Sample records for apurinic sites design

  1. Replication of DNA containing apurinic sites in human and mouse cells probed with parvoviruses MVM and H-1

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

    Vos, J.M.; Rommelaere, J.

    We studied the effect of apurinic sites on DNA replication in mouse and human cells, using parvoviruses MVM (minute virus of mice) and H-1 as probes. Although apurinic sites are efficient blocks to the replication of these single-stranded DNA viruses in vivo, depurinated parvoviruses can be reactivated if host cells have been preexposed to a subtoxic dose of UV light. The target of this conditional reactivation process is the conversion of depurinated input DNA into double-stranded replicative forms; the concomitant increase in viral mutagenesis strongly suggests that apurinic sites can be bypassed in mammalian cells.

  2. Unusual interaction of human apurinic/apyrimidinic endonuclease 1 (APE1) with abasic sites via the Schiff-base-dependent mechanism.

    PubMed

    Ilina, Ekaterina S; Khodyreva, Svetlana N; Lavrik, Olga I

    2018-05-03

    Clustered apurinic/apyrimidinic (AP) sites are more cytotoxic than isolated AP lesions because double strand breaks (DSB) can be formed during repair of closely positioned bistranded AP sites. Formation of DSB due to simultaneous cleavage of bistranded AP sites may be regulated by proteins specifically interacting with this complex lesion. A set of AP DNA duplexes containing AP sites in both strands in different mutual orientation (BS-AP DNAs) was used for search in the extracts of human cells proteins specifically recognizing clustered AP sites. A protein, which formed the Schiff-base-dependent covalent products having an apparent molecular mass of 50 kDa with the subset of BS-AP DNAs, was identified by mass spectrometry as apurinic/apyrimidinic endonuclease 1 (APE1). The identity of trapped protein was confirmed by Western blot analysis with anti-APE1 antibodies. Purified recombinant human APE1 is also capable of forming the 50 kDa-adducts with efficiency of BS-AP DNAs cross-linking to APE1 being dependent on the mutual orientation of AP sites. In spite of formation of the Schiff-base-dependent intermediate, which is prerequisite for the β-elimination mechanism, APE1 is unable to cleave AP sites. APE1 lacking the first 34 amino acids at the N-terminus, unlike wild type enzyme, is unable to form cross-links with BS-AP DNAs that testifies to the involvement of disordered N-terminal extension, which is enriched in lysine residues, in the interaction with AP sites. The yield of APE1-AP DNA cross-links was found to correlate with the enzyme amount in the extracts estimated by the immunochemical approach; therefore the BS-AP DNA-probes can be useful for comparative analysis of APE1 content in cell extracts. Copyright © 2018. Published by Elsevier B.V.

  3. The role of His-83 of yeast apurinic/apyrimidinic endonuclease Apn1 in catalytic incision of abasic sites in DNA.

    PubMed

    Dyakonova, Elena S; Koval, Vladimir V; Lomzov, Alexander A; Ishchenko, Alexander A; Fedorova, Olga S

    2015-06-01

    The apurinic/apyrimidinic (AP) endonuclease Apn1 from Saccharomyces cerevisiae is a key enzyme involved in the base excision repair (BER) at the cleavage stage of abasic sites (AP sites) in DNA. The crystal structure of Apn1 from S. cerevisiae is unresolved. Based on its high amino acid homology to Escherichia coli Endo IV, His-83 is believed to coordinate one of three Zn2+ ions in Apn1's active site similar to His-69 in Endo IV. Substituting His-83 with Ala is proposed to decrease the AP endonuclease activity of Apn1 owing to weak coordination of Zn2+ ions involved in enzymatic catalysis. The kinetics of recognition, binding, and incision of DNA substrates with the H83A Apn1 mutant was investigated. The stopped-flow method detecting fluorescence intensity changes of 2-aminopurine (2-aPu) was used to monitor the conformational dynamics of DNA at pre-steady-state conditions. We found substituting His-83 with Ala influenced catalytic complex formation and further incision of the damaged DNA strand. The H83A Apn1 catalysis depends not only on the location of the mismatch relative to the abasic site in DNA, but also on the nature of damage. We consider His-83 properly coordinates the active site Zn2+ ion playing a crucial role in catalytic incision stage. Our data prove suppressed enzymatic activity of H83A Apn1 results from the reduced number of active site Zn2+ ions. Our study provides insights into mechanistic specialty of AP site repair by yeast AP endonuclease Apn1 of Endo IV family, which members are not found in mammals, but are present in many microorganisms. The results will provide useful guidelines for design of new anti-fungal and anti-malarial agents. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Identification of one of the apurinic/apyrimidinic lyase active sites of topoisomerase V by structural and functional studies

    PubMed Central

    Rajan, Rakhi; Prasad, Rajendra; Taneja, Bhupesh; Wilson, Samuel H.; Mondragón, Alfonso

    2013-01-01

    Topoisomerase V (Topo-V) is the only member of a novel topoisomerase subtype. Topo-V is unique because it is a bifunctional enzyme carrying both topoisomerase and DNA repair lyase activities within the same protein. Previous studies had shown that the topoisomerase domain spans the N-terminus of the protein and is followed by 12 tandem helix–hairpin–helix [(HhH)2] domains. There are at least two DNA repair lyase active sites for apurinic/apyrimidinic (AP) site processing, one within the N-terminal region and the second within the C-terminal domain of Topo-V, but their exact locations and characteristics are unknown. In the present study, the N-terminal 78-kDa fragment of Topo-V (Topo-78), containing the topoisomerase domain and one of the lyase DNA repair domains, was characterized by structural and biochemical studies. The results show that an N-terminal 69-kDa fragment is the minimal fragment with both topoisomerase and AP lyase activities. The lyase active site of Topo-78 is at the junction of the fifth and sixth (HhH)2 domains. From the biochemical and structural data, it appears that Lys571 is the most probable nucleophile responsible for the lyase activity. Our experiments also suggest that Topo-V most likely acts as a Class I AP endonuclease in vivo. PMID:23125368

  5. Proton magnetic resonance studies of ultraviolet-irradiated apurinic acid

    PubMed Central

    Rahn, Ronald O.; Schleich, Thomas

    1974-01-01

    In apurinic acid, a single-stranded polydeoxyribonucleotide easily obtained upon depurination of DNA, the proton resonances arising from thymine and cytosine are readily observable in aqueous solution of 25°C. Two methyl thymine resonances, centered at 1.88 ppm and separated by 0.045 ppm, are observed. We attribute the downfield methyl resonance to thymines with no pyrimidine nearest neighbors and the upfield methyl resonance to thymines having pyrimidine neighbors in the 3′ and/or 5′ positions. Upon ultraviolet irradiation, the upfield methyl and thymine H-6 resonances decrease in amplitude and two methyl resoances appear at 1.63 and 1.52 ppm, corresponding, respectively, to cytosine-thymine and thymine-thymine cyclobutane dimers. Photoreversal eliminates these two minor methyl resonances from the pmr spectrum. We conclude that apurinic acid provides a suitable model system for pmr studies of chemically modified pyrimidine bases in DNA. PMID:10793730

  6. Inhibitors of nuclease and redox activity of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1).

    PubMed

    Laev, Sergey S; Salakhutdinov, Nariman F; Lavrik, Olga I

    2017-05-01

    Human apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional protein which is essential in the base excision repair (BER) pathway of DNA lesions caused by oxidation and alkylation. This protein hydrolyzes DNA adjacent to the 5'-end of an apurinic/apyrimidinic (AP) site to produce a nick with a 3'-hydroxyl group and a 5'-deoxyribose phosphate moiety or activates the DNA-binding activity of certain transcription factors through its redox function. Studies have indicated a role for APE1/Ref-1 in the pathogenesis of cancer and in resistance to DNA-interactive drugs. Thus, this protein has potential as a target in cancer treatment. As a result, major efforts have been directed to identify small molecule inhibitors against APE1/Ref-1 activities. These agents have the potential to become anticancer drugs. The aim of this review is to present recent progress in studies of all published small molecule APE1/Ref-1 inhibitors. The structures and activities of APE1/Ref-1 inhibitors, that target both DNA repair and redox activities, are presented and discussed. To date, there is an urgent need for further development of the design and synthesis of APE1/Ref-1 inhibitors due to high importance of this protein target. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. 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.

  8. RNA-cleaving properties of human apurinic/apyrimidinic endonuclease 1 (APE1)

    PubMed Central

    Kim, Wan-Cheol; King, Dustin; Lee, Chow H.

    2010-01-01

    We have recently identified apurinic/apyrimidinic endonuclease 1 (APE1) as an endoribonuclease that cleaves c-myc mRNA in vitro and regulates c-myc mRNA levels and half-life in cells. This study was undertaken to further unravel the RNA-cleaving properties of APE1. Here, we show that APE1 cleaves RNA in the absence of divalent metal ions and, at 2 mM, Zn2+, Ni2+, Cu2+, or Co2+ inhibited the endoribonuclease activity of APE1. APE1 is able to cleave CD44 mRNA, microRNAs (miR-21, miR-10b), and three RNA components of SARS-corona virus (orf1b, orf3, spike) suggesting that, when challenged, it can cleave any RNAs in vitro. APE1 does not cleave strong doublestranded regions of RNA and it has a strong preference for 3’ of pyrimidine, especially towards UA, CA, and UG sites at single-stranded or weakly paired regions. It also cleaves RNA weakly at UC, CU, AC, and AU sites in single-stranded or weakly paired regions. Finally, we found that APE1 can reduce the ability of the Dicer enzyme to process premiRNAs in vitro. Overall, this study has revealed some previously unknown biochemical properties of APE1 which has implications for its role in vivo. PMID:21968700

  9. 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

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

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

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

    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

  11. APE1 incision activity at abasic sites in tandem repeat sequences.

    PubMed

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

    2014-05-29

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

  12. Selective inhibition by harmane of the apurinic apyrimidinic endonuclease activity of phage T4-induced UV endonuclease.

    PubMed

    Warner, H R; Persson, M L; Bensen, R J; Mosbaugh, D W; Linn, S

    1981-11-25

    1-Methyl-9H-pyrido-[3,4-b]indole (harmane) inhibits the apurinic/apyrimidinic (AP) endonuclease activity of the UV endonuclease induced by phage T4, whereas it stimulates the pyrimidine dimer-DNA glycosylase activity of that enzyme. E. coli endonuclease IV, E. coli endonuclease VI (the AP endonuclease activity associated with E. coli exonuclease III), and E. coli uracil-DNA glycosylase were not inhibited by harmane. Human fibroblast AP endonucleases I and II also were only slightly inhibited. Therefore, harmane is neither a general inhibitor of AP endonucleases, nor a general inhibitor of Class I AP endonucleases which incise DNA on the 3'-side of AP sites. However, E. coli endonuclease III and its associated dihydroxythymine-DNA glycosylase activity were both inhibited by harmane. This observation suggests that harmane may inhibit only AP endonucleases which have associated glycosylase activities.

  13. Selective inhibition by harmane of the apurinic apyrimidinic endonuclease activity of phage T4-induced UV endonuclease.

    PubMed Central

    Warner, H R; Persson, M L; Bensen, R J; Mosbaugh, D W; Linn, S

    1981-01-01

    1-Methyl-9H-pyrido-[3,4-b]indole (harmane) inhibits the apurinic/apyrimidinic (AP) endonuclease activity of the UV endonuclease induced by phage T4, whereas it stimulates the pyrimidine dimer-DNA glycosylase activity of that enzyme. E. coli endonuclease IV, E. coli endonuclease VI (the AP endonuclease activity associated with E. coli exonuclease III), and E. coli uracil-DNA glycosylase were not inhibited by harmane. Human fibroblast AP endonucleases I and II also were only slightly inhibited. Therefore, harmane is neither a general inhibitor of AP endonucleases, nor a general inhibitor of Class I AP endonucleases which incise DNA on the 3'-side of AP sites. However, E. coli endonuclease III and its associated dihydroxythymine-DNA glycosylase activity were both inhibited by harmane. This observation suggests that harmane may inhibit only AP endonucleases which have associated glycosylase activities. PMID:6273822

  14. Apurinic/Apyrimidinic Endonuclease 1 Is the Essential Nuclease during Immunoglobulin Class Switch Recombination

    PubMed Central

    Masani, Shahnaz; Han, Li

    2013-01-01

    Immunoglobulin (Ig) class switch recombination (CSR) is initiated by activation-induced cytidine deaminase (AID) that catalyzes numerous DNA cytosine deaminations within switch regions. The resulting uracils are processed by uracil base excision and/or mismatch repair enzymes that ultimately generate switch region DNA double-strand breaks (DSBs). Uracil glycosylase 2 (UNG2) is required for CSR, most likely by removing uracils to generate abasic sites. Although it is presumed that the apurinic/apyrimidinic endonuclease 1 (APE1) generates DNA strand incisions (a prerequisite for CSR) at these abasic sites, a direct test of the requirement for APE1 in CSR has been difficult because of the embryonic lethality of APE1 ablation in mice. Here, we report the successful deletion of the APE1 gene in a mouse B cell line (CH12F3) capable of robust CSR in vitro. In contrast to the general assumption that APE1 is essential for cellular viability, deletion of APE1 in CH12F3 cells has no apparent effect on cell viability or growth. Moreover, CSR in APE1-null CH12F3 cells is drastically reduced, providing direct evidence for an essential role for APE1 in switch region cleavage and CSR. Finally, deletion of AP endonuclease 2 (APE2) has no effect on CSR in either APE1-proficient or -deficient cells. PMID:23382073

  15. Ultrasensitive apurinic/apyrimidinic endonuclease 1 immunosensing based on self-enhanced electrochemiluminescence of a Ru(II) complex.

    PubMed

    Zhuo, Ying; Liao, Ni; Chai, Ya-Qin; Gui, Guo-Feng; Zhao, Min; Han, Jing; Xiang, Yun; Yuan, Ruo

    2014-01-21

    An alternative "signal on" immunosensor for ultrasensitive detection of apurinic/apyrimidinic endonuclease 1 (APE-1) was designed utilizing the self-enhanced electrochemiluminescence (ECL) of a novel Ru(II) complex functionalized coil-like nanocomposite as signal labels. The desirable self-enhanced ECL luminophore was achieved by combining the coreactant of poly(ethylenimine) (PEI) and the luminophor of bis(2,2'-bipyridine)-5-amino-1,10-phenanthroline ruthenium(II) [Ru(bpy)2(5-NH2-1,10-phen)(2+)] to form one novel Ru(II) complex, which exhibited significantly enhanced ECL efficiency and stability. Moreover, the carbon nanotubes (CNTs) were employed as nanocarriers for self-enhanced Ru(II) complex loading via π-π stacking to obtain the coil-like nanocomposite to act as signal probe. Compared with traditional ECL immunoassay, our proposed strategy is simple and sensitive, avoiding the adding of any coreactant into testing solution for signal amplification, and shows a detection limit down to subfemtogram per milliliter level under the optimized experimental condition.

  16. Analysis of class II (hydrolytic) and class I (beta-lyase) apurinic/apyrimidinic endonucleases with a synthetic DNA substrate.

    PubMed Central

    Levin, J D; Demple, B

    1990-01-01

    We have developed simple and sensitive assays that distinguish the main classes of apurinic/apyrimidinic (AP) endonucleases: Class I enzymes that cleave on the 3' side of AP sites by beta-elimination, and Class II enzymes that cleave by hydrolysis on the 5' side. The distinction of the two types depends on the use of a synthetic DNA polymer that contains AP sites with 5'-[32P]phosphate residues. Using this approach, we now show directly that Escherichia coli endonuclease IV and human AP endonuclease are Class II enzymes, as inferred previously on the basis of indirect assays. The assay method does not exhibit significant interference by nonspecific nucleases or primary amines, which allows the ready determination of different AP endonuclease activities in crude cell extracts. In this way, we show that virtually all of the Class II AP endonuclease activity in E. coli can be accounted for by two enzymes: exonuclease III and endonuclease IV. In the yeast Saccharomyces cerevisiae, the Class II AP endonuclease activity is totally dependent on a single enzyme, the Apn1 protein, but there are probably multiple Class I enzymes. The versatility and ease of our approach should be useful for characterizing this important class of DNA repair enzymes in diverse systems. PMID:1698278

  17. Polyubiquitination of apurinic/apyrimidinic endonuclease 1 by Parkin.

    PubMed

    Scott, Timothy L; Wicker, Christina A; Suganya, Rangaswamy; Dhar, Bithika; Pittman, Thomas; Horbinski, Craig; Izumi, Tadahide

    2017-02-01

    Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential protein crucial for repair of oxidized DNA damage not only in genomic DNA but also in mitochondrial DNA. Parkin, a tumor suppressor and Parkinson's disease (PD) associated gene, is an E3 ubiquitin ligase crucial for mitophagy. Although DNA damage is known to induce mitochondrial stress, Parkin's role in regulating DNA repair proteins has not been elucidated. In this study, we examined the possibility of Parkin-dependent ubiquitination of APE1. Ectopically expressed APE1 was degraded by Parkin and PINK1 via polyubiquitination in mouse embryonic fibroblast cells. PD-causing mutations in Parkin and PINK1 abrogated APE1 ubiquitination. Interaction of APE1 with Parkin was observed by co-immunoprecipitation, proximity ligation assay, and co-localization in the cytoplasm. N-terminal deletion of 41 amino acid residues in APE1 significantly reduced the Parkin-dependent APE1 degradation. These results suggested that Parkin directly ubiquitinated N-terminal Lys residues in APE1 in the cytoplasm. Modulation of Parkin and PINK1 activities under mitochondrial or oxidative stress caused moderate but statistically significant decrease of endogenous APE1 in human cell lines including SH-SY5Y, HEK293, and A549 cells. Analyses of glioblastoma tissues showed an inverse relation between the expression levels of APE1 and Parkin. These results suggest that degradation of endogenous APE1 by Parkin occur when cells are stressed to activate Parkin, and imply a role of Parkin in maintaining the quality of APE1, and loss of Parkin may contribute to elevated APE1 levels in glioblastoma. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Inhibition and recovery of the replication of depurinated parvovirus DNA in mouse fibroblasts

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

    Vos, J.M.; Avalosse, B.; Su, Z.Z.

    Apurinic sites were introduced in the single-stranded DNA of parvovirus minute-virus-of-mice (MVM) and their effect on viral DNA synthesis was measured in mouse fibroblasts. Approximately one apurinic site per viral genome, is sufficient to block its replication in untreated cells. The exposure of host cells to a sublethal dose of UV-light 15 hours prior to virus infection, enhances their ability to support the replication of depurinated MVM. Cell preirradiation induces the apparent overcome of 10-15% of viral DNA replication blocks. These results indicate that apurinic sites prevent mammalian cells from replicating single-stranded DNA unless a recovery process is activated bymore » cell UV-irradiation.« less

  19. 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.

  20. 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 (k cat/K M = 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

  1. The replicative DNA polymerase of herpes simplex virus 1 exhibits apurinic/apyrimidinic and 5′-deoxyribose phosphate lyase activities

    PubMed Central

    Bogani, Federica; Boehmer, Paul E.

    2008-01-01

    Base excision repair (BER) is essential for maintaining genome stability both to counter the accumulation of unusual bases and to protect from base loss in the DNA. Herpes simplex virus 1 (HSV-1) is a large dsDNA virus that encodes its own DNA replication machinery, including enzymes involved in nucleotide metabolism. We report on a replicative family B and a herpesvirus-encoded DNA Pol that possesses DNA lyase activity. We have discovered that the catalytic subunit of the HSV-1 DNA polymerase (Pol) (UL30) exhibits apurinic/apyrimidinic (AP) and 5′-deoxyribose phosphate (dRP) lyase activities. These activities are integral to BER and lead to DNA cleavage on the 3′ side of abasic sites and 5′-dRP residues that remain after cleavage by 5′-AP endonuclease. The UL30-catalyzed reaction occurs independently of divalent cation and proceeds via a Schiff base intermediate, indicating that it occurs via a lyase mechanism. Partial proteolysis of the Schiff base shows that the DNA lyase activity resides in the Pol domain of UL30. These observations together with the presence of a virus-encoded uracil DNA glycosylase indicates that HSV-1 has the capacity to perform critical steps in BER. These findings have implications on the role of BER in viral genome maintenance during lytic replication and reactivation from latency. PMID:18695225

  2. Association of Leukotrichia in Vitiligo and Asp148Glu Polymorphism of Apurinic/Apyrimidinic Endonuclease 1.

    PubMed

    Aydin, A Fatih; Aydıngöz, İkbal Esen; Doğru-Abbasoğlu, Semra; Vural, Pervin; Uysal, Müjdat

    2017-01-01

    Oxidative stress and increased DNA damage have been implicated in the etiopathogenesis of vitiligo. Oxidative DNA damage is mainly repaired by the base excision repair (BER) pathway. We sought to determine whether polymorphisms in DNA repair genes may have a role in the pathogenesis of vitiligo. We conducted a study including 100 patients with vitiligo and age- and sex-matched 193 control subjects to examine the role of single-nucleotide polymorphisms of BER genes, human 8-oxoG DNA N-glycosylase 1 (codon 326), apurinic/apyrimidinic endonuclease 1 (APE1) (codon 148), and X-ray repair cross-complementing group 1 (codon 399) as risk factors for vitiligo. These polymorphisms were determined by quantitative real-time polymerase chain reaction and melting curve analysis. No significant association was observed between the variant alleles of studied genes and vitiligo. However, we showed that the presence of APE1 148Glu variant allele is associated with leukotrichia. This preliminary study suggests that APE1 (codon 148) polymorphism may play a role in vitiligo pathogenesis.

  3. 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

  4. Diverse small molecule inhibitors of human apurinic/apyrimidinic endonuclease APE1 identified from a screen of a large public collection.

    PubMed

    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.

  5. 10 CFR 862.7 - Designation of sites.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 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 necessary...

  6. 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 necessary...

  7. Thermodynamic impact of abasic sites on simulated translesion DNA synthesis.

    PubMed

    Malina, Jaroslav; Brabec, Viktor

    2014-06-16

    Loss of a base in DNA and the creation of an abasic (apurinic/apyrimidinic, AP) site is a frequent lesion that may occur spontaneously, or as a consequence of the action of DNA-damaging agents. The AP lesion is mutagenic or lethal if not repaired. We report a systematic thermodynamic investigation by differential scanning calorimetry on the evolution, during primer extension, of a model AP site in chemically simulated DNA translesion synthesis. Incorporation of dAMP (deoxyadenosine monophosphate), as well as dTMP (deoxythymidine monophosphate), opposite an AP site is enthalpically unfavorable, although incorporation of dTMP is more enthalpically unfavorable than that of dAMP. This finding is in a good agreement with experimental data showing that AP sites block various DNA polymerases of eukaryotic and prokaryotic origin and that, if bypassed, dAMP is preferentially inserted, whereas insertion of dTMP is less likely. The results emphasize the importance of thermodynamic contributions to the insertion of nucleotides opposite an AP site by DNA polymerases. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Crystal structure and DNA repair activities of the AP endonuclease from Leishmania major.

    PubMed

    Vidal, Antonio E; Harkiolaki, Maria; Gallego, Claribel; Castillo-Acosta, Victor M; Ruiz-Pérez, Luis M; Wilson, Keith; González-Pacanowska, Dolores

    2007-11-02

    Apurinic/apyrimidinic endonucleases initiate the repair of abasic sites produced either spontaneously, from attack of bases by reactive oxygen species or as intermediates during base excision repair. The catalytic properties and crystal structure of Leishmania major apurinic/apyrimidinic endonuclease are described and compared with those of human APE1 and bacterial exonuclease III. The purified enzyme is shown to possess apurinic/apyrimidinic endonuclease activity of the same order as eukaryotic and prokaryotic counterparts and an equally robust 3'-phosphodiesterase activity. Consistent with this, expression of the L. major endonuclease confers resistance to both methyl methane sulphonate and H2O2 in Escherichia coli repair-deficient mutants while expression of the human homologue only reverts methyl methane sulphonate sensitivity. Structural analyses and modelling of the enzyme-DNA complex demonstrates a high degree of conservation to previously characterized homologues, although subtle differences in the active site geometry might account for the high 3'-phosphodiesterase activity. Our results confirm that the L. major's enzyme is a key element in mediating repair of apurinic/apyrimidinic sites and 3'-blocked termini and therefore must play an important role in the survival of kinetoplastid parasites after exposure to the highly oxidative environment within the host macrophage.

  9. Lucanthone and Its Derivative Hycanthone Inhibit Apurinic Endonuclease-1 (APE1) by Direct Protein Binding

    PubMed Central

    Naidu, Mamta D.; Agarwal, Rakhi; Pena, Louis A.; Cunha, Luis; Mezei, Mihaly; Shen, Min; Wilson, David M.; Liu, Yuan; Sanchez, Zina; Chaudhary, Pankaj; Wilson, Samuel H.; Waring, Michael J.

    2011-01-01

    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 IC50 values for inhibition of APE1 incision of depurinated plasmid DNA by lucanthone and hycanthone were 5 µM and 80 nM, respectively. The KD 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.g., TRIS and DMSO

  10. Siting, design and operational controls for snow disposal sites.

    PubMed

    Wheaton, S R; Rice, W J

    2003-01-01

    The Municipality of Anchorage (MOA), at 61 degrees north latitude, ploughs and hauls snow from urban streets throughout the winter, incorporating grit and chloride applied to street surfaces for traffic safety. Hauled snow is stored at snow disposal facilities, where it melts at ambient spring temperatures. MOA studies performed from 1998 through 2001 show that disposal site melt processes can be manipulated, through site design and operation practices, to control chloride and turbidity in meltwater. An experimental passive "V-swale" pad configuration tested by MOA investigators reduced site meltwater turbidity by an order of magnitude (to about 50 NTU from the 500 NTU typical of more conventional planar pad geometry). The MOA has developed new siting, design and operational criteria for snow disposal facilities to conform to the tested V-swale pad configuration.

  11. Quantum mechanical design of enzyme active sites.

    PubMed

    Zhang, Xiyun; DeChancie, Jason; Gunaydin, Hakan; Chowdry, Arnab B; Clemente, Fernando R; Smith, Adam J T; Handel, T M; Houk, K N

    2008-02-01

    The design of active sites has been carried out using quantum mechanical calculations to predict the rate-determining transition state of a desired reaction in presence of the optimal arrangement of catalytic functional groups (theozyme). Eleven versatile reaction targets were chosen, including hydrolysis, dehydration, isomerization, aldol, and Diels-Alder reactions. For each of the targets, the predicted mechanism and the rate-determining transition state (TS) of the uncatalyzed reaction in water is presented. For the rate-determining TS, a catalytic site was designed using naturalistic catalytic units followed by an estimation of the rate acceleration provided by a reoptimization of the catalytic site. Finally, the geometries of the sites were compared to the X-ray structures of related natural enzymes. Recent advances in computational algorithms and power, coupled with successes in computational protein design, have provided a powerful context for undertaking such an endeavor. We propose that theozymes are excellent candidates to serve as the active site models for design processes.

  12. Synthesis, Biological Evaluation and Structure-Activity Relationships of a Novel Class of Apurinic/Apyrimidinic Endonuclease 1 Inhibitors

    PubMed Central

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

    2012-01-01

    APE1 is an essential protein that operates in the base excision repair (BER) pathway and is responsible for ≥95% of the total apurinic/apyrimidinic (AP) endonuclease activity in human cells. BER is a major pathway that copes with DNA damage induced by several anti-cancer agents, including ionizing radiation and temozolomide. Overexpression of APE1 and enhanced AP endonuclease activity has been linked to increased resistance of tumor cells to treatment with monofunctional alkylators, implicating inhibition of APE1 as a valid strategy for cancer therapy. We report herein the results of a focused medicinal chemistry effort around a novel APE1 inhibitor, N-(3-(benzo[d]thiazol-2-yl)-6-isopropyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl)acetamide (3). Compound 3 and related analogs exhibit single-digit µM activity against the purified APE1 enzyme, comparable activity in HeLa whole cell extract assays, and potentiate the cytotoxicity of the alkylating agents methylmethane sulfonate and temozolomide. Moreover, this class of compounds possesses a generally favorable in vitro ADME profile, along with good exposure levels in plasma and brain following intraperitoneal dosing (30 mg/kg body weight) in mice. PMID:22455312

  13. A User-centered Model for Web Site Design

    PubMed Central

    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. PMID:12087113

  14. A Design Analysis Model for Developing World Wide Web Sites.

    ERIC Educational Resources Information Center

    Ma, Yan

    2002-01-01

    Examines the relationship between and among designers, text, and users of the Galter Health Sciences Library Web site at Northwestern University by applying reader-response criticism. Highlights include Web site design; comparison of designers' intentions with the actual organization of knowledge on the Web site; and compares designer's intentions…

  15. The contribution of DNA apurinic/apyrimidinic endonuclease genotype and smoking habit to Taiwan lung cancer risk.

    PubMed

    Chen, Wei-Chun; Tsai, Chia-Wen; Hsia, Te-Chun; Chang, Wen-Shin; Lin, Liang-Yi; Liang, Shinn-Jye; Tu, Chih-Yen; Cheng, Wei-Erh; Chen, Hung-Jen; Wang, Shu-Ming; Bau, da-Tian

    2013-06-01

    To evaluate the association and interaction of genotypic polymorphism the gene for DNA-apurinic/apyrimidinic endonuclease (APEX1) with personal smoking habit and lung cancer risk in Taiwan, the polymorphic variants of APEX1, Asp(148)Glu (rs1130409), were analyzed in association with lung cancer risk, and their joint effect with personal smoking habits on lung cancer susceptibility was discussed. In this hospital-based case-control study, 358 patients with lung cancer and 716 cancer-free controls, frequency-matched by age and sex, were recruited and genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The results showed that the percentages of TT, TG and GG APEX1 Asp(148)Glu genotypes were not significantly different at 43.0%, 41.1% and 15.9% in the lung cancer patient group and 39.9%, 46.1% and 14.0% in non-cancer control group, respectively. We further analyzed the genetic-lifestyle effects on lung cancer risk and found the contribution of APEX1 Asp(148)Glu genotypes to lung cancer susceptibility was neither enhanced in the cigarette smokers nor in the non-smokers (p=0.3550 and 0.8019, respectively). Our results provide evidence that the non-synonymous polymorphism of APEX1 Asp(148)Glu may not be directly associated with lung cancer risk, nor enhance the effects of smoking habit on lung cancer development.

  16. 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...

  17. Instructional Design. [SITE 2002 Section].

    ERIC Educational Resources Information Center

    2002

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

  18. 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…

  19. Impact of Site Elevation on Mg Smelter Design

    NASA Astrophysics Data System (ADS)

    Baker, Phillip W.

    Site elevation has many surprising and significant impacts on the engineering design of metallurgical plant of all types. Electrolytic magnesium smelters maybe built at high elevation for a variety of reasons including availability of raw material, energy or electric power. Because of the unit processes they typically involve, Mg smelters can be extensively impacted by site elevation. In this paper, generic examples of the design changes required to adapt a smelter originally designed for sea level to operate at 2700 m are presented. While the examples are drawn from a magnesium plant design case, these changes are generically applicable to all industrial plants utilizing similar unit processes irrespective of product.

  20. 2012 Nitrogen Dioxide Monitoring Site Design Values

    EPA Pesticide Factsheets

    A design value is a statistic that describes the air quality status of a given location relative to the level of the National Ambient Air Quality Standards (NAAQS). Design values are defined to be consistent with the individual NAAQS as described in CFR Part 50. They are typically used to designate and classify nonattainment areas, as well as to assess progress towards meeting the NAAQS. To view a list of areas designated nonattainment, see EPA's Green Book site. Design values are computed and published annually by EPA's Office of Air Quality Planning and Standards and reviewed in conjunction with the EPA Regional Offices. Some of these design values can change after the date of publication for a variety of reasons, including but not limited to: 1) EPA agreement that certain data were influenced by exceptional events and therefore not subject for comparison with the NAAQS, 2) States retroactively entering or changing erroneous data based on later findings, and/or 3) notification of a monitoring issue (e.g. network design, site combination, change in the regulatory status of a monitor) that would prompt a revision.

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

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

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

    1995-12-31

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

  2. Structure of the endonuclease IV homologue from Thermotoga maritima in the presence of active-site divalent metal ions

    PubMed Central

    Tomanicek, Stephen J.; Hughes, Ronny C.; Ng, Joseph D.; Coates, Leighton

    2010-01-01

    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′-phosphodiester bond at an AP site to generate a free 3′-­hydroxyl group and a 5′-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. PMID:20823514

  3. 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 sites...

  4. 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 sites...

  5. 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 sites...

  6. 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 sites...

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Site Development Design Requirements B Exhibit B to... Work Pt. 1924, Subpt. C, Exh. B Exhibit B to Subpart C of Part 1924—Site Development Design... burdens and conditions unsuitable for healthy and pleasant living. Proper site design can preserve...

  8. 7 CFR Exhibit B to Subpart C of... - Site Development Design Requirements

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 12 2013-01-01 2013-01-01 false Site Development Design Requirements B Exhibit B to... Work Pt. 1924, Subpt. C, Exh. B Exhibit B to Subpart C of Part 1924—Site Development Design... burdens and conditions unsuitable for healthy and pleasant living. Proper site design can preserve...

  9. 7 CFR Exhibit B to Subpart C of... - Site Development Design Requirements

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Site Development Design Requirements B Exhibit B to... Work Pt. 1924, Subpt. C, Exh. B Exhibit B to Subpart C of Part 1924—Site Development Design... burdens and conditions unsuitable for healthy and pleasant living. Proper site design can preserve...

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

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Site Development Design Requirements B Exhibit B to... Work Pt. 1924, Subpt. C, Exh. B Exhibit B to Subpart C of Part 1924—Site Development Design... burdens and conditions unsuitable for healthy and pleasant living. Proper site design can preserve...

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

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Site Development Design Requirements B Exhibit B to... Work Pt. 1924, Subpt. C, Exh. B Exhibit B to Subpart C of Part 1924—Site Development Design... burdens and conditions unsuitable for healthy and pleasant living. Proper site design can preserve...

  12. 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 land...

  13. 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 land...

  14. 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 land...

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

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 2 2012-01-01 2012-01-01 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 land...

  16. 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 land...

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

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

    Not Available

    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.

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

    PubMed

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

    2015-10-01

    Angiogenesis plays an important role in tumor growth and metastasis and has been reported to be inversely correlated with overall survival of osteosarcoma patients. It has been shown that apurinic/apyrimidinic endonuclease 1 (APE1), a dually functional protein possessing both base excision repair and redox activities, is involved in tumor angiogenesis, although these mechanisms are not fully understood. Our previous study showed that the expression of transforming growth factor β (TGFβ) was significantly reduced in APE1-deficient osteosarcoma cells. Transforming growth factor β promotes cancer metastasis through various mechanisms including immunosuppression, angiogenesis, and invasion. In the current study, we initially revealed that APE1, TGFβ, and microvessel density (MVD) have pairwise correlation in osteosarcoma tissue samples, whereas TGFβ, tumor size, and MVD were inversely related to the prognosis of the cohort. We found that knocking down APE1 in osteosarcoma cells resulted in TGFβ downregulation. In addition, APE1-siRNA led to suppression of angiogenesis in vitro based on HUVECs in Transwell and Matrigel tube formation assays. Reduced secretory protein level of TGFβ of culture medium also resulted in decreased phosphorylation of Smad3 of HUVECs. In a mouse xenograft model, siRNA-mediated silencing of APE1 downregulated TGFβ expression, tumor size, and MVD. Collectively, the current evidence indicates that APE1 regulates angiogenesis in osteosarcoma by controlling the TGFβ pathway, suggesting a novel target for anti-angiogenesis therapy in human osteosarcoma. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  19. Direct-to-consumer advertising via the Internet: the role of Web site design.

    PubMed

    Sewak, Saurabh S; Wilkin, Noel E; Bentley, John P; Smith, Mickey C

    2005-06-01

    Recent attempts to propose criteria for judging the quality of pharmaceutical and healthcare Web sites do not distinguish between attributes of Web site design related to content and other attributes not related to the content. The Elaboration Likelihood Model from persuasion literature is used as a framework for investigating the effects of Web site design on consequents like attitude and knowledge acquisition. A between-subjects, 2 (high or low involvement)x2 (Web site designed with high or low aspects of visual appeal) factorial design was used in this research. College students were randomly assigned to these treatment groups yielding a balanced design with 29 observations per treatment cell. Analysis of variance results for the effects of involvement and Web site design on attitude and knowledge indicated that the interaction between the independent variables was not significant in both analyses. Examination of main effects revealed that participants who viewed the Web site with higher visual appeal actually had slightly lower knowledge scores (6.32) than those who viewed the Web site with lower visual appeal (7.03, F(1,112)=3.827, P=.053). Results of this research seem to indicate that aspects of Web site design (namely aspects of visual appeal and quality) may not play a role in attaining desired promotional objectives, which can include development of favorable attitudes toward the product and facilitating knowledge acquisition.

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

    PubMed

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

    2012-06-01

    DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3'-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; that is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site. Copyright © 2012 Elsevier Ltd. All rights reserved.

  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. BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1.

    PubMed

    Yang, Jenq-Lin; Lin, Yu-Ting; Chuang, Pei-Chin; Bohr, Vilhelm A; Mattson, Mark P

    2014-03-01

    Brain-derived neurotrophic factor (BDNF) promotes the survival and growth of neurons during brain development and mediates activity-dependent synaptic plasticity and associated learning and memory in the adult. BDNF levels are reduced in brain regions affected in Alzheimer's, Parkinson's, and Huntington's diseases, and elevation of BDNF levels can ameliorate neuronal dysfunction and degeneration in experimental models of these diseases. Because neurons accumulate oxidative lesions in their DNA during normal activity and in neurodegenerative disorders, we determined whether and how BDNF affects the ability of neurons to cope with oxidative DNA damage. We found that BDNF protects cerebral cortical neurons against oxidative DNA damage-induced death by a mechanism involving enhanced DNA repair. BDNF stimulates DNA repair by activating cyclic AMP response element-binding protein (CREB), which, in turn, induces the expression of apurinic/apyrimidinic endonuclease 1 (APE1), a key enzyme in the base excision DNA repair pathway. Suppression of either APE1 or TrkB by RNA interference abolishes the ability of BDNF to protect neurons against oxidized DNA damage-induced death. The ability of BDNF to activate CREB and upregulate APE1 expression is abolished by shRNA of TrkB as well as inhibitors of TrkB, PI3 kinase, and Akt kinase. Voluntary running wheel exercise significantly increases levels of BDNF, activates CREB, and upregulates APE1 in the cerebral cortex and hippocampus of mice, suggesting a novel mechanism whereby exercise may protect neurons from oxidative DNA damage. Our findings reveal a previously unknown ability of BDNF to enhance DNA repair by inducing the expression of the DNA repair enzyme APE1.

  3. Expression, functionality, and localization of apurinic/apyrimidinic endonucleases in replicative and non-replicative forms of Trypanosoma cruzi.

    PubMed

    Sepúlveda, S; Valenzuela, L; Ponce, I; Sierra, S; Bahamondes, P; Ramirez, S; Rojas, V; Kemmerling, U; Galanti, N; Cabrera, G

    2014-02-01

    Trypanosoma cruzi is the etiological agent of Chagas disease. The parasite has to overcome oxidative damage by ROS/RNS all along its life cycle to survive and to establish a chronic infection. We propose that T. cruzi is able to survive, among other mechanisms of detoxification, by repair of its damaged DNA through activation of the DNA base excision repair (BER) pathway. BER is highly conserved in eukaryotes with apurinic/apirimidinic endonucleases (APEs) playing a fundamental role. Previous results showed that T. cruzi exposed to hydrogen peroxide and peroxinitrite significantly decreases its viability when co-incubated with methoxyamine, an AP endonuclease inhibitor. In this work the localization, expression and functionality of two T. cruzi APEs (TcAP1, Homo sapiens APE1 orthologous and TcAP2, orthologous to Homo sapiens APE2 and to Schizosaccaromyces pombe Apn2p) were determined. These enzymes are present and active in the two replicative parasite forms (epimastigotes and amastigotes) as well as in the non-replicative, infective trypomastigotes. TcAP1 and TcAP2 are located in the nucleus of epimastigotes and their expression is constitutive. Epimastigote AP endonucleases as well as recombinant TcAP1 and TcAP2 are inhibited by methoxyamine. Overexpression of TcAP1 increases epimastigotes viability when they are exposed to acute ROS/RNS attack. This protective effect is more evident when parasites are submitted to persistent ROS/RNS exposition, mimicking nature conditions. Our results confirm that the BER pathway is involved in T. cruzi resistance to DNA oxidative damage and points to the participation of DNA AP endonucleases in parasite survival. © 2013 Wiley Periodicals, Inc.

  4. Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site

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

    Strauch, Eva-Maria; Bernard, Steffen M.; La, David

    Many viral surface glycoproteins and cell surface receptors are homo-oligomers1, 2, 3, 4, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites5, 6, 7, 8. In the first step, a small protein ismore » designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.« less

  5. 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…

  6. 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... FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH-RISE RESIDENTIAL BUILDINGS § 433.6 Sustainable principles for siting, design and construction. [Reserved] ...

  7. 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... FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH-RISE RESIDENTIAL BUILDINGS § 433.6 Sustainable principles for siting, design and construction. [Reserved] ...

  8. 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... FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH-RISE RESIDENTIAL BUILDINGS § 433.6 Sustainable principles for siting, design and construction. [Reserved] ...

  9. Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals

    PubMed Central

    Ramana, Chilakamarti V.; Boldogh, Istvan; Izumi, Tadahide; Mitra, Sankar

    1998-01-01

    Apurinic/apyrimidinic (AP) endonuclease (APE; EC 4.2.99.18) plays a central role in repair of DNA damage due to reactive oxygen species (ROS) because its DNA 3′-phosphoesterase activity removes 3′ blocking groups in DNA that are generated by DNA glycosylase/AP-lyases during removal of oxidized bases and by direct ROS reaction with DNA. The major human APE (APE-1) gene is activated selectively by sublethal levels of a variety of ROS and ROS generators, including ionizing radiation, but not by other genotoxicants—e.g., UV light and alkylating agents. Increased expression of APE mRNA and protein was observed both in the HeLa S3 tumor line and in WI 38 primary fibroblasts, and it was accompanied by translocation of the endonuclease to the nucleus. ROS-treated cells showed a significant increase in resistance to the cytotoxicity of such ROS generators as H2O2 and bleomycin, but not to UV light. This “adaptive response” appears to result from enhanced repair of cytotoxic DNA lesions due to an increased activity of APE-1, which may be limiting in the base excision repair process for ROS-induced toxic lesions. PMID:9560228

  10. 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

  11. High probability neurotransmitter release sites represent an energy efficient design

    PubMed Central

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

    2016-01-01

    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 vs. 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 vs. 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. PMID:27593375

  12. Design of Single-Site Photocatalyst using Metal-Organic Framework as Matrix.

    PubMed

    Wen, Meicheng; Mori, Kohsuke; Kuwahara, Yasutaka; An, Taicheng; Yamashita, Hiromi

    2018-05-14

    Single-site photocatalyst generally displays excellent photocatalytic activtiy and considerable high stability as compared to homogeneous catalytic system. A rational structural design of single-site photocatalyst with isolated, uniform and spatially separated active sites in a given solid is of prime importance to achieve high photocatalytic activity. Intense attentions have been focused on the engineering and fabrication of single-site photocatalys by using porous materials as platform. Metal-organic frameworks (MOFs) hold great potential for the design and fabrication of single-site photocatalysts due to their remarkable porosity, ultrahigh surface area, extraordinary tailorability and significant diversity. MOFs can provide abundant number of binding sites for anchoring active sites, result in significant enhancement of photocatalytic performance. In this focus review, the development of single-site MOF photocatalysts that perform in important and challenging chemical redox reaction such as photocatalytic water splitting, photocatalytic CO₂ conversion and organic transformations is summarized thoroughly. The successful strategies applied for the construction of single-site MOF photocatalysts and major challenge toward practical application was summarized and pointed out, respectively. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Sustainable principles for siting, design and construction. [Reserved] 435.6 Section 435.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS...-Rise Residential Buildings. § 435.6 Sustainable principles for siting, design and construction...

  14. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Sustainable principles for siting, design and construction. [Reserved] 435.6 Section 435.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS...-Rise Residential Buildings. § 435.6 Sustainable principles for siting, design and construction...

  15. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Sustainable principles for siting, design and construction. [Reserved] 435.6 Section 435.6 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY STANDARDS...-Rise Residential Buildings. § 435.6 Sustainable principles for siting, design and construction...

  16. A Design of a Surgical Site Verification System.

    PubMed

    Shen, Biyu; He, Yan; Chen, Haoyang

    2017-01-01

    Patient security is a significant issue in medical research and clinical practice at present. The Surgical Verification System (Patent Number: ZL 201420079273.5) is designed to recognize and check surgical sites of patients so as to ensure operation security and decrease the risk for practitioners. Composition: (1) Operating Room Server, (2) Label Reader, (3) E-Label, (4) Surgical Site Display, (5) Ward Client, (6) Label Rader-Writer, and (7) Acousto-Optic Alarm. If the Surgical identification, the surgical site, and so on are incorrect, a flashing label control will appear when the alarm rings. You can specify a sound to play for the alarm, a picture to draw, and a message to send. It is a user-friendly system.

  17. 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…

  18. 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.

  19. 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.

  20. 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…

  1. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. AIAA designates Stennis as historic aerospace site

    NASA Image and Video Library

    2008-04-10

    Picured (left to right) American Institute of Aeronautics and Astronautics (AIAA) representative David Throckmorton presents a plaque designating NASA's John C. Stennis Space Center as a historical aerospace site during an April 10 ceremony. Joining Throckmorton for the presentation were AIAA Greater New Orleans Chapter Chair Mark Hughes, Stennis Space Center Director Bob Cabana and Pratt & Whitney Rocketdyne Vice President John Plowden.

  3. 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.

  4. 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.

  5. Identification of a residue critical for the excision of 3′-blocking ends in apurinic/apyrimidinic endonucleases of the Xth family

    PubMed Central

    Castillo-Acosta, Víctor M.; Ruiz-Pérez, Luis M.; Yang, Wei; González-Pacanowska, Dolores; Vidal, Antonio E.

    2009-01-01

    DNA single-strand breaks containing 3′-blocking groups are generated from attack of the sugar backbone by reactive oxygen species or after base excision by DNA glycosylase/apurinic/apyrimidinic (AP) lyases. In human cells, APE1 excises sugar fragments that block the 3′-ends thus facilitating DNA repair synthesis. In Leishmania major, the causal agent of leishmaniasis, the APE1 homolog is the class II AP endonuclease LMAP. Expression of LMAP but not of APE1 reverts the hypersensitivity of a xth nfo repair-deficient Escherichia coli strain to the oxidative compound hydrogen peroxide (H2O2). To identify the residues specifically involved in the repair of oxidative DNA damage, we generated random mutations in the ape1 gene and selected those variants that conferred protection against H2O2. Among the resistant clones, we isolated a mutant in the nuclease domain of APE1 (D70A) with an increased capacity to remove 3′-blocking ends in vitro. D70 of APE1 aligns with A138 of LMAP and mutation of the latter to aspartate significantly reduces its 3′-phosphodiesterase activity. Kinetic analysis shows a novel role of residue D70 in the excision rate of 3′-blocking ends. The functional and structural differences between the parasite and human enzymes probably reflect a divergent molecular evolution of their DNA repair responses to oxidative damage. PMID:19181704

  6. Optimising web site designs for people with learning disabilities

    PubMed Central

    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. PMID:26097431

  7. Designing a web site for high school geoscience teaching in Iceland

    NASA Astrophysics Data System (ADS)

    Douglas, George R.

    1998-08-01

    The need to construct an earth science teaching site on the web prompted a survey of existing sites which, in spite of containing much of value, revealed many weaknesses in basic design, particularly as regards the organisation of links to information resources. Few web sites take into consideration the particular pedagogic needs of the high school science student and there has, as yet, been little serious attempt to exploit and organise the more outstanding advantages offered by the internet to science teaching, such as accessing real-time data. A web site has been constructed which, through basic design, enables students to access relevant information resources over a wide range of subjects and topics easily and rapidly, while at the same time performing an instructional role in how to handle both on-line and off-line resources. Key elements in the design are selection and monitoring by the teacher, task oriented pages and the use of the Dewey decimal classification system. The intention is to increase gradually the extent to which most teaching tasks are carried out via the web pages, in the belief that they can become an efficient central point for all the earth science curriculum.

  8. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. A Pilot Sampling Design for Estimating Outdoor Recreation Site Visits on the National Forests

    Treesearch

    Stanley J. Zarnoch; S.M. Kocis; H. Ken Cordell; D.B.K. English

    2002-01-01

    A pilot sampling design is described for estimating site visits to National Forest System lands. The three-stage sampling design consisted of national forest ranger districts, site days within ranger districts, and last-exiting recreation visitors within site days. Stratification was used at both the primary and secondary stages. Ranger districts were stratified based...

  10. Procedural Guide for Designation Surveys of Ocean Dredged Material Disposal Sites.

    DTIC Science & Technology

    1981-01-01

    sites in the ocean will be executed by EPA or CE and will be based on Environmental studies of each site, and on historical knowledge of the impact...3 The results of the-s’ studies will be used to prepare an E-A and in some cases an EIS. An important provision regarding the number of separate...assessment for all sites within a particular geographic area may be prepared based on complete disposal site designation or evaluation studies on a typical

  11. Preorganization of molecular binding sites in designed diiron proteins.

    PubMed

    Maglio, Ornella; Nastri, Flavia; Pavone, Vincenzo; Lombardi, Angela; DeGrado, William F

    2003-04-01

    De novo protein design provides an attractive approach to critically test the features that are required for metalloprotein structure and function. Previously we designed and crystallographically characterized an idealized dimeric model for the four-helix bundle class of diiron and dimanganese proteins [Dueferri 1 (DF1)]. Although the protein bound metal ions in the expected manner, access to its active site was blocked by large bulky hydrophobic residues. Subsequently, a substrate-access channel was introduced proximal to the metal-binding center, resulting in a protein with properties more closely resembling those of natural enzymes. Here we delineate the energetic and structural consequences associated with the introduction of these binding sites. To determine the extent to which the binding site was preorganized in the absence of metal ions, the apo structure of DF1 in solution was solved by NMR and compared with the crystal structure of the di-Zn(II) derivative. The overall fold of the apo protein was highly similar to that of the di-Zn(II) derivative, although there was a rotation of one of the helices. We also examined the thermodynamic consequences associated with building a small molecule-binding site within the protein. The protein exists in an equilibrium between folded dimers and unfolded monomers. DF1 is a highly stable protein (K(diss) = 0.001 fM), but the dissociation constant increases to 0.6 nM (deltadeltaG = 5.4 kcalmol monomer) as the active-site cavity is increased to accommodate small molecules.

  12. Chemical and Molecular Biological Aspects of Alkylhydrazine-Induced Carcinogenesis in Human Cells in Vitro. Revised

    DTIC Science & Technology

    1984-04-01

    weights using the following phage DNA markers : lambda, T2 and T7. The number of alkaline labile sites (breaks due to apurinic sites and phosphotriesters...exhibit cell invasiveness in chick embryo skin, human malignancy specific cell- surface antigenic determinants (19), and produce tumors in pre...they eluted from the column, were identified by co-chromatographed markers , (Chart 2). When randomly proliferating cells were treated with either 1,1-DMH

  13. 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…

  14. 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.

  15. BENZO[A]PYRENE-7,8-QUINONE FORMS COVALENT-DNA ADDUCTS IN VITRO BUT NONE WERE DETECTED IN THE LUNGS OR LIVERS OF STRAIN A/J MICE IN VIVO

    EPA Science Inventory

    Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of B[a]P-7,8-dio1-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: 1.] The induction of apurinic sites from radical cati...

  16. Lack of contribution of covalent benzo[a]pyrene-7,8-quinone-DNA adducts in benzo[a]pyrene-induced mouse lung tumorigenesis

    EPA Science Inventory

    Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of anti-trans-B[a]P-7,8-diol-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: 1.] The induction of apurinic sites from r...

  17. 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.

  18. Design Considerations for Siting Grade Control Structures

    DTIC Science & Technology

    2001-12-01

    require consideration before siting grade control structures. In the widest sense, the term grade control can be applied to any alteration in the...control structures. There are two basic types of grade control structures. One type can be referred to as a bed control structure as it is designed to...provide a hard point in the streambed that is capable of resisting the erosive forces of the degradational zone. The second type can be referred to

  19. 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…

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

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

    Kim, Jun-Sang, E-mail: k423j@cnu.ac.kr; Cancer Research Institute, Chungnam National University, Daejeon; Kim, Jin-Man

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

  1. 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

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

    NASA Technical Reports Server (NTRS)

    1978-01-01

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

  3. 41 CFR 102-76.20 - What issues must Federal agencies consider in providing site planning and landscape design services?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  4. 41 CFR 102-76.20 - What issues must Federal agencies consider in providing site planning and landscape design services?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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

  5. 41 CFR 102-76.20 - What issues must Federal agencies consider in providing site planning and landscape design services?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

  6. 41 CFR 102-76.20 - What issues must Federal agencies consider in providing site planning and landscape design services?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  7. 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

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

    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.

  8. 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. [Reserved] 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...

  9. 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. [Reserved] 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...

  10. 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

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

    ERIC Educational Resources Information Center

    Fink, Dieter; Laupase, Ricky

    2000-01-01

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

  12. Designing Metaphorically Appropriate Graphics for a PT3 World Wide Web Site.

    ERIC Educational Resources Information Center

    Henry, Anne; Crawford, Caroline M.

    This paper describes the design and development of a World Wide Web site associated with a Preparing Tomorrow's Teachers to Use Technology (PT3) grant that was awarded to the University of Houston at Clear Lake (Texas) by the U.S. Department of Education. The Web site that created the electronic community (e-community) was to meet the needs and…

  13. 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…

  14. Data for the geochemical investigation of UMTRAP designated site at Durango, Colorado

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

    Markos, G.; Bush, K.J.

    1983-09-01

    This report contains the methods of collection and the data used in the geochemical investigation of the former tailings and raffinate pond sites at Durango, Colorado. The methods of data interpretation and results of the investigation are described in the report, ''Geochemical Investigation of UMTRAP Designated Site at Durango, Colorado''. Data are from a one-time sampling of waters and solid material from the background, the area adjacent to the site, and the site. The 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 analyzedmore » for selected major and trace elements. A few samples were analyzed for radioisotopes.« less

  15. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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...

  16. 10 CFR 435.6 - Sustainable principles for siting, design and construction. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 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...

  17. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  19. Seismic site coefficients and acceleration design response spectra based on conditions in South Carolina : final report.

    DOT National Transportation Integrated Search

    2014-11-15

    The simplified procedure in design codes for determining earthquake response spectra involves : estimating site coefficients to adjust available rock accelerations to site accelerations. Several : investigators have noted concerns with the site coeff...

  20. 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

    ... construction of new facilities, which include— (a) Optimizing site potential; (b) Minimizing non-renewable... development principles must Federal agencies apply to the siting, design, and construction of new facilities... Federal agencies apply to the siting, design, and construction of new facilities? In keeping with the...

  1. 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

    ... construction of new facilities, which include— (a) Optimizing site potential; (b) Minimizing non-renewable... development principles must Federal agencies apply to the siting, design, and construction of new facilities... Federal agencies apply to the siting, design, and construction of new facilities? In keeping with the...

  2. 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

    ... construction of new facilities, which include— (a) Optimizing site potential; (b) Minimizing non-renewable... development principles must Federal agencies apply to the siting, design, and construction of new facilities... Federal agencies apply to the siting, design, and construction of new facilities? In keeping with the...

  3. 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

    ... construction of new facilities, which include— (a) Optimizing site potential; (b) Minimizing non-renewable... development principles must Federal agencies apply to the siting, design, and construction of new facilities... Federal agencies apply to the siting, design, and construction of new facilities? In keeping with the...

  4. 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.

  5. 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

  6. Tornado risks and design windspeeds for the Oak Ridge Plant Site

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

    Not Available

    1975-08-01

    The effects of tornadoes and other extreme winds should be considered in establishing design criteria for structures to resist wind loads. Design standards that are incorporated in building codes do not normally include the effects of tornadoes in their wind load criteria. Some tornado risk models ignore the presence of nontornadic extreme winds. The purpose of this study is to determine the probability of tornadic and straight winds exceeding a threshold value in the geographical region surrounding the Oak Ridge, Tennessee plant site.

  7. Identification and Characterization of New Chemical Entities Targeting Apurinic/Apyrimidinic Endonuclease 1 for the Prevention of Chemotherapy-Induced Peripheral Neuropathy.

    PubMed

    Kelley, Mark R; Wikel, James H; Guo, Chunlu; Pollok, Karen E; Bailey, Barbara J; Wireman, Randy; Fishel, Melissa L; Vasko, Michael R

    2016-11-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a potentially debilitating side effect of a number of chemotherapeutic agents. There are currently no U.S. Food and Drug Administration-approved interventions or prevention strategies for CIPN. Although the cellular mechanisms mediating CIPN remain to be determined, several lines of evidence support the notion that DNA damage caused by anticancer therapies could contribute to the neuropathy. DNA damage in sensory neurons after chemotherapy correlates with symptoms of CIPN. Augmenting apurinic/apyrimidinic endonuclease (APE)-1 function in the base excision repair pathway reverses this damage and the neurotoxicity caused by anticancer therapies. This neuronal protection is accomplished by either overexpressing APE1 or by using a first-generation targeted APE1 small molecule, E3330 [(2E)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)methylene]-undecanoic acid; also called APX3330]. Although E3330 has been approved for phase 1 clinical trials (Investigational New Drug application number IND125360), we synthesized novel, second-generation APE1-targeted molecules and determined whether they would be protective against neurotoxicity induced by cisplatin or oxaliplatin while not diminishing the platins' antitumor effect. We measured various endpoints of neurotoxicity using our ex vivo model of sensory neurons in culture, and we determined that APX2009 [(2E)-2-[(3-methoxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)methylidene]-N,N-diethylpentanamide] is an effective small molecule that is neuroprotective against cisplatin and oxaliplatin-induced toxicity. APX2009 also demonstrated a strong tumor cell killing effect in tumor cells and the enhanced tumor cell killing was further substantiated in a more robust three-dimensional pancreatic tumor model. Together, these data suggest that the second-generation compound APX2009 is effective in preventing or reversing platinum-induced CIPN while not affecting the

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

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

    Not Available

    1991-12-01

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

  9. Influence of active site location on catalytic activity in de novo-designed zinc metalloenzymes.

    PubMed

    Zastrow, Melissa L; Pecoraro, Vincent L

    2013-04-17

    While metalloprotein design has now yielded a number of successful metal-bound and even catalytically active constructs, the question of where to put a metal site along a linear, repetitive sequence has not been thoroughly addressed. Often several possibilities in a given sequence may exist that would appear equivalent but may in fact differ for metal affinity, substrate access, or protein dynamics. We present a systematic variation of active site location for a hydrolytically active ZnHis3O site contained within a de novo-designed three-stranded coiled coil. We find that the maximal rate, substrate access, and metal-binding affinity are dependent on the selected position, while catalytic efficiency for p-nitrophenyl acetate hydrolysis can be retained regardless of the location of the active site. This achievement demonstrates how efficient, tailor-made enzymes which control rate, pKa, substrate and solvent access (and selectivity), and metal-binding affinity may be realized. These findings may be applied to the more advanced de novo design of constructs containing secondary interactions, such as hydrogen-bonding channels. We are now confident that changes to location for accommodating such channels can be achieved without location-dependent loss of catalytic efficiency. These findings bring us closer to our ultimate goal of incorporating the secondary interactions we believe will be necessary in order to improve both active site properties and the catalytic efficiency to be competitive with the native enzyme, carbonic anhydrase.

  10. 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…

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

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

    Gilmore, Tyler; Bonneville, Alain; Sullivan, Charlotte

    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 themore » 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.« less

  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. Estimating open population site occupancy from presence-absence data lacking the robust design.

    PubMed

    Dail, D; Madsen, L

    2013-03-01

    Many animal monitoring studies seek to estimate the proportion of a study area occupied by a target population. The study area is divided into spatially distinct sites where the detected presence or absence of the population is recorded, and this is repeated in time for multiple seasons. However, when occupied sites are detected with probability p < 1, the lack of a detection does not imply lack of occupancy. MacKenzie et al. (2003, Ecology 84, 2200-2207) developed a multiseason model for estimating seasonal site occupancy (ψt ) while accounting for unknown p. Their model performs well when observations are collected according to the robust design, where multiple sampling occasions occur during each season; the repeated sampling aids in the estimation p. However, their model does not perform as well when the robust design is lacking. In this paper, we propose an alternative likelihood model that yields improved seasonal estimates of p and Ψt in the absence of the robust design. We construct the marginal likelihood of the observed data by conditioning on, and summing out, the latent number of occupied sites during each season. A simulation study shows that in cases without the robust design, the proposed model estimates p with less bias than the MacKenzie et al. model and hence improves the estimates of Ψt . We apply both models to a data set consisting of repeated presence-absence observations of American robins (Turdus migratorius) with yearly survey periods. The two models are compared to a third estimator available when the repeated counts (from the same study) are considered, with the proposed model yielding estimates of Ψt closest to estimates from the point count model. Copyright © 2013, The International Biometric Society.

  14. 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…

  15. I've Been Framed! Designing a Library Web Site Within a Government Frame

    ERIC Educational Resources Information Center

    Houghton, Sarah

    2005-01-01

    Often, because of political reasons, a library's site must be designed within the frame of another organization's. In this article, the author, the e-services librarian for the Marin County Free Library in San Rafael, California, details her experience of designing a library website within the frame--and within the rules and limitations--of the…

  16. 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.

  17. Development of a design basis tornado and structural design criteria for the Nevada Test Site, Nevada. Final report

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

    McDonald, J.R.; Minor, J.E.; Mehta, K.C.

    1975-06-01

    In order to evaluate the ability of critical facilities at the Nevada Test Site to withstand the possible damaging effects of extreme winds and tornadoes, parameters for the effects of tornadoes and extreme winds and structural design criteria for the design and evaluation of structures were developed. The meteorological investigations conducted are summarized, and techniques used for developing the combined tornado and extreme wind risk model are discussed. The guidelines for structural design include methods for calculating pressure distributions on walls and roofs of structures and methods for accommodating impact loads from wind-driven missiles. Calculations for determining the design loadsmore » for an example structure are included. (LCL)« less

  18. Achieving full connectivity of sites in the multiperiod reserve network design problem

    USGS Publications Warehouse

    Jafari, Nahid; Nuse, Bryan L.; Moore, Clinton; Dilkina, Bistra; Hepinstall-Cymerman, Jeffrey

    2017-01-01

    The conservation reserve design problem is a challenge to solve because of the spatial and temporal nature of the problem, uncertainties in the decision process, and the possibility of alternative conservation actions for any given land parcel. Conservation agencies tasked with reserve design may benefit from a dynamic decision system that provides tactical guidance for short-term decision opportunities while maintaining focus on a long-term objective of assembling the best set of protected areas possible. To plan cost-effective conservation over time under time-varying action costs and budget, we propose a multi-period mixed integer programming model for the budget-constrained selection of fully connected sites. The objective is to maximize a summed conservation value over all network parcels at the end of the planning horizon. The originality of this work is in achieving full spatial connectivity of the selected sites during the schedule of conservation actions.

  19. 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.

  20. 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

    ...Logic, Inc., Austin, TX; Amended Certification Regarding Eligibility To Apply for Worker Adjustment..., Design Solutions, Inc., Veriseo, SilconElite and MicroLogic, Inc. were employed on-site at the Austin...., Veriseo, SiliconElite and MicroLogic, Inc. working on-site at the Austin, Texas, location of Freescale...

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

    PubMed Central

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

    2013-01-01

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

  3. Groundwater contamination from waste management sites: The interaction between risk-based engineering design and regulatory policy: 2. Results

    NASA Astrophysics Data System (ADS)

    Massmann, Joel; Freeze, R. Allan

    1987-02-01

    The risk-cost-benefit analysis developed in the companion paper (J. Massmann and R. A. Freeze, this issue) is here applied to (1) an assessment of the relative worth of containment-construction activities, site-exploration activities, and monitoring activities as components of a design strategy for the owner/operator of a waste management facility; (2) an assessment of alternative policy options available to a regulatory agency; and (3) a case history. Sensitivity analyses designed to address the first issue show that the allocation of resources by the owner/operator is sensitive to the stochastic parameters used to describe the hydraulic conductivity field at a site. For the cases analyzed, the installation of a dense monitoring network is of less value to the owner/operator than a more conservative containment design. Sensitivity analyses designed to address the second issue suggest that from a regulatory perspective, design standards should be more effective than performance standards in reducing risk, and design specifications on the containment structure should be more effective than those on the monitoring network. Performance bonds posted before construction have a greater potential to influence design than prospective penalties to be imposed at the time of failure. Siting on low-conductivity deposits is a more effective method of risk reduction than any form of regulatory influence. Results of the case history indicate that the methodology can be successfully applied at field sites.

  4. Development of a design basis tornado and structural design criteria for Lawrence Livermore Laboratory's Site 300

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

    McDonald, J.R.; Minor, J.E.; Mehta, K.C.

    1975-11-01

    Criteria are prescribed and guidance is provided for professional personnel who are involved with the evaluation of existing buildings and facilities at Site 300 near Livermore, California to resist the possible effects of extreme winds and tornadoes. The development of parameters for the effects of tornadoes and extreme winds and guidelines for evaluation and design of structures are presented. The investigations conducted are summarized and the techniques used for arriving at the combined tornado and extreme wind risk model are discussed. The guidelines for structural design methods for calculating pressure distributions on walls and roofs of structures and methods formore » accommodating impact loads from missiles are also presented. (auth)« less

  5. Identification of Conserved Water Sites in Protein Structures for Drug Design.

    PubMed

    Jukič, Marko; Konc, Janez; Gobec, Stanislav; Janežič, Dušanka

    2017-12-26

    Identification of conserved waters in protein structures is a challenging task with applications in molecular docking and protein stability prediction. As an alternative to computationally demanding simulations of proteins in water, experimental cocrystallized waters in the Protein Data Bank (PDB) in combination with a local structure alignment algorithm can be used for reliable prediction of conserved water sites. We developed the ProBiS H2O approach based on the previously developed ProBiS algorithm, which enables identification of conserved water sites in proteins using experimental protein structures from the PDB or a set of custom protein structures available to the user. With a protein structure, a binding site, or an individual water molecule as a query, ProBiS H2O collects similar proteins from the PDB and performs local or binding site-specific superimpositions of the query structure with similar proteins using the ProBiS algorithm. It collects the experimental water molecules from the similar proteins and transposes them to the query protein. Transposed waters are clustered by their mutual proximity, which enables identification of discrete sites in the query protein with high water conservation. ProBiS H2O is a robust and fast new approach that uses existing experimental structural data to identify conserved water sites on the interfaces of protein complexes, for example protein-small molecule interfaces, and elsewhere on the protein structures. It has been successfully validated in several reported proteins in which conserved water molecules were found to play an important role in ligand binding with applications in drug design.

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

    PubMed

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

    2016-01-01

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

  7. 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

  8. 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…

  9. 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…

  10. 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…

  11. 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

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,739; TA-W-81,739A] Hewlett-Packard Company, Design Delivery Organization (DDO), Including On-Site Leased Workers From Manpower, Synova Inc., and Pinnacle Technical Resources, Corvallis, OR; Hewlett-Packard Company, Ink Jet & Web Services, World Wide Design Group, Vancouver, WA;...

  12. 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

    2018-04-01

    What is the topic of this review? In this review, we analyse the performance of recently described tools for CRISPR/Cas9 guide RNA design, in particular, design tools that predict CRISPR/Cas9 activity. What advances does it highlight? Recently, many tools designed to predict CRISPR/Cas9 activity have been reported. However, the majority of these tools lack experimental validation. Our analyses indicate that these tools have poor predictive power. Our preliminary results suggest that target site accessibility should be considered in order to develop better guide RNA design tools with improved predictive power. The recent adaptation of the clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system for targeted genome engineering has led to its widespread application in many fields worldwide. In order to gain a better understanding of 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 guide RNA (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 optimization, we hypothesize that it will be possible to increase the predictive power of gRNA design tools by including both sequence and target site accessibility metrics. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

  13. Development of variable LRFD \\0x03C6 factors for deep foundation design due to site variability.

    DOT National Transportation Integrated Search

    2012-04-01

    The current design guidelines of Load and Resistance Factor Design (LRFD) specifies constant values : for deep foundation design, based on analytical method selected and degree of redundancy of the pier. : However, investigation of multiple sites in ...

  14. Colonization of UK coastal realignment sites by mosquitoes: implications for design, management, and public health.

    PubMed

    Medlock, J M; Vaux, A G C

    2013-06-01

    Coastal realignment is now widely instituted in the UK as part of local flood risk management plans to compensate for the loss of European protected habitat and to mitigate the effects of sea-level rise and coastal squeeze. Coastal aquatic habitats have long been known to provide suitable habitats for brackish-water mosquitoes and historically, coastal marshes were considered to support anopheline mosquito populations that were responsible for local malaria transmission. This study surveyed the eight largest managed realignment (MRA) sites in England (Essex and the Humber) for mosquito habitats. The apparent absence of anopheline mosquitoes exploiting aquatic habitats at all of these sites suggests that the risk of malaria associated with MRA sites is currently negligible. However, three of the eight sites supported populations of two nuisance and potential arboviral vector species, Aedes detritus and Aedes caspius. The aquatic habitats that supported mosquitoes resulted from a) specific design aspects of the new sea wall (ballast to mitigate wave action and constructed saline borrow ditches) that could be designed out or managed or b) isolated pools created through silt accretion or expansion of flooded zones to neighbouring pasture. The public health risks and recommendations for management are discussed in this report. This report highlights the need for pro-active public health impact assessments prior to MRA development in consultation with the Health Protection Agency, as well as the need for a case-by-case approach to design and management to mitigate mosquito or mosquito-borne disease issues now and in the future. © 2013 The Society for Vector Ecology.

  15. Barrier Free Site Design.

    ERIC Educational Resources Information Center

    Dee, Richard K., Ed.

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

  16. 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. © 2017 The Author(s).

  17. Designing of Protein Kinase C β-II Inhibitors against Diabetic complications: Structure Based Drug Design, Induced Fit docking and analysis of active site conformational changes

    PubMed Central

    Vijayakumar, Balakrishnan; Velmurugan, Devadasan

    2012-01-01

    Protein Kinase C β-II (PKC β-II) is an important enzyme in the development of diabetic complications like cardiomyopathy, retinopathy, neuropathy, nephropathy and angiopathy. PKC β-II is activated in vascular tissues during diabetic vascular abnormalities. Thus, PKC β-II is considered as a potent drug target and the crystal structure of the kinase domain of PKC β-II (PDB id: 2I0E) was used to design inhibitors using Structure-Based Drug Design (SBDD) approach. Sixty inhibitors structurally similar to Staurosporine were retrieved from PubChem Compound database and High Throughput Virtual screening (HTVs) was carried out with PKC β-II. Based on the HTVs results and the nature of active site residues of PKC β-II, Staurosporine inhibitors were designed using SBDD. Induced Fit Docking (IFD) studies were carried out between kinase domain of PKC β-II and the designed inhibitors. These IFD complexes showed favorable docking score, glide energy, glide emodel and hydrogen bond and hydrophobic interactions with the active site of PKC β-II. Binding free energy was calculated for IFD complexes using Prime MM-GBSA method. The conformational changes induced by the inhibitor at the active site of PKC β-II were observed for the back bone Cα atoms and side-chain chi angles. PASS prediction tool was used to analyze the biological activities for the designed inhibitors. The various physicochemical properties were calculated for the compounds. One of the designed inhibitors successively satisfied all the in silico parameters among the others and seems to be a potent inhibitor against PKC β-II. PMID:22829732

  18. "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…

  19. Heat shock protein 70 enhanced deoxyribonucleic acid base excision repair in human leukemic cells after ionizing radiation

    PubMed Central

    Bases, Robert

    2006-01-01

    Base excision repair (BER) of DNA damage in irradiated THP1 human leukemic cells was stimulated by pretreating the cells with exogenous recombinant Hsp70. The treatment of THP1 cells with recombinant Hsp70 in cell culture promoted repair by reducing the frequency of apurinic, apyrimidinic (AP) sites in DNA before and after 1.3 Gy of radiation. However, by 30 minutes after 2.6 Gy, accelerated repair of abasic sites supervened, which may contribute to the loss of the very-low-dose cell hypersensitivity seen in clonogenic studies of other laboratories. After irradiation with 2.6 Gy, the crucial initial glycosylase step was markedly incomplete when cells had been transfected 24 hours before with a small interfering RNA (siRNA) designed to inhibit synthesis of Hsp70. In confirmation, lysates from irradiated siRNA-treated cells after 2.6 Gy were deficient in uracil glycosylase activity (UDG). Transfection with a scrambled RNA of the same size did not interfere with the glycosylase step, ie, the prompt conversion of damaged pyrimidine sites to abasic sites as well as the subsequent repair of those sites. BER measured by reduction of DNA AP sites before and after low-dose radiation was also deficient in THP1 cells that had been transfected with the siRNA designed to inhibit synthesis of Hsp70. These results implicate BER and the participation of Hsp70 in the repair of DNA in human leukemic cells with the doses of ionizing radiation used in clinical regimens. PMID:17009597

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

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

    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.more » 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.« less

  1. Design of Buoys for Mounting Wind Turbines at Exposed Sites

    NASA Astrophysics Data System (ADS)

    Erdoğan, Beytullah; Çelıkkol, Barbaros; Swift, Robinson

    2018-04-01

    In this study, two designs for a buoy capable of supporting a 10 kW wind turbine and its tower were developed to operate at the University of New Hampshire's Center of Ocean Renewable Energy testing site located off the Isles of Shoals, New Hampshire. The buoys are to be moored by a catenary chain system. To evaluate wave response, two Froude-scaled models were constructed, tested, and compared at the Ocean Engineering wave tank at the University of New Hampshire. These buoys have been implemented and compared with wave tank measurements of the spar displacement at a reference elevation 2.44 m above the mean water level.

  2. Designing tri-branched multiple-site SO2 capture materials.

    PubMed

    Li, Chenchen; Lu, Dongmei; Wu, Chao

    2018-06-07

    SO2 capture materials usually have multiple reactive sites located within a limited space, thus absorptions (or adsorptions) of disparate strengths and low effective capacity per sorption-desorption cycle become the natural results of the so-called "coverage effects" (due to both the electronic and steric effects). Here, we propose a tri-branched framework with separated reactive sites and nearly uniform charge distribution on the reacting atoms. Through density functional theory (DFT)-based calculations and simulated isotherms, two N-centered anionic structures (terminated with amine (TAEA) and imidazolyl (TIA) groups, respectively) are selected from a series of representative tri-branched species. The TAEA-based ILs are predicted to exhibit the highest uptakes (about 6.1 mol SO2 per mole IL) at 1 bar of SO2 and 20 °C, which reach the ceiling capacity that a negative charge can provide. The TIA-based ILs have small differences in their SO2 sequential binding energies and they are estimated to have the best effective SO2 capacity during a sorption-desorption cycle (about 2.6 mol SO2 per mole IL, absorption at 1 bar of SO2 and 20 °C and desorption at 1 bar of SO2 and 120 °C). Moreover, we also find that the designed species can efficiently capture other gases like NO.

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

    NASA Astrophysics Data System (ADS)

    Nigra, Michael Mark

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

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

    NASA Astrophysics Data System (ADS)

    Nowak, W.

    2013-12-01

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

  6. The impact of target site accessibility on the design of effective siRNAs.

    PubMed

    Tafer, Hakim; Ameres, Stefan L; Obernosterer, Gregor; Gebeshuber, Christoph A; Schroeder, Renée; Martinez, Javier; Hofacker, Ivo L

    2008-05-01

    Small-interfering RNAs (siRNAs) assemble into RISC, the RNA-induced silencing complex, which cleaves complementary mRNAs. Despite their fluctuating efficacy, siRNAs are widely used to assess gene function. Although this limitation could be ascribed, in part, to variations in the assembly and activation of RISC, downstream events in the RNA interference (RNAi) pathway, such as target site accessibility, have so far not been investigated extensively. In this study we present a comprehensive analysis of target RNA structure effects on RNAi by computing the accessibility of the target site for interaction with the siRNA. Based on our observations, we developed a novel siRNA design tool, RNAxs, by combining known siRNA functionality criteria with target site accessibility. We calibrated our method on two data sets comprising 573 siRNAs for 38 genes, and tested it on an independent set of 360 siRNAs targeting four additional genes. Overall, RNAxs proves to be a robust siRNA selection tool that substantially improves the prediction of highly efficient siRNAs.

  7. 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.

  8. 40 CFR 228.4 - Procedures for designation of sites.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... environmental studies of each site, regions adjacent to the site, and on historical knowledge of the impact of waste disposal on areas similar to such sites in physical, chemical, and biological characteristics. All studies for the evaluation and potential selection of dumping sites will be conducted in accordance with...

  9. 40 CFR 228.4 - Procedures for designation of sites.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... environmental studies of each site, regions adjacent to the site, and on historical knowledge of the impact of waste disposal on areas similar to such sites in physical, chemical, and biological characteristics. All studies for the evaluation and potential selection of dumping sites will be conducted in accordance with...

  10. 40 CFR 228.4 - Procedures for designation of sites.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... environmental studies of each site, regions adjacent to the site, and on historical knowledge of the impact of waste disposal on areas similar to such sites in physical, chemical, and biological characteristics. All studies for the evaluation and potential selection of dumping sites will be conducted in accordance with...

  11. 40 CFR 228.4 - Procedures for designation of sites.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... environmental studies of each site, regions adjacent to the site, and on historical knowledge of the impact of waste disposal on areas similar to such sites in physical, chemical, and biological characteristics. All studies for the evaluation and potential selection of dumping sites will be conducted in accordance with...

  12. 40 CFR 228.4 - Procedures for designation of sites.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... environmental studies of each site, regions adjacent to the site, and on historical knowledge of the impact of waste disposal on areas similar to such sites in physical, chemical, and biological characteristics. All studies for the evaluation and potential selection of dumping sites will be conducted in accordance with...

  13. Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis

    PubMed Central

    Lu, Duo; Silhan, Jan; MacDonald, James T.; Carpenter, Elisabeth P.; Jensen, Kirsten; Tang, Christoph M.; Baldwin, Geoff S.; Freemont, Paul S.

    2012-01-01

    Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cleaving the phosphodiester backbone 5′ to the abasic site. Despite extensive study, there is no structure of a bacterial AP endonuclease bound to substrate DNA. Furthermore, the structural mechanism for AP-site cleavage is incomplete. Here we report a detailed structural and biochemical study of the AP endonuclease from Neisseria meningitidis that has allowed us to capture structural intermediates providing more complete snapshots of the catalytic mechanism. Our data reveal subtle differences in AP-site recognition and kinetics between the human and bacterial enzymes that may reflect different evolutionary pressures. PMID:23035246

  14. An Experimental and Theoretical Evaluation of Multi-site Cadmium(II) Exchange in Designed Three-Stranded Coiled Coil Peptides

    PubMed Central

    Chakraborty, Saumen; Iranzo, Olga; Zuiderweg, Erik R.P.; Pecoraro, Vincent L.

    2012-01-01

    An important factor that defines the toxicity of elements such as cadmium(II), mercury(II), and lead(II) with biological macromolecules is metal ion exchange dynamics. Intriguingly, little is known about the fundamental rates and mechanisms of metal ion exchange into proteins, especially helical bundles. Herein, we investigate the exchange kinetics of cadmium(II) using de novo designed three-stranded coiled coil peptides that contain metal complexing cysteine thiolates as a model for the incorporation of this ion into trimeric, parallel helical bundles. Peptides were designed containing both single cadmium(II) binding site, GrandL12AL16C [Grand=AcG-(LKALEEK)5-GNH2], GrandL26AL30C, and GrandL26AE28QL30C, as well as GrandL12AL16CL26AL30C with two cadmium(II) binding sites. The binding of cadmium(II) to any of these sites is of high affinity (KA > 3×107 M−1). Using 113Cd NMR spectroscopy, cadmium(II) binding to these designed peptides was monitored. While the cadmium(II) binding is in extreme slow exchange without showing any chemical shift changes, incremental line broadening for the bound 113cadmium(II) signal is observed when excess 113cadmium(II) is titrated into the peptides. Most dramatically, for one site, L26AL30C, all 113cadmium(II) NMR signals disappear once a 1.7:1 ratio of cadmium(II)/(peptide)3 is reached. The observed processes are not compatible with simple “free-bound” two-site exchange kinetics at any time regime. The experimental results can, however, be simulated in detail with a multi-site binding model, which features additional cadmium(II) binding site(s) which, once occupied, perturb the primary binding site. This model is expanded into differential equations for five-site NMR chemical exchange. The numerical integration of these equations exhibits progressive loss of the primary site NMR signal without a chemical shift change and with limited line broadening, in good agreement with the observed experimental data. The mathematical model

  15. Spatial Statistical Models and Optimal Survey Design for Rapid Geophysical characterization of UXO Sites

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

    G. Ostrouchov; W.E.Doll; D.A.Wolf

    2003-07-01

    Unexploded ordnance(UXO)surveys encompass large areas, and the cost of surveying these areas can be high. Enactment of earlier protocols for sampling UXO sites have shown the shortcomings of these procedures and led to a call for development of scientifically defensible statistical procedures for survey design and analysis. This project is one of three funded by SERDP to address this need.

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

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

    Not Available

    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 amore » 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.« less

  17. 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

  18. 78 FR 38672 - Ocean Dumping; Sabine-Neches Waterway (SNWW) Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-27

    ... March 2011 prepared by the U.S. Army Corps of Engineers (also Corps or USACE). Appendix B of Volume III... be considered on the proposed site designations. The U.S. Army Corps of Engineers Final EIS for the... of dredged material from the Sabine-Neches Waterway. Currently, the US Army Corps of Engineers will...

  19. Hydration in drug design. 3. Conserved water molecules at the ligand-binding sites of homologous proteins

    NASA Astrophysics Data System (ADS)

    Poornima, C. S.; Dean, P. M.

    1995-12-01

    Water molecules are known to play an important rôle in mediating protein-ligand interactions. If water molecules are conserved at the ligand-binding sites of homologous proteins, such a finding may suggest the structural importance of water molecules in ligand binding. Structurally conserved water molecules change the conventional definition of `binding sites' by changing the shape and complementarity of these sites. Such conserved water molecules can be important for site-directed ligand/drug design. Therefore, five different sets of homologous protein/protein-ligand complexes have been examined to identify the conserved water molecules at the ligand-binding sites. Our analysis reveals that there are as many as 16 conserved water molecules at the FAD binding site of glutathione reductase between the crystal structures obtained from human and E. coli. In the remaining four sets of high-resolution crystal structures, 2-4 water molecules have been found to be conserved at the ligand-binding sites. The majority of these conserved water molecules are either bound in deep grooves at the protein-ligand interface or completely buried in cavities between the protein and the ligand. All these water molecules, conserved between the protein/protein-ligand complexes from different species, have identical or similar apolar and polar interactions in a given set. The site residues interacting with the conserved water molecules at the ligand-binding sites have been found to be highly conserved among proteins from different species; they are more conserved compared to the other site residues interacting with the ligand. These water molecules, in general, make multiple polar contacts with protein-site residues.

  20. A reliable facility location design model with site-dependent disruption in the imperfect information context

    PubMed Central

    Yun, Lifen; Wang, Xifu; Fan, Hongqiang; Li, Xiaopeng

    2017-01-01

    This paper proposes a reliable facility location design model under imperfect information with site-dependent disruptions; i.e., each facility is subject to a unique disruption probability that varies across the space. In the imperfect information contexts, customers adopt a realistic “trial-and-error” strategy to visit facilities; i.e., they visit a number of pre-assigned facilities sequentially until they arrive at the first operational facility or give up looking for the service. This proposed model aims to balance initial facility investment and expected long-term operational cost by finding the optimal facility locations. A nonlinear integer programming model is proposed to describe this problem. We apply a linearization technique to reduce the difficulty of solving the proposed model. A number of problem instances are studied to illustrate the performance of the proposed model. The results indicate that our proposed model can reveal a number of interesting insights into the facility location design with site-dependent disruptions, including the benefit of backup facilities and system robustness against variation of the loss-of-service penalty. PMID:28486564

  1. Apoptosis-Resistant Cardiac Progenitor Cells Modified With Apurinic/Apyrimidinic Endonuclease/Redox Factor 1 Gene Overexpression Regulate Cardiac Repair After Myocardial Infarction.

    PubMed

    Aonuma, Tatsuya; Takehara, Naofumi; Maruyama, Keisuke; Kabara, Maki; Matsuki, Motoki; Yamauchi, Atsushi; Kawabe, Jun-Ichi; Hasebe, Naoyuki

    2016-08-01

    : Overcoming the insufficient survival of cell grafts is an essential objective in cell-based therapy. Apurinic/apyrimidinic endonuclease/redox factor 1 (APE1) promotes cell survival and may enhance the therapeutic effect of engrafted cells. The aim of this study is to determine whether APE1 overexpression in cardiac progenitor cells (CPCs) could ameliorate the efficiency of cell-based therapy. CPCs isolated from 8- to 10-week-old C57BL/6 mouse hearts were infected with retrovirus harboring APE1-DsRed (APE1-CPC) or a DsRed control (control-CPC). Oxidative stress-induced apoptosis was then assessed in APE1-CPCs, control-CPCs, and neonatal rat ventricular myocytes (NRVMs) cocultured with these CPCs. This analysis revealed that APE1 overexpression inhibited CPC apoptosis with activation of transforming growth factor β-activated kinase 1 (TAK1) and nuclear factor (NF)-κB. In the coculture model, NRVM apoptosis was inhibited to a greater extent in the presence of APE1-CPCs compared with control-CPCs. Moreover, the number of surviving DsRed-positive CPC grafts was significantly higher 7 days after the transplant of APE1-CPCs into a mouse myocardial infarction model, and the left ventricular ejection fraction showed greater improvement with attenuation of fibrosis 28 days after the transplant of APE1-CPCs compared with control-CPCs. Additionally, fewer inflammatory macrophages and a higher percentage of cardiac α-sarcomeric actinin-positive CPC-grafts were observed in mice injected with APE1-CPCs compared with control-CPCs after 7 days. In conclusion, antiapoptotic APE1-CPC graft, which increased TAK1-NF-κB pathway activation, survived effectively in the ischemic heart, restored cardiac function, and reduced cardiac inflammation and fibrosis. APE1 overexpression in CPCs may serve as a novel strategy to improve cardiac cell therapy. Improving the survival of cell grafts is essential to maximize the efficacy of cell therapy. The authors investigated the role of APE1 in

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

    PubMed

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

    2013-06-13

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

  3. 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…

  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

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

    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.more » 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.« less

  5. Capturing Snapshots of APE1 Processing DNA Damage

    PubMed Central

    Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.; Dyrkheeva, Nadezhda S.; Wilson, Samuel H.

    2015-01-01

    DNA apurinic-apyrimidinic (AP) sites are prevalent non-coding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive due in part to limited structural information. We report multiple high-resolution human APE1:DNA structures that divulge novel features of the APE1 reaction, including the metal binding site, nucleophile, and arginine clamps that mediate product release. We also report APE1:DNA structures with a T:G mismatch 5′ to the AP-site, representing a clustered lesion occurring in methylated CpG dinucleotides. These reveal that APE1 molds the T:G mismatch into a unique Watson-Crick like geometry that distorts the active site reducing incision. These snapshots provide mechanistic clarity for APE1, while affording a rational framework to manipulate biological responses to DNA damage. PMID:26458045

  6. 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.

  7. 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.

  8. The Role of Forethought and Serendipity in Designing a Successful Hydrogeological Research Site

    NASA Astrophysics Data System (ADS)

    Shapiro, A. M.; Hsieh, P. A.

    2008-12-01

    Designing and implementing a successful hydrogeologic field research observatory requires careful planning among a multidisciplinary group of research scientists. In addition, a small team of research coordinators needs to assume responsibility for smoothly integrating the multidisciplinary experimental program and promoting the explanation of results across discipline boundaries. A narrow interpretation of success at these hydrogeologic observatories can be viewed as the completion of the field-based experiments and the reporting of results for the field site under investigation. This alone is no small task, given the financial and human resources that are needed to develop and maintain field infrastructure, as well as developing, maintaining, and sharing data and interpretive results. Despite careful planning, however, unexpected or serendipitous results can occur. Such serendipitous results can lead to new understanding and revision of original hypotheses. To fully evaluate such serendipitous results, the field program must collect a broad range of scientifically robust data-beyond what is needed to examine the original hypotheses. In characterizing ground water flow and chemical transport in fractured crystalline rock in the Mirror Lake watershed in central New Hampshire, unexpected effects of scale were observed for hydraulic conductivity and matrix diffusion. Contrary to existing theory, hydraulic conductivity at the site did not increase with scale, whereas the effective coefficient of matrix diffusion was found to increase with scale. These results came to light only after examination of extensive data from carefully designed hydraulic and chemical transport experiments. Experiments were conducted on rock cores, individual fractures and volumes of fractured rock over physical dimensions from meters to kilometers. The interpretation of this data yielded new insight into the effect of scale on chemical transport and hydraulic conductivity of fractured rock

  9. 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. Copyright © 2016. Published by Elsevier B.V.

  10. SU-D-213-05: Design, Evaluation and First Applications of a Off-Site State-Of-The-Art 3D Dosimetry System

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

    Malcolm, J; Mein, S; McNiven, A

    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 ofmore » 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.« less

  11. Effluent quality from 200 on-site sewage systems: design values for guidelines.

    PubMed

    Charles, K J; Ashbolt, N J; Roser, D J; McGuinness, R; Deere, D A

    2005-01-01

    The quality of effluent from an on-site sewage treatment system is a critical factor in designing the disposal area and, hence, ensuring the sustained performance of the system. Contaminant concentrations in effluent are typically specified in regulatory guidelines or standards; however, the accuracy of these guideline values are brought into question due to the poor performance of septic tanks and the high failure rates of disposal systems reported here and elsewhere. Results from studies of septic tank effluent quality indicated that the effluent is of poorer quality than currently suggested by guidelines. Aerated wastewater treatment systems were found to perform to accreditation guidelines; however, insufficient nutrient data is presently available to assess nutrient loads. It is proposed that the 80th percentile of system performance be adopted as the design value for sizing effluent disposal areas to minimise failure associated with overloading. For septic tanks this equates to 660 mg L(-1) SS, 330 mg L(-1) BOD, 250 mg L(-1) TN and 36 mg L(-1) TP.

  12. 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…

  13. 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

  14. Ames expedited site characterization demonstration at the former manufactured gas plant site, Marshalltown, Iowa

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

    Bevolo, A.J.; Kjartanson, B.H.; Wonder, J.D.

    1996-03-01

    The goal of the Ames Expedited Site Characterization (ESC) project is to evaluate and promote both innovative technologies (IT) and state-of-the-practice technologies (SOPT) for site characterization and monitoring. In April and May 1994, the ESC project conducted site characterization, technology comparison, and stakeholder demonstration activities at a former manufactured gas plant (FMGP) owned by Iowa Electric Services (IES) Utilities, Inc., in Marshalltown, Iowa. Three areas of technology were fielded at the Marshalltown FMGP site: geophysical, analytical and data integration. The geophysical technologies are designed to assess the subsurface geological conditions so that the location, fate and transport of the targetmore » contaminants may be assessed and forecasted. The analytical technologies/methods are designed to detect and quantify the target contaminants. The data integration technology area consists of hardware and software systems designed to integrate all the site information compiled and collected into a conceptual site model on a daily basis at the site; this conceptual model then becomes the decision-support tool. Simultaneous fielding of different methods within each of the three areas of technology provided data for direct comparison of the technologies fielded, both SOPT and IT. This document reports the results of the site characterization, technology comparison, and ESC demonstration activities associated with the Marshalltown FMGP site. 124 figs., 27 tabs.« less

  15. Designing artificial 2D crystals with site and size controlled quantum dots.

    PubMed

    Xie, Xuejun; Kang, Jiahao; Cao, Wei; Chu, Jae Hwan; Gong, Yongji; Ajayan, Pulickel M; Banerjee, Kaustav

    2017-08-30

    Ordered arrays of quantum dots in two-dimensional (2D) materials would make promising optical materials, but their assembly could prove challenging. Here we demonstrate a scalable, site and size controlled fabrication of quantum dots in monolayer molybdenum disulfide (MoS 2 ), and quantum dot arrays with nanometer-scale spatial density by focused electron beam irradiation induced local 2H to 1T phase change in MoS 2 . By designing the quantum dots in a 2D superlattice, we show that new energy bands form where the new band gap can be controlled by the size and pitch of the quantum dots in the superlattice. The band gap can be tuned from 1.81 eV to 1.42 eV without loss of its photoluminescence performance, which provides new directions for fabricating lasers with designed wavelengths. Our work constitutes a photoresist-free, top-down method to create large-area quantum dot arrays with nanometer-scale spatial density that allow the quantum dots to interfere with each other and create artificial crystals. This technique opens up new pathways for fabricating light emitting devices with 2D materials at desired wavelengths. This demonstration can also enable the assembly of large scale quantum information systems and open up new avenues for the design of artificial 2D materials.

  16. Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

    PubMed

    Khan, M A; Hossain, M U; Rakib-Uz-Zaman, S M; Morshed, M N

    2015-07-01

    Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments. © 2015 John Wiley & Sons Ltd.

  17. The Concept of Historical Landscape Design at Watugong Archaeological Site Area in Malang City

    NASA Astrophysics Data System (ADS)

    Setyabudi, I.; Alfian, R.; Hastutiningtyas, W. R.

    2017-10-01

    Malang city has the high historical value. It showed by many archaeological situses found, such as: The Dutch Colonial Building until kingdom era on classical history period. Generally, it could be seen at urban affairs like government building even the ancient house. But the last kingdom archaeological site only found at the village. The oldest archaeological site in Malang city was found on Kanjuruhan Kingdom, which is concentrated in Tlogomas. The Watu Gong Hamlet that was located in Tlogomas Political District had an archaeological site. It was a big stone in which the stone looked like a traditional music instrument, it was called Gong. As the archaeological site in megalithicum, before the Hindu and Budha came in from India, that stone was predicted as the foundation structure of the big building. The Watu Gong Hamlet was located in Tlogomas archeological site area, also Merjosari and Karang Besuki. Three of them are the archeological sites for Kanjuruhan Kingdom at eigth century, until Kahuripan Kingdom around the eleventh century, as the heir of the Ancient Mataram Kingdom. The urban government has a program to improve the village required to their region potential and it was possible to revitalize the Tlogomas village, so that the historical character can be seen well. The modernity of a hamlet has impact on the local identity blured. In which, they did not think about economic only and it can be minimized, also the hamlet will be a characterized tourism object. The revitalization purposed to continuing the past, then it’s connected to present. It’s performed as corridored garden planning. The landscape development appropriated to promote about the characters of Kacapiring flower, Rose, Jasmine and Puring. They are the special plants from Kanjuruhan Kingdom, beside the other furniture street model. This research was descriptive explorative and discussed about the concept with architecture design approach, started from data collecting, precedent study

  18. Geochemical investigation of UMTRAP designated site at Durango, Colorado

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

    Markos, G.; Bush, K.J.

    1983-09-01

    This report is the result of a geochemical investigation of the former uranium mill and tailings site at Durango, Colorado. This is one in a series of site specific geochemical investigations performed on the inactive uranium mill tailings included in the UMTRA Project. The objectives of the investigation are to characterize the geochemistry, to determine the contaminant distribution resulting from the former milling activities and tailings, and to infer chemical pathways and transport mechanisms from the contaminant distribution. The results will be used to model contaminant migration and to develop criteria for long-term containment media such as a cover systemmore » which is impermeable to contaminant migration. This report assumes a familiarity with the hydrologic conditions of the site and the geochemical concepts underlying the investigation. The results reported are based on a one-time sampling of waters and solid material from the background, the area adjacent to the site, and the site. The solid samples are water extracted remove easily soluble salts and acids extracted to remove cabonates and hydroxides. The water extracts and solid samples were analyzed for the major and trace elements. A limited number of samples were analyzed for radiological components. The report includes the methods of sampling, sample processing, analysis, and data interpretation. Three major conclusions are: (1) carbonate salts and low TDS characterize the tailings; (2) the adjacent area and raffinate ponds contain contaminants deposited by a single event of fluid permeation of the soils; and (3) the Animas River adjacent to the site has elevated gross alpha activity attributed to /sup 226/Ra in the sediments derived from the tailings or milling activities.« less

  19. Implications of next generation attenuation ground motion prediction equations for site coefficients used in earthquake resistant design

    USGS Publications Warehouse

    Borcherdt, Roger D.

    2014-01-01

    Proposals are developed to update Tables 11.4-1 and 11.4-2 of Minimum Design Loads for Buildings and Other Structures published as American Society of Civil Engineers Structural Engineering Institute standard 7-10 (ASCE/SEI 7–10). The updates are mean next generation attenuation (NGA) site coefficients inferred directly from the four NGA ground motion prediction equations used to derive the maximum considered earthquake response maps adopted in ASCE/SEI 7–10. Proposals include the recommendation to use straight-line interpolation to infer site coefficients at intermediate values of (average shear velocity to 30-m depth). The NGA coefficients are shown to agree well with adopted site coefficients at low levels of input motion (0.1 g) and those observed from the Loma Prieta earthquake. For higher levels of input motion, the majority of the adopted values are within the 95% epistemic-uncertainty limits implied by the NGA estimates with the exceptions being the mid-period site coefficient, Fv, for site class D and the short-period coefficient, Fa, for site class C, both of which are slightly less than the corresponding 95% limit. The NGA data base shows that the median value  of 913 m/s for site class B is more typical than 760 m/s as a value to characterize firm to hard rock sites as the uniform ground condition for future maximum considered earthquake response ground motion estimates. Future updates of NGA ground motion prediction equations can be incorporated easily into future adjustments of adopted site coefficients using procedures presented herein. 

  20. A DNA enzyme with N-glycosylase activity

    NASA Technical Reports Server (NTRS)

    Sheppard, T. L.; Ordoukhanian, P.; Joyce, G. F.

    2000-01-01

    In vitro evolution was used to develop a DNA enzyme that catalyzes the site-specific depurination of DNA with a catalytic rate enhancement of about 10(6)-fold. The reaction involves hydrolysis of the N-glycosidic bond of a particular deoxyguanosine residue, leading to DNA strand scission at the apurinic site. The DNA enzyme contains 93 nucleotides and is structurally complex. It has an absolute requirement for a divalent metal cation and exhibits optimal activity at about pH 5. The mechanism of the reaction was confirmed by analysis of the cleavage products by using HPLC and mass spectrometry. The isolation and characterization of an N-glycosylase DNA enzyme demonstrates that single-stranded DNA, like RNA and proteins, can form a complex tertiary structure and catalyze a difficult biochemical transformation. This DNA enzyme provides a new approach for the site-specific cleavage of DNA molecules.

  1. Implications of NGA for NEHRP site coefficients

    USGS Publications Warehouse

    Borcherdt, Roger D.

    2012-01-01

    Three proposals are provided to update tables 11.4-1 and 11.4-2 of Minimum Design Loads for Buildings and Other Structures (7-10), by the American Society of Civil Engineers (2010) (ASCE/SEI 7-10), with site coefficients implied directly by NGA (Next Generation Attenuation) ground motion prediction equations (GMPEs). Proposals include a recommendation to use straight-line interpolation to infer site coefficients at intermediate values of ̅vs (average shear velocity). Site coefficients are recommended to ensure consistency with ASCE/SEI 7-10 MCER (Maximum Considered Earthquake) seismic-design maps and simplified site-specific design spectra procedures requiring site classes with associated tabulated site coefficients and a reference site class with unity site coefficients. Recommended site coefficients are confirmed by independent observations of average site amplification coefficients inferred with respect to an average ground condition consistent with that used for the MCER maps. The NGA coefficients recommended for consideration are implied directly by the NGA GMPEs and do not require introduction of additional models.

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

    PubMed Central

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

    1997-01-01

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

  3. Culture differences in design of portal sites.

    PubMed

    Fang, Xiaowen; Rau, Pei-Luen Patrick

    2003-01-15

    Two experiments were carried out to examine the effects of cultural differences between the Chinese and the US people on the perceived usability and search performance of World Wide Web (WWW) portal sites. Chinese users in Taiwan and US users in Chicago were recruited to perform searching tasks on two versions of Yahoo! portal site: the standard Yahoo! and Yahoo! Chinese. The layout of Yahoo! Chinese is the same as the layout of Yahoo!, and categories on Yahoo! Chinese have been translated from its US counterpart. A special browser was programmed to record all the keystroke data and participants were asked to fill out a satisfaction questionnaire after finishing the tasks. Significant differences of satisfaction and steps to perform some tasks were found between the two groups. The experiment results also provided more detailed insights into the cultural differences between the Chinese and the US users.

  4. Preliminary design of a solar central receiver for site-specific repowering application (Saguaro Power Plant). Volume II. Preliminary design. Final report, October 1982-September 1983

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

    Weber, E.R.

    1983-09-01

    The solar central receiver technology, site, and specific unit for repowering were selected in prior analyses and studies. The objectives of this preliminary design study were to: develop a solar central receiver repowering design for Saguaro that (1) has potential to be economically competitive with fossil fueled plants in near and long term applications, (2) has the greatest chance for completion without further government funding, (3) will further define technical and economic feasibility of a 66 MWe gross size plant that is adequate to meet the requirements for utility and industrial process heat applications, (4) can potentially be constructed andmore » operated within the next five years, and (5) incorporates solar central receiver technology and represents state-of-the-art development. This volume on the preliminary design includes the following sections: executive summary; introduction; changes from advanced conceptual design; preliminary design; system characteristics; economic analysis; and development plan.« less

  5. An open reading frame in intron seven of the sea urchin DNA-methyltransferase gene codes for a functional AP1 endonuclease.

    PubMed

    Cioffi, Anna Valentina; Ferrara, Diana; Cubellis, Maria Vittoria; Aniello, Francesco; Corrado, Marcella; Liguori, Francesca; Amoroso, Alessandro; Fucci, Laura; Branno, Margherita

    2002-08-01

    Analysis of the genome structure of the Paracentrotus lividus (sea urchin) DNA methyltransferase (DNA MTase) gene showed the presence of an open reading frame, named METEX, in intron 7 of the gene. METEX expression is developmentally regulated, showing no correlation with DNA MTase expression. In fact, DNA MTase transcripts are present at high concentrations in the early developmental stages, while METEX is expressed at late stages of development. Two METEX cDNA clones (Met1 and Met2) that are different in the 3' end have been isolated in a cDNA library screening. The putative translated protein from Met2 cDNA clone showed similarity with Escherichia coli endonuclease III on the basis of sequence and predictive three-dimensional structure. The protein, overexpressed in E. coli and purified, had functional properties similar to the endonuclease specific for apurinic/apyrimidinic (AP) sites on the basis of the lyase activity. Therefore the open reading frame, present in intron 7 of the P. lividus DNA MTase gene, codes for a functional AP endonuclease designated SuAP1.

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

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

    Julyk, L.J.

    1995-09-01

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

  7. Design and fabrication of a low-cost Darrieus vertical-axis wind-turbine system, phase 2. Volume 3: Design, fabrication, and site drawing

    NASA Astrophysics Data System (ADS)

    1983-03-01

    The design, fabrication, and site drawings associated with fabrication, installation, and check out of 100 kW 17 meter Vertical Axis Wind Turbines (VAWTs) were reported. The turbines are Darrieus type VAWTs with rotors 17 meters in diameter and 25.15 meters in height. They can produce 100 kW of electric power at a cost of energy as low as 3 cents per kWh, in an 18 mph wind regime using 12% annualized costs. Four turbines are produced, three are installed and operable.

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

    Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.

    DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. Here we report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylatedmore » CpG dinucleotides. Moreover, these structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. Finally, these snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.« less

  9. Capturing snapshots of APE1 processing DNA damage

    DOE PAGES

    Freudenthal, Bret D.; Beard, William A.; Cuneo, Matthew J.; ...

    2015-10-12

    DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. Here we report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylatedmore » CpG dinucleotides. Moreover, these structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. Finally, these snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.« less

  10. Designing Hydrolytic Zinc Metalloenzymes

    PubMed Central

    2015-01-01

    Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for reproducing native metal sites that may be applied to answering some of these questions and subsequently generating novel zinc enzymes. From examination of the earliest design studies introducing simple Zn(II)-binding sites into de novo and natural protein scaffolds to current studies involving the preparation of efficient hydrolytic zinc sites, it is increasingly likely that protein design will achieve reaction rates previously thought possible only for native enzymes. This Current Topic will review the design and redesign of Zn(II)-binding sites in de novo-designed proteins and native protein scaffolds toward the preparation of catalytic hydrolytic sites. After discussing the preparation of Zn(II)-binding sites in various scaffolds, we will describe relevant examples for reengineering existing zinc sites to generate new or altered catalytic activities. Then, we will describe our work on the preparation of a de novo-designed hydrolytic zinc site in detail and present comparisons to related designed zinc sites. Collectively, these studies demonstrate the significant progress being made toward building zinc metalloenzymes from the bottom up. PMID:24506795

  11. Nuclear power: Siting and safety

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

    Openshaw, S.

    1986-01-01

    By 2030, half, or even two-thirds, of all electricity may be generated by nuclear power. Major reactor accidents are still expected to be rare occurrences, but nuclear safety is largely a matter of faith. Terrorist attacks, sabotage, and human error could cause a significant accident. Reactor siting can offer an additional, design-independent margin of safety. Remote geographical sites for new plants would minimize health risks, protect the industry from negative changes in public opinion concerning nuclear energy, and improve long-term public acceptance of nuclear power. U.K. siting practices usually do not consider the contribution to safety that could be obtainedmore » from remote sites. This book discusses the present trends of siting policies of nuclear power and their design-independent margin of safety.« less

  12. In vitro results of flexible light-emitting antimicrobial bandage designed for prevention of surgical site infections

    NASA Astrophysics Data System (ADS)

    Greenberg, Mitchell; Sharan, Riti; Galbadage, Thushara; Sule, Preeti; Smith, Robert; Lovelady, April; Cirillo, Jeffrey D.; Glowczwski, Alan; Maitland, Kristen C.

    2018-02-01

    Surgical site infections (SSIs) are a leading cause of morbidity and mortality and a significant expense to the healthcare system and hospitals. The majority of these infections are preventable; however, increasing bacterial resistance, biofilm persistence, and human error contribute to the occurrence of these healthcare-associated infections. We present a flexible antimicrobial blue-light emitting bandage designed for use on postoperative incisions and wounds. The photonic device is designed to inactivate bacteria present on the skin and prevent bacterial colonization of the site, thus reducing the occurrence of SSIs. This antimicrobial light emitting bandage uses blue light's proven abilities to inactivate a wide range of clinical pathogens regardless of their resistance to antibiotics, inactivate bacteria without harming mammalian cells, improve wound healing, and inactivate bacteria in biofilms. The antimicrobial bandage consists of a thin 2"x2" silicone sheet with an array of 77 LEDs embedded in multiple layers of the material for thermal management. The 405 nm center wavelength LED array is designed to be a wearable device that integrates with standard hospital infection prevention protocols. The device was characterized for irradiance of 44.5 mW/cm2. Methicillin-resistant Staphylococcus aureus seeded in a petri dish was used to evaluate bacterial inactivation in vitro. Starting with a concentration of 2.16 x 107 colony forming units (CFU)/mL, 45% of the bacteria was inactivated within 15 minutes, 65% had been inactivated by 30 minutes, 99% was inactivated by 60 minutes, and a 7 log reduction and complete sterilization was achieved within 120 minutes.

  13. 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.

  14. Heritage planning and rethinking the meaning and values of designating heritage sites in a post-disaster context: The case of Aceh, Indonesia

    NASA Astrophysics Data System (ADS)

    Meutia, Z. D.; Akbar, R.; Zulkaidi, D.

    2018-05-01

    Heritage has become a driver of development as stated in the New Urban Agenda 2016 report. A starting premise of most recent studies of the concept of heritage suggests that its nature is not as a static inheritance with fixed and enduring values. Rather, the identification of sites as heritage requires a process of identification, or heritage creation. Heritage is a fluid phenomenon rather than a static set of objects or sites with fixed meanings. This paper uses theory from Smith [1] who argued that there is no such thing as a heritage; heritage is essentially a cultural custom and social process. Today, site-based heritage planning only considers the values of old towns and lacks clarity in terms of values that create criteria for the designation of cultural heritage sites in another context. Yet, this approach is needed as a way to maintain urban assets that significantly contribute to the establishment of values and quality parts of the city. Heritage planning is also the act of communicating and remembering the past for the present and the future in the public domain. This paper aims to formulate a conceptual heritage planning of designating heritage sites that challenges the traditional notion of heritage which considers age as a key element in heritage, the privileges monumentality and grand scale, with scientific/aesthetic expert judgment as a requirement of heritage designations. The limited idea of heritage based on exclusive values as something ancient, grand-scale, historical, and with other exclusive values has excluded many places as heritage in communities emerging from disasters. Debates within the critical heritage studies movement argue that heritage is a cultural product linked to activities of remembering and is an act of communication. The dominant hypothesis is that heritage values cannot remain to exist if the physical or material aspects of sites are destroyed and this hypothesis feels flawed. This paper asks us to acknowledge the

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

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

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

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

    Not Available

    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 amore » 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)« less

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

    NASA Astrophysics Data System (ADS)

    El Hussain, I. W.

    2017-12-01

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

  19. School Site Decisions and Dollars. Dollar Consequences of School Site Planning Decisions.

    ERIC Educational Resources Information Center

    Grube, Karl W.

    Sufficient research has been generated to economically justify the necessary capital investment expenditures in developing the public school site into a community land asset. Open space school sites designed, developed, and maintained as community land reserves are self-liquidating economic land units because they contribute significantly to the…

  20. Learning to Design and Implement Educational Web Sites within Pre-Service Training: a Project-Based Learning Environment and its Impact on Student Teachers

    ERIC Educational Resources Information Center

    Papastergiou, Marina

    2005-01-01

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

  1. 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…

  2. Artificial and Solar UV Radiation Induces Strand Breaks and Cyclobutane Pyrimidine Dimers in Bacillus subtilis Spore DNA

    PubMed Central

    Slieman, Tony A.; Nicholson, Wayne L.

    2000-01-01

    The loss of stratospheric ozone and the accompanying increase in solar UV flux have led to concerns regarding decreases in global microbial productivity. Central to understanding this process is determining the types and amounts of DNA damage in microbes caused by solar UV irradiation. While UV irradiation of dormant Bacillus subtilis endospores results mainly in formation of the “spore photoproduct” 5-thyminyl-5,6-dihydrothymine, genetic evidence indicates that an additional DNA photoproduct(s) may be formed in spores exposed to solar UV-B and UV-A radiation (Y. Xue and W. L. Nicholson, Appl. Environ. Microbiol. 62:2221–2227, 1996). We examined the occurrence of double-strand breaks, single-strand breaks, cyclobutane pyrimidine dimers, and apurinic-apyrimidinic sites in spore DNA under several UV irradiation conditions by using enzymatic probes and neutral or alkaline agarose gel electrophoresis. DNA from spores irradiated with artificial 254-nm UV-C radiation accumulated single-strand breaks, double-strand breaks, and cyclobutane pyrimidine dimers, while DNA from spores exposed to artificial UV-B radiation (wavelengths, 290 to 310 nm) accumulated only cyclobutane pyrimidine dimers. DNA from spores exposed to full-spectrum sunlight (UV-B and UV-A radiation) accumulated single-strand breaks, double-strand breaks, and cyclobutane pyrimidine dimers, whereas DNA from spores exposed to sunlight from which the UV-B component had been removed with a filter (“UV-A sunlight”) accumulated only single-strand breaks and double-strand breaks. Apurinic-apyrimidinic sites were not detected in spore DNA under any of the irradiation conditions used. Our data indicate that there is a complex spectrum of UV photoproducts in DNA of bacterial spores exposed to solar UV irradiation in the environment. PMID:10618224

  3. RBSDesigner: software for designing synthetic ribosome binding sites that yields a desired level of protein expression.

    PubMed

    Na, Dokyun; Lee, Doheon

    2010-10-15

    RBSDesigner predicts the translation efficiency of existing mRNA sequences and designs synthetic ribosome binding sites (RBSs) for a given coding sequence (CDS) to yield a desired level of protein expression. The program implements the mathematical model for translation initiation described in Na et al. (Mathematical modeling of translation initiation for the estimation of its efficiency to computationally design mRNA sequences with a desired expression level in prokaryotes. BMC Syst. Biol., 4, 71). The program additionally incorporates the effect on translation efficiency of the spacer length between a Shine-Dalgarno (SD) sequence and an AUG codon, which is crucial for the incorporation of fMet-tRNA into the ribosome. RBSDesigner provides a graphical user interface (GUI) for the convenient design of synthetic RBSs. RBSDesigner is written in Python and Microsoft Visual Basic 6.0 and is publicly available as precompiled stand-alone software on the web (http://rbs.kaist.ac.kr). dhlee@kaist.ac.kr

  4. 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)

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

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

    Lah, J; Shin, D; Kim, G

    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 tomore » 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.« less

  6. Rational design of a conformation-switchable Ca2+- and Tb3+-binding protein without the use of multiple coupled metal-binding sites.

    PubMed

    Li, Shunyi; Yang, Wei; Maniccia, Anna W; Barrow, Doyle; Tjong, Harianto; Zhou, Huan-Xiang; Yang, Jenny J

    2008-10-01

    Ca2+, as a messenger of signal transduction, regulates numerous target molecules via Ca2+-induced conformational changes. Investigation into the determinants for Ca2+-induced conformational change is often impeded by cooperativity between multiple metal-binding sites or protein oligomerization in naturally occurring proteins. To dissect the relative contributions of key determinants for Ca2+-dependent conformational changes, we report the design of a single-site Ca2+-binding protein (CD2.trigger) created by altering charged residues at an electrostatically sensitive location on the surface of the host protein rat Cluster of Differentiation 2 (CD2).CD2.trigger binds to Tb3+ and Ca2+ with dissociation constants of 0.3 +/- 0.1 and 90 +/- 25 microM, respectively. This protein is largely unfolded in the absence of metal ions at physiological pH, but Tb3+ or Ca2+ binding results in folding of the native-like conformation. Neutralization of the charged coordination residues, either by mutation or protonation, similarly induces folding of the protein. The control of a major conformational change by a single Ca2+ ion, achieved on a protein designed without reliance on sequence similarity to known Ca2+-dependent proteins and coupled metal-binding sites, represents an important step in the design of trigger proteins.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Evaluation of a multi-site program designed to strengthen relational bonds for siblings separated by foster care.

    PubMed

    Waid, Jeffrey; Wojciak, Armeda Stevenson

    2017-10-01

    Sibling relationships in foster care settings have received increased attention in recent years. Despite growing evidence regarding the protective potential of sibling relationships for youth in care, some sibling groups continue to experience foster care related separation, and few programs exist to address the needs of these youth. This study describes and evaluates Camp To Belong, a multi-site program designed to provide short-term reunification to separated sibling groups through a week-long summer camp experience. Using a pre-test post-test survey design, this paper examines changes in youth ratings of sibling conflict and sibling support across camps located in six geographically distinct regions of the United States. The effects of youth age, number of prior camp exposures, and camp location were tested using multilevel modeling procedures. Findings suggest that participation in Camp To Belong may reduce sibling conflict, and improvements in sibling support are noted for youth who have had prior exposure to the camp's programming. Camp-level variance in the sibling support outcome highlight the complex nature of relationships for siblings separated by foster care, and suggest the need for additional research. Lessons learned from this multi-site evaluation and future directions are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Evaluating a complex, multi-site, community-based program to improve healthcare quality: the summative research design for the Aligning Forces for Quality initiative.

    PubMed

    Scanlon, Dennis P; Wolf, Laura J; Alexander, Jeffrey A; Christianson, Jon B; Greene, Jessica; Jean-Jacques, Muriel; McHugh, Megan; Shi, Yunfeng; Leitzell, Brigitt; Vanderbrink, Jocelyn M

    2016-08-01

    The Aligning Forces for Quality (AF4Q) initiative was the Robert Wood Johnson Foundation's (RWJF's) signature effort to increase the overall quality of healthcare in targeted communities throughout the country. In addition to sponsoring this 16-site complex program, RWJF funded an independent scientific evaluation to support objective research on the initiative's effectiveness and contributions to basic knowledge in 5 core programmatic areas. The research design, data, and challenges faced during the summative evaluation phase of this near decade-long program are discussed. A descriptive overview of the summative research design and its development for a multi-site, community-based, healthcare quality improvement initiative is provided. The summative research design employed by the evaluation team is discussed. The evaluation team's summative research design involved a data-driven assessment of the effectiveness of the AF4Q program at large, assessments of the impact of AF4Q in the specific programmatic areas, and an assessment of how the AF4Q alliances were positioned for the future at the end of the program. The AF4Q initiative was the largest privately funded community-based healthcare improvement initiative in the United States to date and was implemented at a time of rapid change in national healthcare policy. The implementation of large-scale, multi-site initiatives is becoming an increasingly common approach for addressing problems in healthcare. The summative evaluation research design for the AF4Q initiative, and the lessons learned from its approach, may be valuable to others tasked with evaluating similarly complex community-based initiatives.

  13. 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.

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

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

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

    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

  15. 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

  16. 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…

  17. Mechanistic design data from ODOT instrumented pavement sites : phase II report.

    DOT National Transportation Integrated Search

    2017-03-01

    This investigation examined data obtained from three previously-instrumented pavement test sites in Oregon. Data processing algorithms and templates were developed for each test site that facilitated full processing of all the data to build databases...

  18. Mechanistic design data from ODOT instrumented pavement sites : phase 1 report.

    DOT National Transportation Integrated Search

    2017-03-01

    This investigation examined data obtained from three previously-instrumented pavement test sites in Oregon. Data processing algorithms and templates were developed for each test site that facilitated full processing of all the data to build databases...

  19. Balancing Energy, Food Security, and Critical Ecosystems: Dam Siting, Design and Operations in the Mekong River Basin

    NASA Astrophysics Data System (ADS)

    Wild, T. B.; Reed, P. M.; Loucks, D.

    2016-12-01

    The Mekong River basin in Southeast Asia is one of several river basins with exceptionally high biodiversity value where intensive hydropower dam development is anticipated. In the Mekong basin, over 100 dams are planned to be constructed in the next 20-30 years. As planned, these dams will alter the river's natural water, sediment and nutrient flows, and will fragment fish migration pathways. In doing so, they will degrade one of the world's most productive freshwater fish habitats, upon which some 60 million people depend for food and income security. For those dams that have not yet been constructed, there still exist opportunities to modify their siting, design and operation (SDO) to achieve a more balanced set of tradeoffs among hydropower production, sediment/nutrient passage and adult fish/larvae passage. We present a successful case study wherein we explored such alternative SDO opportunities in partnership with the Government of Cambodia for Sambor Dam, planned to be built on the main stem of the Mekong. Sambor would be one of the world's longest dams, spanning 18 km across the river just upstream of (1) Tonle Sap Lake, which supplies 70% of Cambodians' protein, and (2) the Mekong Delta in Vietnam, responsible for 50% of Vietnam's rice production. We will describe key dam siting and design modifications required to mitigate ecological impacts. We will then focus on the most promising alternative dam siting/design concept, exploring the reservoir operations space to demonstrate that a complex set of tradeoffs exist among a diverse set of energy and ecosystem objectives. Results indicate that even for a hydrologically small reservoir, a wide array of potential reservoir operating policies exist that have vastly different food-energy implications. While some policies would significantly mitigate ecological impacts, many policies exist that would pose a severe threat to the sustainability of the fishery. Failure to sample the reservoir operations space at

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

    PubMed Central

    2013-01-01

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

  1. Toehold-mediated strand displacement reaction-dependent fluorescent strategy for sensitive detection of uracil-DNA glycosylase activity.

    PubMed

    Wu, Yushu; Wang, Lei; Jiang, Wei

    2017-03-15

    Sensitive detection of uracil-DNA glycosylase (UDG) activity is beneficial for evaluating the repairing process of DNA lesions. Here, toehold-mediated strand displacement reaction (TSDR)-dependent fluorescent strategy was constructed for sensitive detection of UDG activity. A single-stranded DNA (ssDNA) probe with two uracil bases and a trigger sequence were designed. A hairpin probe with toehold domain was designed, and a reporter probe was also designed. Under the action of UDG, two uracil bases were removed from ssDNA probe, generating apurinic/apyrimidinic (AP) sites. Then, the AP sites could inhibit the TSDR between ssDNA probe and hairpin probe, leaving the trigger sequence in ssDNA probe still free. Subsequently, the trigger sequence was annealed with the reporter probe, initiating the polymerization and nicking amplification reaction. As a result, numerous G-quadruplex (G4) structures were formed, which could bind with N-methyl-mesoporphyrin IX (NMM) to generate enhanced fluorescent signal. In the absence of UDG, the ssDNA probe could hybridize with the toehold domain of the hairpin probe to initiate TSDR, blocking the trigger sequence, and then the subsequent amplification reaction would not occur. The proposed strategy was successfully implemented for detecting UDG activity with a detection limit of 2.7×10 -5 U/mL. Moreover, the strategy could distinguish UDG well from other interference enzymes. Furthermore, the strategy was also applied for detecting UDG activity in HeLa cells lysate with low effect of cellular components. These results indicated that the proposed strategy offered a promising tool for sensitive quantification of UDG activity in UDG-related function study and disease prognosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Berm design to reduce risks of catastrophic slope failures at solid waste disposal sites.

    PubMed

    De Stefano, Matteo; Gharabaghi, Bahram; Clemmer, Ryan; Jahanfar, M Ali

    2016-11-01

    Existing waste disposal sites are being strained by exceeding their volumetric capacities because of exponentially increasing rates of municipal solid waste generation worldwide, especially in densely populated metropolises. Over the past 40 years, six well-documented and analyzed disposal sites experienced catastrophic failure. This research presents a novel analysis and design method for implementation of a series of in-situ earth berms to slow down the movement of waste material flow following a catastrophic failure. This is the first study of its kind that employs a dynamic landslide analysis model, DAN-W, and the Voellmy rheological model to approximate solid waste avalanche flow. A variety of single and multiple berm configuration scenarios were developed and tested to find an optimum configuration of the various earth berm geometries and number of berms to achieve desired energy dissipation and reduction in total waste material runout length. The case study application of the novel mitigation measure shows that by constructing a series of six relatively inexpensive 3 m high earth berms at an optimum distance of 250 m from the slope toe, the total runout length of 1000 m and associated fatalities of the Leuwigajah dumpsite catastrophic failure in Bandung, Indonesia, could have been reduced by half. © The Author(s) 2016.

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

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

    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 andmore » 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.« less

  4. 10 CFR 26.87 - Collection sites.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Collection sites. 26.87 Section 26.87 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.87 Collection sites. (a) Each FFD program must have one or more designated collection sites that have all necessary personnel...

  5. 10 CFR 26.87 - Collection sites.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Collection sites. 26.87 Section 26.87 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.87 Collection sites. (a) Each FFD program must have one or more designated collection sites that have all necessary personnel...

  6. 10 CFR 26.87 - Collection sites.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Collection sites. 26.87 Section 26.87 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.87 Collection sites. (a) Each FFD program must have one or more designated collection sites that have all necessary personnel...

  7. 10 CFR 26.87 - Collection sites.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Collection sites. 26.87 Section 26.87 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.87 Collection sites. (a) Each FFD program must have one or more designated collection sites that have all necessary personnel...

  8. 10 CFR 26.87 - Collection sites.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Collection sites. 26.87 Section 26.87 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting Specimens for Testing § 26.87 Collection sites. (a) Each FFD program must have one or more designated collection sites that have all necessary personnel...

  9. 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

  10. 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.

  11. Intravenous insertion site protection: moisture accumulation in intravenous site protectors.

    PubMed

    Lee, W E; Vallino, L M

    1996-01-01

    Stabilizing the intravenous catheter after insertion is a significant part of intravenous therapy. Dislodgments of the cannula from its optimal position in the vein can lead to complications such as phlebitis, thrombophlebitis, infiltration, and infection. Intravenous site protector shields are designed to protect the catheter from impact and tissue trauma at the insertion site. Nurses have requested ventilation in these shields to avoid moisture build up that may increase the risk of infections. To address this issue, experimental laboratory testing was performed to determine if moisture accumulation as evidenced by increased weight of the shield and visible evidence of condensation occurred. No moisture condensation problems with the ventilated intravenous site protectors were found.

  12. Designing HIV Testing Algorithms Based on 2015 WHO Guidelines Using Data from Six Sites in Sub-Saharan Africa

    PubMed Central

    Kosack, Cara S.; Shanks, Leslie; Beelaert, Greet; Benson, Tumwesigye; Savane, Aboubacar; Ng'ang'a, Anne; Bita, André; Zahinda, Jean-Paul B. N.; Fransen, Katrien

    2017-01-01

    ABSTRACT Our objective was to evaluate the performance of HIV testing algorithms based on WHO recommendations, using data from specimens collected at six HIV testing and counseling sites in sub-Saharan Africa (Conakry, Guinea; Kitgum and Arua, Uganda; Homa Bay, Kenya; Douala, Cameroon; Baraka, Democratic Republic of Congo). A total of 2,780 samples, including 1,306 HIV-positive samples, were included in the analysis. HIV testing algorithms were designed using Determine as a first test. Second and third rapid diagnostic tests (RDTs) were selected based on site-specific performance, adhering where possible to the WHO-recommended minimum requirements of ≥99% sensitivity and specificity. The threshold for specificity was reduced to 98% or 96% if necessary. We also simulated algorithms consisting of one RDT followed by a simple confirmatory assay. The positive predictive values (PPV) of the simulated algorithms ranged from 75.8% to 100% using strategies recommended for high-prevalence settings, 98.7% to 100% using strategies recommended for low-prevalence settings, and 98.1% to 100% using a rapid test followed by a simple confirmatory assay. Although we were able to design algorithms that met the recommended PPV of ≥99% in five of six sites using the applicable high-prevalence strategy, options were often very limited due to suboptimal performance of individual RDTs and to shared falsely reactive results. These results underscore the impact of the sequence of HIV tests and of shared false-reactivity data on algorithm performance. Where it is not possible to identify tests that meet WHO-recommended specifications, the low-prevalence strategy may be more suitable. PMID:28747371

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

    PubMed

    McCardell, A; Davison, L; Edwards, A

    2005-01-01

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

  14. Novel implant design improves implant survival in multirooted extraction sites: a preclinical pilot study.

    PubMed

    Sivan-Gildor, Adi; Machtei, Eli E; Gabay, Eran; Frankenthal, Shai; Levin, Liran; Suzuki, Marcelo; Coelho, Paulo G; Zigdon-Giladi, Hadar

    2014-10-01

    The primary aim is to evaluate clinical, radiographic, and histologic parameters of novel implants with "three roots" design that were inserted into fresh multirooted extraction sockets. A secondary aim is to compare this new implant to standard root-form dental implants. Immediate implantation of novel or standard design 6 × 6-mm implants was performed bilaterally into multirooted sockets in mandibles of mini-pigs. Twelve weeks later, clinical, radiographic, stability, histomorphometric, and microcomputed tomography (micro-CT) analyses were performed. Survival rates were significantly higher in the test implants compared with control (92.8% versus 33.3%, respectively; P <0.001). Bone loss was greater in the control compared with the test by sounding (mean 3.42 ± 0.68 versus 1.96 ± 0.34 mm) and radiography (mean 3.35 ± 0.62 versus 2.27 ± 0.33 mm). Histologic and micro-CT analyses demonstrated bone fill in the inner part of the test implants. Moreover, bone-to-implant contact was higher in the test implants (55.50% ± 3.68% versus 42.47% ± 9.89%). Contrary to the clinical, radiographic, and histomorphometric results, resonance frequency analysis measurements were greater in the control group (77.74 ± 3.21 implant stability quotient [ISQ]) compared with the test group (31.09 ± 0.28 ISQ), P = 0.008. The novel design implants resulted in significantly greater survival rate in multirooted extraction sites. Further studies will be required to validate these findings.

  15. X-ray structure of the ternary MTX·NADPH complex of the anthrax dihydrofolate reductase: A pharmacophore for dual-site inhibitor design

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

    Bennett, Brad C.; Wan, Qun; Ahmad, Md Faiz

    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 themore » 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.« less

  16. Readability of Online Patient Educational Resources Found on NCI-Designated Cancer Center Web Sites.

    PubMed

    Rosenberg, Stephen A; Francis, David; Hullett, Craig R; Morris, Zachary S; Fisher, Michael M; Brower, Jeffrey V; Bradley, Kristin A; Anderson, Bethany M; Bassetti, Michael F; Kimple, Randall J

    2016-06-01

    The NIH and Department of Health & Human Services recommend online patient information (OPI) be written at a sixth grade level. We used a panel of readability analyses to assess OPI from NCI-Designated Cancer Center (NCIDCC) Web sites. Cancer.gov was used to identify 68 NCIDCC Web sites from which we collected both general OPI and OPI specific to breast, prostate, lung, and colon cancers. This text was analyzed by 10 commonly used readability tests: the New Dale-Chall Readability Formula, Flesch Reading Ease scale, Flesch-Kinaid Grade Level, FORCAST scale, Fry Readability Graph, Simple Measure of Gobbledygook test, Gunning Frequency of Gobbledygook index, New Fog Count, Raygor Readability Estimate Graph, and Coleman-Liau Index. We tested the hypothesis that the readability of NCIDCC OPI was written at the sixth grade level. Secondary analyses were performed to compare readability of OPI between comprehensive and noncomprehensive centers, by region, and to OPI produced by the American Cancer Society (ACS). A mean of 30,507 words from 40 comprehensive and 18 noncomprehensive NCIDCCs was analyzed (7 nonclinical and 3 without appropriate OPI were excluded). Using a composite grade level score, the mean readability score of 12.46 (ie, college level: 95% CI, 12.13-12.79) was significantly greater than the target grade level of 6 (middle-school: P<.001). No difference between comprehensive and noncomprehensive centers was identified. Regional differences were identified in 4 of the 10 readability metrics (P<.05). ACS OPI provides easier language, at the seventh to ninth grade level, across all tests (P<.01). OPI from NCIDCC Web sites is more complex than recommended for the average patient. Copyright © 2016 by the National Comprehensive Cancer Network.

  17. Analysis of Elementary School Web Sites

    ERIC Educational Resources Information Center

    Hartshorne, Richard; Friedman, Adam; Algozzine, Bob; Kaur, Daljit

    2008-01-01

    While researchers have studied the use and value of educational software for many years, study of school Web sites and/or their effectiveness is limited. In this investigation, we identified goals and functions of school Web sites and used the foundations of effective Web site design to develop an evaluation checklist. We then applied these…

  18. School Site Selection and Approval Guide.

    ERIC Educational Resources Information Center

    California State Dept. of Education, Sacramento. Div. of School Facilities Planning.

    This guide is designed to assist school districts in selecting school sites that provide both a safe and supportive environment for the instructional program and the learning process, and gain state approval for the selected sites. The guide includes a set of selection criteria that have proven helpful to site selection teams, information about…

  19. 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

  20. St. Louis Airport Site annual site environmental report. Calendar year 1985

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

    Not Available

    1986-04-01

    During 1985, the environmental monitoring program was continued at the St. Louis Airport Site (SLAPS) in St. Louis County, Missouri. The ditches north and south of the site have been designated for cleanup as part of the Formerly Utilized Sites Remedial Action Program (FUSRAP), a United States Department of Energy (DOE) program to identify, decontaminate, or otherwise control sites where low-level radioactive contamination remains from the early years of the nation's atomic energy program. The site is not currently controlled or regulated by DOE or NRC, although radiological monitoring of the site has been authorized by the DOE. The monitoringmore » program at the SLAPS measures radon gas concentrations in air; external gamma radiation dose rates; and uranium, thorium, and radium concentrations in surface water, groundwater, and sediment. Potential radiation doses to the public are also calculated. Because the site is not controlled or regulated by the DOE, the DOE Derived Concentration Guides (DCGs) are not applicable to SLAPS, but are included as a basis for comparison only. The DOE DCGs and the DOE radiation protection standard have been revised.« less

  1. MDC-Analyzer: a novel degenerate primer design tool for the construction of intelligent mutagenesis libraries with contiguous sites.

    PubMed

    Tang, Lixia; Wang, Xiong; Ru, Beibei; Sun, Hengfei; Huang, Jian; Gao, Hui

    2014-06-01

    Recent computational and bioinformatics advances have enabled the efficient creation of novel biocatalysts by reducing amino acid variability at hot spot regions. To further expand the utility of this strategy, we present here a tool called Multi-site Degenerate Codon Analyzer (MDC-Analyzer) for the automated design of intelligent mutagenesis libraries that can completely cover user-defined randomized sequences, especially when multiple contiguous and/or adjacent sites are targeted. By initially defining an objective function, the possible optimal degenerate PCR primer profiles could be automatically explored using the heuristic approach of Greedy Best-First-Search. Compared to the previously developed DC-Analyzer, MDC-Analyzer allows for the existence of a small amount of undesired sequences as a tradeoff between the number of degenerate primers and the encoded library size while still providing all the benefits of DC-Analyzer with the ability to randomize multiple contiguous sites. MDC-Analyzer was validated using a series of randomly generated mutation schemes and experimental case studies on the evolution of halohydrin dehalogenase, which proved that the MDC methodology is more efficient than other methods and is particularly well-suited to exploring the sequence space of proteins using data-driven protein engineering strategies.

  2. REGENERATIVE SITE LEARNING LABORATORY: A SITE INTERVENTION FOR SUSTAINABILITY EDUCATION

    EPA Science Inventory

    The project will indicate strategies that can be used to mitigate the negative impact of an existing developed site on a watershed and natural habitats. Additionally, the project design will inspire interest in ecological sustainability in an educational context. The project ...

  3. The Four Levels of Web Site Development Expertise.

    ERIC Educational Resources Information Center

    Ingram, Albert L.

    2000-01-01

    Discusses the design of Web pages and sites and proposes a four-level model of Web development expertise that can serve as a curriculum overview or as a plan for an individual's professional development. Highlights include page design, media use, client-side processing, server-side processing, and site structure. (LRW)

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

    PubMed

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

    2015-01-01

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

  5. Nevada National Security Site Environmental Report 2013

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

    Wills, C.

    2014-09-09

    This report was prepared to meet the information needs of the public and the requirements and guidelines of the U.S. Department of Energy (DOE) for annual site environmental reports. It was prepared by National Security Technologies, LLC (NSTec), for the U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office (NNSA/NFO) (formerly designated as the Nevada Site Office [NNSA/NSO]). The new field office designation occurred in March 2013. Published reports cited in this 2013 report, therefore, may bear the name or authorship of NNSA/NSO. This and previous years’ reports, called Annual Site Environmental Reports (ASERs), Nevada Test Site Environmentalmore » Reports (NTSERs), and, beginning in 2010, Nevada National Security Site Environmental Reports (NNSSERs), are posted on the NNSA/NFO website at http://www.nv.energy.gov/library/publications/aser.aspx.« less

  6. Cultivating Collaborations: Site Specific Design for Embodied Science Learning.

    PubMed

    Gill, Katherine; Glazier, Jocelyn; Towns, Betsy

    2018-05-21

    Immersion in well-designed outdoor environments can foster the habits of mind that enable critical and authentic scientific questions to take root in students' minds. Here we share two design cases in which careful, collaborative, and intentional design of outdoor learning environments for informal inquiry provide people of all ages with embodied opportunities to learn about the natural world, developing the capacity for understanding ecology and the ability to empathize, problem-solve and reflect. Embodied learning, as facilitated by and in well-designed outdoor learning environments, leads students to develop new ways of seeing, new scientific questions, new ways to connect with ideas, with others and new ways of thinking about the natural world. Using examples from our collaborative practices as experiential learning designers, we illustrate how creating the habits of mind critical to creating scientists, science-interested, and science-aware individuals benefits from providing students spaces to engage in embodied learning in nature. We show how public landscapes designed in creative partnerships between educators, scientists, designers and the public have potential to amplify science learning for all.

  7. Prescribed Fire: The Influence of Site Visits on Citizen Attitudes

    ERIC Educational Resources Information Center

    Toman, Eric; Shindler, Bruce; Reed, Michelle

    2004-01-01

    This research employed a panel design to measure the effect of site visits on public perceptions of prescribed fire. On-site survey questions were devised to compare answers to a mail questionnaire previously completed by the same respondents. Questions were designed to examine how site visits influence public opinion and affect acceptance of…

  8. 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)

  9. Lack of association between the APEX1 Asp148Glu polymorphism and sporadic amyotrophic lateral sclerosis.

    PubMed

    Coppedè, Fabio; Lo Gerfo, Annalisa; Carlesi, Cecilia; Piazza, Selina; Mancuso, Michelangelo; Pasquali, Livia; Murri, Luigi; Migliore, Lucia; Siciliano, Gabriele

    2010-02-01

    Impairments in DNA repair enzymes have been observed in amyotrophic lateral sclerosis (ALS) tissues, particularly in the activity of the apurinic/apyrimidinic endonuclease 1 (APEX1). Moreover, it was suggested that the common APEX1 Asp148Glu polymorphism might be associated with ALS risk. To further address this question we performed the present study aimed at evaluating the contribution of the APEX1 Asp148Glu polymorphism in sporadic ALS (sALS) risk and clinical presentation, including age and site of onset and disease progression. We screened 134 sALS Italian patients and 129 matched controls for the presence of the APEX1 Asp148Glu polymorphism. No difference in APEX1 Asp148Glu allele and genotype frequencies was found between the groups, nor was the polymorphism associated with age and site of onset or disease progression. Present results do not support a role for the APEX1 Asp148Glu polymorphism in sALS pathogenesis in the Italian population.

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

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

    Ascherl, Laura; Sick, Torben; Margraf, Johannes

    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 guidedmore » 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.« less

  11. 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.

  12. 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.

  13. Leveraging Site Search and Analytics to Maintain a User-Centered Focus

    ERIC Educational Resources Information Center

    Mitchell, Erik

    2011-01-01

    Web design is a necessarily iterative process. During the process, it can be difficult to balance the interests and focus of the library site experts and their novice users. It can also be easy to lose focus on the main goals of site use and become wrapped up in the process of design or coding or in the internal politics of site design. Just as…

  14. Abasic and oxidized ribonucleotides embedded in DNA are processed by human APE1 and not by RNase H2

    PubMed Central

    Malfatti, Matilde Clarissa; Balachander, Sathya; Antoniali, Giulia; Koh, Kyung Duk; Saint-Pierre, Christine; Gasparutto, Didier; Chon, Hyongi; Crouch, Robert J.

    2017-01-01

    Abstract Ribonucleoside 5′-monophosphates (rNMPs) are the most common non-standard nucleotides found in DNA of eukaryotic cells, with over 100 million rNMPs transiently incorporated in the mammalian genome per cell cycle. Human ribonuclease (RNase) H2 is the principal enzyme able to cleave rNMPs in DNA. Whether RNase H2 may process abasic or oxidized rNMPs incorporated in DNA is unknown. The base excision repair (BER) pathway is mainly responsible for repairing oxidized and abasic sites into DNA. Here we show that human RNase H2 is unable to process an abasic rNMP (rAP site) or a ribose 8oxoG (r8oxoG) site embedded in DNA. On the contrary, we found that recombinant purified human apurinic/apyrimidinic endonuclease-1 (APE1) and APE1 from human cell extracts efficiently process an rAP site in DNA and have weak endoribonuclease and 3′-exonuclease activities on r8oxoG substrate. Using biochemical assays, our results provide evidence of a human enzyme able to recognize and process abasic and oxidized ribonucleotides embedded in DNA. PMID:28977421

  15. Abasic and oxidized ribonucleotides embedded in DNA are processed by human APE1 and not by RNase H2.

    PubMed

    Malfatti, Matilde Clarissa; Balachander, Sathya; Antoniali, Giulia; Koh, Kyung Duk; Saint-Pierre, Christine; Gasparutto, Didier; Chon, Hyongi; Crouch, Robert J; Storici, Francesca; Tell, Gianluca

    2017-11-02

    Ribonucleoside 5'-monophosphates (rNMPs) are the most common non-standard nucleotides found in DNA of eukaryotic cells, with over 100 million rNMPs transiently incorporated in the mammalian genome per cell cycle. Human ribonuclease (RNase) H2 is the principal enzyme able to cleave rNMPs in DNA. Whether RNase H2 may process abasic or oxidized rNMPs incorporated in DNA is unknown. The base excision repair (BER) pathway is mainly responsible for repairing oxidized and abasic sites into DNA. Here we show that human RNase H2 is unable to process an abasic rNMP (rAP site) or a ribose 8oxoG (r8oxoG) site embedded in DNA. On the contrary, we found that recombinant purified human apurinic/apyrimidinic endonuclease-1 (APE1) and APE1 from human cell extracts efficiently process an rAP site in DNA and have weak endoribonuclease and 3'-exonuclease activities on r8oxoG substrate. Using biochemical assays, our results provide evidence of a human enzyme able to recognize and process abasic and oxidized ribonucleotides embedded in DNA. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. 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…

  17. Nevada National Security Site Environmental Report 2011 Attachment A: Site Description

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

    Cathy Wills, ed.

    2012-09-12

    This attachment expands on the general description of the Nevada National Security Site (NNSS) presented in the Introduction to the Nevada National Security Site Environmental Report 2011. Included are subsections that summarize the site's geological, hydrological, climatological, and ecological setting and the cultural resources of the NNSS. The subsections are meant to aid the reader in understanding the complex physical and biological environment of the NNSS. An adequate knowledge of the site's environment is necessary to assess the environmental impacts of new projects, design and implement environmental monitoring activities for current site operations, and assess the impacts of site operationsmore » on the public residing in the vicinity of the NNSS. The NNSS environment contributes to several key features of the site that afford protection to the inhabitants of adjacent areas from potential exposure to radioactivity or other contaminants resulting from NNSS operations. These key features include the general remote location of the NNSS, restricted access, extended wind transport times, the great depths to slow-moving groundwater, little or no surface water, and low population density. This attachment complements the annual summary of monitoring program activities and dose assessments presented in the main body of this report.« less

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

    NASA Astrophysics Data System (ADS)

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

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

  19. EPA Region 2 SEMS_CERCLIS Sites All [R2] and SEMS_CERCLIS Sites NPL [R2] GIS Layers

    EPA Pesticide Factsheets

    The Region 2 SEMS_CERCLIS Sites All [R2] GIS layer contains unique Superfund Enterprise Management System (SEMS) site records. These records have the following NPL_STATUS designations: CURRENTLY ON FINAL NPL, DELETED FROM FINAL NPL, NOT ON NPL, PROPOSED FOR NPL, REMOVED FROM PROPOSED NPL, and SITE IS PART OF NPL SITE. The Region 2 SEMS_CERCLIS NPL Sites [R2] GIS layer only has SEMS records with the following NPL_STATUS designations: 'CURRENTLY ON FINAL NPL', 'DELETED FROM FINAL NPL', 'PROPOSED FOR NPL'.The Superfund Enterprise Management System (SEMS) is EPA's official record for tracking hazardous waste sites, potentially hazardous waste sites, and remedial activities performed in support of the Superfund Program across the nation. This includes sites that are on the National Priorities List (NPL) or are being considered for the NPL. SEMS represents a joint development and ongoing collaboration between Superfund's Remedial, Removal, Federal Facilities, Enforcement, and Emergency Response programs. It provides its wide audience base with a means of ongoing analysis of Superfund Program activities and informational needs at the site, regional management, and national management levels. The customers of SEMS or SEMS data are five EPA Headquarters offices and regional staff, citizens, the regulated community, other Federal agencies, States, Tribes, local agencies, and industry. SEMS stakeholders are States, Congress, other Federal agencies, industry groups, and cit

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

    PubMed Central

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

    2015-01-01

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

  1. SUMMARY OF TECNIQUES AND UNIQUE USES FOR DIRECT PUSH METHODS IN SITE CHARACTERIZATION ON CONTAMINATED FIELD SITES

    EPA Science Inventory

    At many of the sites where we have been asked to assist in site characterization, we have discovered severe discrepancies that new technologies may be able to prevent. This presentation is designed to illustrate these new technologies or unique uses of existing technology and the...

  2. Oxygen reactivity of the biferrous site in the de novo designed four helix bundle peptide DFsc: nature of the "intermediate" and reaction mechanism.

    PubMed

    Calhoun, Jennifer R; Bell, Caleb B; Smith, Thomas J; Thamann, Thomas J; DeGrado, William F; Solomon, Edward I

    2008-07-23

    The DFsc and DFscE11D de novo designed protein scaffolds support biomimetic diiron cofactor sites that react with dioxygen forming a 520 nm "intermediate" species with an apparent pseudo-first-order formation rate constant of 2.2 and 4.8 s-1, respectively. Resonance Raman spectroscopy shows that this absorption feature is due to a phenolate-to-ferric charge transfer transition arising from a single tyrosine residue coordinating terminally to one of the ferric ions in the site. Phenol coordination could provide a proton to promote rapid loss of a putative peroxo species.

  3. Design and Synthesis of Irreversible Analogues of Bardoxolone Methyl for the Identification of Pharmacologically Relevant Targets and Interaction Sites.

    PubMed

    Wong, Michael H L; Bryan, Holly K; Copple, Ian M; Jenkins, Rosalind E; Chiu, Pak Him; Bibby, Jaclyn; Berry, Neil G; Kitteringham, Neil R; Goldring, Christopher E; O'Neill, Paul M; Park, B Kevin

    2016-03-24

    Semisynthetic triterpenoids such as bardoxolone methyl (methyl-2-cyano 3,12-dioxooleano-1,9-dien-28-oate; CDDO-Me) (4) are potent inducers of antioxidant and anti-inflammatory signaling pathways, including those regulated by the transcription factor Nrf2. However, the reversible nature of the interaction between triterpenoids and thiols has hindered attempts to identify pharmacologically relevant targets and characterize the sites of interaction. Here, we report a shortened synthesis and SAR profiling of 4, enabling the design of analogues that react irreversibly with model thiols, as well as the model protein glutathione S-transferase P1, in vitro. We show that one of these analogues, CDDO-epoxide (13), is comparable to 4 in terms of cytotoxicity and potency toward Nrf2 in rat hepatoma cells and stably modifies specific cysteine residues (namely, Cys-257, -273, -288, -434, -489, and -613) within Keap1, the major repressor of Nrf2, both in vitro and in living cells. Supported by molecular modeling, these data demonstrate the value of 13 for identifying site(s) of interaction with pharmacologically relevant targets and informing the continuing development of triterpenoids as novel drug candidates.

  4. Site-wide seismic risk model for Savannah River Site nuclear facilities

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

    Eide, S.A.; Shay, R.S.; Durant, W.S.

    1993-09-01

    The 200,000 acre Savannah River Site (SRS) has nearly 30 nuclear facilities spread throughout the site. The safety of each facility has been established in facility-specific safety analysis reports (SARs). Each SAR contains an analysis of risk from seismic events to both on-site workers and the off-site population. Both radiological and chemical releases are considered, and air and water pathways are modeled. Risks to the general public are generally characterized by evaluating exposure to the maximally exposed individual located at the SRS boundary and to the off-site population located within 50 miles. Although the SARs are appropriate methods for studyingmore » individual facility risks, there is a class of accident initiators that can simultaneously affect several of all of the facilities, Examples include seismic events, strong winds or tornados, floods, and loss of off-site electrical power. Overall risk to the off-site population from such initiators is not covered by the individual SARs. In such cases multiple facility radionuclide or chemical releases could occur, and off-site exposure would be greater than that indicated in a single facility SAR. As a step towards an overall site-wide risk model that adequately addresses multiple facility releases, a site-wide seismic model for determining off-site risk has been developed for nuclear facilities at the SRS. Risk from seismic events up to the design basis earthquake (DBE) of 0.2 g (frequency of 2.0E-4/yr) is covered by the model. Present plans include expanding the scope of the model to include other types of initiators that can simultaneously affect multiple facilities.« less

  5. 50 kW on-site concentrating solar photovoltaic power system. Phase I: design. Final report, 1 June 1978-28 February 1979

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

    Pittman, P F

    1979-03-30

    This contract is part of a three phase program to design, fabricate, and operate a solar photovoltaic electric power system with concentrating optics. The system will be located beside a Local Operating Headquarters of the Georgia Power Company in Atlanta, Georgia and will provide part of the power for the on-site load. Fresnel lens concentrators will be used in 2-axis tracking arrays to focus solar energy onto silicon solar cells producing a peak power output of 56 kW. The present contract covers Phase I which has as its objective the complete design of the system and necessary subsystems.

  6. Lys98 Substitution in Human AP Endonuclease 1 Affects the Kinetic Mechanism of Enzyme Action in Base Excision and Nucleotide Incision Repair Pathways

    PubMed Central

    Timofeyeva, Nadezhda A.; Koval, Vladimir V.; Ishchenko, Alexander A.; Saparbaev, Murat K.; Fedorova, Olga S.

    2011-01-01

    Human apurinic/apyrimidinic endonuclease 1 (APE1) is a key enzyme in the base excision repair (BER) and nucleotide incision repair (NIR) pathways. We recently analyzed the conformational dynamics and kinetic mechanism of wild-type (wt) protein, in a stopped-flow fluorescence study. In this study, we investigated the mutant enzyme APE1K98A using the same approach. Lys98 was known to hydrogen bond to the carboxyl group of Asp70, a residue implicated in binding the divalent metal ion. Our data suggested that the conformational selection and induced fit occur during the enzyme action. We expanded upon the evidence that APE1 can pre-exist in two conformations. The isomerization of an enzyme-product complex in the BER process and the additional isomerization stage of enzyme-substrate complex in the NIR process were established for APE1K98A. These stages had not been registered for the wtAPE1. We found that the K98A substitution resulted in a 12-fold reduction of catalytic constant of 5′-phosphodiester bond hydrolysis in (3-hydroxytetrahydrofuran-2-yl)methyl phosphate (F, tetrahydrofuran) containing substrate, and in 200-fold reduction in 5,6-dihydrouridine (DHU) containing substrate. Thus, the K98A substitution influenced NIR more than BER. We demonstrated that the K98A mutation influenced the formation of primary unspecific enzyme-substrate complex in a complicated manner, depending on the Mg2+ concentration and pH. This mutation obstructed the induced fit of enzyme in the complex with undamaged DNA and F-containing DNA and appreciably decreased the stability of primary complex upon interaction of enzyme with DNA, containing the natural apurinic/apyrimidinic (AP) site. Furthermore, it significantly delayed the activation of the less active form of enzyme during NIR and slowed down the conformational conversion of the complex of enzyme with the cleavage product of DHU-substrate. Our data revealed that APE1 uses the same active site to catalyze the cleavage of DHU- and

  7. Transitioning from Marketing-Oriented Design to User-Oriented Design: A Case Study

    ERIC Educational Resources Information Center

    Laster, Shari; Stitz, Tammy; Bove, Frank J.; Wise, Casey

    2011-01-01

    The transition to a new architecture and design for an academic library Web site does not always proceed smoothly. In this case study, a library at a large research university hired an outside Web development contractor to create a new architecture and design for the university's Web site using dotCMS, an open-source content management system. The…

  8. 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.

  9. Information Architecture for Bilingual Web Sites.

    ERIC Educational Resources Information Center

    Cunliffe, Daniel; Jones, Helen; Jarvis, Melanie; Egan, Kevin; Huws, Rhian; Munro, Sian

    2002-01-01

    Discusses creating an information architecture for a bilingual Web site and reports work in progress on the development of a content-based bilingual Web site to facilitate shared resources between speech and language therapists. Considers a structural analysis of existing bilingual Web designs and explains a card-sorting activity conducted with…

  10. Event-based soil loss models for construction sites

    NASA Astrophysics Data System (ADS)

    Trenouth, William R.; Gharabaghi, Bahram

    2015-05-01

    The elevated rates of soil erosion stemming from land clearing and grading activities during urban development, can result in excessive amounts of eroded sediments entering waterways and causing harm to the biota living therein. However, construction site event-based soil loss simulations - required for reliable design of erosion and sediment controls - are one of the most uncertain types of hydrologic models. This study presents models with improved degree of accuracy to advance the design of erosion and sediment controls for construction sites. The new models are developed using multiple linear regression (MLR) on event-based permutations of the Universal Soil Loss Equation (USLE) and artificial neural networks (ANN). These models were developed using surface runoff monitoring datasets obtained from three sites - Greensborough, Cookstown, and Alcona - in Ontario and datasets mined from the literature for three additional sites - Treynor, Iowa, Coshocton, Ohio and Cordoba, Spain. The predictive MLR and ANN models can serve as both diagnostic and design tools for the effective sizing of erosion and sediment controls on active construction sites, and can be used for dynamic scenario forecasting when considering rapidly changing land use conditions during various phases of construction.

  11. Building a Playground: General Guidelines for Creating Educational Web Sites for Children

    PubMed Central

    Meloncon, Lisa; Haynes, Erin; Varelmann, Megan; Groh, Lisa

    2015-01-01

    Purpose Since 2004, the number of children online has increased 18%, compared with a 10% increase in total users. Not only do children represent a growing segment of Internet users, much of what they do online has a specific purpose: education. To help technical communicators create educational Web sites for children, we offer a set of guidelines to direct the design process. Method Nine children participated in a usability test of the CARES Playground, an educational Web site geared toward 7- to 9-year-olds. The site was designed by a group of graduate students in professional writing based on a review of the (admittedly limited) literature dealing with designing Web sites for children. This paper matches common themes from existing literature to the results of the usability tests. Results Since all the information on designing Web sites for children emerged from the literature of designing Web sites for adults, the themes of navigation, appearance, and content are not unfamiliar. However, the interpretation of those common issues for children—as well as the children’s reaction to them—may be surprising. Conclusion Technical communicators need to be conscious and deliberate when designing Web sites for children. To ensure that educational Web sites are able to meet their learning goals, careful consideration of children’s developmental abilities and Web preferences must be considered. We present several guidelines as a starting point, though further research is needed to confirm and expand upon them. PMID:26633909

  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. National Site for the Regional IPM Centers

    Science.gov Websites

    Click on a state to see IPM site(s) available US Map United States Department of Agriculture - National Institute of Food and Agriculture Website managed by the Southern IPM Center. Design adapted from work by and Agriculture.

  15. Rationally Designed Sensing Selectivity and Sensitivity of an Aerolysin Nanopore via Site-Directed Mutagenesis.

    PubMed

    Wang, Ya-Qian; Cao, Chan; Ying, Yi-Lun; Li, Shuang; Wang, Ming-Bo; Huang, Jin; Long, Yi-Tao

    2018-04-27

    Selectivity and sensitivity are two key parameters utilized to describe the performance of a sensor. In order to investigate selectivity and sensitivity of the aerolysin nanosensor, we manipulated its surface charge at different locations via single site-directed mutagenesis. To study the selectivity, we replaced the positively charged R220 at the entrance of the pore with negatively charged glutamic acid, resulting in barely no current blockages for sensing negatively charged oligonucleotides. For the sensitivity, we substituted the positively charged lumen-exposed amino acid K238 located at trans-ward third of the β-barrel stem with glutamic acid. This leads to a surprisingly longer duration time at +140 mV, which is about 20 times slower in translocation speed for Poly(dA) 4 compared to that of wild-type aerolysin, indicating the stronger pore-analyte interactions and enhanced sensitivity. Therefore, it is both feasible and understandable to rationally design confined biological nanosensors for single molecule detection with high selectivity and sensitivity.

  16. Usability Evaluation of Public Web Mapping Sites

    NASA Astrophysics Data System (ADS)

    Wang, C.

    2014-04-01

    Web mapping sites are interactive maps that are accessed via Webpages. With the rapid development of Internet and Geographic Information System (GIS) field, public web mapping sites are not foreign to people. Nowadays, people use these web mapping sites for various reasons, in that increasing maps and related map services of web mapping sites are freely available for end users. Thus, increased users of web mapping sites led to more usability studies. Usability Engineering (UE), for instance, is an approach for analyzing and improving the usability of websites through examining and evaluating an interface. In this research, UE method was employed to explore usability problems of four public web mapping sites, analyze the problems quantitatively and provide guidelines for future design based on the test results. Firstly, the development progress for usability studies were described, and simultaneously several usability evaluation methods such as Usability Engineering (UE), User-Centered Design (UCD) and Human-Computer Interaction (HCI) were generally introduced. Then the method and procedure of experiments for the usability test were presented in detail. In this usability evaluation experiment, four public web mapping sites (Google Maps, Bing maps, Mapquest, Yahoo Maps) were chosen as the testing websites. And 42 people, who having different GIS skills (test users or experts), gender (male or female), age and nationality, participated in this test to complete the several test tasks in different teams. The test comprised three parts: a pretest background information questionnaire, several test tasks for quantitative statistics and progress analysis, and a posttest questionnaire. The pretest and posttest questionnaires focused on gaining the verbal explanation of their actions qualitatively. And the design for test tasks targeted at gathering quantitative data for the errors and problems of the websites. Then, the results mainly from the test part were analyzed. The

  17. MOBILE ON-SITE RECYCLING OF METALWORKING FLUIDS

    EPA Science Inventory

    Product quality, waste reduction, and economic issues were evaluated for a technology designed to recycle metalworking fluids. mulsion-type fluids were tested at two sites and a synthetic fluid was tested at a third site. he specific recycling unit evaluated is based on the techn...

  18. Design of evidence-based gardens and garden therapy for neurodisability in Scandinavia: data from 14 sites.

    PubMed

    Spring, Josephine Anne

    2016-04-01

    A total of 14 Scandinavian therapy gardens were visited and data collected on plantings, therapeutic activities and assessment of effectiveness in Spring 2014. Data were gathered by a questionnaire and by interviewing staff in Sweden, Denmark and Norway. The data collection structured proforma used the post-occupation assessment method. Gardening promoted physical movement, presented cognitive challenges and provided opportunities for social participation. Half the gardens were enclosed with sensory plants and 85% were adapted for wheelchairs. A total of 57% of gardens visited had simple designs with flowers, shrubs, lawns and trees. A social center was important especially for dementia clients. Planted pots were used in 79% of gardens. The effectiveness of therapy gardens was assessed at 71% of sites.

  19. Optimization Under Uncertainty of Site-Specific Turbine Configurations

    NASA Astrophysics Data System (ADS)

    Quick, J.; Dykes, K.; Graf, P.; Zahle, F.

    2016-09-01

    Uncertainty affects many aspects of wind energy plant performance and cost. In this study, we explore opportunities for site-specific turbine configuration optimization that accounts for uncertainty in the wind resource. As a demonstration, a simple empirical model for wind plant cost of energy is used in an optimization under uncertainty to examine how different risk appetites affect the optimal selection of a turbine configuration for sites of different wind resource profiles. If there is unusually high uncertainty in the site wind resource, the optimal turbine configuration diverges from the deterministic case and a generally more conservative design is obtained with increasing risk aversion on the part of the designer.

  20. 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.

  1. SMARTe Site Characterization Tool. In: SMARTe20ll, EPA/600/C-10/007

    EPA Science Inventory

    The purpose of the Site Characterization Tool is to: (1) develop a sample design for collecting site characterization data and (2) perform data analysis on uploaded data. The sample design part helps to determine how many samples should be collected to characterize a site with ...

  2. Catalytic-site design for inverse heavy-enzyme isotope effects in human purine nucleoside phosphorylase

    PubMed Central

    Harijan, Rajesh K.; Zoi, Ioanna; Antoniou, Dimitri; Schwartz, Steven D.; Schramm, Vern L.

    2017-01-01

    Heavy-enzyme isotope effects (15N-, 13C-, and 2H-labeled protein) explore mass-dependent vibrational modes linked to catalysis. Transition path-sampling (TPS) calculations have predicted femtosecond dynamic coupling at the catalytic site of human purine nucleoside phosphorylase (PNP). Coupling is observed in heavy PNPs, where slowed barrier crossing caused a normal heavy-enzyme isotope effect (kchem light/kchem heavy > 1.0). We used TPS to design mutant F159Y PNP, predicted to improve barrier crossing for heavy F159Y PNP, an attempt to generate a rare inverse heavy-enzyme isotope effect (kchem light/kchem heavy < 1.0). Steady-state kinetic comparison of light and heavy native PNPs to light and heavy F159Y PNPs revealed similar kinetic properties. Pre–steady-state chemistry was slowed 32-fold in F159Y PNP. Pre–steady-state chemistry compared heavy and light native and F159Y PNPs and found a normal heavy-enzyme isotope effect of 1.31 for native PNP and an inverse effect of 0.75 for F159Y PNP. Increased isotopic mass in F159Y PNP causes more efficient transition state formation. Independent validation of the inverse isotope effect for heavy F159Y PNP came from commitment to catalysis experiments. Most heavy enzymes demonstrate normal heavy-enzyme isotope effects, and F159Y PNP is a rare example of an inverse effect. Crystal structures and TPS dynamics of native and F159Y PNPs explore the catalytic-site geometry associated with these catalytic changes. Experimental validation of TPS predictions for barrier crossing establishes the connection of rapid protein dynamics and vibrational coupling to enzymatic transition state passage. PMID:28584087

  3. Site vegetation report: Terrestrial vegetation survey (1993--1995) for the Rocky Flats Environmental Technology Site

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

    NONE

    1997-06-01

    The Ecological Monitoring Program (EcMP) was designed to investigate the long-term ecological trends in terrestrial and aquatic ecosystems at the US Department of energy`s (DOE`s) Rocky Flats Environmental Technology Site (Site) (DOE 1993). Field sampling was conducted during 1993, 1994, and 1995, until the program was terminated in late 1995. This report presents the terrestrial vegetation data that were gathered by the EcMP. The site is located on the Colorado Piedmont, east of the Front Range, between Boulder and Golden, approximately 25 km (16 miles) northwest of Denver. The topography and proximity of the Site to the mountain front resultmore » in an interesting mixture of prairie and mountain plant species. The Site is one of the few large, relatively undisturbed areas of its kind that remains along the Colorado Piedmont. Until 1989, the primary mission of the Site was the production of nuclear weapons components (DOE 1993). After production ceased, Site personnel shifted their focus to cleanup and closure.« less

  4. Optimization Review: Carson River Mercury Superfund Site, Carson City, Nevada

    EPA Pesticide Factsheets

    The Carson River Mercury Site (CRMS) (Figure 1) is located in northwest Nevada and was designated a Superfund site in 1990 because of elevated mercury concentrations observed in surface water, sediments and biota inhabiting the site.

  5. Nevada National Security Site Environmental Report 2012 Attachment A: Site Description

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

    Wills, Cathy A

    This attachment expands on the general description of the Nevada National Security Site (NNSS) presented in the Introduction to the Nevada National Security Site Environmental Report 2012 (National Security Technologies, LLC [NSTec], 2013). Included are subsections that summarize the site’s geological, hydrological, climatological, and ecological setting and the cultural resources of the NNSS. The subsections are meant to aid the reader in understanding the complex physical and biological environment of the NNSS. An adequate knowledge of the site’s environment is necessary to assess the environmental impacts of new projects, design and implement environmental monitoring activities for current site operations, andmore » assess the impacts of site operations on the public residing in the vicinity of the NNSS. The NNSS environment contributes to several key features of the site that afford protection to the inhabitants of adjacent areas from potential exposure to radioactivity or other contaminants resulting from NNSS operations. These key features include the general remote location of the NNSS, restricted access, extended wind transport times, the great depths to slow-moving groundwater, little or no surface water, and low population density. This attachment complements the annual summary of monitoring program activities and dose assessments presented in the main body of this report.« less

  6. Nevada National Security Site Environmental Report 2013 Attachment A: Site Description

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

    Wills, C.

    This attachment expands on the general description of the Nevada National Security Site (NNSS) presented in the Introduction to the Nevada National Security Site Environmental Report 2012 (National Security Technologies, LLC [NSTec], 2013). Included are subsections that summarize the site’s geological, hydrological, climatological, and ecological setting and the cultural resources of the NNSS. The subsections are meant to aid the reader in understanding the complex physical and biological environment of the NNSS. An adequate knowledge of the site’s environment is necessary to assess the environmental impacts of new projects, design and implement environmental monitoring activities for current site operations, andmore » assess the impacts of site operations on the public residing in the vicinity of the NNSS. The NNSS environment contributes to several key features of the site that afford protection to the inhabitants of adjacent areas from potential exposure to radioactivity or other contaminants resulting from NNSS operations. These key features include the general remote location of the NNSS, restricted access, extended wind transport times, the great depths to slow-moving groundwater, little or no surface water, and low population density. This attachment complements the annual summary of monitoring program activities and dose assessments presented in the main body of this report.« less

  7. 23 CFR 1340.5 - Selection of observation sites.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... STATE OBSERVATIONAL SURVEYS OF SEAT BELT USE Survey Design Requirements § 1340.5 Selection of... observation sites. The survey design shall include at a minimum the following protocols: (1) Protocol when...

  8. 23 CFR 1340.5 - Selection of observation sites.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... STATE OBSERVATIONAL SURVEYS OF SEAT BELT USE Survey Design Requirements § 1340.5 Selection of... observation sites. The survey design shall include at a minimum the following protocols: (1) Protocol when...

  9. 23 CFR 1340.5 - Selection of observation sites.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... STATE OBSERVATIONAL SURVEYS OF SEAT BELT USE Survey Design Requirements § 1340.5 Selection of... observation sites. The survey design shall include at a minimum the following protocols: (1) Protocol when...

  10. Optimization Under Uncertainty of Site-Specific Turbine Configurations

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

    Quick, J.; Dykes, K.; Graf, P.

    Uncertainty affects many aspects of wind energy plant performance and cost. In this study, we explore opportunities for site-specific turbine configuration optimization that accounts for uncertainty in the wind resource. As a demonstration, a simple empirical model for wind plant cost of energy is used in an optimization under uncertainty to examine how different risk appetites affect the optimal selection of a turbine configuration for sites of different wind resource profiles. Lastly, if there is unusually high uncertainty in the site wind resource, the optimal turbine configuration diverges from the deterministic case and a generally more conservative design is obtainedmore » with increasing risk aversion on the part of the designer.« less

  11. Optimization Under Uncertainty of Site-Specific Turbine Configurations

    DOE PAGES

    Quick, J.; Dykes, K.; Graf, P.; ...

    2016-10-03

    Uncertainty affects many aspects of wind energy plant performance and cost. In this study, we explore opportunities for site-specific turbine configuration optimization that accounts for uncertainty in the wind resource. As a demonstration, a simple empirical model for wind plant cost of energy is used in an optimization under uncertainty to examine how different risk appetites affect the optimal selection of a turbine configuration for sites of different wind resource profiles. Lastly, if there is unusually high uncertainty in the site wind resource, the optimal turbine configuration diverges from the deterministic case and a generally more conservative design is obtainedmore » with increasing risk aversion on the part of the designer.« less

  12. Design of the aerosol sampling manifold for the Southern Great Plains site

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

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

    1995-04-01

    To meet the needs of the ARM program, the Environmental Measurements Laboratory (EML) has the responsibility to establish a surface aerosol measurements program at the Southern Great Plains (SGP) site in Lamont, OK. At the present time, EML has scheduled installation of five instruments at SGP: a single wavelength nephelometer, an optical particle counter (OPC), a condensation particle counter (CPC), an optical absorption monitor (OAM), and an ozone monitor. ARM`s operating protocol requires that all the observational data be placed online and sent to the main computer facility in real time. EML currently maintains a computer file containing back trajectorymore » (BT) analyses for the SGP site. These trajectories are used to characterize air mass types as they pass over the site. EML is continuing to calculate and store the resulting trajectory analyses for future use by the ARM science team.« less

  13. Scaling up kangaroo mother care in South Africa: 'on-site' versus 'off-site' educational facilitation

    PubMed Central

    Bergh, Anne-Marie; van Rooyen, Elise; Pattinson, Robert C

    2008-01-01

    Background Scaling up the implementation of new health care interventions can be challenging and demand intensive training or retraining of health workers. This paper reports on the results of testing the effectiveness of two different kinds of face-to-face facilitation used in conjunction with a well-designed educational package in the scaling up of kangaroo mother care. Methods Thirty-six hospitals in the Provinces of Gauteng and Mpumalanga in South Africa were targeted to implement kangaroo mother care and participated in the trial. The hospitals were paired with respect to their geographical location and annual number of births. One hospital in each pair was randomly allocated to receive either 'on-site' facilitation (Group A) or 'off-site' facilitation (Group B). Hospitals in Group A received two on-site visits, whereas delegates from hospitals in Group B attended one off-site, 'hands-on' workshop at a training hospital. All hospitals were evaluated during a site visit six to eight months after attending an introductory workshop and were scored by means of an existing progress-monitoring tool with a scoring scale of 0–30. Successful implementation was regarded as demonstrating evidence of practice (score >10) during the site visit. Results There was no significant difference between the scores of Groups A and B (p = 0.633). Fifteen hospitals in Group A and 16 in Group B demonstrated evidence of practice. The median score for Group A was 16.52 (range 00.00–23.79) and that for Group B 14.76 (range 07.50–23.29). Conclusion A previous trial illustrated that the implementation of a new health care intervention could be scaled up by using a carefully designed educational package, combined with face-to-face facilitation by respected resource persons. This study demonstrated that the site of facilitation, either on site or at a centre of excellence, did not influence the ability of a hospital to implement KMC. The choice of outreach strategy should be guided by

  14. Non-Invasive Seismic Methods for Earthquake Site Classification Applied to Ontario Bridge Sites

    NASA Astrophysics Data System (ADS)

    Bilson Darko, A.; Molnar, S.; Sadrekarimi, A.

    2017-12-01

    How a site responds to earthquake shaking and its corresponding damage is largely influenced by the underlying ground conditions through which it propagates. The effects of site conditions on propagating seismic waves can be predicted from measurements of the shear wave velocity (Vs) of the soil layer(s) and the impedance ratio between bedrock and soil. Currently the seismic design of new buildings and bridges (2015 Canadian building and bridge codes) requires determination of the time-averaged shear-wave velocity of the upper 30 metres (Vs30) of a given site. In this study, two in situ Vs profiling methods; Multichannel Analysis of Surface Waves (MASW) and Ambient Vibration Array (AVA) methods are used to determine Vs30 at chosen bridge sites in Ontario, Canada. Both active-source (MASW) and passive-source (AVA) surface wave methods are used at each bridge site to obtain Rayleigh-wave phase velocities over a wide frequency bandwidth. The dispersion curve is jointly inverted with each site's amplification function (microtremor horizontal-to-vertical spectral ratio) to obtain shear-wave velocity profile(s). We apply our non-invasive testing at three major infrastructure projects, e.g., five bridge sites along the Rt. Hon. Herb Gray Parkway in Windsor, Ontario. Our non-invasive testing is co-located with previous invasive testing, including Standard Penetration Test (SPT), Cone Penetration Test and downhole Vs data. Correlations between SPT blowcount and Vs are developed for the different soil types sampled at our Ontario bridge sites. A robust earthquake site classification procedure (reliable Vs30 estimates) for bridge sites across Ontario is evaluated from available combinations of invasive and non-invasive site characterization methods.

  15. Perceptions of Business Students' Feature Requirements in Educational Web Sites

    ERIC Educational Resources Information Center

    Hazari, Sunil; Johnson, Barbara

    2007-01-01

    There is paucity of original research that explains phenomena related to content organization and site design of educational Web sites. Educational Web sites are often used to provide Web-based instruction, which itself is a relatively recent phenomenon for business schools, and additional research is needed in this area. Educational Web sites are…

  16. Lessons Learned from the 200 West Pump and Treatment Facility Construction Project at the US DOE Hanford Site - A Leadership for Energy and Environmental Design (LEED) Gold-Certified Facility - 13113

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

    Dorr, Kent A.; Freeman-Pollard, Jhivaun R.; Ostrom, Michael J.

    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 tomore » 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)« less

  17. Humboldt Open Ocean Disposal Site (HOODS) Survey Work 2014

    EPA Pesticide Factsheets

    The Humboldt Open Ocean Disposal Site (HOODS) is a dredged material disposal site located 3 nautical miles (nm) offshore of Humboldt Bay in Northern California. HOODS was permanently designated by EPA Region 9 in 1995, and has been actively used for dredged material disposal operations since then. The HOODS has received higher volumes of dredged material than predicted since its designation in 1995, mainly from USACE construction and maintenance dredging.

  18. Global Mapping of Transcription Factor Binding Sites by Sequencing Chromatin Surrogates: a Perspective on Experimental Design, Data Analysis, and Open Problems.

    PubMed

    Wei, Yingying; Wu, George; Ji, Hongkai

    2013-05-01

    Mapping genome-wide binding sites of all transcription factors (TFs) in all biological contexts is a critical step toward understanding gene regulation. The state-of-the-art technologies for mapping transcription factor binding sites (TFBSs) couple chromatin immunoprecipitation (ChIP) with high-throughput sequencing (ChIP-seq) or tiling array hybridization (ChIP-chip). These technologies have limitations: they are low-throughput with respect to surveying many TFs. Recent advances in genome-wide chromatin profiling, including development of technologies such as DNase-seq, FAIRE-seq and ChIP-seq for histone modifications, make it possible to predict in vivo TFBSs by analyzing chromatin features at computationally determined DNA motif sites. This promising new approach may allow researchers to monitor the genome-wide binding sites of many TFs simultaneously. In this article, we discuss various experimental design and data analysis issues that arise when applying this approach. Through a systematic analysis of the data from the Encyclopedia Of DNA Elements (ENCODE) project, we compare the predictive power of individual and combinations of chromatin marks using supervised and unsupervised learning methods, and evaluate the value of integrating information from public ChIP and gene expression data. We also highlight the challenges and opportunities for developing novel analytical methods, such as resolving the one-motif-multiple-TF ambiguity and distinguishing functional and non-functional TF binding targets from the predicted binding sites. The online version of this article (doi:10.1007/s12561-012-9066-5) contains supplementary material, which is available to authorized users.

  19. Correlation of bistranded clustered abasic DNA lesion processing with structural and dynamic DNA helix distortion

    PubMed Central

    Bignon, Emmanuelle; Gattuso, Hugo; Morell, Christophe; Dehez, François; Georgakilas, Alexandros G.; Monari, Antonio; Dumont, Elise

    2016-01-01

    Clustered apurinic/apyrimidinic (AP; abasic) DNA lesions produced by ionizing radiation are by far more cytotoxic than isolated AP lesion entities. The structure and dynamics of a series of seven 23-bp oligonucleotides featuring simple bistranded clustered damage sites, comprising of two AP sites, zero, one, three or five bases 3′ or 5′ apart from each other, were investigated through 400 ns explicit solvent molecular dynamics simulations. They provide representative structures of synthetically engineered multiply damage sites-containing oligonucleotides whose repair was investigated experimentally (Nucl. Acids Res. 2004, 32:5609-5620; Nucl. Acids Res. 2002, 30: 2800–2808). The inspection of extrahelical positioning of the AP sites, bulge and non Watson–Crick hydrogen bonding corroborates the experimental measurements of repair efficiencies by bacterial or human AP endonucleases Nfo and APE1, respectively. This study provides unprecedented knowledge into the structure and dynamics of clustered abasic DNA lesions, notably rationalizing the non-symmetry with respect to 3′ to 5′ position. In addition, it provides strong mechanistic insights and basis for future studies on the effects of clustered DNA damage on the recognition and processing of these lesions by bacterial or human DNA repair enzymes specialized in the processing of such lesions. PMID:27587587

  20. Designed topology and site-selective metal composition in tetranuclear [MM'...M'M] linear complexes.

    PubMed

    Barrios, Leoní A; Aguilà, David; Roubeau, Olivier; Gamez, Patrick; Ribas-Ariño, Jordi; Teat, Simon J; Aromí, Guillem

    2009-10-26

    The ligand 1,3-bis[3-oxo-3-(2-hydroxyphenyl)propionyl]benzene (H(4)L), designed to align transition metals into tetranuclear linear molecules, reacts with M(II) salts (M=Ni, Co, Cu) to yield complexes with the expected [MMMM] topology. The novel complexes [Co(4)L(2)(py)(6)] (2; py=pyridine) and [Na(py)(2)][Cu(4)L(2)(py)(4)](ClO(4)) (3) have been crystallographically characterised. The metal sites in complexes 2 and 3, together with previously characterised [Ni(4)L(2)(py)(6)] (1), favour different coordination geometries. These have been exploited for the deliberate synthesis of the heterometallic complex [Cu(2)Ni(2)L(2)(py)(6)] (4). Complexes 1, 2, 3 and 4 exhibit antiferromagnetic interactions between pairs of metals within each cluster, leading to S=0 spin ground states, except for the latter cluster, which features two quasi-independent S=1/2 moieties within the molecule. Complex 4 gathers the structural and physical conditions, thus allowing it to be considered as prototype of a two-qbit quantum gate.

  1. Library Web Sites in Pakistan: An Analysis of Content

    ERIC Educational Resources Information Center

    Qutab, Saima; Mahmood, Khalid

    2009-01-01

    Purpose: The purpose of this paper is to investigate library web sites in Pakistan, to analyse their content and navigational strengths and weaknesses and to give recommendations for developing better web sites and quality assessment studies. Design/methodology/approach: Survey of web sites of 52 academic, special, public and national libraries in…

  2. Digital Accessible Knowledge and well-inventoried sites for birds in Mexico: baseline sites for measuring faunistic change

    PubMed Central

    Navarro-Sigüenza, Adolfo G.; Martínez-Meyer, Enrique

    2016-01-01

    Background Faunal change is a basic and fundamental element in ecology, biogeography, and conservation biology, yet vanishingly few detailed studies have documented such changes rigorously over decadal time scales. This study responds to that gap in knowledge, providing a detailed analysis of Digital Accessible Knowledge of the birds of Mexico, designed to marshal DAK to identify sites that were sampled and inventoried rigorously prior to the beginning of major global climate change (1980). Methods We accumulated DAK records for Mexican birds from all relevant online biodiversity data portals. After extensive cleaning steps, we calculated completeness indices for each 0.05° pixel across the country; we also detected ‘hotspots’ of sampling, and calculated completeness indices for these broader areas as well. Sites were designated as well-sampled if they had completeness indices above 80% and >200 associated DAK records. Results We identified 100 individual pixels and 20 broader ‘hotspots’ of sampling that were demonstrably well-inventoried prior to 1980. These sites are catalogued and documented to promote and enable resurvey efforts that can document events of avifaunal change (and non-change) across the country on decadal time scales. Conclusions Development of repeated surveys for many sites across Mexico, and particularly for sites for which historical surveys document their avifaunas prior to major climate change processes, would pay rich rewards in information about distributional dynamics of Mexican birds. PMID:27651986

  3. Digital Accessible Knowledge and well-inventoried sites for birds in Mexico: baseline sites for measuring faunistic change.

    PubMed

    Peterson, A Townsend; Navarro-Sigüenza, Adolfo G; Martínez-Meyer, Enrique

    2016-01-01

    Faunal change is a basic and fundamental element in ecology, biogeography, and conservation biology, yet vanishingly few detailed studies have documented such changes rigorously over decadal time scales. This study responds to that gap in knowledge, providing a detailed analysis of Digital Accessible Knowledge of the birds of Mexico, designed to marshal DAK to identify sites that were sampled and inventoried rigorously prior to the beginning of major global climate change (1980). We accumulated DAK records for Mexican birds from all relevant online biodiversity data portals. After extensive cleaning steps, we calculated completeness indices for each 0.05° pixel across the country; we also detected 'hotspots' of sampling, and calculated completeness indices for these broader areas as well. Sites were designated as well-sampled if they had completeness indices above 80% and >200 associated DAK records. We identified 100 individual pixels and 20 broader 'hotspots' of sampling that were demonstrably well-inventoried prior to 1980. These sites are catalogued and documented to promote and enable resurvey efforts that can document events of avifaunal change (and non-change) across the country on decadal time scales. Development of repeated surveys for many sites across Mexico, and particularly for sites for which historical surveys document their avifaunas prior to major climate change processes, would pay rich rewards in information about distributional dynamics of Mexican birds.

  4. Database for landscape-scale carbon monitoring sites

    Treesearch

    Jason A. Cole; Kristopher D. Johnson; Richard A. Birdsey; Yude Pan; Craig A. Wayson; Kevin McCullough; Coeli M. Hoover; David Y. Hollinger; John B. Bradford; Michael G. Ryan; Randall K. Kolka; Peter Wieshampel; Kenneth L. Clark; Nicholas S. Skowronski; John Hom; Scott V. Ollinger; Steven G. McNulty; Michael J. Gavazzi

    2013-01-01

    This report describes the database used to compile, store, and manage intensive ground-based biometric data collected at research sites in Colorado, Minnesota, New Hampshire, New Jersey, North Carolina, and Wyoming, supporting research activities of the U.S. North American Carbon Program (NACP). This report also provides details of each site, the sampling design and...

  5. Northeast Oregon Hatchery Project, Final Siting Report.

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

    Watson, Montgomery

    1995-03-01

    This report presents the results of site analysis for the Bonneville Power Administration Northeast Oregon Hatchery Project. The purpose of this project is to provide engineering services for the siting and conceptual design of hatchery facilities for the Bonneville Power Administration. The hatchery project consists of artificial production facilities for salmon and steelhead to enhance production in three adjacent tributaries to the Columbia River in northeast Oregon: the Grande Ronde, Walla Walla, and Imnaha River drainage basins. Facilities identified in the master plan include adult capture and holding facilities; spawning incubation, and early rearing facilities; full-term rearing facilities; and directmore » release or acclimation facilities. The evaluation includes consideration of a main production facility for one or more of the basins or several smaller satellite production facilities to be located within major subbasins. The historic and current distribution of spring and fall chinook salmon and steelhead was summarized for the Columbia River tributaries. Current and future production and release objectives were reviewed. Among the three tributaries, forty seven 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.« less

  6. Hanford Site 1998 Environmental Report

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

    RL Dirkes; RW Hanf; TM Poston

    This Hanford Site environmental report is prepared annually to summarize environmental data and information, to describe environmental management performance, to demonstrate the status of compliance with environmental regulations, and to highlight major environmental programs and efforts. The report is written to meet requirements and guidelines of the U.S. Department of Energy (DOE) and to meet the needs of the public. This summary has been written with a minimum of technical terminology. Individual sections of the report are designed to: describe the Hanford Site and its mission; summarize the status of compliance with environmental regulations; describe the environmental programs at themore » Hanford Site; discuss the estimated radionuclide exposure to the public from 1998 Hanford Site activities; present the effluent monitoring, environmental surveillance, and groundwater protection and monitoring information; and discuss the activities to ensure quality.« less

  7. Does your web site draw new patients?

    PubMed

    Wallin, Wendy S

    2009-11-01

    The absence of scientific data forces orthodontists to guess at how best to design Internet sites that persuade prospective patients to call for appointments. This study was conducted to identify the Web-site factors that lead prospective patients to make appointments or, conversely, to reject a practice. Ten participants actively looking online for an orthodontist were recruited to participate. They reviewed 64 orthodontic Web sites in their geographic areas and rated their likelihood of calling each practice for an appointment. The sessions were videotaped. Analysis of participant comments, navigation patterns, and ratings suggested 25 distinguishing factors. Statistical analysis showed 10 Web-site characteristics that predict the success of an orthodontic Web site in attracting new patients.

  8. Mars Pathfinder Landing Site Workshop

    NASA Technical Reports Server (NTRS)

    Golombek, Matthew (Editor)

    1994-01-01

    The Mars Pathfinder Project is an approved Discovery-class mission that will place a lander and rover on the surface of the Red Planet in July 1997. The Mars Pathfinder Landing Site Workshop was designed to allow the Mars scientific community to provide input as to where to land Pathfinder on Mars. The workshop was attended by over 60 people from around the United States and from Europe. Over 20 landing sites were proposed at the workshop, and the scientific questions and problems concerning each were addressed. The workshop and the discussion that occured during and afterward have significantly improved the ability to select a scientifically exciting but safe landing site on Mars.

  9. Creating Patient and Family Education Web Sites

    PubMed Central

    YADRICH, DONNA MACAN; FITZGERALD, SHARON A.; WERKOWITCH, MARILYN; SMITH, CAROL E.

    2013-01-01

    This article gives details about the methods and processes used to ensure that usability and accessibility were achieved during development of the Home Parenteral Nutrition Family Caregivers Web site, an evidence-based health education Web site for the family members and caregivers of chronically ill patients. This article addresses comprehensive definitions of usability and accessibility and illustrates Web site development according to Section 508 standards and the national Health and Human Services’ Research-Based Web Design and Usability Guidelines requirements. PMID:22024970

  10. AFB/open cycle gas turbine conceptual design study

    NASA Technical Reports Server (NTRS)

    Dickinson, T. W.; Tashjian, R.

    1983-01-01

    Applications of coal fired atmospheric fluidized bed gas turbine systems in industrial cogeneration are identified. Based on site-specific conceptual designs, the potential benefits of the AFB/gas turbine system were compared with an atmospheric fluidized design steam boiler/steam turbine system. The application of these cogeneration systems at four industrial plant sites is reviewed. A performance and benefit analysis was made along with a study of the representativeness of the sites both in regard to their own industry and compared to industry as a whole. A site was selected for the conceptual design, which included detailed site definition, AFB/gas turbine and AFB/steam turbine cogeneration system designs, detailed cost estimates, and comparative performance and benefit analysis. Market and benefit analyses identified the potential market penetration for the cogeneration technologies and quantified the potential benefits.

  11. AFB/open cycle gas turbine conceptual design study

    NASA Astrophysics Data System (ADS)

    Dickinson, T. W.; Tashjian, R.

    1983-09-01

    Applications of coal fired atmospheric fluidized bed gas turbine systems in industrial cogeneration are identified. Based on site-specific conceptual designs, the potential benefits of the AFB/gas turbine system were compared with an atmospheric fluidized design steam boiler/steam turbine system. The application of these cogeneration systems at four industrial plant sites is reviewed. A performance and benefit analysis was made along with a study of the representativeness of the sites both in regard to their own industry and compared to industry as a whole. A site was selected for the conceptual design, which included detailed site definition, AFB/gas turbine and AFB/steam turbine cogeneration system designs, detailed cost estimates, and comparative performance and benefit analysis. Market and benefit analyses identified the potential market penetration for the cogeneration technologies and quantified the potential benefits.

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

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

    Not Available

    1990-02-01

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

  13. Improving design phase evaluations for high pile rebound sites : final report.

    DOT National Transportation Integrated Search

    2016-05-31

    A testing program performed to help determine typical soils properties encountered during pile installation when high rebound : occurs produced a decision matrix for geotechnical engineers. High pile rebound (HPR) occurred at numerous sites in Florid...

  14. Development of designed site-directed pseudopeptide-peptido-mimetic immunogens as novel minimal subunit-vaccine candidates for malaria.

    PubMed

    Lozano, José Manuel; Lesmes, Liliana P; Carreño, Luisa F; Gallego, Gina M; Patarroyo, Manuel Elkin

    2010-12-06

    Synthetic vaccines constitute the most promising tools for controlling and preventing infectious diseases. When synthetic immunogens are designed from the pathogen native sequences, these are normally poorly immunogenic and do not induce protection, as demonstrated in our research. After attempting many synthetic strategies for improving the immunogenicity properties of these sequences, the approach consisting of identifying high binding motifs present in those, and then performing specific changes on amino-acids belonging to such motifs, has proven to be a workable strategy. In addition, other strategies consisting of chemically introducing non-natural constraints to the backbone topology of the molecule and modifying the α-carbon asymmetry are becoming valuable tools to be considered in this pursuit. Non-natural structural constraints to the peptide backbone can be achieved by introducing peptide bond isosters such as reduced amides, partially retro or retro-inverso modifications or even including urea motifs. The second can be obtained by strategically replacing L-amino-acids with their enantiomeric forms for obtaining both structurally site-directed designed immunogens as potential vaccine candidates and their Ig structural molecular images, both having immuno-therapeutic effects for preventing and controlling malaria.

  15. Geology of the Apollo 17 site

    NASA Technical Reports Server (NTRS)

    Muehlberger, W. R.

    1992-01-01

    The Apollo 17 landing site was unique in several aspects: (1) it was the only site that was not selected from telescopic-based geologic interpretation--interest in the site was generated by the visual observations of Al Worden, Apollo 15 Command Module pilot, who interpreted dark-haloed craters as possible cinder cones; (2) instead of 20-m-resolution photographs, as was the norm for all earlier missions, this site had Apollo 15 panoramic camera photography coverage that had 2-m resolution; and (3) it had a geologist-astronaut aboard who was intimately involved in all stages of planning and mission operation, and was also instrumental in the design of a long-handled sample bag holder that eliminated the need for crew to dismount before collecting a sample, which then permitted sampling between major stations. Details of site geology, sample description, and geologic synthesis of the site as viewed from studies through 1976 are summarized.

  16. The study designed by a committee: design of the Multisite Violence Prevention Project.

    PubMed

    Henry, David B; Farrell, Albert D

    2004-01-01

    This article describes the research design of the Multisite Violence Prevention Project (MVPP), organized and funded by the National Center for Injury Prevention and Control (NCIPC) at the Centers for Disease Control and Prevention (CDC). CDC's objectives, refined in the course of collaboration among investigators, were to evaluate the efficacy of universal and targeted interventions designed to produce change at the school level. The project's design was developed collaboratively, and is a 2 x 2 cluster-randomized true experimental design in which schools within four separate sites were assigned randomly to four conditions: (1) no-intervention control group, (2) universal intervention, (3) targeted intervention, and (4) combined universal and targeted interventions. A total of 37 schools are participating in this study with 8-12 schools per site. The impact of the interventions on two successive cohorts of sixth-grade students will be assessed based on multiple waves of data from multiple sources of information, including teachers, students, parents, and archival data. The nesting of students within teachers, families, schools and sites created a number of challenges for designing and implementing the study. The final design represents both resolution and compromise on a number of creative tensions existing in large-scale prevention trials, including tensions between cost and statistical power, and between internal and external validity. Strengths and limitations of the final design are discussed.

  17. The utility of Geographical Information Systems (GIS) in systems-oriented obesity intervention projects: the selection of comparable study sites for a quasi-experimental intervention design--TX CORD.

    PubMed

    Oluyomi, Abiodun O; Byars, Allison; Byrd-Williams, Courtney; Sharma, Shreela V; Durand, Casey; Hoelscher, Deanna M; Butte, Nancy F; Kelder, Steven H

    2015-02-01

    The Texas Childhood Obesity Research Demonstration project (TX CORD) uses a systems-oriented approach to address obesity that includes individual and family interventions, community-level action, as well as environmental and policy initiatives. Given that randomization is seldom possible in community-level intervention studies, TX CORD uses a quasi-experimental design. Comparable intervention and comparison study sites are needed to address internal validity bias. TX CORD was designed to be implemented in low-income, ethnically diverse communities in Austin and Houston, Texas. A three-stage Geographical Information System (GIS) methodology was used to establish and ascertain the comparability of the intervention and comparison study sites. Census tract (stage 1) and school (stage 2) data were used to identify spatially exclusive geographic areas that were comparable. In stage 3, study sites were compared on demographic characteristics, socioeconomic status (SES), food assets, and physical activity (PA) assets. Student's t-test was used to examine significant differences between the selected sites. The methodology that was used resulted in the selection of catchment areas with demographic and socioeconomic characteristics that fit the target population: ethnically diverse population; lower-median household income; and lower home ownership rates. Additionally, the intervention and comparison sites were statistically comparable on demographic and SES variables, as well as food assets and PA assets. This GIS approach can provide researchers, program evaluators, and policy makers with useful tools for both research and practice. Area-level information that allows for robust understanding of communities can enhance analytical procedures in community health research and offer significant contributions in terms of community assessment and engagement.

  18. Primer on the Implementation of a Pharmacy Intranet Site to Improve Department Communication

    PubMed Central

    Hale, Holly J.

    2013-01-01

    Purpose: The purpose of the article is to describe the experience of selecting, developing, and implementing a pharmacy department intranet site with commentary regarding application to other institutions. Clinical practitioners and supporting staff need an effective, efficient, organized, and user-friendly communication tool to utilize and relay information required to optimize patient care. Summary: To create a functional and user-friendly department intranet site, department leadership and staff should be involved in the process from selection of product through implementation. A product that supports both document storage management and communication delivery and has the capability to be customized to provide varied levels of site access is desirable. The designation of an intranet site owner/developer within the department will facilitate purposeful site design and site maintenance execution. A well-designed and up-to-date site along with formal end-user training are essential for staff adoption and continued utilization. Conclusion: Development of a department intranet site requires a considerable time investment by several members of the department. The implementation of an intranet site can be an important step toward achieving improved communications. Staff utilization of this resource is key to its success. PMID:24421523

  19. Primer on the implementation of a pharmacy intranet site to improve department communication.

    PubMed

    Hale, Holly J

    2013-07-01

    The purpose of the article is to describe the experience of selecting, developing, and implementing a pharmacy department intranet site with commentary regarding application to other institutions. Clinical practitioners and supporting staff need an effective, efficient, organized, and user-friendly communication tool to utilize and relay information required to optimize patient care. To create a functional and user-friendly department intranet site, department leadership and staff should be involved in the process from selection of product through implementation. A product that supports both document storage management and communication delivery and has the capability to be customized to provide varied levels of site access is desirable. The designation of an intranet site owner/developer within the department will facilitate purposeful site design and site maintenance execution. A well-designed and up-to-date site along with formal end-user training are essential for staff adoption and continued utilization. Development of a department intranet site requires a considerable time investment by several members of the department. The implementation of an intranet site can be an important step toward achieving improved communications. Staff utilization of this resource is key to its success.

  20. Hanford Site Environmental Report 1999

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

    TM Poston; RW Hanf; RL Dirkes

    This Hanford Site environmental report is prepared annually to summarize environmental data and information, to describe environmental management performance, to demonstrate the status of compliance with environmental regulations, and to highlight major environmental programs and efforts. The report is written to meet requirements and guidelines of the U.S. Department of Energy (DOE) and to meet the needs of the public. This summary has been written with a minimum of technical terminology. Individual sections of the report are designed to: (1) describe the Hanford Site and its mission; (2) summarize the status of compliance with environmental regulations; (3) describe the environmentalmore » programs at the Hanford Site; (4) discuss the estimated radionuclide exposure to the public from 1999 Hanford Site activities; (5) present the effluent monitoring, environmental surveillance, groundwater protection and monitoring information; and (6) discuss the activities to ensure quality.« less

  1. Humid site stabilization and closure

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

    Cutshall, N.H.

    1981-01-01

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

  2. Surveying the Commons: Current Implementation of Information Commons Web sites

    ERIC Educational Resources Information Center

    Leeder, Christopher

    2009-01-01

    This study assessed the content of 72 academic library Information Commons (IC) Web sites using content analysis, quantitative assessment and qualitative surveys of site administrators to analyze current implementation by the academic library community. Results show that IC Web sites vary widely in content, design and functionality, with few…

  3. The interaction of APEX1 variant with polycyclic aromatic hydrocarbons on increasing chromosome damage and lung cancer risk among male Chinese.

    PubMed

    Li, Xiaoliang; Wei, Jinyu; Xu, Ping; Yin, Xiangqian; Hu, Die; Zhang, Xiao; Liu, Li; Zhang, Kai; Zhou, Changchun; Wang, Tian; Zhang, Xiaomin; He, Meian; Wu, Tangchun; Yang, Ming; Guo, Huan

    2015-06-01

    Polycyclic aromatic hydrocarbons (PAHs) are the most significant contributors to tobacco-induced lung carcinogenesis. Apurinic/apyrimidinic endonuclease 1 (APE1) is a central enzyme in the removal of apurinic/apyrimidinic sites caused by DNA damaging agents. This study aimed to investigate the potential interaction of APEX1 polymorphisms and PAHs on genetic damage and lung cancer risk among male Chinese. We recruited an occupational cohort of 922 male coke oven workers and determined their DNA damage levels by calculating the lymphocytic micronucleus (MN) frequencies. Two well-studied APEX1 polymorphisms (-307A > C and Asp148Glu) and their associations with MN frequencies were examined. The impact of MN-related single nucleotide polymorphism (SNP) on lung cancer risk was further investigated in two case-control studies including 1634 male lung cancer patients and 1678 controls. It was shown that, the APEX1 148Glu allele was associated with significantly higher MN frequencies than 148Asp allele, with strongest associations among the highest PAH-exposure workers (P = 0.008). The APEX1 148Glu allele was also associated with increased lung cancer risk among male smokers, especially among heavy smokers in both case-control studies (odd ratio: 4.40, 95%CI: 3.29-5.72). In addition, APEX1 148Glu variant interacts with smoking in increasing male lung cancer risk, as measured by the attributable proportion due to interaction, which was 0.23 (95%CI: 0.06-0.39). This study showed evidence on interaction between APEX1 148Glu variant and cigarette smoking in increasing lung cancer susceptibility among male Chinese, which may be due to the synergistic effects of APEX1 148Glu and PAHs in increasing chromosome damage levels. The results provide a new insight into gene-interactions in lung carcinogenesis. © 2014 Wiley Periodicals, Inc.

  4. The Methodology of Interactive Parametric Modelling of Construction Site Facilities in BIM Environment

    NASA Astrophysics Data System (ADS)

    Kozlovská, Mária; Čabala, Jozef; Struková, Zuzana

    2014-11-01

    Information technology is becoming a strong tool in different industries, including construction. The recent trend of buildings designing is leading up to creation of the most comprehensive virtual building model (Building Information Model) in order to solve all the problems relating to the project as early as in the designing phase. Building information modelling is a new way of approaching to the design of building projects documentation. Currently, the building site layout as a part of the building design documents has a very little support in the BIM environment. Recently, the research of designing the construction process conditions has centred on improvement of general practice in planning and on new approaches to construction site layout planning. The state of art in field of designing the construction process conditions indicated an unexplored problem related to connection of knowledge system with construction site facilities (CSF) layout through interactive modelling. The goal of the paper is to present the methodology for execution of 3D construction site facility allocation model (3D CSF-IAM), based on principles of parametric and interactive modelling.

  5. Controlling and fine tuning the physical properties of two identical metal coordination sites in de novo designed three stranded coiled coil peptides.

    PubMed

    Iranzo, Olga; Chakraborty, Saumen; Hemmingsen, Lars; Pecoraro, Vincent L

    2011-01-19

    Herein we report how de novo designed peptides can be used to investigate whether the position of a metal site along a linear sequence that folds into a three-stranded α-helical coiled coil defines the physical properties of Cd(II) ions in either CdS(3) or CdS(3)O (O-being an exogenous water molecule) coordination environments. Peptides are presented that bind Cd(II) into two identical coordination sites that are located at different topological positions at the interior of these constructs. The peptide GRANDL16PenL19IL23PenL26I binds two Cd(II) as trigonal planar 3-coordinate CdS(3) structures whereas GRANDL12AL16CL26AL30C sequesters two Cd(II) as pseudotetrahedral 4-coordinate CdS(3)O structures. We demonstrate how for the first peptide, having a more rigid structure, the location of the identical binding sites along the linear sequence does not affect the physical properties of the two bound Cd(II). However, the sites are not completely independent as Cd(II) bound to one of the sites ((113)Cd NMR chemical shift of 681 ppm) is perturbed by the metalation state (apo or [Cd(pep)(Hpep)(2)](+) or [Cd(pep)(3)](-)) of the second center ((113)Cd NMR chemical shift of 686 ppm). GRANDL12AL16CL26AL30C shows a completely different behavior. The physical properties of the two bound Cd(II) ions indeed depend on the position of the metal center, having pK(a2) values for the equilibrium [Cd(pep)(Hpep)(2)](+) → [Cd(pep)(3)](-) + 2H(+) (corresponding to deprotonation and coordination of cysteine thiols) that range from 9.9 to 13.9. In addition, the L26AL30C site shows dynamic behavior, which is not observed for the L12AL16C site. These results indicate that for these systems one cannot simply assign a "4-coordinate structure" and assume certain physical properties for that site since important factors such as packing of the adjacent Leu, size of the intended cavity (endo vs exo) and location of the metal site play crucial roles in determining the final properties of the bound

  6. MUTATIONS INDUCED BY BENZO[ A ]PYRENE AND DIBENZO[ A,L ]PYRENE IN LACI TRANSGENIC B6C3F1 MOUSE LUNG RESULT FROM STABLE DNA ADDUCTS

    EPA Science Inventory

    Dibenzo[a,l]pyrene (DB[a,l]P) and benzo[a]pyrene (B[a]P) are carcinogenic polycyclic aromatic hydrocarbons (PAH) that are each capable of forming a variety of covalent adducts with DNA, some of which spontaneously depurinate, producing apurinic (AP) si...

  7. Optimization under Uncertainty of Site-Specific Turbine Configurations: Preprint

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

    Quick, Julian; Dykes, Katherine; Graf, Peter

    Uncertainty affects many aspects of wind energy plant performance and cost. In this study, we explore opportunities for site-specific turbine configuration optimization that accounts for uncertainty in the wind resource. As a demonstration, a simple empirical model for wind plant cost of energy is used in an optimization under uncertainty to examine how different risk appetites affect the optimal selection of a turbine configuration for sites of different wind resource profiles. If there is unusually high uncertainty in the site wind resource, the optimal turbine configuration diverges from the deterministic case and a generally more conservative design is obtained withmore » increasing risk aversion on the part of the designer.« less

  8. Informational ergonomics and design: signage design for Monte Sião Camp.

    PubMed

    Marques, Luiz Guilherme Oliveira; Cardoso, Vânia Maria Batalha

    2012-01-01

    This paper refers to the development of a signage system, driven by the vector of Signage Design and Informational Ergonomics associated with Regulatory Standards. The methodology of the Ergonomic Intervention of Moraes and Mont'Alvão (2003), in its early stages, and the Method of the Signage Pyramid of Calori (2007) were used to develop the research, data collection and analysis and to guide the design by a signaling system. The system contemplated by this job is called Mount Zion, a site of 19 hectares, which has signs of disturbance. As a result, we obtained a signaling system, with graphic features that refer to formal-site, capable of meeting the needs of orientation and displacement inherent to the site.

  9. 10 CFR 712.34 - Site Occupational Medical Director.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Site Occupational Medical Director. 712.34 Section 712.34 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.34 Site Occupational Medical Director. (a) The SOMD must nominate a physician to serve as the Designated Physician and a...

  10. 10 CFR 712.34 - Site Occupational Medical Director.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Site Occupational Medical Director. 712.34 Section 712.34 Energy DEPARTMENT OF ENERGY HUMAN RELIABILITY PROGRAM Medical Standards § 712.34 Site Occupational Medical Director. (a) The SOMD must nominate a physician to serve as the Designated Physician and a...

  11. Nevada National Security Site Environmental Report 2016, Attachment A: Site Description

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

    Wills, Cathy

    This attachment expands on the general description of the Nevada National Security Site (NNSS) presented in the Introduction to the Nevada National Security Site Environmental Report 2016 (prepared by National Security Technologies, LLC [NSTec], 2017). Included are subsections that summarize the site’s geological, hydrological, climatological, and ecological settings and the cultural resources of the NNSS. The subsections are meant to aid the reader in understanding the complex physical and biological environment of the NNSS. An adequate knowledge of the site’s environment is necessary to assess the environmental impacts of new projects, design and implement environmental monitoring activities for current sitemore » operations, and assess the impacts of site operations on the public residing in the vicinity of the NNSS. The NNSS environment contributes to several key features of the site that afford protection to the inhabitants of adjacent areas from potential exposure to radioactivity or other contaminants resulting from NNSS operations. These key features include the general remote location of the NNSS, restricted access, extended wind transport times, the great depths to slow-moving groundwater, little or no surface water, and low population density. This attachment complements the annual summary of monitoring program activities and dose assessments presented in the main body of this report.« less

  12. CEO Sites Mission Management System (SMMS)

    NASA Technical Reports Server (NTRS)

    Trenchard, Mike

    2014-01-01

    Late in fiscal year 2011, the Crew Earth Observations (CEO) team was tasked to upgrade its science site database management tool, which at the time was integrated with the Automated Mission Planning System (AMPS) originally developed for Earth Observations mission planning in the 1980s. Although AMPS had been adapted and was reliably used by CEO for International Space Station (ISS) payload operations support, the database structure was dated, and the compiler required for modifications would not be supported in the Windows 7 64-bit operating system scheduled for implementation the following year. The Sites Mission Management System (SMMS) is now the tool used by CEO to manage a heritage Structured Query Language (SQL) database of more than 2,000 records for Earth science sites. SMMS is a carefully designed and crafted in-house software package with complete and detailed help files available for the user and meticulous internal documentation for future modifications. It was delivered in February 2012 for test and evaluation. Following acceptance, it was implemented for CEO mission operations support in April 2012. The database spans the period from the earliest systematic requests for astronaut photography during the shuttle era to current ISS mission support of the CEO science payload. Besides logging basic image information (site names, locations, broad application categories, and mission requests), the upgraded database management tool now tracks dates of creation, modification, and activation; imagery acquired in response to requests; the status and location of ancillary site information; and affiliations with studies, their sponsors, and collaborators. SMMS was designed to facilitate overall mission planning in terms of site selection and activation and provide the necessary site parameters for the Satellite Tool Kit (STK) Integrated Message Production List Editor (SIMPLE), which is used by CEO operations to perform daily ISS mission planning. The CEO team

  13. DECISION ANALYSIS OF INCINERATION COSTS IN SUPERFUND SITE REMEDIATION

    EPA Science Inventory

    This study examines the decision-making process of the remedial design (RD) phase of on-site incineration projects conducted at Superfund sites. Decisions made during RD affect the cost and schedule of remedial action (RA). Decision analysis techniques are used to determine the...

  14. Characteristics of Food Industry Web Sites and "Advergames" Targeting Children

    ERIC Educational Resources Information Center

    Culp, Jennifer; Bell, Robert A.; Cassady, Diana

    2010-01-01

    Objective: To assess the content of food industry Web sites targeting children by describing strategies used to prolong their visits and foster brand loyalty; and to document health-promoting messages on these Web sites. Design: A content analysis was conducted of Web sites advertised on 2 children's networks, Cartoon Network and Nickelodeon. A…

  15. An alternate binding site for PPARγ ligands

    PubMed Central

    Hughes, Travis S.; Giri, Pankaj Kumar; de Vera, Ian Mitchelle S.; Marciano, David P.; Kuruvilla, Dana S.; Shin, Youseung; Blayo, Anne-Laure; Kamenecka, Theodore M.; Burris, Thomas P.; Griffin, Patrick R.; Kojetin, Douglas J.

    2014-01-01

    PPARγ is a target for insulin sensitizing drugs such as glitazones, which improve plasma glucose maintenance in patients with diabetes. Synthetic ligands have been designed to mimic endogenous ligand binding to a canonical ligand-binding pocket to hyperactivate PPARγ. Here we reveal that synthetic PPARγ ligands also bind to an alternate site, leading to unique receptor conformational changes that impact coregulator binding, transactivation and target gene expression. Using structure-function studies we show that alternate site binding occurs at pharmacologically relevant ligand concentrations, and is neither blocked by covalently bound synthetic antagonists nor by endogenous ligands indicating non-overlapping binding with the canonical pocket. Alternate site binding likely contributes to PPARγ hyperactivation in vivo, perhaps explaining why PPARγ full and partial or weak agonists display similar adverse effects. These findings expand our understanding of PPARγ activation by ligands and suggest that allosteric modulators could be designed to fine tune PPARγ activity without competing with endogenous ligands. PMID:24705063

  16. Site characterization and analysis penetrometer system

    NASA Astrophysics Data System (ADS)

    Heath, Jeff

    1995-04-01

    The site characterization and analysis penetrometer system (SCAPS) with laser induced fluorescence (LIF) sensors is being demonstrated as a quick field screening technique to determine the physical and chemical characteristics of subsurface soil and contaminants at hazardous waste sites SCAPS is a collaborative development effort of the Navy, Army, and Air Force under the Tri-Service SCAPS Program. The current SCAPS configuration is designed to quickly and cost-effectively distinguish areas contaminated with petroleum products (hydrocarbons) from unaffected areas.

  17. Concepts & Procedures. [SITE 2002 Section].

    ERIC Educational Resources Information Center

    Sarner, Ronald, Ed.; Mullick, Rosemary J., Ed.; Bauder, Deborah Y., Ed.

    This document contains the following full and short papers on concepts and procedures from the SITE (Society for Information Technology & Teacher Education) 2002 conference: "Exploring Minds Network" (Marino C. Alvarez and others); "Learning Communities: A Kaleidoscope of Ecological Designs" (Alain Breuleux and others);…

  18. Translating access into utilization: lessons from the design and evaluation of a health insurance Web site to promote reproductive health care for young women in Massachusetts.

    PubMed

    Janiak, Elizabeth; Rhodes, Elizabeth; Foster, Angel M

    2013-12-01

    Following state-level health care reform in Massachusetts, young women reported confusion over coverage of contraception and other sexual and reproductive health services under newly available health insurance products. To address this gap, a plain-language Web site titled "My Little Black Book for Sexual Health" was developed by a statewide network of reproductive health stakeholders. The purpose of this evaluation was to assess the health literacy demands and usability of the site among its target audience, women ages 18-26 years. We performed an evaluation of the literacy demands of the Web site's written content and tested the Web site's usability in a health communications laboratory. Participants found the Web site visually appealing and its overall design concept accessible. However, the Web site's literacy demands were high, and all participants encountered problems navigating through the Web site. Following this evaluation, the Web site was modified to be more usable and more comprehensible to women of all health literacy levels. To avail themselves of sexual and reproductive health services newly available under expanded health insurance coverage, young women require customized educational resources that are rigorously evaluated to ensure accessibility. To maximize utilization of reproductive health services under expanded health insurance coverage, US women require customized educational resources commensurate with their literacy skills. The application of established research methods from the field of health communications will enable advocates to evaluate and adapt these resources to best serve their targeted audiences. © 2013.

  19. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Attachment 4, Water resources protection strategy

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

    Not Available

    1991-12-01

    To achieve compliance with the proposed US Environmental Protection Agency (EPA) groundwater protection standards (Subpart A of 40 CFR 192), 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 (Cliff House/Menefee aquifer) at the point of compliance (POC) at the Uranium Mill Tailings Remedial Action (UMTRA) Project disposal site in Bodo Canyon near Durango, Colorado (DOE, 1989). Details of hydrologic site characterization at the disposal site are provided in Attachment 3, Groundwater Hydrology Report. The principal features of the water resources protectionmore » strategy for the Bodo Canyon disposal site are presented in this document.« less

  20. 10 CFR 100.10 - Factors to be considered when evaluating sites.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Section 100.10 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) REACTOR SITE CRITERIA Evaluation Factors for Stationary Power Reactor Site Applications Before January 10, 1997 and for Testing Reactors § 100... include those relating both to the proposed reactor design and the characteristics peculiar to the site...

  1. 10 CFR 100.10 - Factors to be considered when evaluating sites.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Section 100.10 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) REACTOR SITE CRITERIA Evaluation Factors for Stationary Power Reactor Site Applications Before January 10, 1997 and for Testing Reactors § 100... include those relating both to the proposed reactor design and the characteristics peculiar to the site...

  2. Surface Sites for Engineering Allosteric Control in Proteins

    PubMed Central

    Lee, Jeeyeon; Natarajan, Madhusudan; Nashine, Vishal C.; Socolich, Michael; Vo, Tina; Russ, William P.; Benkovic, Stephen J.; Ranganathan, Rama

    2010-01-01

    Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the activity of one protein might control the activity of the other. We tested this idea by creating PAS-DHFR, a designed chimeric protein that connects a light-sensing signaling domain from a plant member of the Per/Arnt/Sim (PAS) family of proteins with Escherichia coli dihydrofolate reductase (DHFR). With no optimization, PAS-DHFR exhibited light-dependent catalytic activity that depended on the site of connection and on known signaling mechanisms in both proteins. PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites. PMID:18927392

  3. Evidence for the binding of the carcinogen 3-methylcholanthrene to both the purine and the pyrimidine bases of hamster fibroblast deoxyribonucleic acid (Short Communication)

    PubMed Central

    Jones, Peter A.; Gevers, Wieland; Hawtrey, Arthur O.

    1973-01-01

    The binding of [3H]3-methylcholanthrene to the DNA of hamster fibroblasts was studied by using chemical methods for DNA degradation. DNA depurinated by mild acid hydrolysis released approximately half of the radioactivity at the same rate as the purine bases, but the resulting apurinic acid still contained radioactive carcinogen. PMID:4797167

  4. THE OHIO RIVER BASIN ENERGY FACILITY SITING MODEL. VOLUME II: SITES AND ON-LINE DATES

    EPA Science Inventory

    The report was prepared as part of the Ohio River Basin Energy Study (ORBES), a multidisciplinary policy research program. The siting model developed for ORBES is specifically designed for regional policy analysis. The region includes 423 counties in an area that consists of all ...

  5. Site scientific mission plan for the Southern Great Plains CART site, January-June 1995

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

    Schneider, J.M.; Lamb, P.J.; Sisterson, D.L.

    1994-12-01

    The Southern Great Plains (SGP) Cloud and Radiation Testbed (CART) site is designed to help satisfy the data needs of the Atmospheric Measurement (ARM) Program Science Team. This document defines the scientific priorities for site activities during the six months beginning on January 1, 1995, and also looks forward in lesser detail to subsequent six-month periods. The primary purpose of this Site Scientific Mission Plan is to provide guidance for the development of plans for site operations. It also provides information on current plans to the ARM functional teams (Management Team, Experiment Support Team [EST], Operations Team, Data Management Teammore » [DMT], Instrument Team [IT], and Campaign Team) and serves to disseminate the plans more generally within the ARM Program and among the members of the Science Team. This document includes a description of the operational status of the site and the primary envisaged site activities, together with information concerning approved and proposed Intensive Observation Periods (IOPs). Amendments will be prepared and distributed whenever the content changes by more than 30% within a six-month period. The primary users of this document are the site operator, the site scientist, the Science Team through the ARM Program Science Director, The ARM Program Experiment Center, and the aforementioned ARM Program functional teams. This plan is a living document that will be updated and reissued every six months as the observational facilities are developed, tested, and augmented and as priorities are adjusted in response to developments in scientific planning and understanding.« less

  6. OTEC riser cable system, Phase II: conceptual design

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

    Not Available

    1980-10-01

    Studies are summarized of conceptual designs of riser cable systems for OTEC pilot plants of both the spar and plantship configurations located at sites off the southeast coast of Puerto Rico. The studies utilize a baseline pilot plant riser cable, the design of which has been developed and reported on in other reports. Baseline riser cable systems for OTEC pilot plants are identified, system hardware consistent with these designs are conceptualized, and comparisons of the various system concepts are provided. It is concluded that there are three riser cable systems feasible for a spar pilot plant platform at the Puntamore » Yeguas site, and two riser cable systems feasible at the plantship pilot plant at the Punta Tuna site. Recommendations for further investigations in the areas of materials, hardware design and pre-installation site surveys are also addressed.« less

  7. Development of a laboratory niche Web site.

    PubMed

    Dimenstein, Izak B; Dimenstein, Simon I

    2013-10-01

    This technical note presents the development of a methodological laboratory niche Web site. The "Grossing Technology in Surgical Pathology" (www.grossing-technology.com) Web site is used as an example. Although common steps in creation of most Web sites are followed, there are particular requirements for structuring the template's menu on methodological laboratory Web sites. The "nested doll principle," in which one object is placed inside another, most adequately describes the methodological approach to laboratory Web site design. Fragmentation in presenting the Web site's material highlights the discrete parts of the laboratory procedure. An optimally minimal triad of components can be recommended for the creation of a laboratory niche Web site: a main set of media, a blog, and an ancillary component (host, contact, and links). The inclusion of a blog makes the Web site a dynamic forum for professional communication. By forming links and portals, cloud computing opens opportunities for connecting a niche Web site with other Web sites and professional organizations. As an additional source of information exchange, methodological laboratory niche Web sites are destined to parallel both traditional and new forms, such as books, journals, seminars, webinars, and internal educational materials. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. SP-100 ground engineering system test site description and progress update

    NASA Astrophysics Data System (ADS)

    Baxter, William F.; Burchell, Gail P.; Fitzgibbon, Davis G.; Swita, Walter R.

    1991-01-01

    The SP-100 Ground Engineering System Test Site will provide the facilities for the testing of an SP-100 reactor, which is technically prototypic of the generic design for producing 100 kilowatts of electricity. This effort is part of the program to develop a compact, space-based power system capable of producing several hundred kilowatts of electrical power. The test site is located on the U.S. Department of Energy's Hanford Site near Richland, Washington. The site is minimizing capital equipment costs by utilizing existing facilities and equipment to the maximum extent possible. The test cell is located in a decommissioned reactor containment building, and the secondary sodium cooling loop will use equipment from the Fast Flux Test Facility plant which has never been put into service. Modifications to the facility and special equipment are needed to accommodate the testing of the SP-100 reactor. Definitive design of the Ground Engineering System Test Site facility modifications and systems is in progress. The design of the test facility and the testing equipment will comply with the regulations and specifications of the U.S. Department of Energy and the State of Washington.

  9. Checklist for Design of Vertical Barrier Walls for Hazardous Waste Sites

    DTIC Science & Technology

    1996-06-30

    Sites. ETL 1110-2-282 ETL 1110-2-282, Rock Mass Classification Data Requirements for Rippability . EPA/530/R-93/001 EPA/530/R-93/001, RCRA Ground-Water...discontinuities, rock hardness, and rippability . (3) Hydrology. In addition to understanding the geology, it is imperative to have an understanding of the

  10. Relations Between Residential Proximity to EPA-Designated Toxic Release Sites and Diffuse Large B-Cell Lymphoma Incidence.

    PubMed

    Bulka, Catherine; Nastoupil, Loretta J; Koff, Jean L; Bernal-Mizrachi, Leon; Ward, Kevin C; Williams, Jessica N; Bayakly, A Rana; Switchenko, Jeffrey M; Waller, Lance A; Flowers, Christopher R

    2016-10-01

    Examining the spatial patterns of diffuse large B-cell lymphoma (DLBCL) incidence and residential proximity to toxic release locations may provide insight regarding environmental and sociodemographic risk factors. We linked and geocoded cancer incidence data for the period 1999-2008 from the Georgia Comprehensive Cancer Registry with population data from the US Census and the Environmental Protection Agency's Toxics Release Inventory. We conducted cluster analyses and constructed Poisson regression models to assess DLBCL incidence as a function of mean distance to the toxic release sites. In total, 3851 incident DLBCL cases occurred among adults residing in Georgia between 1999 and 2008. Significant focal clustering was observed around 57% of ethylene oxide sites, 5% of benzene sites, 9% of tetrachloroethylene sites, 7% of styrene sites, 10% of formaldehyde sites, 5% of trichloroethylene sites, and 10% of all release sites. Mean distance to sites was significantly associated with DLBCL risk for all chemicals. Proximity to Toxics Release Inventory sites can be linked to increased DLBCL risk as assessed through focal clustering and Poisson regression, and confirmatory studies using geospatial mapping can aid in further specifying risk factors for DLBCL.

  11. Recent Progress in the Design and Discovery of RXR Modulators Targeting Alternate Binding Sites of the Receptor.

    PubMed

    Su, Ying; Zeng, Zhiping; Chen, Ziwen; Xu, Dan; Zhang, Weidong; Zhang, Xiao-Kun

    2017-01-01

    Retinoid X receptors (RXRs) occupy a central position within the nuclear receptor superfamily. They not only function as important transcriptional factors but also exhibit diverse nongenomic biological activities. The pleiotropic actions of RXRs under both physiological and pathophysiological conditions confer RXRs important drug targets for the treatment of cancer, and metabolic and neurodegenerative diseases. RXR modulators have been studied for the purpose of developing both drug molecules and chemical tools for biological investigation of RXR. Development of RXR modulators has focused on small molecules targeting the canonical ligand-binding pocket. However, accumulating results have demonstrated that there are other binding mechanisms by which small molecules interact with RXR to act as RXR modulators. This review discusses the recent development in the design and discovery of RXR modulators with a focus on those targeting novel binding sites on RXR.

  12. Formerly Utilized Sites Remedial Action Program (FUSRAP) Hazelwood Interim Storage Site annual site environmental report. Calendar year 1985. [FUSRAP

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

    Not Available

    1986-04-01

    The Hazelwood Interim Storage Site (HISS) is presently used for the storage of low-level radioactively contaminated soils. Monitoring results show that the HISS is in compliance with DOE concentration guides and radiation protection standards. Derived Concentration Guides (DCGs) represent the concentrations of radionuclides in air or water that would limit the radiation dose to 100 mrem/y. The applicable limits have been revised since the 1984 environmental monitoring report was published. The limits applied in 1984 were based on a radiation protection standard of 500 mrem/y; the limits applied for 1985 are based on a standard of 100 mrem/y. The HISSmore » is part of the Formerly Utilized Sites Remedial Action Program (FUSRAP), a DOE program to decontaminate or otherwise control sites where low-level radioactive contamination remains from the early years of the nation's atomic energy program. To determine whether the site is in compliance with DOE standards, environmental measurements are expressed as percentages of the applicable DCG, while the calculated doses to the public are expressed as percentages of the applicable radiation protection standard. The monitoring program at the HISS measures uranium, radium, and thorium concentrations in surface water, groundwater, and sediment; radon gas concentrations in air; and external gamma radiation exposure rates. Potential radiation doses to the public are also calculated. The HISS was designated for remedial action under FUSRAP because radioactivity above applicable limits was found to exist at the site and its vicinity. Elevated levels of radiation still exist in areas where remedial action has not yet been completed.« less

  13. Social media and patient self-management: not all sites are created equal.

    PubMed

    Ellis, Leonie; Showell, Chris; Turner, Paul

    2013-01-01

    This paper compares two social media sites that aim to support patients to enhance self-management. The first site, PatientsLikeMe is a well established global site designed to allow peer-to-peer communication between people with similar conditions. The second, HealthShare, is a recently developed site for Australians described as "Australia's Social Health Network". The comparison conducted examines the purpose, ownership, and design of both sites as well as how the data they collect is used. Analysis highlights that PatientsLikeMe actively facilitates patient self-management, while HealthShare is revealed to be a professionally moderated health information portal presented as a social networking site. While the impetus for the development of PatientsLikeMe is clear, the motives underpinning HealthShare are less obvious. With increasing patient interest in connecting with, and sharing information with one another, awareness of the nature and motivations underpinning sites that provide these services is of increasing relevance.

  14. 40 CFR 228.6 - Specific criteria for site selection.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Specific criteria for site selection. 228.6 Section 228.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN... designation promulgation as an environmental assessment of the impact of the use of the site for disposal, and...

  15. 40 CFR 228.5 - General criteria for the selection of sites.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... levels or to undetectable contaminant concentrations or effects before reaching any beach, shoreline..., designate ocean dumping sites beyond the edge of the continental shelf and other such sites that have been...

  16. 40 CFR 228.5 - General criteria for the selection of sites.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... levels or to undetectable contaminant concentrations or effects before reaching any beach, shoreline..., designate ocean dumping sites beyond the edge of the continental shelf and other such sites that have been...

  17. 40 CFR 228.5 - General criteria for the selection of sites.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... levels or to undetectable contaminant concentrations or effects before reaching any beach, shoreline..., designate ocean dumping sites beyond the edge of the continental shelf and other such sites that have been...

  18. 40 CFR 228.5 - General criteria for the selection of sites.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... levels or to undetectable contaminant concentrations or effects before reaching any beach, shoreline..., designate ocean dumping sites beyond the edge of the continental shelf and other such sites that have been...

  19. 40 CFR 228.5 - General criteria for the selection of sites.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... levels or to undetectable contaminant concentrations or effects before reaching any beach, shoreline..., designate ocean dumping sites beyond the edge of the continental shelf and other such sites that have been...

  20. BENZO[ A ]PYRENE-7,8-QUINONE FORMS COVALENT-DNA ADDUCTS IN VITRO BUT NONE WERE DETECTED IN THE LUNGS OR LIVERS OF STRAIN A/J MICE IN VIVO

    EPA Science Inventory

    Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of B[a]P-7,8-diol-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: 1.] The induction of apurinic si...

  1. Designing a New Urban Internet.

    ERIC Educational Resources Information Center

    Burke, Lauren

    2002-01-01

    Discusses Web site design and information architecture in light of principles of New Urbanism that are being applied in urban planning situations. Topics include networked electronic environment design; user-centered network design; multidisciplinary approaches; knowledge access and collaboration; and the Global Information Infrastructure…

  2. 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

  3. St. Louis Airport Site. Annual site environmental report, calendar year 1985. Formerly Utilized Sites Remedial Action Program (FUSRAP). Revision 1

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

    Not Available

    1986-09-01

    During 1985, the environmental monitoring program was continued at the St. Louis Airport Site (SLAPS) in St. Louis County, Missouri. The ditches north and south of the site have been designated for cleanup as part of the Formerly Utilized Sites Remedial Action Program (FUSRAP). The monitoring program at the SLAPS measures radon gas concentrations in air; external gamma radiation dose rates; and uranium, thorium, and radium concentrations in surface water, groundwater, and sediment. Potential radiation doses to the public are also calculated. Because the site is not controlled or regulated by the DOE, the DOE Derived Concentration Guides (DCGs) aremore » not applicable to SLAPS, but are included only as a basis for comparison. The DOE DCGs and the DOE radiation protection standard have been revised. (Appendix B). During 1985, annual average radon levels in air at the SLAPS were below the DCG for uncontrolled areas. External gamma monitoring in 1985 showed measured annual gamma dose rates ranging from 3 to 2087 mrem/y, with the highest value occurring in an area known to be contaminated. The calculated maximum dose at the site boundary, assuming limited occupancy, would be 6 mrem/y. Average annual concentrations of /sup 230/Th, /sup 226/Ra, and total uranium in surface waters remained below the DOE DCG. The on-site groundwater measurements showed that average annual concentrations of /sup 230/Th, /sup 226/Ra and total uranium were within the DOE DCGs. Although there are no DCGs for sediments, all concentrations of total uraniu, /sup 230/Th, and /sup 226/Ra were below the FUSRAP Guidelines.« less

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

    ERIC Educational Resources Information Center

    Wassom, Julie

    2002-01-01

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

  5. Yucca Mountain Project Subsurface Facilities Design

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

    A. Linden; R.S. Saunders; R.J. Boutin

    2002-11-19

    Four units of the Topopah Springs formation (volcanic tuff) are considered for the proposed repository: the upper lithophysal, the middle non-lithophysal, the lower lithophysal, and the lower non-lithophysal. Yucca Mountain was recently designated the site for a proposed repository to dispose of spent nuclear fuel and high-level radioactive waste. Work is proceeding to advance the design of subsurface facilities to accommodate emplacing waste packages in the proposed repository. This paper summarized recent progress in the design of subsurface layout of the proposed repository. The original Site Recommendation (SR) concept for the subsurface design located the repository largely within the lowermore » lithophysal zone (approximately 73%) of the Topopah The Site Recommendation characterized area suitable for emplacement consisted of the primary upper block, the lower block and the southern upper block extension. The primary upper block accommodated the mandated 70,000 metric tons of heavy metal (MTHM) at a 1.45 kW/m hear heat load. Based on further study of the Site Recommendation concept, the proposed repository siting area footprint was modified to make maximum use of available site characterization data, and thus, reduce uncertainties associated with performance assessment. As a result of this study, a modified repository footprint has been proposed and is presently being review for acceptance by the DOE. A panel design concept was developed to reduce overall costs and reduce the overall emplacement schedule. This concept provides flexibility to adjust the proposed repository subsurface layout with time, as it makes it unnecessary to ''commit'' to development of a large single panel at the earliest stages of construction. A description of the underground layout configuration and influencing factors that affect the layout configuration are discussed in the report.« less

  6. Comparison of the active-site design of molybdenum oxo-transfer enzymes by quantum mechanical calculations.

    PubMed

    Li, Jilai; Ryde, Ulf

    2014-11-17

    There are three families of mononuclear molybdenum enzymes that catalyze oxygen atom transfer (OAT) reactions, named after a typical example from each family, viz., dimethyl sulfoxide reductase (DMSOR), sulfite oxidase (SO), and xanthine oxidase (XO). These families differ in the construction of their active sites, with two molybdopterin groups in the DMSOR family, two oxy groups in the SO family, and a sulfido group in the XO family. We have employed density functional theory calculations on cluster models of the active sites to understand the selection of molybdenum ligands in the three enzyme families. Our calculations show that the DMSOR active site has a much stronger oxidative power than the other two sites, owing to the extra molybdopterin ligand. However, the active sites do not seem to have been constructed to make the OAT reaction as exergonic as possible, but instead to keep the reaction free energy close to zero (to avoid excessive loss of energy), thereby making the reoxidation (SO and XO) or rereduction of the active sites (DMSOR) after the OAT reaction facile. We also show that active-site models of the three enzyme families can all catalyze the reduction of DMSO and that the DMSOR model does not give the lowest activation barrier. Likewise, all three models can catalyze the oxidation of sulfite, provided that the Coulombic repulsion between the substrate and the enzyme model can be overcome, but for this harder reaction, the SO model gives the lowest activation barrier, although the differences are not large. However, only the XO model can catalyze the oxidation of xanthine, owing to its sulfido ligand.

  7. DeepSite: protein-binding site predictor using 3D-convolutional neural networks.

    PubMed

    Jiménez, J; Doerr, S; Martínez-Rosell, G; Rose, A S; De Fabritiis, G

    2017-10-01

    An important step in structure-based drug design consists in the prediction of druggable binding sites. Several algorithms for detecting binding cavities, those likely to bind to a small drug compound, have been developed over the years by clever exploitation of geometric, chemical and evolutionary features of the protein. Here we present a novel knowledge-based approach that uses state-of-the-art convolutional neural networks, where the algorithm is learned by examples. In total, 7622 proteins from the scPDB database of binding sites have been evaluated using both a distance and a volumetric overlap approach. Our machine-learning based method demonstrates superior performance to two other competitive algorithmic strategies. DeepSite is freely available at www.playmolecule.org. Users can submit either a PDB ID or PDB file for pocket detection to our NVIDIA GPU-equipped servers through a WebGL graphical interface. gianni.defabritiis@upf.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. Efficiency of Fiscal Allocations in Site-Based Empowered Schools

    ERIC Educational Resources Information Center

    Meyer, Jerome Jay

    2011-01-01

    This study implemented a two phase concurrent mixed-methods design to generate a greater understanding of how elementary schools with increased autonomy in fiscal decision making allocated their money, how their site-based decisions affected allocative efficiency, and how increased autonomy affected site-based decision making when compared with a…

  9. Seismic design parameters - A user guide

    USGS Publications Warehouse

    Leyendecker, E.V.; Frankel, A.D.; Rukstales, K.S.

    2001-01-01

    The 1997 NEHRP Recommended Provisions for Seismic Regulations for New Buildings (1997 NEHRP Provisions) introduced seismic design procedure that is based on the explicit use of spectral response acceleration rather than the traditional peak ground acceleration and/or peak ground velocity or zone factors. The spectral response accelerations are obtained from spectral response acceleration maps accompanying the report. Maps are available for the United States and a number of U.S. territories. Since 1997 additional codes and standards have also adopted seismic design approaches based on the same procedure used in the NEHRP Provisions and the accompanying maps. The design documents using the 1997 NEHRP Provisions procedure may be divided into three categories -(1) Design of New Construction, (2) Design and Evaluation of Existing Construction, and (3) Design of Residential Construction. A CD-ROM has been prepared for use in conjunction with the design documents in each of these three categories. The spectral accelerations obtained using the software on the CD are the same as those that would be obtained by using the maps accompanying the design documents. The software has been prepared to operate on a personal computer using a Windows (Microsoft Corporation) operating environment and a point and click type of interface. The user can obtain the spectral acceleration values that would be obtained by use of the maps accompanying the design documents, include site factors appropriate for the Site Class provided by the user, calculate a response spectrum that includes the site factor, and plot a response spectrum. Sites may be located by providing the latitude-longitude or zip code for all areas covered by the maps. All of the maps used in the various documents are also included on the CDROM

  10. Making Web Sites Work for People with Disabilities.

    ERIC Educational Resources Information Center

    Foster, Andrea L.

    2001-01-01

    Demands from students with disabilities and regulations from the federal government are prompting colleges to seek new designs in software and hardware. Many colleges are buying computer workstations and designing Web sites that meet the needs of students with disabilities. The university's attitude and organization tends to be the main stumbling…

  11. A Multi-site, Two-Phase, Prescription Opioid Addiction Treatment Study (POATS): Rationale, Design, and Methodology

    PubMed Central

    Weiss, Roger D.; Potter, Jennifer Sharpe; Provost, Scott E.; Huang, Zhen; Jacobs, Petra; Hasson, Albert; Lindblad, Robert; Connery, Hilary Smith; Prather, Kristi; Ling, Walter

    2010-01-01

    The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age ≥18 who met Diagnostic and Statistical Manual, 4th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4 weeks of bup/nx treatment, including a 14-day dose taper, with 8 weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12 weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12 weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8 weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study. PMID:20116457

  12. A multi-site, two-phase, Prescription Opioid Addiction Treatment Study (POATS): rationale, design, and methodology.

    PubMed

    Weiss, Roger D; Potter, Jennifer Sharpe; Provost, Scott E; Huang, Zhen; Jacobs, Petra; Hasson, Albert; Lindblad, Robert; Connery, Hilary Smith; Prather, Kristi; Ling, Walter

    2010-03-01

    The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age > or =18 who met Diagnostic and Statistical Manual, 4th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4 weeks of bup/nx treatment, including a 14-day dose taper, with 8 weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12 weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12 weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8 weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study. Copyright 2010 Elsevier Inc. All rights reserved.

  13. Molecular insights of protein contour recognition with ligand pharmacophoric sites through combinatorial library design and MD simulation in validating HTLV-1 PR inhibitors.

    PubMed

    Selvaraj, Chandrabose; Omer, Ankur; Singh, Poonam; Singh, Sanjeev Kumar

    2015-01-01

    Retroviruses HIV-1 and HTLV-1 are chiefly considered to be the most dangerous pathogens in Homo sapiens. These two viruses have structurally unique protease (PR) enzymes, which are having common function of its replication mechanism. Though HIV PR drugs failed to inhibit HTLV-1 infections, they emphatically emphasise the need for designing new lead compounds against HTLV-1 PR. Therefore, we tried to understand the binding level interactions through the charge environment present in both ligand and protein active sites. The domino effect illustrates that libraries of purvalanol-A are attuned to fill allosteric binding site of HTLV-1 PR through molecular recognition and shows proper binding of ligand pharmacophoric features in receptor contours. Our screening evaluates seven compounds from purvalanol-A libraries, and these compounds' pharmacophore searches for an appropriate place in the binding site and it places well according to respective receptor contour surfaces. Thus our result provides a platform for the progress of more effective compounds, which are better in free energy calculation, molecular docking, ADME and molecular dynamics studies. Finally, this research provided novel chemical scaffolds for HTLV-1 drug discovery.

  14. Part 2: Conserving and Planting Trees at Development Sites

    Treesearch

    Karen Cappiella; Tom Schueler; Tiffany Wright

    2006-01-01

    This manual presents specific ways to enable developers, engineers or landscape architects to incorporate more trees into a development site. The proposed approach focuses on protecting existing trees, planting trees in storm water treatment practices, and planting trees in other open spaces at the development site. This manual introduces conceptual designs for storm...

  15. 40 CFR 228.11 - Modification in disposal site use.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....11 Section 228.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.11 Modification in disposal site use... designation set forth in this part 228 and will be based on the results of the analyses of impact described in...

  16. 40 CFR 228.11 - Modification in disposal site use.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....11 Section 228.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.11 Modification in disposal site use... designation set forth in this part 228 and will be based on the results of the analyses of impact described in...

  17. 40 CFR 228.11 - Modification in disposal site use.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....11 Section 228.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.11 Modification in disposal site use... designation set forth in this part 228 and will be based on the results of the analyses of impact described in...

  18. 40 CFR 228.11 - Modification in disposal site use.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....11 Section 228.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.11 Modification in disposal site use... designation set forth in this part 228 and will be based on the results of the analyses of impact described in...

  19. 40 CFR 228.11 - Modification in disposal site use.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....11 Section 228.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING CRITERIA FOR THE MANAGEMENT OF DISPOSAL SITES FOR OCEAN DUMPING § 228.11 Modification in disposal site use... designation set forth in this part 228 and will be based on the results of the analyses of impact described in...

  20. A DFT+U study of A-site and B-site substitution in BaFeO3-δ.

    PubMed

    Baiyee, Zarah Medina; Chen, Chi; Ciucci, Francesco

    2015-09-28

    BaFeO3-δ (BFO)-based perovskites have emerged as cheap and effective oxygen electrocatalysts for oxygen reduction reaction at high temperatures. The BFO cubic phase facilitates a high oxygen deficiency and is commonly stabilised by partial substitution. Understanding the electronic mechanisms of substitution and oxygen deficiency is key to rational material design, and can be realised through DFT analysis. In this work an in-depth first principle DFT+U study is undertaken to determine site distinctive characteristics for 12.5%, Y, La and Ce substitutions in BFO. In particular, it is shown that B-site doped structures exhibit a lower energy cost for oxygen vacancy formation relative to A site doping and pristine BFO. This is attributed to the stabilisation of holes in the oxygen sub-lattice and increased covalency of the Fe-O bonds of the FeO6 octahedra in B-site-substituted BFO. Charge analysis shows that A-site substitution amounts to donor doping and consequently impedes the accommodation of other donors (i.e. oxygen vacancies). However, A-site substitution may also exhibit a higher electronic conductivity due to less lattice distortion for oxygen deficiency compared to B-site doped structures. Furthermore, analysis of the local structural effects provides physical insight into stoichiometric expansions observed for this material.

  1. Optimizing Restriction Site Placement for Synthetic Genomes

    NASA Astrophysics Data System (ADS)

    Montes, Pablo; Memelli, Heraldo; Ward, Charles; Kim, Joondong; Mitchell, Joseph S. B.; Skiena, Steven

    Restriction enzymes are the workhorses of molecular biology. We introduce a new problem that arises in the course of our project to design virus variants to serve as potential vaccines: we wish to modify virus-length genomes to introduce large numbers of unique restriction enzyme recognition sites while preserving wild-type function by substitution of synonymous codons. We show that the resulting problem is NP-Complete, give an exponential-time algorithm, and propose effective heuristics, which we show give excellent results for five sample viral genomes. Our resulting modified genomes have several times more unique restriction sites and reduce the maximum gap between adjacent sites by three to nine-fold.

  2. Molecular Determinants of Radio Resistance in Prostate Cancer

    DTIC Science & Technology

    2005-08-01

    Pathway Gene Accession # Ratio H/N Ratio Hypoxia/Normoxla (Log,) NER ERCCt NM001983 1.3 BER APE,2 NM_014481 1.0 MMR PMS2 NM_000535 1.3 HR RAD51...cross-complementing group 1; APEX2, apurinic!apyrimidinic endonuclease/redox factor 2; PMS2 , postmeiotic segregation increased 2; RAD51, RAD51 homolog

  3. Cloud computing for protein-ligand binding site comparison.

    PubMed

    Hung, Che-Lun; Hua, Guan-Jie

    2013-01-01

    The proteome-wide analysis of protein-ligand binding sites and their interactions with ligands is important in structure-based drug design and in understanding ligand cross reactivity and toxicity. The well-known and commonly used software, SMAP, has been designed for 3D ligand binding site comparison and similarity searching of a structural proteome. SMAP can also predict drug side effects and reassign existing drugs to new indications. However, the computing scale of SMAP is limited. We have developed a high availability, high performance system that expands the comparison scale of SMAP. This cloud computing service, called Cloud-PLBS, combines the SMAP and Hadoop frameworks and is deployed on a virtual cloud computing platform. To handle the vast amount of experimental data on protein-ligand binding site pairs, Cloud-PLBS exploits the MapReduce paradigm as a management and parallelizing tool. Cloud-PLBS provides a web portal and scalability through which biologists can address a wide range of computer-intensive questions in biology and drug discovery.

  4. Plasmin substrate binding site cooperativity guides the design of potent peptide aldehyde inhibitors.

    PubMed

    Swedberg, Joakim E; Harris, Jonathan M

    2011-10-04

    Perioperative bleeding is a cause of major blood loss and is associated with increased rates of postoperative morbidity and mortality. To combat this, antifibrinolytic inhibitors of the serine protease plasmin are commonly used to reduce bleeding during surgery. The most effective and previously widely used of these is the broad range serine protease inhibitor aprotinin. However, adverse clinical outcomes have led to use of alternative serine lysine analogues to inhibit plasmin. These compounds suffer from low selectivity and binding affinity. Consequently, a concerted effort to discover potent and selective plasmin inhibitors has developed. This study used a noncombinatorial peptide library to define plasmin's extended substrate specificity and guide the design of potent transition state analogue inhibitors. The various substrate binding sites of plasmin were found to exhibit a higher degree of cooperativity than had previously been appreciated. Peptide sequences capitalizing on these features produced high-affinity inhibitors of plasmin. The most potent of these, Lys-Met(sulfone)-Tyr-Arg-H [KM(O(2))YR-H], inhibited plasmin with a K(i) of 3.1 nM while maintaining 25-fold selectivity over plasma kallikrein. Furthermore, 125 nM (0.16 μg/mL) KM(O(2))YR-H attenuated fibrinolysis in vitro with an efficacy similar to that of 15 nM (0.20 μg/mL) aprotinin. To date, this is the most potent peptide inhibitor of plasmin that exhibits selectivity against plasma kallikrein, making this compound an attractive candidate for further therapeutic development.

  5. 22 CFR 502.3 - Availability of program materials on public Web sites.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... sites. 502.3 Section 502.3 Foreign Relations BROADCASTING BOARD OF GOVERNORS DOMESTIC REQUESTS FOR BROADCASTING BOARD OF GOVERNORS PROGRAM MATERIALS § 502.3 Availability of program materials on public Web sites... information Web sites designed for foreign audiences. To access currently-available Agency program materials...

  6. Mesoscale carbon sequestration site screening and CCS infrastructure analysis.

    PubMed

    Keating, Gordon N; Middleton, Richard S; Stauffer, Philip H; Viswanathan, Hari S; Letellier, Bruce C; Pasqualini, Donatella; Pawar, Rajesh J; Wolfsberg, Andrew V

    2011-01-01

    We explore carbon capture and sequestration (CCS) at the meso-scale, a level of study between regional carbon accounting and highly detailed reservoir models for individual sites. We develop an approach to CO(2) sequestration site screening for industries or energy development policies that involves identification of appropriate sequestration basin, analysis of geologic formations, definition of surface sites, design of infrastructure, and analysis of CO(2) transport and storage costs. Our case study involves carbon management for potential oil shale development in the Piceance-Uinta Basin, CO and UT. This study uses new capabilities of the CO(2)-PENS model for site screening, including reservoir capacity, injectivity, and cost calculations for simple reservoirs at multiple sites. We couple this with a model of optimized source-sink-network infrastructure (SimCCS) to design pipeline networks and minimize CCS cost for a given industry or region. The CLEAR(uff) dynamical assessment model calculates the CO(2) source term for various oil production levels. Nine sites in a 13,300 km(2) area have the capacity to store 6.5 GtCO(2), corresponding to shale-oil production of 1.3 Mbbl/day for 50 years (about 1/4 of U.S. crude oil production). Our results highlight the complex, nonlinear relationship between the spatial deployment of CCS infrastructure and the oil-shale production rate.

  7. Simulations & Case Studies. [SITE 2002 Section].

    ERIC Educational Resources Information Center

    Seymour, Cathy R., Ed.

    This document contains the following papers on simulations and case studies from the SITE (Society for Information Technology & Teacher Education) 2002 conference: "3-D Virtual Classroom Technology" (Kimberly Arseneau Miller, Angela Glod); "Simulated Lesson Design Studios" (Willis Copeland); "Lights, Camera, Integration: Presentation Programs and…

  8. Design approaches in quarrying and pit-mining reclamation

    USGS Publications Warehouse

    Arbogast, Belinda F.

    1999-01-01

    Reclaimed mine sites have been evaluated so that the public, industry, and land planners may recognize there are innovative designs available for consideration and use. People tend to see cropland, range, and road cuts as a necessary part of their everyday life, not as disturbed areas despite their high visibility. Mining also generates a disturbed landscape, unfortunately one that many consider waste until reclaimed by human beings. The development of mining provides an economic base and use of a natural resource to improve the quality of human life. Equally important is a sensitivity to the geologic origin and natural pattern of the land. Wisely shaping out environment requires a design plan and product that responds to a site's physiography, ecology, function, artistic form, and publication perception. An examination of selected sites for their landscape design suggested nine approaches for mining reclamation. The oldest design approach around is nature itself. Humans may sometimes do more damage going to an area in the attempt to repair it. Given enough geologic time, a small-site area, and stable adjacent ecosystems, disturbed areas recover without mankind's input. Visual screens and buffer zones conceal the facility in a camouflage approach. Typically, earth berms, fences, and plantings are used to disguise the mining facility. Restoration targets social or economic benefits by reusing the site for public amenities, most often in urban centers with large populations. A mitigation approach attempts to protect the environment and return mined areas to use with scientific input. The reuse of cement, building rubble, macadam meets only about 10% of the demand from aggregate. Recognizing the limited supply of mineral resources and encouraging recycling efforts are steps are steps in a renewable resource approach. An educative design approach effectively communicates mining information through outreach, land stewardship, and community service. Mine sites used for

  9. A GIS-Interface Web Site: Exploratory Learning for Geography Curriculum

    ERIC Educational Resources Information Center

    Huang, Kuo Hung

    2011-01-01

    Although Web-based instruction provides learners with sufficient resources for self-paced learning, previous studies have confirmed that browsing navigation-oriented Web sites possibly hampers users' comprehension of information. Web sites designed as "categories of materials" for navigation demand more cognitive effort from users to orient their…

  10. Estimation of empirical site amplification factors in Taiwan

    NASA Astrophysics Data System (ADS)

    Chung, Chi-Hsuan; Wen, Kuo-Liang; Kuo, Chun-Hsiang

    2017-04-01

    Lots of infrastructures are under construction in metropolises in Taiwan in recent years and thus leads to increasement of population density and urbanization in those area. Taiwan island is located in plate boundaries in which the high seismicity is caused by active tectonic plates. The Chi-Chi earthquake (Mw 7.6) in 1999 caused a fatality of more than 2000, and the Meinong earthquake (Mw 6.5) in 2016 caused a fatality of 117 in Tainan city as well as damages on hundreds of buildings. The cases imply seismic vulnerability of urban area. During the improvements for seismic hazard analysis and seismic design, consideration of seismic site amplifications in different site conditions is one of important issues. This study used selected and processed strong motion records observed by the TSMIP network. The site conditions considered as Vs30 used in this study were investigated at most stations (Kuo et al. 2012; Kuo et al. 2016). Since strong motion records and site conditions are both available, we are able to use the data to analyze site amplifications of seismic waves at different periods. The result may be a reference for future modification of seismic design codes to decrease potential seismic hazards and losses. We adopted the strong motion and site database of the SSHAC (Senior Seismic Hazard Analysis Committee) Level 3 project in Taiwan. The selected significant crustal and subduction events of magnitude larger than six for analysis. The amplification factors of PGA, PGV, PGD, and spectra acceleration at 0.3, 1.0, and 3.0 seconds were evaluated using the processed strong motions. According to the recommendation of SSHAC Level 3 project, the site condition of Vs30 = 760 m/s is considered as the reference rock site in this study. The stations with Vs30 between 600 m/s and 900 m/s and used as the reference rock sites in reality. For each event, we find a reference rock site and other site within a certain distance (region dependent) to calculate site amplifications

  11. The 50 Constellation Priority Sites

    NASA Technical Reports Server (NTRS)

    Noble, S.; Joosten, K.; Eppler, D.; Gruener, J.; Mendell, W.; French, R.; Plescia, J.; Spudis, P.; Wargo, M.; Robinson, M.; hide

    2009-01-01

    The Constellation program (CxP) has developed a list of 50 sites of interest on the Moon which will be targeted by the LRO narrow angle camera. The list has also been provided to the M team to supplement their targeting list. This list does not represent a "site selection" process; rather the goal was to find "representative" sites and terrains to understand the range of possible surface conditions for human lunar exploration to aid engineering design and operational planning. The list compilers leveraged heavily on past site selection work (e.g. Geoscience and a Lunar Base Workshop - 1988, Site Selection Strategy for a Lunar Outpost - 1990, Exploration Systems Architecture Study (ESAS) - 2005). Considerations included scientific, resource utilization, and operational merits, and a desire to span lunar terrain types. The targets have been organized into two "tiers" of 25 sites each to provide a relative priority ranking in the event of mutual interference. A LEAG SAT (special action team) was established to validate and recommend modifications to the list. This SAT was chaired by Dr. Paul Lucey. They provided their final results to CxP in May. Dr. Wendell Mendell will organize an on-going analysis of the data as they come down to ensure data quality and determine if and when a site has sufficient data to be retired from the list. The list was compiled using the best available data, however, it is understood that with the flood of new lunar data, minor modifications or adjustments may be required.

  12. 1001 Best Internet Sites for Educators. 2nd Edition.

    ERIC Educational Resources Information Center

    Treadwell, Mark

    This second edition of a resource designed to help teachers find relevant information on the Internet for both themselves and their students, provides concise reviews of more than 1,000 Web sites sorted by subject area. Each site is evaluated with one to five stars for content, presentation and grade level. Easy-to-follow explanations are provided…

  13. Guidelines for Interpretive Building Design.

    ERIC Educational Resources Information Center

    Manly, Richard J., Ed.

    This booklet is intended to assist those planning nature centers to choose building designs appropriate for intended purposes. The publication presents a set of general interpretive building-site and design considerations compiled over years of experience in nature center design. These generalizations are complemented by examples of floor plans,…

  14. De Novo Enzyme Design Using Rosetta3

    PubMed Central

    Richter, Florian; Leaver-Fay, Andrew; Khare, Sagar D.; Bjelic, Sinisa; Baker, David

    2011-01-01

    The Rosetta de novo enzyme design protocol has been used to design enzyme catalysts for a variety of chemical reactions, and in principle can be applied to any arbitrary chemical reaction of interest, The process has four stages: 1) choice of a catalytic mechanism and corresponding minimal model active site, 2) identification of sites in a set of scaffold proteins where this minimal active site can be realized, 3) optimization of the identities of the surrounding residues for stabilizing interactions with the transition state and primary catalytic residues, and 4) evaluation and ranking the resulting designed sequences. Stages two through four of this process can be carried out with the Rosetta package, while stage one needs to be done externally. Here, we demonstrate how to carry out the Rosetta enzyme design protocol from start to end in detail using for illustration the triosephosphate isomerase reaction. PMID:21603656

  15. Thermodynamic Characterization of Hydration Sites from Integral Equation-Derived Free Energy Densities: Application to Protein Binding Sites and Ligand Series.

    PubMed

    Güssregen, Stefan; Matter, Hans; Hessler, Gerhard; Lionta, Evanthia; Heil, Jochen; Kast, Stefan M

    2017-07-24

    Water molecules play an essential role for mediating interactions between ligands and protein binding sites. Displacement of specific water molecules can favorably modulate the free energy of binding of protein-ligand complexes. Here, the nature of water interactions in protein binding sites is investigated by 3D RISM (three-dimensional reference interaction site model) integral equation theory to understand and exploit local thermodynamic features of water molecules by ranking their possible displacement in structure-based design. Unlike molecular dynamics-based approaches, 3D RISM theory allows for fast and noise-free calculations using the same detailed level of solute-solvent interaction description. Here we correlate molecular water entities instead of mere site density maxima with local contributions to the solvation free energy using novel algorithms. Distinct water molecules and hydration sites are investigated in multiple protein-ligand X-ray structures, namely streptavidin, factor Xa, and factor VIIa, based on 3D RISM-derived free energy density fields. Our approach allows the semiquantitative assessment of whether a given structural water molecule can potentially be targeted for replacement in structure-based design. Finally, PLS-based regression models from free energy density fields used within a 3D-QSAR approach (CARMa - comparative analysis of 3D RISM Maps) are shown to be able to extract relevant information for the interpretation of structure-activity relationship (SAR) trends, as demonstrated for a series of serine protease inhibitors.

  16. A GIS connection between brownfield sites, transportation and economic development.

    DOT National Transportation Integrated Search

    2011-08-01

    "This report outlines the design and development of a web-based data distribution system for brownfield site redevelopment in Toledo-Lucas County, Ohio. The system is designed to advance smart growth initiatives by creating the link between transport...

  17. The Study Designed by a Committee

    PubMed Central

    Henry, David B.; Farrell, Albert D.

    2009-01-01

    This article describes the research design of the Multisite Violence Prevention Project (MVPP), organized and funded by the National Center for Injury Prevention and Control (NCIPC) at the Centers for Disease Control and Prevention (CDC). CDC's objectives, refined in the course of collaboration among investigators, were to evaluate the efficacy of universal and targeted interventions designed to produce change at the school level. The project's design was developed collaboratively, and is a 2 × 2 cluster-randomized true experimental design in which schools within four separate sites were assigned randomly to four conditions: (1) no-intervention control group, (2) universal intervention, (3) targeted intervention, and (4) combined universal and targeted interventions. A total of 37 schools are participating in this study with 8–12 schools per site. The impact of the interventions on two successive cohorts of sixth-grade students will be assessed based on multiple waves of data from multiple sources of information, including teachers, students, parents, and archival data. The nesting of students within teachers, families, schools and sites created a number of challenges for designing and implementing the study. The final design represents both resolution and compromise on a number of creative tensions existing in large-scale prevention trials, including tensions between cost and statistical power, and between internal and external validity. Strengths and limitations of the final design are discussed. PMID:14732183

  18. Automatic Optimization of Wayfinding Design.

    PubMed

    Huang, Haikun; Lin, Ni-Ching; Barrett, Lorenzo; Springer, Darian; Wang, Hsueh-Cheng; Pomplun, Marc; Yu, Lap-Fai

    2017-10-10

    Wayfinding signs play an important role in guiding users to navigate in a virtual environment and in helping pedestrians to find their ways in a real-world architectural site. Conventionally, the wayfinding design of a virtual environment is created manually, so as the wayfinding design of a real-world architectural site. The many possible navigation scenarios, and the interplay between signs and human navigation, can make the manual design process overwhelming and non-trivial. As a result, creating a wayfinding design for a typical layout can take months to several years. In this paper, we introduce the Way to Go! approach for automatically generating a wayfinding design for a given layout. The designer simply has to specify some navigation scenarios; our approach will automatically generate an optimized wayfinding design with signs properly placed considering human agents' visibility and possibility of making navigation mistakes. We demonstrate the effectiveness of our approach in generating wayfinding designs for different layouts. We evaluate our results by comparing different wayfinding designs and show that our optimized designs can guide pedestrians to their destinations effectively. Our approach can also help the designer visualize the accessibility of a destination from different locations, and correct any "blind zone" with additional signs.

  19. Detection of the CLOCK/BMAL1 heterodimer using a nucleic acid probe with cycling probe technology.

    PubMed

    Nakagawa, Kazuhiro; Yamamoto, Takuro; Yasuda, Akio

    2010-09-15

    An isothermal signal amplification technique for specific DNA sequences, known as cycling probe technology (CPT), has enabled rapid acquisition of genomic information. Here we report an analogous technique for the detection of an activated transcription factor, a transcription element-binding assay with fluorescent amplification by apurinic/apyrimidinic (AP) site lysis cycle (TEFAL). This simple amplification assay can detect activated transcription factors by using a unique nucleic acid probe containing a consensus binding sequence and an AP site, which enables the CPT reaction with AP endonuclease. In this article, we demonstrate that this method detects the functional CLOCK/BMAL1 heterodimer via the TEFAL probe containing the E-box consensus sequence to which the CLOCK/BMAL1 heterodimer binds. Using TEFAL combined with immunoassays, we measured oscillations in the amount of CLOCK/BMAL1 heterodimer in serum-stimulated HeLa cells. Furthermore, we succeeded in measuring the circadian accumulation of the functional CLOCK/BMAL1 heterodimer in human buccal mucosa cells. TEFAL contributes greatly to the study of transcription factor activation in mammalian tissues and cell extracts and is a powerful tool for less invasive investigation of human circadian rhythms. 2010 Elsevier Inc. All rights reserved.

  20. NASA Cold Land Processes Experiment (CLPX 2002/03): Local scale observation site

    Treesearch

    Janet Hardy; Robert Davis; Yeohoon Koh; Don Cline; Kelly Elder; Richard Armstrong; Hans-Peter Marshall; Thomas Painter; Gilles Castres Saint-Martin; Roger DeRoo; Kamal Sarabandi; Tobias Graf; Toshio Koike; Kyle McDonald

    2008-01-01

    The local scale observation site (LSOS) is the smallest study site (0.8 ha) of the 2002/03 Cold Land Processes Experiment (CLPX) and is located within the Fraser mesocell study area. It was the most intensively measured site of the CLPX, and measurements here had the greatest temporal component of all CLPX sites. Measurements made at the LSOS were designed to produce a...

  1. Site action, environmental justice and an urban community: A unique approach at a Superfund site

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

    Seppi, P.K.; Richman, L.R.; Wireman, J.M.

    1994-12-31

    The US Environmental Protection Agency`s (EPA) project at the Diamond Alkali Superfund Site is an example of how technical, environmental justice, and community relations issues all affect actions at a Superfund Site. The Diamond Alkali Superfund Site is divided into two operable units. The site consists of the former pesticides manufacturing facility at 80 and 120 Lister Avenue in Newark, New Jersey, and the adjoining six mile reach of the Passaic River known as the ``Passaic River Study Area``. EPA has negotiated Consent Orders with the Potentially Responsible Party (PRP) to design and construct the selected containment remedy at themore » land-based properties, and to conduct the Remedial Investigation (RI) of the river under EPA oversight. Pesticides, dioxin, polychlorinated biphenyls (PCBs), metals and other hazardous substances have been found at the Site. Evidence indicates that the ecology of the Passaic River has been adversely impacted by the presence of these hazardous substances. The State of New Jersey issued a ban on the consumption of fish and crabs from affected sections of the Passaic River; yet reportedly, many residents still consume seafood from the river. Community relations at the Site had deteriorated because of the community`s lack of trust and loss of confidence in EPA. To address these issues, EPA has implemented an innovative public outreach program to improve how it communicates with racial minority and low-income communities living in the vicinity of the Site, and to involve them in the decision-making process.« less

  2. Decision Support System For Management Of Low-Level Radioactive Waste Disposal At The Nevada Test Site

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

    Shott, G.; Yucel, V.; Desotell, L.

    2006-07-01

    The long-term safety of U.S. Department of Energy (DOE) low-level radioactive disposal facilities is assessed by conducting a performance assessment -- a systematic analysis that compares estimated risks to the public and the environment with performance objectives contained in DOE Manual 435.1-1, Radioactive Waste Management Manual. Before site operations, facilities design features such as final inventory, waste form characteristics, and closure cover design may be uncertain. Site operators need a modeling tool that can be used throughout the operational life of the disposal site to guide decisions regarding the acceptance of problematic waste streams, new disposal cell design, environmental monitoringmore » program design, and final site closure. In response to these needs the National Nuclear Security Administration Nevada Site Office (NNSA/NSO) has developed a decision support system for the Area 5 Radioactive Waste Management Site in Frenchman Flat on the Nevada Test Site. The core of the system is a probabilistic inventory and performance assessment model implemented in the GoldSim{sup R} simulation platform. The modeling platform supports multiple graphic capabilities that allow clear documentation of the model data sources, conceptual model, mathematical implementation, and results. The combined models have the capability to estimate disposal site inventory, contaminant concentrations in environmental media, and radiological doses to members of the public engaged in various activities at multiple locations. The model allows rapid assessment and documentation of the consequences of waste management decisions using the most current site characterization information, radionuclide inventory, and conceptual model. The model is routinely used to provide annual updates of site performance, evaluate the consequences of disposal of new waste streams, develop waste concentration limits, optimize the design of new disposal cells, and assess the adequacy of

  3. 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

  4. Aeromagnetic investigations of hazardous waste sites

    USGS Publications Warehouse

    ,

    1995-01-01

    Aeromagnetic survey data collected by helicopter over hazardous waste sites can be used to map the distribution of buried metallic (ferrous) objects at these sites, including drums and scrap metal. Thorough knowledge of the locations and nature of hazardous waste containers and contaminated objects is needed prior to the start of remediation efforts. Non-invasive geophysical techniques such as the aeromagnetic method provide the best way to obtain this knowledge. The U.S. Geological Survey (USGS) not only has experience in processing and interpreting aeromagnetic surveys of this type but also offers aid in the design and monitoring of contracts for such surveys.

  5. Hanford Site Environmental Report 1993

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

    Dirkes, R.L.; Hanf, R.W.; Woodruff, R.K.

    The Hanford Site Environmental Report is prepared annually to summarize environmental data and information, describe environmental management performance, and demonstrate the status of compliance with environmental regulations. The report also highlights major environmental programs and efforts. The report is written to meet reporting requirements and Guidelines of the U.S. Department of Energy (DOE) an to meet the needs of the public. This summary has been written with a minimum of technical terminology. Individual sections of the report are designed to (a) describe the Hanford Site and its mission, (b) summarize the status in 1993 of compliance with environmental regulations, (c)more » describe the environmental programs at the Hanford Site, (d) discuss estimated radionuclide exposure to the public from 1993 Hanford activities, (e) present information on effluent monitoring and environmental surveillance, including ground-water protection and monitoring, (f) discuss activities to ensure quality. More detailed information can be found in the body of the report, the appendixes, and the cited references.« less

  6. QUESTION--WHAT MAKES A SCHOOL SITE SAFE. ANSWER--DEFINITE PLANNING.

    ERIC Educational Resources Information Center

    GEORGE, N.L.; GILLILAND, LONNIE, SR.

    TWO STAFF MEMBERS FROM A SYSTEM OF PUBLIC SCHOOLS, THE ASSISTANT SUPERINTENDENT, AND THE DIRECTOR OF SAFETY EDUCATION DISCUSSED THE PROBLEMS OF TRAFFIC SAFETY ON AND AROUND THE SCHOOL SITE. FACTORS WHICH WERE CONSIDERED INCLUDE--(1) SCHOOL SITE AND BUILDING LOCATION, (2) SAFETY REQUIREMENTS, PRACTICES AND PRINCIPLES, (3) SIDEWALK DESIGN AND…

  7. VS30, site amplifications and some comparisons: The Adapazari (Turkey) case

    NASA Astrophysics Data System (ADS)

    Ozcep, Tazegul; Ozcep, Ferhat; Ozel, Oguz

    The aim of this study was to investigate the role of VS30 in site amplifications in the Adapazari region, Turkey. To fulfil this aim, amplifications from VS30 measurements were compared with earthquake data for different soil types in the seismic design codes. The Adapazari area was selected as the study area, and shear-wave velocity distribution was obtained by the multichannel analysis of surface waves (MASWs) method at 100 sites for the top 50 m of soil. Aftershock data following the Mw 7.4 Izmit earthquake of 17 August 1999 gave magnitudes between 4.0 and 5.6 at six stations installed in and around the Adapazari Basin, at Babalı, Şeker, Genç, Hastane, Toyota and Imar. This data was used to estimate site amplifications by the reference-station method. In addition, the fundamental periods of the station sites were estimated by the single station method. Site classifications based on VS30 in the seismic design codes were compared with the fundamental periods and amplification values. It was found that site amplifications (from earthquake data) and relevant spectra (from VS30) are not in good agreement for soils in Adapazari (Turkey).

  8. Simulations in site error estimation for direction finders

    NASA Astrophysics Data System (ADS)

    López, Raúl E.; Passi, Ranjit M.

    1991-08-01

    The performance of an algorithm for the recovery of site-specific errors of direction finder (DF) networks is tested under controlled simulated conditions. The simulations show that the algorithm has some inherent shortcomings for the recovery of site errors from the measured azimuth data. These limitations are fundamental to the problem of site error estimation using azimuth information. Several ways for resolving or ameliorating these basic complications are tested by means of simulations. From these it appears that for the effective implementation of the site error determination algorithm, one should design the networks with at least four DFs, improve the alignment of the antennas, and increase the gain of the DFs as much as it is compatible with other operational requirements. The use of a nonzero initial estimate of the site errors when working with data from networks of four or more DFs also improves the accuracy of the site error recovery. Even for networks of three DFs, reasonable site error corrections could be obtained if the antennas could be well aligned.

  9. 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…

  10. A Perioperative Systems Design to Improve Intraoperative Glucose Monitoring Is Associated with a Reduction in Surgical Site Infections in a Diabetic Patient Population.

    PubMed

    Ehrenfeld, Jesse M; Wanderer, Jonathan P; Terekhov, Maxim; Rothman, Brian S; Sandberg, Warren S

    2017-03-01

    recovery room hyperglycemia, and fewer surgical site infections. Their analysis is limited by its applied quasiexperimental design.

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

    PubMed Central

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

    2016-01-01

    In eukaryotes the bimetallic Cu/Zn superoxide dismutase (SOD) enzymes play important roles in the biology of reactive oxygen species by disproportionating superoxide anion. Recently, 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. Despite 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. 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. PMID:27535222

  12. Web Application Design Using Server-Side JavaScript

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

    Hampton, J.; Simons, R.

    1999-02-01

    This document describes the application design philosophy for the Comprehensive Nuclear Test Ban Treaty Research & Development Web Site. This design incorporates object-oriented techniques to produce a flexible and maintainable system of applications that support the web site. These techniques will be discussed at length along with the issues they address. The overall structure of the applications and their relationships with one another will also be described. The current problems and future design changes will be discussed as well.

  13. Assessment of vegetation establishment on tailings dam at an iron ore mining site of suburban Beijing, China, 7 years after reclamation with contrasting site treatment methods.

    PubMed

    Yan, Demin; Zhao, Fangying; Sun, Osbert Jianxin

    2013-09-01

    Strip-mining operations greatly disturb soil, vegetation and landscape elements, causing many ecological and environmental problems. Establishment of vegetation is a critical step in achieving the goal of ecosystem restoration in mining areas. At the Shouyun Iron Ore Mine in suburban Beijing, China, we investigated selective vegetation and soil traits on a tailings dam 7 years after site treatments with three contrasting approaches: (1) soil covering (designated as SC), (2) application of a straw mat, known as "vegetation carpet", which contains prescribed plant seed mix and water retaining agent (designated as VC), on top of sand piles, and (3) combination of soil covering and application of vegetation carpet (designated as SC+VC). We found that after 7 years of reclamation, the SC+VC site had twice the number of plant species and greater biomass than the SC and VC sites, and that the VC site had a comparable plant abundance with the SC+VC site but much less biodiversity and plant coverage. The VC site did not differ with the SC site in the vegetation traits, albeit low soil fertility. It is suggested that application of vegetation carpet can be an alternative to introduction of topsoil for treatment of tailings dam with fine-structured substrate of ore sands. However, combination of topsoil treatment and application of vegetation carpet greatly increases vegetation coverage and plant biodiversity, and is therefore a much better approach for assisting vegetation establishment on the tailings dam of strip-mining operations. While application of vegetation carpet helps to stabilize the loose surface of fine-structured mine wastes and to introduce seed bank, introduction of fertile soil is necessary for supplying nutrients to plant growth in the efforts of ecosystem restoration of mining areas.

  14. Carnegie Science Academy Web Site

    NASA Astrophysics Data System (ADS)

    Kotwicki, John; Atzinger, Joe; Turso, Denise

    1997-11-01

    The Carnegie Science Academy is a professional society "For Teens...By Teens" at the Carnegie Science Center in Pittsburgh. The CSA Web Site [ http://csa.clpgh.org ] is designed for teens who have an interest in science and technology. This online or virtual science academy provides resources for teens in high school science classes. The Web site also allows students around the world to participate and communicate with other students, discuss current events in science, share opinions, find answers to questions, or make online friends. Visitors can enjoy the main components of the site or sign up for a free membership which allows access to our chat room for monthly meeting, online newsletter, members forum, and much more. Main components to the site include a spot for cool links and downloads, available for any visitor to download or view. Online exhibits are created by students to examine and publish an area of study and also allow teachers to easily post classroom activities as exhibits by submitting pictures and text. Random Access, the interactive part of the academy, allows users to share ideas and opinions. Planet CSA focuses on current events in science and the academy. In the future the CSA Web site will become a major resource for teens and science teachers providing materials that will allow students to further enhance their interest and experiences in science.

  15. Orion Entry, Descent, and Landing Performance and Mission Design

    NASA Technical Reports Server (NTRS)

    Broome, Joel M.; Johnson, Wyatt

    2007-01-01

    The Orion Vehicle is the next spacecraft to take humans into space and will include missions to ISS as well as missions to the Moon. As part of that challenge, the vehicle will have to accommodate multiple mission design concepts, since return from Low Earth Orbit and return from the Moon can be quite different. Commonality between the different missions as it relates to vehicle systems, guidance capability, and operations concepts is the goal. Several unique mission design concepts include the specification of multiple land-based landing sites for a vehicle with closed-loop direct and skip entry guidance, followed by a parachute descent and landing attenuation system. This includes the ability of the vehicle to accurately target and land at a designated landing site, including site location aspects, landing site size, and landing opportunities assessments. Analyses associated with these mission design and flight performance challenges and constraints will be discussed as well as potential operational concepts to provide feasibility and/or mission commonality.

  16. 77 FR 20590 - Ocean Dumping; Designation of Ocean Dredged Material Disposal Sites Offshore of Yaquina Bay, OR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-05

    ... Criteria (40 CFR 228.5) 1. Sites must be selected to minimize interference with other activities in the... conflicts. The proposed Sites spatially overlap with recreational activities such as boating and whale... expected to more heavily use areas that are shoreward of the Sites and to focus their activities on Yaquina...

  17. Card-Sorting Usability Tests of the WMU Libraries' Web Site

    ERIC Educational Resources Information Center

    Whang, Michael

    2008-01-01

    This article describes the card-sorting techniques used by several academic libraries, reports and discusses the results of card-sorting usability tests of the Western Michigan University Libraries' Web site, and reveals how the WMU libraries incorporated the findings into a new Web site redesign, setting the design direction early on. The article…

  18. Loblolly Pine Growth 16 Years After Four Site Preparation Treatments

    Treesearch

    John C. Adams; Clyde Vidrine

    2002-01-01

    Thirteen-year growth results of 1-0 planted loblolly pine seedlings (Pinus taeda L.) on differently prepared upland mixed pine-hardwood sites located in north western Louisiana are presented. The study was designed as a randomized complete block consisting of three blocks of four site preparation treatments, which included: chop and burn, windrow,...

  19. Using Dirichlet Processes for Modeling Heterogeneous Treatment Effects across Sites

    ERIC Educational Resources Information Center

    Miratrix, Luke; Feller, Avi; Pillai, Natesh; Pati, Debdeep

    2016-01-01

    Modeling the distribution of site level effects is an important problem, but it is also an incredibly difficult one. Current methods rely on distributional assumptions in multilevel models for estimation. There it is hoped that the partial pooling of site level estimates with overall estimates, designed to take into account individual variation as…

  20. Cloud Computing for Protein-Ligand Binding Site Comparison

    PubMed Central

    2013-01-01

    The proteome-wide analysis of protein-ligand binding sites and their interactions with ligands is important in structure-based drug design and in understanding ligand cross reactivity and toxicity. The well-known and commonly used software, SMAP, has been designed for 3D ligand binding site comparison and similarity searching of a structural proteome. SMAP can also predict drug side effects and reassign existing drugs to new indications. However, the computing scale of SMAP is limited. We have developed a high availability, high performance system that expands the comparison scale of SMAP. This cloud computing service, called Cloud-PLBS, combines the SMAP and Hadoop frameworks and is deployed on a virtual cloud computing platform. To handle the vast amount of experimental data on protein-ligand binding site pairs, Cloud-PLBS exploits the MapReduce paradigm as a management and parallelizing tool. Cloud-PLBS provides a web portal and scalability through which biologists can address a wide range of computer-intensive questions in biology and drug discovery. PMID:23762824

  1. 75 FR 54497 - Ocean Dumping; Guam Ocean Dredged Material Disposal Site Designation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-08

    ... of special scientific importance, and other legitimate uses of the ocean. Minor short-term... option available since 1997. EPA determined that there is a long-term need for an ocean disposal site... Guam and surrounding waters. This is based on the long-term need to support the Naval and commercial...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  3. A Task-oriented Approach for Hydrogeological Site Characterization

    NASA Astrophysics Data System (ADS)

    Rubin, Y.; Nowak, W.; de Barros, F.

    2010-12-01

    Hydrogeological site characterization is a challenging task from several reasons: (1) the large spatial variability and scarcity of prior information render the outcome of any planned sampling campaign uncertain; (2) there are no simple tools for comparing between the many alternative measurement techniques and data acquisition strategies, and (3) physical and budgetary constraints associated with data acquisition. This paper presents several ideas on how to plan sampling campaigns in a rational manner while addressing these challenges. The first idea is to recognize that different sites and different problems require different characterization strategies. Hence the idea is to plan data acquisition according to its capability for meeting site-specific goals. For example, the characterization needs at a “research problem” site (e.g., a site intended to investigate the transport of uranium in the subsurface such as in Hanford) are different from those of a “problem” site (e.g., contaminated site associated with a health risk to human such as Camp Lejeune, or determining the safe yield of an aquifer). This distinction requires planners to define the characterization goal(s) in a quantitative manner. The second idea is to define metrics that could link specific data types and data acquisition strategies with the site-specific goals in a way that would allow planners to compare between strongly different, alternatives strategies at the design stage (even prior to data acquisition) and to modify the strategies as more data become available. To meet this goal, we developed the concept of the (comparative) information yield curve. Finally, we propose to look at site characterization from the perspective of statistical hypothesis testing, whereby data acquisition strategies could be evaluated in terms of their ability to support or refute various hypotheses made with regard to the characterization goals, and the strategies could be modified once the test is

  4. Quantifying and visualizing site performance in clinical trials.

    PubMed

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

    2018-03-01

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

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

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

    Morin, Andrew; Kaufmann, Kristian W.; Fortenberry, Carie

    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 characterizationmore » 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.« less

  6. Influence of gamma-ray skyshine on nuclear facilities design

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

    Ohta, M.; Tsuji, M.; Kimura, Y.

    1986-01-01

    In safety analysis of nuclear facilities, skyshine dose rate at site boundary is one of the most important shielding design problems. For nuclear power stations in Japan, the skyshine dose rate at the site boundary has been specified not to exceed 5 mR/yr by the authorities, including total dose contribution from all structures on site, and this guide is commonly applied to other nuclear fuel cycle facilities. Therefore the design criterion dose of each structure on site is, considering plot planning, shielding condition, and so on, defined as a value <5 mR/yr. The purpose of this study is to investigatemore » how skyshine dose standards or other factors have an influence on the design of nuclear facilities, in a parametric survey of gamma-ray skyshine.« less

  7. Closure Plan for the Area 5 Radioactive Waste Management Site at the Nevada Test Site

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

    NSTec Environmental Management

    The Area 5 Radioactive Waste Management Site (RMWS) at the Nevada Test Site (NTS) is managed and operated by National Security Technologies, LLC (NSTec), for the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO). This document is the first update of the preliminary closure plan for the Area 5 RWMS at the NTS that was presented in the Integrated Closure and Monitoring Plan (DOE, 2005a). The major updates to the plan include a new closure schedule, updated closure inventory, updated site and facility characterization data, the Title II engineering cover design, and the closure processmore » for the 92-Acre Area of the RWMS. The format and content of this site-specific plan follows the Format and Content Guide for U.S. Department of Energy Low-Level Waste Disposal Facility Closure Plans (DOE, 1999a). This interim closure plan meets closure and post-closure monitoring requirements of the order DOE O 435.1, manual DOE M 435.1-1, Title 40 Code of Federal Regulations (CFR) Part 191, 40 CFR 265, Nevada Administrative Code (NAC) 444.743, and Resource Conservation and Recovery Act (RCRA) requirements as incorporated into NAC 444.8632. The Area 5 RWMS accepts primarily packaged low-level waste (LLW), low-level mixed waste (LLMW), and asbestiform low-level waste (ALLW) for disposal in excavated disposal cells.« less

  8. Application for a Permit to Operate a Class III Solid Waste Disposal Site at the Nevada Test Site Area 5 Asbestiform Low-Level Solid Waste Disposal Site

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

    NSTec Environmental Programs

    ''Management Plan for the Disposal of Low-Level Waste with Regulated Asbestos Waste.'' A requirement of the authorization was that on or before October 9, 1999, a permit was required to be issued. Because of NDEP and NNSA/NSO review cycles, the final permit was issued on April 5, 2000, for the operation of the Area 5 Low-Level Waste Disposal Site, utilizing Pit 7 (P07) as the designated disposal cell. The original permit applied only to Pit 7, with a total design capacity of 5,831 cubic yards (yd{sup 3}) (157,437 cubic feet [ft{sup 3}]). NNSA/NSO is expanding the SWDS to include the adjacent Upper Cell of Pit 6 (P06), with an additional capacity of 28,037 yd{sup 3} (756,999 ft{sup 3}) (Figure 3). The proposed total capacity of ALLW in Pit 7 and P06 will be approximately 33,870 yd{sup 3} (0.9 million ft{sup 3}). The site will be used for the disposal of regulated ALLW, small quantities of low-level radioactive hydrocarbon-burdened (LLHB) media and debris, LLW, LLW that contains PCB Bulk Product Waste greater than 50 ppm that leaches at a rate of less than 10 micrograms of PCB per liter of water, and small quantities of LLHB demolition and construction waste (hereafter called permissible waste). Waste containing free liquids, or waste that is regulated as hazardous waste under the Resource Conservation and Recovery Act (RCRA) or state-of-generation hazardous waste regulations, will not be accepted for disposal at the site. The only waste regulated under the Toxic Substances Control Act (TSCA) that will be accepted at the disposal site is regulated asbestos-containing materials (RACM). The term asbestiform is used throughout this document to describe this waste. Other TSCA waste (i.e., polychlorinated biphenyls [PCBs]) will not be accepted for disposal at the SWDS. The disposal site will be used as a depository of permissible waste generated both on site and off site. All generators designated by NNSA/NSO will be eligible to dispose regulated ALLW at the Asbestiform Low

  9. 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

    ... location to dispose of material dredged from the Siuslaw River navigation channel, and to provide a... sediments from Site A back into the dredged channel resulted in a selection of disposal Sites B and C by the... conflicts. The final Sites are located close to the approach to the Siuslaw River entrance channel but are...

  10. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Attachment 3, Groundwater hydrology report. Revised final report

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

    Not Available

    1991-12-01

    The US Environmental Protection Agency (EPA) has established health and environmental protection regulations to correct and prevent groundwater contamination resulting from processing activities at inactive uranium milling sites. According to the Uranium Mill Tailings Radiation Control Act of 1978, (UMTRCA) the US Department of Energy (DOE) is responsible for assessing the inactive uranium processing sites. The DOE has determined this assessment shall include information on hydrogeologic site characterization. The water resources protection strategy that describes how the proposed action will comply with the EPA groundwater protection standards is presented in Attachment 4. Site characterization activities discussed in this section include:more » Characterization of the hydrogeologic environment; characterization of existing groundwater quality; definition of physical and chemical characteristics of the potential contaminant source; and description of local water resources.« less

  11. Students as Web Site Authors: Effects on Motivation and Achievement

    ERIC Educational Resources Information Center

    Jones, Brett D.

    2003-01-01

    This study examined the effects of a Web site design project on students' motivation and achievement. Tenth-grade biology students worked together in teams on an ecology project that required them to locate relevant information on the Internet, decide which information should be included on their Web site, organize the information into Web pages,…

  12. Building Student-Centered Web Sites in the K12 Classroom.

    ERIC Educational Resources Information Center

    Hall, Alison; Basile, Brigitte

    This paper examines the process of constructing a student-centered World Wide Web site and provides recommendations for improving this process. In the project, preservice teachers instructed the fifth grade students about how to design and develop a Web site on weather. The topics of the sessions included Internet ethics, using the Web,…

  13. The problem of site variation within red pine provenance experiments

    Treesearch

    Mark J. Holst

    1966-01-01

    In spite of care taken in the selection of site and experimental design of provenance experiments, site heterogenity within the experimental area may be more complex than was anticipated when the experiment was established. The present paper describes a problem of this nature encountered in a red pine (Pinus resinosa Ait.) provenance experiment at...

  14. Data Gaps in Remedial Design (USACE)

    EPA Pesticide Factsheets

    As the number of Supertund sites In the phases of Remedial Design (RD) and Remedial Action (RA) has grown. we have become increasingly aware of the adverse effects of inadequate or insufficient design data.

  15. 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

  16. A Site to Behold: Creating Curricula about Local Urban Environmental Art.

    ERIC Educational Resources Information Center

    Thurber, Frances E.

    1997-01-01

    Describes "Site Omaha" an interactive public arts project designed to explore alternative art venues in the urban environment and to create a common link between artists and other community members. "Site Omaha" initiated innovative community arts projects. Provides a brief overview of urban environmental art. (MJP)

  17. Resolving protein structure-function-binding site relationships from a binding site similarity network perspective.

    PubMed

    Mudgal, Richa; Srinivasan, Narayanaswamy; Chandra, Nagasuma

    2017-07-01

    Functional annotation is seldom straightforward with complexities arising due to functional divergence in protein families or functional convergence between non-homologous protein families, leading to mis-annotations. An enzyme may contain multiple domains and not all domains may be involved in a given function, adding to the complexity in function annotation. To address this, we use binding site information from bound cognate ligands and catalytic residues, since it can help in resolving fold-function relationships at a finer level and with higher confidence. A comprehensive database of 2,020 fold-function-binding site relationships has been systematically generated. A network-based approach is employed to capture the complexity in these relationships, from which different types of associations are deciphered, that identify versatile protein folds performing diverse functions, same function associated with multiple folds and one-to-one relationships. Binding site similarity networks integrated with fold, function, and ligand similarity information are generated to understand the depth of these relationships. Apart from the observed continuity in the functional site space, network properties of these revealed versatile families with topologically different or dissimilar binding sites and structural families that perform very similar functions. As a case study, subtle changes in the active site of a set of evolutionarily related superfamilies are studied using these networks. Tracing of such similarities in evolutionarily related proteins provide clues into the transition and evolution of protein functions. Insights from this study will be helpful in accurate and reliable functional annotations of uncharacterized proteins, poly-pharmacology, and designing enzymes with new functional capabilities. Proteins 2017; 85:1319-1335. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Dancing in Place: Site-Specific Work

    ERIC Educational Resources Information Center

    Metal-Corbin, Josie

    2012-01-01

    In her lecture the 2012 NDA Scholar/Artist, Josie Metal-Corbin, chronicles four decades of working with artists, educators, librarians, and scientists. The kinetic language of dance and the visual impact of specific environments provide provocative opportunities for collaboration, wherein the site becomes the framework or map for the dance design.…

  19. Participant Observation, Anthropology Methodology and Design Anthropology Research Inquiry

    ERIC Educational Resources Information Center

    Gunn, Wendy; Løgstrup, Louise B.

    2014-01-01

    Within the design studio, and across multiple field sites, the authors compare involvement of research tools and materials during collaborative processes of designing. Their aim is to trace temporal dimensions (shifts/ movements) of where and when learning takes place along different sites of practice. They do so by combining participant…

  20. AutoSite: an automated approach for pseudo-ligands prediction—from ligand-binding sites identification to predicting key ligand atoms

    PubMed Central

    Ravindranath, Pradeep Anand; Sanner, Michel F.

    2016-01-01

    Motivation: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. Results: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand. In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. Availability and Implementation: http://adfr.scripps.edu/AutoDockFR/autosite.html Contact: sanner@scripps.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354702

  1. Design tradeoffs for trend assessment in aquatic biological monitoring programs

    USGS Publications Warehouse

    Gurtz, Martin E.; Van Sickle, John; Carlisle, Daren M.; Paulsen, Steven G.

    2013-01-01

    Assessments of long-term (multiyear) temporal trends in biological monitoring programs are generally undertaken without an adequate understanding of the temporal variability of biological communities. When the sources and levels of variability are unknown, managers cannot make informed choices in sampling design to achieve monitoring goals in a cost-effective manner. We evaluated different trend sampling designs by estimating components of both short- and long-term variability in biological indicators of water quality in streams. Invertebrate samples were collected from 32 sites—9 urban, 6 agricultural, and 17 relatively undisturbed (reference) streams—distributed throughout the United States. Between 5 and 12 yearly samples were collected at each site during the period 1993–2008, plus 2 samples within a 10-week index period during either 2007 or 2008. These data allowed calculation of four sources of variance for invertebrate indicators: among sites, among years within sites, interaction among sites and years (site-specific annual variation), and among samples collected within an index period at a site (residual). When estimates of these variance components are known, changes to sampling design can be made to improve trend detection. Design modifications that result in the ability to detect the smallest trend with the fewest samples are, from most to least effective: (1) increasing the number of years in the sampling period (duration of the monitoring program), (2) decreasing the interval between samples, and (3) increasing the number of repeat-visit samples per year (within an index period). This order of improvement in trend detection, which achieves the greatest gain for the fewest samples, is the same whether trends are assessed at an individual site or an average trend of multiple sites. In multiple-site surveys, increasing the number of sites has an effect similar to that of decreasing the sampling interval; the benefit of adding sites is greater when

  2. PRO_LIGAND: An approach to de novo molecular design. 4. Application to the design of peptides

    NASA Astrophysics Data System (ADS)

    Frenkel, David; Clark, David E.; Li, Jin; Murray, Christopher W.; Robson, Barry; Waszkowycz, Bohdan; Westhead, David R.

    1995-06-01

    In some instances, peptides can play an important role in the discovery of lead compounds. This paper describes the peptide design facility of the de novo drug design package, PRO_LIGAND. The package provides a unified framework for the design of peptides that are similar or complementary to a specified target. The approach uses single amino acid residues, selected from preconstructed libraries of different residues and conformations, and places them on top of predefined target interaction sites. This approach is a well-tested methodology for the design of organics but has not been used for peptides before. Peptides represent a difficulty because of their great conformational flexibility and a study of the advantages and disavantages of this simple approach is an important step in the development of design tools. After a description of our general approach, a more detailed discussion of its adaptation to peptides is given. The method is then applied to the design of peptide-based inhibitors to HIV-1 protease and the design of structural mimics of the surface region of lysozyme. The results are encouraging and point the way towards further development of interaction site-based approaches for peptide design.

  3. U.S. EPA SITE DEMONSTRATION OF AWD TECHNOLOGIES, INC AQUADETOX/SVE SYSTEM

    EPA Science Inventory

    Under the Superfund Innovation TechnologyEvaluation (SITE) Program, a technology developed by AWD Technologies, Inc. was demonstrated in September 1990. This paper presents the major results of the SITE demonstration of AWD Technologies" AquaDetox/SVE Treatment system designed f...

  4. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Attachment 4, Water resources protection strategy. Revised final report

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

    Not Available

    1991-12-01

    To achieve compliance with the proposed US Environmental Protection Agency (EPA) groundwater protection standards (Subpart A of 40 CFR 192), 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 (Cliff House/Menefee aquifer) at the point of compliance (POC) at the Uranium Mill Tailings Remedial Action (UMTRA) Project disposal site in Bodo Canyon near Durango, Colorado (DOE, 1989). Details of hydrologic site characterization at the disposal site are provided in Attachment 3, Groundwater Hydrology Report. The principal features of the water resources protectionmore » strategy for the Bodo Canyon disposal site are presented in this document.« less

  5. 10 CFR 100.20 - Factors to be considered when evaluating sites.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 2 2012-01-01 2012-01-01 false Factors to be considered when evaluating sites. 100.20 Section 100.20 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) REACTOR SITE CRITERIA Evaluation Factors... analysis or that may have an impact upon plant design (such as maximum probable wind speed and...

  6. 10 CFR 100.20 - Factors to be considered when evaluating sites.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Factors to be considered when evaluating sites. 100.20 Section 100.20 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) REACTOR SITE CRITERIA Evaluation Factors... analysis or that may have an impact upon plant design (such as maximum probable wind speed and...

  7. 10 CFR 100.20 - Factors to be considered when evaluating sites.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Factors to be considered when evaluating sites. 100.20 Section 100.20 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) REACTOR SITE CRITERIA Evaluation Factors... analysis or that may have an impact upon plant design (such as maximum probable wind speed and...

  8. Mojo Hand, a TALEN design tool for genome editing applications.

    PubMed

    Neff, Kevin L; Argue, David P; Ma, Alvin C; Lee, Han B; Clark, Karl J; Ekker, Stephen C

    2013-01-16

    Recent studies of transcription activator-like (TAL) effector domains fused to nucleases (TALENs) demonstrate enormous potential for genome editing. Effective design of TALENs requires a combination of selecting appropriate genetic features, finding pairs of binding sites based on a consensus sequence, and, in some cases, identifying endogenous restriction sites for downstream molecular genetic applications. We present the web-based program Mojo Hand for designing TAL and TALEN constructs for genome editing applications (http://www.talendesign.org). We describe the algorithm and its implementation. The features of Mojo Hand include (1) automatic download of genomic data from the National Center for Biotechnology Information, (2) analysis of any DNA sequence to reveal pairs of binding sites based on a user-defined template, (3) selection of restriction-enzyme recognition sites in the spacer between the TAL monomer binding sites including options for the selection of restriction enzyme suppliers, and (4) output files designed for subsequent TALEN construction using the Golden Gate assembly method. Mojo Hand enables the rapid identification of TAL binding sites for use in TALEN design. The assembly of TALEN constructs, is also simplified by using the TAL-site prediction program in conjunction with a spreadsheet management aid of reagent concentrations and TALEN formulation. Mojo Hand enables scientists to more rapidly deploy TALENs for genome editing applications.

  9. Recognition of functional sites in protein structures.

    PubMed

    Shulman-Peleg, Alexandra; Nussinov, Ruth; Wolfson, Haim J

    2004-06-04

    Recognition of regions on the surface of one protein, that are similar to a binding site of another is crucial for the prediction of molecular interactions and for functional classifications. We first describe a novel method, SiteEngine, that assumes no sequence or fold similarities and is able to recognize proteins that have similar binding sites and may perform similar functions. We achieve high efficiency and speed by introducing a low-resolution surface representation via chemically important surface points, by hashing triangles of physico-chemical properties and by application of hierarchical scoring schemes for a thorough exploration of global and local similarities. We proceed to rigorously apply this method to functional site recognition in three possible ways: first, we search a given functional site on a large set of complete protein structures. Second, a potential functional site on a protein of interest is compared with known binding sites, to recognize similar features. Third, a complete protein structure is searched for the presence of an a priori unknown functional site, similar to known sites. Our method is robust and efficient enough to allow computationally demanding applications such as the first and the third. From the biological standpoint, the first application may identify secondary binding sites of drugs that may lead to side-effects. The third application finds new potential sites on the protein that may provide targets for drug design. Each of the three applications may aid in assigning a function and in classification of binding patterns. We highlight the advantages and disadvantages of each type of search, provide examples of large-scale searches of the entire Protein Data Base and make functional predictions.

  10. Statistical activities during 1976 and the design and initial analysis of nuclear site studies. [/sup 241/Am, /sup 137/Cs, /sup 239/Pu, /sup 240/Pu

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

    Gilbert, R O; Essington, E H; Brady, D N

    Statistical design and analysis activities for the Nevada Applied Ecology Group (NAEG) during 1976 are briefly outlined. This is followed by a description of soil data collected thus far at nuclear study sites. Radionuclide concentrations in surface soil collected along a transect from ground zero (GZ) along the main fallout pattern are given for Nuclear Site (NS) 201. Concentrations in soil collected at 315 locations on a grid system at 200 foot spacings are also given for this site. The /sup 241/Am to /sup 137/Cs ratios change over NS 201 depending on location relative to GZ. They range from lessmore » than one where /sup 241/Am is at low levels, to more than fifty where /sup 241/Am levels are high (near GZ). The estimated median /sup 239/ /sup 240/Pu to /sup 241/Am ratio is 11 and appears to be relatively constant over the area (the 95 percent lower and upper limits on the true median ratio are about 8 and 14).« less

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

    PubMed

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

    2017-03-08

    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.

  12. Discriminative structural approaches for enzyme active-site prediction.

    PubMed

    Kato, Tsuyoshi; Nagano, Nozomi

    2011-02-15

    Predicting enzyme active-sites in proteins is an important issue not only for protein sciences but also for a variety of practical applications such as drug design. Because enzyme reaction mechanisms are based on the local structures of enzyme active-sites, various template-based methods that compare local structures in proteins have been developed to date. In comparing such local sites, a simple measurement, RMSD, has been used so far. This paper introduces new machine learning algorithms that refine the similarity/deviation for comparison of local structures. The similarity/deviation is applied to two types of applications, single template analysis and multiple template analysis. In the single template analysis, a single template is used as a query to search proteins for active sites, whereas a protein structure is examined as a query to discover the possible active-sites using a set of templates in the multiple template analysis. This paper experimentally illustrates that the machine learning algorithms effectively improve the similarity/deviation measurements for both the analyses.

  13. How Accessible Are Public Libraries' Web Sites? A Study of Georgia Public Libraries

    ERIC Educational Resources Information Center

    Ingle, Emma; Green, Ravonne A.; Huprich, Julia

    2009-01-01

    One issue that public librarians must consider when planning Web site design is accessibility for patrons with disabilities. This article reports a study of Web site accessibility of public libraries in Georgia. The focus of the report is whether public libraries use accessible guidelines and standards in making their Web sites accessible. An…

  14. SABER: A computational method for identifying active sites for new reactions

    PubMed Central

    Nosrati, Geoffrey R; Houk, K N

    2012-01-01

    A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644–1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were l-Ala d/l-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. PMID:22492397

  15. SABER: a computational method for identifying active sites for new reactions.

    PubMed

    Nosrati, Geoffrey R; Houk, K N

    2012-05-01

    A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644-1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were L-Ala D/L-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. Copyright © 2012 The Protein Society.

  16. ELECTROFISHING IN BOATABLE RIVERS: DOES SAMPLING DESIGN AFFECT BIOASSESSMENT METRICS?

    EPA Science Inventory

    Data were collected from 60 boatable sites using an electrofishing design that permitted comparisons of the effects of designs and distances on fish assemblage metrics. Sites were classified a priori as Run-of-the-River (ROR) or Restricted Flow (RF). Data representing four diff...

  17. Design Your Own Opera!... Online!

    ERIC Educational Resources Information Center

    Nardo, Rachel

    2010-01-01

    This article discusses how to design an opera on the internet and introduces a site that offers the educational keys to the musical kingdom when it comes to unlocking a child's interest in opera. The combination of attractive, animated artwork, fun interactivity, and sound musical learning make this site very useful in a general music classroom.…

  18. Green Power Partnership Top 30 On-site Generation

    EPA Pesticide Factsheets

    EPA's Green Power Partnership is a voluntary program designed to reduce the environmental impact of electricity generation by promoting renewable energy. These partners are generating and consuming the most green power on-site within the GPP.

  19. Web site access statistics and delivery of research results

    Treesearch

    Daniel L. Schmoldt; Matthew F. Winn; Philip A. Araman

    1998-01-01

    For the past 2-1/2 years, our Research Work Unit (RWU) has been operating a Web site (http://www.se4702.forprod.vt.edu). The site became operational in October 1995. In the beginning, it was primarily designed to stake out a piece of the Internet with our name and our RWU’s organizational mission. Quickly, it became apparent to us, however, that our user community...

  20. Designing Hypercontextualized Games: A Case Study with LieksaMyst

    ERIC Educational Resources Information Center

    Sedano, Carolina Islas; Sutinen, Erkki; Vinni, Mikko; Laine, Teemu H.

    2012-01-01

    Digital technology empowers one to access vast amounts of on-line data. From a learning perspective, however, it is difficult to access meaningful on-site information within a given context. The Hypercontextualized Game (HCG) design model interweaves on-site resources, translated as content, and the digital game. As a local game design process,…

  1. Analogue Study of Actinide Transport at Sites in Russia

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

    Novikov, A P; Simmons, A M; Halsey, W G

    2003-02-12

    The U. S. Department of Energy (DOE) and the Russian Academy of Sciences (RAS) are engaged in a three-year cooperative study to observe the behavior of actinides in the natural environment at selected disposal sites and/or contamination sites in Russia. The purpose is to develop experimental data and models for actinide speciation, mobilization and transport processes in support of geologic repository design, safety and performance analyses. Currently at the mid-point of the study, the accomplishments to date include: evaluation of existing data and data needs, site screening and selection, initial data acquisition, and development of preliminary conceptual models.

  2. Fuzzy logic controllers for electrotechnical devices - On-site tuning approach

    NASA Astrophysics Data System (ADS)

    Hissel, D.; Maussion, P.; Faucher, J.

    2001-12-01

    Fuzzy logic offers nowadays an interesting alternative to the designers of non linear control laws for electrical or electromechanical systems. However, due to the huge number of tuning parameters, this kind of control is only used in a few industrial applications. This paper proposes a new, very simple, on-site tuning strategy for a PID-like fuzzy logic controller. Thanks to the experimental designs methodology, we will propose sets of optimized pre-established settings for this kind of fuzzy controllers. The proposed parameters are only depending on one on-site open-loop identification test. In this way, this on-site tuning methodology has to be compared to the Ziegler-Nichols one's for conventional controllers. Experimental results (on a permanent magnets synchronous motor and on a DC/DC converter) will underline all the efficiency of this tuning methodology. Finally, the field of validity of the proposed pre-established settings will be given.

  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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. 10 CFR 100.20 - Factors to be considered when evaluating sites.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... analysis or that may have an impact upon plant design (such as maximum probable wind speed and... for Stationary Power Reactor Site Applications on or After January 10, 1997 § 100.20 Factors to be... determining the acceptability of a site for a stationary power reactor: (a) Population density and use...

  5. 10 CFR 100.20 - Factors to be considered when evaluating sites.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... analysis or that may have an impact upon plant design (such as maximum probable wind speed and... for Stationary Power Reactor Site Applications on or After January 10, 1997 § 100.20 Factors to be... determining the acceptability of a site for a stationary power reactor: (a) Population density and use...

  6. The New Bedford Harbor Superfund Site Long Term Monitoring Program (1993-2009)

    EPA Science Inventory

    New Bedford Harbor (NBH), located in southeastern Massachusetts, was designated as a marine Superfund site in 1983 due to sediment contamination by polychlorinated biphenyls (PCBs). Based on risks to human health and the environment, the first two phases of the site cleanup invo...

  7. Constraints and Approach for Selecting the Mars Surveyor '01 Landing Site

    NASA Technical Reports Server (NTRS)

    Golombek, M.; Bridges, N.; Gilmore, M.; Haldemann, A.; Parker, T.; Saunders, R.; Spencer, D.; Smith, J.; Weitz, C.

    1999-01-01

    There are many similarities between the Mars Surveyor '01 (MS '01) landing site selection process and that of Mars Pathfinder. The selection process includes two parallel activities in which engineers define and refine the capabilities of the spacecraft through design, testing and modeling and scientists define a set of landing site constraints based on the spacecraft design and landing scenario. As for Pathfinder, the safety of the site is without question the single most important factor, for the simple reason that failure to land safely yields no science and exposes the mission and program to considerable risk. The selection process must be thorough and defensible and capable of surviving multiple withering reviews similar to the Pathfinder decision. On Pathfinder, this was accomplished by attempting to understand the surface properties of sites using available remote sensing data sets and models based on them. Science objectives are factored into the selection process only after the safety of the site is validated. Finally, as for Pathfinder, the selection process is being done in an open environment with multiple opportunities for community involvement including open workshops, with education and outreach opportunities.

  8. Constraints, Approach, and Status of Mars Surveyor 2001 Landing Site Selection

    NASA Technical Reports Server (NTRS)

    Golombek, M.; Bridges, N.; Briggs, G.; Gilmore, M.; Haldemann, A.; Parker, T.; Saunders, R.; Spencer, D.; Smith, J.; Soderblom, L.

    1999-01-01

    There are many similarities between the Mars Surveyor '01 (MS '01) landing site selection process and that of Mars Pathfinder. The selection process includes two parallel activities in which engineers define and refine the capabilities of the spacecraft through design, testing and modeling and scientists define a set of landing site constraints based on the spacecraft design and landing scenario. As for Pathfinder, the safety of the site is without question the single most important factor, for the simple reason that failure to land safely yields no science and exposes the mission and program to considerable risk. The selection process must be thorough and defensible and capable of surviving multiple withering reviews similar to the Pathfinder decision. On Pathfinder, this was accomplished by attempting to understand the surface properties of sites using available remote sensing data sets and models based on them. Science objectives are factored into the selection process only after the safety of the site is validated. Finally, as for Pathfinder, the selection process is being done in an open environment with multiple opportunities for community involvement including open workshops, with education and outreach opportunities. Additional information is contained in the original extended abstract.

  9. Converting an intranet site to the cloud: using CampusGuides to refresh a library portal.

    PubMed

    Osterhaus Trzasko, Leah C; Farrell, Ann M; Rethlefsen, Melissa L

    2012-01-01

    After a major redesign project in 2002, Mayo Clinic Libraries' heavily used intranet portal remained largely static. Library staff were unable to make substantive design changes or introduce tools that would make the content more dynamic. CampusGuides offered a practical, user-friendly, web-based solution to add dynamic content to the library site. A task force was formed both to establish design and style guidelines that would integrate with the library site and to plan the conversion of content to CampusGuides. Converting intranet site content to CampusGuides gave the task force the opportunity to examine, re-imagine, and revitalize site content.

  10. ON-SITE CAVITY LOCATION-SEISMIC PROFILING AT NEVADA TEST SITE

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

    Forbes, C.B.; Peterson, R.A.; Heald, C.L.

    1961-10-25

    Experimental seismic studies were conducted at the Nevada Test Site for the purpose of designing and evaluating the most promising seismic techniques for on-site inspection. Post-explosion seismic profiling was done in volcanic tuff in the vicinity of the Rainier and Blanca underground explosions. Pre-explosion seismic profiling was done over granitic rock outcrops in the Climax Stock area, and over tuff at proposed location for Linen and Orchid. Near surface velocity profiling techniques based on measurements of seismic time-distance curves gave evidence of disturbances in near surface rock velocities over the Rainier and Refer als0 to abstract 30187. Blanca sites. Thesemore » disturbances appear to be related to near surface fracturing and spallation effects resulting from the reflection of the original intense compression wave pulse at the near surface as a tension pulse. Large tuned seismometer arrays were used for horizontal seismic ranging in an attempt to record back-scattered'' or reflected seismic waves from subsurface cavities or zones of rock fracturing around the underground explosions. Some possible seismic events were recorded from the near vicinities of the Rainier and Blanca sites. However, many more similar events were recorded from numerous other locations, presumably originating from naturally occurring underground geological features. No means was found for discriminating between artificial and natural events recorded by horizontal seismic ranging, and the results were, therefore, not immediately useful for inspection purposes. It is concluded that in some instances near surface velocity profiling methods may provide a useful tool in verifying the presence of spalled zones above underground nuclear explosion sites. In the case of horizontal seismic ranging it appears that successful application would require development of satisfactory means for recognition of and discrimination against seismic responses to naturally occurring geological

  11. Osmotically regulated floating asymmetric membrane capsule for controlled site-specific delivery of ranitidine hydrochloride: optimization by central composite design.

    PubMed

    Chauhan, Manvendra S; Kumar, Anil; Pathak, Kamla

    2012-12-01

    A nondisintegrating, floating asymmetric membrane capsule (FAMC) was developed to achieve site-specific osmotic flow of a highly water-soluble drug, ranitidine hydrochloride (RHCl), in a controlled manner. Solubility suppression of RHCl was achieved by the common ion effect, using optimized coated sodium chloride as a formulation component. The capsular wall of FAMC was prepared by the phase inversion process wherein the polymeric membrane was precipitated on glass pins by dipping them in a solution of cellulose acetate followed by quenching. Central composite design was utilized to investigate the influence of independent variables, namely, level(s) of membrane former, pore former, and osmogen, on percent cumulative drug release (response). The release mechanism of RHCl through FAMC was confirmed as osmotic pumping. The asymmetry of the membrane was characterized by scanning electron microscopy that revealed a dense nonporous outer region of membrane supported by an inner porous region. Differential scanning calorimetry indicated no incompatibility between the drug and excipients. In vitro drug release in three biorelevant media, pH 2.5 (low fed), pH 4.5 (intermediate fed), and pH 6.5 (high fed), demonstrated pH-independent release of RHCl (P > 0.05). Floating ability for 12 h of the optimized FAMC9 was visually examined during the in vitro release studies that showed maximal drug release with zero-order kinetics (r (2) = 0.9991). Thus, a novel osmotically regulated floating capsular system was developed for site-specific delivery of RHCl.

  12. Recharge at the Hanford Site: Status report

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

    Gee, G.W.

    A variety of field programs designed to evaluate recharge and other water balance components including precipitation, infiltration, evaporation, and water storage changes, have been carried out at the Hanford Site since 1970. Data from these programs have indicated that a wide range of recharge rates can occur depending upon specific site conditions. Present evidence suggests that minimum recharge occurs where soils are fine-textured and surfaces are vegetated with deep-rooted plants. Maximum recharge occurs where coarse soils or gravels exist at the surface and soils are kept bare. Recharge can occur in areas where shallow-rooted plants dominate the surface, particularly wheremore » soils are coarse-textured. Recharge estimates have been made for the site using simulation models. A US Geological Survey model that attempts to account for climate variability, soil storage parameters, and plant factors has calculated recharge values ranging from near zero to an average of about 1 cm/yr for the Hanford Site. UNSAT-H, a deterministic model developed for the site, appears to be the best code available for estimating recharge on a site-specific basis. Appendix I contains precipitation data from January 1979 to June 1987. 42 refs., 11 figs., 11 tabs.« less

  13. 17. Photographic copy of intial site plan for North Base: ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. Photographic copy of intial site plan for North Base: AF Job No. 1045, Military Construction: Muroc Bombing Range, Muroc Lake, California; Materiel Test Site: Location Plan, Sheet No. 1 of 11, May 1942. Records on file at AFFTC/CE-CECC-B (Design/Construction Flight/RPMC), Edwards AFB, California. - Edwards Air Force Base, North Base, North Base Road, Boron, Kern County, CA

  14. End-user perspectives on e-commerce and health care web site quality.

    PubMed

    Le Rouge, Cynthia; De Leo, Gianluca

    2008-11-06

    We explore and compare the importance of various quality dimensions for health care and e-commerce web sites. The results show that the importance of various quality attributes for all except four of ten quality dimensions studied differ between health care and e-commerce web sites. These results can help health care managers to improve and/or to guide the design of their web sites.

  15. 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…

  16. Downregulation of hPMC2 imparts chemotherapeutic sensitivity to alkylating agents in breast cancer cells.

    PubMed

    Krishnamurthy, Nirmala; Liu, Lili; Xiong, Xiahui; Zhang, Junran; Montano, Monica M

    2015-01-01

    Triple negative breast cancer cell lines have been reported to be resistant to the cyotoxic effects of temozolomide (TMZ). We have shown previously that a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2) has a role in the repair of estrogen-induced abasic sites. Our present study provides evidence that downregulation of hPMC2 in MDA-MB-231 and MDA-MB-468 breast cancer cells treated with temozolomide (TMZ) decreases cell survival. This increased sensitivity to TMZ is associated with an increase in number of apurinic/apyrimidinic (AP) sites in the DNA. We also show that treatment with another alkylating agent, BCNU, results in an increase in AP sites and decrease in cell survival. Quantification of western blot analyses and immunofluorescence experiments reveal that treatment of hPMC2 downregulated cells with TMZ results in an increase in γ-H2AX levels, suggesting an increase in double strand DNA breaks. The enhancement of DNA double strand breaks in TMZ treated cells upon downregulation of hPCM2 is also revealed by the comet assay. Overall, we provide evidence that downregulation of hPMC2 in breast cancer cells increases cytotoxicity of alkylating agents, representing a novel mechanism of treatment for breast cancer. Our data thus has important clinical implications in the management of breast cancer and brings forth potentially new therapeutic strategies.

  17. Overcoming Drug Resistant Prostate Cancer with APE1/Ref-1 Blockade

    DTIC Science & Technology

    2015-10-01

    cells avoid being killed by chemotherapy: Apurinic/apyrimidinic endonuclease/ redox -factor 1, or simply, Ref-1, for short. In this report, we...survivin signaling in human prostate cancer specimens. Genetic knockdown of APE1/Ref-1 disrupts prostate cancer cell growth and survival in cell culture...In addition, inhibition of the redox function selectively of Ref-1 results in cell growth inhibition, with this therapy preferentially inhibiting

  18. Overcoming Drug Resistant Prostate Cancer with APE1/Ref 1 Blockade

    DTIC Science & Technology

    2015-10-01

    cells avoid being killed by chemotherapy: Apurinic/apyrimidinic endonuclease/ redox -factor 1, or simply, Ref-1, for short. In this report, we...survivin signaling in human prostate cancer specimens. Genetic knockdown of APE1/Ref-1 disrupts prostate cancer cell growth and survival in cell culture...In addition, inhibition of the redox function selectively of Ref-1 results in cell growth inhibition, with this therapy preferentially inhibiting

  19. Can a Social Networking Site Support Afterschool Group Learning of Mandarin?

    ERIC Educational Resources Information Center

    Yang, Yang; Crook, Charles; O'Malley, Claire

    2014-01-01

    Schools are often encouraged to facilitate extra-curricular learning within their own premises. This study addresses the potential of social networking sites (SNS) for supporting such out-of-class study. Given concerns that learning on these sites may happen at a surface level, we adopted self-determination theory for designing a social networking…

  20. Remaining Sites Verification Package for the 116-C-3, 105-C Chemical Waste Tanks, Waste Site Reclassification Form 2008-002

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

    L. M. Dittmer

    2008-01-31

    The 116-C-3 waste site consisted of two underground storage tanks designed to receive mixed waste from the 105-C Reactor Metals Examination Facility chemical dejacketing process. Confirmatory evaluation and subsequent characterization of the site determined that the southern tank contained approximately 34,000 L (9,000 gal) of dejacketing wastes, and that the northern tank was unused. In accordance with this evaluation, the verification sampling and modeling results support a reclassification of this site to Interim Closed Out. The results of verification sampling demonstrate that residual contaminant concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils.more » The results also show that residual contaminant concentrations are protective of groundwater and the Columbia River.« less