) suggest that the 3' RNA phosphatase activity shares the same active center as its other known nuclease activities. A number of APE1 variants previously identified in the human population, including the most common D148E variant, have greater than 80% reduction in the 3' RNA phosphatase activity. APE1 can remove a ribonucleotide from the 3' overhang of RNA decay product, but its 3'-5' exoribonuclease activity against unstructured poly(A), poly(C), and poly(U) RNAs is relatively weak. This study further underscores the significance of understanding the role of APE1 in RNA metabolism in vivo.

  7. Using Participatory Design to Improve Web Sites

    ERIC Educational Resources Information Center

    Nikolova-Houston, Tatiana

    2005-01-01

    In this article, the author, a doctoral candidate from the School of Information at the University of Texas-Austin, describes the experience gathered from her attempt to redesign her existing Web sites in order to supply online resources for Slavic and Byzantine studies. The use of participatory design, which involves the users in creating the…

  8. 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.

  9. 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...

  10. 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.

  11. 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

  12. 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 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 (Reference 5.5), 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.

  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. Construction of a Full-Atomic Mechanistic Model of Human Apurinic/Apyrimidinic Endonuclease APE1 for Virtual Screening of Novel Inhibitors.

    PubMed

    Khaliullin, I G; Nilov, D K; Shapovalova, I V; Svedas, V K

    2012-04-01

    A full-atomic molecular model of human apurinic/apyrimidinic endonuclease APE1, an important enzyme in the DNA repair system, has been constructed. The research consisted of hybrid quantum mechanics/molecular mechanics modeling of the enzyme-substrate interactions, as well as calculations of the ionization states of the amino acid residues of the active site of the enzyme. The choice of the APE1 mechanism with an Asp210 residue as a proton acceptor was validated by means of a generalization of modeling and experimental data. Interactions were revealed in the active site that are of greatest significance for binding the substrate and potential APE1 inhibitors (potential co-drugs of interest in the chemo- and radiotherapy of oncological diseases).

  15. 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

  16. Cloning and Characterization of a Wheat Homologue of Apurinic/Apyrimidinic Endonuclease Ape1L

    PubMed Central

    Grin, Inga R.; Zharkov, Dmitry O.; Ishenko, Alexander A.; Tudek, Barbara; Bissenbaev, Amangeldy K.; Saparbaev, Murat

    2014-01-01

    Background Apurinic/apyrimidinic (AP) endonucleases are key DNA repair enzymes involved in the base excision repair (BER) pathway. In BER, an AP endonuclease cleaves DNA at AP sites and 3′-blocking moieties generated by DNA glycosylases and/or oxidative damage. A Triticum aestivum cDNA encoding for a putative homologue of ExoIII family AP endonucleases which includes E. coli Xth, human APE1 and Arabidopsis thaliana AtApe1L has been isolated and its protein product purified and characterized. Methodology/Principal Findings We report that the putative wheat AP endonuclease, referred here as TaApe1L, contains AP endonuclease, 3′-repair phosphodiesterase, 3′-phosphatase and 3′→5′ exonuclease activities. Surprisingly, in contrast to bacterial and human AP endonucleases, addition of Mg2+ and Ca2+ (5–10 mM) to the reaction mixture inhibited TaApe1L whereas the presence of Mn2+, Co2+ and Fe2+ cations (0.1–1.0 mM) strongly stimulated all its DNA repair activities. Optimization of the reaction conditions revealed that the wheat enzyme requires low divalent cation concentration (0.1 mM), mildly acidic pH (6–7), low ionic strength (20 mM KCl) and has a temperature optimum at around 20°C. The steady-state kinetic parameters of enzymatic reactions indicate that TaApe1L removes 3′-blocking sugar-phosphate and 3′-phosphate groups with good efficiency (kcat/KM = 630 and 485 μM−1·min−1, respectively) but possesses a very weak AP endonuclease activity as compared to the human homologue, APE1. Conclusions/Significance Taken together, these data establish the DNA substrate specificity of the wheat AP endonuclease and suggest its possible role in the repair of DNA damage generated by endogenous and environmental factors. PMID:24667595

  17. 40 CFR 228.4 - Procedures for designation of sites.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... designation or evaluation studies on a typical site or sites in that area. In such cases, sufficient studies... environmental studies of each site, regions adjacent to the site, and on historical knowledge of the impact of... studies for the evaluation and potential selection of dumping sites will be conducted in accordance...

  18. Synthetic lethal targeting of DNA double strand break repair deficient cells by human apurinic/apyrimidinic endonuclease (APE1) inhibitors

    PubMed Central

    Sultana, Rebeka; McNeill, Daniel R.; Abbotts, Rachel; Mohammed, Mohammed Z.; Zdzienicka, Małgorzata Z.; Qutob, Haitham; Seedhouse, Claire; Laughton, Charles A.; Fischer, Peter M.; Patel, Poulam M.; Wilson, David M.; Madhusudan, Srinivasan

    2013-01-01

    An apurinic/apyrimidinic (AP) site is an obligatory cytotoxic intermediate in DNA Base Excision Repair (BER) that is processed by human AP endonuclease 1 (APE1). APE1 is essential for BER and an emerging drug target in cancer. We have isolated novel small molecule inhibitors of APE1. In the current study we have investigated the ability of APE1 inhibitors to induce synthetic lethality in a panel of DNA double strand break (DSB) repair deficient and proficient cells; a) Chinese hamster (CH) cells: BRCA2 deficient (V-C8), ATM deficient (V-E5), wild type (V79) and BRCA2 revertant (V-C8(Rev1)). b) Human cancer cells: BRCA1 deficient (MDA-MB-436), BRCA1 proficient (MCF-7), BRCA2 deficient (CAPAN-1 and HeLa SilenciX cells), BRCA2 proficient (PANC1 and control SilenciX cells). We also tested synthetic lethality (SL) in CH ovary cells expressing a dominant–negative form of APE1 (E8 cells) using ATM inhibitors and DNA-PKcs inhibitors (DSB inhibitors). APE1 inhibitors are synthetically lethal in BRCA and ATM deficient cells. APE1 inhibition resulted in accumulation of DNA DSBs and G2/M cell cycle arrest. Synthetic lethality was also demonstrated in CH cells expressing a dominant–negative form of APE1 treated with ATM or DNA-PKcs inhibitors. We conclude that APE1 is a promising synthetic lethality target in cancer. PMID:22377908

  19. 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…

  20. Design criteria for stabilization of inactive uranium mill tailings sites

    SciTech Connect

    1984-06-01

    The site-specific Remedial Action Plan (RAP), which includes the Site Conceputal Design (SCD); the Processing Site Characterization Report (PSCR); the Disposal Site Characterization Report (DSCR), (if required); and the project Site Design Criteria (SDC), as a set, have been prepared by the Technical Assistance Contractor (TAC) at the direction of the Department of Energy (DOE), and provide the Remedial Action Contractor (RAC) with sufficient information to complete the remedial action engineering designs. This Site Design Criteria (SDC) provides the basis or guidelines for the RAC to prepare the final design documentation for the Uranium Mill Tailings Remedial Action (UMTRA) Project sites. This document provides a set of operating procedures, formats for drawings, specifications, calculations, schedules and cost estimates, and minimum design constraints.

  1. Brownfields Recommendations for Sustainable Site Design — Green Landscape Plan

    EPA Pesticide Factsheets

    The assessment of conditions contained in this report focuses on site-specific environmental and soil conditions that might affect recommendations related to sustainable landscaping and site design, stormwater management, and stormwater reuse.

  2. Specifications for the Design of the School Site.

    ERIC Educational Resources Information Center

    Brubaker, C. William

    1986-01-01

    The school site design is now seen as part of community planning. Recreational, cultural, social, and educational facilities for adults are included in educational specifications. Three illustrations and two photographs demonstrated attractive school sites. Site area requirements for a new high school in Santa Fe, New Mexico are summarized. (MLF)

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

    PubMed

    Estrada, Javier; Ruiz-Herrero, Teresa; 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/.

  7. 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

  8. OSU TOMF Program Site Selection and Preliminary Concept Design Report

    SciTech Connect

    Spadling, Steve

    2012-05-10

    The purpose of this report is to confirm the programmatic requirements for the new facilities, identify the most appropriate project site, and develop preliminary site and building concepts that successfully address the overall project goals and site issues. These new facilities will be designed to accommodate the staff, drivers and maintenance requirements for the future mixed fleet of passenger vehicles, Transit Style Buses and School Buses.

  9. Designing Search: Effective Search Interfaces for Academic Library Web Sites

    ERIC Educational Resources Information Center

    Teague-Rector, Susan; Ghaphery, Jimmy

    2008-01-01

    Academic libraries customize, support, and provide access to myriad information systems, each with complex graphical user interfaces. The number of possible information entry points on an academic library Web site is both daunting to the end-user and consistently challenging to library Web site designers. Faced with the challenges inherent in…

  10. 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...

  11. 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.

  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. A design method for an intuitive web site

    SciTech Connect

    Quinniey, M.L.; Diegert, K.V.; Baca, B.G.; Forsythe, J.C.; Grose, E.

    1999-11-03

    The paper describes a methodology for designing a web site for human factor engineers that is applicable for designing a web site for a group of people. Many web pages on the World Wide Web are not organized in a format that allows a user to efficiently find information. Often the information and hypertext links on web pages are not organized into intuitive groups. Intuition implies that a person is able to use their knowledge of a paradigm to solve a problem. Intuitive groups are categories that allow web page users to find information by using their intuition or mental models of categories. In order to improve the human factors engineers efficiency for finding information on the World Wide Web, research was performed to develop a web site that serves as a tool for finding information effectively. The paper describes a methodology for designing a web site for a group of people who perform similar task in an organization.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Structure-based virtual screening toward the discovery of novel inhibitors of the DNA repair activity of the human apurinic/apyrimidinic endonuclease 1.

    PubMed

    Guerreiro, Patrícia S; Estácio, Sílvia G; Antunes, Fernando; Fernandes, Ana S; Pinheiro, Pedro F; Costa, João G; Castro, Matilde; Miranda, Joana P; Guedes, Rita C; Oliveira, Nuno G

    2016-12-01

    The DNA repair activity of human apurinic/apyrimidinic endonuclease 1 (APE1) has been recognized as a promising target for the development of small-molecule inhibitors to be used in combination with anticancer agents. In an attempt to identify novel inhibitors of APE1, we present a structure-based virtual screening (SBVS) study based on molecular docking analysis of the compounds of NCI database using the GOLD 5.1.0 (Genetic Optimization for Ligand Docking) suite of programs. Compounds selected in this screening were tested with a fluorescence-based APE1 endonuclease activity assay. Two compounds (37 and 41) were able to inhibit the multifunctional enzyme APE1 in the micromolar range, while compound 22 showed inhibitory effects at nanomolar concentrations. These results were confirmed by a plasmid DNA nicking assay. In addition, the potential APE1 inhibitors did not affect the cell viability of non-tumor MCF10A cells. Overall, compounds 22, 37, and 41 appear to be important scaffolds for the design of novel APE1 inhibitors and this study highlights the relevance of in silico-based approaches as valuable tools in drug discovery.

  20. Remedial design of the Fultz Landfill Site, Byesville, Ohio

    SciTech Connect

    Rajaram, V.; Riesing, R.; Bloom, T.

    1994-12-31

    The Fultz Landfill Superfund (Fultz) site is a 30-acre hazardous waste landfill located near Byesville, Ohio. The site is approximately 75 miles east of Columbus and 3 miles southwest of Cambridge, the largest city in Guernsey County, Ohio. The landfill is situated on the north slope of a ridge that overlies abandoned coal mines in the Upper Freeport Coal seam. The north half of the landfill lies in an unreclaimed strip mine in the Upper Freeport Coal seam, where saturated portions of surface mine spoils and natural soils form the ``shallow aquifer``. The south half of the landfill lies 40 to 50 feet (ft.) above an abandoned, flooded deep mine in the same coal seam. The flooded deep mine forms an aquifer referred to as the ``coal mine aquifer``. This paper presents the results of design studies completed by PRC Environmental Management, Inc. (PRC), during 1993, and the remedial design (RD) of the components specified by the US Environmental Protection Agency (EPA) Record of Decision (ROD) for the Fultz site (EPA 1991). The remedy specified in the ROD includes a multilayer landfill cap that is compliant with Resource Conservation and Recovery Act (RCRA) Subtitle C guidelines, a leachate collection and groundwater extraction and treatment system, and stabilizing mine voids underlying the southern portion of the site. Vinyl chloride is the only contaminant exceeding a maximum contaminant limit (MCL) in the coal mine aquifer.

  1. The Hanford Site 1000-Year Cap Design Test

    SciTech Connect

    Gee, Glendon W. ); Ward, Anderson L. ); Wittreich, Curtis D.

    2002-12-27

    Surface barrier or capping technology is needed to isolate buried wastes. A successful cap must prevent the intrusion of plants, animals, and man into the underlying waste, minimize wind and water erosion, require minimal maintenance, and limit water intrusion to near-zero amounts. For some sites where wastes are long-lived, caps should potentially last a thousand years or more. At the U.S. Department of Energy (DOE) Hanford Site in Washington State, a surface cap with a 1000-year design life was constructed and then tested and monitored for performance under wetting conditions that are extreme for the region. The cap was built in 1994 over an existing waste site as a part of a Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) treatability test. The above-grade barrier or cap consists of a 2-m-thick silt-loam soil overlying layers (from top down) of sand, gravel, basalt rock (riprap), and a low-permeability asphalt. Two sideslope configurations, a clean-fill gravel on a 10:1 slope and a basalt riprap on a 2:1 slope were part of the overall design and testing. Design considerations included constructability; water-balance monitoring; wind and water erosion control and monitoring; surface revegetation, biointrusion control, subsidence, and sideslope stability; and durability of the asphalt layer.

  2. Optimising web site designs for people with learning disabilities.

    PubMed

    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 usability were elicited. A study comparing web sites of different design layouts exhibiting these attributes is discussed, with the emphasis on methodology. Eight interfaces were compared using various combinations of menu position (vertical or horizontal), text size and the absence or presence of images to determine which attributes of a site have the greatest performance impact. Study participants were also asked for their preferences, via a 'smiley-face' rating scale and simple interviews. 'Acquiescence bias' was minimised by avoiding polar ('yes/no') interrogatives, achieved by asking participants to compare layouts (such as horizontal versus vertical menu), with reasons coaxed from those able to articulate them. Preferred designs were for large text and images. This was the reverse of those facilitating fastest retrieval times, a discrepancy due to preferences being judged on aesthetic considerations. Design recommendations that reconcile preference and performance findings are offered. These include using a horizontal menu, juxtaposing images and text, and reducing text from sentences to phrases, thus facilitating preferred large text without increasing task times.

  3. DNA base-excision repair enzyme apurinic/apyrimidinic endonuclease/redox factor-1 is increased and competent in the brain and spinal cord of individuals with amyotrophic lateral sclerosis.

    PubMed

    Shaikh, Arif Y; Martin, Lee J

    2002-01-01

    Motor neurons degenerate in amyotrophic lateral sclerosis (ALS). The mechanisms for this neuronal cell death are not known, although apoptosis has been implicated. Oxidative damage to DNA and activation of p53 has been identified directly in motor neurons in cases of ALS. We evaluated whether motor neuron degeneration in ALS is associated with changes in the levels and function of the multifunctional protein apurinic/apyrimidinic endonuclease (APE/Ref-1). APE/Ref-1 functions as an enzyme in the DNA base-excision repair pathway and as a redox-regulation protein for transcription factors. The protein level and localization of APE/Ref-1 are changed in ALS. Immunoblotting showed that APE/Ref-1 protein levels are increased in selectively vulnerable central nervous system (CNS) regions in individuals with ALS compared to age-matched controls. Plasmid DNA repair assay demonstrated that APE from individuals with ALS is competent in repairing apurinic (AP) sites. DNA repair function in nuclear fractions is increased significantly in ALS motor cortex and spinal cord. Immunocytochemistry and single-cell densitometry revealed that APE/Ref-1 is expressed at lower levels in control motor neurons than in ALS motor neurons, which are decreased in number by 42% in motor cortex. APE/Ref-1 is increased in the nucleus of remaining upper motor neurons in ALS, which show a 38% loss of nuclear area. APE-Ref-1 is also upregulated in astrocytes in spinal cord white matter pathways in familial ALS. We conclude that mechanisms for DNA repair are activated in ALS, supporting the possibility that DNA damage is an upstream mechanism for motor neuron degeneration in this disease.

  4. Coordination of Steps in Single-nucleotide Base Excision Repair Mediated by Apurinic/Apyrimidinic Endonuclease 1 and DNA Polymerase β*

    PubMed Central

    Liu, Yuan; Prasad, Rajendra; Beard, William A.; Kedar, Padmini S.; Hou, Esther W.; Shock, David D.; Wilson, Samuel H.

    2008-01-01

    The individual steps in single-nucleotide base excision repair (SN-BER) are coordinated to enable efficient repair without accumulation of cytotoxic DNA intermediates. The DNA transactions and various proteins involved in SN-BER of abasic sites are well known in mammalian systems. Yet, despite a wealth of information on SN-BER, the mechanism of step-by-step coordination is poorly understood. In this study we conducted experiments toward understanding step-by-step coordination during BER by comparing DNA binding specificities of two major human SN-BER enzymes, apurinic/aprymidinic endonuclease 1 (APE) and DNA polymerase β (Pol β). It is known that these enzymes do not form a stable complex in solution. For each enzyme, we found that DNA binding specificity appeared sufficient to explain the sequential processing of BER intermediates. In addition, however, we identified at higher enzyme concentrations a ternary complex of APE·Pol β·DNA that formed specifically at BER intermediates containing a 5′-deoxyribose phosphate group. Formation of this ternary complex was associated with slightly stronger Pol β gap-filling and much stronger 5′-deoxyribose phosphate lyase activities than was observed with the Pol β·DNA binary complex. These results indicate that step-by-step coordination in SN-BER can rely on DNA binding specificity inherent in APE and Pol β, although coordination also may be facilitated by APE·Pol β·DNA ternary complex formation with appropriate enzyme expression levels or enzyme recruitment to sites of repair. PMID:17355977

  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. Brownfields Green Avenue Sites: Technical Memorandum - Conceptual Design for Sustainable Redevelopment

    EPA Pesticide Factsheets

    This technical memorandum briefly describes the site and proposed conceptual site plan, indicates conceptual design considerations, specifies recommended green and sustainable features, and offers other recommendations

  7. Designing for Differences: Cultural Issues in the Design of WWW-based Course-support Sites.

    ERIC Educational Resources Information Center

    Collis, Betty

    1999-01-01

    Examines factors affecting the cultural appropriateness of Web-based course-support sites. Identifies a strategy for accommodating different values of these factors in Web-based course-support systems, based on a set of 10 design guidelines. Describes and evaluates the TeleTOP Method from the University of Twente (The Netherlands) to illustrate…

  8. A reagentless electrochemiluminescent immunosensor for apurinic/apyrimidinic endonuclease 1 detection based on the new Ru(bpy)3(2+)/bi-arginine system.

    PubMed

    Zhao, Min; Chai, Xi Deng Ya-Qin; Han, Jing; Gui, Guo-Feng; Yuan, Ruo; Zhuo, Ying

    2014-10-10

    Apurinic/apyrimidinic endonuclease 1 (APE-1), a kind of multifunctional protein widely-distributed in the body, plays an essential role in the DNA base excision repair and serves as multiple possible roles in the response of human cancer to radiotherapy and chemotherapy. In this work, an ultrasensitive solid-state electrochemiluminescence (ECL) immunosensor is designed to determine APE-1 based on the new Ru(bpy)3(2+)/bi-arginine system. The bi-arginine (bi-Arg) is decorated on the Au nanoparticles functionalized magnetic Fe3O4/reduced graphene oxide (bi-Arg/Au@Fe3O4-rGO) according to the self-assembling and covalent cross-linking interaction to obtain the functionalized nanocomposite of bi-Arg/Au@Fe3O4-rGO. Herein, the bi-Arg/Au@Fe3O4-rGO plays not only an amplification label to enhance the ECL signal of Ru(bpy)3(2+) due to the coreactant of bi-Arg but also an ideal nanocarrier to load numerous secondary antibody. Based on sandwich-type immunoassay format, this proposed method offers a linear range of 1.0fgmL(-1)-5.0pgmL(-1) and an estimated detection limit of 0.3fgmL(-1) for the APE-1. Moreover, the reagentless ECL immunosensor also exhibits high sensitivity, excellent selectivity and good stability, which has greatly potential development and application in clinical diagnostics, immunology and biomedical research.

  9. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Tuba City, Arizona. Apendix D, Site characteriztion

    SciTech Connect

    Not Available

    1987-05-01

    This appendix assesses the present conditions and data for the inactive uranium mill site near Tuba City, Arizona. It consolidates available engineering, radiological, geotechnical, hydrological, meterological, and other information pertinent to the design of the Remedial Action Plan (RAP). The data characterize conditions at the mill and tailings site so that the Remedial Action Contractor (RAC) may complete final designs of the remedial actions.

  10. 78 FR 37759 - Ocean Dumping; Atchafalaya-West Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ... 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, ``Designation of the Atchafalaya River Bar Channel Ocean Dredged Material Disposal Site Pursuant to Section...

  11. 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...

  12. 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...

  13. 40 CFR 228.15 - Dumping sites designated on a final basis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 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...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true 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, 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...

  16. 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…

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

    PubMed

    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.

  18. 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

  19. 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

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

    DOE PAGES

    Suresh Kumar, M. A.; Peluso, Michael; Chaudhary, Pankaj; ...

    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

  1. User-Centered Design and Usability Testing of a Web Site: An Illustrative Case Study.

    ERIC Educational Resources Information Center

    Corry, Michael D.; Frick, Theodore W.; Hansen, Lisa

    1997-01-01

    Presents an overview of user-centered design and usability testing. Describes a Web site evaluation project at a university, the iterative process of rapid prototyping and usability testing, and how the findings helped to improve the design. Discusses recommendations for university Web site design and reflects on problems faced in usability…

  2. Criteria for the management of disposal sites for ocean dumping extension of interim designations

    SciTech Connect

    Not Available

    1980-01-16

    The US Environmental Protection Agency has promulgated amendments to its regulations on ocean dumping which extend the interim designation of certain ocean dumping sites pending completion of Environmental Impact Statements (EIS) and formal rulemaking procedures. Other sites, mainly those for dredged material disposal, will be extended pending completion of site designation studies and formal designation. The schedule for availability of draft EIS on 25 dumping sites and extension dates for the affected interim sites are discussed. This rule is effective as of 1/16/80. Comments must be received by 2/15/80.

  3. 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)

  4. 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…

  5. Basic repository environmental assessment design basis: Deaf Smith County site

    SciTech Connect

    Not Available

    1988-03-01

    This study examines the engineering factors and costs associated with the construction, operation, and decommissioning of a high-level nuclear waste repository in salt in the Palo Duro Basin in Deaf Smith County, Texas. The study assumes a repository capacity of 36,000 metric tons of heavy metal (MTHM) of unreprocessed spent fuel and 36,000 MTHM of commercial high-level reprocessing waste, along with 7,020 canisters of defense high-level reprocessing waste and associated quantities or remote- and contact-handled transuranic waste (TRU). With the exception of TRU, all the waste forms are placed in 300- to 1000-year-life carbon-steel waste packages in a collocated waste handling and packaging facility (WHPF), which is also described. The construction, operation, and decommissioning of the proposed repository is estimated to cost approximately $4.64 billion. Costs include those for the collocate WHPF, engineering, and contingency, but exclude waste form assembly and shipment to the site and waste package fabrication and shipment to the site. These costs reflect the relative average wage rates of the region, the relatively easy access to the site, and the relatively weak nature of the salt at this site. Construction would require an estimated 7 to 7.5 years. Engineering factors and costs are not strongly influenced by environmental considerations. 62 refs., 24 figs., 20 tabs.

  6. 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…

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. New "persona" concept helps site designers cater to target user segments' needs.

    PubMed

    2004-09-01

    Using the relatively new "persona" design concept, Web strategists create a set of archetypical user characters, each one representing one of their site's primary audiences. Then, as their site is constructed or upgraded, they champion the personas, arguing on their behalf and forcing the design team to take each audience's needs and wants into account.

  12. 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…

  13. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Disposal site design for land disposal. 61.51 Section 61.51 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Technical Requirements for Land Disposal Facilities § 61.51 Disposal site design for...

  14. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Disposal site design for land disposal. 61.51 Section 61.51 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Technical Requirements for Land Disposal Facilities § 61.51 Disposal site design for...

  15. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Disposal site design for land disposal. 61.51 Section 61.51 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Technical Requirements for Land Disposal Facilities § 61.51 Disposal site design for...

  16. 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 RADIOACTIVE WASTE Technical Requirements for Land Disposal Facilities § 61.51 Disposal site design for...

  17. 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.

  18. Basic repository environmental assessment design basis, Lavender Canyon site

    SciTech Connect

    Not Available

    1988-01-01

    This study examines the engineering factors and costs associated with the construction, operation, and decommissioning of a high-level nuclear waste repository in salt in the Paradox Basin in Lavender Canyon, Utah. The study assumes a repository capacity of 36,000 metric tons of heavy metal (MTHM) of unreprocessed spent fuel and 36,000 MTHM of commercial high-level reprocessing waste, along with 7020 canisters of defense high-level reprocessing waste and associated quantities of remote- and contact-handled transuranic waste (TRU). With the exception of TRU, all the waste forms are placed in 300- to 1000-year-life carbon-steel waste packages in a collocated waste handling and packaging facility (WHPF), which is also described. The construction, operation, and decommissioning of the proposed repository is estimated to cost approximately $5.51 billion. Costs include those for the collocated WHPP, engineering, and contingency, but exclude waste form assembly and shipment to the site and waste package fabrication and shipment to the site. These costs reflect the relative average wage rates of the region and the relatively sound nature of the salt at this site. Construction would require an estimated 7.75 years. Engineering factors and costs are not strongly influenced by environmental considerations. 51 refs., 24 figs., 20 tabs.

  19. 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.…

  20. 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...

  1. Site study plan for EDBH (Engineering Design Boreholes) seismic surveys, Deaf Smith County site, Texas: Revision 1

    SciTech Connect

    Hume, H.

    1987-12-01

    This site study plan describes seismic reflection surveys to run north-south and east-west across the Deaf Smith County site, and intersecting near the Engineering Design Boreholes (EDBH). Both conventional and shallow high-resolution surveys will be run. The field program has been designed to acquire subsurface geologic and stratigraphic data to address information/data needs resulting from Federal and State regulations and Repository program requirements. The data acquired by the conventional surveys will be common-depth- point, seismic reflection data optimized for reflection events that indicate geologic structure near the repository horizon. The data will also resolve the basement structure and shallow reflection events up to about the top of the evaporite sequence. Field acquisition includes a testing phase to check/select parameters and a production phase. The field data will be subjected immediately to conventional data processing and interpretation to determine if there are any anamolous structural for stratigraphic conditions that could affect the choice of the EDBH sites. After the EDBH's have been drilled and logged, including vertical seismic profiling, the data will be reprocessed and reinterpreted for detailed structural and stratigraphic information to guide shaft development. The shallow high-resulition seismic reflection lines will be run along the same alignments, but the lines will be shorter and limited to immediate vicinity of the EDBH sites. These lines are planned to detect faults or thick channel sands that may be present at the EDBH sites. 23 refs. , 7 figs., 5 tabs.

  2. 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.

  3. 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

  4. 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.

  5. Fracture analysis and rock quality designation estimation for the Yucca Mountain Site Characterization Project; Yucca Mountain Site Characterization Project

    SciTech Connect

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

    1993-02-01

    Within the Yucca Mountain Site Characterization Project, the design of drifts and ramps and evaluation of the impacts of thermomechanical loading of the host rock requires definition of the rock mass mechanical properties. Ramps and exploratory drifts will intersect both welded and nonwelded tuffs with varying abundance of fractures. The rock mass mechanical properties are dependent on the intact rock properties and the fracture joint characteristics. An understanding of the effects of fractures on the mechanical properties of the rock mass begins with a detailed description of the fracture spatial location and abundance, and includes a description of their physical characteristics. This report presents a description of the abundance, orientation, and physical characteristics of fractures and the Rock Quality Designation in the thermomechanical stratigraphic units at the Yucca Mountain site. Data was reviewed from existing sources and used to develop descriptions for each unit. The product of this report is a data set of the best available information on the fracture characteristics.

  6. 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.

  7. 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.

  8. 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

  9. Site Planning and Design to Enable Planetary Science and Human Exploration

    NASA Astrophysics Data System (ADS)

    Lewis, R.; Lupisella, M.; Bleacher, J.

    2017-02-01

    It is critical to properly plan site layout and design of science and habitation assets about and within planetary exploration zones following planetary protection policies and environment management practices for effective robotic and human missions.

  10. Identification and Characterization of Inhibitors of Human Apurinic/apyrimidinic Endonuclease APE1

    PubMed Central

    Simeonov, Anton; Kulkarni, Avanti; Dorjsuren, Dorjbal; Jadhav, Ajit; Shen, Min; McNeill, Daniel R.; Austin, Christopher P.; Wilson, David M.

    2009-01-01

    APE1 is the major nuclease for excising abasic (AP) sites and particular 3′-obstructive termini from DNA, and is an integral participant in the base excision repair (BER) pathway. BER capacity plays a prominent role in dictating responsiveness to agents that generate oxidative or alkylation DNA damage, as well as certain chain-terminating nucleoside analogs and 5-fluorouracil. We describe within the development of a robust, 1536-well automated screening assay that employs a deoxyoligonucleotide substrate operating in the red-shifted fluorescence spectral region to identify APE1 endonuclease inhibitors. This AP site incision assay was used in a titration-based high-throughput screen of the Library of Pharmacologically Active Compounds (LOPAC1280), a collection of well-characterized, drug-like molecules representing all major target classes. Prioritized hits were authenticated and characterized via two high-throughput screening assays – a Thiazole Orange fluorophore-DNA displacement test and an E. coli endonuclease IV counterscreen – and a conventional, gel-based radiotracer incision assay. The top, validated compounds, i.e. 6-hydroxy-DL-DOPA, Reactive Blue 2 and myricetin, were shown to inhibit AP site cleavage activity of whole cell protein extracts from HEK 293T and HeLa cell lines, and to enhance the cytotoxic and genotoxic potency of the alkylating agent methylmethane sulfonate. The studies herein report on the identification of novel, small molecule APE1-targeted bioactive inhibitor probes, which represent initial chemotypes towards the development of potential pharmaceuticals. PMID:19484131

  11. 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…

  12. 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…

  13. Facilitating Participation: From the EML Web Site to the Learning Network for Learning Design

    ERIC Educational Resources Information Center

    Hummel, Hans G. K.; Tattersall, Colin; Burgos, Daniel; Brouns, Francis; Kurvers, Hub; Koper, Rob

    2005-01-01

    This article investigates conditions for increasing active participation in on-line communities. As a case study, we use three generations of facilities designed to promote learning in the area of Educational Modelling Languages. Following a description of early experience with a conventional web site and with a community site offering facilities…

  14. Designing a Web Site for One Imaginary Persona that Reflect the Needs of Many

    ERIC Educational Resources Information Center

    Cunningham, Heather

    2005-01-01

    Does designing a large academic library Web site for an imaginary person seem a sensible thing to do? As a reference librarian and member of the Web team of the Gerstein Science Information Centre (Gerstein Library), that is exactly what this author set out to do in May 2005. She proposed that the best way to ensure that the Web site meets the…

  15. 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…

  16. 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…

  17. 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…

  18. A user-centered model for web site design: needs assessment, user interface design, and rapid prototyping.

    PubMed

    Kinzie, Mable B; Cohn, Wendy F; Julian, Marti F; Knaus, William A

    2002-01-01

    As the Internet continues to grow as a delivery medium for health information, the design of effective Web sites becomes increasingly important. In this paper, the authors provide an overview of one effective model for Web site design, a user-centered process that includes techniques for needs assessment, goal/task analysis, user interface design, and rapid prototyping. They detail how this approach was employed to design a family health history Web site, Health Heritage . This Web site helps patients record and maintain their family health histories in a secure, confidential manner. It also supports primary care physicians through analysis of health histories, identification of potential risks, and provision of health care recommendations. Visual examples of the design process are provided to show how the use of this model resulted in an easy-to-use Web site that is likely to meet user needs. The model is effective across diverse content arenas and is appropriate for applications in varied media.

  19. 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.

  20. Nevada test site low-level and mixed waste repository design in the unsaturated zone

    SciTech Connect

    Kawamura, T.A.; Warren, D.M.; USDOE Nevada Operations Office, Las Vegas, NV )

    1989-01-01

    The Area 5 Radioactive Waste Management Site (RWMS) at the Nevada Test Site (NTS) is used for shallow land disposal of Low-Level Radioactive (LLW) and for retrievable disposal of Mixed Wastes (MW) from various Department of Energy (DOE) facilities. The site is situated in southern Nevada, one of the most arid regions of the United States. Design considerations include vadose zone monitoring in lieu of groundwater monitoring, stringent waste acceptance and packaging criteria, a waste examination and real-time radiography facility, and trench design. 4 refs.

  1. 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.

  2. 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...

  3. 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...

  4. Interfacing Media: User-Centered Design for Media-Rich Web Sites.

    ERIC Educational Resources Information Center

    Horton, Sarah

    2000-01-01

    Discusses multimedia Web site design that may include images, animations, audio, and video. Highlights include interfaces that stress user-centered design; using only relevant media; placing high-demand content on secondary pages and keeping the home page simpler; providing information about the media; considering users with disabilities; and user…

  5. Probing Enhanced Double-Strand Break Formation at Abasic Sites within Clustered Lesions in Nucleosome Core Particles.

    PubMed

    Banerjee, Samya; Chakraborty, Supratim; Jacinto, Marco Paolo; Paul, Michael D; Balster, Morgan V; Greenberg, Marc M

    2017-01-10

    DNA is rapidly cleaved under mild alkaline conditions at apyrimidinic/apurinic sites, but the half-life is several weeks in phosphate buffer (pH 7.5). However, abasic sites are ∼100-fold more reactive within nucleosome core particles (NCPs). Histone proteins catalyze the strand scission, and at superhelical location 1.5, the histone H4 tail is largely responsible for the accelerated cleavage. The rate constant for strand scission at an abasic site is enhanced further in a nucleosome core particle when it is part of a bistranded lesion containing a proximal strand break. Cleavage of this form results in a highly deleterious double-strand break. This acceleration is dependent upon the position of the abasic lesion in the NCP and its structure. The enhancement in cleavage rate at an apurinic/apyrimidinic site rapidly drops off as the distance between the strand break and abasic site increases and is negligible once the two forms of damage are separated by 7 bp. However, the enhancement of the rate of double-strand break formation increases when the size of the gap is increased from one to two nucleotides. In contrast, the cleavage rate enhancement at 2-deoxyribonolactone within bistranded lesions is more modest, and it is similar in free DNA and nucleosome core particles. We postulate that the enhanced rate of double-strand break formation at bistranded lesions containing apurinic/apyrimidinic sites within nucleosome core particles is a general phenomenon and is due to increased DNA flexibility.

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

    PubMed

    Huang, Wenkang; Nussinov, Ruth; Zhang, Jian

    2017-01-01

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

  7. 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.

  8. Linkage between site characterization program and performance and design data needs

    SciTech Connect

    Blanchard, M.B.; Dobson, D.C.; Younker, J.L.; Voegele, M.D.

    1990-04-01

    The basis for identifying site-specific data needs for the Yucca Mountain site was a thorough review and evaluation of the regulatory requirements for a geologic repository. The US Nuclear Regulatory Commission`s (NRC) regulation governing disposal of high-level waste in a geologic repository utilizes a multiple barrier approach that includes reliance on both engineered and natural elements. Given an understanding of the regulatory requirements, the next step was to identify the natural features of the site and the components of the engineered barriers considered most likely to make significant contributions to isolation of waste at Yucca Mountain. The intent was to develop a site testing program that focused on understanding those natural site characteristics and processes most likely to contribute to waste isolation; and providing site data necessary to design and assess the performance of engineered barriers. 3 refs., 3 figs.

  9. Comparison of SARS and NL63 papain-like protease binding sites and binding site dynamics: inhibitor design implications.

    PubMed

    Chaudhuri, Rima; Tang, Sishi; Zhao, Guijun; Lu, Hui; Case, David A; Johnson, Michael E

    2011-11-25

    The human severe acute respiratory syndrome coronavirus (SARS-CoV) and the NL63 coronaviruses are human respiratory pathogens for which no effective antiviral treatment exists. The papain-like cysteine proteases encoded by the coronavirus (SARS-CoV: PLpro; NL63: PLP1 and PLP2) represent potential targets for antiviral drug development. Three recent inhibitor-bound PLpro structures highlight the role of an extremely flexible six-residue loop in inhibitor binding. The high binding site plasticity is a major challenge in computational drug discovery/design efforts. From conventional molecular dynamics and accelerated molecular dynamics (aMD) simulations, we find that with conventional molecular dynamics simulation, PLpro translationally samples the open and closed conformation of BL2 loop on a picosecond-nanosecond timescale but does not reproduce the peptide bond inversion between loop residues Tyr269 and Gln270 that is observed on inhibitor GRL0617 binding. Only aMD simulation, starting from the closed loop conformation, reproduced the 180° ϕ-ψ dihedral rotation back to the open loop state. The Tyr-Gln peptide bond inversion appears to involve a progressive conformational change of the full loop, starting at one side, and progressing to the other. We used the SARS-CoV apo X-ray structure to develop a model of the NL63-PLP2 catalytic site. Superimposition of the PLP2 model on the PLpro X-ray structure identifies binding site residues in PLP2 that contribute to the distinct substrate cleavage site specificities between the two proteases. The topological and electrostatic differences between the two protease binding sites also help explain the selectivity of non-covalent PLpro inhibitors.

  10. 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.

  11. High-Probability Neurotransmitter Release Sites Represent an Energy-Efficient Design.

    PubMed

    Lu, Zhongmin; Chouhan, Amit K; Borycz, Jolanta A; Lu, Zhiyuan; Rossano, Adam J; Brain, Keith L; Zhou, You; Meinertzhagen, Ian A; Macleod, Gregory T

    2016-10-10

    Nerve terminals contain multiple sites specialized for the release of neurotransmitters. Release usually occurs with low probability, a design thought to confer many advantages. High-probability release sites are not uncommon, but their advantages are not well understood. Here, we test the hypothesis that high-probability release sites represent an energy-efficient design. We examined release site probabilities and energy efficiency at the terminals of two glutamatergic motor neurons synapsing on the same muscle fiber in Drosophila larvae. Through electrophysiological and ultrastructural measurements, we calculated release site probabilities to differ considerably between terminals (0.33 versus 0.11). We estimated the energy required to release and recycle glutamate from the same measurements. The energy required to remove calcium and sodium ions subsequent to nerve excitation was estimated through microfluorimetric and morphological measurements. We calculated energy efficiency as the number of glutamate molecules released per ATP molecule hydrolyzed, and high-probability release site terminals were found to be more efficient (0.13 versus 0.06). Our analytical model indicates that energy efficiency is optimal (∼0.15) at high release site probabilities (∼0.76). As limitations in energy supply constrain neural function, high-probability release sites might ameliorate such constraints by demanding less energy. Energy efficiency can be viewed as one aspect of nerve terminal function, in balance with others, because high-efficiency terminals depress significantly during episodic bursts of activity.

  12. 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.

  13. 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.

  14. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Tuba City, Arizona. [Uranium Mill Tailings Remedial Action (UMTRA) Project

    SciTech Connect

    Not Available

    1987-05-01

    This appendix assesses the present conditions and data for the inactive uranium mill site near Tuba City, Arizona. It consolidates available engineering, radiological, geotechnical, hydrological, meterological, and other information pertinent to the design of the Remedial Action Plan (RAP). The data characterize conditions at the mill and tailings site so that the Remedial Action Contractor (RAC) may complete final designs of the remedial actions.

  15. 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.

  16. Design Guidelines for Teaching about Design Guidelines for Educational WWW Sites.

    ERIC Educational Resources Information Center

    Collis, Betty; Winnips, Koos

    This paper describes how the authors use a mixture of World Wide Web (WWW)-based functionalities and new didactics to teach educational technology students at the University of Twente (Netherlands) about the design of WWW-based learning environments. Topics discussed include: (1) the content of courses about the design of educational WWW…

  17. Are biophilic-designed site office buildings linked to health benefits and high performing occupants?

    PubMed

    Gray, Tonia; Birrell, Carol

    2014-11-26

    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.

  18. 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

  19. 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.

  20. 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.

  1. Two interacting binding sites for quinacrine derivatives in the active site of trypanothione reductase – a template for drug design

    PubMed Central

    Saravanamuthu, Ahilan; Vickers, Tim J.; Bond, Charles S.; Peterson, Mark R.; Hunter, William N.; Fairlamb, Alan H.

    2012-01-01

    SUMMARY Trypanothione reductase is a key enzyme in the trypanothione-based redox metabolism of pathogenic trypanosomes. Since this system is absent in humans, being replaced with glutathione and glutathione reductase, it offers a target for selective inhibition. The rational design of potent inhibitors requires accurate structures of enzyme-inhibitor complexes, but this is lacking for trypanothione reductase. We therefore used quinacrine mustard, an alkylating derivative of the competitive inhibitor quinacrine, to probe the active site of this dimeric flavoprotein. Quinacrine mustard irreversibly inactivates Trypanosoma cruzi trypanothione reductase, but not human glutathione reductase, in a time-dependent manner with a stoichiometry of two inhibitors bound per monomer. The rate of inactivation is dependent upon the oxidation state of trypanothione reductase, with the NADPH-reduced form being inactivated significantly faster than the oxidised form. Inactivation is slowed by clomipramine and a melarsen oxide-trypanothione adduct (both are competitive inhibitors) but accelerated by quinacrine. The structure of the trypanothione reductase-quinacrine mustard adduct was determined to 2.7 Å, revealing two molecules of inhibitor bound in the trypanothione-binding site. The acridine moieties interact with each other through π-stacking effects, and one acridine interacts in a similar fashion with a tryptophan residue. These interactions provide a molecular explanation for the differing effects of clomipramine and quinacrine on inactivation by quinacrine mustard. Synergism with quinacrine occurs as a result of these planar acridines being able to stack together in the active site cleft, thereby gaining an increased number of binding interactions, whereas antagonism occurs with non-planar molecules, such as clomipramine, where stacking is not possible. PMID:15102853

  2. 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.

  3. HTP-OligoDesigner: An Online Primer Design Tool for High-Throughput Gene Cloning and Site-Directed Mutagenesis.

    PubMed

    Camilo, Cesar M; Lima, Gustavo M A; Maluf, Fernando V; Guido, Rafael V C; Polikarpov, Igor

    2016-01-01

    Following burgeoning genomic and transcriptomic sequencing data, biochemical and molecular biology groups worldwide are implementing high-throughput cloning and mutagenesis facilities in order to obtain a large number of soluble proteins for structural and functional characterization. Since manual primer design can be a time-consuming and error-generating step, particularly when working with hundreds of targets, the automation of primer design process becomes highly desirable. HTP-OligoDesigner was created to provide the scientific community with a simple and intuitive online primer design tool for both laboratory-scale and high-throughput projects of sequence-independent gene cloning and site-directed mutagenesis and a Tm calculator for quick queries.

  4. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    .... 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 Low-Rise Residential Buildings. § 435.6 Sustainable principles for siting, design and construction....

  5. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    .... 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 Low-Rise Residential Buildings. § 435.6 Sustainable principles for siting, design and construction....

  6. 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...

  7. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... 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 Low-Rise Residential Buildings. § 435.6 Sustainable principles for siting, design and construction....

  8. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .... 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 Low-Rise Residential Buildings. § 435.6 Sustainable principles for siting, design and construction....

  9. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    .... 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 Low-Rise Residential Buildings. § 435.6 Sustainable principles for siting, design and construction....

  10. 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...

  11. 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...

  12. 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…

  13. 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.

  14. Design, synthesis, and characterization of nucleosomes containing site-specific DNA damage.

    PubMed

    Taylor, John-Stephen

    2015-12-01

    How DNA damaged is formed, recognized, and repaired in chromatin is an area of intense study. To better understand the structure activity relationships of damaged chromatin, mono and dinucleosomes containing site-specific damage have been prepared and studied. This review will focus on the design, synthesis, and characterization of model systems of damaged chromatin for structural, physical, and enzymatic studies.

  15. 7 CFR Exhibit B to Subpart C of... - Site Development Design Requirements

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Catch Basins 1. Openings 2. Access G. Drywells V. Water Supply Systems A. Individual Water Systems 1. General 2. Well Location 3. Well Construction 4. Pumps and Equipment 5. Storage Tanks B. Community Water... drainage of surface water away from buildings and adjacent sites. Grading design shall conform with...

  16. 7 CFR Exhibit B to Subpart C of... - Site Development Design Requirements

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Catch Basins 1. Openings 2. Access G. Drywells V. Water Supply Systems A. Individual Water Systems 1. General 2. Well Location 3. Well Construction 4. Pumps and Equipment 5. Storage Tanks B. Community Water... drainage of surface water away from buildings and adjacent sites. Grading design shall conform with...

  17. 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

  18. GMT site, enclosure, and facilities design and development overview and update

    NASA Astrophysics Data System (ADS)

    Teran, Jose; Burgett, William S.; Grigel, Eric; Bigelow, Bruce C.; Donoso, Eduardo; Figueroa, Francisco

    2016-07-01

    The Giant Magellan Telescope (GMT) will have a 25.4-meter diameter effective aperture, and is one the three currently planned next generation extremely large telescopes (ELTs). The GMT will be located at the summit of Cerro Campanas at the Las Campanas Observatory (LCO) in Chile, one the world's best observing sites. This paper provides an overview of the site master plan comprising site infrastructure, enclosure, and facilities, and outlines the analysis of alternative trade studies that will lead to the final design. Also presented is an update of the site infrastructure development and preconstruction activities currently underway that will be completed prior to the beginning of enclosure construction near the end of 2016.

  19. 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.

  20. 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.

  1. Custom-Designed Molecular Scissors for Site-Specific Manipulation of the Plant and Mammalian Genomes

    NASA Astrophysics Data System (ADS)

    Kandavelou, Karthikeyan; Chandrasegaran, Srinivasan

    Zinc finger nucleases (ZFNs) are custom-designed molecular scissors, engineered to cut at specific DNA sequences. ZFNs combine the zinc finger proteins (ZFPs) with the nonspecific cleavage domain of the FokI restriction enzyme. The DNA-binding specificity of ZFNs can be easily altered experimentally. This easy manipulation of the ZFN recognition specificity enables one to deliver a targeted double-strand break (DSB) to a genome. The targeted DSB stimulates local gene targeting by several orders of magnitude at that specific cut site via homologous recombination (HR). Thus, ZFNs have become an important experimental tool to make site-specific and permanent alterations to genomes of not only plants and mammals but also of many other organisms. Engineering of custom ZFNs involves many steps. The first step is to identify a ZFN site at or near the chosen chromosomal target within the genome to which ZFNs will bind and cut. The second step is to design and/or select various ZFP combinations that will bind to the chosen target site with high specificity and affinity. The DNA coding sequence for the designed ZFPs are then assembled by polymerase chain reaction (PCR) using oligonucleotides. The third step is to fuse the ZFP constructs to the FokI cleavage domain. The ZFNs are then expressed as proteins by using the rabbit reticulocyte in vitro transcription/translation system and the protein products assayed for their DNA cleavage specificity.

  2. 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.

  3. Event-based design tool for construction site erosion and sediment controls

    NASA Astrophysics Data System (ADS)

    Trenouth, William R.; Gharabaghi, Bahram

    2015-09-01

    This paper provides additional discussion surrounding the novel event-based soil loss models developed by Trenouth and Gharabaghi (2015) for the design of erosion and sediment controls (ESCs) for various phases of construction - from pre-development to post-development conditions. The datasets for the study were obtained from three Ontario sites - Greensborough, Cookstown, and Alcona - in addition to datasets mined from the literature for three additional sites - Treynor, Iowa, Coshocton, Ohio and Cordoba, Spain. Model performances were evaluated for each of the study sites, and quantified using commonly-reported statistics. This work is nested within a broader conceptual framework, which includes the estimation of ambient receiving water quality, the prediction of event mean runoff quality for a given design storm, and the calculation of the required level of protection using adequate ESCs to meet receiving water quality guidelines. These models allow design engineers and regulatory agencies to assess the potential risk of ecological damage to receiving waters due to inadequate soil erosion and sediment control practices using dynamic scenario forecasting when considering rapidly changing land use conditions during various phases of construction, typically for a 2- or 5-year design storm return period.

  4. Compressed-air energy storage preliminary design and site development program in an aquifer. Volume 5, Part 1: Turbomachinery design

    NASA Astrophysics Data System (ADS)

    Berman, P. A.; Bonk, J. S.; Kobett, W. F.; Kosanovich, N. S.; Long, L. J.; Marinacci, D. J.

    1982-11-01

    The development of the design approach for a combustion turbine heat cycle and the major mechanical equipment for use by an electric utility at a selected aquifer air storage site is documented. A compressed air energy storage (CAES) system utilizes off peak electric power, available from base load power plants, to store compressed air underground in an aquifer. During subsequent periods, the stored air is extracted from the aquifer and used as an air supply for a generating combustion turbine expander. The aquifer has an initial discovery pressure of 840 psia. An initial air injection temperature of 1500 F was selected. The major mechanical equipment considered includes: the turbine motor/generator compressor train, intercooler and aftercooler system, and the exhaust gas regenerator. The cycle and machinery configuration and the specific mechanical equipment were selected for their Media site characteristics. These characteristics and the effect of component interdependency are considered when a conservative component design approach is established which satisfies the Media site CAES system requirements.

  5. 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.

  6. ONWI (Office of Nuclear Waste Isolation) 30% design review findings report for Exploratory Shaft Facility, Deaf Smith site

    SciTech Connect

    Not Available

    1987-05-08

    This document describes a review of the standards for the design of the high-level radioactive waste facility at the Deaf Smith, Texas site. It includes public comments and the official responses to the designs produced to date. (TEM)

  7. 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.

  8. Region and site specific design guidelines for the northeastern Venezuela development

    SciTech Connect

    Gajardo, E.; Paga, M.; Sully, J.P.

    1996-12-31

    Several site specific studies were performed for the northeastern Venezuelan offshore development in order to determine the environmental parameters for the engineering design. The geotechnical parameters were obtained from the analysis of the soil borings, in situ tests and the high resolution seismic surveys. An evaluation of the seismic hazard was done, based on a detailed neotectonic study, the compilation of historical and instrumental seismological information, and an attenuation relationship developed for the studied area. Seismic response analyses were performed using the seismic parameters and dynamic characteristics obtained form the soil borings and in situ tests of shear waves. The met-ocean design loads of the local conditions were obtained from mathematical modeling based on in situ and regional measurements. This study defines the platforms design conditions based on a probabilistic reliability approach and it has been used, among others, as a basis for the earthquake design guidelines proposed by the International Standards Organization. A sensitivity analysis was performed starting from the uncertainties of all the input parameters, in order to obtain the best estimate average design spectrum and associated coefficient of variability. The specific approach was to maintain the same safety index adopted by API RP2A code, with a bias modification factor that relates the site nominal spectra with the spectral acceleration that would be used in order to satisfy the API requirements. The results of this approach make possible the use of site specific detailed environmental data and the proven standard procedures established on the API RP2 codes, with significant cost reduction in terms of both platform and foundation design. The considerable amount of tectonic, seismological, and geotechnical information was the principal factor allowing the above methodology.

  9. Design Status and Applications of Small Reactors Without On-Site Refuelling

    SciTech Connect

    Kuznetsov, Vladimir

    2006-07-01

    Small reactors without on-site refuelling (SRWORs) are the reactors that can operate without reloading and shuffling of fuel for a reasonably long period with no refuelling equipment being present in the reactor and no fuel being stored at the site during reactor operation. By virtue of being small, transportable and requiring no operations with fuel from a customer, such reactors form an attractive domain for fuel or even NPP leasing. SRWORs could simplify the implementation of safeguards and provide certain guarantees of sovereignty to those countries that would agree to forego the development of the indigenous fuel cycle. About 30 concepts of such reactors are being analyzed or developed in 6 IAEA member states. Based on intermediate results of IAEA activities in support of the design and technology development for such reactors, the paper provides technical details on the design status, fuel cycle options and possible applications of SRWORs. (authors)

  10. Automated Design of Synthetic Ribosome Binding Sites to Precisely Control Protein Expression

    PubMed Central

    Salis, Howard M.; Mirsky, Ethan A.; Voigt, Christopher A.

    2009-01-01

    Microbial engineering often requires fine control over protein expression; for example, to connect genetic circuits 1-7 or control flux through a metabolic pathway 8-13. We have developed a predictive design method for synthetic ribosome binding sites that enables the rational control of a protein's production rate on a proportional scale. Experimental validation of over 100 predictions in Escherichia coli shows that the method is accurate to within a factor of 2.3 over a range of 100,000-fold. The design method also correctly predicts that reusing a ribosome binding site sequence in different genetic contexts can result in different protein expression levels. We demonstrate the method's utility by rationally optimizing a protein's expression level to connect a genetic sensor to a synthetic circuit. The proposed forward engineering approach will accelerate the construction and systematic optimization of large genetic systems. PMID:19801975

  11. The design of a Phase I non site-specific Centralized Interim Storage Facility

    SciTech Connect

    Stringer, J.; Kane, D.

    1997-10-28

    The Department of Energy (DOE), Office of Civilian Radioactive Waste Management (OCRWM) recently completed a Topical Safety Analysis Report (TSAR) for a Phase 1 non site specific Centralized Interim Storage Facility (CISF). The TSAR will be used in licensing the CISF when and if a site is designated. The combined Phase 1 and Phase 2 CISF will provide federal storage capability for 40,000 metric tons of uranium (MTU) Spent Nuclear Fuel (SNF) under the oversight of the DOE. The Phase 1 TSAR was submitted to the NRC on May 1, 1997 and is currently under review having been docketed on June 10, 1997. This paper generally describes the Phase 1 CISF design and its operations as presented in the CISF TSAR.

  12. Molecular dynamics explorations of active site structure in designed and evolved enzymes.

    PubMed

    Osuna, Sílvia; Jiménez-Osés, Gonzalo; Noey, Elizabeth L; Houk, K N

    2015-04-21

    This Account describes the use of molecular dynamics (MD) simulations to reveal how mutations alter the structure and organization of enzyme active sites. As proposed by Pauling about 70 years ago and elaborated by many others since then, biocatalysis is efficient when functional groups in the active site of an enzyme are in optimal positions for transition state stabilization. Changes in mechanism and covalent interactions are often critical parts of enzyme catalysis. We describe our explorations of the dynamical preorganization of active sites using MD, studying the fluctuations between active and inactive conformations normally concealed to static crystallography. MD shows how the various arrangements of active site residues influence the free energy of the transition state and relates the populations of the catalytic conformational ensemble to the enzyme activity. This Account is organized around three case studies from our laboratory. We first describe the importance of dynamics in evaluating a series of computationally designed and experimentally evolved enzymes for the Kemp elimination, a popular subject in the enzyme design field. We find that the dynamics of the active site is influenced not only by the original sequence design and subsequent mutations but also by the nature of the ligand present in the active site. In the second example, we show how microsecond MD has been used to uncover the role of remote mutations in the active site dynamics and catalysis of a transesterase, LovD. This enzyme was evolved by Tang at UCLA and Codexis, Inc., and is a useful commercial catalyst for the production of the drug simvastatin. X-ray analysis of inactive and active mutants did not reveal differences in the active sites, but relatively long time scale MD in solution showed that the active site of the wild-type enzyme preorganizes only upon binding of the acyl carrier protein (ACP) that delivers the natural acyl group to the active site. In the absence of bound ACP

  13. 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.

  14. Metal-binding sites are designed to achieve optimal mechanical and signaling properties

    PubMed Central

    Dutta, Anindita; Bahar, Ivet

    2010-01-01

    Many proteins require bound metals to achieve their function. We take advantage of increasing structural data on metal-binding proteins to elucidate three properties: the involvement of metal-binding sites in the global dynamics of the protein, predicted by elastic network models, their exposure/burial to solvent, and their signal-processing properties indicated by Markovian stochastics analysis. Systematic analysis of a dataset of 145 structures reveals that the residues that coordinate metal ions enjoy remarkably efficient and precise signal transduction properties. These properties are rationalized in terms of their physical properties: participation in hinge sites that control the softest modes collectively accessible to the protein and occupancy of central positions minimally exposed to solvent. Our observations suggest that metal-binding sites may have been evolutionary selected to achieve optimum allosteric communication. They also provide insights into basic principles for designing metal-binding sites, which are verified to be met by recently designed de novo metal-binding proteins. PMID:20826340

  15. Characterization and design of the FutureGen 2.0 carbon storage site

    SciTech Connect

    Gilmore, Tyler; Bonneville, Alain; Sullivan, Charlotte; Kelley, Mark; Appriou, Delphine; Vermeul, Vince; White, Signe; Zhang, Fred; Bjornstad, Bruce; Cornet, Francois; Gerst, Jacqueline; Gupta, Neeraj; Hund, Gretchen; Horner, Jake; Last, George; Lanigan, Dave; Oostrom, Mart; McNeil, Caitlin; Moody, Mark; Rockhold, Mark; Elliott, Mike; Spane, Frank; Strickland, Chris; Swartz, Lucy; Thorne, Paul; Brown, Christopher; Hoffmann, Jeffrey; Humphreys, Kenneth

    2016-10-01

    The objective of the FutureGen 2.0 Project was to demonstrate, at the commercial scale, the technical feasibility of implementing carbon capture and storage (CCS) in a deep saline formation in Illinois, USA. Over approximately 5 years, the FutureGen Alliance conducted a detailed site-selection process and identified a site for carbon sequestration storage in Morgan County, Illinois. The storage site was fully characterized, including the collection of seismic data and the drilling and characterization of a stratigraphic borehole. The characterization data provided critical input for developing a site-specific conceptual model and subsequent numerical modeling simulations. The modeling simulations, coupled with the upstream designs of the pipeline and power plant supported the development of a detailed 90 percent design that included the injection wells and associated control and monitoring infrastructure. Collectively, all these data were used by the FutureGen Alliance to develop the required documentation to support the applications for four underground injection control (UIC) permits (one for each proposed well). In August 2014, the U.S. Environmental Protection Agency issued four, first-of-their-kind, Class VI UIC permits for carbon sequestration in the United States to the FutureGen Alliance. The information and data generated under this project have been made publically available through reports and publications, including this journal and others.

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

    PubMed

    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

    2016-08-16

    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.

  17. 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.

  18. On-site wastewater management system design and landslide risk assessment.

    PubMed

    Whitehead, J H; Leventhal, A

    2005-01-01

    On-site wastewater management system design and performance is significant in assessing landslide risk in areas with potential for slope instability. Much of the development in Pittwater, NSW, local government area is on steep coastal land which has a history of slope instability. Concern over cases of poorly performing or failing on-site wastewater systems and the recognition that these and newly designed systems could be contributory to slope instability has been a factor in Pittwater Council, NSW, requiring that landslide risk assessment be undertaken for new and amended on-site wastewater management systems in potentially unstable areas. This paper describes the wastewater management system design and landslide risk assessment undertaken at Pittwater Youth Hostel in accordance with the Australian Geomechanics Society's Geotechnical Risk Management procedure to comply with the Pittwater Policy. The work completed illustrates both necessary and effective interaction of the wastewater and geotechnical professions to achieve a successful outcome for the client. It is likely that this professional interaction will be increasingly common along the NSW coast and elsewhere.

  19. 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

    ... 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 Micro... Technologies, Inc., Manpower, Ion Design, Design Solutions, Inc., Veriseo, SiliconElite and MicroLogic,...

  20. 75 FR 27783 - Decision To Evaluate a Petition To Designate a Class of Employees From the Mound Site in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-18

    ... Doc No: 2010-11875] DEPARTMENT OF HEALTH AND HUMAN SERVICES Decision To Evaluate a Petition To Designate a Class of Employees From the Mound Site in Miamisburg, OH, To Be Included in the Special Exposure... decision to evaluate a petition to designate a class of employees from the Mound site in Miamisburg,...

  1. 77 FR 46439 - Decision To Evaluate a Petition To Designate a Class of Employees From the Baker Brothers Site in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-03

    ... HUMAN SERVICES Decision To Evaluate a Petition To Designate a Class of Employees From the Baker Brothers Site in Toledo, Ohio, To Be Included in the Special Exposure Cohort AGENCY: National Institute for... to evaluate a petition to designate a class of employees from the Bakers Brothers site in...

  2. 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

  3. Informatics in radiology (infoRAD): HTML and Web site design for the radiologist: a primer.

    PubMed

    Ryan, Anthony G; Louis, Luck J; Yee, William C

    2005-01-01

    A Web site has enormous potential as a medium for the radiologist to store, present, and share information in the form of text, images, and video clips. With a modest amount of tutoring and effort, designing a site can be as painless as preparing a Microsoft PowerPoint presentation. The site can then be used as a hub for the development of further offshoots (eg, Web-based tutorials, storage for a teaching library, publication of information about one's practice, and information gathering from a wide variety of sources). By learning the basics of hypertext markup language (HTML), the reader will be able to produce a simple and effective Web page that permits display of text, images, and multimedia files. The process of constructing a Web page can be divided into five steps: (a) creating a basic template with formatted text, (b) adding color, (c) importing images and multimedia files, (d) creating hyperlinks, and (e) uploading one's page to the Internet. This Web page may be used as the basis for a Web-based tutorial comprising text documents and image files already in one's possession. Finally, there are many commercially available packages for Web page design that require no knowledge of HTML.

  4. 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.

  5. 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.

  6. 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

  7. Autonomous Underwater Vehicle Survey Design for Monitoring Carbon Capture and Storage Sites

    NASA Astrophysics Data System (ADS)

    Bull, J. M.; Cevatoglu, M.; Connelly, D.; Wright, I. C.; McPhail, S.; Shitashima, K.

    2013-12-01

    Long-term monitoring of sub-seabed Carbon Capture and Storage (CCS) sites will require systems that are flexible, independent, and have long-endurance. In this presentation we will discuss the utility of autonomous underwater vehicles equipped with different sensor packages in monitoring storage sites. We will present data collected using Autosub AUV, as part of the ECO2 project, from the Sleipner area of the North Sea. The Autosub AUV was equipped with sidescan sonar, an EM2000 multibeam systems, a Chirp sub-bottom profiler, and a variety of chemical sensors. Our presentation will focus on survey design, and the simultaneous use of multiple sensor packages in environmental monitoring on the continental shelf.

  8. Computational approaches for de novo design and redesign of metal-binding sites on proteins.

    PubMed

    Akcapinar, Gunseli Bayram; Sezerman, Osman Ugur

    2017-04-28

    Metal ions play pivotal roles in protein structure, function and stability. The functional and structural diversity of proteins in nature expanded with the incorporation of metal ions or clusters in proteins. Approximately one-third of these proteins in the databases contain metal ions. Many biological and chemical processes in nature involve metal ion-binding proteins, aka metalloproteins. Many cellular reactions that underpin life require metalloproteins. Most of the remarkable, complex chemical transformations are catalysed by metalloenzymes. Realization of the importance of metal-binding sites in a variety of cellular events led to the advancement of various computational methods for their prediction and characterization. Furthermore, as structural and functional knowledgebase about metalloproteins is expanding with advances in computational and experimental fields, the focus of the research is now shifting towards de novo design and redesign of metalloproteins to extend nature's own diversity beyond its limits. In this review, we will focus on the computational toolbox for prediction of metal ion-binding sites, de novo metalloprotein design and redesign. We will also give examples of tailor-made artificial metalloproteins designed with the computational toolbox.

  9. 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)).

  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. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. Uncertainty based optimal monitoring network design for a chlorinated hydrocarbon contaminated site.

    PubMed

    Chadalavada, Sreenivasulu; Datta, Bithin; Naidu, Ravi

    2011-02-01

    An application of a newly developed optimal monitoring network for the delineation of contaminants in groundwater is demonstrated in this study. Designing a monitoring network in an optimal manner helps to delineate the contaminant plume with a minimum number of monitoring wells at optimal locations at a contaminated site. The basic principle used in this study is that the wells are installed where the measurement uncertainties are minimum at the potential monitoring locations. The development of the optimal monitoring network is based on the utilization of contaminant concentration data from an existing initial arbitrary monitoring network. The concentrations at the locations that were not sampled in the study area are estimated using geostatistical tools. The uncertainty in estimating the contaminant concentrations at such locations is used as design criteria for the optimal monitoring network. The uncertainty in the study area was quantified by using the concentration estimation variances at all the potential monitoring locations. The objective function for the monitoring network design minimizes the spatial concentration estimation variances at all potential monitoring well locations where a monitoring well is not to be installed as per the design criteria. In the proposed methodology, the optimal monitoring network is designed for the current management period and the contaminant concentration data estimated at the potential observation locations are then used as the input to the network design model. The optimal monitoring network is designed for the consideration of two different cases by assuming different initial arbitrary existing data. Three different scenarios depending on the limit of the maximum number of monitoring wells that can be allowed at any period are considered for each case. In order to estimate the efficiency of the developed optimal monitoring networks, mass estimation errors are compared for all the three different scenarios of the two

  18. Design and Construction of Deinococcus Radiodurans for Biodegradation of Organic Toxins at Radioactive DOE Waste Sites

    SciTech Connect

    Michael J. Daly; Lawrence P. Wackett; James K. Fredrickson

    2001-04-22

    Seventy million cubic meters of ground and three trillion liters of groundwater have been contaminated by leaking radioactive waste generated in the United States during the Cold War. A cleanup technology is being developed based on the extremely radiation resistant bacterium Deinococcus radiodurans that is being engineered to express bioremediating functions. Research aimed at developing D. radiodurans for organic toxin degradation in highly radioactive waste sites containing radionuclides, heavy metals, and toxic organic compounds was started by this group.Work funded by the existing grant has already contributed to eleven papers on the fundamental biology of D. radiodurans and its design for bioremediation of highly radioactive waste environments

  19. 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

  20. Oxidative stress alters base excision repair pathway and increases apoptotic response in Apurinic/apyrimidinic endonuclease 1/Redox factor-1 haploinsufficient mice

    PubMed Central

    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.

    2009-01-01

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is the redox regulator of multiple stress-inducible transcription factors, such as NF-κB, and the major 5’-endonuclease in base excision repair (BER). We utilized mice containing 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-κB DNA binding activity in response to oxidative stress in liver. In addition, loss of APE1/Ref-1 increases the apoptotic response to oxidative stress where a significant increase in GADD45g expression, p53 protein stability and caspase activity are observed. Oxidative stress displays a differential impact on monofunctional (UDG) and bifunctional (OGG1) DNA glycosylase initiated BER in liver of Apex+/- mice. APE1/Ref-1 haploinsufficiency results in a significant decline in the repair of oxidized bases (e.g., 8-OHdG), while 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

  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

    DOE PAGES

    Liu, Daniel S.; Nivon, Lucas G.; Richter, Florian; ...

    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

  3. 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

    ... 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 mouth... an EIS to designate a new ODMDS offshore the mouth of the St. Johns River. The EIS will provide...

  4. 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

    ...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 76-DESIGN AND CONSTRUCTION Design and Construction § 102-76.20... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false What issues must Federal agencies consider in providing site planning and landscape design services? 102-76.20 Section...

  5. 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

    ...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 76-DESIGN AND CONSTRUCTION Design and Construction § 102-76.20... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What issues must Federal agencies consider in providing site planning and landscape design services? 102-76.20 Section...

  6. 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

    ... Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 76-DESIGN AND CONSTRUCTION Design... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false What sustainable development principles must Federal agencies apply to the siting, design, and construction of new...

  7. 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

    ...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 76-DESIGN AND CONSTRUCTION Design and Construction § 102-76.20... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false What issues must Federal agencies consider in providing site planning and landscape design services? 102-76.20 Section...

  8. 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

    ... Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 76-DESIGN AND CONSTRUCTION Design... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false What sustainable development principles must Federal agencies apply to the siting, design, and construction of new...

  9. 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

    ...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 76-DESIGN AND CONSTRUCTION Design and Construction § 102-76.20... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What issues must Federal agencies consider in providing site planning and landscape design services? 102-76.20 Section...

  10. 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

    ... Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 76-DESIGN AND CONSTRUCTION Design... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false What sustainable development principles must Federal agencies apply to the siting, design, and construction of new...

  11. 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

    ... Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 76-DESIGN AND CONSTRUCTION Design... 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...

  12. 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.

  13. Structure-based drug design: exploring the proper filling of apolar pockets at enzyme active sites.

    PubMed

    Zürcher, Martina; Diederich, François

    2008-06-20

    The proper filling of apolar pockets at enzyme active sites is central for increasing binding activity and selectivity of hits and leads in medicinal chemistry. In our structure-based design approach toward the generation of potent enzyme inhibitors, we encountered a variety of challenges in gaining suitable binding affinity from the occupation of such pockets. We summarize them here for the first time. A fluorine scan of tricyclic thrombin inhibitors led to the discovery of favorable orthogonal dipolar C-F...CO interactions. Efficient cation-pi interactions were established in the S4 pocket of factor Xa, another serine protease from the blood coagulation cascade. Changing from mono- to bisubstrate inhibitors of catechol O-methyltransferase, a target in the L-Dopa-based treatment of Parkinson's disease, enabled the full exploitation of a previously unexplored hydrophobic pocket. Conformational preorganization of a pocket at an enzyme active site is crucial for harvesting binding affinity. This is demonstrated for two enzymes from the nonmevalonate pathway of isoprenoid biosynthesis, IspE and IspF, which are pursued as antimalarial targets. Disrupting crystallographically defined water networks on the way into a pocket might cost all of the binding free enthalpy gained from its occupation, as revealed in studies with tRNA-guanine transglycosylase, a target against shigellosis. Investigations of the active site of plasmepsin II, another antimalarial target, showed that principles for proper apolar cavity filling, originally developed for synthetic host-guest systems, are also applicable to enzyme environments.

  14. The water network in galectin-3 ligand binding site guides inhibitor design.

    PubMed

    Su, Jiyong; Zhang, Tao; Wang, Peiqi; Liu, Fengjian; Tai, Guihua; Zhou, Yifa

    2015-03-01

    Galectin-3 (Gal-3) which shows affinity of β-galactosides is a cancer-related protein. Thus, it is important to understand its ligand binding mechanism and then design its specific inhibitor. It was suggested that the positions of water molecules in Gal-3 ligand-binding site could be replaced by appropriate chemical groups of ideal inhibitors. However, the reported structures of Gal-3 carbohydrate recognition domain (CRD) complexed with lactose showed that the number of water molecules are different and the water positions are inconsistent in the ligand-binding site. This study reported four high-resolution (1.24-1.19 Å) structures of Gal-3 CRD complexed with lactose, and accurately located 12 conserved water molecules in the water network of Gal-3 CRD ligand-binding site by merging these structures. These water molecules either directly stabilize the binding of Gal-3 CRD and lactose, or hold the former water molecules at the right place. In particular, water molecule 4 (W4) which only coordinates with water molecule 5 (W5) and water molecule 6 (W6) plays a key role in stabilizing galactose residue. In addition, by three-dimensional alignment of the positions of all residues, 14 flexible parts of Gal-3 CRD were found to dynamically fluctuate in the crystalline environment.

  15. Development and application of site mapping methods for the design of glycosaminoglycans.

    PubMed

    Agostino, Mark; Gandhi, Neha S; Mancera, Ricardo L

    2014-09-01

    Glycosaminoglycans (GAGs) are complex polysaccharides involved in a wide range of biological signaling events, as well as being important as biological structural materials. Despite the ubiquity and importance of GAG-protein interactions in biological systems and potentially as therapeutic targets, detailed structures of such interactions are sparse in availability. Computational methods can provide detailed structural knowledge of these interactions; however, they should be evaluated against suitable test systems prior to their widespread use. In this study, we have investigated the application of automated molecular docking and interaction mapping techniques to characterizing GAG-protein interactions. A series of high-resolution X-ray crystal structures of GAGs in complex with proteins was used to evaluate the approaches. Accurately scoring the pose fitting best with the crystal structure was a challenge for all docking programs evaluated. The site mapping technique offered excellent prediction of the key residues involved in ligand recognition, comparable to the best pose and improved over the top-ranked pose. A design protocol incorporating site- and ligand-based mapping techniques was developed and applied to identify GAGs capable of binding to acidic fibroblast growth factor (aFGF). The protocol was able to identify ligands known to bind to aFGF and accurately able to predict the binding modes of those ligands when using a known ligand-binding conformation of the protein. This study demonstrates the value of mapping-based techniques in identifying specific GAG epitopes recognized by proteins and for GAG-based drug design.

  16. Structure-guided inhibitor design for human FAAH by interspecies active site conversion.

    PubMed

    Mileni, Mauro; Johnson, Douglas S; Wang, Zhigang; Everdeen, Daniel S; Liimatta, Marya; Pabst, Brandon; Bhattacharya, Keshab; Nugent, Richard A; Kamtekar, Satwik; Cravatt, Benjamin F; Ahn, Kay; Stevens, Raymond C

    2008-09-02

    The integral membrane enzyme fatty acid amide hydrolase (FAAH) hydrolyzes the endocannabinoid anandamide and related amidated signaling lipids. Genetic or pharmacological inactivation of FAAH produces analgesic, anxiolytic, and antiinflammatory phenotypes but not the undesirable side effects of direct cannabinoid receptor agonists, indicating that FAAH may be a promising therapeutic target. Structure-based inhibitor design has, however, been hampered by difficulties in expressing the human FAAH enzyme. Here, we address this problem by interconverting the active sites of rat and human FAAH using site-directed mutagenesis. The resulting humanized rat (h/r) FAAH protein exhibits the inhibitor sensitivity profiles of human FAAH but maintains the high-expression yield of the rat enzyme. We report a 2.75-A crystal structure of h/rFAAH complexed with an inhibitor, N-phenyl-4-(quinolin-3-ylmethyl)piperidine-1-carboxamide (PF-750), that shows strong preference for human FAAH. This structure offers compelling insights to explain the species selectivity of FAAH inhibitors, which should guide future drug design programs.

  17. 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.

  18. 77 FR 29644 - Decision To Evaluate a Petition To Designate a Class of Employees From the Hanford Site in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ...: 2012-12094] DEPARTMENT OF HEALTH AND HUMAN SERVICES Decision To Evaluate a Petition To Designate a Class of Employees From the Hanford Site in Richland, WA, To Be Included in the Special Exposure Cohort... Hanford site in Richland, Washington, to be included in the Special Exposure Cohort under the...

  19. Creating patient and family education web sites: design and content of the home parenteral nutrition family caregivers web site.

    PubMed

    Fitzgerald, Sharon A; Macan Yadrich, Donna; Werkowitch, Marilyn; Piamjariyakul, Ubolrat; Smith, Carol E

    2011-11-01

    When managing chronic illnesses, caregivers repeatedly seek online information about providing complex, long-term care but often neglect to find information about how to care for themselves. Poor health among caregivers is not only detrimental to their own well-being but may also result in harm to those for whom they care. For this reason, caregivers need access to information and activities about caring for themselves in addition to the information about managing home care they are already likely to seek. The HPN Family Caregivers Web site was developed to guide caregivers through the process of caring for themselves by establishing a caregiving routine, self-monitoring their mental and physical health, and practicing good sleep hygiene, while also managing the complexities of home care. While Web site information, activities, and algorithms for managing chronic illnesses need to be specific to each population, the content guiding caregivers to care for their own health is universal.

  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. 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.

  2. 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

  3. 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.

  4. 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

    ... AGENCY Designation of an Ocean Dredged Material Disposal Site (ODMDS) in the Gulf of Mexico Off the Mouth... of an ODMDS in the Gulf of Mexico off the mouth of the Atchafalaya River, St. Mary Parish, LA... the designation of an ODMDS in the Gulf of Mexico off the mouth of the Atchafalaya River, St....

  5. 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

    ... On-Site Leased Workers From Manpower, Synova Inc., and Pinnacle Technical Resources, Corvallis, OR; Hewlett-Packard Company, Ink Jet & Web Services, World Wide Design Group, Vancouver, WA; Amended..., Ink Jet & Web Services, World Wide Design Group, Vancouver, Washington ] operated in conjunction...

  6. Activation of GLP-1 Receptor Enhances Neuronal Base Excision Repair via PI3K-AKT-Induced Expression of Apurinic/Apyrimidinic Endonuclease 1

    PubMed Central

    Yang, Jenq-Lin; Chen, Wei-Yu; Chen, Yin-Ping; Kuo, Chao-Ying; Chen, Shang-Der

    2016-01-01

    Glucagon-like peptide-1 (GLP-1) is an intestinal-secreted incretin that increases cellular glucose up-take to decrease blood sugar. Recent studies, however, suggest that the function of GLP-1 is not only to decrease blood sugar, but also acts as a neurotrophic factor that plays a role in neuronal survival, neurite outgrowth, and protects synaptic plasticity and memory formation from effects of β-amyloid. Oxidative DNA damage occurs during normal neuron-activity and in many neurological diseases. Our study describes how GLP-1 affected the ability of neurons to ameliorate oxidative DNA damage. We show that activation of GLP-1 receptor (GLP-1R) protect cortical neurons from menadione induced oxidative DNA damage via a signaling pathway involving enhanced DNA repair. GLP-1 stimulates DNA repair by activating the cyclic AMP response element binding protein (CREB) which, consequently, induces the expression of apurinic/apyrimidinic endonuclease 1 (APE1), a key enzyme in the base excision DNA repair (BER) pathway. In this study, APE1 expression was down-regulated as a consequence phosphatidylinositol-3 kinase (PI3K) suppression by the inhibitor LY294002, but not by the suppression of MEK activity. Ischemic stroke is typically caused by overwhelming oxidative-stress in brain cells. Administration of exentin-4, an analogue of GLP-1, efficiently enhanced DNA repair in brain cells of ischemic stroke rats. Our study suggests that a new function of GLP-1 is to elevate DNA repair by inducing the expression of the DNA repair protein APE1. PMID:27698937

  7. 17β-estradiol increases expression of the oxidative stress response and DNA repair protein apurinic endonuclease (Ape1) in the cerebral cortex of female mice following hypoxia.

    PubMed

    Dietrich, Alicia K; Humphreys, Gwendolyn I; Nardulli, Ann M

    2013-11-01

    While it is well established that 17β-estradiol (E2) protects the rodent brain from ischemia-induced damage, it has been unclear how this neuroprotective effect is mediated. Interestingly, convincing evidence has also demonstrated that maintaining or increasing the expression of the oxidative stress response and DNA repair protein apurinic endonuclease 1 (Ape1) is instrumental in reducing ischemia-induced damage in the brain. Since E2 increases expression of the oxidative stress response proteins Cu/Zn superoxide dismutase and thioredoxin in the brain, we hypothesized that E2 may also increase Ape1 expression and that this E2-induced expression of Ape1 may help to mediate the neuroprotective effects of E2 in the brain. To test this hypothesis, we utilized three model systems including primary cortical neurons, brain slice cultures, and whole animals. Although estrogen receptor α and Ape1 were expressed in primary cortical neurons, E2 did not alter Ape1 expression in these cells. However, immunofluorescent staining and quantitative Western blot analysis demonstrated that estrogen receptor α and Ape1 were expressed in the nuclei of cortical neurons in brain slice cultures and that E2 increased Ape1 expression in the cerebral cortex of these cultures. Furthermore, Ape1 expression was increased and oxidative DNA damage was decreased in the cerebral cortices of ovariectomized female C57Bl/6J mice that had been treated with E2 and exposed to hypoxia. Taken together, our studies demonstrate that the neuronal microenvironment may be required for increased Ape1 expression and that E2 enhances expression of Ape1 and reduces oxidative DNA damage, which may in turn help to reduce ischemia-induced damage in the cerebral cortex and mediate the neuroprotective effects of E2.

  8. 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

  9. 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.

  10. 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.

  11. 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

    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.

  12. 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.

  13. 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.

  14. Remedial action plan and site design for stabilization of the inactive uranium mill tailings site at Lakeview, Oregon: Volume 1, Text and appendices A through D

    SciTech Connect

    Chernoff, A R; Ervin, C

    1992-07-01

    The Lakeview inactive uranium processing site is in Lake County, Oregon, approximately one mile northwest of the town of Lakeview, sixteen miles north of the California-Oregon border, and 96 miles east of Klamath Falls. The total designated site covers an area of 258 acres consisting of a tailings pile (30 acres). seven evaporation ponds (69 acres), the mill buildings, and related structures. The mill buildings and other structures have been decontaminated and are currently being used by Goose Lake Lumber Company. The tailings pile at the processing site was originally stabilized by Atlantic Richfield with an earthen cover 18--24 inches thick. The average depth of the tailings, including the cover, varied from six to eight feet. There were estimated to be 662,000 cubic yards of tailings, windblown contaminated materials, and vicinity property materials. During remedial action under the Uranium Mill Tailings Remedial Action (UMTRA) Project, approximately 264,000 cubic yards of additional contaminated materials were identified from excavations required to remove thorium- and arsenic-contaminated soils. The remedial action for the Lakeview site consisted of the cleanup, relocation, consolidation, and stabilization of all residual radioactive materials and thorium- and arsenic-contaminated materials in a partially below-grade disposal cell at a location approximately seven miles northwest of the tailings site, identified as the Collins Ranch site. A cover, including a radon/infiltration barrier and rock layer for protection from erosion, was Placed on top of the tailings. A rock-soil matrix covers the topslope and provides a growth medium for vegetation. The US Department of Energy (DOE) will retain the license and surveillance and maintenance responsibilities for the final restricted site of 13 acres.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Site-specific integration and tailoring of cassette design for sustainable gene transfer.

    PubMed

    Lombardo, Angelo; Cesana, Daniela; Genovese, Pietro; Di Stefano, Bruno; Provasi, Elena; Colombo, Daniele F; Neri, Margherita; Magnani, Zulma; Cantore, Alessio; Lo Riso, Pietro; Damo, Martina; Pello, Oscar M; Holmes, Michael C; Gregory, Philip D; Gritti, Angela; Broccoli, Vania; Bonini, Chiara; Naldini, Luigi

    2011-08-21

    Integrative gene transfer methods are limited by variable transgene expression and by the consequences of random insertional mutagenesis that confound interpretation in gene-function studies and may cause adverse events in gene therapy. Site-specific integration may overcome these hurdles. Toward this goal, we studied the transcriptional and epigenetic impact of different transgene expression cassettes, targeted by engineered zinc-finger nucleases to the CCR5 and AAVS1 genomic loci of human cells. Analyses performed before and after integration defined features of the locus and cassette design that together allow robust transgene expression without detectable transcriptional perturbation of the targeted locus and its flanking genes in many cell types, including primary human lymphocytes. We thus provide a framework for sustainable gene transfer in AAVS1 that can be used for dependable genetic manipulation, neutral marking of the cell and improved safety of therapeutic applications, and demonstrate its feasibility by rapidly generating human lymphocytes and stem cells carrying targeted and benign transgene insertions.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

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

    PubMed

    Young, John A; Smith, David R; Snyder, Craig D; Lemarie, David P

    2002-06-01

    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.

  8. Preliminary thermal/thermomechanical analyses of the Site Characterization Plan's Conceptual Design for a repository containing horizontally emplaced waste packages at the Deaf Smith County site

    SciTech Connect

    Ghantous, N.Y.; Raines, G.E.

    1987-10-01

    This report presents thermal/thermomechanical analyses of the Site Characterization Plan Conceptual Design for horizontal package emplacement at the Deaf Smith County site, Texas. The repository was divided into three geometric regions. Then two-dimensional finite-element models were set up to approximate the three-dimensional nature of each region. Thermal and quasistatic thermomechanical finite-element analyses were performed to evaluate the thermal/thermomechanical responses of the three regions. The exponential-time creep law was used to represent the creep behavior of salt rock. The repository design was evaluated by comparing the thermal/thermomechanical responses obtained for the three regions with interim performance constraints. The preliminary results show that all the performance constraints are met except for those of the waste package. The following factors were considered in interpreting these results: (1) the qualitative description of the analytical responses; (2) the limitations of the analyses; and (3) either the conclusions based on overall evaluation of limitations and analytical results or the conclusions based on the fact that the repository design may be evaluated only after further analyses. Furthermore, a parametric analysis was performed to estimate the effect of material parameters on the predicted thermal/thermomechanical response. 23 refs., 34 figs., 9 tabs.

  9. 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.

  10. 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

  11. Human Apurinic/Apyrimidinic Endonuclease siRNA Inhibits the Angiogenesis Induced by X-Ray Irradiation in Lung Cancer Cells

    PubMed Central

    Gu, Xianqing; Cun, Yanping; Li, Mengxia; Qing, Yi; Jin, Feng; Zhong, Zhaoyang; Dai, Nan; Qian, Chengyuan; Sui, Jiangdong; Wang, Dong

    2013-01-01

    Objective: Radiotherapy is an important and effective treatment method for non-small cell lung cancer (NSCLC). Nonetheless, radiotherapy can alter the expression of proangiogenic molecules and induce angiogenesis. Human apurinic/apyrimidinic endonuclease (APE1) is a multifunctional protein, which has DNA repair and redox function. Our previous studies indicated APE1 is also a crucial angiogenic regulator. Thus, we investigated the effect of APE1 on radiation-induced angiogenesis in lung cancer and its underlying mechanism. Methods: Tumor specimens of 136 patients with NSCLC were obtained from 2003 to 2008. The APE1 and vascular endothelial growth factor (VEGF) expression, as well as microvessel density (MVD) were observed with immunohistochemistry in tumor samples. Human lung adenocarcinoma A549 cells were treated with Ad5/F35-APE1 siRNA and/or irradiation, and then the cells were used for APE1 analysis by Western blot and VEGF analysis by RT-PCR and ELISA. To elucidate the underline mechanism of APE1 on VEGF expression, HIF-1α protein level was determined by Western blot, and the DNA binding activity of HIF-1α was detected by EMSA. Transwell migration assay and capillary-like structure assay were used to observe the migration and capillary-like structure formation ability of human umbilical veins endothelial cells (HUVECs) that were co-cultured with Ad5/F35-APE1 siRNA and (or) irradiation treated A549 cells culture medium. Results: The high expression rates of APE1 and VEGF in NSCLC were 77.94% and 66.18%, respectively. The expressions of APE1 was significantly correlated with VEGF and MVD (r=0.369, r=0.387). APE1 and VEGF high expression were significantly associated with reduced disease free survival (DFS) time. The high expressions of APE1 and VEGF on A549 cells were concurrently induced by X-ray irradiation in a dose-dependent manner. Silencing of APE1 by Ad5/F35-APE1 siRNA significantly decreased DNA binding activity of HIF-1α and suppressed the expression

  12. 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).

  13. Independent Design Review: Grants Chlorinated Solvents Plume, Superfund Site, Grants, Cibola County, New Mexico, EPA Region 6

    EPA Pesticide Factsheets

    The Grants Chlorinated Solvents Plume Superfund Site in Grants, Cibola County, New Mexico was selected by EPA OSRTI based on a nomination from EPA Region 6. The remedy is in the early design stage and has an estimated cost of $29.5 million.

  14. 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…

  15. 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...

  16. Designing personable and informative job recruiting web sites: testing the effect of the design on attractiveness and intent to apply.

    PubMed

    Thoms, Peg; Chinn, Susan J; Goodrich, Jana; Howard, Gary

    2004-06-01

    To date, most of the limited research conducted about the efficacy of corporate job recruiting web sites has been either anecdotal or based on field surveys. In this study, the effects of using a photograph, a friendly text message, and a list of job tasks in job descriptions were measured on undergraduates' ratings of the Personableness and Informativeness of recruiting web sites. In addition, the relationships between ratings of Personableness and Informativeness on perceptions of organizational Attractiveness and Intent to Apply were tested. Use of a photograph increased ratings of both Personableness and Informativeness. Additional results are provided and directions for research suggested.

  17. Self-catalyzed site-specific depurination of G residues mediated by cruciform extrusion in closed circular DNA plasmids.

    PubMed

    Amosova, Olga; Kumar, Veena; Deutsch, Aaron; Fresco, Jacques R

    2011-10-21

    A major variety of "spontaneous" genomic damage is endogenous generation of apurinic sites. Depurination rates vary widely across genomes, occurring with higher frequency at "depurination hot spots." Recently, we discovered a site-specific self-catalyzed depurinating activity in short (14-18 nucleotides) DNA stem-loop-forming sequences with a 5'-G(T/A)GG-3' loop and T·A or G·C as the first base pair at the base of the loop; the 5'-G residue of the loop self-depurinates at least 10(5)-fold faster than random "spontaneous" depurination at pH 5. Formation of the catalytic intermediate for self-depurination in double-stranded DNA requires a stem-loop to extrude as part of a cruciform. In this study, evidence is presented for self-catalyzed depurination mediated by cruciform formation in plasmid DNA in vitro. Cruciform extrusion was confirmed, and its extent was quantitated by digestion of the plasmid with single strand-specific mung bean endonuclease, followed by restriction digestion and sequencing of resulting mung bean-generated fragments. Appearance of the apurinic site in the self-depurinating stem-loop was confirmed by digestion of plasmid DNA with apurinic endonuclease IV, followed by primer extension and/or PCR amplification to detect the endonuclease-generated strand break and identify its location. Self-catalyzed depurination was contingent on the plasmid being supercoiled and was not observed in linearized plasmids, consistent with the presence of the extruded cruciform in the supercoiled plasmid and not in the linear one. These results indicate that self-catalyzed depurination is not unique to single-stranded DNA; rather, it can occur in stem-loop structures extruding from double-stranded DNA and therefore could, in principle, occur in vivo.

  18. 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…

  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. Examination of CRISPR/Cas9 design tools and the effect of target site accessibility on Cas9 activity.

    PubMed

    Lee, Ciaran M; Davis, Timothy H; Bao, Gang

    2017-03-16

    The recent adaptation of the CRISPR/Cas9 system for targeted genome engineering has led to its widespread applications in many fields worldwide. In order to better understand the design rules of CRISPR/Cas9 systems, several groups have carried out large library-based screens leading to some insight into sequence preferences among highly active target sites. To facilitate CRISPR/Cas9 design these studies have spawned a plethora of gRNA design tools with algorithms based solely on direct or indirect sequence features. Here we demonstrate that the predictive power of these tools is poor, suggesting that sequence features alone cannot accurately inform the cutting efficiency of a particular CRISPR/Cas9 gRNA design. Furthermore we demonstrate that DNA target site accessibility influences the activity of CRISPR/Cas9. With further optimisation we hypothesise that it will be possible to increase the predictive power of gRNA design tools by including both sequence and target site accessibility metrics. This article is protected by copyright. All rights reserved.

  1. 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.

  2. Rational design of a functional metalloenzyme: introduction of a site for manganese binding and oxidation into a heme peroxidase.

    PubMed

    Wilcox, S K; Putnam, C D; Sastry, M; Blankenship, J; Chazin, W J; McRee, D E; Goodin, D B

    1998-12-01

    The design of a series of functionally active models for manganese peroxidase (MnP) is described. Artificial metal binding sites were created near the heme of cytochrome c peroxidase (CCP) such that one of the heme propionates could serve as a metal ligand. At least two of these designs, MP6.1 and MP6.8, bind Mn2+ with Kd congruent with 0.2 mM, react with H2O2 to form stable ferryl heme species, and catalyze the steady-state oxidation of Mn2+ at enhanced rates relative to WT CCP. The kinetic parameters for this activity vary considerably in the presence of various dicarboxylic acid chelators, suggesting that the similar features displayed by native MnP are largely intrinsic to the manganese oxidation reaction rather than due to a specific interaction between the chelator and enzyme. Analysis of pre-steady-state data shows that electron transfer from Mn2+ to both the Trp-191 radical and the ferryl heme center of compound ES is enhanced by the metal site mutations, with transfer to the ferryl center showing the greatest stimulation. These properties are perplexingly similar to those reported for an alternate model for this site (1), despite rather distinct features of the two designs. Finally, we have determined the crystal structure at 1.9 A of one of our designs, MP6.8, in the presence of MnSO4. A weakly occupied metal at the designed site appears to coordinate two of the proposed ligands, Asp-45 and the heme 7-propionate. Paramagnetic nuclear magnetic resonance spectra also suggest that Mn2+ is interacting with the heme 7-propionate in MP6.8. The structure provides a basis for understanding the similar results of Yeung et al. (1), and suggests improvements for future designs.

  3. Data for the geochemical investigation of UMTRAP designated site at Tuba City, Arizona

    SciTech Connect

    Markos, G.; Bush, K.J.

    1983-09-01

    This report contains the geochemical data and the methods of data collection from the former tailings site at Tuba City, Arizona. Data are from a one-time sampling of waters and solid material from the background, the area adjacent to the site, and the site. Selected solid samples are water extracted to remove easily soluble salts and acid extracted to remove carbonates and hydroxides. The waters, extracts, and solid samples were analyzed for selected major and trace elements. 4 refs., 2 figs., 1 tab.

  4. 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.

  5. Final Report: Independent Design Review, Celanese Fiber Operations Superfund Site, Shelby, North Carolina, EPA Region 4

    EPA Pesticide Factsheets

    The Celanese site is located in Shelby, North Carolina. Operation of the P&T system was discontinued on a trial basis for two years to evaluate monitored natural attenuation as a potential ground water remedy.

  6. System-wide design issues for the stellar interferometer technology experiment (SITE)

    NASA Astrophysics Data System (ADS)

    Miller, David W.; Crawford, Samuel L.; Hyde, Tristram T.; Masters, B. P.; Crawley, Edward F.; Blackwood, Gary H.; Colavita, M. Mark; Yu, Jeffrey W.; Shao, Michael; Laskin, Robert A.

    1995-06-01

    The Stellar Interferometer Technology Experiment (SITE) is a near-term precursor mission for spaceborne optical interferometry. Proposed by the MIT Space Engineering Research Center and NASA's Jet Propulsion Laboratory, SITE is a two-aperture stellar interferometer located in the payload bay of the Space Shuttle. It has a baseline of four meters, operates with a detection bandwidth of 300 nanometers in the visible spectrum, and consists of three optical benches kinematically mounted inside a precision truss structure. The objective of SITE is to demonstrate system-level functionality of a space-based stellar interferometer through the use of enabling and enhancing Controlled Structures Technologies such as vibration isolation and suppression. Moreover, SITE will validate, in the space environment, technologies such as optical delay lines, laser metrology systems, fringe detectors, active fringe trackers, and high- bandwidth pointing control systems which are critical for realizing future space-based astrometric and imaging interferometers.

  7. 75 FR 54497 - Ocean Dumping; Guam Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-08

    ... surveillance programs to prevent adverse long-range impacts. The size, configuration, and location of any... other such sites that have been historically used. The island of Guam is volcanic and not part of...

  8. 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...

  9. Cognitive Issues in the Design and Deployment of Interactive Hypermedia: Implications for Authoring WWW Sites.

    ERIC Educational Resources Information Center

    Ebersole, Samuel

    1997-01-01

    In designing effective interactive media, cognitive psychology, human factors, psycholinguistics, semiotics, and communication theory should be considered. This article defines interactive media, considers interactive hypermedia design and the cognitive processes of designer and user, and examines the World Wide Web and Netscape Navigator, a…

  10. 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…

  11. Site-specific investigations and preliminary design for the Gorleben repository

    SciTech Connect

    Brennecke, P.; Kranz, H.; Schneider, H. )

    1992-01-01

    In the Federal Republic of Germany, the disposal of radioactive waste is being planned for deep geologic formations only. A repository will be constructed in the Gorleben salt dome for all kinds of radioactive waste, in particular, heat-generating waste from reprocessing and spent fuel. Pusuant to German safety criteria, a detailed site characterization program including above-ground and underground investigations must be performed to provide all necessary data for the site-specific safety assessment.

  12. ICRPfinder: a fast pattern design algorithm for coding sequences and its application in finding potential restriction enzyme recognition sites

    PubMed Central

    Li, Chao; Li, Yuhua; Zhang, Xiangmin; Stafford, Phillip; Dinu, Valentin

    2009-01-01

    Background Restriction enzymes can produce easily definable segments from DNA sequences by using a variety of cut patterns. There are, however, no software tools that can aid in gene building -- that is, modifying wild-type DNA sequences to express the same wild-type amino acid sequences but with enhanced codons, specific cut sites, unique post-translational modifications, and other engineered-in components for recombinant applications. A fast DNA pattern design algorithm, ICRPfinder, is provided in this paper and applied to find or create potential recognition sites in target coding sequences. Results ICRPfinder is applied to find or create restriction enzyme recognition sites by introducing silent mutations. The algorithm is shown capable of mapping existing cut-sites but importantly it also can generate specified new unique cut-sites within a specified region that are guaranteed not to be present elsewhere in the DNA sequence. Conclusion ICRPfinder is a powerful tool for finding or creating specific DNA patterns in a given target coding sequence. ICRPfinder finds or creates patterns, which can include restriction enzyme recognition sites, without changing the translated protein sequence. ICRPfinder is a browser-based JavaScript application and it can run on any platform, in on-line or off-line mode. PMID:19747395

  13. Catalytic residues in hydrolases: analysis of methods designed for ligand-binding site prediction

    PubMed Central

    Jadczyk, Tomasz; Roterman, Irena

    2010-01-01

    The comparison of eight tools applicable to ligand-binding site prediction is presented. The methods examined cover three types of approaches: the geometrical (CASTp, PASS, Pocket-Finder), the physicochemical (Q-SiteFinder, FOD) and the knowledge-based (ConSurf, SuMo, WebFEATURE). The accuracy of predictions was measured in reference to the catalytic residues documented in the Catalytic Site Atlas. The test was performed on a set comprising selected chains of hydrolases. The results were analysed with regard to size, polarity, secondary structure, accessible solvent area of predicted sites as well as parameters commonly used in machine learning (F-measure, MCC). The relative accuracies of predictions are presented in the ROC space, allowing determination of the optimal methods by means of the ROC convex hull. Additionally the minimum expected cost analysis was performed. Both advantages and disadvantages of the eight methods are presented. Characterization of protein chains in respect to the level of difficulty in the active site prediction is introduced. The main reasons for failures are discussed. Overall, the best performance offers SuMo followed by FOD, while Pocket-Finder is the best method among the geometrical approaches. Electronic supplementary material The online version of this article (doi:10.1007/s10822-010-9402-0) contains supplementary material, which is available to authorized users. PMID:21104192

  14. Catalytic residues in hydrolases: analysis of methods designed for ligand-binding site prediction

    NASA Astrophysics Data System (ADS)

    Prymula, Katarzyna; Jadczyk, Tomasz; Roterman, Irena

    2011-02-01

    The comparison of eight tools applicable to ligand-binding site prediction is presented. The methods examined cover three types of approaches: the geometrical (CASTp, PASS, Pocket-Finder), the physicochemical (Q-SiteFinder, FOD) and the knowledge-based (ConSurf, SuMo, WebFEATURE). The accuracy of predictions was measured in reference to the catalytic residues documented in the Catalytic Site Atlas. The test was performed on a set comprising selected chains of hydrolases. The results were analysed with regard to size, polarity, secondary structure, accessible solvent area of predicted sites as well as parameters commonly used in machine learning (F-measure, MCC). The relative accuracies of predictions are presented in the ROC space, allowing determination of the optimal methods by means of the ROC convex hull. Additionally the minimum expected cost analysis was performed. Both advantages and disadvantages of the eight methods are presented. Characterization of protein chains in respect to the level of difficulty in the active site prediction is introduced. The main reasons for failures are discussed. Overall, the best performance offers SuMo followed by FOD, while Pocket-Finder is the best method among the geometrical approaches.

  15. 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).

  16. 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.

  17. The design and implementation of web mining in web sites security

    NASA Astrophysics Data System (ADS)

    Li, Jian; Zhang, Guo-Yin; Gu, Guo-Chang; Li, Jian-Li

    2003-06-01

    The backdoor or information leak of Web servers can be detected by using Web Mining techniques on some abnormal Web log and Web application log data. The security of Web servers can be enhanced and the damage of illegal access can be avoided. Firstly, the system for discovering the patterns of information leakages in CGI scripts from Web log data was proposed. Secondly, those patterns for system administrators to modify their codes and enhance their Web site security were provided. The following aspects were described: one is to combine web application log with web log to extract more information, so web data mining could be used to mine web log for discovering the information that firewall and Information Detection System cannot find. Another approach is to propose an operation module of web site to enhance Web site security. In cluster server session, Density-Based Clustering technique is used to reduce resource cost and obtain better efficiency.

  18. Design of protease-resistant myelin basic protein-derived peptides by cleavage site directed amino acid substitutions.

    PubMed

    Burster, Timo; Marin-Esteban, Viviana; Boehm, Bernhard O; Dunn, Shannon; Rotzschke, Olaf; Falk, Kirsten; Weber, Ekkehard; Verhelst, Steven H L; Kalbacher, Hubert; Driessen, Christoph

    2007-11-15

    Multiple Sclerosis (MS) is considered to be a T cell-mediated autoimmune disease. An attractive strategy to prevent activation of autoaggressive T cells in MS, is the use of altered peptide ligands (APL), which bind to major histocompatibility complex class II (MHC II) molecules. To be of clinical use, APL must be capable of resisting hostile environments including the proteolytic machinery of antigen presenting cells (APC). The current design of APL relies on cost- and labour-intensive strategies. To overcome these major drawbacks, we used a deductive approach which involved modifying proteolytic cleavage sites in APL. Cleavage site-directed amino acid substitution of the autoantigen myelin basic protein (MBP) resulted in lysosomal protease-resistant, high-affinity binding peptides. In addition, these peptides mitigated T cell activation in a similar fashion as conventional APL. The strategy outlined allows the development of protease-resistant APL and provides a universal design strategy to improve peptide-based immunotherapeutics.

  19. 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.

  20. Two Simple Leg Net Devices Designed to Protect Lower-Extremity Skin Grafts and Donor Sites and Prevent Decubitus Ulcer

    DTIC Science & Technology

    2007-02-01

    Two Simple Leg Net Devices Designed to Protect Lower-Extremity Skin Grafts and Donor Sites and Prevent Decubitus Ulcer Travis L. Hedman, MPT, OCS... decubitus . Pressure ulcer is a serious health prob- lem and can cause pain, suffering, disability, and even death.1,2 The cost of treatment for a...single pressure decubitus has been estimated to be as high as $70,000.3 Therefore, prevention is paramount. The prevention of pressure ulcers is far less

  1. 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

  2. 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…

  3. 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.…

  4. 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...

  5. 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...

  6. 75 FR 19311 - Ocean Dumping; Guam Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-14

    ... and surveillance programs to prevent adverse long-range impacts. The size, configuration, and location... other such sites that have been historically used. The island of Guam is volcanic and not part of a... islands areas, exacerbating the problem-- Prevailing currents to the west would prevent these...

  7. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 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 result in erosion that will require ongoing active maintenance in the future. (6) The disposal site...

  8. 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.

  9. 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

  10. 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.

  11. "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…

  12. 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.

  13. 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)

  14. HPC Analysis of Multiple Binding Sites Communication and Allosteric Modulations in Drug Design: The HSP Case Study.

    PubMed

    Chiappori, Federica; Milanesi, Luciano; Merelli, Ivan

    2016-01-01

    Allostery is a long-range macromolecular mechanism of internal regulation, in which the binding of a ligand in an allosteric site induces distant conformational changes in a distant portion of the protein, modifying its activity. From the drug design point of view, this mechanism can be exploited to achieve important therapeutic effects, since ligands able to bind allosteric sites may be designed to regulate target proteins. Computational tools are a valid support in this sense, since they allow the characterization of allosteric communications within proteins, which are essential to design modulator ligands. While considering long-range interactions in macromolecules, the principal drug design tool available to researcher is molecular dynamics, and related applications, since it allows the evaluation of conformational changes of a protein bound to a ligand. In particular, all-atoms molecular dynamics is suitable to verify the internal mechanisms that orchestrate allosteric communications, in order to identify key residues and internal pathways that modify the protein behaviour. The problem is that these techniques are heavily time-consuming and computationally intensive, thus high performance computing systems, including parallel computing and GPU-accelerated computations, are necessary to achieve results in a reasonable time. In this review, we will discuss how it is possible to exploit in silico approaches to characterize allosteric modulations and long-range interactions within proteins, describing the case study of the Heat Shock Proteins, a class of chaperons regulated by stress conditions, which is particularly important since it is involved in many cancers and neurodegenerative diseases.

  15. 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)

  16. Biological Characterization of an Improved Pyrrole-Based Colchicine Site Agent Identified through Structure-Based Design

    PubMed Central

    Rohena, Cristina C.; Telang, Nakul S.; Da, Chenxiao; Risinger, April L.; Sikorski, James A.; Kellogg, Glen E.; Gupton, John T.

    2016-01-01

    A refined model of the colchicine site on tubulin was used to design an improved analog of the pyrrole parent compound, JG-03-14. The optimized compound, NT-7-16, was evaluated in biological assays that confirm that it has potent activities as a new colchicine site microtubule depolymerizer. NT-7-16 exhibits antiproliferative and cytotoxic activities against multiple cancer cell lines, with IC50 values of 10–16 nM, and it is able to overcome drug resistance mediated by the expression of P-glycoprotein and the βIII isotype of tubulin. NT-7-16 initiated the concentration-dependent loss of cellular microtubules and caused the formation of abnormal mitotic spindles, leading to mitotic accumulation. The direct interaction of NT-7-16 with purified tubulin was confirmed, and it was more potent than combretastatin A-4 in these assays. Binding studies verified that NT-7-16 binds to tubulin within the colchicine site. The antitumor effects of NT-7-16 were evaluated in an MDA-MB-435 xenograft model and it had excellent activity at concentrations that were not toxic. A second compound, NT-9-21, which contains dichloro moieties in place of the 3,5-dibromo substituents of NT-7-16, had a poorer fit within the colchicine site as predicted by modeling and the Hydropathic INTeractions score. Biological evaluations showed that NT-9-21 has 10-fold lower potency than NT-7-16, confirming the modeling predictions. These studies highlight the value of the refined colchicine-site model and identify a new pyrrole-based colchicine-site agent with potent in vitro activities and promising in vivo antitumor actions. PMID:26655304

  17. Design.

    ERIC Educational Resources Information Center

    Online-Offline, 1998

    1998-01-01

    Provides an annotated bibliography of resources on this month's theme "Design" for K-8 language arts, art and architecture, music and dance, science, math, social studies, health, and physical education. Includes Web sites, CD-ROMs and software, videos, books, audiotapes, magazines, professional resources and classroom activities.…

  18. The Phylogeny and Active Site Design of Eukaryotic Copper-only Superoxide Dismutases

    DOE PAGES

    Peterson, Ryan L.; Galaleldeen, Ahmad; Villarreal, Johanna; ...

    2016-08-17

    In eukaryotes the bimetallic Cu/Zn superoxide dismutase (SOD) enzymes play important roles in the biology of reactive oxygen species by disproportionating superoxide anion. We reported that the fungal pathogen Candida albicans expresses a novel copper-only SOD, known as SOD5, that lacks the zinc cofactor and electrostatic loop (ESL) domain of Cu/Zn-SODs for substrate guidance. In spite of these abnormalities, C. albicans SOD5 can disproportionate superoxide at rates limited only by diffusion. Here we demonstrate that this curious copper-only SOD occurs throughout the fungal kingdom as well as in phylogenetically distant oomycetes or “pseudofungi” species. It is the only form ofmore » extracellular SOD in fungi and oomycetes, in stark contrast to the extracellular Cu/Zn-SODs of plants and animals. Through structural biology and biochemical approaches we demonstrate that these copper-only SODs have evolved with a specialized active site consisting of two highly conserved residues equivalent to SOD5 Glu-110 and Asp-113. The equivalent positions are zinc binding ligands in Cu/Zn-SODs and have evolved in copper-only SODs to control catalysis and copper binding in lieu of zinc and the ESL. Similar to the zinc ion in Cu/Zn-SODs, SOD5 Glu-110 helps orient a key copper-coordinating histidine and extends the pH range of enzyme catalysis. Furthermore, SOD5 Asp-113 connects to the active site in a manner similar to that of the ESL in Cu/Zn-SODs and assists in copper cofactor binding. Copper-only SODs are virulence factors for certain fungal pathogens; thus this unique active site may be a target for future anti-fungal strategies.« less

  19. The Phylogeny and Active Site Design of Eukaryotic Copper-only Superoxide Dismutases

    SciTech Connect

    Peterson, Ryan L.; Galaleldeen, Ahmad; Villarreal, Johanna; Taylor, Alexander B.; Cabelli, Diane E.; Hart, P. John; Culotta, Valeria C.

    2016-08-17

    In eukaryotes the bimetallic Cu/Zn superoxide dismutase (SOD) enzymes play important roles in the biology of reactive oxygen species by disproportionating superoxide anion. We reported that the fungal pathogen Candida albicans expresses a novel copper-only SOD, known as SOD5, that lacks the zinc cofactor and electrostatic loop (ESL) domain of Cu/Zn-SODs for substrate guidance. In spite of these abnormalities, C. albicans SOD5 can disproportionate superoxide at rates limited only by diffusion. Here we demonstrate that this curious copper-only SOD occurs throughout the fungal kingdom as well as in phylogenetically distant oomycetes or “pseudofungi” species. It is the only form of extracellular SOD in fungi and oomycetes, in stark contrast to the extracellular Cu/Zn-SODs of plants and animals. Through structural biology and biochemical approaches we demonstrate that these copper-only SODs have evolved with a specialized active site consisting of two highly conserved residues equivalent to SOD5 Glu-110 and Asp-113. The equivalent positions are zinc binding ligands in Cu/Zn-SODs and have evolved in copper-only SODs to control catalysis and copper binding in lieu of zinc and the ESL. Similar to the zinc ion in Cu/Zn-SODs, SOD5 Glu-110 helps orient a key copper-coordinating histidine and extends the pH range of enzyme catalysis. Furthermore, SOD5 Asp-113 connects to the active site in a manner similar to that of the ESL in Cu/Zn-SODs and assists in copper cofactor binding. Copper-only SODs are virulence factors for certain fungal pathogens; thus this unique active site may be a target for future anti-fungal strategies.

  20. 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.

  1. 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.

  2. 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.

  3. 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…

  4. 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…

  5. 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…

  6. Biomimetic Single-Site Heterogeneous Catalysts: Design Strategies and Catalytic Potential

    NASA Astrophysics Data System (ADS)

    Xuereb, David; Dzierzak, Joanna; Raja, Robert

    Enzymes catalyze the most fundamental reactions in organic chemistry from simple oxidations of straight chain alkanes to complex C-C bond forming reactions with exceptional selectivity. Mimicking the active site of an enzyme by immobilising a well defined amino acid containing transition-metal centre on a robust inorganic framework, provides a powerful catalyst that can be utilized in the production of fine chemicals and complicated drug molecules. Porous aluminosilicates and mesoporous silicas offer suitable supports for single-site bio-derived catalysts. These materials can be created from a range of methodologies and the different strategies used for immobilisation can greatly affect the nature of the active catalyst. The routes by which these catalysts are immobilised have also given the potential to derivatize inorganic structures with amino acids, not just for complexation to metal centres but for use as organocatalysts as well. These metal free bio-derivatized frameworks offer advantages over their homogeneous counterparts and can carry out stereoselective reactions with great effectiveness. Herein, the routes to heterogenizing biomimetic catalysts will be critically assessed and depending on the methods used, suitable active catalysts for use in chemo- and stereoselective transformations can be developed.

  7. X-ray structures of a designed binding site in trypsin show metal-dependent geometry.

    PubMed

    Brinen, L S; Willett, W S; Craik, C S; Fletterick, R J

    1996-05-14

    The three-dimensional structures of complexes of trypsin N143H, E151H bound to ecotin A86H are determined at 2.0 A resolution via X-ray crystallography in the absence and presence of the transition metals Zn2+, Ni2+, and Cu2+. The binding site for these transition metals was constructed by substitution of key amino acids with histidine at the trypsin-ecotin interface in the S2'/P2' pocket. Three histidine side chains, two on trypsin at positions 143 and 151 and one on ecotin at position 86, anchor the metals and provide extended catalytic recognition for substrates with His in the P2' pocket. Comparisons of the three-dimensional structures show the different geometries that result upon the binding of metal in the engineered tridentate site and suggest a structural basis for the kinetics of the metal-regulated catalysis. Of the three metals, the binding of zinc results in the most favorable binding geometry, not dissimilar to those observed in naturally occurring zinc binding proteins.

  8. Design of Visco-Elastic Dampers for RC Frame for Site-Specific Earthquake

    NASA Astrophysics Data System (ADS)

    Kamatchi, P.; Rama Raju, K.; Ravisankar, K.; Iyer, Nagesh R.

    2016-12-01

    Number of Reinforced Concrete (RC) framed buildings have got damaged at Ahmedabad city, India located at about 240 km away from epicenter during January 2001, 7.6 moment magnitude (Mw) Bhuj earthquake. In the present study, two dimensional nonlinear time history dynamic analyses of a typical 13 storey frame assumed to be located at Ahmedabad is carried out with the rock level and surface level site-specific ground motion for scenario earthquake of Mw 7.6 from Bhuj. Artificial ground motions are generated using extended finite source stochastic model with seismological parameters reported in literature for 2001 Bhuj earthquake. Surface level ground motions are obtained for a typical soil profile of 100 m depth reported in literature through one dimensional equivalent linear wave propagation analyses. From the analyses, failure of frame is observed for surface level ground motions which indicates that, in addition to the in-adequacy of the cross sections and reinforcement of the RC members of the frame chosen, the rich energy content of the surface level ground motion near the fundamental time period of the frame has also contributed for the failure of frame. As a part of retrofitting measure, five Visco-elastic Dampers (VED) in chevron bracing are added to frame. For the frame considered in the present study, provision of VED is found to be effective to mitigate damage for the soil site considered.

  9. 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.

  10. 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.

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

    SciTech Connect

    Groat, C.; Stevenson, D.

    1990-01-01

    The research objectives of this report are to: implement and maintain the ongoing environmental monitoring program around DOE geopressured-geothermal test well in Louisiana and Texas; analyze and interpret collected data for evidence of subsidence and induced microearthquakes which may be brought about by geopressured-geothermal well testing and development; continue geological-geophysical studies of the Hulin and Gladys McCall sites incorporating new seismic data; continue review of previously identified and tested geopressured-geothermal prospects in Louisiana to determine if any link exists between such reservoirs and the existence of free gas in commercial or subcommercial quantities; and initiate review of geology, co-location and properties of geopressured brines with medium and heavy oil reservoirs in Louisiana utilizing existing maps, databases, reports, and journal articles.

  13. Active site similarity between human and Plasmodium falciparum phosphodiesterases: considerations for antimalarial drug design

    NASA Astrophysics Data System (ADS)

    Howard, Brittany L.; Thompson, Philip E.; Manallack, David T.

    2011-08-01

    The similarity between Plasmodium falciparum phosphodiesterase enzymes ( PfPDEs) and their human counterparts have been examined and human PDE9A was found to be a suitable template for the construction of homology models for each of the four PfPDE isoforms. In contrast, the architecture of the active sites of each model was most similar to human PDE1. Molecular docking was able to model cyclic guanosine monophosphate (cGMP) substrate binding in each case but a docking mode supporting cyclic adenosine monophosphate (cAMP) binding could not be found. Anticipating the potential of PfPDE inhibitors as anti-malarial drugs, a range of reported PDE inhibitors including zaprinast and sildenafil were docked into the model of PfPDEα. The results were consistent with their reported biological activities, and the potential of PDE1/9 inhibitor analogues was also supported by docking.

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

    SciTech Connect

    Not Available

    1991-01-01

    The research objectives of this report are to: implement and maintain the ongoing environmental monitoring program around DOE geopressured-geothermal test wells in Louisiana and Texas; analyze and interpret collected data for evidence of subsidence and induced microearthquakes which may be brought about by geopressured-geothermal well testing and development; continue geological-geophysical studies of the Hulin and Gladys McCall sites incorporating new seismic data; continue review of previously identified and tested geopressured-geothermal prospects in Louisiana to determine if any link exists between such reservoirs and the existence of free gas in commercial or subcommercial quantities; and initiate review of geology, co-location and properties of geopressured brines with medium and heavy oil reservoirs in Louisiana utilizing existing maps, databases, reports, and journal articles. 2 figs.

  15. 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.

  16. In silico designing of a new cysteine analogue of hirudin variant 3 for site specific PEGylation

    PubMed Central

    Sajjadi, Seyed Mehdi; Rahimi, Hamzeh; Mohammadi, Saeed; Faranoush, Mohammad; Mirzahoseini, Hasan; Toogeh, Gholamreza

    2017-01-01

    Hirudin is an anticoagulant agent of the salivary glands of the medicinal leech. Recombinant hirudin (r-Hir) displays certain drawbacks including bleeding and immunogenicity. To solve these problems, cysteine-specific PEGylation has been proposed as a successful technique. However, proper selection of the appropriate cysteine residue for substitution is a critical step. This study has, for the first time, used a computational approach aimed at identifying a single potential PEGylation site for replacement by cysteine residue in the hirudin variant 3 (HV3). Homology modeling (HM) was performed using MODELLER. All non-cysteine residues of the HV3 were replaced with the cysteine. The best model was selected based on the results of discrete optimized protein energy score, PROCHECK software, and Verify3D. The receptor binding was investigated using protein-protein docking by ClusPro web tool which was then visualized using LigPlot+ software and PyMOL. Finally, multiple sequence alignment (MSA) using ClustalW software and disulfide bond prediction were performed. According to the results of HM and docking, Q33C, which was located on the surface of the protein, was the best site for PEGylation. Furthermore, MSA showed that Q33 was not a conserved residue and LigPlot+ software showed that it is not involved in the hirudin-thrombin binding pocket. Moreover, prediction softwares established that it is not involved in disulfide bond formation. In this study, for the first time, the utility of the in silico approach for creating a cysteine analogue of HV3 was introduced. Our study demonstrated that the substitution of Q33 by cysteine probably has no effect on the biological activity of the HV3. However, experimental analyses are required to confirm the results. PMID:28255315

  17. 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.

  18. 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

  19. Design of a soil cutting resistance sensor for application in site-specific tillage.

    PubMed

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

    2013-05-10

    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.

  20. 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

  1. 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

  2. Design of accurate predictors for DNA-binding sites in proteins using hybrid SVM-PSSM method.

    PubMed

    Ho, Shinn-Ying; Yu, Fu-Chieh; Chang, Chia-Yun; Huang, Hui-Ling

    2007-01-01

    In this paper, we investigate the design of accurate predictors for DNA-binding sites in proteins from amino acid sequences. As a result, we propose a hybrid method using support vector machine (SVM) in conjunction with evolutionary information of amino acid sequences in terms of their position-specific scoring matrices (PSSMs) for prediction of DNA-binding sites. Considering the numbers of binding and non-binding residues in proteins are significantly unequal, two additional weights as well as SVM parameters are analyzed and adopted to maximize net prediction (NP, an average of sensitivity and specificity) accuracy. To evaluate the generalization ability of the proposed method SVM-PSSM, a DNA-binding dataset PDC-59 consisting of 59 protein chains with low sequence identity on each other is additionally established. The SVM-based method using the same six-fold cross-validation procedure and PSSM features has NP=80.15% for the training dataset PDNA-62 and NP=69.54% for the test dataset PDC-59, which are much better than the existing neural network-based method by increasing the NP values for training and test accuracies up to 13.45% and 16.53%, respectively. Simulation results reveal that SVM-PSSM performs well in predicting DNA-binding sites of novel proteins from amino acid sequences.

  3. 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.

  4. 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.

  5. 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.

  6. A Versatile Photoactivatable Probe Designed to Label the Diphosphate Binding Site of Farnesyl Diphosphate Utilizing Enzymes

    PubMed Central

    Henry, Olivier; Lopez-Gallego, Fernando; Agger, Sean A.; Schmidt-Dannert, Claudia; Sen, Stephanie; Shintani, David; Cornish, Katrina; Distefano, Mark D.

    2009-01-01

    Farnesyl diphosphate (FPP) is a substrate for a diverse number of enzymes found in nature. Photoactive analogues of isoprenoid diphosphates containing either benzophenone, diazotrifluropropionate or azide groups have been useful for studying both the enzymes that synthesize FPP as well as those that employ FPP as a substrate. Here we describe the synthesis and properties of a new class of FPP analogues that links an unmodified farnesyl group to a diphosphate mimic containing a photoactive benzophenone moiety; thus, importantly, these compounds are photoactive FPP analogues that contain no modifications of the isoprenoid portion of the molecule that may interfere with substrate binding in the active site of an FPP utilizing enzyme. Two isomeric compounds containing meta- and para-substituted benzophenones were prepared. These two analogues inhibit S. cerevisiae protein farnesyltransferase (ScPFTase) with IC50 values of 5.8 (meta isomer) and 3.0 µM (para isomer); the more potent analogue, the para isomer, was shown to be a competitive inhibitor of ScPFTase with respect to FPP with a KI of 0.46 µM. Radiolabeled forms of both analogues selectively labelled the β-subunit of ScPFTase. The para isomer was also shown to label E. coli farnesyl diphosphate synthase and Drosophila melanogaster farnesyl diphosphate synthase. Finally, the para isomer was shown to be an alternative substrate for a sesquiterpene synthase from Nostoc sp. strain PCC7120, a cyanobacterial source; the compound also labeled the purified enzyme upon photolysis. Taken together, these results using a number of enzymes demonstrate that this new class of probes should be useful for a plethora of studies of FPP-utilizing enzymes. PMID:19447628

  7. "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

  8. 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

  9. Site-specifically modified oligodeoxynucleotides as probes for the structural and biological effect of DNA-damaging agents

    SciTech Connect

    Basu, A.K.; Essigmann, J.M.

    1988-01-01

    This review critically analyzes the state of knowledge on the preparation, characterization, and uses of site-specifically modified DNA segments. Although these substrates have begun to have an impact upon several fields, the review focuses upon their applications in site-directed mutagenesis studies and for defining the effect of chemical damage upon DNA structure. Oligonucleotides have been synthesized containing alkylated DNA bases, aromatic amine adducts, base oxidation products, cyclic nucleic acid adducts, model apurinic/apyrimidinic sites, UV and psoralen photoadducts, and several antitumor drug-DNA covalent complexes. Below, the authors shall describe the progress to date on synthesis of site-specifically modified DNA segments and how these oligonucleotides have been used to further their understanding of the roles of individual DNA adducts in toxicology. The structures of the DNA adducts and adduct-derived products discussed in this review are presented. 168 references.

  10. Reports of Public Scoping Meetings for the Supplemental Environmental Impact Statement for the Designation of Dredged Material Disposal Sites in Eastern Long Island Sound

    EPA Pesticide Factsheets

    These reports provide summaries of the scoping meetings as part of the Supplemental Environmental Impact Statement (SEIS) process for the designation of dredged material disposal sites in Eastern Long Island Sound.

  11. 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.

  12. Compressed air energy storage: Preliminary design and site development program in an aquifer. Task 1: Establish facility design criteria and utility benefits

    NASA Astrophysics Data System (ADS)

    1980-10-01

    Compressed air energy storage (CAES) 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. 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 system results in increased net generation and greater premium fuel economy. Work performed in establishing facility design criteria for a CAES system with aquifer storage includes: 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.

  13. 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…

  14. 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…

  15. 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.

  16. 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

  17. 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

  18. Bioinspired Design and Oriented Synthesis of Immunogenic Site-Specifically Penicilloylated Peptides.

    PubMed

    Scornet, Noémie; Delarue-Cochin, Sandrine; Azoury, Marie Eliane; Le Mignon, Maxime; Chemelle, Julie-Anne; Nony, Emmanuel; Maillère, Bernard; Terreux, Raphaël; Pallardy, Marc; Joseph, Delphine

    2016-11-16

    β-Lactam antibiotics allergy is recognized as a public health concern. By covalently binding to serum proteins, penicillins are known to form immunogenic complexes. The latter are recognized and digested by antigen-presenting cells into drug-hapten peptides leading to the immunization of treated persons and IgE-mediated hypersensitivity reactions encompassing anaphylaxis. If type I allergic reactions to drugs are often unpredictable, they are known to be dependent on CD4(+) T-cells. This fundamental study revisits the chemical basis of the benzylpenicillin (BP) allergy with the aim of identifying immunologically relevant biomimetic benzylpenicilloylated peptides through the analysis of BP-conjugated human serum albumin (BP-HSA) profile and the evaluation of the naı̈ve CD4(+) T-cell responses to candidate BP-HSA-derived peptides. The chemical structures of BP-HSA bioconjugates synthesized in vitro at both physiological and basic pH were investigated by mass spectrometry. From the ten most representative lysine residues grafted by BP-hapten, HSA-bioinspired 15-mer peptide sequences were designed and the potential T-cell epitope profile of each peptide was predicted using two complementary in silico approaches, i.e., HLA class II binding prediction tools from the Immune Epitope Database and Analysis Resource (IEDB) and computational alanine scanning mutagenesis. Twelve structurally diversified benzylpenicilloylated peptides (BP-Ps) were selected and synthesized with the aid of a flexible synthesis pathway using an original benzylpenicilloylated lysine monomer as common precursor. In order to corroborate their predicted "epitope" profile, the naı̈ve CD4(+) T-cell response specific to BP was evaluated through a coculture approach. To our knowledge, this study showed for the first time the ability of bioinspired peptides structurally stemming from BP-HSA to be recognized by naı̈ve CD4(+) T-cells thus identifying a pre-existing T-cell repertoire for penicillin

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Design of a carbonic anhydrase IX active-site mimic to screen inhibitors for possible anticancer properties.

    PubMed

    Genis, Caroli; Sippel, Katherine H; Case, Nicolette; Cao, Wengang; Avvaru, Balendu Sankara; Tartaglia, Lawrence J; Govindasamy, Lakshmanan; Tu, Chingkuang; Agbandje-McKenna, Mavis; Silverman, David N; Rosser, Charles J; McKenna, Robert

    2009-02-17

    Recently, a convincing body of evidence has accumulated suggesting that the overexpression of carbonic anhydrase isozyme IX (CA IX) in some cancers contributes to the acidification of the extracellular matrix, which in turn promotes the growth and metastasis of the tumor. These observations have made CA IX an attractive drug target for the selective treatment of certain cancers. Currently, there is no available X-ray crystal structure of CA IX, and this lack of availability has hampered the rational design of selective CA IX inhibitors. In light of these observations and on the basis of structural alignment homology, using the crystal structure of carbonic anhydrase II (CA II) and the sequence of CA IX, a double mutant of CA II with Ala65 replaced by Ser and Asn67 replaced by Gln has been constructed to resemble the active site of CA IX. This CA IX mimic has been characterized kinetically using (18)O-exchange and structurally using X-ray crystallography, alone and in complex with five CA sulfonamide-based inhibitors (acetazolamide, benzolamide, chlorzolamide, ethoxzolamide, and methazolamide), and compared to CA II. This structural information has been evaluated by both inhibition studies and in vitro cytotoxicity assays and shows a correlated structure-activity relationship. Kinetic and structural studies of CA II and CA IX mimic reveal chlorzolamide to be a more potent inhibitor of CA IX, inducing an active-site conformational change upon binding. Additionally, chlorzolamide appears to be cytotoxic to prostate cancer cells. This preliminary study demonstrates that the CA IX mimic may provide a useful model to design more isozyme-specific CA IX inhibitors, which may lead to development of new therapeutic treatments of some cancers.

  4. sgRNAcas9: a software package for designing CRISPR sgRNA and evaluating potential off-target cleavage sites.

    PubMed

    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.

  5. 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

  6. Investigation of the histamine H3 receptor binding site. Design and synthesis of hybrid agonists with a lipophilic side chain.

    PubMed

    Ishikawa, Makoto; Watanabe, Takashi; Kudo, Toshiaki; Yokoyama, Fumikazu; Yamauchi, Miki; Kato, Kazuhiko; Kakui, Nobukazu; Sato, Yasuo

    2010-09-09

    As a part of our search for novel histamine H3 receptor agonists, we designed and synthesized hybrid compounds in which the lipophilic (4'-alkylphenylthio)ethyl moiety of a novel H3 receptor agonist, 4-(2-(4'-tert-butylphenylthio)ethyl)-1H-imidazole (1), was incorporated into N(alpha)-methylhistamine, immepip, and immethridine derivatives. These hybrid compounds were expected to interact concurrently with the histamine-binding site and a putative hydrophobic region in the H3 receptor. Among them, piperidine- and pyridine-type derivatives displayed partial agonist activity, and (S)-4-(1-(1H-imidazol-4-yl)-2-(4-(trifluoromethyl)phenylthio)ethyl)piperidine (36) was identified as a potent H3 agonist. We performed computational docking studies to examine the binding mode of the agonists. The results indicated that immepip interacts with the key residues, Asp114 and Glu206, in a different manner from histamine. The binding mode of 36 to these residues is similar to that of immepip, and the lipophilic tail of 36 has an additional interaction with a hydrophobic region in transmembrane helix 6 of the receptor. These results indicated that 36 served as a useful tool for studies on receptor-agonist interactions and drug design.

  7. Site-specific non-LTR retrotransposons.

    PubMed

    Fujiwara, Haruhiko

    2015-04-01

    Although most of non-long terminal repeat (non-LTR) retrotransposons are incorporated in the host genome almost randomly, some non-LTR retrotransposons are incorporated into specific sequences within a target site. On the basis of structural and phylogenetic features, non-LTR retrotransposons are classified into two large groups, restriction enzyme-like endonuclease (RLE)-encoding elements and apurinic/apyrimidinic endonuclease (APE)-encoding elements. All clades of RLE-encoding non-LTR retrotransposons include site-specific elements. However, only two of more than 20 APE-encoding clades, Tx1 and R1, contain site-specific non-LTR elements. Site-specific non-LTR retrotransposons usually target within multi-copy RNA genes, such as rRNA gene (rDNA) clusters, or repetitive genomic sequences, such as telomeric repeats; this behavior may be a symbiotic strategy to reduce the damage to the host genome. Site- and sequence-specificity are variable even among closely related non-LTR elements and appeared to have changed during evolution. In the APE-encoding elements, the primary determinant of the sequence- specific integration is APE itself, which nicks one strand of the target DNA during the initiation of target primed reverse transcription (TPRT). However, other factors, such as interaction between mRNA and the target DNA, and access to the target region in the nuclei also affect the sequence-specificity. In contrast, in the RLE-encoding elements, DNA-binding motifs appear to affect their sequence-specificity, rather than the RLE domain itself. Highly specific integration properties of these site-specific non-LTR elements make them ideal alternative tools for sequence-specific gene delivery, particularly for therapeutic purposes in human diseases.

  8. 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.

  9. Rational Design of Fatty Acid Amide Hydrolase Inhibitors that Act by Covalently Bonding to Two Active Site Residues

    PubMed Central

    Otrubova, Katerina; Brown, Monica; McCormick, Michael S.; Han, Gye W.; O’Neal, Scott T.; Cravatt, Benjamin F.; Stevens, Raymond C.; Lichtman, Aron H.; Boger, Dale L.

    2013-01-01

    The design and characterization of α-ketoheterocycle fatty acid amide hydrolase (FAAH) inhibitors are disclosed that additionally and irreversibly target a cysteine (Cys269) found in the enzyme cytosolic port while maintaining the reversible covalent Ser241 attachment responsible for their rapid and initially reversible enzyme inhibition. Two α-ketooxazoles (3 and 4) containing strategically placed electrophiles at the C5 position of the pyridyl substituent of 2 (OL-135) were prepared and examined as inhibitors of FAAH. Consistent with the observed time-dependent non-competitive inhibition, the co-crystal X-ray structure of 3 bound to a humanized variant of rat FAAH revealed that 3 was not only covalently bound to the active site catalytic nucleophile Ser241 as a deprotonated hemiketal, but also to Cys269 through the pyridyl C5-substituent, thus providing an inhibitor with dual covalent attachment in the enzyme active site. In vivo characterization of the prototypical inhibitors in mice demonstrate that they raise endogenous brain levels of FAAH substrates to a greater extent and for a much longer duration (>6 h) than the reversible inhibitor 2, indicating that the inhibitors accumulate and persist in the brain to completely inhibit FAAH for a prolonged period. Consistent with this behavior and the targeted irreversible enzyme inhibition, 3 reversed cold allodynia in the chronic constriction injury model of neuropathic pain in mice for a sustained period (>6 h) beyond that observed with the reversible inhibitor 2, providing effects that were unchanged over the 1–6 h time course monitored. PMID:23581831

  10. 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

  11. 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

  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

    ... disposal location during disposal. This method of release is expected to spread material at the Sites to... suspended by wave action near the seafloor. The Sites are not expected to change these characteristics....

  13. 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

    ... disposal. This method of release is expected to spread material at the Sites to minimize mounding and to... action near the seafloor. The proposed Sites are not expected to change these characteristics....

  14. A Hierarchical Modeling Approach to Data Analysis and Study Design in a Multi-Site Experimental fMRI Study

    ERIC Educational Resources Information Center

    Zhou, Bo; Konstorum, Anna; Duong, Thao; Tieu, Kinh H.; Wells, William M.; Brown, Gregory G.; Stern, Hal S.; Shahbaba, Babak

    2013-01-01

    We propose a hierarchical Bayesian model for analyzing multi-site experimental fMRI studies. Our method takes the hierarchical structure of the data (subjects are nested within sites, and there are multiple observations per subject) into account and allows for modeling between-site variation. Using posterior predictive model checking and model…

  15. 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.

  16. 77 FR 55144 - Ocean Dumping; Designation of Ocean Dredged Material Disposal Sites Offshore of Yaquina Bay, Oregon

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-07

    ... higher cost of monitoring sites in deeper waters and further offshore. Historic disposal has occurred at... continental shelf and other such sites where historical disposal has occurred (40 CFR 228.5(e)). Disposal... Proximity to the Site of any Significant Natural or Cultural Feature of Historical Importance (40 CFR...

  17. Detailed computational study of the active site of the hepatitis C viral RNA polymerase to aid novel drug design.

    PubMed

    Barakat, Khaled H; Law, John; Prunotto, Alessio; Magee, Wendy C; Evans, David H; Tyrrell, D Lorne; Tuszynski, Jack; Houghton, Michael

    2013-11-25

    The hepatitis C virus (HCV) RNA polymerase, NS5B, is a leading target for novel and selective HCV drug design. The enzyme has been the subject of intensive drug discovery aimed at developing direct acting antiviral (DAA) agents that inhibit its activity and hence prevent the virus from replicating its genome. In this study, we focus on one class of NS5B inhibitors, namely nucleos(t)ide mimetics. Forty-one distinct nucleotide structures have been modeled within the active site of NS5B for the six major HCV genotypes. Our comprehensive modeling protocol employed 287 different molecular dynamics simulations combined with the molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) methodology to rank and analyze these structures for all genotypes. The binding interactions of the individual compounds have been investigated and reduced to the atomic level. The present study significantly refines our understanding of the mode of action of NS5B-nucleotide-inhibitors, identifies the key structural elements necessary for their activity, and implements the tools for ranking the potential of additional much needed novel inhibitors of NS5B.

  18. 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.

  19. 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.

  20. Design of aquifer remediation systems: (2) Estimating site-specific performance and benefits of partial source removal

    NASA Astrophysics Data System (ADS)

    Wood, A. Lynn; Enfield, Carl G.; Espinoza, Felipe P.; Annable, Michael; Brooks, Michael C.; Rao, P. S. C.; Sabatini, David; Knox, Robert

    2005-12-01

    A Lagrangian stochastic model is proposed as a tool that can be utilized in forecasting remedial performance and estimating the benefits (in terms of flux and mass reduction) derived from a source zone remedial effort. The stochastic functional relationships that describe the hydraulic "structure" and non-aqueous phase liquid (NAPL) "architecture" have been described in a companion paper (Enfield, C.G., Wood, A.L., Espinoza, F.P., Brooks, M.C., Annable, M., Rao, P.S.C., this issue. Design of aquifer remediation systems: (1) describing hydraulic structure and NAPL architecture using tracers. J. Contam. Hydrol.). The previously defined functions were used along with the properties of the remedial fluids to describe remedial performance. There are two objectives for this paper. First, is to show that a simple analytic element model can be used to give a reasonable estimate of system performance. This is accomplished by comparing forecast performance to observed performance. The second objective is to display the model output in terms of change in mass flux and mass removal as a function of pore volumes of remedial fluid injected. The modelling results suggest that short term benefits are obtained and related to mass reduction at the sites where the model was tested.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Ocean Disposal Site Monitoring

    EPA Pesticide Factsheets

    EPA is responsible for managing all designated ocean disposal sites. Surveys are conducted to identify appropriate locations for ocean disposal sites and to monitor the impacts of regulated dumping at the disposal sites.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. The National Cross-Site Evaluation of High-Risk Youth Programs: Findings on Designing and Implementing Effective Prevention Programs for Youth at High Risk. Monograph Series.

    ERIC Educational Resources Information Center

    Hermann, Jack; Sambrano, Soledad; Springer, J. Fred; Nister, Mary; Sale, Elizabeth; Brounstein, Paul J.; Cordray, David; Shadish, Will; Kasim, Rafa; Pan, Wei

    This document summarizes findings from the Center for Substance Abuse Prevention's National Cross-Site Evaluation of High-Risk Youth Programs, which identified characteristics associated with strong substance abuse prevention outcomes in 48 prevention programs. It provides concrete guidance regarding what elements of design and implementation are…

  12. 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.

  13. 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…

  14. 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.

  15. 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.

  16. 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.

  17. Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes.

    PubMed Central

    Demple, B; Herman, T; Chen, D S

    1991-01-01

    Abasic (AP) sites are common, potentially mutagenic DNA damages that are attacked by AP endonucleases. The biological roles of these enzymes in metazoans have not been tested. We have cloned the human cDNA (APE) that encodes the main nuclear AP endonuclease. The predicted Ape protein, which contains likely nuclear transport signals, is a member of a family of DNA repair enzymes that includes two bacterial AP endonucleases (ExoA protein of Streptococcus pneumoniae and exonuclease III of Escherichia coli) and Rrp1 protein of Drosophila melanogaster. Purified Ape protein lacks the 3'-exonuclease activity against undamaged DNA that is found in the bacterial and Drosophila enzymes, but the lack of obvious amino acid changes to account for this difference suggests that the various enzyme functions evolved by fine tuning a conserved active site. Expression of the active human enzyme in AP endonuclease-deficient E. coli conferred significant resistance to killing by the DNA-alkylating agent methyl methanesulfonate. The APE cDNA provides a molecular tool for analyzing the role of this central enzyme in maintaining genetic stability in humans. Images PMID:1722334

  18. 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

  19. The designed protein M(II)-Gly-Lys-His-Fos(138-211) specifically cleaves the AP-1 binding site containing DNA.

    PubMed

    Harford, C; Narindrasorasak, S; Sarkar, B

    1996-04-09

    A new specific DNA cleavage protein, Gly-Lys-His-Fos(138-211), was designed, expressed, and characterized. The DNA-binding component of the design uses the basic and leucine zipper regions of the leucine zipper Fos, which are represented by Fos(138-211). The DNA cleavage moiety was provided by the design of the amino-terminal Cu(II)-, Ni(II)-binding site GKH at the amino terminus of Fos(138-211). Binding of Cu(II) or Ni(II) by the protein activates its cleavage ability. The GKH motif was predicted to form a specific amino-terminal Cu(II)-, Ni(II)-binding motif as previously defined [Predki, P. F., Harford, C., Brar, P., & Sarkar, B. (1992) Biochem. J. 287, 211 -215]. This prediction was verified as the tripeptide, GKH, and the expressed protein, GKH-Fos(138-211), were both shown to be capable of binding Cu(II) and Ni(II). The designed protein upon heterodimerization with Jun(248-334) was shown to bind to and cleave several forms of DNA which contained an AP-1 binding site. The cleavage was shown to be specific. This design demonstrates the versatility of the amino-terminal Cu(II)-, Ni(II)-binding motif and the variety of motifs which can be generated. The site of cleavage by GKH-Fos(138-211) on DNA provides further information regarding the bending of DNA upon binding to Fos-Jun heterodimers.

  20. 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.

  1. 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.

  2. Optimizing potentiometric ionophore and electrode design for environmental on-site control of antibiotic drugs: application to sulfamethoxazole.

    PubMed

    Almeida, S A A; Truta, Liliana A A N A; Queirós, Raquel B; Montenegro, M C B S M; Cunha, Alexandre L; Sales, M G F

    2012-05-15

    Potentiometric sensors are typically unable to carry out on-site monitoring of environmental drug contaminants because of their high limits of detection (LODs). Designing a novel ligand material for the target analyte and managing the composition of the internal reference solution have been the strategies employed here to produce for the first time a potentiometric-based direct reading method for an environmental drug contaminant. This concept has been applied to sulfamethoxazole (SMX), one of the many antibiotics used in aquaculture practices that may occur in environmental waters. The novel ligand has been produced by imprinting SMX on the surface of graphitic carbon nanostructures (CN)<500 nm. The imprinted carbon nanostructures (ICN) were dispersed in plasticizer and entrapped in a PVC matrix that included (or not) a small amount of a lipophilic additive. The membrane composition was optimized on solid-contact electrodes, allowing near-Nernstian responses down to 5.2 μg/mL and detecting 1.6 μg/mL. The membranes offered good selectivity against most of the ionic compounds in environmental water. The best membrane cocktail was applied on the smaller end of a 1000 μL micropipette tip made of polypropylene. The tip was then filled with inner reference solution containing SMX and chlorate (as interfering compound). The corresponding concentrations were studied for 1 × 10(-5) to 1 × 10(-10) and 1 × 10(-3) to 1 × 10(-8)mol/L. The best condition allowed the detection of 5.92 ng/L (or 2.3 × 10(-8)mol/L) SMX for a sub-Nernstian slope of -40.3 mV/decade from 5.0 × 10(-8) to 2.4 × 10(-5)mol/L. The described sensors were found promising devices for field applications. The good selectivity of the sensory materials together with a carefully selected composition for the inner reference solution allowed LODs near the nanomolar range. Both solid-contact and "pipette tip"-based sensors were successfully applied to the analysis of aquaculture waters.

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

    PubMed

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

    2014-03-01

    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.

  4. 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.

  5. 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

  6. Remedial Design-Stage Optimization Review Report: Sandy Beach Ground Water Plume Superfund Site, Tarrant County, Texas, EPA Region 6

    EPA Pesticide Factsheets

    The Sandy Beach Road Ground Water Plume Superfund Site, CERCLIS ID No. TXN000605649, is located within incorporated areas of Pelican Bay and Azle, Texas and an unincorporated portion of Tarrant County, Texas.

  7. 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.

  8. 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.

  9. 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…

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. Multi-site effectiveness trials of treatments for substance abuse and co-occurring problems: Have we chosen the best designs?

    PubMed Central

    Nunes, Edward V.; Ball, Samuel; Booth, Robert; Brigham, Gregory; Calsyn, Donald A.; Carroll, Kathleen; Feaster, Daniel J.; Hien, Denise; Hubbard, Robert L.; Ling, Walter; Petry, Nancy M.; Rotrosen, John; Selzer, Jeffrey; Stitzer, Maxine; Tross, Susan; Wakim, Paul; Winhusen, Theresa; Woody, George

    2010-01-01

    Multi-site effectiveness trials such as those carried out in the National Drug Abuse Treatment Clinical Trials Network (CTN) are a critical step in the development and dissemination of evidence-based treatments, because they address how such treatments perform in real-world clinical settings. As Brigham and colleagues summarized in a recent article (Brigham, Feaster, Wakim, & Dempsey, 2009), several possible experimental designs may be chosen for such effectiveness trials. These include: 1) A new treatment intervention (Tx) is compared to an existing mode of community based treatment as usual (TAU): Tx versus TAU; 2) A new intervention is added to TAU and compared to TAU alone: Tx + TAU versus TAU; or 3) A new intervention is added to TAU and compared to a control condition added to TAU: Tx + TAU versus control + TAU. Each of these designs addresses a different question and has different potential strengths and weaknesses. As of December 2009, the primary outcome paper had been published for 16 of the multi-site randomized clinical trials conducted in the CTN, testing various treatments for drug abuse, HIV risk behavior, or related problems. This paper systematically examines, for each of the completed trials, the experimental design type chosen and its original rationale, the main findings of the trial, and the strengths and weaknesses of the design in hindsight. Based on this review, recommendations are generated to inform the design of future effectiveness trials on treatments for substance abuse, HIV risk, and other behavioral health problems. PMID:20307801

  17. 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…

  18. ONWI (Office of Nuclear Waste Isolation) 30% design review findings report for Exploratory Shaft Facility, Deaf Smith site

    SciTech Connect

    Not Available

    1987-05-08

    Based on the performance of a TMP-05 Design Review with integration into the review, via TMP-22, of comments by SRP contractors other than ONWI, the Design Review Board has developed conclusions and recommendations with respect to the 30% design effort submitted by PB/PB-KBB for interim design review. A number of comments were submitted on the design basis criteria and requirements furnished as guidance to PB/PB-KBB. These comments are forwarded to SRPO for disposition and resolution. Additionally, comments whose resolution by PB/PB-KBB require input from other SRP contractors are included. All comments forwarded to SRPO are compiled and subdivided by appropriate category in Section 11.0 of this Findings Report.

  19. Recognizing critical mine spoil health characteristics to design biochars for site improvement to promote stabilizing plant growth

    EPA Science Inventory

    Biochar can be used as an amendment to remediate metal-contaminated mine spoils for improved site phytostabilization. For successful phytostabilization to occur, biochar amendments must improve mine spoil health with respect to plant rooting plus uptake of water and nutrients. ...

  20. 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

    ..., Windmill Islands, Wilkes Land, East Antarctica ASPA 161Terra Nova Bay, Ross Sea ASPA 162Mawson's Huts, Cape... Island, Terra Nova Bay, constructed in March 1912 by Victor Campbell's Northern Party. HSM 15Hut at Cape.... HSM 68Site of depot at Hells Gate Moraine, Inexpressible Island, Terra Nova Bay. HSM 69Message post...

  1. 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

    ..., Windmill Islands, Wilkes Land, East Antarctica ASPA 161Terra Nova Bay, Ross Sea ASPA 162Mawson's Huts, Cape... Island, Terra Nova Bay, constructed in March 1912 by Victor Campbell's Northern Party. HSM 15Hut at Cape.... HSM 68Site of depot at Hells Gate Moraine, Inexpressible Island, Terra Nova Bay. HSM 69Message post...

  2. 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

    ..., Windmill Islands, Wilkes Land, East Antarctica ASPA 161Terra Nova Bay, Ross Sea ASPA 162Mawson's Huts, Cape... Island, Terra Nova Bay, constructed in March 1912 by Victor Campbell's Northern Party. HSM 15Hut at Cape.... HSM 68Site of depot at Hells Gate Moraine, Inexpressible Island, Terra Nova Bay. HSM 69Message post...

  3. 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

  4. 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.

  5. 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.

  6. Synthesis and evaluation of M. tuberculosis salicylate synthase (MbtI) inhibitors designed to probe plasticity in the active site.

    PubMed

    Manos-Turvey, Alexandra; Cergol, Katie M; Salam, Noeris K; Bulloch, Esther M M; Chi, Gamma; Pang, Angel; Britton, Warwick J; West, Nicholas P; Baker, Edward N; Lott, J Shaun; Payne, Richard J

    2012-12-14

    Mycobacterium tuberculosis salicylate synthase (MbtI) catalyses the first committed step in the biosynthesis of mycobactin T, an iron-chelating siderophore essential for the virulence and survival of M. tuberculosis. Co-crystal structures of MbtI with members of a first generation inhibitor library revealed large inhibitor-induced rearrangements within the active site of the enzyme. This plasticity of the MbtI active site was probed via the preparation of a library of inhibitors based on a 2,3-dihydroxybenzoate scaffold with a range of substituted phenylacrylate side chains appended to the C3 position. Most compounds exhibited moderate inhibitory activity against the enzyme, with inhibition constants in the micromolar range, while several dimethyl ester variants possessed promising anti-tubercular activity in vitro.

  7. Preliminary recommendations on the design of the characterization program for the Hanford Site single-shell tanks: A system analysis

    SciTech Connect

    Buck, J.W.; Peffers, M.S.; Hwang, S.T.

    1991-11-01

    The work described in this volume was conducted by Pacific Northwest Laboratory to provide preliminary recommendations on data quality objectives (DQOs) to support the Waste Characterization Plan (WCP) and closure decisions for the Hanford Site single-shell tanks (SSTs). The WCP describes the first of a two-phase characterization program that will obtain information to assess and implement disposal options for SSTs. This work was performed for the Westinghouse Hanford Company (WHC), the current operating contractor on the Hanford Site. The preliminary DQOs contained in this volume deal with the analysis of SST wastes in support of the WCP and final closure decisions. These DQOs include information on significant contributors and detection limit goals (DLGs) for SST analytes based on public health risk.

  8. Homology modeling and molecular dynamics simulation of N-myristoyltransferase from protozoan parasites: active site characterization and insights into rational inhibitor design

    NASA Astrophysics Data System (ADS)

    Sheng, Chunquan; Ji, Haitao; Miao, Zhenyuan; Che, Xiaoyin; Yao, Jianzhong; Wang, Wenya; Dong, Guoqiang; Guo, Wei; Lü, Jiaguo; Zhang, Wannian

    2009-06-01

    Myristoyl-CoA:protein N-myristoyltransferase (NMT) is a cytosolic monomeric enzyme that catalyzes the transfer of the myristoyl group from myristoyl-CoA to the N-terminal glycine of a number of eukaryotic cellular and viral proteins. Recent experimental data suggest NMT from parasites could be a promising new target for the design of novel antiparasitic agents with new mode of action. However, the active site topology and inhibitor specificity of these enzymes remain unclear. In this study, three-dimensional models of NMT from Plasmodium falciparum (PfNMT), Leishmania major (LmNMT) and Trypanosoma brucei (TbNMT) were constructed on the basis of the crystal structures of fungal NMTs using homology modeling method. The models were further refined by energy minimization and molecular dynamics simulations. The active sites of PfNMT, LmNMT and TbNMT were characterized by multiple copy simultaneous search (MCSS). MCSS functional maps reveal that PfNMT, LmNMT and TbNMT share a similar active site topology, which is defined by two hydrophobic pockets, a hydrogen-bonding (HB) pocket, a negatively-charged HB pocket and a positively-charged HB pocket. Flexible docking approaches were then employed to dock known inhibitors into the active site of PfNMT. The binding mode, structure-activity relationships and selectivity of inhibitors were investigated in detail. From the results of molecular modeling, the active site architecture and certain key residues responsible for inhibitor binding were identified, which provided insights for the design of novel inhibitors of parasitic NMTs.

  9. 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.

  10. SU-E-T-760: Tolerance Design for Site-Specific Range in Proton Patient QA Process Using the Six Sigma Model

    SciTech Connect

    Lah, J; Shin, D; Kim, G

    2015-06-15

    Purpose: To show how tolerance design and tolerancing approaches can be used to predict and improve the site-specific range in patient QA process in implementing the Six Sigma. Methods: In this study, patient QA plans were selected according to 6 site-treatment groups: head &neck (94 cases), spine (76 cases), lung (89 cases), liver (53 cases), pancreas (55 cases), and prostate (121 cases), treated between 2007 and 2013. We evaluated a model of the Six Sigma that determines allowable deviations in design parameters and process variables in patient-specific QA, where possible, tolerance may be loosened, then customized if it necessary to meet the functional requirements. A Six Sigma problem-solving methodology is known as DMAIC phases, which are used stand for: Define a problem or improvement opportunity, Measure process performance, Analyze the process to determine the root causes of poor performance, Improve the process by fixing root causes, Control the improved process to hold the gains. Results: The process capability for patient-specific range QA is 0.65 with only ±1 mm of tolerance criteria. Our results suggested the tolerance level of ±2–3 mm for prostate and liver cases and ±5 mm for lung cases. We found that customized tolerance between calculated and measured range reduce that patient QA plan failure and almost all sites had failure rates less than 1%. The average QA time also improved from 2 hr to less than 1 hr for all including planning and converting process, depth-dose measurement and evaluation. Conclusion: The objective of tolerance design is to achieve optimization beyond that obtained through QA process improvement and statistical analysis function detailing to implement a Six Sigma capable design.

  11. 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.

  12. 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.'

  13. 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.

  14. 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.

  15. 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…

  16. Library Home Page Design: A Comparison of Page Layout for Front-Ends to ARL Library Web Sites.

    ERIC Educational Resources Information Center

    King, David L.

    1998-01-01

    Describes a study that examined the home pages of all 120 libraries in the Association of Research Libraries (ARL) to compare design similarities and differences. Highlights include background; document headers and footers; graphics; hypertext links; and unlinked text. (Author/LRW)

  17. Kinetic analysis of bypass of abasic site by the catalytic core of yeast DNA polymerase eta.

    PubMed

    Yang, Juntang; Wang, Rong; Liu, Binyan; Xue, Qizhen; Zhong, Mengyu; Zeng, Hao; Zhang, Huidong

    2015-09-01

    Abasic sites (Apurinic/apyrimidinic (AP) sites), produced ∼ 50,000 times/cell/day, are very blocking and miscoding. To better understand miscoding mechanisms of abasic site for yeast DNA polymerase η, pre-steady-state nucleotide incorporation and LC-MS/MS sequence analysis of extension product were studied using pol η(core) (catalytic core, residues 1-513), which can completely eliminate the potential effects of the C-terminal C2H2 motif of pol η on dNTP incorporation. The extension beyond the abasic site was very inefficient. Compared with incorporation of dCTP opposite G, the incorporation efficiencies opposite abasic site were greatly reduced according to the order of dGTP > dATP > dCTP and dTTP. Pol η(core) showed no fast burst phase for any incorporation opposite G or abasic site, suggesting that the catalytic step is not faster than the dissociation of polymerase from DNA. LC-MS/MS sequence analysis of extension products showed that 53% products were dGTP misincorporation, 33% were dATP and 14% were -1 frameshift, indicating that Pol η(core) bypasses abasic site by a combined G-rule, A-rule and -1 frameshift deletions. Compared with full-length pol η, pol η(core) relatively reduced the efficiency of incorporation of dCTP opposite G, increased the efficiencies of dNTP incorporation opposite abasic site and the exclusive incorporation of dGTP opposite abasic site, but inhibited the extension beyond abasic site, and increased the priority in extension of A: abasic site relative to G: abasic site. This study provides further understanding in the mutation mechanism of abasic sites for yeast DNA polymerase η.

  18. Synthesis and binding properties of new selective ligands for the nucleobase opposite the AP site.

    PubMed

    Abe, Yukiko; Nakagawa, Osamu; Yamaguchi, Rie; Sasaki, Shigeki

    2012-06-01

    DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3'-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; that is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site.

  19. 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.

  20. Movement Patterns and Site Utilization of Fishes as Determined by Acoustic Telemetry: Implications for the Design of Marine Reserves

    DTIC Science & Technology

    2003-09-01

    PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) NOAAs Stellwagen Bank National Marine...the design of marine reserves James Lindholm 1,2, Peter Auster 2, Les Kaufman 3, Steven Miller 4, and Greg Stone 5 1) NOAA’s Stellwagen Bank ...going telemetry studies in the western North Atlantic: Stellwagen Bank National Marine Sanctuary (SBNMS) in the Gulf of Maine and in the northern

  1. Target sites for the design of anti-trypanosomatid drugs based on the structure of dihydroorotate dehydrogenase.

    PubMed

    Pinheiro, Matheus Pinto; Emery, Flávio da Silva; Nonato, M Cristina

    2013-01-01

    Trypanosomatids consist of a large group of flagellated parasitic protozoa, including parasites from the genera Leishmania and Trypanosoma, responsible for causing infections in millions of humans worldwide and for which currently no appropriate therapy is available. The significance of pyrimidines in cellular metabolism makes their de novo and salvage pathways ideal druggable targets for pharmacological intervention and open an opportunity for pharmaceutical innovation. In the current review, we discuss the merits in targeting the enzyme dihydroorotate dehydrogenase (DHODH), a flavin-dependent enzyme that catalyzes the fourth and only redox step in pyrimidine de novo biosynthesis, as a strategy for the development of efficient therapeutic strategies for trypanosomatid-related diseases.We also describe the advances and perspectives from the structural biology point of view in order to unravel the structure-function relationship of trypanosomatid DHODHs, and to identify and validate target sites for drug development.

  2. 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.

  3. 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.

  4. Discovering key residues of dengue virus NS2b-NS3-protease: New binding sites for antiviral inhibitors design.

    PubMed

    Aguilera-Pesantes, D; Robayo, L E; Méndez, P E; Mollocana, D; Marrero-Ponce, Y; Torres, F J; Méndez, M A

    2017-03-23

    The NS2B-NS3 protease is essential for the Dengue Virus (DENV) replication process. This complex constitutes a target for efficient antiviral discovery because a drug could inhibit the viral polyprotein processing. Furthermore, since the protease is highly conserved between the four Dengue virus serotypes, it is probable that a drug would be equally effective against all of them. In this article, a strategy is reported that allowed us to identify influential residues on the function of the Dengue NS2b-NS3 Protease. Moreover, this is a strategy that could be applied to virtually any protein for the search of alternative influential residues, and for non-competitive inhibitor development. First, we incorporated several features derived from computational alanine scanning mutagenesis, sequence, structure conservation, and other structure-based characteristics. Second, these features were used as variables to obtain a multilayer perceptron model to identify defined groups (clusters) of key residues as possible candidate pockets for binding sites of new leads on the DENV protease. The identified residues included: i) amino acids close to the beta sheet-loop-beta sheet known to be important in its closed conformation for NS2b ii) residues close to the active site, iii) several residues evenly spread on the NS2b-NS3 contact surface, and iv) some inner residues most likely related to the overall stability of the protease. In addition, we found concordance on our list of residues with previously identified amino acids part of a highly conserved peptide studied for vaccine development.

  5. 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.

  6. 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.

  7. A study of the active site of influenza virus sialidase: an approach to the rational design of novel anti-influenza drugs.

    PubMed

    von Itzstein, M; Dyason, J C; Oliver, S W; White, H F; Wu, W Y; Kok, G B; Pegg, M S

    1996-01-19

    The development of sialidase inhibitor-based potential anti-influenza drugs using rational drug design techniques has been of recent interest. The present study details as investigation of the active site of influenza virus sialidase by using the program GRID in an attempt to design more potent inhibitors in the hope they will eventually lead to anti-influenza drugs. A number of different probes (amino, carboxy, hydroxy, methyl, etc) have been used in an effort to determine the functional groups most likely to improve the binding of the starting template 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en). The data have correctly predicted the binding regions for the carboxylate, acetamido (NH and methyl), and glycerol (OH) groups of N-acetylneuraminic acid. Moreover, the data suggest that the addition of certain functionalities (amino group) at the C-4 position should enhance the overall binding.

  8. HP3-RAD: a compact radiometer design with on-site calibration for in-situ exploration

    NASA Astrophysics Data System (ADS)

    Kopp, Emanuel; Mueller, Nils; Grott, Matthias; Walter, Ingo; Knollenberg, Jörg; Hanschke, Frank; Kessler, Ernst; Meyer, Hans-Georg

    2016-09-01

    Many processes on planetary bodies are driven by their respective surface energy balance, and while planetary climate is influenced by the dynamics of the atmospheric boundary layer, surface radiation drives the Yarkovksy and YORB effects on small airless bodies. In addition, insolation governs cometary activity and drives the dust cycle on Mars. The radiative flux received and emitted at the surface of solar system bodies is thus a fundamental quantity, which is driven by the reception of solar radiation in the visible wavelength band, while re-radiation primarily occurs in the thermal infrared. Knowledge of the relevant radiative fluxes enables studies of thermo-physical surface properties, and radiometers to measure surface brightness temperatures have been payloads on many missions. The HP3-RAD is part of the Heat Flow and Physical Properties Package (HP3) on the InSight mission to Mars. It is a light-weight thermal infrared radiometer with compact design. HP3-RAD measures radiative flux in 3 spectral bands using thermopile detectors. The 120 g device includes integrated front-end electronics as well as a deployable cover that protects the sensors from dust contamination during landing. In addition, the cover is simultaneously used as a calibration target. The instrument concept as well as its implementation will be described, and special emphasis will be put on technological challenges encountered during instrument development. Potential future improvements of the design will be discussed.

  9. 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.

  10. Structural elements of ligand recognition site in secretory phospho-lipase A2 and structure-based design of specific inhibitors.

    PubMed

    Singh, Nagendra; Somvanshi, Rishi K; Sharma, Sujata; Dey, Sharmistha; Kaur, Punit; Singh, Tej P

    2007-01-01

    Phospholipases A2 (phosphotide 2-acylhydrolases, PLA2s, EC 3.1.1.4) are widely distributed enzymes in the animal world. They catalyze the hydrolysis of the sn-2 acyl ester linkage of phospholipids, producing fatty acids and lysophospholipids. The mammalian type II secreted phospholipase A2 (PLA2-II) is one of the most extensively studied member of low molecular weight (13-18 kDa) PLA2s. PLA2-II contains 120-125 amino acid residues and seven disulphide bridges. The important features of overall structure of PLA2-II contain an N-terminal helix, H1 (residues: 2-12), an external loop (residues: 14-23), a calcium binding loop (Ca2+-loop, residues: 25-35), a second alpha-helix, H2 (residues: 40-55), a short two stranded anti-parallel beta-sheet referred to as beta-wing (residues: 75-84), a third alpha-helix, H3 (residues: 90-108) which is antiparallel to H2 and two single helical turns, SH4 (residues: 114-117) and SH5 (residues: 121-125). The three-dimensional structure of PLA2-II has defined a conserved active site within a hydrophobic channel lined by invariant hydrophobic residues. The active site residues His48, Asp49, Tyr52 and Asp99 are directly connected to the channel. An important water molecule that bridges His48 and Asp49 through hydrogen bonds is a part of catalytic network. Based on the structures of various complexes of group II PLA2, the ligand-recognition site has been divided into six subsites consisting of residues 2-10 (subsite 1), residues 17-23 (subsite 2), residues 28-32 (subsite 3), residues 48-52 (subsite 4), residues 68-70 (subsite 5) and residues 98-106 (subsite 6). It is observed that most of the currently available ligands saturate only part of the ligand-recognition site leaving a wide scope to improve the ligand complementarity. Naturally, the ligands that interact with the largest number of subsites would also correspond to the maximum affinity. Therefore, for the design of potent inhibitors of PLA2, the stereochemical knowledge of the

  11. 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

  12. Design and Elementary Evaluation of a Highly-Automated Fluorescence-Based Instrument System for On-Site Detection of Food-Borne Pathogens

    PubMed Central

    Lu, Zhan; Zhang, Jianyi; Xu, Lizhou; Li, Yanbin; Chen, Siyu; Ye, Zunzhong; Wang, Jianping

    2017-01-01

    A simple, highly-automated instrument system used for on-site detection of foodborne pathogens based on fluorescence was designed, fabricated, and preliminarily tested in this paper. A corresponding method has been proved effective in our previous studies. This system utilizes a light-emitting diode (LED) to excite fluorescent labels and a spectrometer to record the fluorescence signal from samples. A rotation stage for positioning and switching samples was innovatively designed for high-throughput detection, ten at most in one single run. We also developed software based on LabVIEW for data receiving, processing, and the control of the whole system. In the test of using a pure quantum dot (QD) solution as a standard sample, detection results from this home-made system were highly-relevant with that from a well-commercialized product and even slightly better reproducibility was found. And in the test of three typical kinds of food-borne pathogens, fluorescence signals recorded by this system are highly proportional to the variation of the sample concentration, with a satisfied limit of detection (LOD) (nearly 102–103 CFU·mL−1 in food samples). Additionally, this instrument system is low-cost and easy-to-use, showing a promising potential for on-site rapid detection of food-borne pathogens. PMID:28241478

  13. Design and Elementary Evaluation of a Highly-Automated Fluorescence-Based Instrument System for On-Site Detection of Food-Borne Pathogens.

    PubMed

    Lu, Zhan; Zhang, Jianyi; Xu, Lizhou; Li, Yanbin; Chen, Siyu; Ye, Zunzhong; Wang, Jianping

    2017-02-23

    A simple, highly-automated instrument system used for on-site detection of foodborne pathogens based on fluorescence was designed, fabricated, and preliminarily tested in this paper. A corresponding method has been proved effective in our previous studies. This system utilizes a light-emitting diode (LED) to excite fluorescent labels and a spectrometer to record the fluorescence signal from samples. A rotation stage for positioning and switching samples was innovatively designed for high-throughput detection, ten at most in one single run. We also developed software based on LabVIEW for data receiving, processing, and the control of the whole system. In the test of using a pure quantum dot (QD) solution as a standard sample, detection results from this home-made system were highly-relevant with that from a well-commercialized product and even slightly better reproducibility was found. And in the test of three typical kinds of food-borne pathogens, fluorescence signals recorded by this system are highly proportional to the variation of the sample concentration, with a satisfied limit of detection (LOD) (nearly 10²-10³ CFU·mL(-1) in food samples). Additionally, this instrument system is low-cost and easy-to-use, showing a promising potential for on-site rapid detection of food-borne pathogens.

  14. 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)

  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. 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

  17. 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…

  18. The mechanism of human tyrosyl-DNA phosphodiesterase 1 in the cleavage of AP site and its synthetic analogs.

    PubMed

    Lebedeva, Natalia A; Rechkunova, Nadejda I; Ishchenko, Alexander A; Saparbaev, Murat; Lavrik, Olga I

    2013-12-01

    The mechanism of hydrolysis of the apurinic/apyrimidinic (AP) site and its synthetic analogs by using tyrosyl-DNA phosphodiesterase 1 (Tdp1) was analyzed. Tdp1 catalyzes the cleavage of AP site and the synthetic analog of the AP site, 3-hydroxy-2(hydroxymethyl)-tetrahydrofuran (THF), in DNA by hydrolysis of the phosphodiester bond between the substituent and 5' adjacent phosphate. The product of Tdp1 cleavage in the case of the AP site is unstable and is hydrolyzed with the formation of 3'- and 5'-margin phosphates. The following repair demands the ordered action of polynucleotide kinase phosphorylase, with XRCC1, DNA polymerase β, and DNA ligase. In the case of THF, Tdp1 generates break with the 5'-THF and the 3'-phosphate termini. Tdp1 is also able to effectively cleave non-nucleotide insertions in DNA, decanediol and diethyleneglycol moieties by the same mechanism as in the case of THF cleavage. The efficiency of Tdp1 catalyzed hydrolysis of AP-site analog correlates with the DNA helix distortion induced by the substituent. The following repair of 5'-THF and other AP-site analogs can be processed by the long-patch base excision repair pathway.

  19. Recombinant plasmepsin 1 from the human malaria parasite Plasmodium falciparum: Enzymatic characterization, active site inhibitor design, and structural analysis

    PubMed Central

    Liu, Peng; Marzahn, Melissa R.; Robbins, Arthur H.; Gutiérrez-de-Terán, Hugo; Rodríguez, David; McClung, Scott; Stevens, Stanley M.; Yowell, Charles A.; Dame, John B.; McKenna, Robert; Dunn, Ben M.

    2009-01-01

    A mutated form of truncated proplasmepsin 1 (proPfPM1) from the human malaria parasite Plasmodium falciparum, proPfPM1 K110pN, was generated and overexpressed in E. coli. The auto-maturation process was carried out at pH 4.0 and 4.5, and the optimal catalytic pH of the resulting mature PfPM1 was determined to be pH 5.5. This mature PfPM1 showed comparable binding affinity to peptide substrates and inhibitors with the naturally-occurring form isolated from parasites. The S3-S3’ subsite preferences of the recombinant mature PfPM1 were explored using combinatorial chemistry based peptide libraries. Based on the results, a peptidomimetic inhibitor (compound 1) was designed and yielded 5-fold selectivity for binding to PfPM1 versus the homologous human cathepsin D (hcatD). The 2.8 Å structure of the PfPMP2-compound 1 complex is reported. Modeling studies were conducted using a series of peptidomimetic inhibitors (compounds 1–6, Table 3) and three plasmepsins: the crystal structure of PfPM2, and homology derived models of PfPM1 and PfPM4. PMID:19271776

  20. Effect of the multifunctional proteins RPA, YB-1, and XPC repair factor on AP site cleavage by DNA glycosylase NEIL1.

    PubMed

    Pestryakov, Pavel; Zharkov, Dmitry O; Grin, Inga; Fomina, Elizaveta E; Kim, Ekaterina R; Hamon, Loïc; Eliseeva, Irina A; Petruseva, Irina O; Curmi, Patrick A; Ovchinnikov, Lev P; Lavrik, Olga I

    2012-04-01

    DNA glycosylases are key enzymes in the first step of base excision DNA repair, recognizing DNA damage and catalyzing the release of damaged nucleobases. Bifunctional DNA glycosylases also possess associated apurinic/apyrimidinic (AP) lyase activity that nick the damaged DNA strand at an abasic (or AP) site, formed either spontaneously or at the first step of repair. NEIL1 is a bifunctional DNA glycosylase capable of processing lesions, including AP sites, not only in double-stranded but also in single-stranded DNA. Here, we show that proteins participating in DNA damage response, YB-1 and RPA, affect AP site cleavage by NEIL1. Stimulation of the AP lyase activity of NEIL1 was observed when an AP site was located in a 60 nt-long double-stranded DNA. Both RPA and YB-1 inhibited AP site cleavage by NEIL1 when the AP site was located in single-stranded DNA. Taking into account a direct interaction of YB-1 with the AP site, located in single-stranded DNA, and the high affinity of both YB-1 and RPA for single-stranded DNA, this behavior is presumably a consequence of a competition with NEIL1 for the DNA substrate. Xeroderma pigmentosum complementation group C protein (XPC), a key protein of another DNA repair pathway, was shown to interact directly with AP sites but had no effect on AP site cleavage by NEIL1.

  1. Self-catalyzed site-specific depurination of guanine residues within gene sequences.

    PubMed

    Amosova, Olga; Coulter, Richard; Fresco, Jacques R

    2006-03-21

    A self-catalyzed, site-specific guanine-depurination activity has been found to occur in short gene sequences with a potential to form a stem-loop structure. The critical features of that catalytic intermediate are a 5'-G-T-G-G-3' loop and an adjacent 5'-T.A-3' base pair of a short duplex stem stable enough to fix the loop structure required for depurination of its 5'-G residue. That residue is uniquely depurinated with a rate some 5 orders of magnitude faster than that of random "spontaneous" depurination. In contrast, all other purine residues in the sequence depurinate at the spontaneous background rate. The reaction requires no divalent cations or other cofactors and occurs under essentially physiological conditions. Such stem-loops can form in duplex DNA under superhelical stress, and their critical sequence features have been found at numerous sites in the human genome. Self-catalyzed stem-loop-mediated depurination leading to flexible apurinic sites may therefore serve some important biological role, e.g., in nucleosome positioning, genetic recombination, or chromosome superfolding.

  2. Remote engineering for a cheese whey biorefinery: an Internet-based application for process design, economic analysis, monitoring, and control of multiple plant sites.

    PubMed

    Pinto, Gilson A; Giordano, Raquel L C; Giordano, Roberto C

    2009-01-01

    The proteolysis of cheese whey with the aid of immobilized enzymes is an attractive alternative for this by-product of the dairy industry. Among some possible applications for whey protein hydrolysates, one may cite their use as protein source for individuals with reduced capacity of digestion, or with genetic metabolic disorders (phenylketonuria patients, for instance). The multipurpose plant that processes whey is named here as a cheese whey biorefinery. This work presents the remote control and monitoring of the whey biorefineries using the Internet. In an integrated environment, the web application also enables simulation and economic analyses of the process. This technology might allow small companies to access a remote "engineering centre", with know-how on plant design and advanced control techniques. The idea can also be extended to large dairy companies, providing the remote control of geographically spread sites of production.

  3. 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.

  4. Site-directed mutagenesis of α-L-rhamnosidase from Alternaria sp. L1 to enhance synthesis yield of reverse hydrolysis based on rational design.

    PubMed

    Xu, Li; Liu, Xiaohong; Yin, Zhenhao; Liu, Qian; Lu, Lili; Xiao, Min

    2016-12-01

    The α-L-rhamnosidase catalyzes the hydrolytic release of rhamnose from polysaccharides and glycosides and is widely used due to its applications in a variety of industrial processes. Our previous work reported that a wild-type α-L-rhamnosidase (RhaL1) from Alternaria sp. L1 could synthesize rhamnose-containing chemicals (RCCs) though reverse hydrolysis reaction with inexpensive rhamnose as glycosyl donor. To enhance the yield of reverse hydrolysis reaction and to determine the amino acid residues essential for the catalytic activity of RhaL1, site-directed mutagenesis of 11 residues was performed in this study. Through rationally designed mutations, the critical amino acid residues which may form direct or solvent-mediated hydrogen bonds with donor rhamnose (Asp(252), Asp(257), Asp(264), Glu(530), Arg(548), His(553), and Trp(555)) and may form the hydrophobic pocket in stabilizing donor (Trp(261), Tyr(302), Tyr(316), and Trp(369)) in active-site of RhaL1 were analyzed, and three positive mutants (W261Y, Y302F, and Y316F) with improved product yield stood out. From the three positive variants, mutant W261Y accelerated the reverse hydrolysis with a prominent increase (43.7 %) in relative yield compared to the wild-type enzyme. Based on the 3D structural modeling, we supposed that the improved yield of mutant W261Y is due to the adjustment of the spatial position of the putative catalytic acid residue Asp(257). Mutant W261Y also exhibited a shift in the pH-activity profile in hydrolysis reaction, indicating that introducing of a polar residue in the active site cavity may affect the catalysis behavior of the enzyme.

  5. 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.

  6. Max-E47, a Designed Minimalist Protein that Targets the E-Box DNA Site In Vivo and In Vitro

    PubMed Central

    Xu, Jing; Chen, Gang; De Jong, Antonia T.; Shahravan, S. Hesam; Shin, Jumi A.

    2009-01-01

    Max-E47 is a designed hybrid protein comprising the Max DNA-binding basic region and E47 HLH dimerization subdomain. In the yeast one-hybrid system (Y1H), Max-E47 shows strong transcriptional activation from the E-box site, 5'-CACGTG, targeted by the Myc/Max/Mad network of transcription factors; two mutants, Max-E47Y and Max-E47YF, activate more weakly from the E-box in the Y1H. Quantitative fluorescence anisotropy titrations to gain free energies of protein:DNA binding gave low nM Kd values for the native MaxbHLHZ, Max-E47, and the Y and YF mutants binding to the E-box site (14 nM, 15 nM, 9 nM, and 6 nM, respectively), with no detectable binding to a nonspecific control duplex. Because these minimalist, E-box-binding hybrids have no activation domain and no interactions with the c-MycbHLHZ, as shown by the yeast two-hybrid assay, they can potentially serve as dominant-negative inhibitors that suppress activation of E-box-responsive genes targeted by transcription factors including the c-Myc/Max complex. As proof-of-principle, we used our modified Y1H, which allows direct competition between two proteins vying for a DNA target, to show that Max-E47 effectively outcompetes the native MaxbHLHZ for the E-box; weaker competition is observed from the two mutants, consistent with Y1H results. These hybrids provide a minimalist scaffold for further exploration of the relationship between protein structure and DNA-binding function and may have applications as protein therapeutics or biochemical probes capable of targeting the E-box site. PMID:19449889

  7. A new design for a green calcium indicator with a smaller size and a reduced number of calcium-binding sites

    PubMed Central

    Barykina, Natalia V.; Subach, Oksana M.; Doronin, Danila A.; Sotskov, Vladimir P.; Roshchina, Marina A.; Kunitsyna, Tatiana A.; Malyshev, Aleksey Y.; Smirnov, Ivan V.; Azieva, Asya M.; Sokolov, Ilya S.; Piatkevich, Kiryl D.; Burtsev, Mikhail S.; Varizhuk, Anna M.; Pozmogova, Galina E.; Anokhin, Konstantin V.; Subach, Fedor V.; Enikolopov, Grigori N.

    2016-01-01

    Genetically encoded calcium indicators (GECIs) are mainly represented by two- or one-fluorophore-based sensors. One type of two-fluorophore-based sensor, carrying Opsanus troponin C (TnC) as the Ca2+-binding moiety, has two binding sites for calcium ions, providing a linear response to calcium ions. One-fluorophore-based sensors have four Ca2+-binding sites but are better suited for in vivo experiments. Herein, we describe a novel design for a one-fluorophore-based GECI with two Ca2+-binding sites. The engineered sensor, called NTnC, uses TnC as the Ca2+-binding moiety, inserted in the mNeonGreen fluorescent protein. Monomeric NTnC has higher brightness and pH-stability in vitro compared with the standard GECI GCaMP6s. In addition, NTnC shows an inverted fluorescence response to Ca2+. Using NTnC, we have visualized Ca2+ dynamics during spontaneous activity of neuronal cultures as confirmed by control NTnC and its mutant, in which the affinity to Ca2+ is eliminated. Using whole-cell patch clamp, we have demonstrated that NTnC dynamics in neurons are similar to those of GCaMP6s and allow robust detection of single action potentials. Finally, we have used NTnC to visualize Ca2+ neuronal activity in vivo in the V1 cortical area in awake and freely moving mice using two-photon microscopy or an nVista miniaturized microscope. PMID:27677952

  8. Computational fragment-based drug design to explore the hydrophobic sub-pocket of the mitotic kinesin Eg5 allosteric binding site

    NASA Astrophysics Data System (ADS)

    Oguievetskaia, Ksenia; Martin-Chanas, Laetitia; Vorotyntsev, Artem; Doppelt-Azeroual, Olivia; Brotel, Xavier; Adcock, Stewart A.; de Brevern, Alexandre G.; Delfaud, Francois; Moriaud, Fabrice

    2009-08-01

    Eg5, a mitotic kinesin exclusively involved in the formation and function of the mitotic spindle has attracted interest as an anticancer drug target. Eg5 is co-crystallized with several inhibitors bound to its allosteric binding pocket. Each of these occupies a pocket formed by loop 5/helix α2 (L5/α2). Recently designed inhibitors additionally occupy a hydrophobic pocket of this site. The goal of the present study was to explore this hydrophobic pocket with our MED-SuMo fragment-based protocol, and thus discover novel chemical structures that might bind as inhibitors. The MED-SuMo software is able to compare and superimpose similar interaction surfaces upon the whole protein data bank (PDB). In a fragment-based protocol, MED-SuMo retrieves MED-Portions that encode protein-fragment binding sites and are derived from cross-mining protein-ligand structures with libraries of small molecules. Furthermore we have excluded intra-family MED-Portions derived from Eg5 ligands that occupy the hydrophobic pocket and predicted new potential ligands by hybridization that would fill simultaneously both pockets. Some of the latter having original scaffolds and substituents in the hydrophobic pocket are identified in libraries of synthetically accessible molecules by the MED-Search software.

  9. Systematic Design of Trypsin Cleavage Site Mutated Exendin4-Cysteine 1, an Orally Bioavailable Glucagon-Like Peptide-1 Receptor Agonist

    PubMed Central

    Sai, Wenbo; Tian, Hong; Yang, Kangmin; Tang, Daoqi; Bao, Jinxiao; Ge, Yang; Song, Xiaoda; Zhang, Yu; Luo, Cheng; Gao, Xiangdong; Yao, Wenbing

    2017-01-01

    Exendin-4 is a strong therapeutic candidate for the treatment of metabolic syndrome. Related receptor agonist drugs have been on the market since 2005. However, technical limitations and the pain caused by subcutaneous injection have severely limited patient compliance. The goal of the study is to investigate a biologically active exendin-4 analog could be administered orally. Using intraperitoneal glucose tolerance tests, we discovered that exendin4-cysteine administered by oral gavage had a distinct hypoglycemic effect in C57BL/6J mice. Using Rosetta Design and Amber, we designed and screened a series of exendin4-cysteine analogs to identify those that retained biological activity while resisting trypsin digestion. Trypsin Cleavage Site Mutated Exendin4-cysteine 1 (TSME-1), an analog whose bioactivity was similar to exendin-4 and was almost completely resistant to trypsin, was screened out. In addition, TSME-1 significantly normalized the blood glucose levels and the availability of TSME-1 was significantly higher than that of exendin-4 and exendin4-cysteine. Collectively orally administered TSME-1, a trypsin-resistant exendin-4 analog obtained by the system, is a strong candidate for future treatments of type 2 diabetes. PMID:28282854

  10. 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.

  11. 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.

  12. 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

  13. Remedial Design Optimization Review Report: East 67th Street Ground Water Plume NPL Site, Odessa, Ector County, Texas, EPA Region 6

    EPA Pesticide Factsheets

    The East 67th Street Ground Water Plume Superfund Site (East 67th Street Site) is located in Odessa, Ector County, Texas in EPA Region 6. The site was added to the National Priorities List (NPL) on March 7, 2007, and is managed as a fund-lead site.

  14. 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

  15. Design Support of an Above Cap-rock Early Detection Monitoring System using Simulated Leakage Scenarios at the FutureGen2.0 Site

    DOE PAGES

    Williams, Mark D.; USA, Richland Washington; Vermuel, Vince R.; ...

    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

  16. 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…

  17. Tapping Site Planning and Design

    DTIC Science & Technology

    2010-06-17

    Green Roof Seattle, Washington BUILDING STRONG® Washington Mutual Center Green Roof Seattle...Washington BUILDING STRONG® Washington Mutual Center Green Roof Seattle, Washington UUULJUUUU d BUILDING STRONG® Washington Mutual Center Green Roof Seattle...Washington BUILDING STRONG® Washington Mutual Center Green Roof Seattle, Washington BUILDING STRONG® Washington Mutual Center Green Roof

  18. 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.

  19. Poly(ADP-ribose)polymerase 1 stimulates the AP-site cleavage activity of tyrosyl-DNA phosphodiesterase 1.

    PubMed

    Lebedeva, Natalia A; Anarbaev, Rashid O; Sukhanova, Maria; Vasil'eva, Inna A; Rechkunova, Nadejda I; Lavrik, Olga I

    2015-06-15

    The influence of poly(ADP-ribose)polymerase 1 (PARP1) on the apurinic/apyrimidinic (AP)-site cleavage activity of tyrosyl-DNA phosphodiesterase 1 (TDP1) and interaction of PARP1 and TDP1 were studied. The efficiency of single or clustered AP-site hydrolysis catalysed by TDP1 was estimated. It was shown that the efficiency of AP-site cleavage increases in the presence of an additional AP-site in the opposite DNA strand depending on its position. PARP1 stimulates TDP1; the stimulation effect was abolished in the presence of NAD(+). The interaction of these two proteins was characterized quantitatively by measuring the dissociation constant for the TDP1-PARP1 complex using fluorescently-labelled proteins. The distance between the N-termini of the proteins within the complex was estimated using FRET. The data obtained suggest that PARP1 and TDP1 bind in an antiparallel orientation; the N-terminus of the former protein interacts with the C-terminal domain of the latter. The functional significance of PARP1 and TDP1 interaction in the process of DNA repair was demonstrated for the first time.

  20. Remedial action plan and site design for stabilization of the inactive uranium processing site at Naturita, Colorado. Appendix B of Attachment 3: Groundwater hydrology report, Attachment 4: Water resources protection strategy, Final

    SciTech Connect

    Not Available

    1994-03-01

    Attachment 3 Groundwater Hydrology Report describes the hydrogeology, water quality, and water resources at the processing site and Dry Flats disposal site. The Hydrological Services calculations contained in Appendix A of Attachment 3, are presented in a separate report. Attachment 4 Water Resources Protection Strategy describes how the remedial action will be in compliance with the proposed EPA groundwater standards.

  1. DNA-AP sites generation by Etoposide in whole blood cells

    PubMed Central

    2009-01-01

    Background Etoposide is currently one of the most commonly used antitumor drugs. The mechanisms of action proposed for its antitumor activity are based mainly on its interaction with topoisomerase II. Etoposide effects in transformed cells have been described previously. The aim of the present study was to evaluate the genotoxic effects of this drug in non-transformed whole blood cells, such as occurs as collateral damage induced by some chemotherapies. Methods To determine etoposide genotoxicity, we employed Comet assay in two alkaline versions. To evaluate single strand breaks and delay repair sites we use pH 12.3 conditions and pH >13 to evidence alkali labile sites. With the purpose to quantified apurinic or apyrimidine (AP) sites we employed a specific restriction enzyme. Etoposide effects were determined on whole blood cells cultured in absence or presence of phytohemagglutinin (PHA) treated during 2 and 24 hours of cultured. Results Alkaline (pH > 13) single cell gel electrophoresis (SCGE) assay experiments revealed etoposide-induced increases in DNA damage in phytohemaglutinine (PHA)-stimulated blood and non-stimulated blood cells. When the assay was performed at a less alkaline pH, 12.3, we observed DNA damage in PHA-stimulated blood cells consistent with the existence of alkali labile sites (ALSs). In an effort to elucidate the molecular events underlying this result, we applied exonuclease III (Exo III) in conjunction with a SCGE assay, enabling detection of DNA-AP sites along the genome. More DNA AP-sites were revealed by Exo III and ALSs were recognized by the SCGE assay only in the non-stimulated blood cells treated with etoposide. Conclusion Our results indicate that etoposide induces DNA damage specifically at DNA-AP sites in quiescent blood cells. This effect could be involved in the development of secondary malignancies associated with etoposide chemotherapy. PMID:19917085

  2. Design and baseline findings of a multi-site non-randomized evaluation of the effect of a health programme on microfinance clients in India.

    PubMed

    Saha, Somen

    2013-10-12

    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.

  3. Clearance and early hydrolysis of atrial natriuretic factor in vivo. Structural analysis of cleavage sites and design of an analogue that inhibits hormone cleavage.

    PubMed Central

    Condra, C L; Leidy, E A; Bunting, P; Colton, C D; Nutt, R F; Rosenblatt, M; Jacobs, J W

    1988-01-01

    This study examines the clearance and early hydrolysis of atrial natriuretic factor (ANF) in vivo. Radiolabeled ANF was cleared from the circulation of the rat with biphasic kinetics; the majority (90%) of ANF cleared with a t1/2 of 15 s, the remaining peptide was cleared with a t1/2 of 5 min. Microsequence analysis of ANF peptides recovered from the circulation of rats revealed five major degradation products of the intact hormone. The first cleavage occurred between amino acids 12 and 13 of the hormone and would inactivate ANF. Over time, additional fragments of the hormone were generated, including fragments of 6, 7, 21, and 24 amino acids in length. Whole body radioautography of rats injected with [123I]-ANF revealed the kidney as a predominant organ involved in clearance of ANF. Subsequent amino acid sequence analyses of radiolabeled ANF exposed to the kidney in vivo indicated that this organ generated four of the five major hydrolysis products observed in circulation, namely, the 6, 7, 16, and 21 amino acid fragments of the hormone. In an attempt to stabilize ANF in vivo, a synthetic analogue of the hormone was prepared that contained the amino acid analogue, aminoisobutyric acid, substituted at position 13. This analogue completely abolished the in vivo cleavage of ANF at this site. These studies demonstrate the usefulness of a protein chemistry approach in characterizing hormone metabolism in vivo and designing analogues with enhanced in vivo stability to cleavage. Images PMID:2966813

  4. Programming for SITE.

    ERIC Educational Resources Information Center

    Mody, Bella

    1979-01-01

    Describes the Satellite Instructional Television Experiment (SITE) project in India during 1975-76, including programing patterns, formats, and audiences. Demonstrates that countries like India have the technical and managerial capability to design, operate, and maintain advanced communication technology. (JMF)

  5. 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.

  6. 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%…

  7. Site Planning and Layout.

    ERIC Educational Resources Information Center

    Moore, Gary T.

    1998-01-01

    Examines five issues related to child care facility design: (1) siting the building, outdoor play, and service areas; (2) creating favorable microclimates; (3) developmentally appropriate play yards; (4) pedestrian access and site circulation; and (5) vehicular access and parking away from pedestrians and play. (KB)

  8. 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.

  9. 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.

  10. 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)

  11. Bulk Site Reference Materials

    SciTech Connect

    Barich, J.J. III; Jones, R.R. Sr.

    1996-12-31

    The selection, manufacture and use of Bulk Site Reference Materials (BSRMs) at hazardous waste sites is discussed. BSRMs are useful in preparing stabilization/solidification (S/S) formulations for soils, ranking competing S/S processes, comparing S/S alternatives to other technologies, and in interpreting data from different test types. BSRMs are large volume samples that are representative of the physical and chemical characteristics of a site soil, and that contain contaminants at reasonably high levels. A successful BSRM is extremely homogeneous and well-characterized. While not representative of any point on the site, they contain the contaminants of the site in the matrices of the site. Design objectives for a BSRM are to produce a material that (1) maintains good fidelity to site matrices and contaminants, and (2) exhibits the lowest possible relative standard deviation.

  12. 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

  13. 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

  14. 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).

  15. 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.

  16. Designing a Highly Active Metal-Free Oxygen Reduction Catalyst in Membrane Electrode Assemblies for Alkaline Fuel Cells: Effects of Pore Size and Doping-Site Position.

    PubMed

    Lee, Seonggyu; Choun, Myounghoon; Ye, Youngjin; Lee, Jaeyoung; Mun, Yeongdong; Kang, Eunae; Hwang, Jongkook; Lee, Young-Ho; Shin, Chae-Ho; Moon, Seung-Hyeon; Kim, Soo-Kil; Lee, Eunsung; Lee, Jinwoo

    2015-08-03

    To promote the oxygen reduction reaction of metal-free catalysts, the introduction of porous structure is considered as a desirable approach because the structure can enhance mass transport and host many catalytic active sites. However, most of the previous studies reported only half-cell characterization; therefore, studies on membrane electrode assembly (MEA) are still insufficient. Furthermore, the effect of doping-site position in the structure has not been investigated. Here, we report the synthesis of highly active metal-free catalysts in MEAs by controlling pore size and doping-site position. Both influence the accessibility of reactants to doping sites, which affects utilization of doping sites and mass-transport properties. Finally, an N,P-codoped ordered mesoporous carbon with a large pore size and precisely controlled doping-site position showed a remarkable on-set potential and produced 70% of the maximum power density obtained using Pt/C.

  17. [On-site quality control of acupuncture randomized controlled trial: design of content and checklist of quality control based on PICOST].

    PubMed

    Li, Hong-Jiao; He, Li-Yun; Liu, Zhi-Shun; Sun, Ya-Nan; Yan, Shi-Yan; Liu, Jia; Zhao, Ye; Liu, Bao-Yan

    2014-02-01

    To effectively guarantee quality of randomized controlld trial (RCT) of acupuncture and develop reasonable content and checklist of on-site quality control, influencing factors on quality of acupuncture RCT are analyzed and scientificity of quality control content and feasibility of on-site manipulation are put into overall consideration. Based on content and checklist of on-site quality control in National 11th Five-Year Plan Project Optimization of Comprehensive Treatment Plan for TCM in Prevention and Treatment of Serious Disease and Clinical Assessment on Generic Technology and Quality Control Research, it is proposed that on-site quality control of acupuncture RCT should be conducted with PICOST (patient, intervention, comparison, out come, site and time) as core, especially on quality control of interveners' skills and outcome assessment of blinding, and checklist of on-site quality control is developed to provide references for undertaking groups of the project.

  18. Embedded-sensor network design for snow cover measurements around snow pillow and snow course sites in the Sierra Nevada of California

    NASA Astrophysics Data System (ADS)

    Rice, Robert; Bales, Roger C.

    2010-03-01

    The design of sensor networks for measuring the mean and spatial distribution of snow depth at the scale of 1-16 km2 was evaluated by deploying an embedded-sensor network consisting of ultrasonic snow depth sensors to capture the variable physiographic features around an operational snow course in Yosemite National Park in the Sierra Nevada of California. Manual snow surveys were also carried out during accumulation and ablation periods. Four years of continuous data from the embedded-sensor network showed that snow depths during both accumulation and ablation periods can vary as much as 50% based on variability in topography and vegetation across a 0.4 ha study area. Spatial snow surveys showed that such a sensor network can be deployed so as to capture both the variability and mean for accumulation and ablation periods across a 1 km2 area surrounding the sensor network, with a broader network required to extend this to 4 and 16 km2 areas. In forested areas, higher canopy densities, greater than 60% closure, were associated with the lowest snow depths. Analysis of historical snow course records from 14 sites in Yosemite, including the 10 spatial measurements made during each monthly snow course survey, showed snow depths across the 300 m snow course transects to be relatively uniform, with 68% of all monthly values having standard deviations no more than 10% of the mean. Although existing snow courses do little to help define the spatial patterns of snow distribution at the 1-16 km2 scales, it is feasible to extend the representativeness of current operational networks by deploying low-cost embedded-sensor networks nearby. Such networks should be strategically located to also capture elevational differences in snow accumulation and melt, as well as local-scale variability in canopy cover and aspect.

  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. 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

  1. 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…

  2. 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.

  3. 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.

  4. 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)

  5. Evaluation of site-selection criteria, well design, monitoring techniques, and cost analysis for a ground-water supply in Piedmont crystalline rocks, North Carolina

    USGS Publications Warehouse

    Daniel, Charles C.

    1990-01-01

    A statistical analysis of data from wells drilled into the crystalline rocks of the Piedmont and Blue Ridge provinces of North Carolina verified and refined previously proposed criteria for the siting of wells to obtain greater than average yields. An opportunity to test the criteria was provided by the expansion of the town of Cary's municipal ground-water system. Three criteria were used: type of rock, thickness of saturated regolith based upon topography, and presence of fractures and joints based upon drainage lineations. A conceptual model of the local hydrogeologic system was developed to guide the selection of the most favorable well sites, and on the basis of the model, six type sites were determined. Eleven of 12 test wells that were located on the basis of type sites yielded from slightly above average to as much as six times the average yield to be expected from particular rock types as reported in the literature. Only one well drilled at a type site had a less than average yield. One well not located at any of the type sites produced little water. Long-term testing and monitoring after the wells were put into production showed that an 18-hour-on, 6-hour-off pumping cycle was much more effective in terms of total production, reduced head loss, and less drawdown than a 5-day-on and 2-day-off cycle. It was also observed that long-term yields by the production wells were about 75 percent of those predicted on the basis of 24-hour pumping tests and only about 60 percent of the driller's reported yields. Cost analysis showed that, by using criteria-selected well sites, a cost-effective well system can be developed that will provide water at an equivalent or lower cost than a surface-water supply. The analysis showed that the system would be cost effective if only one high-yield well were obtained out of every four drilled.

  6. 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.

  7. Prediction of exposure degree diagram and sites of limited proteolysis in globular proteins as an approach to computer-aided design of protein bioregulators with prolonged action.

    PubMed

    Rodionov, M A; Galaktionov, S G; Akhrem, A A

    1987-11-02

    In order to prolong the lifetime of protein bioregulators in blood it is possible to engineer analogs with protected sites of limited proteolysis. To determine the sites, primarily accessible to trypsin-like proteases, a computer procedure has been developed, including a prediction algorithm, to produce the residue diagram of a globular protein and a discriminant algorithm to determine the sites most liable to proteolysis. The accuracy of prediction of amino acid residue exposure is characterised by correlation coefficients between experimental and theoretical exposure values, the coefficients being about 0.7 as calculated for 10 globular proteins. The classification of Arg and Lys residues into two groups, susceptible or insusceptible to protease, has an error percentage of about 25.

  8. Compressed-Air Energy Storage: Preliminary design and site development program in an aquifer. Volume 7: Environmental, safety, and licensing considerations

    NASA Astrophysics Data System (ADS)

    1981-07-01

    The behavior and suitability of aquifers as compressed-air energy storage (CAFS) sites was studied. The probability, severity, and recommended control measures for the environmental and safety impacts that could result from the construction and operation of a CAES facility are described. The permits and approvals that would be required and the time estimated for their acquisition are also described.

  9. Use of the Performance Diagnostic Checklist to Select an Intervention Designed to Increase the Offering of Promotional Stamps at Two Sites of a Restaurant Franchise

    ERIC Educational Resources Information Center

    Rodriguez, Manuel; Wilder, David A.; Therrien, Kelly; Wine, Byron; Miranti, Reylissa; Daratany, Kenneth; Salume, Gloria; Baranovsky, Greg; Rodriquez, Matias

    2006-01-01

    The performance diagnostic checklist (PDC) was administered to examine the variables influencing the offering of promotional stamps by employees at two sites of a restaurant franchise. PDC results suggested that a lack of appropriate antecedents, equipment and processes, and consequences were responsible for the deficits. Based on these results,…

  10. ADASS XII Meeting Web Site

    NASA Astrophysics Data System (ADS)

    Liou, C.; Hulbert, S.

    We present the architecture, design, and implementation details of the ADASS XII web site. The web site was implemented in Zope, a high-performance application server, web server, and content management system rolled into one. Zope includes a robust, scalable object database, web services architecture, and powerful programming capabilities. The web site was built to conform to HTML, CSS, and accessibility standards as adopted by the W3C. This dynamic web site also taps into a back-end Sybase database while requiring a minimal amount of coding. We offer this site as a prototype web site suitable for reuse in supporting future ADASS meetings.

  11. Design, Development, Pre-Testing and Preparation for Full Scale Cold Testing of a System for Field Remediation of Vertical Pipe Units at the Hanford Site 618-10 Burial Grounds -12495

    SciTech Connect

    Halliwell, Stephen

    2012-07-01

    At the Hanford site, in the 1950's and 60's, radioactive waste materials, including Transuranic (TRU) wastes from a number of laboratories were stored in vertical pipe units (VPUs) in what are now the 618-10 and 618-11 burial grounds. Although the current physical condition of the VPUs is unknown, initial R and D studies had shown that in-ground size reduction and stabilization of VPU contents was feasible. This paper describes the R and D work and testing activities to validate the concept of in-ground size reduction and stabilization of VPU contents, and the design and pre-testing of major plant items and augering systems on full size simulated VPUs. The paper also describes the full size prototype equipment which will be used in full size cold testing of simulated VPUs off the Hanford site, to prove the equipment, develop operating procedures, and train operators prior to deployment on site. Safe and effective field remediation, removal and disposal of the VPUs in the 600 area are critical to the success of the River Corridor Closure Contract at the U.S. Department of Energy's Hanford Site. Safe and effective field remediation, removal and disposal of the VPUs in the 600 area are critical to the success of the River Corridor Closure Contract at the U.S. Department of Energy's Hanford Site. (authors)

  12. Site selection

    SciTech Connect

    Olsen, C.W.

    1983-07-01

    The conditions and criteria for selecting a site for a nuclear weapons test at the Nevada Test Site are summarized. Factors considered are: (1) scheduling of drill rigs, (2) scheduling of site preparation (dirt work, auger hole, surface casing, cementing), (3) schedule of event (when are drill hole data needed), (4) depth range of proposed W.P., (5) geologic structure (faults, Pz contact, etc.), (6) stratigraphy (alluvium, location of Grouse Canyon Tuff, etc.), (7) material properties (particularly montmorillonite and CO/sub 2/ content), (8) water table depth, (9) potential drilling problems (caving), (10) adjacent collapse craters and chimneys, (11) adjacent expended but uncollapsed sites, (12) adjacent post-shot or other small diameter holes, (13) adjacent stockpile emplacement holes, (14) adjacent planned events (including LANL), (15) projected needs of Test Program for various DOB's and operational separations, and (16) optimal use of NTS real estate.

  13. Site characterization handbook

    SciTech Connect

    Not Available

    1988-06-01

    This Handbook discusses both management and technical elements that should be considered in developing a comprehensive site characterization program. Management elements typical of any project of a comparable magnitude and complexity are combined with a discussion of strategies specific to site characterization. Information specific to the technical elements involved in site characterization is based on guidance published by the Nuclear Regulatory Commission (NRC) with respect to licensing requirements for LLW disposal facilities. The objective of this Handbook is to provide a reference for both NRC Agreement States and non-Agreement States for use in developing a comprehensive site characterization program that meets the specific objectives of the State and/or site developer/licensee. Each site characterization program will vary depending on the objectives, licensing requirements, schedules/budgets, physical characteristics of the site, proposed facility design, and the specific concerns raised by government agencies and the public. Therefore, the Handbook is not a prescriptive guide to site characterization. 18 refs., 6 figs.

  14. Optimum utilization of site energy sources for all-season thermal comfort in new residential construction for single-family attached (rowhouse/townhouse) designs

    SciTech Connect

    Not Available

    1981-02-26

    A proposed design analysis is presented of a passive solar energy efficient system for a typical three-level, three bedroom, two story, garage-under townhouse. The design incorporates the best, most performance-proven and cost effective products, materials, processes, technologies, and sub-systems which are available today. Seven distinct categories recognized for analysis are identified as: the exterior environment; the interior environment; conservation of energy; natural energy utilization; auxiliary energy utilization; control and distribution systems; and occupant adaptation. Preliminary design features, fenestration sysems, the plenum-supply system, the thermal-storage party-fire walls, direct gain storage, the radiant comfort system, and direct passive cooling systems are briefly described. Features of the design under analysis and on which conclusions have not yet been formulated are: the energy reclamation system, auxiliary energy back-up systems, the distribution system and operating modes, the control systems, and non-comfort energy systems and inputs. (MCW)

  15. A Site Characterization Methodology for Aquifer in Support of Bioreclamation Activities. Volume 1: Well Network Design, Well Equations, and Aquifier Multiwell and Single-Well Tests

    DTIC Science & Technology

    1993-08-01

    trcludir; tfttie lr, ot reviewing instuctions. sear~ h ;n ex.$,`@ cat& $out Ces.gatpe~r, and mamnlaflng the data -*eded and comrgete 9 anO re. ew nq...Geological Survey and for an aquifer composed of glacial till in Borden , Canada, studied by Stanford and Waterloo Universities, are less than 0.5. The...NIELSEN NEIL 1BColonel, USAF, BSC 7 PjDirector, Environics Directorate OBERT G. LAPOE, t jor, USAF, BSCChief, Site Remedittion Division xi (The

  16. Installation Restoration Program, Rickenbacker Air National Guard Base, Columbus, Ohio. Site Inspection/Remedial Investigation/Feasibility Study/Remedial Design

    DTIC Science & Technology

    1988-06-01

    ants. Good decon for baking soda . base labile compounds. D. An aqueous solu- To ten gallons of See uses/remarks for tion containing water, add two... mouth of each major drainage network is a potential site of contamination concentration. An initial well will be installed near each of the separator...drilling tools (auger flights, bits and center rods) will be decontaminated with steam cleaning followed by a detergent wash, a clean-water rinse , a

  17. Near Surface Gas Simulator (NSGS): A Visual Basic program to improve the design of near-surface gas geochemistry surveys above CO2 geological storage sites

    NASA Astrophysics Data System (ADS)

    Beaubien, S. E.; Annunziatellis, A.; Ciotoli, G.; Lombardi, S.

    2009-04-01

    If CO2 were to leak from a geological storage site and be released to the atmosphere, where would it occur and how large would the leak be in terms of dimension and flow rate? There are many options available to monitor storage sites, including deep and shallow geophysical or geochemical methods, biological markers, or remote sensing techniques, each with its advantages and disadvantages. However only the direct measurement of CO2 at the earth's surface, that is soil gas or gas flux analyses, can give a definitive answer to these questions. Considering that these methods involve point measurements, the question has be raised regarding the sampling density that would be needed to locate a leak above a storage site, or, conversely, to ensure that a leak does not exist. To address this issue we have written a program in Visual Basic which uses highly-detailed, gridded synthetic data (with user-defined gas leakage areas) to study the link between sampling density and anomaly size and to find a sampling strategy which minimises the number of samples collected while maximizing the probability that an anomaly (i.e. a leak) will be found. At the beginning of a run the user is asked to define the location, size, and intensity of leakage areas; these areas are then superimposed on a grid (1 x 1 m step size) of normally-distributed background CO2 flux values. Then the user is asked to provide a series of sampling densities (for example, x = 10, 50, 100, 500, and 1000 samples km-2) and the number of simulations that must be conducted for each sampling density (e.g. y = 100). The program then uses a nested loop structure whereby the synthetic dataset is randomly subsampled at the sampling density "x" for a total of "y" times - each of these smaller datasets is then analysed statistically and spatially using subroutines from the programs Statistica and Surfer, and the resultant data from each simulation for that "x" sampling density is combined to define its statistical

  18. Initiatives to Develop Web Sites Including Information about Brownfields Properties

    EPA Pesticide Factsheets

    This web site was created to assist in planning, designing, and operating web sites that include information about individual brownfields properties. The report is of value to parties designing or managing such sites.

  19. Solar site test module

    NASA Technical Reports Server (NTRS)

    Kissel, R. R.; Scott, D. R.

    1980-01-01

    A solar site test module using the Rockwell AIM 65microcomputer is described. The module is designed to work at any site where an IBM site data acquisition system (SDAS) is installed and is intended primarily as a troubleshooting tool. It collects sensor information (temperatures, flow rates, etc.) and displays or prints it immediately in calibrated engineering units. It will read one sensor on demand, periodically read up to 10sensors or periodically read all sensors. Performance calculations can also be included with sensor data. Unattended operation is possible to, e.g., monitor a group of sensors once per hour. Work is underway to add a data acquisition system to the test module so that it can be used at sites which have no SDAS.

  20. Process design and economics of on-site cellulase production on various carbon sources in a softwood-based ethanol plant.

    PubMed

    Barta, Zsolt; Kovacs, Krisztina; Reczey, Kati; Zacchi, Guido

    2010-06-28

    On-site cellulase enzyme fermentation in a softwood-to-ethanol process, based on SO(2)-catalysed steam pretreatment followed by simultaneous saccharification and fermentation, was investigated from a techno-economic aspect using Aspen Plus© and Aspen Icarus Process Evaluator© softwares. The effect of varying the carbon source of enzyme fermentation, at constant protein and mycelium yields, was monitored through the whole process. Enzyme production step decreased the overall ethanol yield (270 L/dry tonne of raw material in the case of purchased enzymes) by 5-16 L/tonne. Capital cost was found to be the main cost contributor to enzyme fermentation, constituting to 60-78% of the enzyme production cost, which was in the range of 0.42-0.53 SEK/L ethanol. The lowest minimum ethanol selling prices (4.71 and 4.82 SEK/L) were obtained in those scenarios, where pretreated liquid fraction supplemented with molasses was used as carbon source. In some scenarios, on-site enzyme fermentation was found to be a feasible alternative.