Sample records for abasic site analog

  1. Structural and Kinetic Analysis of Nucleoside Triphosphate Incorporation Opposite an Abasic Site by Human Translesion DNA Polymerase η

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

    Patra, Amritaj; Zhang, Qianqian; Lei, Li

    2015-02-09

    The most prevalent lesion in DNA is an abasic site resulting from glycolytic cleavage of a base. In a number of cellular studies, abasic sites preferentially code for dATP insertion (the “A rule”). In some cases frameshifts are also common. X-ray structures with abasic sites in oligonucleotides have been reported for several microbial and human DNA polymerases (pols), e.g. Dpo4, RB69, KlenTaq, yeast pol ι, human (h) pol ι, and human pol β. We reported previously that hpol η is a major pol involved in abasic site bypass (Choi, J.-Y., Lim, S., Kim, E. J., Jo, A., and Guengerich, F.more » P. (2010 J. Mol. Biol. 404, 34–44). hpol η inserted all four dNTPs in steady-state and pre-steady-state assays, preferentially inserting A and G. In LC-MS analysis of primer-template pairs, A and G were inserted but little C or T was inserted. Frameshifts were observed when an appropriate pyrimidine was positioned 5' to the abasic site in the template. In x-ray structures of hpol η with a non-hydrolyzable analog of dATP or dGTP opposite an abasic site, H-bonding was observed between the phosphate 5' to the abasic site and water H-bonded to N1 and N6 of A and N1 and O6 of G nucleoside triphosphate analogs, offering an explanation for what appears to be a “purine rule.” A structure was also obtained for an A inserted and bonded in the primer opposite the abasic site, but it did not pair with a 5' T in the template. Finally, we conclude that hpol η, a major copying enzyme with abasic sites, follows a purine rule, which can also lead to frameshifts. The phenomenon can be explained with H-bonds.« less

  2. The chemical stability of abasic RNA compared to abasic DNA

    PubMed Central

    Küpfer, Pascal A.; Leumann, Christian J.

    2007-01-01

    We describe the synthesis of an abasic RNA phosphoramidite carrying a photocleavable 1-(2-nitrophenyl)ethyl (NPE) group at the anomeric center and a triisopropylsilyloxymethyl (TOM) group as 2′-O-protecting group together with the analogous DNA and the 2′-OMe RNA abasic building blocks. These units were incorporated into RNA-, 2′-OMe-RNA- and DNA for the purpose of studying their chemical stabilities towards backbone cleavage in a comparative way. Stability measurements were performed under basic conditions (0.1 M NaOH) and in the presence of aniline (pH 4.6) at 37°C. The kinetics and mechanisms of strand cleavage were followed by High pressure liquid chromotography and ESI-MS. Under basic conditions, strand cleavage at abasic RNA sites can occur via β,δ-elimination and 2′,3′-cyclophosphate formation. We found that β,δ-elimination was 154-fold slower compared to the same mechanism in abasic DNA. Overall strand cleavage of abasic RNA (including cyclophosphate formation) was still 16.8 times slower compared to abasic DNA. In the presence of aniline at pH 4.6, where only β,δ-elimination contributes to strand cleavage, a 15-fold reduced cleavage rate at the RNA abasic site was observed. Thus abasic RNA is significantly more stable than abasic DNA. The higher stability of abasic RNA is discussed in the context of its potential biological role. PMID:17151071

  3. 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.

  4. Quadruplexes of human telomere dG{sub 3}(TTAG{sub 3}){sub 3} sequences containing guanine abasic sites

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

    Skolakova, Petra; Bednarova, Klara; Vorlickova, Michaela

    Research highlights: {yields} Loss of a guanine base does not hinder the formation of G-quadruplex of human telomere sequence. {yields} Each depurination strongly destabilizes the quadruplex of dG{sub 3}(TTAG{sub 3}){sub 3} in NaCl and KCl. {yields} Conformational change of the abasic analogs of dG{sub 3}(TTAG{sub 3}){sub 3} is inhibited in KCl. {yields} The effects abasic sites may affect telomere-end structures in vivo. -- Abstract: This study was performed to evaluate how the loss of a guanine base affects the structure and stability of the three-tetrad G-quadruplex of 5'-dG{sub 3}(TTAG{sub 3}){sub 3}, the basic quadruplex-forming unit of the human telomere DNA.more » None of the 12 possible abasic sites hindered the formation of quadruplexes, but all reduced the thermodynamic stability of the parent quadruplex in both NaCl and KCl. The base loss did not change the Na{sup +}-stabilized intramolecular antiparallel architecture, based on CD spectra, but held up the conformational change induced in dG{sub 3}(TTAG{sub 3}){sub 3} in physiological concentration of KCl. The reduced stability and the inhibited conformational transitions observed here in vitro for the first time may predict that unrepaired abasic sites in G-quadruplexes could lead to changes in the chromosome's terminal protection in vivo.« less

  5. The Effects of Molecular Crowding on the Structure and Stability of G-Quadruplexes with an Abasic Site

    PubMed Central

    Fujimoto, Takeshi; Nakano, Shu-ichi; Miyoshi, Daisuke; Sugimoto, Naoki

    2011-01-01

    Both cellular environmental factors and chemical modifications critically affect the properties of nucleic acids. However, the structure and stability of DNA containing abasic sites under cell-mimicking molecular crowding conditions remain unclear. Here, we investigated the molecular crowding effects on the structure and stability of the G-quadruplexes including a single abasic site. Structural analysis by circular dichroism showed that molecular crowding by PEG200 did not affect the topology of the G-quadruplex structure with or without an abasic site. Thermodynamic analysis further demonstrated that the degree of stabilization of the G-quadruplex by molecular crowding decreased with substitution of an abasic site for a single guanine. Notably, we found that the molecular crowding effects on the enthalpy change for G-quadruplex formation had a linear relationship with the abasic site effects depending on its position. These results are useful for predicting the structure and stability of G-quadruplexes with abasic sites in the cell-mimicking conditions. PMID:21949901

  6. Miscoding and mutagenic properties of 8-oxoguanine and abasic sites: Ubiquitous lesions in damaged DNA

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

    Grollman, A.P.; Takeshita, Masaru

    1995-12-31

    More than twenty oxidatively-damaged bases, including 8-oxoguanine, have been found to occur in genomic DNA. Some of these lesions block DNA replication and are potentially lethal; others generate mutations which can initiate carcinogenesis and promote cellular aging. In this report, the authors focus attention on the mutagenicity and repair of 8-oxoguanine. Kasai and Nishimura`s discovery that hydroxyl radicals react with guanine residues in DNA to form 8-oxoguanine and the development of sensitive methods for the detection and quantitation of this modified base led to the observation that approximately 1 in 10{sup 5} guanine residues in mammalian DNA are oxidized atmore » the C-8 position. DNA containing 8-oxoguanine and synthetic analogs of the abasic site have been used to investigate the miscoding and mutagenic potential of these ubiquitous lesions. Studies in the laboratory were facilitated by the development of solid state synthetic methods by which these lesions could be introduced at defined positions in DNA. In this paper, the authors review studies in which 8-oxoguanine and abasic sites have been used in model systems to explore various early events in the replication of selectively damaged DNA.« less

  7. Resistance to Nucleotide Excision Repair of Bulky Guanine Adducts Opposite Abasic Sites in DNA Duplexes and Relationships between Structure and Function

    PubMed Central

    Liu, Zhi; Ding, Shuang; Kropachev, Konstantin; Lei, Jia; Amin, Shantu; Broyde, Suse; Geacintov, Nicholas E.

    2015-01-01

    The nucleotide excision repair of certain bulky DNA lesions is abrogated in some specific non-canonical DNA base sequence contexts, while the removal of the same lesions by the nucleotide excision repair mechanism is efficient in duplexes in which all base pairs are complementary. Here we show that the nucleotide excision repair activity in human cell extracts is moderate-to-high in the case of two stereoisomeric DNA lesions derived from the pro-carcinogen benzo[a]pyrene (cis- and trans-B[a]P-N 2-dG adducts) in a normal DNA duplex. By contrast, the nucleotide excision repair activity is completely abrogated when the canonical cytosine base opposite the B[a]P-dG adducts is replaced by an abasic site in duplex DNA. However, base excision repair of the abasic site persists. In order to understand the structural origins of these striking phenomena, we used NMR and molecular spectroscopy techniques to evaluate the conformational features of 11mer DNA duplexes containing these B[a]P-dG lesions opposite abasic sites. Our results show that in these duplexes containing the clustered lesions, both B[a]P-dG adducts adopt base-displaced intercalated conformations, with the B[a]P aromatic rings intercalated into the DNA helix. To explain the persistence of base excision repair in the face of the opposed bulky B[a]P ring system, molecular modeling results suggest how the APE1 base excision repair endonuclease, that excises abasic lesions, can bind productively even with the trans-B[a]P-dG positioned opposite the abasic site. We hypothesize that the nucleotide excision repair resistance is fostered by local B[a]P residue—DNA base stacking interactions at the abasic sites, that are facilitated by the absence of the cytosine partner base in the complementary strand. More broadly, this study sets the stage for elucidating the interplay between base excision and nucleotide excision repair in processing different types of clustered DNA lesions that are substrates of nucleotide

  8. DNA Polymerase λ Inactivation by Oxidized Abasic Sites&

    PubMed Central

    Stevens, Adam J.; Guan, Lirui; Bebenek, Katarzyna; Kunkel, Thomas A.; Greenberg, Marc M.

    2013-01-01

    Base excision repair plays a vital role in maintaining genomic integrity in mammalian cells. DNA polymerase λ is believed to play a backup role to DNA polymerase β in base excision repair. Two oxidized abasic lesions that are produced by a variety of DNA damaging agents, including several antitumor antibiotics, the C4′-oxidized abasic site following Ape1 incision (pC4-AP) and 5′-(2-phosphoryl-1,4-dioxobutane) (DOB), irreversibly inactivate Pol β and Pol λ. The interactions of DOB and pC4-AP with Pol λ are examined in detail using DNA substrates containing these lesions at defined sites. Single turnover kinetic experiments show that Pol λ excises DOB almost 13-times more slowly than a 5′-phosphorylated 2-deoxyribose (dRP). pC4-AP is excised approximately twice as fast as DOB. The absolute rate constants are considerably slower than those reported for Pol β at the respective reactions, suggesting that Pol λ may be an inefficient backup in BER. DOB inactivates Pol λ approximately 3-fold less efficiently than it does Pol β and the difference is attributable to a higher KI (33 ± 7 nM). Inactivation of Pol λ’s lyase activity by DOB also prevents the enzyme from carrying out polymerization following preincubation of the protein and DNA. Mass spectral analysis of GluC digested Pol λ inactivated by DOB shows that Lys324 is modified. There is inferential support that Lys312 may also be modified. Both residues are within the Pol λ lyase active site. Protein modification involves reaction with released but-2-ene-1,4-dial. When acting on pC4-AP, Pol λ achieves approximately 4 turnovers on average before being inactivated. Lyase inactivation by pC4-AP is also accompanied by loss of polymerase activity and mass spectrometry indicates that Lys312 and Lys324 are modified by the lesion. The ability of DOB and pC4-AP to inactivate Pol λ provides additional evidence that these lesions are significant sources of the cytotoxicity of DNA damaging agents that

  9. Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1

    PubMed Central

    Malina, Jaroslav; Scott, Peter; Brabec, Viktor

    2015-01-01

    Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo–helical ‘flexicate’ complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3]4+ incorporating the common NN–NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo–helical complexes for cancer chemotherapy. PMID:25940617

  10. 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.

  11. Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1.

    PubMed

    Malina, Jaroslav; Scott, Peter; Brabec, Viktor

    2015-06-23

    Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo-helical 'flexicate' complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3](4+) incorporating the common NN-NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo-helical complexes for cancer chemotherapy. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Preparation and Analysis of Oligonucleotides Containing the C4′-Oxidized Abasic Site and Related Mechanistic Probes

    PubMed Central

    Kim, Jaeseung; Kreller, Cortney R.; Greenberg, Marc M.

    2005-01-01

    The C4′-oxidized abasic site (C4-AP) is produced by a variety of DNA damaging agents. This alkali labile lesion can exist in up to four diastereomeric cyclic forms, in addition to the acyclic keto-aldehyde. Synthetic oligonucleotides containing the lesion were prepared from a stable photochemical precursor. Chemical integrity of the lesion containing oligonucleotides was probed using phosphodiesterase lability. Analysis of the 3′,5′-phosphate diester of the monomeric lesion released from single diastereomers of photolabile precursors by 1H NMR indicates that isomerization of the hemiacetal and/or hemiketal is rapid. The syntheses and characterization of oligonucleotides containing configurationally stable analogues of C4-AP, which serve as mechanistic probes for deciphering the structural basis of the biochemical and biological effects of the C4′-oxidized abasic lesion, are also described. PMID:16277338

  13. 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.

  14. DNA abasic site-directed formation of fluorescent silver nanoclusters for selective nucleobase recognition

    NASA Astrophysics Data System (ADS)

    Ma, Kun; Cui, Qinghua; Liu, Guiying; Wu, Fei; Xu, Shujuan; Shao, Yong

    2011-07-01

    DNA single-nucleotide polymorphism (SNP) detection has attracted much attention due to mutation related diseases. Various methods for SNP detection have been proposed and many are already in use. Here, we find that the abasic site (AP site) in the DNA duplex can be developed as a capping scaffold for the generation of fluorescent silver nanoclusters (Ag NCs). As a proof of concept, the DNA sequences from fragments near codon 177 of cancer supression gene p53 were used as a model for SNP detection by in situ formed Ag NCs. The formation of fluorescent Ag NCs in the AP site-containing DNA duplex is highly selective for cytosine facing the AP site and guanines flanking the site and can be employed in situ as readout for SNP detection. The fluorescent signal-on sensing for SNP based on this inorganic fluorophore is substantially advantageous over the previously reported signal-off responses using low-molecular-weight organic ligands. The strong dependence of fluorescent Ag NC formation on the sequences surrounding the AP site was successfully used to identify mutations in codon 177 of cancer supression gene p53. We anticipate that this approach will be employed to develop a practical SNP detection method by locating an AP site toward the midway cytosine in a target strand containing more than three consecutive cytosines.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. Mechanisms by which herpes simplex virus DNA polymerase limits translesion synthesis through abasic sites.

    PubMed

    Zhu, Yali; Song, Liping; Stroud, Jason; Parris, Deborah S

    2008-01-01

    Results suggest a high probability that abasic (AP) sites occur at least once per herpes simplex virus type 1 (HSV-1) genome. The parameters that control the ability of HSV-1 DNA polymerase (pol) to engage in AP translesion synthesis (TLS) were examined because AP lesions could influence the completion and fidelity of viral DNA synthesis. Pre-steady-state kinetic experiments demonstrated that wildtype (WT) and exonuclease-deficient (exo-) pol could incorporate opposite an AP lesion, but full TLS required absence of exo function. Virtually all of the WT pol was bound at the exo site to AP-containing primer-templates (P/Ts) at equilibrium, and the pre-steady-state rate of excision by WT pol was higher on AP-containing than on matched DNA. However, several factors influencing polymerization work synergistically with exo activity to prevent HSV-1 pol from engaging in TLS. Although the pre-steady-state catalytic rate constant for insertion of dATP opposite a T or AP site was similar, ground-state-binding affinity of dATP for insertion opposite an AP site was reduced 3-9-fold. Single-turnover running-start experiments demonstrated a reduced proportion of P/Ts extended to the AP site compared to the preceding site during processive synthesis by WT or exo- pol. Only the exo- pol engaged in TLS, though inefficiently and without burst kinetics, suggesting a much slower rate-limiting step for extension beyond the AP site.

  20. Structural insights into abasic site for Fpg specific binding and catalysis: comparative high-resolution crystallographic studies of Fpg bound to various models of abasic site analogues-containing DNA

    PubMed Central

    de Jésus, Karine Pereira; Serre, Laurence; Zelwer, Charles; Castaing, Bertrand

    2005-01-01

    Fpg is a DNA glycosylase that recognizes and excises the mutagenic 8-oxoguanine (8-oxoG) and the potentially lethal formamidopyrimidic residues (Fapy). Fpg is also associated with an AP lyase activity which successively cleaves the abasic (AP) site at the 3′ and 5′ sides by βδ-elimination. Here, we present the high-resolution crystal structures of the wild-type and the P1G defective mutant of Fpg from Lactococcus lactis bound to 14mer DNA duplexes containing either a tetrahydrofuran (THF) or 1,3-propanediol (Pr) AP site analogues. Structures show that THF is less extrahelical than Pr and its backbone C5′–C4′–C3′ diverges significantly from those of Pr, rAP, 8-oxodG and FapydG. Clearly, the heterocyclic oxygen of THF is pushed back by the carboxylate of the strictly conserved E2 residue. We can propose that the ring-opened form of the damaged deoxyribose is the structure active form of the sugar for Fpg catalysis process. Both structural and functional data suggest that the first step of catalysis mediated by Fpg involves the expulsion of the O4′ leaving group facilitated by general acid catalysis (involving E2), rather than the immediate cleavage of the N-glycosic bond of the damaged nucleoside. PMID:16243784

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  2. Interstrand cross-links arising from strand breaks at true abasic sites in duplex DNA

    PubMed Central

    Yang, Zhiyu; Price, Nathan E.; Johnson, Kevin M.

    2017-01-01

    Abstract Interstrand cross-links are exceptionally bioactive DNA lesions. Endogenous generation of interstrand cross-links in genomic DNA may contribute to aging, neurodegeneration, and cancer. Abasic (Ap) sites are common lesions in genomic DNA that readily undergo spontaneous and amine-catalyzed strand cleavage reactions that generate a 2,3-didehydro-2,3-dideoxyribose sugar remnant (3’ddR5p) at the 3’-terminus of the strand break. Interestingly, this strand scission process leaves an electrophilic α,β-unsaturated aldehyde residue embedded within the resulting nicked duplex. Here we present evidence that 3’ddR5p derivatives generated by spermine-catalyzed strand cleavage at Ap sites in duplex DNA can react with adenine residues on the opposing strand to generate a complex lesion consisting of an interstrand cross-link adjacent to a strand break. The cross-link blocks DNA replication by ϕ29 DNA polymerase, a highly processive polymerase enzyme that couples synthesis with strand displacement. This suggests that 3’ddR5p-derived cross-links have the potential to block critical cellular DNA transactions that require strand separation. LC-MS/MS methods developed herein provide powerful tools for studying the occurrence and properties of these cross-links in biochemical and biological systems. PMID:28531327

  3. Selective amyloid β oligomer assay based on abasic site-containing molecular beacon and enzyme-free amplification.

    PubMed

    Zhu, Linling; Zhang, Junying; Wang, Fengyang; Wang, Ya; Lu, Linlin; Feng, Chongchong; Xu, Zhiai; Zhang, Wen

    2016-04-15

    Amyloid-beta (Aβ) oligomers are highly toxic species in the process of Aβ aggregation and are regarded as potent therapeutic targets and diagnostic markers for Alzheimer's disease (AD). Herein, a label-free molecular beacon (MB) system integrated with enzyme-free amplification strategy was developed for simple and highly selective assay of Aβ oligomers. The MB system was constructed with abasic site (AP site)-containing stem-loop DNA and a fluorescent ligand 2-amino-5,6,7-trimethyl-1,8-naphyridine (ATMND), of which the fluorescence was quenched upon binding to the AP site in DNA stem. Enzyme-free amplification was realized by target-triggered continuous opening of two delicately designed MBs (MB1 and MB2). Target DNA hybridization with MB1 and then MB2 resulted in the release of two ATMND molecules in one binding event. Subsequent target recycling could greatly amplify the detection sensitivity due to the greatly enhanced turn-on emission of ATMND fluorescence. Combining with Aβ oligomers aptamers, the strategy was applied to analyze Aβ oligomers and the results showed that it could quantify Aβ oligomers with high selectivity and monitor the Aβ aggregation process. This novel method may be conducive to improve the diagnosis and pathogenic study of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Interstrand cross-links arising from strand breaks at true abasic sites in duplex DNA.

    PubMed

    Yang, Zhiyu; Price, Nathan E; Johnson, Kevin M; Wang, Yinsheng; Gates, Kent S

    2017-06-20

    Interstrand cross-links are exceptionally bioactive DNA lesions. Endogenous generation of interstrand cross-links in genomic DNA may contribute to aging, neurodegeneration, and cancer. Abasic (Ap) sites are common lesions in genomic DNA that readily undergo spontaneous and amine-catalyzed strand cleavage reactions that generate a 2,3-didehydro-2,3-dideoxyribose sugar remnant (3'ddR5p) at the 3'-terminus of the strand break. Interestingly, this strand scission process leaves an electrophilic α,β-unsaturated aldehyde residue embedded within the resulting nicked duplex. Here we present evidence that 3'ddR5p derivatives generated by spermine-catalyzed strand cleavage at Ap sites in duplex DNA can react with adenine residues on the opposing strand to generate a complex lesion consisting of an interstrand cross-link adjacent to a strand break. The cross-link blocks DNA replication by ϕ29 DNA polymerase, a highly processive polymerase enzyme that couples synthesis with strand displacement. This suggests that 3'ddR5p-derived cross-links have the potential to block critical cellular DNA transactions that require strand separation. LC-MS/MS methods developed herein provide powerful tools for studying the occurrence and properties of these cross-links in biochemical and biological systems. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Repair Rate of Clustered Abasic DNA Lesions by Human Endonuclease: Molecular Bases of Sequence Specificity.

    PubMed

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

    2016-10-06

    In the present contribution, the interaction between damaged DNA and repair enzymes is examined by means of molecular dynamics simulations. More specifically, we consider clustered abasic DNA lesions processed by the primary human apurinic/apyrimidinic (AP) endonuclease, APE1. Our results show that, in stark contrast with the corresponding bacterial endonucleases, human APE1 imposes strong geometrical constraints on the DNA duplex. As a consequence, the level of recognition and, hence, the repair rate is higher. Important features that guide the DNA/protein interactions are the presence of an extended positively charged region and of a molecular tweezers that strongly constrains DNA. Our results are on very good agreement with the experimentally determined repair rate of clustered abasic lesions. The lack of repair for one particular arrangement of the two abasic sites is also explained considering the peculiar destabilizing interaction between the recognition region and the second lesion, resulting in a partial opening of the molecular tweezers and, thus, a less stable complex. This contribution cogently establishes the molecular bases for the recognition and repair of clustered DNA lesions by means of human endonucleases.

  6. Conformational dynamics of abasic DNA upon interactions with AP endonuclease 1 revealed by stopped-flow fluorescence analysis.

    PubMed

    Kanazhevskaya, Lyubov Yu; Koval, Vladimir V; Vorobjev, Yury N; Fedorova, Olga S

    2012-02-14

    Apurinic/apyrimidinic (AP) sites are abundant DNA lesions arising from exposure to UV light, ionizing radiation, alkylating agents, and oxygen radicals. In human cells, AP endonuclease 1 (APE1) recognizes this mutagenic lesion and initiates its repair via a specific incision of the phosphodiester backbone 5' to the AP site. We have investigated a detailed mechanism of APE1 functioning using fluorescently labeled DNA substrates. A fluorescent adenine analogue, 2-aminopurine, was introduced into DNA substrates adjacent to the abasic site to serve as an on-site reporter of conformational transitions in DNA during the catalytic cycle. Application of a pre-steady-state stopped-flow technique allows us to observe changes in the fluorescence intensity corresponding to different stages of the process in real time. We also detected an intrinsic Trp fluorescence of the enzyme during interactions with 2-aPu-containing substrates. Our data have revealed a conformational flexibility of the abasic DNA being processed by APE1. Quantitative analysis of fluorescent traces has yielded a minimal kinetic scheme and appropriate rate constants consisting of four steps. The results obtained from stopped-flow data have shown a substantial influence of the 2-aPu base location on completion of certain reaction steps. Using detailed molecular dynamics simulations of the DNA substrates, we have attributed structural distortions of AP-DNA to realization of specific binding, effective locking, and incision of the damaged DNA. The findings allowed us to accurately discern the step that corresponds to insertion of specific APE1 amino acid residues into the abasic DNA void in the course of stabilization of the precatalytic complex.

  7. 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

  8. Correlation of Thermal Stability and Structural Distortion of DNA Interstrand Cross-Links Produced from Oxidized Abasic Sites with Their Selective Formation and Repair.

    PubMed

    Ghosh, Souradyuti; Greenberg, Marc M

    2015-10-13

    C4'-oxidized (C4-AP) and C5'-oxidized abasic sites (DOB) that are produced following abstraction of a hydrogen atom from the DNA backbone reversibly form cross-links selectively with dA opposite a 3'-adjacent nucleotide, despite the comparable proximity of an opposing dA. A previous report on UvrABC incision of DNA substrates containing stabilized analogues of the ICLs derived from C4-AP and DOB also indicated that the latter is repaired more readily by nucleotide excision repair [Ghosh, S., and Greenberg, M. M. (2014) Biochemistry 53, 5958-5965]. The source for selective cross-link formation was probed by comparing the reactivity of ICL analogues of C4-AP and DOB that mimic the preferred and disfavored cross-links with that of reagents that indirectly detect distortion by reacting with the nucleobases. The disfavored C4-AP and DOB analogues were each more reactive than the corresponding preferred cross-link substrates, suggesting that the latter are more stable, which is consistent with selective ICL formation. In addition, the preferred DOB analogue is more reactive than the respective C4-AP ICL, which is consistent with its more efficient incision by UvrABC. The conclusions drawn from the chemical probing experiments are corroborated by UV melting studies. The preferred ICLs exhibit melting temperatures higher than those of the corresponding disfavored isomers. These studies suggest that oxidized abasic sites form reversible interstrand cross-links with dA opposite the 3'-adjacent thymidine because these products are more stable and the thermodynamic preference is reflected in the transition states for their formation.

  9. Simultaneous fluorescence light-up and selective multicolor nucleobase recognition based on sequence-dependent strong binding of berberine to DNA abasic site.

    PubMed

    Wu, Fei; Shao, Yong; Ma, Kun; Cui, Qinghua; Liu, Guiying; Xu, Shujuan

    2012-04-28

    Label-free DNA nucleobase recognition by fluorescent small molecules has received much attention due to its simplicity in mutation identification and drug screening. However, sequence-dependent fluorescence light-up nucleobase recognition and multicolor emission with individual emission energy for individual nucleobases have been seldom realized. Herein, an abasic site (AP site) in a DNA duplex was employed as a binding field for berberine, one of isoquinoline alkaloids. Unlike weak binding of berberine to the fully matched DNAs without the AP site, strong binding of berberine to the AP site occurs and the berberine's fluorescence light-up behaviors are highly dependent on the target nucleobases opposite the AP site in which the targets thymine and cytosine produce dual emission bands, while the targets guanine and adenine only give a single emission band. Furthermore, more intense emissions are observed for the target pyrimidines than purines. The flanking bases of the AP site also produce some modifications of the berberine's emission behavior. The binding selectivity of berberine at the AP site is also confirmed by measurements of fluorescence resonance energy transfer, excited-state lifetime, DNA melting and fluorescence quenching by ferrocyanide and sodium chloride. It is expected that the target pyrimidines cause berberine to be stacked well within DNA base pairs near the AP site, which results in a strong resonance coupling of the electronic transitions to the particular vibration mode to produce the dual emissions. The fluorescent signal-on and emission energy-modulated sensing for nucleobases based on this fluorophore is substantially advantageous over the previously used fluorophores. We expect that this approach will be developed as a practical device for differentiating pyrimidines from purines by positioning an AP site toward a target that is available for readout by this alkaloid probe. This journal is © The Royal Society of Chemistry 2012

  10. Abasic pivot substitution harnesses target specificity of RNA interference

    PubMed Central

    Lee, Hye-Sook; Seok, Heeyoung; Lee, Dong Ha; Ham, Juyoung; Lee, Wooje; Youm, Emilia Moonkyung; Yoo, Jin Seon; Lee, Yong-Seung; Jang, Eun-Sook; Chi, Sung Wook

    2015-01-01

    Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA–target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at ∼80–100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome-wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications. PMID:26679372

  11. Roles of Rev1, Pol ζ, Pol32 and Pol η in the bypass of chromosomal abasic sites in Saccharomyces cerevisiae

    PubMed Central

    Auerbach, Paul A.; Demple, Bruce

    2010-01-01

    Translesion synthesis (TLS) on DNA is a process by which potentially cytotoxic replication-blocking lesions are bypassed, but at the risk of increased mutagenesis. The exact in vivo role of the individual TLS enzymes in Saccharomyces cerevisiae has been difficult to determine from previous studies due to differing results from the variety of systems used. We have generated a series of S.cerevisiae strains in which each of the TLS-related genes REV1, REV3, REV7, RAD30 and POL32 was deleted, and in which chromosomal apyrimidinic sites were generated during normal cell growth by the activity of altered forms of human uracil-DNA glycosylase that remove undamaged cytosines or thymines. Deletion of REV1, REV3 or REV7 resulted in slower growth dependent on (rev3Δ and rev7Δ) or enhanced by (rev1Δ) expression of the mutator glycosylases and a nearly complete abolition of glycosylase-induced mutagenesis. Deletion of POL32 resulted in cell death when the mutator glycosylases were expressed and, in their absence, diminished spontaneous mutagenesis. RAD30 appeared to be unnecessary for mutagenesis in response to abasic sites, as deleting this gene caused no significant change in either the mutation rates or the mutational spectra due to glycosylase expression. PMID:19901007

  12. Use of Hawaii Analog Sites for Lunar Science and In-Situ Resource Utilization

    NASA Astrophysics Data System (ADS)

    Sanders, G. B.; Larson, W. E.; Picard, M.; Hamilton, J. C.

    2011-10-01

    In-Situ Resource Utilization (ISRU) and lunar science share similar objectives with respect to analyzing and characterizing the physical, mineral, and volatile materials and resources at sites of robotic and human exploration. To help mature and stress instruments, technologies, and hardware and to evaluate operations and procedures, space agencies have utilized demonstrations at analog sites on Earth before use in future missions. The US National Aeronautics and Space Administration (NASA), the Canadian Space Agency (CSA), and the German Space Agency (DLR) have utilized an analog site on the slope of Mauna Kea on the Big Island of Hawaii to test ISRU and lunar science hardware and operations in two previously held analog field tests. NASA and CSA are currently planning on a 3rd analog field test to be held in June, 2012 in Hawaii that will expand upon the successes from the previous two field tests.

  13. Use of Hawaii Analog Sites for Lunar Science and In-Situ Resource Utilization

    NASA Technical Reports Server (NTRS)

    Sanders, G. B.; Larson, W. E.; Picard, M.; Hamilton, J. C.

    2011-01-01

    In-Situ Resource Utilization (ISRU) and lunar science share similar objectives with respect to analyzing and characterizing the physical, mineral, and volatile materials and resources at sites of robotic and human exploration. To help mature and stress instruments, technologies, and hardware and to evaluate operations and procedures, space agencies have utilized demonstrations at analog sites on Earth before use in future missions. The US National Aeronautics and Space Administration (NASA), the Canadian Space Agency (CSA), and the German Space Agency (DLR) have utilized an analog site on the slope of Mauna Kea on the Big Island of Hawaii to test ISRU and lunar science hardware and operations in two previously held analog field tests. NASA and CSA are currently planning on a 3rd analog field test to be held in June, 2012 in Hawaii that will expand upon the successes from the previous two field tests.

  14. Detecting single-abasic residues within a DNA strand immobilized in a biological nanopore using an integrated CMOS sensor.

    PubMed

    Kim, Jungsuk; Maitra, Raj D; Pedrotti, Ken; Dunbar, William B

    2013-02-01

    In this paper, we demonstrate the application of a novel current-measuring sensor (CMS) customized for nanopore applications. The low-noise CMS is fabricated in a 0.35μm CMOS process and is implemented in experiments involving DNA captured in an α-hemolysin (α-HL) nanopore. Specifically, the CMS is used to build a current amplitude map as a function of varying positions of a single-abasic residue within a homopolymer cytosine single-stranded DNA (ssDNA) that is captured and held in the pore. Each ssDNA is immobilized using a biotin-streptavidin linkage. Five different DNA templates are measured and compared: one all-cytosine ssDNA, and four with a single-abasic residue substitution that resides in or near the ~1.5nm aperture of the α-HL channel when the strand is immobilized. The CMOS CMS is shown to resolves the ~5Å displacements of the abasic residue within the varying templates. The demonstration represents an advance in application-specific circuitry that is optimized for small-footprint nanopore applications, including genomic sequencing.

  15. Engineering streptokinase for generation of active site-labeled plasminogen analogs*

    PubMed Central

    Laha, Malabika; Panizzi, Peter; Nahrendorf, Matthias; Bock, Paul E.

    2011-01-01

    We previously demonstrated that streptokinase (SK) can be used to generate active site-labeled fluorescent analogs of plasminogen (Pg) by virtue of its non-proteolytic activation of the zymogen. The method is versatile and allows for stoichiometric and active site-specific incorporation of any one of many molecular probes. The limitation of the labeling approach is that it is both time-consuming and low yield. Here we demonstrate an improved method for the preparation of labeled Pg analogs by the use of an engineered SK mutant fusion protein with both COOH- and NH2-terminal His6-tags. The NH2-terminal tag is followed by a tobacco etch virus proteinase cleavage site to ensure that the SK Ile1 residue, essential for conformational activation of Pg, is preserved. The SK COOH-terminal Lys414 residue and residues Arg253-Leu260 in the SK β-domain were deleted to prevent cleavage by plasmin (Pm), and to disable Pg substrate binding to the SK·Pg*/Pm catalytic complexes, respectively. Near-elimination of Pm generation with the SKΔ(R253-L260)ΔK414-His6 mutant increased the yield of labeled Pg 2.6-fold and reduced the time required >2-fold. The versatility of the labeling method was extended to the application of Pg labeled with a near-infrared probe to quantitate Pg receptors on immune cells by flow cytometry. PMID:21570944

  16. Influence of C-5 substituted cytosine and related nucleoside analogs on the formation of benzo[a]pyrene diol epoxide-dG adducts at CG base pairs of DNA

    PubMed Central

    Guza, Rebecca; Kotandeniya, Delshanee; Murphy, Kristopher; Dissanayake, Thakshila; Lin, Chen; Giambasu, George Madalin; Lad, Rahul R.; Wojciechowski, Filip; Amin, Shantu; Sturla, Shana J.; Hudson, Robert H.E.; York, Darrin M.; Jankowiak, Ryszard; Jones, Roger; Tretyakova, Natalia Y.

    2011-01-01

    Endogenous 5-methylcytosine (MeC) residues are found at all CG dinucleotides of the p53 tumor suppressor gene, including the mutational ‘hotspots’ for smoking induced lung cancer. MeC enhances the reactivity of its base paired guanine towards carcinogenic diolepoxide metabolites of polycyclic aromatic hydrocarbons (PAH) present in cigarette smoke. In the present study, the structural basis for these effects was investigated using a series of unnatural nucleoside analogs and a representative PAH diolepoxide, benzo[a]pyrene diolepoxide (BPDE). Synthetic DNA duplexes derived from a frequently mutated region of the p53 gene (5′-CCCGGCACCC GC[15N3,13C1-G]TCCGCG-3′, + strand) were prepared containing [15N3, 13C1]-guanine opposite unsubstituted cytosine, MeC, abasic site, or unnatural nucleobase analogs. Following BPDE treatment and hydrolysis of the modified DNA to 2′-deoxynucleosides, N2-BPDE-dG adducts formed at the [15N3, 13C1]-labeled guanine and elsewhere in the sequence were quantified by mass spectrometry. We found that C-5 alkylcytosines and related structural analogs specifically enhance the reactivity of the base paired guanine towards BPDE and modify the diastereomeric composition of N2-BPDE-dG adducts. Fluorescence and molecular docking studies revealed that 5-alkylcytosines and unnatural nucleobase analogs with extended aromatic systems facilitate the formation of intercalative BPDE–DNA complexes, placing BPDE in a favorable orientation for nucleophilic attack by the N2 position of guanine. PMID:21245046

  17. Analog earthquakes

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

    Hofmann, R.B.

    1995-09-01

    Analogs are used to understand complex or poorly understood phenomena for which little data may be available at the actual repository site. Earthquakes are complex phenomena, and they can have a large number of effects on the natural system, as well as on engineered structures. Instrumental data close to the source of large earthquakes are rarely obtained. The rare events for which measurements are available may be used, with modfications, as analogs for potential large earthquakes at sites where no earthquake data are available. In the following, several examples of nuclear reactor and liquified natural gas facility siting are discussed.more » A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository.« less

  18. Expanding the Planetary Analog Test Sites in Hawaii - Planetary Basalt Manipulation

    NASA Astrophysics Data System (ADS)

    Kelso, R.

    2013-12-01

    The Pacific International Space Center for Exploration Systems (PISCES) is one of the very few planetary surface research test sites in the country that is totally funded by the state legislature. In recent expansions, PISCES is broadening its work in planetary test sites to include much more R&D work in the planetary surface systems, and the manipulation of basalt materials. This is to include laser 3D printing of basalt, 'lunar-concrete' construction in state projects for Hawaii, renewable energy, and adding lava tubes/skylights to their mix of high-quality planetary analog test sites. PISCES Executive Director, Rob Kelso, will be providing program updates on the interest of the Hawaii State Legislature in planetary surface systems, new applied research initiatives in planetary basalts and interests in planetary construction.

  19. Influence of C-5 substituted cytosine and related nucleoside analogs on the formation of benzo[a]pyrene diol epoxide-dG adducts at CG base pairs of DNA.

    PubMed

    Guza, Rebecca; Kotandeniya, Delshanee; Murphy, Kristopher; Dissanayake, Thakshila; Lin, Chen; Giambasu, George Madalin; Lad, Rahul R; Wojciechowski, Filip; Amin, Shantu; Sturla, Shana J; Hudson, Robert H E; York, Darrin M; Jankowiak, Ryszard; Jones, Roger; Tretyakova, Natalia Y

    2011-05-01

    Endogenous 5-methylcytosine ((Me)C) residues are found at all CG dinucleotides of the p53 tumor suppressor gene, including the mutational 'hotspots' for smoking induced lung cancer. (Me)C enhances the reactivity of its base paired guanine towards carcinogenic diolepoxide metabolites of polycyclic aromatic hydrocarbons (PAH) present in cigarette smoke. In the present study, the structural basis for these effects was investigated using a series of unnatural nucleoside analogs and a representative PAH diolepoxide, benzo[a]pyrene diolepoxide (BPDE). Synthetic DNA duplexes derived from a frequently mutated region of the p53 gene (5'-CCCGGCACCC GC[(15)N(3),(13)C(1)-G]TCCGCG-3', + strand) were prepared containing [(15)N(3), (13)C(1)]-guanine opposite unsubstituted cytosine, (Me)C, abasic site, or unnatural nucleobase analogs. Following BPDE treatment and hydrolysis of the modified DNA to 2'-deoxynucleosides, N(2)-BPDE-dG adducts formed at the [(15)N(3), (13)C(1)]-labeled guanine and elsewhere in the sequence were quantified by mass spectrometry. We found that C-5 alkylcytosines and related structural analogs specifically enhance the reactivity of the base paired guanine towards BPDE and modify the diastereomeric composition of N(2)-BPDE-dG adducts. Fluorescence and molecular docking studies revealed that 5-alkylcytosines and unnatural nucleobase analogs with extended aromatic systems facilitate the formation of intercalative BPDE-DNA complexes, placing BPDE in a favorable orientation for nucleophilic attack by the N(2) position of guanine. © The Author(s) 2011. Published by Oxford University Press.

  20. Drilling Automation Tests At A Lunar/Mars Analog Site

    NASA Technical Reports Server (NTRS)

    Glass, B.; Cannon, H.; Hanagud, S.; Lee, P.; Paulsen, G.

    2006-01-01

    Future in-situ lunar/martian resource utilization and characterization, as well as the scientific search for life on Mars, will require access to the subsurface and hence drilling. Drilling on Earth is hard - an art form more than an engineering discipline. The limited mass, energy and manpower in planetary drilling situations makes application of terrestrial drilling techniques problematic. The Drilling Automation for Mars Exploration (DAME) project is developing drilling automation and robotics for projected use in missions to the Moon and Mars in the 2011-15 period. This has been tested recently, drilling in permafrost at a lunar/martian analog site (Haughton Crater, Devon Island, Canada).

  1. The exonuclease activity of hPMC2 is required for transcriptional regulation of the QR gene and repair of estrogen-induced abasic sites.

    PubMed

    Krishnamurthy, N; Ngam, C R; Berdis, A J; Montano, M M

    2011-11-24

    We have previously reported that the expression of antioxidative stress enzymes is upregulated by trans-hydroxytamoxifen (TOT) in breast epithelial cell lines providing protection against estrogen-induced DNA damage. This regulation involves Estrogen Receptor β (ERβ) recruitment to the Electrophile Response Element (EpRE) and a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2). We have also demonstrated that ERβ and hPMC2 are required for TOT-dependent recruitment of poly (ADP-ribose) polymerase 1 (PARP-1) and Topoisomerase IIβ (Topo IIβ) to the EpRE. Sequence analysis reveals that the C-terminus of hPMC2 encodes a putative exonuclease domain. Using in vitro kinetic assays, we found that hPMC2 is a 3'-5' non-processive exonuclease that degrades both single-stranded and double-stranded substrates. Mutation of two conserved carboxylate residues drastically reduced the exonuclease activity of hPMC2, indicating the relative importance of the catalytic residues. Western blot analysis of breast cancer cell lines for Quinone Reductase (QR) levels revealed that the intrinsic exonuclease activity of hPMC2 was required for TOT-induced QR upregulation. Chromatin immunoprecipitation (ChIP) assays also indicated that hPMC2 was involved in the formation of strand breaks observed with TOT treatment and is specific for the EpRE-containing region of the QR gene. We also determined that the transcription factor NF-E2-related factor-2 (Nrf2) is involved in the specificity of hPMC2 for the EpRE. In addition, we determined that the catalytic activity of hPMC2 is required for repair of abasic sites that result from estrogen-induced DNA damage. Thus, our study provides a mechanistic basis for transcriptional regulation by hPMC2 and provides novel insights into its role in cancer prevention.

  2. The exonuclease activity of hPMC2 is required for transcriptional regulation of the QR gene and repair of estrogen-induced abasic sites

    PubMed Central

    Krishnamurthy, Nirmala; Ngam, Caitlyn R.; Berdis, Anthony J.; Montano, Monica M.

    2011-01-01

    We have previously reported that the expression of antioxidative stress enzymes are upregulated by trans-hydroxytamoxifen (TOT) in breast epithelial cell lines providing protection against estrogen-induced DNA damage. This regulation involves Estrogen Receptor beta (ERβ) recruitment to the Electrophile Response Element (EpRE) and a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2). We have also demonstrated that ERβ and hPMC2 are required for TOT-dependent recruitment of poly (ADP-ribose) polymerase 1 (PARP-1) and Topoisomerase IIβ (Topo IIβ) to the EpRE. Sequence analysis reveals that the C-terminus of hPMC2 encodes a putative exonuclease domain. Using in vitro kinetic assays, we found that hPMC2 is a 3'–5' non-processive exonuclease that degrades both single stranded and double stranded substrates. Mutation of two conserved carboxylate residues drastically reduced the exonuclease activity of hPMC2 indicating the relative importance of the catalytic residues. Western blot analysis of breast cancer cell lines for Quinone Reductase (QR) levels revealed that the intrinsic exonuclease activity of hPMC2 was required for TOT-induced QR upregulation. Chromatin immunoprecipitation assays (ChIP) also indicated that hPMC2 was involved in the formation of strand breaks observed with TOT-treatment and is specific for the EpRE-containing region of the QR gene. We also determined that the transcription factor NF-E2-related factor-2 (Nrf2) is involved in the specificity of hPMC2 for the EpRE. In addition, we determined that the catalytic activity of hPMC2 is required for repair of abasic sites that result from estrogen-induced DNA damage. Thus our study provides a mechanistic basis for transcriptional regulation by hPMC2 and provides novel insights into its role in cancer prevention. PMID:21602889

  3. Icebreaker-3 Drill Integration and Testing at Two Mars-Analog Sites

    NASA Technical Reports Server (NTRS)

    Glass, B.; Bergman, D.; Yaggi, B.; Dave, A.; Zacny, K.

    2016-01-01

    A decade of evolutionary development of integrated automated drilling and sample handling at analog sites and in test chambers has made it possible to go 1 meter through hard rocks and ice layers on Mars. The latest Icebreaker-3 drill has been field tested in 2014 at the Haughton Crater Marsanalog site in the Arctic and in 2015 with a Mars lander mockup in Rio Tinto, Spain, (with sample transfer arm and with a prototype life-detection instrument). Tests in Rio Tinto in 2015 successfully demonstrated that the drill sample (cuttings) was handed-off from the drill to the sample transfer arm and thence to the on-deck instrument inlet where it was taken in and analyzed ("dirt-to-data").

  4. Lava Tubes as Martian Analog sites on Hawaii Island

    NASA Astrophysics Data System (ADS)

    Andersen, Christian; Hamilton, J. C.; Adams, M.

    2013-10-01

    The existence of geologic features similar to skylights seen in Mars Reconnaissance Orbiter HIRISE imagery suggest Martian lava tube networks. Along with pit craters, these features are evidence of a past era of vulcanism. If these were contemporary with the wet Mars eras, then it is suggestive that any Martian life may have retreated into these subsurface oases. Hawaii island has numerous lava tubes of differing ages, humidity, lengths and sizes that make ideal analog test environments for future Mars exploration. PISCES has surveyed multiple candidate sites during the past summer with a team of University of Hawaii at Hilo student interns. It should be noted that Lunar features have also been similarly discovered via Lunar Reconnaissance Orbiter LROC imagery.

  5. On the Formation and Properties of Interstrand DNA-DNA Cross-links Forged by Reaction of an Abasic Site With the Opposing Guanine Residue of 5′-CAp Sequences in Duplex DNA

    PubMed Central

    Johnson, Kevin M.; Price, Nathan E.; Wang, Jin; Fekry, Mostafa I.; Dutta, Sanjay; Seiner, Derrick R.; Wang, Yinsheng; Gates, Kent S.

    2014-01-01

    We recently reported that the aldehyde residue of an abasic (Ap) site in duplex DNA can generate an interstrand cross-link via reaction with a guanine residue on the opposing strand. This finding is intriguing because the highly deleterious nature of interstrand cross-links suggests that even small amounts of Ap-derived cross-links could make a significant contribution to the biological consequences stemming from the generation of Ap sites in cellular DNA. Incubation of 21-bp duplexes containing a central 5′-CAp sequence under conditions of reductive amination (NaCNBH3, pH 5.2) generated much higher yields of cross-linked DNA than reported previously. At pH 7, in the absence of reducing agents, these Ap-containing duplexes also produced cross-linked duplexes that were readily detected on denaturing polyacrylamide gels. Cross-link formation was not highly sensitive to reaction conditions and, once formed, the cross-link was stable to a variety of work-up conditions. Results of multiple experiments including MALDI-TOF mass spectrometry, gel mobility, methoxyamine capping of the Ap aldehyde, inosine-for-guanine replacement, hydroxyl radical footprinting, and LCMS/MS were consistent with a cross-linking mechanism involving reversible reaction of the Ap aldehyde residue with the N2-amino group of the opposing guanine residue in 5′-CAp sequences to generate hemiaminal, imine, or cyclic hemiaminal cross-links (7-10) that were irreversibly converted under conditions of reductive amination (NaCNBH3/pH 5.2) to a stable amine linkage. Further support for the importance of the exocyclic N2-amino group in this reaction was provided by an experiment showing that installation of a 2-aminopurine-thymine base pair at the cross-linking site produced high yields (15-30%) of a cross-linked duplex at neutral pH, in the absence of NaCNBH3. PMID:23215239

  6. The Mojave Desert: A Martian Analog Site for Future Astrobiology Themed Missions

    NASA Technical Reports Server (NTRS)

    Salas, E.; Abbey, W.; Bhartia, R.; Beegle, L. W.

    2011-01-01

    Astrobiological interest in Mars is highlighted by evidence that Mars was once warm enough to have liquid water present on its surface long enough to create geologic formations that could only exist in the presense of extended fluvial periods. These periods existed at the same time life on Earth arose. If life began on Mars as well during this period, it is reasonable to assume it may have adapted to the subsurface as environments at the surface changed into the inhospitable state we find today. If the next series of Mars missions (Mars Science Laboratory, the ExoMars Trace Gas Orbiter proposed for launch in 2016, and potential near surface sample return) fail to discover either extinct or extant life on Mars, a subsurface mission would be necessary to attempt to "close the book" on the existence of martian life. Mars is much colder and drier than Earth, with a very low pressure CO2 environment and no obvious habitats. Terrestrial regions with limited precipitation, and hence reduced active biota, are some of the best martian low to mid latitude analogs to be found on Earth, be they the Antarctic dry valleys, the Atacama or Mojave Deserts. The Mojave Desert/Death Valley region is considered a Mars analog site by the Terrestrial Analogs Panel of the NSF-sponsored decadal survey; a field guide was even developed and a workshop was held on its applicability as a Mars analog. This region has received a great deal of attention due to its accessibility and the variety of landforms and processes observed relevant to martian studies.

  7. Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA

    PubMed Central

    Hata, Kuniki; Urushibara, Ayumi; Yamashita, Shinichi; Lin, Mingzhang; Muroya, Yusa; Shikazono, Naoya; Yokoya, Akinari; Fu, Haiying; Katsumura, Yosuke

    2015-01-01

    Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 108 dm3 mol−1 s−1 and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10–1000 μmol dm−3) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid. PMID:25212600

  8. MGS-TES Phase Effects and Thermal Infrared Directional Emissivity Field Measurements of Martian Analog Sites

    NASA Astrophysics Data System (ADS)

    Pitman, K. M.; Bandfield, J. L.; Wolff, M. J.

    2006-03-01

    We present a set of on- and off-nadir thermal IR field and laboratory emissivity spectra for three undisturbed Mars terrain analog sites and analyze them for presence or absence of directional emissivity effects. Comparisons to moderate and low albedo surface MGS-TES EPF sequences are discussed.

  9. Lesion-induced DNA weak structural changes detected by pulsed EPR spectroscopy combined with site-directed spin labelling.

    PubMed

    Sicoli, Giuseppe; Mathis, Gérald; Aci-Sèche, Samia; Saint-Pierre, Christine; Boulard, Yves; Gasparutto, Didier; Gambarelli, Serge

    2009-06-01

    Double electron-electron resonance (DEER) was applied to determine nanometre spin-spin distances on DNA duplexes that contain selected structural alterations. The present approach to evaluate the structural features of DNA damages is thus related to the interspin distance changes, as well as to the flexibility of the overall structure deduced from the distance distribution. A set of site-directed nitroxide-labelled double-stranded DNA fragments containing defined lesions, namely an 8-oxoguanine, an abasic site or abasic site analogues, a nick, a gap and a bulge structure were prepared and then analysed by the DEER spectroscopic technique. New insights into the application of 4-pulse DEER sequence are also provided, in particular with respect to the spin probes' positions and the rigidity of selected systems. The lesion-induced conformational changes observed, which were supported by molecular dynamics studies, confirm the results obtained by other, more conventional, spectroscopic techniques. Thus, the experimental approaches described herein provide an efficient method for probing lesion-induced structural changes of nucleic acids.

  10. Simulation analysis of formycin 5?-monophosphate analog substrates in the ricin A-chain active site

    NASA Astrophysics Data System (ADS)

    Olson, Mark A.; Scovill, John P.; Hack, Dallas C.

    1995-06-01

    Ricin is an RNA N-glycosidase that hydrolyzes a single adenine base from a conserved loop of 28S ribosomal RNA, thus inactivating protein synthesis. Molecular-dynamics simulation methods are used to analyze the structural interactions and thermodynamics that govern the binding of formycin 5'-monophosphate (FMP) and several of its analogs to the active site of ricin A-chain. Simulations are carried out initiated from the X-ray crystal structure of the ricin-FMP complex with the ligand modeled as a dianion, monoanion and zwitterion. Relative changes in binding free energies are estimated for FMP analogs constructed from amino substitutions at the 2- and 2'-positions, and from hydroxyl substitution at the 2'-position.

  11. Simulation analysis of formycin 5'-monophosphate analog substrates in the ricin A-chain active site.

    PubMed

    Olson, M A; Scovill, J P; Hack, D C

    1995-06-01

    Ricin is an RNA N-glycosidase that hydrolyzes a single adenine base from a conserved loop of 28S ribosomal RNA, thus inactivating protein synthesis. Molecular-dynamics simulation methods are used to analyze the structural interactions and thermodynamics that govern the binding of formycin 5'-monophosphate (FMP) and several of its analogs to the active site of ricin A-chain. Simulations are carried out initiated from the X-ray crystal structure of the ricin-FMP complex with the ligand modeled as a dianion, monoanion and zwitterion. Relative changes in binding free energies are estimated for FMP analogs constructed from amino substitutions at the 2- and 2'-positions, and from hydroxyl substitution at the 2'-position.

  12. Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA.

    PubMed

    Hata, Kuniki; Urushibara, Ayumi; Yamashita, Shinichi; Lin, Mingzhang; Muroya, Yusa; Shikazono, Naoya; Yokoya, Akinari; Fu, Haiying; Katsumura, Yosuke

    2015-01-01

    Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 10(8) dm(3) mol(-1) s(-1) and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10-1000 μmol dm(-3)) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  13. Exobiology site selection for future Mars missions: Martian paleolake sediments and terrestrial analogs

    NASA Technical Reports Server (NTRS)

    Wharton, Robert A., Jr.

    1989-01-01

    This research was conducted to establish the scientific framework for the exobiological study of sediments on Mars and to encourage the selection of these sedimentary deposits as sampling sites for future Mars missions. A study was completed on the Antarctic Dry Valley Lakes (terrestrial analogs of the purported Martian paleolakes) and their sediments that allowed the development of quantitative models relating environmental factors to the nature of the biological community and sediment forming processes. The publications presented include: (1) Diversity of micro-fungi isolated in an Antarctic dry valley; (2) Lake Hoare, Antarctica--sedimentation through a thick perennial ice cover; (3) The possibility of life on Mars during a water-rich past; (4) An Antarctic research outpost as a model for planetary exploration; (5) Early Martian environments--the Antarctic and other terrestrial analogs; (6) Lipophilic pigments from the benthos of a perennially ice-covered Antarctic lake; and (7) Perennially ice-covered Lake Hoare, Antarctica--physical environment, biology, and sedimentation.

  14. Probing the ATP site of GRP78 with nucleotide triphosphate analogs

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

    Hughes, Scott J.; Antoshchenko, Tetyana; Chen, Yun

    conformation of the bound nucleotide flipped out of the active site, explaining the low affinity binding to GRP78 and suggesting that the 2'-OH group is essential for the high affinity binding to GRP78. Altogether, our results demonstrate that GRP78 ATPase possesses nucleotide specificity more relaxed than previously anticipated and can tolerate certain modifications to the nucleobase 7-position and, to a lesser extent, the beta-gamma bridging atom, thereby providing a possible atomic mechanism underlying the transmembrane transport of the ATP analogs.« less

  15. Probing the ATP site of GRP78 with nucleotide triphosphate analogs

    DOE PAGES

    Hughes, Scott J.; Antoshchenko, Tetyana; Chen, Yun; ...

    2016-05-04

    conformation of the bound nucleotide flipped out of the active site, explaining the low affinity binding to GRP78 and suggesting that the 2'-OH group is essential for the high affinity binding to GRP78. Altogether, our results demonstrate that GRP78 ATPase possesses nucleotide specificity more relaxed than previously anticipated and can tolerate certain modifications to the nucleobase 7-position and, to a lesser extent, the beta-gamma bridging atom, thereby providing a possible atomic mechanism underlying the transmembrane transport of the ATP analogs.« less

  16. Carbinolamine Formation and Dehydration in a DNA Repair Enzyme Active Site

    PubMed Central

    Dodson, M. L.; Walker, Ross C.; Lloyd, R. Stephen

    2012-01-01

    In order to suggest detailed mechanistic hypotheses for the formation and dehydration of a key carbinolamine intermediate in the T4 pyrimidine dimer glycosylase (T4PDG) reaction, we have investigated these reactions using steered molecular dynamics with a coupled quantum mechanics–molecular mechanics potential (QM/MM). We carried out simulations of DNA abasic site carbinolamine formation with and without a water molecule restrained to remain within the active site quantum region. We recovered potentials of mean force (PMF) from thirty replicate reaction trajectories using Jarzynski averaging. We demonstrated feasible pathways involving water, as well as those independent of water participation. The water–independent enzyme–catalyzed reaction had a bias–corrected Jarzynski–average barrier height of approximately for the carbinolamine formation reaction and ) for the reverse reaction at this level of representation. When the proton transfer was facilitated with an intrinsic quantum water, the barrier height was approximately in the forward (formation) reaction and for the reverse. In addition, two modes of unsteered (free dynamics) carbinolamine dehydration were observed: in one, the quantum water participated as an intermediate proton transfer species, and in the other, the active site protonated glutamate hydrogen was directly transferred to the carbinolamine oxygen. Water–independent unforced proton transfer from the protonated active site glutamate carboxyl to the unprotonated N–terminal amine was also observed. In summary, complex proton transfer events, some involving water intermediates, were studied in QM/MM simulations of T4PDG bound to a DNA abasic site. Imine carbinolamine formation was characterized using steered QM/MM molecular dynamics. Dehydration of the carbinolamine intermediate to form the final imine product was observed in free, unsteered, QM/MM dynamics simulations, as was unforced acid-base transfer between the active site

  17. Interactions of p-Nitrobenzene Diazonium Fluoroborate and Analogs with the Active Sites of Acetylcholine-Receptor and -Esterase*

    PubMed Central

    Mautner, Henry G.; Bartels, Eva

    1970-01-01

    p-Nitrobenzene diazonium fluoroborate (NDF) is a potent inhibitor of the carbamylcholine-induced depolarization of the electroplax and of acetylcholinesterase. It probably forms covalent bonds with the acetylcholine-receptor and -esterase at the active site of the proteins. Its inhibitory strength is at least the same as that of trimethylammonium diazonium fluoroborate (TDF). The p-acetoxy analog, with its weaker electron-withdrawing group, is about ten times weaker as an inhibitor than the trimethylammonium or p-nitro analogs, both of which have strong electron-withdrawing groups. After treatment of the electroplax preparation with dithiothreitol, NDF remains an irreversible receptor-inhibitor, while TDF becomes a potent reversible receptor-activator. TDF is self-inhibitory: applied before reduction, it no longer depolarizes. Although the first observations on TDF suggested that the compound labels both proteins by virtue of the steric complementary of its trimethylammonium group to a negative subsite in the proteins, the present study indicates that it is the positively charged diazonium group that reacts with the active sites of the proteins to form a covalent bond with an appropriate amino-acid residue. PMID:5272331

  18. Probing the active site tryptophan of Staphylococcus aureus thioredoxin with an analog

    PubMed Central

    Englert, Markus; Nakamura, Akiyoshi; Wang, Yane-Shih; Eiler, Daniel; Söll, Dieter; Guo, Li-Tao

    2015-01-01

    Genetically encoded non-canonical amino acids are powerful tools of protein research and engineering; in particular they allow substitution of individual chemical groups or atoms in a protein of interest. One such amino acid is the tryptophan (Trp) analog 3-benzothienyl-l-alanine (Bta) with an imino-to-sulfur substitution in the five-membered ring. Unlike Trp, Bta is not capable of forming a hydrogen bond, but preserves other properties of a Trp residue. Here we present a pyrrolysyl-tRNA synthetase-derived, engineered enzyme BtaRS that enables efficient and site-specific Bta incorporation into proteins of interest in vivo. Furthermore, we report a 2.1 Å-resolution crystal structure of a BtaRS•Bta complex to show how BtaRS discriminates Bta from canonical amino acids, including Trp. To show utility in protein mutagenesis, we used BtaRS to introduce Bta to replace the Trp28 residue in the active site of Staphylococcus aureus thioredoxin. This experiment showed that not the hydrogen bond between residues Trp28 and Asp58, but the bulky aromatic side chain of Trp28 is important for active site maintenance. Collectively, our study provides a new and robust tool for checking the function of Trp in proteins. PMID:26582921

  19. Sulfates on Mars as Markers of Aqueous Processes: An Integrated Multidisciplinary Study of Minerals, Mars Analog sites and Recent Mission Data

    NASA Technical Reports Server (NTRS)

    Bishop, J. L.; Lane, M. D.; Dyar, M. D.; Brown, A. J.; Parente, M.

    2006-01-01

    Our analyses of sulfate minerals, analog sites, and Martian spectra and spectral images is focused on characterization of the Martian surface and in particular identification of aqueous processes there.

  20. Geochemical Influence on Microbial Communities at CO2-Leakage Analog Sites.

    PubMed

    Ham, Baknoon; Choi, Byoung-Young; Chae, Gi-Tak; Kirk, Matthew F; Kwon, Man Jae

    2017-01-01

    Microorganisms influence the chemical and physical properties of subsurface environments and thus represent an important control on the fate and environmental impact of CO 2 that leaks into aquifers from deep storage reservoirs. How leakage will influence microbial populations over long time scales is largely unknown. This study uses natural analog sites to investigate the long-term impact of CO 2 leakage from underground storage sites on subsurface biogeochemistry. We considered two sites with elevated CO 2 levels (sample groups I and II) and one control site with low CO 2 content (group III). Samples from sites with elevated CO 2 had pH ranging from 6.2 to 4.5 and samples from the low-CO 2 control group had pH ranging from 7.3 to 6.2. Solute concentrations were relatively low for samples from the control group and group I but high for samples from group II, reflecting varying degrees of water-rock interaction. Microbial communities were analyzed through clone library and MiSeq sequencing. Each 16S rRNA analysis identified various bacteria, methane-producing archaea, and ammonia-oxidizing archaea. Both bacterial and archaeal diversities were low in groundwater with high CO 2 content and community compositions between the groups were also clearly different. In group II samples, sequences classified in groups capable of methanogenesis, metal reduction, and nitrate reduction had higher relative abundance in samples with relative high methane, iron, and manganese concentrations and low nitrate levels. Sequences close to Comamonadaceae were abundant in group I, while the taxa related to methanogens, Nitrospirae , and Anaerolineaceae were predominant in group II. Our findings provide insight into subsurface biogeochemical reactions that influence the carbon budget of the system including carbon fixation, carbon trapping, and CO 2 conversion to methane. The results also suggest that monitoring groundwater microbial community can be a potential tool for tracking CO 2

  1. Geochemical Influence on Microbial Communities at CO2-Leakage Analog Sites

    PubMed Central

    Ham, Baknoon; Choi, Byoung-Young; Chae, Gi-Tak; Kirk, Matthew F.; Kwon, Man Jae

    2017-01-01

    Microorganisms influence the chemical and physical properties of subsurface environments and thus represent an important control on the fate and environmental impact of CO2 that leaks into aquifers from deep storage reservoirs. How leakage will influence microbial populations over long time scales is largely unknown. This study uses natural analog sites to investigate the long-term impact of CO2 leakage from underground storage sites on subsurface biogeochemistry. We considered two sites with elevated CO2 levels (sample groups I and II) and one control site with low CO2 content (group III). Samples from sites with elevated CO2 had pH ranging from 6.2 to 4.5 and samples from the low-CO2 control group had pH ranging from 7.3 to 6.2. Solute concentrations were relatively low for samples from the control group and group I but high for samples from group II, reflecting varying degrees of water-rock interaction. Microbial communities were analyzed through clone library and MiSeq sequencing. Each 16S rRNA analysis identified various bacteria, methane-producing archaea, and ammonia-oxidizing archaea. Both bacterial and archaeal diversities were low in groundwater with high CO2 content and community compositions between the groups were also clearly different. In group II samples, sequences classified in groups capable of methanogenesis, metal reduction, and nitrate reduction had higher relative abundance in samples with relative high methane, iron, and manganese concentrations and low nitrate levels. Sequences close to Comamonadaceae were abundant in group I, while the taxa related to methanogens, Nitrospirae, and Anaerolineaceae were predominant in group II. Our findings provide insight into subsurface biogeochemical reactions that influence the carbon budget of the system including carbon fixation, carbon trapping, and CO2 conversion to methane. The results also suggest that monitoring groundwater microbial community can be a potential tool for tracking CO2 leakage from

  2. Natural analog studies: Licensing perspective

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

    Bradbury, J.W.

    1995-09-01

    This report describes the licensing perspective of the term {open_quotes}natural analog studies{close_quotes} as used in CFR Part 60. It describes the misunderstandings related to its definition which has become evident during discussions at the U.S Nuclear Regulatory Commission meetings and tries to clarify the appropriate applications of natural analog studies to aspects of repository site characterization.

  3. NaturAnalogs for the Unsaturated Zone

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

    A. Simmons; A. Unger; M. Murrell

    2000-03-08

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturatedmore » Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model.« less

  4. A commercial PCV2a-based vaccine is effective in protection from experimental challenge of PCV2 mutant with two amino acids elongation in capsid protein.

    PubMed

    Guo, Long-Jun; Fu, Yu-Jie; Huang, Li-Ping; Wang, Yi-Ping; Wei, Yan-Wu; Wu, Hong-Li; Liu, Chang-Ming

    2015-07-17

    Current commercial PCV2 vaccines are almost based on PCV2a and have been shown to be effective in reducing PCV2a and PCV2b viremia and PCV2-associated lesions and diseases. The recent emergence of novel mutant PCV2 (mPCV2) strains and linkage of mPCV2 with cases of porcine circovirus associated disease (PCVAD) in pig herds have raised concerns over emergence of vaccine-escape mutants and reduced efficacy of PCV2a-based vaccines. The aim of this study was to determine the ability of a commercial PCV2a-based vaccine developed by our laboratory to protect conventional pigs against experimental challenge with mPCV2 at 9 weeks of age. Twenty 4-week-old pigs free of PCV2 infection were randomly divided into four treatment groups with 5 pigs each. Two groups were unvaccinated as positive and negative controls. Another two groups were vaccinated with the commercial PCV2a-based vaccine (PCV2-LG strain, China) at 4 weeks of age and identical booster immunization was conducted 3 weeks post primary immunization. At 9 weeks of age, all pigs except the negative control were challenged with a mutant PCV2b/YJ (mPCV2b/YJ) with two amino acids elongation in capsid protein. The experiment was terminated 28 days after challenge. Under the conditions of this study, vaccinated pigs were protected against PCV2 viremia and lesions whereas unvaccinated pigs were not. Moreover, mPCV2b/YJ infection was demonstrated in positive control and almost all had macroscopic or microscopic lesions consistent with PCVAD while negative control did not develop PCVAD. This study indicates that mPCV2b/YJ infection alone can trigger PCVAD development and that the commercial vaccine (PCV2-LG) is still effective in protecting conventional pigs against the emerging mPCV2b/YJ strain in China. Copyright © 2015. Published by Elsevier Ltd.

  5. Plutonium Particle Migration in the Shallow Vadose Zone: The Nevada Test Site as an Analog Site

    NASA Astrophysics Data System (ADS)

    Hunt, J. R.; Smith, D. K.

    2004-12-01

    The upper meter of the vadose zone in desert environments is the horizon where wastes have been released and human exposure is determined through dermal, inhalation, and food uptake pathways. This region is also characterized by numerous coupled processes that determine contaminant transport, including precipitation infiltration, evapotranspiration, daily and annual temperature cycling, dust resuspension, animal burrowing, and geochemical weathering reactions. While there is considerable interest in colloidal transport of minerals, pathogenic organisms, and contaminants in the vadose zone, there are limited field sites where the actual occurrence of contaminant migration can be quantified over the appropriate spatial and temporal scales of interest. At the US Department of Energy Nevada Test Site, there have been numerous releases of radionuclides since the 1950's that have become field-scale tracer tests. One series of tests was the four safety shots conducted in an alluvial valley of Area 11 in the 1950's. These experiments tested the ability of nuclear materials to survive chemical explosions without initiating fission reactions. Four above-ground tests were conducted and they released plutonium and uranium on the desert valley floor with only one of the tests undergoing some fission. Shortly after the tests, the sites were surveyed for radionuclide distribution on the land surface using aerial surveys and with depth. Additional studies were conducted in the 1970's to better understand the fate of plutonium in the desert that included studies of depth distribution and dust resuspension. More recently, plutonium particle distribution in the soil profile was detected using autoradiography. The results to date demonstrate the vertical migration of plutonium particles to depths in excess of 30 cm in this arid vadose zone. While plutonium migration at the Nevada Test Site has been and continues to be a concern, these field experiments have become analog sites for the

  6. Geologic analyses of LANDSAT-1 multispectral imagery of a possible power plant site employing digital and analog image processing. [in Pennsylvania

    NASA Technical Reports Server (NTRS)

    Lovegreen, J. R.; Prosser, W. J.; Millet, R. A.

    1975-01-01

    A site in the Great Valley subsection of the Valley and Ridge physiographic province in eastern Pennsylvania was studied to evaluate the use of digital and analog image processing for geologic investigations. Ground truth at the site was obtained by a field mapping program, a subsurface exploration investigation and a review of available published and unpublished literature. Remote sensing data were analyzed using standard manual techniques. LANDSAT-1 imagery was analyzed using digital image processing employing the multispectral Image 100 system and using analog color processing employing the VP-8 image analyzer. This study deals primarily with linears identified employing image processing and correlation of these linears with known structural features and with linears identified manual interpretation; and the identification of rock outcrops in areas of extensive vegetative cover employing image processing. The results of this study indicate that image processing can be a cost-effective tool for evaluating geologic and linear features for regional studies encompassing large areas such as for power plant siting. Digital image processing can be an effective tool for identifying rock outcrops in areas of heavy vegetative cover.

  7. Covalent trapping of human DNA polymerase beta by the oxidative DNA lesion 2-deoxyribonolactone.

    PubMed

    DeMott, Michael S; Beyret, Ergin; Wong, Donny; Bales, Brian C; Hwang, Jae-Taeg; Greenberg, Marc M; Demple, Bruce

    2002-03-08

    Oxidized abasic residues in DNA constitute a major class of radiation and oxidative damage. Free radical attack on the nucleotidyl C-1' carbon yields 2-deoxyribonolactone (dL) as a significant lesion. Although dL residues are efficiently incised by the main human abasic endonuclease enzyme Ape1, we show here that subsequent excision by human DNA polymerase beta is impaired at dL compared with unmodified abasic sites. This inhibition is accompanied by accumulation of a protein-DNA cross-link not observed in reactions of polymerase beta with unmodified abasic sites, although a similar form can be trapped by reduction with sodium borohydride. The formation of the stably cross-linked species with dL depends on the polymerase lysine 72 residue, which forms a Schiff base with the C-1 aldehyde during excision of an unmodified abasic site. In the case of a dL residue, attack on the lactone C-1 by lysine 72 proceeds more slowly and evidently produces an amide linkage, which resists further processing. Consequently dL residues may not be readily repaired by "short-patch" base excision repair but instead function as suicide substrates in the formation of protein-DNA cross-links that may require alternative modes of repair.

  8. CO 2 leakage impacts on shallow groundwater. Field-scale reactive-transport simulations informed by observations at a natural analog site

    DOE PAGES

    Keating, Elizabeth H.; Hakala, J. Alexandra; Viswanathan, Hari; ...

    2013-03-01

    It is challenging to predict the degree to which shallow groundwater might be affected by leaks from a CO 2 sequestration reservoir, particularly over long time scales and large spatial scales. In this study observations at a CO 2 enriched shallow aquifer natural analog were used to develop a predictive model which is then used to simulate leakage scenarios. This natural analog provides the opportunity to make direct field observations of groundwater chemistry in the presence of elevated CO 2, to collect aquifer samples and expose them to CO 2 under controlled conditions in the laboratory, and to test themore » ability of multiphase reactive transport models to reproduce measured geochemical trends at the field-scale. The field observations suggest that brackish water entrained with the upwelling CO 2 are a more significant source of trace metals than in situ mobilization of metals due to exposure to CO 2. The study focuses on a single trace metal of concern at this site: U. Experimental results indicate that cation exchange/adsorption and dissolution/precipitation of calcite containing trace amounts of U are important reactions controlling U in groundwater at this site, and that the amount of U associated with calcite is fairly well constrained. Simulations incorporating these results into a 3-D multi-phase reactive transport model are able to reproduce the measured ranges and trends between pH, pCO 2, Ca, total C, U and Cl -at the field site. Although the true fluxes at the natural analog site are unknown, the cumulative CO 2 flux inferred from these simulations are approximately equivalent to 37.8E-3 MT, approximately corresponding to a .001% leak rate for injection at a large (750 MW) power plant. The leakage scenario simulations suggest that if the leak only persists for a short time the volume of aquifer contaminated by CO 2-induced mobilization of U will be relatively small, yet persistent over 100 a.« less

  9. Pyrrole-Based Antitubulin Agents: Two Distinct Binding Modalities are Predicted for C-2 Analogs in the Colchicine Site.

    PubMed

    Da, Chenxiao; Telang, Nakul; Barelli, Peter; Jia, Xin; Gupton, John T; Mooberry, Susan L; Kellogg, Glen E

    2012-01-12

    3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester is a promising antitubulin lead agent that targets the colchicine site of tubulin. C-2 analogs were synthesized and tested for microtubule depolymerizing and antiproliferative activity. Molecular modeling studies using both GOLD docking and HINT (Hydropathic INTeraction) scoring revealed two distinct binding modes that explain the structural-activity relationships and are in accord with the structural basis of colchicine binding to tubulin. The binding mode of higher activity compounds is buried deeper in the site and overlaps well with rings A and C of colchicine, while the lower activity binding mode shows fewer critical contacts with tubulin. The model distinguishes highly active compounds from those with weaker activities and provides novel insights into the colchicine site and compound design.

  10. Charge-regulation phase transition on surface lattices of titratable sites adjacent to electrolyte solutions: An analog of the Ising antiferromagnet in a magnetic field

    PubMed Central

    Shore, Joel D.; Thurston, George M.

    2018-01-01

    We report a charge-patterning phase transition on two-dimensional square lattices of titratable sites, here regarded as protonation sites, placed in a low-dielectric medium just below the planar interface between this medium and a salt solution. We calculate the work-of-charging matrix of the lattice with use of a linear Debye-Hückel model, as input to a grand-canonical partition function for the distribution of occupancy patterns. For a large range of parameter values, this model exhibits an approximate inverse cubic power-law decrease of the voltage produced by an individual charge, as a function of its in-lattice separation from neighboring titratable sites. Thus, the charge coupling voltage biases the local probabilities of proton binding as a function of the occupancy of sites for many neighbors beyond the nearest ones. We find that even in the presence of these longer-range interactions, the site couplings give rise to a phase transition in which the site occupancies exhibit an alternating, checkerboard pattern that is an analog of antiferromagnetic ordering. The overall strength W of this canonical charge coupling voltage, per unit charge, is a function of the Debye length, the charge depth, the Bjerrum length, and the dielectric coefficients of the medium and the solvent. The alternating occupancy transition occurs above a curve of thermodynamic critical points in the (pH-pK,W) plane, the curve representing a charge-regulation analog of variation of the Néel temperature of an Ising antiferromagnet as a function of an applied, uniform magnetic field. The analog of a uniform magnetic field in the antiferromagnet problem is a combination of pH-pK and W, and 1/W is the analog of the temperature in the antiferromagnet problem. We use Monte Carlo simulations to study the occupancy patterns of the titratable sites, including interactions out to the 37th nearest-neighbor category (a distance of 74 lattice constants), first validating simulations through

  11. Charge-regulation phase transition on surface lattices of titratable sites adjacent to electrolyte solutions: An analog of the Ising antiferromagnet in a magnetic field.

    PubMed

    Shore, Joel D; Thurston, George M

    2015-12-01

    We report a charge-patterning phase transition on two-dimensional square lattices of titratable sites, here regarded as protonation sites, placed in a low-dielectric medium just below the planar interface between this medium and a salt solution. We calculate the work-of-charging matrix of the lattice with use of a linear Debye-Hückel model, as input to a grand-canonical partition function for the distribution of occupancy patterns. For a large range of parameter values, this model exhibits an approximate inverse cubic power-law decrease of the voltage produced by an individual charge, as a function of its in-lattice separation from neighboring titratable sites. Thus, the charge coupling voltage biases the local probabilities of proton binding as a function of the occupancy of sites for many neighbors beyond the nearest ones. We find that even in the presence of these longer-range interactions, the site couplings give rise to a phase transition in which the site occupancies exhibit an alternating, checkerboard pattern that is an analog of antiferromagnetic ordering. The overall strength W of this canonical charge coupling voltage, per unit charge, is a function of the Debye length, the charge depth, the Bjerrum length, and the dielectric coefficients of the medium and the solvent. The alternating occupancy transition occurs above a curve of thermodynamic critical points in the (pH-pK,W) plane, the curve representing a charge-regulation analog of variation of the Néel temperature of an Ising antiferromagnet as a function of an applied, uniform magnetic field. The analog of a uniform magnetic field in the antiferromagnet problem is a combination of pH-pK and W, and 1/W is the analog of the temperature in the antiferromagnet problem. We use Monte Carlo simulations to study the occupancy patterns of the titratable sites, including interactions out to the 37th nearest-neighbor category (a distance of √74 lattice constants), first validating simulations through

  12. Charge-regulation phase transition on surface lattices of titratable sites adjacent to electrolyte solutions: An analog of the Ising antiferromagnet in a magnetic field

    NASA Astrophysics Data System (ADS)

    Shore, Joel D.; Thurston, George M.

    2015-12-01

    We report a charge-patterning phase transition on two-dimensional square lattices of titratable sites, here regarded as protonation sites, placed in a low-dielectric medium just below the planar interface between this medium and a salt solution. We calculate the work-of-charging matrix of the lattice with use of a linear Debye-Hückel model, as input to a grand-canonical partition function for the distribution of occupancy patterns. For a large range of parameter values, this model exhibits an approximate inverse cubic power-law decrease of the voltage produced by an individual charge, as a function of its in-lattice separation from neighboring titratable sites. Thus, the charge coupling voltage biases the local probabilities of proton binding as a function of the occupancy of sites for many neighbors beyond the nearest ones. We find that even in the presence of these longer-range interactions, the site couplings give rise to a phase transition in which the site occupancies exhibit an alternating, checkerboard pattern that is an analog of antiferromagnetic ordering. The overall strength W of this canonical charge coupling voltage, per unit charge, is a function of the Debye length, the charge depth, the Bjerrum length, and the dielectric coefficients of the medium and the solvent. The alternating occupancy transition occurs above a curve of thermodynamic critical points in the (p H-p K ,W ) plane, the curve representing a charge-regulation analog of variation of the Néel temperature of an Ising antiferromagnet as a function of an applied, uniform magnetic field. The analog of a uniform magnetic field in the antiferromagnet problem is a combination of p H-p K and W , and 1 /W is the analog of the temperature in the antiferromagnet problem. We use Monte Carlo simulations to study the occupancy patterns of the titratable sites, including interactions out to the 37th nearest-neighbor category (a distance of √{74 } lattice constants), first validating simulations

  13. Use of an analog site near Raymond, California, to develop equipment and methods for characterizing a potential high-level, nuclear waste repository site at Yucca Mountain, Nevada

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

    Umari, A.M.J.; Geldon, A.; Patterson, G.

    1994-12-31

    Yucca Mountain, Nevada, currently is being investigated by the U.S. Geological Survey as a potential site for a high-level nuclear waste repository. Planned hydraulic-stress and tracer tests in fractured, tuffaceous rocks below the water table at Yucca Mountain will require work at depths in excess of 1,300 feet. To facilitate prototype testing of equipment and methods to be used in aquifer tests at Yucca Mountain, an analog site was selected in the foothills of the Sierra Nevada near Raymond, California. Two of nine 250- to 300-feet deep wells drilled into fractured, granitic rocks at the Raymond site have been instrumentedmore » with packers, pressure transducers, and other equipment that will be used at Yucca Mountain. Aquifer tests conducted at the Raymond site to date have demonstrated a need to modify some of the equipment and methods conceived for use at Yucca Mountain.« less

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

    Xia, Shuangluo; Vashishtha, Ashwani; Bulkley, David

    During DNA synthesis, base stacking and Watson-Crick (WC) hydrogen bonding increase the stability of nascent base pairs when they are in a ternary complex. To evaluate the contribution of base stacking to the incorporation efficiency of dNTPs when a DNA polymerase encounters an abasic site, we varied the penultimate base pairs (PBs) adjacent to the abasic site using all 16 possible combinations. We then determined pre-steady-state kinetic parameters with an RB69 DNA polymerase variant and solved nine structures of the corresponding ternary complexes. The efficiency of incorporation for incoming dNTPs opposite an abasic site varied between 2- and 210-fold dependingmore » on the identity of the PB. We propose that the A rule can be extended to encompass the fact that DNA polymerase can bypass dA/abasic sites more efficiently than other dN/abasic sites. Crystal structures of the ternary complexes show that the surface of the incoming base was stacked against the PB's interface and that the kinetic parameters for dNMP incorporation were consistent with specific features of base stacking, such as surface area and partial charge-charge interactions between the incoming base and the PB. Without a templating nucleotide residue, an incoming dNTP has no base with which it can hydrogen bond and cannot be desolvated, so that these surrounding water molecules become ordered and remain on the PB's surface in the ternary complex. When these water molecules are on top of a hydrophobic patch on the PB, they destabilize the ternary complex, and the incorporation efficiency of incoming dNTPs is reduced.« less

  15. Terrestrial Analogs to Mars

    NASA Astrophysics Data System (ADS)

    Farr, T. G.; Arcone, S.; Arvidson, R. W.; Baker, V.; Barlow, N. G.; Beaty, D.; Bell, M. S.; Blankenship, D. D.; Bridges, N.; Briggs, G.; Bulmer, M.; Carsey, F.; Clifford, S. M.; Craddock, R. A.; Dickerson, P. W.; Duxbury, N.; Galford, G. L.; Garvin, J.; Grant, J.; Green, J. R.; Gregg, T. K. P.; Guinness, E.; Hansen, V. L.; Hecht, M. H.; Holt, J.; Howard, A.; Keszthelyi, L. P.; Lee, P.; Lanagan, P. D.; Lentz, R. C. F.; Leverington, D. W.; Marinangeli, L.; Moersch, J. E.; Morris-Smith, P. A.; Mouginis-Mark, P.; Olhoeft, G. R.; Ori, G. G.; Paillou, P.; Reilly, J. F., II; Rice, J. W., Jr.; Robinson, C. A.; Sheridan, M.; Snook, K.; Thomson, B. J.; Watson, K.; Williams, K.; Yoshikawa, K.

    2002-08-01

    It is well recognized that interpretations of Mars must begin with the Earth as a reference. The most successful comparisons have focused on understanding geologic processes on the Earth well enough to extrapolate to Mars' environment. Several facets of terrestrial analog studies have been pursued and are continuing. These studies include field workshops, characterization of terrestrial analog sites, instrument tests, laboratory measurements (including analysis of Martian meteorites), and computer and laboratory modeling. The combination of all these activities allows scientists to constrain the processes operating in specific terrestrial environments and extrapolate how similar processes could affect Mars. The Terrestrial Analogs for Mars Community Panel has considered the following two key questions: (1) How do terrestrial analog studies tie in to the Mars Exploration Payload Assessment Group science questions about life, past climate, and geologic evolution of Mars, and (2) How can future instrumentation be used to address these questions. The panel has considered the issues of data collection, value of field workshops, data archiving, laboratory measurements and modeling, human exploration issues, association with other areas of solar system exploration, and education and public outreach activities.

  16. Analysis of Structural Flexibility of Damaged DNA Using Thiol-Tethered Oligonucleotide Duplexes

    PubMed Central

    Fujita, Masashi; Watanabe, Shun; Yoshizawa, Mariko; Yamamoto, Junpei; Iwai, Shigenori

    2015-01-01

    Bent structures are formed in DNA by the binding of small molecules or proteins. We developed a chemical method to detect bent DNA structures. Oligonucleotide duplexes in which two mercaptoalkyl groups were attached to the positions facing each other across the major groove were prepared. When the duplex contained the cisplatin adduct, which was proved to induce static helix bending, interstrand disulfide bond formation under an oxygen atmosphere was detected by HPLC analyses, but not in the non-adducted duplex, when the two thiol-tethered nucleosides were separated by six base pairs. When the insert was five and seven base pairs, the disulfide bond was formed and was not formed, respectively, regardless of the cisplatin adduct formation. The same reaction was observed in the duplexes containing an abasic site analog and the (6–4) photoproduct. Compared with the cisplatin case, the disulfide bond formation was slower in these duplexes, but the reaction rate was nearly independent of the linker length. These results indicate that dynamic structural changes of the abasic site- and (6–4) photoproduct-containing duplexes could be detected by our method. It is strongly suggested that the UV-damaged DNA-binding protein, which specifically binds these duplexes and functions at the first step of global-genome nucleotide excision repair, recognizes the easily bendable nature of damaged DNA. PMID:25679955

  17. Crew/Robot Coordinated Planetary EVA Operations at a Lunar Base Analog Site

    NASA Technical Reports Server (NTRS)

    Diftler, M. A.; Ambrose, R. O.; Bluethmann, W. J.; Delgado, F. J.; Herrera, E.; Kosmo, J. J.; Janoiko, B. A.; Wilcox, B. H.; Townsend, J. A.; Matthews, J. B.; hide

    2007-01-01

    Under the direction of NASA's Exploration Technology Development Program, robots and space suited subjects from several NASA centers recently completed a very successful demonstration of coordinated activities indicative of base camp operations on the lunar surface. For these activities, NASA chose a site near Meteor Crater, Arizona close to where Apollo Astronauts previously trained. The main scenario demonstrated crew returning from a planetary EVA (extra-vehicular activity) to a temporary base camp and entering a pressurized rover compartment while robots performed tasks in preparation for the next EVA. Scenario tasks included: rover operations under direct human control and autonomous modes, crew ingress and egress activities, autonomous robotic payload removal and stowage operations under both local control and remote control from Houston, and autonomous robotic navigation and inspection. In addition to the main scenario, participants had an opportunity to explore additional robotic operations: hill climbing, maneuvering heaving loads, gathering geo-logical samples, drilling, and tether operations. In this analog environment, the suited subjects and robots experienced high levels of dust, rough terrain, and harsh lighting.

  18. Fostering Multilateral Involvement in Analog Research

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2015-01-01

    International collaboration in space flight research is an effective means for conducting investigations and utilizing limited resources to the fullest extent. Through these multilateral collaborations mutual research questions can be investigated and resources contributed by each international partner to maximize the scientific benefits to all parties. Recently the international partners embraced this approach to initiate collaborations in ground-based space flight analog environments. In 2011, the International Analog Research Working Group was established, and later named the International Human Space Flight Analog Research Coordination Group (HANA). Among the goals of this working group are to 1) establish a framework to coordinate research campaigns, as appropriate, to minimize duplication of effort and enhance synergy; 2) define what analogs are best to use for collaborative interests; and 3) facilitate interaction between discipline experts in order to have the full benefit of international expertise. To accomplish these goals, HANA is currently engaged in developing international research campaigns in ground-based analogs. Plans are being made for an international solicitation for proposals to address research of common interest to all international partners. This solicitation with identify an analog environment that will best accommodate the types of investigations requested. Once selected, studies will be integrated into a campaign and implemented at the analog site. Through these combined efforts, research beneficial to all partners will be conducted efficiently to further address human risks of space exploration.

  19. Analog current mode analog/digital converter

    NASA Technical Reports Server (NTRS)

    Hadidi, Khayrollah (Inventor)

    1996-01-01

    An improved subranging or comparator circuit is provided for an analog-to-digital converter. As a subranging circuit, the circuit produces a residual signal representing the difference between an analog input signal and an analog of a digital representation. This is achieved by subdividing the digital representation into two or more parts and subtracting from the analog input signal analogs of each of the individual digital portions. In another aspect of the present invention, the subranging circuit comprises two sets of differential input pairs in which the transconductance of one differential input pair is scaled relative to the transconductance of the other differential input pair. As a consequence, the same resistor string may be used for two different digital-to-analog converters of the subranging circuit.

  20. Bioconjugation of Oligodeoxynucleotides Carrying 1,4-Dicarbonyl Groups via Reductive Amination with Lysine Residues.

    PubMed

    Yang, Bo; Jinnouchi, Akiko; Usui, Kazuteru; Katayama, Tsutomu; Fujii, Masayuki; Suemune, Hiroshi; Aso, Mariko

    2015-08-19

    We evaluated the efficacy of bioconjugation of oligodeoxynucleotides (ODNs) containing 1,4-dicarbonyl groups, a C4'-oxidized abasic site (OAS), and a newly designed 2'-methoxy analogue, via reductive amination with lysine residues. Dicarbonyls, aldehyde and ketone at C1- and C4-positions of deoxyribose in the ring-opened form of OAS allowed efficient reaction with amines. Kinetic studies indicated that reductive amination of OAS-containing ODNs with a proximal amine on the complementary strand proceeded 10 times faster than the corresponding reaction of an ODN containing an abasic site with C1-aldehyde. Efficient reductive amination between the DNA-binding domain of Escherichia coli DnaA protein and ODNs carrying OAS in the DnaA-binding sequence proceeded at the lysine residue in proximity to the phosphate group at the 5'-position of the OAS, in contrast to unsuccessful conjugation with abasic site ODNs, even though they have similar aldehydes. Theoretical calculation indicated that the C1-aldehyde of OAS was more accessible to the target lysine than that of the abasic site. These results demonstrate the potential utility of cross-linking strategies that use dicarbonyl-containing ODNs for the study of protein-nucleic acid interactions. Conjugation with a lysine-containing peptide that lacked specific affinity for ODN was also successful, further highlighting the advantages of 1,4-dicarbonyls.

  1. High resolution multi-facies realizations of sedimentary reservoir and aquifer analogs

    PubMed Central

    Bayer, Peter; Comunian, Alessandro; Höyng, Dominik; Mariethoz, Gregoire

    2015-01-01

    Geological structures are by nature inaccessible to direct observation. This can cause difficulties in applications where a spatially explicit representation of such structures is required, in particular when modelling fluid migration in geological formations. An increasing trend in recent years has been to use analogs to palliate this lack of knowledge, i.e., exploiting the spatial information from sites where the geology is accessible (outcrops, quarry sites) and transferring the observed properties to a study site deemed geologically similar. While this approach is appealing, it is difficult to put in place because of the lack of access to well-documented analog data. In this paper we present comprehensive analog data sets which characterize sedimentary structures from important groundwater hosting formations in Germany and Brazil. Multiple 2-D outcrop faces are described in terms of hydraulic, thermal and chemical properties and interpolated in 3-D using stochastic techniques. These unique data sets can be used by the wider community to implement analog approaches for characterizing reservoir and aquifer formations. PMID:26175910

  2. Chemical repair of base lesions, AP-sites, and strand breaks on plasmid DNA in dilute aqueous solution by ascorbic acid

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

    Hata, Kuniki; Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakatashirane, Tokai-mura, Naka-gun, Ibaraki 319-1195; Urushibara, Ayumi

    Highlights: •We report a novel mechanism of radiation protection of DNA by chemical activity of ascorbic acid. •The “chemical repair” of DNA damage was revealed using biochemical assay and chemical kinetics analysis. •We found that ascorbic acid significantly repairs precursors of nucleobase lesions and abasic sites. •However, ascorbic acid seldom repairs precursors of DNA-strand breaks. -- Abstract: We quantified the damage yields produced in plasmid DNA by γ-irradiation in the presence of low concentrations (10–100 μM) of ascorbic acid, which is a major antioxidant in living systems, to clarify whether it chemically repairs radiation damage in DNA. The yield ofmore » DNA single strand breaks induced by irradiation was analyzed with agarose gel electrophoresis as conformational changes in closed circular plasmids. Base lesions and abasic sites were also observed as additional conformational changes by treating irradiated samples with glycosylase proteins. By comparing the suppression efficiencies to the induction of each DNA lesion, in addition to scavenging of the OH radicals derived from water radiolysis, it was found that ascorbic acid promotes the chemical repair of precursors of AP-sites and base lesions more effectively than those of single strand breaks. We estimated the efficiency of the chemical repair of each lesion using a kinetic model. Approximately 50–60% of base lesions and AP-sites were repaired by 10 μM ascorbic acid, although strand breaks were largely unrepaired by ascorbic acid at low concentrations. The methods in this study will provide a route to understanding the mechanistic aspects of antioxidant activity in living systems.« less

  3. In vitro characterization of DNA gyrase inhibition by microcin B17 analogs with altered bisheterocyclic sites

    PubMed Central

    Zamble, Deborah B.; Miller, Deborah A.; Heddle, Jonathan G.; Maxwell, Anthony; Walsh, Christopher T.; Hollfelder, Florian

    2001-01-01

    Microcin B17 (MccB17) is a 3.1-kDa Escherichia coli antibiotic that contains thiazole and oxazole heterocycles in a peptide backbone. MccB17 inhibits its cellular target, DNA gyrase, by trapping the enzyme in a complex that is covalently bound to double-strand cleaved DNA, in a manner similar to the well-known quinolone drugs. The identification of gyrase as the target of MccB17 provides an opportunity to analyze the relationship between the structure of this unusual antibiotic and its activity. In this report, steady-state parameters are used to describe the induction of the cleavable complex by MccB17 analogs containing modified bisheterocyclic sites. The relative potency of these analogs corresponds to the capacity of the compounds to prevent growth of sensitive cells. In contrast to previously reported experiments, inhibition of DNA gyrase supercoiling activity by wild-type MccB17 also was observed. These results suggest that DNA gyrase is the main intracellular target of MccB17. This study probes the structure-function relationship of a new class of gyrase inhibitors and demonstrates that these techniques could be used to analyze compounds in the search for clinically useful antibiotics that block DNA gyrase. PMID:11427730

  4. Correlations Between Life-Detection Techniques and Implications for Sampling Site Selection in Planetary Analog Missions

    NASA Astrophysics Data System (ADS)

    Gentry, Diana M.; Amador, Elena S.; Cable, Morgan L.; Chaudry, Nosheen; Cullen, Thomas; Jacobsen, Malene B.; Murukesan, Gayathri; Schwieterman, Edward W.; Stevens, Adam H.; Stockton, Amanda; Tan, George; Yin, Chang; Cullen, David C.; Geppert, Wolf

    2017-10-01

    We conducted an analog sampling expedition under simulated mission constraints to areas dominated by basaltic tephra of the Eldfell and Fimmvörðuháls lava fields (Iceland). Sites were selected to be "homogeneous" at a coarse remote sensing resolution (10-100 m) in apparent color, morphology, moisture, and grain size, with best-effort realism in numbers of locations and replicates. Three different biomarker assays (counting of nucleic-acid-stained cells via fluorescent microscopy, a luciferin/luciferase assay for adenosine triphosphate, and quantitative polymerase chain reaction (qPCR) to detect DNA associated with bacteria, archaea, and fungi) were characterized at four nested spatial scales (1 m, 10 m, 100 m, and >1 km) by using five common metrics for sample site representativeness (sample mean variance, group F tests, pairwise t tests, and the distribution-free rank sum H and u tests). Correlations between all assays were characterized with Spearman's rank test. The bioluminescence assay showed the most variance across the sites, followed by qPCR for bacterial and archaeal DNA; these results could not be considered representative at the finest resolution tested (1 m). Cell concentration and fungal DNA also had significant local variation, but they were homogeneous over scales of >1 km. These results show that the selection of life detection assays and the number, distribution, and location of sampling sites in a low biomass environment with limited a priori characterization can yield both contrasting and complementary results, and that their interdependence must be given due consideration to maximize science return in future biomarker sampling expeditions.

  5. Long-acting follicle-stimulating hormone analogs containing N-linked glycosylation exhibited increased bioactivity compared with o-linked analogs in female rats.

    PubMed

    Weenen, C; Peña, J E; Pollak, S V; Klein, J; Lobel, L; Trousdale, R K; Palmer, S; Lustbader, E G; Ogden, R T; Lustbader, J W

    2004-10-01

    The effects of altering the number and type of additional carbohydrate moieties on the pharmacokinetic and pharmacodynamic properties of FSH were examined in this report. A series of single-chain follitropins, containing variable numbers of additional N- (or O-) linked carbohydrates, were designed and expressed in Chinese hamster ovary cells. Proper folding, efficient receptor binding, and signal transduction were confirmed by in vitro assays. Pharmacokinetic and pharmacodynamic parameters were evaluated in immature female Sprague Dawley rats. Increasing the number of glycosylation sites with either N- (or O-) linked moieties extended the elimination half-life as much as 2-fold compared with recombinant human FSH (rhFSH). However, there was a maximum elimination half-life such that further glycosylation provided no additional lengthening of the half-life. Conversely, biopotency, as assessed by inhibin A levels 74 h post injection, and follicle production were significantly higher for the N-linked analogs. Rats stimulated with the longest acting analogs (either N- or O-linked) showed significantly higher ovarian weights than rats receiving a single injection of rhFSH. The analog containing four additional N-linked sites (rhFSH-N4) had the greatest number of large, preovulatory follicles. Although the half-life of rhFSH-N4 displayed no further enhancement beyond the other longest acting analogs, this analog exhibited significantly increased biopotency in rats. This work provides the basis for the generation of a series of reagents potentially useful for therapeutic applications.

  6. Lesion bypass activity of DNA polymerase θ (POLQ) is an intrinsic property of the pol domain and depends on unique sequence inserts.

    PubMed

    Hogg, Matthew; Seki, Mineaki; Wood, Richard D; Doublié, Sylvie; Wallace, Susan S

    2011-01-21

    DNA polymerase θ (POLQ, polθ) is a large, multidomain DNA polymerase encoded in higher eukaryotic genomes. It is important for maintaining genetic stability in cells and helping protect cells from DNA damage caused by ionizing radiation. POLQ contains an N-terminal helicase-like domain, a large central domain of indeterminate function, and a C-terminal polymerase domain with sequence similarity to the A-family of DNA polymerases. The enzyme has several unique properties, including low fidelity and the ability to insert and extend past abasic sites and thymine glycol lesions. It is not known whether the abasic site bypass activity is an intrinsic property of the polymerase domain or whether helicase activity is also required. Three "insertion" sequence elements present in POLQ are not found in any other A-family DNA polymerase, and it has been proposed that they may lend some unique properties to POLQ. Here, we analyzed the activity of the DNA polymerase in the absence of each sequence insertion. We found that the pol domain is capable of highly efficient bypass of abasic sites in the absence of the helicase-like or central domains. Insertion 1 increases the processivity of the polymerase but has little, if any, bearing on the translesion synthesis properties of the enzyme. However, removal of insertions 2 and 3 reduces activity on undamaged DNA and completely abrogates the ability of the enzyme to bypass abasic sites or thymine glycol lesions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Non-Covalent Fluorescent Labeling of Hairpin DNA Probe Coupled with Hybridization Chain Reaction for Sensitive DNA Detection.

    PubMed

    Song, Luna; Zhang, Yonghua; Li, Junling; Gao, Qiang; Qi, Honglan; Zhang, Chengxiao

    2016-04-01

    An enzyme-free signal amplification-based assay for DNA detection was developed using fluorescent hairpin DNA probes coupled with hybridization chain reaction (HCR). The hairpin DNAs were designed to contain abasic sites in the stem moiety. Non-covalent labeling of the hairpin DNAs was achieved when a fluorescent ligand was bound to the abasic sites through hydrogen bonding with the orphan cytosine present on the complementary strand, accompanied by quench of ligand fluorescence. As a result, the resultant probes, the complex formed between the hairpin DNA and ligand, showed almost no fluorescence. Upon hybridization with target DNA, the probe underwent a dehybridization of the stem moiety containing an abasic site. The release of ligand from the abasic site to the solution resulted in an effective fluorescent enhancement, which can be used as a signal. Compared with a sensing system without HCR, a 20-fold increase in the sensitivity was achieved using the sensing system with HCR. The fluorescent intensity of the sensing system increased with the increase in target DNA concentration from 0.5 nM to 100 nM. A single mismatched target ss-DNA could be effectively discriminated from complementary target DNA. Genotyping of a G/C single-nucleotide polymorphism of polymerase chain reaction (PCR) products was successfully demonstrated with the sensing system. Therefore, integrating HCR strategy with non-covalent labeling of fluorescent hairpin DNA probes provides a sensitive and cost-effective DNA assay. © The Author(s) 2016.

  8. Temperature and electrolyte optimization of the α-hemolysin latch sensing zone for detection of base modification in double-stranded DNA.

    PubMed

    Johnson, Robert P; Fleming, Aaron M; Jin, Qian; Burrows, Cynthia J; White, Henry S

    2014-08-19

    The latch region of the wild-type protein pore α-hemolysin (α-HL) constitutes a sensing zone for individual abasic sites (and furan analogs) in double-stranded DNA (dsDNA). The presence of an abasic site or furan within a DNA duplex, electrophoretically captured in the α-HL vestibule and positioned at the latch region, can be detected based on the current blockage prior to duplex unzipping. We investigated variations in blockage current as a function of temperature (12-35°C) and KCl concentration (0.15-1.0 M) to understand the origin of the current signature and to optimize conditions for identifying the base modification. In 1 M KCl solution, substitution of a furan for a cytosine base in the latch region results in an ∼ 8 kJ mol(-1) decrease in the activation energy for ion transport through the protein pore. This corresponds to a readily measured ∼ 2 pA increase in current at room temperature. Optimal resolution for detecting the presence of a furan in the latch region is achieved at lower KCl concentrations, where the noise in the measured blockage current is significantly lower. The noise associated with the blockage current also depends on the stability of the duplex (as measured from the melting temperature), where a greater noise in the measured blockage current is observed for less stable duplexes. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Conformational Dynamics of DNA Repair by Escherichia coli Endonuclease III*

    PubMed Central

    Kuznetsov, Nikita A.; Kladova, Olga A.; Kuznetsova, Alexandra A.; Ishchenko, Alexander A.; Saparbaev, Murat K.; Zharkov, Dmitry O.; Fedorova, Olga S.

    2015-01-01

    Escherichia coli endonuclease III (Endo III or Nth) is a DNA glycosylase with a broad substrate specificity for oxidized or reduced pyrimidine bases. Endo III possesses two types of activities: N-glycosylase (hydrolysis of the N-glycosidic bond) and AP lyase (elimination of the 3′-phosphate of the AP-site). We report a pre-steady-state kinetic analysis of structural rearrangements of the DNA substrates and uncleavable ligands during their interaction with Endo III. Oligonucleotide duplexes containing 5,6-dihydrouracil, a natural abasic site, its tetrahydrofuran analog, and undamaged duplexes carried fluorescent DNA base analogs 2-aminopurine and 1,3-diaza-2-oxophenoxazine as environment-sensitive reporter groups. The results suggest that Endo III induces several fast sequential conformational changes in DNA during binding, lesion recognition, and adjustment to a catalytically competent conformation. A comparison of two fluorophores allowed us to distinguish between the events occurring in the damaged and undamaged DNA strand. Combining our data with the available structures of Endo III, we conclude that this glycosylase uses a multistep mechanism of damage recognition, which likely involves Gln41 and Leu81 as DNA lesion sensors. PMID:25869130

  10. Correlations Between Life-Detection Techniques and Implications for Sampling Site Selection in Planetary Analog Missions.

    PubMed

    Gentry, Diana M; Amador, Elena S; Cable, Morgan L; Chaudry, Nosheen; Cullen, Thomas; Jacobsen, Malene B; Murukesan, Gayathri; Schwieterman, Edward W; Stevens, Adam H; Stockton, Amanda; Tan, George; Yin, Chang; Cullen, David C; Geppert, Wolf

    2017-10-01

    We conducted an analog sampling expedition under simulated mission constraints to areas dominated by basaltic tephra of the Eldfell and Fimmvörðuháls lava fields (Iceland). Sites were selected to be "homogeneous" at a coarse remote sensing resolution (10-100 m) in apparent color, morphology, moisture, and grain size, with best-effort realism in numbers of locations and replicates. Three different biomarker assays (counting of nucleic-acid-stained cells via fluorescent microscopy, a luciferin/luciferase assay for adenosine triphosphate, and quantitative polymerase chain reaction (qPCR) to detect DNA associated with bacteria, archaea, and fungi) were characterized at four nested spatial scales (1 m, 10 m, 100 m, and >1 km) by using five common metrics for sample site representativeness (sample mean variance, group F tests, pairwise t tests, and the distribution-free rank sum H and u tests). Correlations between all assays were characterized with Spearman's rank test. The bioluminescence assay showed the most variance across the sites, followed by qPCR for bacterial and archaeal DNA; these results could not be considered representative at the finest resolution tested (1 m). Cell concentration and fungal DNA also had significant local variation, but they were homogeneous over scales of >1 km. These results show that the selection of life detection assays and the number, distribution, and location of sampling sites in a low biomass environment with limited a priori characterization can yield both contrasting and complementary results, and that their interdependence must be given due consideration to maximize science return in future biomarker sampling expeditions. Key Words: Astrobiology-Biodiversity-Microbiology-Iceland-Planetary exploration-Mars mission simulation-Biomarker. Astrobiology 17, 1009-1021.

  11. Identification of Propofol Binding Sites in a Nicotinic Acetylcholine Receptor with a Photoreactive Propofol Analog*

    PubMed Central

    Jayakar, Selwyn S.; Dailey, William P.; Eckenhoff, Roderic G.; Cohen, Jonathan B.

    2013-01-01

    Propofol, a widely used intravenous general anesthetic, acts at anesthetic concentrations as a positive allosteric modulator of γ-aminobutyric acid type A receptors and at higher concentration as an inhibitor of nicotinic acetylcholine receptors (nAChRs). Here, we characterize propofol binding sites in a muscle-type nAChR by use of a photoreactive analog of propofol, 2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenol (AziPm). Based upon radioligand binding assays, AziPm stabilized the Torpedo nAChR in the resting state, whereas propofol stabilized the desensitized state. nAChR-rich membranes were photolabeled with [3H]AziPm, and labeled amino acids were identified by Edman degradation. [3H]AziPm binds at three sites within the nAChR transmembrane domain: (i) an intrasubunit site in the δ subunit helix bundle, photolabeling in the nAChR desensitized state (+agonist) δM2-18′ and two residues in δM1 (δPhe-232 and δCys-236); (ii) in the ion channel, photolabeling in the nAChR resting, closed channel state (−agonist) amino acids in the M2 helices (αM2-6′, βM2-6′ and -13′, and δM2-13′) that line the channel lumen (with photolabeling reduced by >90% in the desensitized state); and (iii) at the γ-α interface, photolabeling αM2-10′. Propofol enhanced [3H]AziPm photolabeling at αM2-10′. Propofol inhibited [3H]AziPm photolabeling within the δ subunit helix bundle at lower concentrations (IC50 = 40 μm) than it inhibited ion channel photolabeling (IC50 = 125 μm). These results identify for the first time a single intrasubunit propofol binding site in the nAChR transmembrane domain and suggest that this is the functionally relevant inhibitory binding site. PMID:23300078

  12. Small constrained SP1-7 analogs bind to a unique site and promote anti-allodynic effects following systemic injection in mice.

    PubMed

    Jonsson, A; Fransson, R; Haramaki, Y; Skogh, A; Brolin, E; Watanabe, H; Nordvall, G; Hallberg, M; Sandström, A; Nyberg, F

    2015-07-09

    Previous results have shown that the substance P (SP) N-terminal fragment SP1-7 may attenuate hyperalgesia and produce anti-allodynia in animals using various experimental models for neuropathic pain. The heptapeptide was found to induce its effects through binding to and activating specific sites apart from any known neurokinin or opioid receptor. Furthermore, we have applied a medicinal chemistry program to develop lead compounds mimicking the effect of SP1-7. The present study was designed to evaluate the pharmacological effect of these compounds using the mouse spared nerve injury (SNI) model of chronic neuropathic pain. Also, as no comprehensive screen with the aim to identify the SP1-7 target has yet been performed we screened our lead compound H-Phe-Phe-NH2 toward a panel of drug targets. The extensive target screen, including 111 targets, did not reveal any hit for the binding site among a number of known receptors or enzymes involved in pain modulation. Our animal studies confirmed that SP1-7, but also synthetic analogs thereof, possesses anti-allodynic effects in the mouse SNI model of neuropathic pain. One of the lead compounds, a constrained H-Phe-Phe-NH2 analog, was shown to exhibit a significant anti-allodynic effect. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Evaluation of the Tindouf Basin Region in Southern Morocco as an Analog Site for Soil Geochemistry on Noachian Mars.

    PubMed

    Oberlin, Elizabeth A; Claire, Mark W; Kounaves, Samuel P

    2018-02-09

    Locations on Earth that provide insights into processes that may be occurring or may have occurred throughout martian history are often broadly deemed "Mars analog environments." As no single locale can precisely represent a past or present martian environment, it is important to focus on characterization of terrestrial processes that produce analogous features to those observed in specific regions of Mars or, if possible, specific time periods during martian history. Here, we report on the preservation of ionic species in soil samples collected from the Tindouf region of Morocco and compare them with the McMurdo Dry Valleys of Antarctica, the Atacama Desert in Chile, the martian meteorite EETA79001, and the in situ Mars analyses from the Phoenix Wet Chemistry Laboratory (WCL). The Moroccan samples show the greatest similarity with those from Victoria Valley, Beacon Valley, and the Atacama, while being consistently depleted compared to University Valley and enriched compared to Taylor Valley. The NO 3 /Cl ratios are most similar to Victoria Valley and Atacama, while the SO 4 /Cl ratios are similar to those from Beacon Valley, Victoria Valley, and the Atacama. While perchlorate concentrations in the Moroccan samples are typically lower than those found in samples of other analog sites, conditions in the region are sufficiently arid to retain oxychlorines at detectable levels. Our results suggest that the Tindouf Basin in Morocco can serve as a suitable analogue for the soil geochemistry and subsequent aridification of the Noachian epoch on Mars. Key Words: Mars analogues-Antarctica-Morocco-Oxyanions-Perchlorate-Nitrate. Astrobiology 18, xxx-xxx.

  14. Lunar Analog

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2009-01-01

    In this viewgraph presentation, a ground-based lunar analog is developed for the return of manned space flight to the Moon. The contents include: 1) Digital Astronaut; 2) Bed Design; 3) Lunar Analog Feasibility Study; 4) Preliminary Data; 5) Pre-pilot Study; 6) Selection of Stockings; 7) Lunar Analog Pilot Study; 8) Bed Design for Lunar Analog Pilot.

  15. Analogical scaffolding: Making meaning in physics through representation and analogy

    NASA Astrophysics Data System (ADS)

    Podolefsky, Noah Solomon

    This work reviews the literature on analogy, introduces a new model of analogy, and presents a series of experiments that test and confirm the utility of this model to describe and predict student learning in physics with analogy. Pilot studies demonstrate that representations (e.g., diagrams) can play a key role in students' use of analogy. A new model of analogy, Analogical Scaffolding, is developed to explain these initial empirical results. This model will be described in detail, and then applied to describe and predict the outcomes of further experiments. Two large-scale (N>100) studies will demonstrate that: (1) students taught with analogies, according to the Analogical Scaffolding model, outperform students taught without analogies on pre-post assessments focused on electromagnetic waves; (2) the representational forms used to teach with analogy can play a significant role in student learning, with students in one treatment group outperforming students in other treatment groups by factors of two or three. It will be demonstrated that Analogical Scaffolding can be used to predict these results, as well as finer-grained results such as the types of distracters students choose in different treatment groups, and to describe and analyze student reasoning in interviews. Abstraction in physics is reconsidered using Analogical Scaffolding. An operational definition of abstraction is developed within the Analogical Scaffolding framework and employed to explain (a) why physicists consider some ideas more abstract than others in physics, and (b) how students conceptions of these ideas can be modeled. This new approach to abstraction suggests novel approaches to curriculum design in physics using Analogical Scaffolding.

  16. A site-specific PEGylated analog of exendin-4 with improved pharmacokinetics and pharmacodynamics in vivo.

    PubMed

    Gao, Mingming; Jin, Yuhao; Tong, Yue; Tian, Hong; Gao, Xiangdong; Yao, Wenbing

    2012-11-01

    Our aim was to improve the in vivo pharmacokinetics and pharmacodynamics of exendin-4 by using site-specific PEGylation. We designed the PEGylated peptide based on its structure and activity relationship and prepared the conjugate by two steps of chromatographic purification. After obtained the conjugate we confirmed its glucose-lowering activity in normal mice and determined its half-life in SD rats. Then we evaluated its anti-diabetic activity in a multiple low-dose Streptozocin (STZ)-induced diabetic mice model. With the process established in this study the product conjugate was obtained with a yield of over 60% and purity of above 99%. The conjugate maintained its original conformation after modification. In SD rats its half-life was prolonged to 27.12 ± 5.75 h which was 17.61-fold longer than that of the natural exendin-4 for which the half-life was only 1.54 ± 0.47 h. Its anti-diabetic activity was significantly improved in the diabetic mice. Compare with native exendin-4, the C-terminal site-specific PEGylated analog of exendin-4 obtained in this study has an improved pharmacokinetics and pharmacodynamics in vivo and could be regarded as a potential candidate for the future development of anti-diabetic drugs. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  17. Cyber Analogies

    DTIC Science & Technology

    2014-02-28

    distribution is unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT This anthology of cyber analogies will resonate with readers whose duties call for them...THIS PAGE INTENTIONALLY LEFT BLANK v ABSTRACT This anthology of cyber analogies will resonate with readers...fresh insights. THE CASE FOR ANALOGIES All of us on the cyber analogies team hope that this anthol- ogy will resonate with readers whose duties call

  18. Commercial PCV2a-based vaccines are effective in protecting naturally PCV2b-infected finisher pigs against experimental challenge with a 2012 mutant PCV2.

    PubMed

    Opriessnig, Tanja; Gerber, Priscilla F; Xiao, Chao-Ting; Halbur, Patrick G; Matzinger, Shannon R; Meng, Xiang-Jin

    2014-07-23

    Current commercial PCV2 vaccines are all based on PCV2a and have been shown to be effective in reducing PCV2a and PCV2b viremia and PCV2-associated lesions and disease. The recent emergence of novel mutant PCV2 (mPCV2) strains and linkage of mPCV2 with cases of porcine circovirus associated disease (PCVAD) in vaccinated herds have raised concerns over emergence of vaccine-escape mutants and reduced efficacy of PCV2a-based vaccines. The aim of this study was to determine the ability of three commercial PCV2a-based vaccines administered in the presence of an ongoing PCV2b infection and passively-acquired anti-PCV2 antibodies to protect conventional pigs against experimental challenge with mPCV2 at 11 weeks of age. Fifty naturally PCV2b-infected 2-week-old pigs were divided into five treatment groups with 10 pigs each. Pigs were unvaccinated (positive and negative controls) or vaccinated at 3 (VAC-A, VAC-B, VAC-C) and at 5 weeks of age (VAC-C). At 11 weeks of age, all pigs except the negative controls were challenged with a 2012 U.S. strain of mPCV2. The experiment was terminated 21 days after challenge. Under the conditions of this study, vaccinated pigs were protected against PCV2 viremia and lesions whereas non-vaccinated pigs were not. Moreover, concurrent PCV2b and mPCV2 infection was demonstrated in all positive controls and 3/10 had microscopic lesions consistent with PCVAD while negative controls infected with PCV2b alone did not develop PCVAD. The results indicate that concurrent PCV2b/mPCV2 infection can trigger PCVAD development and that commercial vaccines are effective in protecting conventional pigs against emerging mPCV2 strains. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Detecting Analogies Unconsciously

    PubMed Central

    Reber, Thomas P.; Luechinger, Roger; Boesiger, Peter; Henke, Katharina

    2014-01-01

    Analogies may arise from the conscious detection of similarities between a present and a past situation. In this functional magnetic resonance imaging study, we tested whether young volunteers would detect analogies unconsciously between a current supraliminal (visible) and a past subliminal (invisible) situation. The subliminal encoding of the past situation precludes awareness of analogy detection in the current situation. First, participants encoded subliminal pairs of unrelated words in either one or nine encoding trials. Later, they judged the semantic fit of supraliminally presented new words that either retained a previously encoded semantic relation (“analog”) or not (“broken analog”). Words in analogs versus broken analogs were judged closer semantically, which indicates unconscious analogy detection. Hippocampal activity associated with subliminal encoding correlated with the behavioral measure of unconscious analogy detection. Analogs versus broken analogs were processed with reduced prefrontal but enhanced medial temporal activity. We conclude that analogous episodes can be detected even unconsciously drawing on the episodic memory network. PMID:24478656

  20. Molecular Interactions between (−)-Epigallocatechin Gallate Analogs and Pancreatic Lipase

    PubMed Central

    Wang, Shihui; Sun, Zeya; Dong, Shengzhao; Liu, Yang; Liu, Yun

    2014-01-01

    The molecular interactions between pancreatic lipase (PL) and four tea polyphenols (EGCG analogs), like (−)-epigallocatechin gallate (EGCG), (−)-gallocatechin gallate (GCG), (−)-epicatechin gallate (ECG), and (−)-epigallocatechin (EC), were studied from PL activity, conformation, kinetics and thermodynamics. It was observed that EGCG analogs inhibited PL activity, and their inhibitory rates decreased by the order of EGCG>GCG>ECG>EC. PL activity at first decreased rapidly and then slowly with the increase of EGCG analogs concentrations. α-Helix content of PL secondary structure decreased dependent on EGCG analogs concentration by the order of EGCG>GCG>ECG>EC. EGCG, ECG, and EC could quench PL fluorescence both dynamically and statically, while GCG only quenched statically. EGCG analogs would induce PL self-assembly into complexes and the hydrodynamic radii of the complexes possessed a close relationship with the inhibitory rates. Kinetics analysis showed that EGCG analogs non-competitively inhibited PL activity and did not bind to PL catalytic site. DSC measurement revealed that EGCG analogs decreased the transition midpoint temperature of PL enzyme, suggesting that these compounds reduced PL enzyme thermostability. In vitro renaturation through urea solution indicated that interactions between PL and EGCG analogs were weak and non-covalent. PMID:25365042

  1. IADE: a system for intelligent automatic design of bioisosteric analogs

    NASA Astrophysics Data System (ADS)

    Ertl, Peter; Lewis, Richard

    2012-11-01

    IADE, a software system supporting molecular modellers through the automatic design of non-classical bioisosteric analogs, scaffold hopping and fragment growing, is presented. The program combines sophisticated cheminformatics functionalities for constructing novel analogs and filtering them based on their drug-likeness and synthetic accessibility using automatic structure-based design capabilities: the best candidates are selected according to their similarity to the template ligand and to their interactions with the protein binding site. IADE works in an iterative manner, improving the fitness of designed molecules in every generation until structures with optimal properties are identified. The program frees molecular modellers from routine, repetitive tasks, allowing them to focus on analysis and evaluation of the automatically designed analogs, considerably enhancing their work efficiency as well as the area of chemical space that can be covered. The performance of IADE is illustrated through a case study of the design of a nonclassical bioisosteric analog of a farnesyltransferase inhibitor—an analog that has won a recent "Design a Molecule" competition.

  2. IADE: a system for intelligent automatic design of bioisosteric analogs.

    PubMed

    Ertl, Peter; Lewis, Richard

    2012-11-01

    IADE, a software system supporting molecular modellers through the automatic design of non-classical bioisosteric analogs, scaffold hopping and fragment growing, is presented. The program combines sophisticated cheminformatics functionalities for constructing novel analogs and filtering them based on their drug-likeness and synthetic accessibility using automatic structure-based design capabilities: the best candidates are selected according to their similarity to the template ligand and to their interactions with the protein binding site. IADE works in an iterative manner, improving the fitness of designed molecules in every generation until structures with optimal properties are identified. The program frees molecular modellers from routine, repetitive tasks, allowing them to focus on analysis and evaluation of the automatically designed analogs, considerably enhancing their work efficiency as well as the area of chemical space that can be covered. The performance of IADE is illustrated through a case study of the design of a nonclassical bioisosteric analog of a farnesyltransferase inhibitor--an analog that has won a recent "Design a Molecule" competition.

  3. Dosimetric Comparison between Three-Dimensional Magnetic Resonance Imaging-Guided and Conventional Two-Dimensional Point A-Based Intracavitary Brachytherapy Planning for Cervical Cancer

    PubMed Central

    Ren, Juan; Yuan, Wei; Wang, Ruihua; Wang, Qiuping; Li, Yi; Xue, Chaofan; Yan, Yanli; Ma, Xiaowei; Tan, Li; Liu, Zi

    2016-01-01

    Objective The purpose of this study was to comprehensively compare the 3-dimensional (3D) magnetic resonance imaging (MRI)-guided and conventional 2-dimensional (2D) point A-based intracavitary brachytherapy (BT) planning for cervical cancer with regard to target dose coverage and dosages to adjacent organs-at risk (OARs). Methods A total of 79 patients with cervical cancer were enrolled to receive 2D point A-based BT planning and then immediately to receive 3D planning between October 2011 and April 2013 at the First Hospital Affiliated to Xi’an Jiao Tong University (Xi’an, China). The dose-volume histogram (DVH) parameters for gross tumor volume (GTV), high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV) and OARs were compared between the 2D and 3D planning. Results In small tumors, there was no significant difference in most of the DVHs between 2D and 3D planning (all p>0.05). While in big tumors, 3D BT planning significantly increased the DVHs for most of the GTV, HR-CTV and IR-CTV, and some OARs compared with 2D planning (all P<0.05). In 3D planning, DVHs for GTV, HR-CTV, IR-CTV and some OARs were significantly higher in big tumors than in small tumors (all p<0.05). In contrast, in 2D planning, DVHs for almost all of the HR-CTV and IR-CTV were significantly lower in big tumors (all p<0.05). In eccentric tumors, 3D planning significantly increased dose coverage but decreased dosages to OARs compared with 2D planning (p<0.05). In tumors invading adjacent tissues, the target dose coverage in 3D planning was generally significantly higher than in 2D planning (P<0.05); the dosages to the adjacent rectum and bladder were significantly higher but those to sigmoid colon were lower in 3D planning (all P<0.05). Conclusions 3D MRI image-guided BT planning exhibits advantages over 2D planning in a complex way, generally showing advantages for the treatment of cervical cancer except small tumors. PMID:27611853

  4. Radioiodinated nondegradable gonadotropin-releasing hormone analogs: new probes for the investigation of pituitary gonadotropin-releasing hormone receptors.

    PubMed

    Clayton, R N; Shakespear, R A; Duncan, J A; Marshall, J C; Munson, P J; Rodbard, D

    1979-12-01

    Studies of pituitary plasma membrane gonadotropin-releasing hormone (GnRH) receptors using [125I]-iodo-GnRH suffer major disadvantages. Only a small (less than 25%) proportion of specific tracer binding is to high affinity sites, with more than 70% bound to low affinity sites (Ka = 1 x 10(6) M-1). [125I]Iodo-GnRH is also inactivated during incubation with pituitary plasma membrane preparations. Two superactive analongs of GnRH, substituted in positions 6 and 10, were used as the labeled ligand to overcome these problems. Both analogs bound to the same high affinity sites as GnRH on bovine pituitary plasma membranes, though the affinity of the analogs was higher than that of the natural decapeptide (Ka = 2.0 x 10(9), 6.0 x 10(9), and 3.0 x 10(8) M-1 for [D-Ser(TBu)6]des-Gly10-GnRH ethylamide, [D-Ala6]des-Gly10-GnRH ethylamide, and GnRH, respectively. The labeled analogs bound to a single class of high affinity sites with less than 15% of the specific binding being to low affinity sites (Ka approximately equal to 1 x 10(6) M-1). The labeled analogs were not inactivated during incubation with the pituitary membrane preparations. Using the analogs as tracer, a single class of high affinity sites (K1 = 4.0 x 10(9) M-1) was also demonstrated on crude 10,800 x g rat pituitary membrane preparations. Use of these analogs as both the labeled and unlabeled ligand offers substantial advantages over GnRH for investigation of GnRH receptors, allowing accurate determination of changes in their numbers and affinities under various physiological conditions.

  5. Community Decadal Panel for Terrestrial Analogs to Mars

    NASA Astrophysics Data System (ADS)

    Barlow, N. G.; Farr, T.; Baker, V. R.; Bridges, N.; Carsey, F.; Duxbury, N.; Gilmore, M. S.; Green, J. R.; Grin, E.; Hansen, V.; Keszthelyi, L.; Lanagan, P.; Lentz, R.; Marinangeli, L.; Morris, P. A.; Ori, G. G.; Paillou, P.; Robinson, C.; Thomson, B.

    2001-11-01

    It is well recognized that interpretations of Mars must begin with the Earth as a reference. The most successful comparisons have focused on understanding geologic processes on the Earth well enough to extrapolate to Mars' environment. Several facets of terrestrial analog studies have been pursued and are continuing. These studies include field workshops, characterization of terrestrial analog sites for Mars, instrument tests, laboratory measurements (including analysis of martian meteorites), and computer and laboratory modeling. The combination of all these activities allows scientists to constrain the processes operating in specific terrestrial environments and extrapolate how similar processes could affect Mars. The Terrestrial Analogs for Mars Community Panel is considering the following two key questions: (1) How do terrestrial analog studies tie in to the MEPAG science questions about life, past climate, and geologic evolution of Mars, and (2) How can future instrumentation be used to address these questions. The panel is considering the issues of data collection, value of field workshops, data archiving, laboratory measurements and modeling, human exploration issues, association with other areas of solar system exploration, and education and public outreach activities.

  6. New cytotoxic benzosuberene analogs. Synthesis, molecular modeling and biological evaluation.

    PubMed

    Chen, Zecheng; Maderna, Andreas; Sukuru, Sai Chetan K; Wagenaar, Melissa; O'Donnell, Christopher J; Lam, My-Hanh; Musto, Sylvia; Loganzo, Frank

    2013-12-15

    In this Letter we describe the synthesis and biological evaluation of new benzosuberene analogs with structural modifications on the B-ring. The focus was initially to probe the chemical space around the B-ring C-8 position. This position was readily available for derivatization chemistry using our recently developed new synthesis for this compound class. Furthermore, we describe two new B-ring analogs, one containing a diene and the other a cyclic ether group. Both new analogs show excellent potencies in tumor cell proliferation assays. In addition, we describe molecular modeling studies that provide a binding rationale for reference compound 8 in the colchicine binding site using the known colchicine crystal structure. We also examine whether the cell based potency data obtained with selected new analogs are supported by modeling results. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. 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.

  8. Evaluating The Global Inventory of Planetary Analog Environments on Earth: An Ontological Approach

    NASA Astrophysics Data System (ADS)

    Conrad, P. G.

    2010-12-01

    Introduction: Field sites on Earth are routinely used to simulate planetary environments so that we can try to understand the evidence of processes such as sedimentary deposition, weathering, evolution of habitable environments, and behavior of spacecraft and instrumentation prior to selection of mission architectures, payload investigations and landing sites for in situ exploration of other planets. The rapid evolution of astrobiology science drivers for space exploration as well as increasing capability to explore planetary surfaces in situ has led to a proliferation of declarations that various Earth environments are analogs for less accessible planetary environments. We have not yet progressed to standardized measures of analog fidelity, and the analog value of field sites can be variable de-pending upon a variety of factors. Here we present a method of evaluating the fidelity and hence utility of analog environments by using an ontological approach to evaluating how well the analogs work. The use of ontologies as specification constructs is now quite common in artificial intelligence, systems engineering, business development and various informatics systems. We borrow from these developments just as they derive from the original use of ontology in philosophy, where it was meant as a systematic approach to describing the fundamental elements that define “being,” or existence [1]. An ontology is a framework for the specification of a concept or domain of interest. The knowledge regarding that domain, eg., inventory of objects, hierarchical classes, relationships and functions is what describes and defines the domain as a declarative formalism [2]. In the case of planetary environments, one can define a list of fundamen-tal attributes without which the domain (environment) in question must be defined (classified) otherwise. In particu-lar this is problematic when looking at ancient environments because of their alteration over time. In other words, their

  9. Analog computation of auto and cross-correlation functions

    NASA Technical Reports Server (NTRS)

    1974-01-01

    For analysis of the data obtained from the cross beam systems it was deemed desirable to compute the auto- and cross-correlation functions by both digital and analog methods to provide a cross-check of the analysis methods and an indication as to which of the two methods would be most suitable for routine use in the analysis of such data. It is the purpose of this appendix to provide a concise description of the equipment and procedures used for the electronic analog analysis of the cross beam data. A block diagram showing the signal processing and computation set-up used for most of the analog data analysis is provided. The data obtained at the field test sites were recorded on magnetic tape using wide-band FM recording techniques. The data as recorded were band-pass filtered by electronic signal processing in the data acquisition systems.

  10. Analog synthetic biology.

    PubMed

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

  11. Adenomatous Polyposis Coli-Mediated Accumulation of Abasic DNA Lesions Lead to Cigarette Smoke Condensate-Induced Neoplastic Transformation of Normal Breast Epithelial Cells1

    PubMed Central

    Jaiswal, Aruna S; Panda, Harekrushna; Pampo, Christine A; Siemann, Dietmar W; Gairola, C Gary; Hromas, Robert; Narayan, Satya

    2013-01-01

    Adenomatous polyposis coli (APC) is a multifunctional protein having diverse cellular functions including cell migration, cell-cell adhesion, cell cycle control, chromosomal segregation, and apoptosis. Recently, we found a new role of APC in base excision repair (BER) and showed that it interacts with DNA polymerase β and 5′-flap endonuclease 1 and interferes in BER. Previously, we have also reported that cigarette smoke condensate (CSC) increases expression of APC and enhances the growth of normal human breast epithelial (MCF10A) cells in vitro. In the present study, using APC overexpression and knockdown systems, we have examined the molecular mechanisms by which CSC and its major component, Benzo[α]pyrene, enhances APC-mediated accumulation of abasic DNA lesions, which is cytotoxic and mutagenic in nature, leading to enhanced neoplastic transformation of MCF10A cells in an orthotopic xenograft model. PMID:23555190

  12. Enzymatic Transition States, Transition-State Analogs, Dynamics, Thermodynamics, and Lifetimes

    PubMed Central

    Schramm, Vern L.

    2017-01-01

    Experimental analysis of enzymatic transition-state structures uses kinetic isotope effects (KIEs) to report on bonding and geometry differences between reactants and the transition state. Computational correlation of experimental values with chemical models permits three-dimensional geometric and electrostatic assignment of transition states formed at enzymatic catalytic sites. The combination of experimental and computational access to transition-state information permits (a) the design of transition-state analogs as powerful enzymatic inhibitors, (b) exploration of protein features linked to transition-state structure, (c) analysis of ensemble atomic motions involved in achieving the transition state, (d) transition-state lifetimes, and (e) separation of ground-state (Michaelis complexes) from transition-state effects. Transition-state analogs with picomolar dissociation constants have been achieved for several enzymatic targets. Transition states of closely related isozymes indicate that the protein’s dynamic architecture is linked to transition-state structure. Fast dynamic motions in catalytic sites are linked to transition-state generation. Enzymatic transition states have lifetimes of femtoseconds, the lifetime of bond vibrations. Binding isotope effects (BIEs) reveal relative reactant and transition-state analog binding distortion for comparison with actual transition states. PMID:21675920

  13. Analogs of methyllycaconitine as novel noncompetitive inhibitors of nicotinic receptors: pharmacological characterization, computational modeling, and pharmacophore development.

    PubMed

    McKay, Dennis B; Chang, Cheng; González-Cestari, Tatiana F; McKay, Susan B; El-Hajj, Raed A; Bryant, Darrell L; Zhu, Michael X; Swaan, Peter W; Arason, Kristjan M; Pulipaka, Aravinda B; Orac, Crina M; Bergmeier, Stephen C

    2007-05-01

    As a novel approach to drug discovery involving neuronal nicotinic acetylcholine receptors (nAChRs), our laboratory targeted nonagonist binding sites (i.e., noncompetitive binding sites, negative allosteric binding sites) located on nAChRs. Cultured bovine adrenal cells were used as neuronal models to investigate interactions of 67 analogs of methyllycaconitine (MLA) on native alpha3beta4* nAChRs. The availability of large numbers of structurally related molecules presents a unique opportunity for the development of pharmacophore models for noncompetitive binding sites. Our MLA analogs inhibited nicotine-mediated functional activation of both native and recombinant alpha3beta4* nAChRs with a wide range of IC(50) values (0.9-115 microM). These analogs had little or no inhibitory effects on agonist binding to native or recombinant nAChRs, supporting noncompetitive inhibitory activity. Based on these data, two highly predictive 3D quantitative structure-activity relationship (comparative molecular field analysis and comparative molecular similarity index analysis) models were generated. These computational models were successfully validated and provided insights into the molecular interactions of MLA analogs with nAChRs. In addition, a pharmacophore model was constructed to analyze and visualize the binding requirements to the analog binding site. The pharmacophore model was subsequently applied to search structurally diverse molecular databases to prospectively identify novel inhibitors. The rapid identification of eight molecules from database mining and our successful demonstration of in vitro inhibitory activity support the utility of these computational models as novel tools for the efficient retrieval of inhibitors. These results demonstrate the effectiveness of computational modeling and pharmacophore development, which may lead to the identification of new therapeutic drugs that target novel sites on nAChRs.

  14. Analog synthetic biology

    PubMed Central

    Sarpeshkar, R.

    2014-01-01

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA–protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. PMID:24567476

  15. In silico designing of hyper-glycosylated analogs for the human coagulation factor IX.

    PubMed

    Ghasemi, Fahimeh; Zomorodipour, Alireza; Karkhane, Ali Asghar; Khorramizadeh, M Reza

    2016-07-01

    N-glycosylation is a process during which a glycan moiety attaches to the asparagine residue in the N-glycosylation consensus sequence (Asn-Xxx-Ser/Thr), where Xxx can be any amino acid except proline. Introduction of a new N-glycosylation site into a protein backbone leads to its hyper-glycosylation, and may improve the protein properties such as solubility, folding, stability, and secretion. Glyco-engineering is an approach to facilitate the hyper-glycosylation of recombinant proteins by application of the site-directed mutagenesis methods. In this regard, selection of a suitable location on the surface of a protein for introduction of a new N-glycosylation site is a main concern. In this work, a computational approach was conducted to select suitable location(s) for introducing new N-glycosylation sites into the human coagulation factor IX (hFIX). With this aim, the first 45 residues of mature hFIX were explored to find out suitable positions for introducing either Asn or Ser/Thr residues, to create new N-glycosylation site(s). Our exploration lead to detection of five potential positions, for hyper-glycosylation. For each suggested position, an analog was defined and subjected for N-glycosylation efficiency prediction. After generation of three-dimensional structures, by homology-based modeling, the five designed analogs were examined by molecular dynamic (MD) simulations, to predict their stability levels and probable structural distortions caused by amino acid substitutions, relative to the native counterpart. Three out of five suggested analogs, namely; E15T, K22N, and R37N, reached equilibration state with relatively constant Root Mean Square Deviation values. Additional analysis on the data obtained during MD simulations, lead us to conclude that, R37N is the only qualified analog with the most similar structure and dynamic behavior to that of the native counterpart, to be considered for further experimental investigations. Copyright © 2016 Elsevier Inc

  16. Label-free functional nucleic acid sensors for detecting target agents

    DOEpatents

    Lu, Yi; Xiang, Yu

    2015-01-13

    A general methodology to design label-free fluorescent functional nucleic acid sensors using a vacant site approach and an abasic site approach is described. In one example, a method for designing label-free fluorescent functional nucleic acid sensors (e.g., those that include a DNAzyme, aptamer or aptazyme) that have a tunable dynamic range through the introduction of an abasic site (e.g., dSpacer) or a vacant site into the functional nucleic acids. Also provided is a general method for designing label-free fluorescent aptamer sensors based on the regulation of malachite green (MG) fluorescence. A general method for designing label-free fluorescent catalytic and molecular beacons (CAMBs) is also provided. The methods demonstrated here can be used to design many other label-free fluorescent sensors to detect a wide range of analytes. Sensors and methods of using the disclosed sensors are also provided.

  17. Nonvolatile Analog Memory

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd C. (Inventor)

    2007-01-01

    A nonvolatile analog memory uses pairs of ferroelectric field effect transistors (FFETs). Each pair is defined by a first FFET and a second FFET. When an analog value is to be stored in one of the pairs, the first FFET has a saturation voltage applied thereto, and the second FFET has a storage voltage applied thereto that is indicative of the analog value. The saturation and storage voltages decay over time in accordance with a known decay function that is used to recover the original analog value when the pair of FFETs is read.

  18. Terrestrial Analogs to Mars: NRC Community Panel Decadal Report

    NASA Astrophysics Data System (ADS)

    Farr, T. G.

    2002-12-01

    A report was completed recently by a Community Panel for the NRC Decadal Study of Solar System Exploration. The desire was for a review of the current state of knowledge and for recommendations for action over the next decade. The topic of this panel, Terrestrial Analogs to Mars, was chosen to bring attention to the need for an increase in analog studies in support of the increased pace of Mars exploration. It is well recognized that interpretations of Mars must begin with the Earth as a reference. The most successful comparisons have focused on understanding geologic processes on the Earth well enough to extrapolate to Mars' environment. Several facets of terrestrial analog studies have been pursued and are continuing. These studies include field workshops, characterization of terrestrial analog sites, instrument tests, laboratory measurements (including analysis of martian meteorites), and computer and laboratory modeling. The combination of all of these activities allows scientists to constrain the processes operating in specific terrestrial environments and extrapolate how similar processes could affect Mars. The Terrestrial Analogs for Mars Community Panel has considered the following two key questions: (1) How do terrestrial analog studies tie in to the overarching science questions about life, past climate, and geologic evolution of Mars, and (2) How can future instrumentation be used to address these questions. The panel considered the issues of data collection and archiving, value of field workshops, laboratory measurements and modeling, human exploration issues, association with other areas of solar system exploration, and education and public outreach activities. Parts of this work were performed under contract to NASA.

  19. Structure-activity relationship of ibogaine analogs interacting with nicotinic acetylcholine receptors in different conformational states.

    PubMed

    Arias, Hugo R; Feuerbach, Dominik; Targowska-Duda, Katarzyna M; Jozwiak, Krzysztof

    2011-09-01

    The interaction of ibogaine analogs with nicotinic acetylcholine receptors (AChRs) in different conformational states was studied by functional and structural approaches. The results established that ibogaine analogs: (a) inhibit (±)-epibatidine-induced Ca²⁺ influx in human embryonic muscle AChRs with the following potency sequence (IC(50) in μM): (±)-18-methylaminocoronaridine (5.9±0.3)∼(±)-18-methoxycoronaridine (18-MC) (6.8±0.8)>(-)-ibogaine (17±3)∼(+)-catharanthine (20±1)>(±)-albifloranine (46±13), (b) bind to the [³H]TCP binding site with higher affinity when the Torpedo AChR is in the desensitized state compared to that in the resting state. Similar results were obtained using [³H]18-MC. These and docking results suggest a steric interaction between TCP and ibogaine analogs for the same site, (c) enhance [³H]cytisine binding to resting but not to desensitized AChRs, with desensitizing potencies (apparent EC₅₀) that correlate very well with the pK(i) values in the desensitized state, and (d) there are good bilinear correlations between the ligand molecular volumes and their affinities in the desensitized and resting states, with an optimal volume of ∼345 ų for the ibogaine site. These results indicate that the size of the binding sites for ibogaine analogs, located between the serine and nonpolar rings and shared with TCP, is an important structural feature for binding and for inducing desensitization. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Crystal structure of the unactivated ribulose 1,5-bisphosphate carboxylase/oxygenase complexed with a transition state analog, 2-carboxy-D-arabinitol 1,5-bisphosphate.

    PubMed Central

    Zhang, K. Y.; Cascio, D.; Eisenberg, D.

    1994-01-01

    The crystal structure of unactivated ribulose 1,5-bisphosphate carboxylase/oxygenase from Nicotiana tabacum complexed with a transition state analog, 2-carboxy-D-arabinitol 1,5-bisphosphate, was determined to 2.7 A resolution by X-ray crystallography. The transition state analog binds at the active site in an extended conformation. As compared to the binding of the same analog in the activated enzyme, the analog binds in a reverse orientation. The active site Lys 201 is within hydrogen bonding distance of the carboxyl oxygen of the analog. Loop 6 (residues 330-339) remains open and flexible upon binding of the analog in the unactivated enzyme, in contrast to the closed and ordered loop 6 in the activated enzyme complex. The transition state analog is exposed to solvent due to the open conformation of loop 6. PMID:8142899

  1. Analog Signal Correlating Using an Analog-Based Signal Conditioning Front End

    NASA Technical Reports Server (NTRS)

    Prokop, Norman; Krasowski, Michael

    2013-01-01

    This innovation is capable of correlating two analog signals by using an analog-based signal conditioning front end to hard-limit the analog signals through adaptive thresholding into a binary bit stream, then performing the correlation using a Hamming "similarity" calculator function embedded in a one-bit digital correlator (OBDC). By converting the analog signal into a bit stream, the calculation of the correlation function is simplified, and less hardware resources are needed. This binary representation allows the hardware to move from a DSP where instructions are performed serially, into digital logic where calculations can be performed in parallel, greatly speeding up calculations.

  2. Lunar and Planetary Science XXXV: Mars: Remote Sensing and Terrestrial Analogs

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The session "Mars: Remote Sensing and Terrestrial Analogs" included the following:Physical Meaning of the Hapke Parameter for Macroscopic Roughness: Experimental Determination for Planetary Regolith Surface Analogs and Numerical Approach; Near-Infrared Spectra of Martian Pyroxene Separates: First Results from Mars Spectroscopy Consortium; Anomalous Spectra of High-Ca Pyroxenes: Correlation Between Ir and M ssbauer Patterns; THEMIS-IR Emissivity Spectrum of a Large Dark Streak near Olympus Mons; Geomorphologic/Thermophysical Mapping of the Athabasca Region, Mars, Using THEMIS Infrared Imaging; Mars Thermal Inertia from THEMIS Data; Multispectral Analysis Methods for Mapping Aqueous Mineral Depostis in Proposed Paleolake Basins on Mars Using THEMIS Data; Joint Analysis of Mars Odyssey THEMIS Visible and Infrared Images: A Magic Airbrush for Qualitative and Quantitative Morphology; Analysis of Mars Thermal Emission Spectrometer Data Using Large Mineral Reference Libraries ; Negative Abundance : A Problem in Compositional Modeling of Hyperspectral Images; Mars-LAB: First Remote Sensing Data of Mineralogy Exposed at Small Mars-Analog Craters, Nevada Test Site; A Tool for the 2003 Rover Mini-TES: Downwelling Radiance Compensation Using Integrated Line-Sight Sky Measurements; Learning About Mars Geology Using Thermal Infrared Spectral Imaging: Orbiter and Rover Perspectives; Classifying Terrestrial Volcanic Alteration Processes and Defining Alteration Processes they Represent on Mars; Cemented Volcanic Soils, Martian Spectra and Implications for the Martian Climate; Palagonitic Mars: A Basalt Centric View of Surface Composition and Aqueous Alteration; Combining a Non Linear Unmixing Model and the Tetracorder Algorithm: Application to the ISM Dataset; Spectral Reflectance Properties of Some Basaltic Weathering Products; Morphometric LIDAR Analysis of Amboy Crater, California: Application to MOLA Analysis of Analog Features on Mars; Airborne Radar Study of Soil Moisture at

  3. Mars Analog Mission: Glacier Simulation AMADEE-15 by Austrian Space Forum

    NASA Astrophysics Data System (ADS)

    Groemer, Gernot; Losiak, Anna; Soucek, Alexander; Plank, Clemens; Zanardini, Laura; Sejkora, Nina; Sams, Sebastian

    2016-04-01

    Austrian Space Forum: The Austrian Space Forum (OeWF, Österreichisches Weltraum Forum) is a non-profit, citizen-science organization of aerospace specialists and enthusiasts. One of its specialisations is Mars analog research. Analog studies and analog instrument validation supported all planetary surface missions so far [1] and are considered as an effective tool to prepare for future missions to Mars [2,3,4,5,6,7]. Since 2006, OeWF has conducted 11 Mars analog field campaigns in diverse locations that represented: 1) average current Mars conditions (the Mars Desert Research Station (MDRS) in Utah in 2006 [8] and the Northern Sahara near Erfoud, Morocco in 2013 [9]); 2) the early and wet Mars (analog site of Rio Tinto Spain in 2011 [10]); and 3) subsurface exploration (Dachstein Ice Caves in 2012). During these campaigns, 68 experiments and major engineering tests were performed, whichwere mostly focused on astrobiology, robotics, human factors, geoscience and spacesuit operations. Major assets of OeWF include two advanced spacesuit simulators Aouda [11], an increasingly evolving Mission Support Center, a dedicated Remote Science Support team [12], and a growing set of Standard Operating Procedures defining major workflows within a mission team. The spacesuit simulators were operated by a total of 18 analog astronauts, who were selected and trained during a >6 month program. Total EVA time is nearly 600 hours, leading to a significant experience in analog field simulations. AMADEE-15: The mission took place between August 2nd and 14th 2015 at the Kaunertal Glacier in Tyrol, Austria. This glacier was selected as a study site because of its accessibility and high number of micro-landscapes analogous to those expected on Mars in locations where abundant water ice is present. As such it is considered a first-tier Mars analog [13]. The Base station was located at N 46.86320, E 10.71401 at 2800 masl, the highest reached location was on elevation of 2887 m. Eleven

  4. Lessons from Natural Analog Studies for Geologic Disposal of High-Level Nuclear Waste (Invited)

    NASA Astrophysics Data System (ADS)

    Murphy, W. M.

    2009-12-01

    For over fifty years natural analog studies have provided lessons addressing scientific, technical, and social problems concerning geologic disposal of high-level nuclear waste. Idealized concepts for permanent disposal environments evolved from an understanding of the geological, geochemical and hydrological characteristics of analogous rocks including natural salt deposits (as advocated by the US National Academy of Sciences in 1957), ancient cratonic rocks (as investigated at Lac du Bonnet, Canada, Aspö, Sweden, and Vienne, France), and marine sedimentary rock formations (as studied at Mol, Belgium, and Bure, France). Additional multidisciplinary studies have been conducted at natural sites that bear characteristics analogous to potential repository systems, notably at natural uranium (and thorium) deposits including Poços de Caldas, Brazil, Alligator Rivers, Australia, Peña Blanca, Mexico, and Oklo, Gabon. Researchers of natural analogs for geologic disposal have addressed technical uncertainties regarding processes that have transpired over large time and space scales, which are generally inaccessible to laboratory studies. Principal questions for nuclear waste disposal include the geochemical stability and alteration rates of radionuclide bearing minerals and the mechanisms and rates of transport of radionuclides in groundwater. In their most direct applications, natural analogs studies have been devoted to testing specific models for repository performance and the experimental data that support those models. Parameters used in predictive performance assessment modeling have been compared to natural system data, including mineral solubilities, sorption coefficients, diffusion rates, and colloid transport properties. For example, the rate of uraninite oxidation and the natural paragenesis of uranium mineral alteration at Peña Blanca have been compared favorably to results of experimental studies of spent fuel alteration related to the proposed repository

  5. Principles for Integrating Mars Analog Science, Operations, and Technology Research

    NASA Technical Reports Server (NTRS)

    Clancey, William J.

    2003-01-01

    During the Apollo program, the scientific community and NASA used terrestrial analog sites for understanding planetary features and for training astronauts to be scientists. Human factors studies (Harrison, Clearwater, & McKay 1991; Stuster 1996) have focused on the effects of isolation in extreme environments. More recently, with the advent of wireless computing, we have prototyped advanced EVA technologies for navigation, scheduling, and science data logging (Clancey 2002b; Clancey et al., in press). Combining these interests in a single expedition enables tremendous synergy and authenticity, as pioneered by Pascal Lee's Haughton-Mars Project (Lee 2001; Clancey 2000a) and the Mars Society s research stations on a crater rim on Devon Island in the High Canadian Arctic (Clancey 2000b; 2001b) and the Morrison Formation of southeast Utah (Clancey 2002a). Based on this experience, the following principles are proposed for conducting an integrated science, operations, and technology research program at analog sites: 1) Authentic work; 2) PI-based projects; 3) Unencumbered baseline studies; 4) Closed simulations; and 5) Observation and documentation. Following these principles, we have been integrating field science, operations research, and technology development at analog sites on Devon Island and in Utah over the past five years. Analytic methods include work practice simulation (Clancey 2002c; Sierhuis et a]., 2000a;b), by which the interaction of human behavior, facilities, geography, tools, and procedures are formalized in computer models. These models are then converted into the runtime EVA system we call mobile agents (Clancey 2002b; Clancey et al., in press). Furthermore, we have found that the Apollo Lunar Surface Journal (Jones, 1999) provides a vast repository or understanding astronaut and CapCom interactions, serving as a baseline for Mars operations and quickly highlighting opportunities for computer automation (Clancey, in press).

  6. Analogical Reasoning in Geometry Education

    ERIC Educational Resources Information Center

    Magdas, Ioana

    2015-01-01

    The analogical reasoning isn't used only in mathematics but also in everyday life. In this article we approach the analogical reasoning in Geometry Education. The novelty of this article is a classification of geometrical analogies by reasoning type and their exemplification. Our classification includes: analogies for understanding and setting a…

  7. Computational and Biochemical Docking of the Irreversible Cocaine Analog RTI 82 Directly Demonstrates Ligand Positioning in the Dopamine Transporter Central Substrate-binding Site*

    PubMed Central

    Dahal, Rejwi Acharya; Pramod, Akula Bala; Sharma, Babita; Krout, Danielle; Foster, James D.; Cha, Joo Hwan; Cao, Jianjing; Newman, Amy Hauck; Lever, John R.; Vaughan, Roxanne A.; Henry, L. Keith

    2014-01-01

    The dopamine transporter (DAT) functions as a key regulator of dopaminergic neurotransmission via re-uptake of synaptic dopamine (DA). Cocaine binding to DAT blocks this activity and elevates extracellular DA, leading to psychomotor stimulation and addiction, but the mechanisms by which cocaine interacts with DAT and inhibits transport remain incompletely understood. Here, we addressed these questions using computational and biochemical methodologies to localize the binding and adduction sites of the photoactivatable irreversible cocaine analog 3β-(p-chlorophenyl)tropane-2β-carboxylic acid, 4′-azido-3′-iodophenylethyl ester ([125I]RTI 82). Comparative modeling and small molecule docking indicated that the tropane pharmacophore of RTI 82 was positioned in the central DA active site with an orientation that juxtaposed the aryliodoazide group for cross-linking to rat DAT Phe-319. This prediction was verified by focused methionine substitution of residues flanking this site followed by cyanogen bromide mapping of the [125I]RTI 82-labeled mutants and by the substituted cysteine accessibility method protection analyses. These findings provide positive functional evidence linking tropane pharmacophore interaction with the core substrate-binding site and support a competitive mechanism for transport inhibition. This synergistic application of computational and biochemical methodologies overcomes many uncertainties inherent in other approaches and furnishes a schematic framework for elucidating the ligand-protein interactions of other classes of DA transport inhibitors. PMID:25179220

  8. Natural CO 2 accumulations in the western Williston Basin: A mineralogical analog for CO 2 injection at the Weyburn site

    DOE PAGES

    Ryerson, F. J.; Lake, John; Whittaker, Steven; ...

    2013-01-17

    The Devonian carbonates of the Duperow Formation on the western flank of the Williston Basin in southwest Saskatchewan contain natural accumulations of CO 2, and may have done so for as long as 50 million years. These carbonate sediments are characterized by a succession of carbonate cycles capped by anhydrite-rich evaporites that are thought to act as seals to fluid migration. The Weyburn CO 2 injection site lies 400 km to the east in a series of Mississippian carbonates that were deposited in a similar depositional environment. That long-term isolation of natural CO 2 can be accomplished within carbonate stratamore » has motivated the investigation of the Duperow rocks as a potential natural analog for storage of anthropogenic CO 2 in carbonate lithologies. For the Duperow strata to represent a legitimate analog for Midale injection and storage, the similarity in lithofacies, whole rock compositions, mineral compositions and porosity with the Midale Beds must be established. Here we compare lithofacies, whole rock compositions, mineralogy and mineral compositions from both locales. The major mineral phases at both locales are calcite, dolomite and anhydrite. In addition, accessory pyrite, fluorite, quartz and celestine (strontium sulfate) are also observed. Dawsonite, a potential CO 2-trapping mineral, is not observed within the CO 2-bearing horizons of the Duperow Formation, however. The distribution of porosity in the Midale Vuggy units is similar to that of the Duperow Formation, but the Marly units of the Midale have significantly higher porosity. The Duperow Formation is topped by the Dinesmore evaporite that is rich in anhydrite, and often contains authigenic K-feldspar. The chemistry of dolomite and calcite from the two localities also overlaps. Silicate minerals are in low abundance (<3%) within the analyzed Duperow samples, with quartz and K-feldspar the only silicates observed petrographically or in X-ray diffraction patterns. The Midale Beds contain

  9. Autoradiographic Distribution and Applied Pharmacological Characteristics of Dextromethorphan and Related Antitissue/Anticonvulsant Drugs and Novel Analogs.

    DTIC Science & Technology

    1992-08-01

    OF DEXTROMETHORPHAN AND RELATED ANTITISSUE/ANTICONVULSANT DRUGS AND NOVEL ANALOGS PRINCIPAL INVESTIGATOR: Norman G. Bowery, Ph.D., DSc CONTRACTING...Characteristics of Dextromethorphan and DAMD17-90-C-0124 Related Anti ti ssue/ Anticonvul sant Drugs and Novel 6. AUTHOR(S) Analogs 61102A...13. ABSTRACT (Maximum 200 words) Binding of dextromethorphan and its analogues to the dextromethorphan binding site and to the PCP and glycine binding

  10. Meat analog: a review.

    PubMed

    Malav, O P; Talukder, S; Gokulakrishnan, P; Chand, S

    2015-01-01

    The health-conscious consumers are in search of nutritious and convenient food item which can be best suited in their busy life. The vegetarianism is the key for the search of such food which resembles the meat in respect of nutrition and sensory characters, but not of animal origin and contains vegetable or its modified form, this is the point when meat analog evolved out and gets shape. The consumers gets full satisfaction by consumption of meat analog due to its typical meaty texture, appearance and the flavor which are being imparted during the skilled production of meat analog. The supplement of protein in vegetarian diet through meat alike food can be fulfilled by incorporating protein-rich vegetative food grade materials in meat analog and by adopting proper technological process which can promote the proper fabrication of meat analog with acceptable meat like texture, appearance, flavor, etc. The easily available vegetables, cereals, and pulses in India have great advantages and prospects to be used in food products and it can improve the nutritional and functional characters of the food items. The various form and functional characters of food items are available world over and attracts the meat technologists and the food processors to bring some innovativeness in meat analog and its presentation and marketability so that the acceptability of meat analog can be overgrown by the consumers.

  11. Evidence that a burst of DNA depurination in SENCAR mouse skin induces error-prone repair and forms mutations in the H-ras gene.

    PubMed

    Chakravarti, D; Mailander, P C; Li, K M; Higginbotham, S; Zhang, H L; Gross, M L; Meza, J L; Cavalieri, E L; Rogan, E G

    2001-11-29

    Treatment of SENCAR mouse skin with dibenzo[a,l]pyrene results in abundant formation of abasic sites that undergo error-prone excision repair, forming oncogenic H-ras mutations in the early preneoplastic period. To examine whether the abundance of abasic sites causes repair infidelity, we treated SENCAR mouse skin with estradiol-3,4-quinone (E(2)-3,4-Q) and determined adduct levels 1 h after treatment, as well as mutation spectra in the H-ras gene between 6 h and 3 days after treatment. E(2)-3,4-Q formed predominantly (> or =99%) the rapidly-depurinating 4-hydroxy estradiol (4-OHE(2))-1-N3Ade adduct and the slower-depurinating 4-OHE(2)-1-N7Gua adduct. Between 6 h and 3 days, E(2)-3,4-Q induced abundant A to G mutations in H-ras DNA, frequently in the context of a 3'-G residue. Using a T.G-DNA glycosylase (TDG)-PCR assay, we determined that the early A to G mutations (6 and 12 h) were in the form of G.T heteroduplexes, suggesting misrepair at A-specific depurination sites. Since G-specific mutations were infrequent in the spectra, it appears that the slow rate of depurination of the N7Gua adducts during active repair may not generate a threshold level of G-specific abasic sites to affect repair fidelity. These results also suggest that E(2)-3,4-Q, a suspected endogenous carcinogen, is a genotoxic compound and could cause mutations.

  12. Digital and analog communication systems

    NASA Technical Reports Server (NTRS)

    Shanmugam, K. S.

    1979-01-01

    The book presents an introductory treatment of digital and analog communication systems with emphasis on digital systems. Attention is given to the following topics: systems and signal analysis, random signal theory, information and channel capacity, baseband data transmission, analog signal transmission, noise in analog communication systems, digital carrier modulation schemes, error control coding, and the digital transmission of analog signals.

  13. Terrestrial subaqueous seafloor dunes: Possible analogs for Venus

    USGS Publications Warehouse

    Neakrase, Lynn D.V.; Klose, Martina; Titus, Timothy N.

    2017-01-01

    Dunes on Venus, first discovered with Magellan Synthetic Aperture Radar (SAR) in the early 1990s, have fueled discussions about the viability of Venusian dunes and aeolian grain transport. Confined to two locations on Venus, the existence of the interpreted dunes provides evidence that there could be transportable material being mobilized into aeolian bedforms at the surface. However, because of the high-pressure high-temperature surface conditions, laboratory analog studies are difficult to conduct and results are difficult to extrapolate to full-sized, aeolian bedforms. Field sites of desert dunes, which are well-studied on Earth and Mars, are not analogous to what is observed on Venus because of the differences in the fluid environments. One potentially underexplored possibility in planetary science for Venus-analog dune fields could be subaqueous, seafloor dune fields on Earth. Known to the marine geology communities since the early 1960s, seafloor dunes are rarely cited in planetary aeolian bedform literature, but could provide a necessary thick-atmosphere extension to the classically studied aeolian dune environment literature for thinner atmospheres. Through discussion of the similarity of the two environments, and examples of dunes and ripples cited in marine literature, we provide evidence that subaqueous seafloor dunes could serve as analogs for dunes on Venus. Furthermore, the evidence presented here demonstrates the usefulness of the marine literature for thick-atmosphere planetary environments and potentially for upcoming habitable worlds and oceanic environment research program opportunities. Such useful cross-disciplinary discussion of dune environments is applicable to many planetary environments (Earth, Mars, Venus, Titan, etc.) and potential future missions.

  14. Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

    NASA Technical Reports Server (NTRS)

    Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J.; Lowenstein, D. I. (Principal Investigator)

    2000-01-01

    Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

  15. Hydraulic Capacitor Analogy

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  16. Analog pulse processor

    DOEpatents

    Wessendorf, Kurt O.; Kemper, Dale A.

    2003-06-03

    A very low power analog pulse processing system implemented as an ASIC useful for processing signals from radiation detectors, among other things. The system incorporates the functions of a charge sensitive amplifier, a shaping amplifier, a peak sample and hold circuit, and, optionally, an analog to digital converter and associated drivers.

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

    Zahn, Karl E.; Averill, April M.; Aller, Pierre

    DNA polymerase θ protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks. Polymerase θ is overexpressed in breast, lung and oral cancers, and reduction of its activity in mammalian cells increases sensitivity to double-strand break–inducing agents, including ionizing radiation. Reported in this paper are crystal structures of the C-terminal polymerase domain from human polymerase θ, illustrating two potential modes of dimerization. One structure depicts insertion of ddATP opposite an abasic-site analog during translesion DNA synthesis. The second structure describes a cognate ddGTP complex. Polymerase θ uses a specialized thumb subdomain to establish unique upstream contactsmore » to the primer DNA strand, including an interaction with the 3'-terminal phosphate from one of five distinctive insertion loops. Finally, these observations demonstrate how polymerase θ grasps the primer to bypass DNA lesions or extend poorly annealed DNA termini to mediate end-joining.« less

  18. Human DNA polymerase θ grasps the primer terminus to mediate DNA repair

    DOE PAGES

    Zahn, Karl E.; Averill, April M.; Aller, Pierre; ...

    2015-03-16

    DNA polymerase θ protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks. Polymerase θ is overexpressed in breast, lung and oral cancers, and reduction of its activity in mammalian cells increases sensitivity to double-strand break–inducing agents, including ionizing radiation. Reported in this paper are crystal structures of the C-terminal polymerase domain from human polymerase θ, illustrating two potential modes of dimerization. One structure depicts insertion of ddATP opposite an abasic-site analog during translesion DNA synthesis. The second structure describes a cognate ddGTP complex. Polymerase θ uses a specialized thumb subdomain to establish unique upstream contactsmore » to the primer DNA strand, including an interaction with the 3'-terminal phosphate from one of five distinctive insertion loops. Finally, these observations demonstrate how polymerase θ grasps the primer to bypass DNA lesions or extend poorly annealed DNA termini to mediate end-joining.« less

  19. Abasic Phosphorothioate Oligomers Inhibit HIV-1 Reverse Transcription and Block Virus Transmission across Polarized Ectocervical Organ Cultures

    PubMed Central

    Fraietta, Joseph A.; Mueller, Yvonne M.; Lozenski, Karissa L.; Ratner, Deena; Boesteanu, Alina C.; Hancock, Aidan S.; Lackman-Smith, Carol; Zentner, Isaac J.; Chaiken, Irwin M.; Chung, Suhman; LeGrice, Stuart F. J.; Snyder, Beth A.; Mankowski, Marie K.; Jones, Natalie M.; Hope, Jennifer L.; Gupta, Phalguni; Anderson, Sharon H.; Wigdahl, Brian

    2014-01-01

    In the absence of universally available antiretroviral (ARV) drugs or a vaccine against HIV-1, microbicides may offer the most immediate hope for controlling the AIDS pandemic. The most advanced and clinically effective microbicides are based on ARV agents that interfere with the earliest stages of HIV-1 replication. Our objective was to identify and characterize novel ARV-like inhibitors, as well as demonstrate their efficacy at blocking HIV-1 transmission. Abasic phosphorothioate 2′ deoxyribose backbone (PDB) oligomers were evaluated in a variety of mechanistic assays and for their ability to inhibit HIV-1 infection and virus transmission through primary human cervical mucosa. Cellular and biochemical assays were used to elucidate the antiviral mechanisms of action of PDB oligomers against both lab-adapted and primary CCR5- and CXCR4-utilizing HIV-1 strains, including a multidrug-resistant isolate. A polarized cervical organ culture was used to test the ability of PDB compounds to block HIV-1 transmission to primary immune cell populations across ectocervical tissue. The antiviral activity and mechanisms of action of PDB-based compounds were dependent on oligomer size, with smaller molecules preventing reverse transcription and larger oligomers blocking viral entry. Importantly, irrespective of molecular size, PDBs potently inhibited virus infection and transmission within genital tissue samples. Furthermore, the PDB inhibitors exhibited excellent toxicity and stability profiles and were found to be safe for vaginal application in vivo. These results, coupled with the previously reported intrinsic anti-inflammatory properties of PDBs, support further investigations in the development of PDB-based topical microbicides for preventing the global spread of HIV-1. PMID:25224013

  20. Are Scientific Analogies Metaphors?

    DTIC Science & Technology

    1981-02-01

    attraction is certainly familiar, but its rules are unfortunately unclear; so this analogy does not tell the student precisely what to map from the...seriously. The rules of analogical mappings are such that, unless there is a principled reason to exempt a given predicate, it must be mapped if it belongs...contributes to their richness, for no possible mapping need be ruled out. Mutually contradictory inferences can co-exist. These analogies derive much

  1. Inhibition of Glucuronokinase by Substrate Analogs 1

    PubMed Central

    Gillard, Douglas F.; Dickinson, David B.

    1978-01-01

    Glucuronokinase from Lilium longiflorum pollen was purified 30- to 40- fold on a blue dextran-Sepharose column. Substrate analogs were tested for inhibitory effects, and nucleotide substrate specificity of the enzyme was determined. Nine nucleotides were tested, and all were inhibitory when the substrate was ATP. ADP was competitive with ATP and had a Ki value of 0.23 mm. None of the other nucleotide triphosphates could effectively substitute for ATP as a nucleotide substrate. Ten mm dATP and ITP reacted only 3% as rapidly as 10 mm ATP, while the rates for 10 mm GTP, CTP, UTP, and TTP were less than 1%. The glucuronic acid analogs, methyl α-glucuronoside, methyl β-glucuronoside, β-glucuronic acid-1-phosphate, and 4-O-methylglucuronic acid were tested as possible enzyme inhibitors. The three methyl derivatives showed little or no inhibition. The β-glucuronic acid-1-phosphate was inhibitory, with 50% inhibition obtained at 1 to 3 mm depending on the concentration of the glucuronic acid. It is concluded that the glucuronic acid-binding site on the enzyme is highly selective. PMID:16660589

  2. Workshop on the role of natural analogs in geologic disposal of high-level nuclear waste

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

    Murphy, W.M.

    1995-09-01

    A workshop on the Role of Natural Analogs in Geologic Disposal of High-Level Nuclear Waste (HLW) was held in San Antonio, Texas, on July 22-25, 1991. It was sponsored by the US Nuclear Regulatory Commission (NRC) and the Center for Nuclear Waste Regulatory Analyses (CNWRA). Invitations to the workshop were extended to a large number of individuals with a variety of technical and professional interests related to geologic disposal of nuclear waste and natural analog studies. The objective of the workshop was to examine the role of natural analog studies in performance assessment, site characterization, and prioritization of research relatedmore » to geologic disposal of HLW.« less

  3. Accumulation of True Single Strand Breaks and AP sites in Base Excision Repair Deficient Cells

    PubMed Central

    Luke, April M.; Chastain, Paul D.; Pachkowski, Brian F.; Afonin, Valeriy; Takeda, Shunichi; Kaufman, David G.; Swenberg, James A.; Nakamura, Jun

    2010-01-01

    Single strand breaks (SSBs) are one of the most frequent DNA lesions caused by endogenous and exogenous agents. The most utilized alkaline-based assays for SSB detection frequently give false positive results due to the presence of alkali-labile sites that are converted to SSBs. Methoxyamine, an acidic O-hydroxylamine, has been utilized to measure DNA damage in cells. However, the neutralization of methoxyamine is required prior to usage. Here we developed a convenient, specific SSB assay using alkaline gel electrophoresis (AGE) coupled with a neutral O-hydroxylamine, O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (OTX). OTX stabilizes abasic sites (AP sites) to prevent their alkaline incision while still allowing for strong alkaline DNA denaturation. DNA from DT40 and isogenic polymerase β null cells exposed to methyl methanesulfonate were applied to the OTX-coupled AGE (OTX-AGE) assay. Time-dependent increases in SSBs were detected in each cell line with more extensive SSB formation in the null cells. These findings were supported by an assay that indirectly detects SSBs through measuring NAD(P)H depletion. An ARP-slot blot assay demonstrated a significant time-dependent increase in AP sites in both cell lines by 1 mM MMS compared to control. Furthermore, the Pol β-null cells displayed greater AP site formation than the parental DT40 cells. OTX use represents a facile approach for assessing SSB formation, whose benefits can also be applied to other established SSB assays. PMID:20851134

  4. Analogy Just Looks Like High Level Perception: Why a Domain-General Approach to Analogical Mapping is Right

    DTIC Science & Technology

    1998-01-01

    rerepresentation processes) will be able to use analogy better than those who have not. There is some psychological evidence for this gentrification of knowledge... useful as a technical proposal. We focus on five issues: (1) how perception relates to analogy, (2) how flexibility arises in analogical processing, (3...whether analogy is a domain-general process, (4) how should micro-worlds be used in the study of analogy, and (5) how best to assess the psychological

  5. Fast-Turnoff Transient Electromagnetic (TEM) Field Study at the Mars Analog Site of Rio Tinto, Spain

    NASA Astrophysics Data System (ADS)

    Jernsletten, J. A.

    2005-03-01

    This report describes a Fast-Turnoff Transient Electromagnetic (TEM) study at the Peña de Hierro ("Berg of Iron") field area of the Mars Analog Research and Technology Experiment (MARTE), near the towns Rio Tinto and Nerva, Andalucia region, Spain.

  6. Analogical reasoning in children with specific language impairment: Evidence from a scene analogy task.

    PubMed

    Krzemien, Magali; Jemel, Boutheina; Maillart, Christelle

    2017-01-01

    Analogical reasoning is a human ability that maps systems of relations. It develops along with relational knowledge, working memory and executive functions such as inhibition. It also maintains a mutual influence on language development. Some authors have taken a greater interest in the analogical reasoning ability of children with language disorders, specifically those with specific language impairment (SLI). These children apparently have weaker analogical reasoning abilities than their aged-matched peers without language disorders. Following cognitive theories of language acquisition, this deficit could be one of the causes of language disorders in SLI, especially those concerning productivity. To confirm this deficit and its link to language disorders, we use a scene analogy task to evaluate the analogical performance of SLI children and compare them to controls of the same age and linguistic abilities. Results show that children with SLI perform worse than age-matched peers, but similar to language-matched peers. They are more influenced by increased task difficulty. The association between language disorders and analogical reasoning in SLI can be confirmed. The hypothesis of limited processing capacity in SLI is also being considered.

  7. N-terminal domains of human DNA polymerase lambda promote primer realignment during translesion DNA synthesis

    PubMed Central

    Taggart, David J.; Dayeh, Daniel M.; Fredrickson, Saul W.; Suo, Zucai

    2014-01-01

    The X-family DNA polymerases λ (Polλ) and β (Polβ) possess similar 5′-2-deoxyribose-5-phosphatelyase (dRPase) and polymerase domains. Besides these domains, Polλ also possesses a BRCA1 C-terminal (BRCT) domain and a proline-rich domain at its N terminus. However, it is unclear how these non-enzymatic domains contribute to the unique biological functions of Polλ. Here, we used primer extension assays and a newly developed high-throughput short oligonucleotide sequencing assay (HT-SOSA) to compare the efficiency of lesion bypass and fidelity of human Polβ, Polλ and two N-terminal deletion constructs of Polλ during the bypass of either an abasic site or a 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) lesion. We demonstrate that the BRCT domain of Polλ enhances the efficiency of abasic site bypass by approximately 1.6-fold. In contrast, deletion of the N-terminal domains of Polλ did not affect the efficiency of 8-oxodG bypass relative to nucleotide incorporations opposite undamaged dG. HT-SOSA analysis demonstrated that Polλ and Polβ preferentially generated −1 or −2 frameshift mutations when bypassing an abasic site and the single or double base deletion frequency was highly sequence dependent. Interestingly, the BRCT and proline-rich domains of Polλ cooperatively promoted the generation of −2 frameshift mutations when the abasic site was situated within a sequence context that was susceptible to homology-driven primer realignment. Furthermore, both N-terminal domains of Polλ increased the generation of −1 frameshift mutations during 8-oxodG bypass and influenced the frequency of substitution mutations produced by Polλ opposite the 8-oxodG lesion. Overall, our data support a model wherein the BRCT and proline-rich domains of Polλ act cooperatively to promote primer/template realignment between DNA strands of limited sequence homology. This function of the N-terminal domains may facilitate the role of Polλ as a gap-filling polymerase

  8. Science Teachers' Analogical Reasoning

    ERIC Educational Resources Information Center

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-01-01

    Analogies can play a relevant role in students' learning. However, for the effective use of analogies, teachers should not only have a well-prepared repertoire of validated analogies, which could serve as bridges between the students' prior knowledge and the scientific knowledge they desire them to understand, but also know how to…

  9. Architecture of PFC supports analogy, but PFC is not an analogy machine.

    PubMed

    Speed, Ann

    2010-06-01

    In the preceding discussion paper, I proposed a theory of prefrontal cortical organization that was fundamentally intended to address the question: How does prefrontal cortex (PFC) support the various functions for which it seems to be selectively recruited? In so doing, I chose to focus on a particular function, analogy, that seems to have been largely ignored in the theoretical treatments of PFC, but that does underlie many other cognitive functions (Hofstadter, 2001 ; Holyoak & Thagard, 1997 ). At its core, this paper was intended to use analogy as a foundation for exploring one possibility for prefrontal function in general, although it is easy to see how the analogy-specific interpretation arises (as in the comment by Ibáñez). In an attempt to address this more foundational question, this response will step away from analogy as a focus, and will address first the various comments from the perspective of the initial motivation for developing this theory, and then specific issues raised by the commentators.

  10. All-optical analog comparator.

    PubMed

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-08-23

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical '1' or '0' by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function.

  11. The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ

    PubMed Central

    Hirota, Kouji; Yoshikiyo, Kazunori; Guilbaud, Guillaume; Tsurimoto, Toshiki; Murai, Junko; Tsuda, Masataka; Phillips, Lara G.; Narita, Takeo; Nishihara, Kana; Kobayashi, Kaori; Yamada, Kouich; Nakamura, Jun; Pommier, Yves; Lehmann, Alan; Sale, Julian E.; Takeda, Shunichi

    2015-01-01

    The replicative DNA polymerase Polδ consists of a catalytic subunit POLD1/p125 and three regulatory subunits POLD2/p50, POLD3/p66 and POLD4/p12. The ortholog of POLD3 in Saccharomyces cerevisiae, Pol32, is required for a significant proportion of spontaneous and UV-induced mutagenesis through its additional role in translesion synthesis (TLS) as a subunit of DNA polymerase ζ. Remarkably, chicken DT40 B lymphocytes deficient in POLD3 are viable and able to replicate undamaged genomic DNA with normal kinetics. Like its counterpart in yeast, POLD3 is required for fully effective TLS, its loss resulting in hypersensitivity to a variety of DNA damaging agents, a diminished ability to maintain replication fork progression after UV irradiation and a significant decrease in abasic site-induced mutagenesis in the immunoglobulin loci. However, these defects appear to be largely independent of Polζ, suggesting that POLD3 makes a significant contribution to TLS independently of Polζ in DT40 cells. Indeed, combining polη, polζ and pold3 mutations results in synthetic lethality. Additionally, we show in vitro that POLD3 promotes extension beyond an abasic by the Polδ holoenzyme suggesting that while POLD3 is not required for normal replication, it may help Polδ to complete abasic site bypass independently of canonical TLS polymerases. PMID:25628356

  12. Synchronous in-field application of life-detection techniques in planetary analog missions

    NASA Astrophysics Data System (ADS)

    Amador, Elena S.; Cable, Morgan L.; Chaudry, Nosheen; Cullen, Thomas; Gentry, Diana; Jacobsen, Malene B.; Murukesan, Gayathri; Schwieterman, Edward W.; Stevens, Adam H.; Stockton, Amanda; Yin, Chang; Cullen, David C.; Geppert, Wolf

    2015-02-01

    Field expeditions that simulate the operations of robotic planetary exploration missions at analog sites on Earth can help establish best practices and are therefore a positive contribution to the planetary exploration community. There are many sites in Iceland that possess heritage as planetary exploration analog locations and whose environmental extremes make them suitable for simulating scientific sampling and robotic operations. We conducted a planetary exploration analog mission at two recent lava fields in Iceland, Fimmvörðuháls (2010) and Eldfell (1973), using a specially developed field laboratory. We tested the utility of in-field site sampling down selection and tiered analysis operational capabilities with three life detection and characterization techniques: fluorescence microscopy (FM), adenine-triphosphate (ATP) bioluminescence assay, and quantitative polymerase chain reaction (qPCR) assay. The study made use of multiple cycles of sample collection at multiple distance scales and field laboratory analysis using the synchronous life-detection techniques to heuristically develop the continuing sampling and analysis strategy during the expedition. Here we report the operational lessons learned and provide brief summaries of scientific data. The full scientific data report will follow separately. We found that rapid in-field analysis to determine subsequent sampling decisions is operationally feasible, and that the chosen life detection and characterization techniques are suitable for a terrestrial life-detection field mission. In-field analysis enables the rapid obtainment of scientific data and thus facilitates the collection of the most scientifically relevant samples within a single field expedition, without the need for sample relocation to external laboratories. The operational lessons learned in this study could be applied to future terrestrial field expeditions employing other analytical techniques and to future robotic planetary exploration

  13. Synthetic Analogs of Phospholipid Metabolites as Antimalarials.

    DTIC Science & Technology

    1979-07-01

    phosphatidic acid analogs containing ether and phosphonate groups; completely non-hydrolyzable lecithin analogs containing phosphinate and ether groups...The phosphatidic acid and lecithin target compounds were successfully synthesized and submitted, together with a number of intermediates. A model of a... Phosphatidic acid analogs ......................... 5 Z.Z Lecithin Analogs .................................. 6 2.3 Analogs of Cytidine Diphosphate

  14. Anatomic Customization of Root-Analog Dental Implants With Cone-Beam CT and CAD/CAM Fabrication: A Cadaver-Based Pilot Evaluation.

    PubMed

    Evans, Zachary P; Renne, Walter G; Bacro, Thierry R; Mennito, Anthony S; Ludlow, Mark E; Lecholop, Michael K

    2018-02-01

    Existing root-analog dental implant systems have no standardized protocols regarding retentive design, surface manipulation, or prosthetic attachment design relative to the site's unique anatomy. Historically, existing systems made those design choices arbitrarily. For this report, strategies were developed that deliberately reference the adjacent anatomy, implant and restorable path of draw, and bone density for implant and retentive design. For proof of concept, dentate arches from human cadavers were scanned using cone-beam computed tomography and then digitally modeled. Teeth of interest were virtually extracted and manipulated via computer-aided design to generate root-analog implants from zirconium. We created a stepwise protocol for analyzing and developing the implant sites, implant design and retention, and prosthetic emergence and connection all from the pre-op cone-beam data. Root-analog implants were placed at the time of extraction and examined radiographically and mechanically concerning ideal fit and stability. This study provides proof of concept that retentive root-analog implants can be produced from cone-beam data while improving fit, retention, safety, esthetics, and restorability when compared to the existing protocols. These advancements may provide the critical steps necessary for clinical relevance and success of immediately placed root-analog implants. Additional studies are necessary to validate the model prior to clinical trial.

  15. Students' Pre- and Post-Teaching Analogical Reasoning when They Draw Their Analogies

    ERIC Educational Resources Information Center

    Mozzer, Nilmara Braga; Justi, Rosaria

    2012-01-01

    Analogies are parts of human thought. From them, we can acquire new knowledge or change that which already exists in our cognitive structure. In this sense, understanding the analogical reasoning process becomes an essential condition to understand how we learn. Despite the importance of such an understanding, there is no general agreement in…

  16. All-optical analog comparator

    PubMed Central

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-01-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function. PMID:27550874

  17. All-optical analog comparator

    NASA Astrophysics Data System (ADS)

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-08-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function.

  18. Resistive RAMs as analog trimming elements

    NASA Astrophysics Data System (ADS)

    Aziza, H.; Perez, A.; Portal, J. M.

    2018-04-01

    This work investigates the use of Resistive Random Access Memory (RRAM) as an analog trimming device. The analog storage feature of the RRAM cell is evaluated and the ability of the RRAM to hold several resistance states is exploited to propose analog trim elements. To modulate the memory cell resistance, a series of short programming pulses are applied across the RRAM cell allowing a fine calibration of the RRAM resistance. The RRAM non volatility feature makes the analog device powers up already calibrated for the system in which the analog trimmed structure is embedded. To validate the concept, a test structure consisting of a voltage reference is evaluated.

  19. Site-directed DNA crosslinking of large multisubunit protein-DNA complexes.

    PubMed

    Persinger, Jim; Bartholomew, Blaine

    2009-01-01

    Several methods have been developed to site-specifically incorporate photoreactive nucleotide analogs into DNA for the purpose of identifying the proteins and their domains that are in contact with particular regions of DNA. The synthesis of several deoxynucleotide analogs that have a photoreactive group tethered to the nucleotide base and the incorporation of these analogs into DNA are described. In a second approach, oligonucleotide with a photoreactive group attached to the phosphate backbone is chemically synthesized. The photoreactive oligonucleotide is then enzymatically incorporated into DNA by annealing it to a complementary DNA template and extending with DNA polymerase. Both approaches have been effectively used to map protein-DNA interactions in large multisubunit complexes such as the eukaryotic transcription or ATP-dependent chromatin remodeling complexes. Not only do these techniques map the binding sites of the various subunits in these complexes, but when coupled with peptide mapping also determine the protein domain that is in close proximity to the different DNA sites. The strength of these techniques is the ability to scan a large number of potential sites by making combinations of different DNA probes and is facilitated by using an immobilized DNA template for synthesis.

  20. Synthetic Analogs of Curcumin Modulate the Function of Multidrug Resistance-Linked ATP-Binding Cassette Transporter ABCG2.

    PubMed

    Murakami, Megumi; Ohnuma, Shinobu; Fukuda, Michihiro; Chufan, Eduardo E; Kudoh, Katsuyoshi; Kanehara, Keigo; Sugisawa, Norihiko; Ishida, Masaharu; Naitoh, Takeshi; Shibata, Hiroyuki; Iwabuchi, Yoshiharu; Ambudkar, Suresh V; Unno, Michiaki

    2017-11-01

    Multidrug resistance (MDR) caused by the overexpression of ATP-binding cassette (ABC) transporters in cancer cells is a major obstacle in cancer chemotherapy. Previous studies have shown that curcumin, a natural product and a dietary constituent of turmeric, inhibits the function of MDR-related ABC transporters, including ABCB1, ABCC1, and especially ABCG2. However, the limited bioavailability of curcumin prevents its use for modulation of the function of these transporters in the clinical setting. In this study, we investigated the effects of 24 synthetic curcumin analogs with increased bioavailability on the transport function of ABCG2. The screening of the 24 synthetic analogs by means of flow cytometry revealed that four of the curcumin analogs (GO-Y030, GO-Y078, GO-Y168, and GO-Y172) significantly inhibited the efflux of the ABCG2 substrates, mitoxantrone and pheophorbide A, from ABCG2-overexpressing K562/breast cancer resistance protein (BCRP) cells. Biochemical analyses showed that GO-Y030, GO-Y078, and GO-Y172 stimulated the ATPase activity of ABCG2 at nanomolar concentrations and inhibited the photolabeling of ABCG2 with iodoarylazidoprazosin, suggesting that these analogs interact with the substrate-binding sites of ABCG2. In addition, when used in cytotoxicity assays, GO-Y030 and GO-Y078 were found to improve the sensitivity of the anticancer drug, SN-38, in K562/BCRP cells. Taken together, these results suggest that nontoxic synthetic curcumin analogs with increased bioavailability, especially GO-Y030 and GO-Y078, inhibit the function of ABCG2 by directly interacting at the substrate-binding site. These synthetic curcumin analogs could therefore be developed as potent modulators to overcome ABCG2-mediated MDR in cancer cells. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  1. Field Characterization of the Mineralogy and Organic Chemistry of Carbonates from the 2010 Arctic Mars Analog Svalbard Expedition by Evolved Gas Analysis

    NASA Technical Reports Server (NTRS)

    McAdam, A. C.; Ten Kate, I. L.; Stern, J. C.; Mahaffy, P. R.; Blake, D. F.; Morris, R. V.; Steele, A.; Amundson, H. E. F.

    2011-01-01

    The 2010 Arctic Mars Analog Svalbard Expedition (AMASE) investigated two geologic settings using methodologies and techniques being developed or considered for future Mars missions, such as the Mars Science Laboratory (MSL), ExoMars, and Mars Sample Return. The Sample Analysis at Mars (SAM) [1] instrument suite, which will be on MSL, consists of a quadrupole mass spectrometer (QMS), a gas chromatograph (GC), and a tunable laser mass spectrometer (TLS); all will be applied to analyze gases created by pyrolysis of samples. During AMASE, a Hiden Evolved Gas Analysis-Mass Spectrometer (EGA-MS) system represented the EGA-MS capability of SAM. Another MSL instrument, CheMin, will use x-ray diffraction (XRD) and x-ray fluorescence (XRF) to perform quantitative mineralogical characterization of samples [e.g., 2]. Field-portable versions of CheMin were used during AMASE. AMASE 2010 focused on two sites that represented biotic and abiotic analogs. The abiotic site was the basaltic Sigurdfjell vent complex, which contains Mars-analog carbonate cements including carbonate globules which are excellent analogs for the globules in the ALH84001 martian meteorite [e.g., 3, 4]. The biotic site was the Knorringfjell fossil methane seep, which featured carbonates precipitated in a methane-supported chemosynthetic community [5]. This contribution focuses on EGA-MS analyses of samples from each site, with mineralogy comparisons to CheMin team results. The results give insight into organic content and organic-mineral associations, as well as some constraints on the minerals present.

  2. Electrical Circuits and Water Analogies

    ERIC Educational Resources Information Center

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  3. Inviting Argument by Analogy: Analogical-Mapping-Based Comparison Activities as a Scaffold for Small-Group Argumentation

    ERIC Educational Resources Information Center

    Emig, Brandon R.; McDonald, Scott; Zembal-Saul, Carla; Strauss, Susan G.

    2014-01-01

    This study invited small groups to make several arguments by analogy about simple machines. Groups were first provided training on analogical (structure) mapping and were then invited to use analogical mapping as a scaffold to make arguments. In making these arguments, groups were asked to consider three simple machines: two machines that they had…

  4. Challenges in Using Analogies

    ERIC Educational Resources Information Center

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  5. Working memory predicts children's analogical reasoning.

    PubMed

    Simms, Nina K; Frausel, Rebecca R; Richland, Lindsey E

    2018-02-01

    Analogical reasoning is the cognitive skill of drawing relationships between representations, often between prior knowledge and new representations, that allows for bootstrapping cognitive and language development. Analogical reasoning proficiency develops substantially during childhood, although the mechanisms underlying this development have been debated, with developing cognitive resources as one proposed mechanism. We explored the role of executive function (EF) in supporting children's analogical reasoning development, with the goal of determining whether predicted aspects of EF were related to analogical development at the level of individual differences. We assessed 5- to 11-year-old children's working memory, inhibitory control, and cognitive flexibility using measures from the National Institutes of Health Toolbox Cognition battery. Individual differences in children's working memory best predicted performance on an analogical mapping task, even when controlling for age, suggesting a fundamental interrelationship between analogical reasoning and working memory development. These findings underscore the need to consider cognitive capacities in comprehensive theories of children's reasoning development. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Optical analog-to-digital converter

    DOEpatents

    Vawter, G Allen [Corrales, NM; Raring, James [Goleta, CA; Skogen, Erik J [Albuquerque, NM

    2009-07-21

    An optical analog-to-digital converter (ADC) is disclosed which converts an input optical analog signal to an output optical digital signal at a sampling rate defined by a sampling optical signal. Each bit of the digital representation is separately determined using an optical waveguide interferometer and an optical thresholding element. The interferometer uses the optical analog signal and the sampling optical signal to generate a sinusoidally-varying output signal using cross-phase-modulation (XPM) or a photocurrent generated from the optical analog signal. The sinusoidally-varying output signal is then digitized by the thresholding element, which includes a saturable absorber or at least one semiconductor optical amplifier, to form the optical digital signal which can be output either in parallel or serially.

  7. In silico design and screening of hypothetical MOF-74 analogs and their experimental synthesis

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

    Witman, Matthew; Ling, Sanliang; Anderson, Samantha

    Here, we present the in silico design of metal-organic frameworks (MOFs) exhibiting 1-dimensional rod topologies. We then introduce an algorithm for construction of this family of MOF topologies, and illustrate its application for enumerating MOF-74-type analogs. Furthermore, we perform a broad search for new linkers that satisfy the topological requirements of MOF-74 and consider the largest database of known chemical space for organic compounds, the PubChem database. Our in silico crystal assembly, when combined with dispersion-corrected density functional theory (DFT) calculations, is demonstrated to generate a hypothetical library of open-metal site containing MOF-74 analogs in the 1-D rod topology frommore » which we can simulate the adsorption behavior of CO 2 . We conclude that these hypothetical structures have synthesizable potential through computational identification and experimental validation of a novel MOF-74 analog, Mg 2 (olsalazine).« less

  8. In silico design and screening of hypothetical MOF-74 analogs and their experimental synthesis

    DOE PAGES

    Witman, Matthew; Ling, Sanliang; Anderson, Samantha; ...

    2016-06-21

    Here, we present the in silico design of metal-organic frameworks (MOFs) exhibiting 1-dimensional rod topologies. We then introduce an algorithm for construction of this family of MOF topologies, and illustrate its application for enumerating MOF-74-type analogs. Furthermore, we perform a broad search for new linkers that satisfy the topological requirements of MOF-74 and consider the largest database of known chemical space for organic compounds, the PubChem database. Our in silico crystal assembly, when combined with dispersion-corrected density functional theory (DFT) calculations, is demonstrated to generate a hypothetical library of open-metal site containing MOF-74 analogs in the 1-D rod topology frommore » which we can simulate the adsorption behavior of CO 2 . We conclude that these hypothetical structures have synthesizable potential through computational identification and experimental validation of a novel MOF-74 analog, Mg 2 (olsalazine).« less

  9. Basic Electricity--a Novel Analogy.

    ERIC Educational Resources Information Center

    Grant, Richard

    1996-01-01

    Uses the analogy of water flow to introduce concepts in basic electricity. Presents a demonstration that uses this analogy to help students grasp the relationship between current, voltage, and resistance. (JRH)

  10. Activity-based assay for ricin-like toxins

    DOEpatents

    Keener, William K.; Ward, Thomas E.

    2007-02-06

    A method of detecting N-glycosylase activity in a sample involves incubating an oligodeoxyribonucleotide substrate containing a deoxyadenosine or deoxyuridine residue with the sample to be tested such that the N-glycosylase, if present, hydrolyzes the deoxyadenosine or deoxyuridine residue to result in an N-glycosylase product having an abasic site. A primer is annealed to the N-glycosylase product, and the primer is extended with a DNA polymerase, such as Taq DNA polymerase, that pauses at abasic sites. The resulting extension products are melted from the N-glycosylase product, allowed to form hairpins due to self-complementarity, and further extended in the presence of labeled precursors to result in labeled products. Extension products synthesized from undigested substrate as template do not result in labeled products. Thus, detection of labeled products results in detection of N-glycosylase activity. Oligodeoxyribonucleotide substrates, primer, and positive controls and a kit for N-glycosylase assay are also disclosed.

  11. Moessbauer/XRF MIMOS Instrumentation and Operation During the 2012 Analog Field Test on Mauna Kea Volcano, Hawaii

    NASA Technical Reports Server (NTRS)

    Graff, Trevor G.; Morris, R. V.; Klingelhofer, G.; Blumers, M.

    2013-01-01

    Field testing and scientific investigations were conducted on the Mauna Kea Volcano, Hawaii, as part of the 2012 Moon and Mars Analog Mission Activities (MMAMA). Measurements were conducted using both stand-alone and rover-mounted instruments to determine the geophysical and geochemical properties of the field site, as well as provide operational constraints and science considerations for future robotic and human missions [1]. Reported here are the results from the two MIMOS instruments deployed as part of this planetary analog field test.

  12. Analogies and the 5E Model

    ERIC Educational Resources Information Center

    Orgill, Mary Kay; Thomas, Megan

    2007-01-01

    Science classes are full of abstract or challenging concepts that are easier to understand if an analogy is used to illustrate the points. Effective analogies motivate students, clarify students' thinking, help students overcome misconceptions, and give students ways to visualize abstract concepts. When they are used appropriately, analogies can…

  13. The nicotinic acetylcholine receptor: Binding of nitroxide analogs of a local anesthetic and a photoactivatable analog of phosphatidylserine

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

    Blanton, M.P.

    1989-01-01

    Electron spin resonance was used to contrast the accessibility of tertiary and quaternary amine local anesthetics to their high affinity binding site in the desensitized Torpedo californica acetylcholine receptor (AchR). Preincubation of AchR-rich membranes with agonist resulted in a substantial reduction in the initial association of the quaternary amine local anesthetic C6SLMEI with the receptor. The time-dependent reduction in association follows a biphasic exponential function having rate constants of 0.19 min{sup {minus}1} and 0.03 min{sup {minus}1}. In contrast, agonist preincubation did not produce a comparable decrease in the association of C6SL, a tertiary amine analog, with the AchR. The resultsmore » are modeled in two ways: (1) A charge gate near the channel mouth in the desensitized receptor limits access of the permanently charged cationic local anesthetic (C6SLMEI), but not for the uncharged form of the tertiary amine anesthetic C6SL. (2) A hydrophobic pathway, possibly through a corridor in the annular lipid surrounding receptor subunits, allows the uncharged form of C6SL to reach the high affinity binding site in the AchR. A photoactivatable analog of phosphatidylserine {sup 125}I 4-azido salicylic acid-phosphatidylserine ({sup 125}I ASA-PS) was use to label both Torpedo californica acetylcholine receptor-rich membranes and reconstituted AchR membranes. All four subunits of the AchR were found to incorporate label, with the {alpha} subunit incorporating approximately twice as much as each of the other subunits on a per mole basis. The regions of the AchR {alpha} subunit that incorporate {sup 125}I ASA-PS were mapped by Staphylococcus aureus V8 protease digestion. Eighty-one per cent of the incorporated label was localized to 11.7 and 10.1 kdal V8 cleavage fragments.« less

  14. [Adenylate cyclase from rabbit heart: substrate binding site].

    PubMed

    Perfil'eva, E A; Khropov, Iu V; Khachatrian, L; Bulargina, T V; Baranova, L A

    1981-08-01

    The effects of 17 ATP analogs on the solubilized rabbit heart adenylate cyclase were studied. The triphosphate chain, position 8 of the adenine base and the ribose residue of the ATP molecule were modified. Despite the presence of the alkylating groups in two former types of the analogs tested, no covalent blocking of the active site of the enzyme was observed. Most of the compounds appeared to be competitive reversible inhibitors. The kinetic data confirmed the importance of the triphosphate chain for substrate binding in the active site of adenylate cyclase. (Formula: See Text) The inhibitors with different substituents in position 8 of the adenine base had a low affinity for the enzyme. The possible orientation of the triphosphate chain and the advantages of anti-conformation of the ATP molecule for their binding in the active site of adenylate cyclase are discussed.

  15. Using thermodynamic integration MD simulation to compute relative protein-ligand binding free energy of a GSK3β kinase inhibitor and its analogs.

    PubMed

    Lee, Hsing-Chou; Hsu, Wen-Chi; Liu, An-Lun; Hsu, Chia-Jen; Sun, Ying-Chieh

    2014-06-01

    Thermodynamic integration molecular dynamics simulation was used to investigate how TI-MD simulation preforms in reproducing relative protein-ligand binding free energy of a pair of analogous GSK3β kinase inhibitors of available experimental data (see Fig. 1), and to predict the affinity for other analogs. The computation for the pair gave a ΔΔG of 1.0 kcal/mol, which was in reasonably good agreement with the experimental value of -0.1 kcal/mol. The error bar was estimated at 0.5 kcal/mol. Subsequently, we employed the same protocol to proceed with simulations to find analogous inhibitors with a stronger affinity. Four analogs with a substitution at one site inside the binding pocket were the first to be tried, but no significant enhancement in affinity was found. Subsequent simulations for another 7 analogs was focused on substitutions at the benzene ring of another site, which gave two analogs (analogs 9 and 10) with ΔΔG values of -0.6 and -0.8 kcal/mol, respectively. Both analogs had a OH group at the meta position and another OH group at the ortho position at the other side of the benzene ring, as shown in Table 3. To explore further, another 4 analogs with this characteristic were investigated. Three analogs with ΔΔG values of -2.2, -1.7 and -1.2 kcal/mol, respectively, were found. Hydrogen bond analysis suggested that the additional hydrogen bonds of the added OH groups with Gln185 and/or Asn64, which did not appear in the reference inhibitor or as an analog with one substitution only in the examined cases, were the main contributors to an enhanced affinity. A prediction for better inhibitors should interest experimentalists of enzyme and/or cell assays. Analysis of the interactions between GSK3β kinase and the investigated analogs will be useful in the design of GSK3β kinase inhibitors for compounds of this class. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Is the Link from Working Memory to Analogy Causal? No Analogy Improvements following Working Memory Training Gains

    PubMed Central

    Richey, J. Elizabeth; Phillips, Jeffrey S.; Schunn, Christian D.; Schneider, Walter

    2014-01-01

    Analogical reasoning has been hypothesized to critically depend upon working memory through correlational data [1], but less work has tested this relationship through experimental manipulation [2]. An opportunity for examining the connection between working memory and analogical reasoning has emerged from the growing, although somewhat controversial, body of literature suggests complex working memory training can sometimes lead to working memory improvements that transfer to novel working memory tasks. This study investigated whether working memory improvements, if replicated, would increase analogical reasoning ability. We assessed participants’ performance on verbal and visual analogy tasks after a complex working memory training program incorporating verbal and spatial tasks [3], [4]. Participants’ improvements on the working memory training tasks transferred to other short-term and working memory tasks, supporting the possibility of broad effects of working memory training. However, we found no effects on analogical reasoning. We propose several possible explanations for the lack of an impact of working memory improvements on analogical reasoning. PMID:25188356

  17. Analogies: Explanatory Tools in Web-Based Science Instruction

    ERIC Educational Resources Information Center

    Glynn, Shawn M.; Taasoobshirazi, Gita; Fowler, Shawn

    2007-01-01

    This article helps designers of Web-based science instruction construct analogies that are as effective as those used in classrooms by exemplary science teachers. First, the authors explain what analogies are, how analogies foster learning, and what form analogies should take. Second, they discuss science teachers' use of analogies. Third, they…

  18. NASA Cribs: Human Exploration Research Analog

    NASA Image and Video Library

    2017-07-20

    Follow along as interns at NASA’s Johnson Space Center show you around the Human Exploration Research Analog (HERA), a mission simulation environment located onsite at the Johnson Space Center in Houston. HERA is a unique three-story habitat designed to serve as an analog for isolation, confinement, and remote conditions in exploration scenarios. This video gives a tour of where crew members live, work, sleep, and eat during the analog missions. Find out more about HERA mission activities: https://www.nasa.gov/analogs/hera Find out how to be a HERA crew member: https://www.nasa.gov/analogs/hera/want-to-participate For more on NASA internships: https://intern.nasa.gov/ For Johnson Space Center specific internships: https://pathways.jsc.nasa.gov/ https://www.nasa.gov/centers/johnson/education/interns/index.html HD download link: https://archive.org/details/jsc2017m000730_NASA-Cribs-Human-Exploration-Research-Analog --------------------------------- FOLLOW JOHNSON SPACE CENTER INTERNS! Facebook: @NASA.JSC.Students https://www.facebook.com/NASA.JSC.Students/ Instagram: @nasajscstudents https://www.instagram.com/nasajscstudents/ Twitter: @NASAJSCStudents https://twitter.com/nasajscstudents

  19. FGF growth factor analogs

    DOEpatents

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  20. The Robustness of Acoustic Analogies

    NASA Technical Reports Server (NTRS)

    Freund, J. B.; Lele, S. K.; Wei, M.

    2004-01-01

    Acoustic analogies for the prediction of flow noise are exact rearrangements of the flow equations N(right arrow q) = 0 into a nominal sound source S(right arrow q) and sound propagation operator L such that L(right arrow q) = S(right arrow q). In practice, the sound source is typically modeled and the propagation operator inverted to make predictions. Since the rearrangement is exact, any sufficiently accurate model of the source will yield the correct sound, so other factors must determine the merits of any particular formulation. Using data from a two-dimensional mixing layer direct numerical simulation (DNS), we evaluate the robustness of two analogy formulations to different errors intentionally introduced into the source. The motivation is that since S can not be perfectly modeled, analogies that are less sensitive to errors in S are preferable. Our assessment is made within the framework of Goldstein's generalized acoustic analogy, in which different choices of a base flow used in constructing L give different sources S and thus different analogies. A uniform base flow yields a Lighthill-like analogy, which we evaluate against a formulation in which the base flow is the actual mean flow of the DNS. The more complex mean flow formulation is found to be significantly more robust to errors in the energetic turbulent fluctuations, but its advantage is less pronounced when errors are made in the smaller scales.

  1. Biotoxicity of Mars soils: 2. Survival of Bacillus subtilis and Enterococcus faecalis in aqueous extracts derived from six Mars analog soils

    NASA Astrophysics Data System (ADS)

    Schuerger, Andrew C.; Ming, Doug W.; Golden, D. C.

    2017-07-01

    The search for an extant microbiota on Mars depends on exploring sites that contain transient or permanent liquid water near the surface. Examples of possible sites for liquid water may be active recurring slope lineae (RSL) and fluid inclusions in ice or salt deposits. The presence of saline fluids on Mars will act to depress the freezing points of liquid water to as low as ‒60 °C, potentially permitting the metabolism and growth of halophilic microorganisms to temperatures significantly below the freezing point of pure water at 0 °C. In order to predict the potential risks of forward contamination by Earth microorganisms to subsurface sites on Mars with liquid brines, experiments were designed to characterize the short-term survival of two bacteria in aqueous soil solutions from six analog soils. The term ''soil'' is used here to denote any loose, unconsolidated matrix with no implications for the presence or absence of organics or biology. The analog soils were previously described (Schuerger et al., 2012, Planetary Space Sci., 72, 91-101), and represented crushed Basalt (benign control), Salt, Acid, Alkaline, Aeolian, and Phoenix analogs on Mars. The survival rates of spores of Bacillus subtilis and vegetative cells of Enterococcus faecalis were tested in soil solutions from each analog at 24, 0, or ‒70 °C for time periods up to 28 d. Survival of dormant spores of B. subtilis were mostly unaffected by incubation in the aqueous extracts of all six Mars analogs. In contrast, survival rates of E. faecalis cells were suppressed by all soil solutions when incubated at 24 °C but improved at 0 and ‒70 °C, except for assays in the Salt and Acid soil solutions in which most cells were killed. Results suggest that Earth microorganisms that form spores may persist in liquid brines on Mars better than non-spore forming species, and thus, spore-forming species may pose a potential forward contamination risk to sites with liquid brines.

  2. Not All Analogies Are Created Equal: Associative and Categorical Analogy Processing following Brain Damage

    ERIC Educational Resources Information Center

    Schmidt, Gwenda L.; Cardillo, Eileen R.; Kranjec, Alexander; Lehet, Matthew; Widick, Page; Chatterjee, Anjan

    2012-01-01

    Current research on analogy processing assumes that different conceptual relations are treated similarly. However, just as words and concepts are related in distinct ways, different kinds of analogies may employ distinct types of relationships. An important distinction in how words are related is the difference between associative (dog-bone) and…

  3. Activation and inhibition of adenylyl cyclase isoforms by forskolin analogs.

    PubMed

    Pinto, Cibele; Papa, Dan; Hübner, Melanie; Mou, Tung-Chung; Lushington, Gerald H; Seifert, Roland

    2008-04-01

    Adenylyl cyclase (AC) isoforms 1 to 9 are differentially expressed in tissues and constitute an interesting drug target. ACs 1 to 8 are activated by the diterpene, forskolin (FS). It is unfortunate that there is a paucity of AC isoform-selective activators. To develop such compounds, an understanding of the structure/activity relationships of diterpenes is necessary. Therefore, we examined the effects of FS and nine FS analogs on ACs 1, 2, and 5 expressed in Spodoptera frugiperda insect cells. Diterpenes showed the highest potencies at AC1 and the lowest potencies at AC2. We identified full agonists, partial agonists, antagonists, and inverse agonists, i.e., diterpenes that reduced basal AC activity. Each AC isoform exhibited a distinct pharmacological profile. AC2 showed the highest basal activity of all AC isoforms and highest sensitivity to inverse agonistic effects of 1-deoxy-forskolin, 7-deacetyl-1,9-dideoxy-forskolin, and, particularly, BODIPY-forskolin. In contrast, BODIPY-forskolin acted as partial agonist at the other ACs. 1-Deoxy-forskolin analogs were devoid of agonistic activity at ACs but antagonized the effects of FS in a mixed competitive/noncompetitive manner. At purified catalytic AC subunits, BODIPY-forskolin acted as weak partial agonist/strong partial antagonist. Molecular modeling revealed that the BODIPY group rotates promiscuously outside of the FS-binding site. Collectively, ACs are not uniformly activated and inhibited by FS and FS analogs, demonstrating the feasibility to design isoform-selective FS analogs. The two- and multiple-state models, originally developed to conceptualize ligand effects at G-protein-coupled receptors, can be applied to ACs to explain certain experimental data.

  4. Enhancing programming logic thinking using analogy mapping

    NASA Astrophysics Data System (ADS)

    Sukamto, R. A.; Megasari, R.

    2018-05-01

    Programming logic thinking is the most important competence for computer science students. However, programming is one of the difficult subject in computer science program. This paper reports our work about enhancing students' programming logic thinking using Analogy Mapping for basic programming subject. Analogy Mapping is a computer application which converts source code into analogies images. This research used time series evaluation and the result showed that Analogy Mapping can enhance students' programming logic thinking.

  5. Gemini analogs of vitamin D.

    PubMed

    Pazos, Gonzalo; Rivadulla, Marcos L; Pérez-García, Xenxo; Gandara, Zoila; Pérez, Manuel

    2014-01-01

    The Gemini analogs are the last significant contribution to the family of vitamin D derivatives in medicine, for the treatment of cancer. The first Gemini analog was characterized by two symmetric side chains at C-20. Following numerous modifications, the most active analog bears a C-23-triple bond, C-26, 27- hexafluoro substituents on one side chain and a terminal trideuteromethylhydroxy group on the other side chain. This progression was possible due to improvements in the synthetic methods for the preparation of these derivatives, which allowed for increasing molecular complexity and complete diastereoselective control at C-20 and the substituted sidechains.

  6. Radioreceptor assay for analysis of fentanyl and its analogs in biological samples

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

    Alburges, M.E.

    The assay is based on the competition of these drugs with ({sup 3}H) fentanyl for opioid receptors in membrane preparations of rat forebrain in vitro. The binding in stereospecific, reversible and saturable. Scatchard plots of saturation suggest the presence of high and low affinity binding sites. Morphine and hydromorphone complete with ({sup 3}H)fentanyl for the opioid receptor, but other morphine-like compounds were relatively weak displacers of ({sup 3}H)fentanyl. Many other commonly abused drugs do not compete with ({sup 3}H)fentanyl for the opioid receptors. Urine samples from animals injected with fentanyl, ({plus minus})-cis-3-methylfentanyl, alpha-methylfentanyl, butyrylfentanyl and benzylfentanyl were analyzed by radioreceptormore » assay, radioimmunoassay, and gas chromatography/mass spectrometry. Urinary analysis of fentanyl showed a good correlation with these three methods; however, discrepancies were observed in the analysis of fentanyl analogs. This radioreceptor assay is well-suited as an initial assay for the detection of active analogs of fentanyl in urine with good correlation with other techniques in the analysis of fentanyl; however, there is substantial disagreement between techniques in the quantitation of fentanyl analogs. The implications of these discrepancies are discussed.« less

  7. Multiple Analogies for Complex Concepts: Antidotes for Analogy-Induced Misconception in Advanced Knowledge Acquisition. Technical Report No. 439.

    ERIC Educational Resources Information Center

    Spiro, Rand J.; And Others

    This report argues that there exists a pervasive tendency for analogies to contribute to the development of entrenched misconceptions in the form of reducing complex new knowledge to the core of a source analogy. The report presents a taxonomy of ways that simple analogy induces conceptual error and an alternative approach involving integrated…

  8. The Effect of Analogy-Based Teaching on Students' Achievement and Students' Views about Analogies

    ERIC Educational Resources Information Center

    Genc, Murat

    2013-01-01

    The purpose of this study is to determine the effect of the analogy-based teaching on students' achievement and students' views about analogies. In this research, Solomon group design which is one of the experimental designs, was implemented. The sample of the research consists of 108 students in four 6th grade classes in Turkey. The achievement…

  9. Antibacterial and Antibiofilm Activities of Makaluvamine Analogs

    PubMed Central

    Nijampatnam, Bhavitavya; Nadkarni, Dwayaja H.; Wu, Hui; Velu, Sadanandan E.

    2014-01-01

    Streptococcus mutans is a key etiological agent in the formation of dental caries. The major virulence factor is its ability to form biofilms. Inhibition of S. mutans biofilms offers therapeutic prospects for the treatment and the prevention of dental caries. In this study, 14 analogs of makaluvamine, a marine alkaloid, were evaluated for their antibacterial activity against S. mutans and for their ability to inhibit S. mutans biofilm formation. All analogs contained the tricyclic pyrroloiminoquinone core of makaluvamines. The structural variations of the analogs are on the amino substituents at the 7-position of the ring and the inclusion of a tosyl group on the pyrrole ring N of the makaluvamine core. The makaluvamine analogs displayed biofilm inhibition with IC50 values ranging from 0.4 μM to 88 μM. Further, the observed bactericidal activity of the majority of the analogs was found to be consistent with the anti-biofilm activity, leading to the conclusion that the anti-biofilm activity of these analogs stems from their ability to kill S. mutans. However, three of the most potent N-tosyl analogs showed biofilm IC50 values at least an order of magnitude lower than that of bactericidal activity, indicating that the biofilm activity of these analogs is more selective and perhaps independent of bactericidal activity. PMID:25767719

  10. Modification of adenylate cyclase by photoaffinity analogs of forskolin

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

    Ho, L.T.; Nie, Z.M.; Mende, T.J.

    1989-01-01

    Photoaffinity labeling analogs of the adenylate cyclase activator forskolin (PF) have been synthesized, purified and tested for their effect on preparations of membrane-bound, Lubrol solubilized and forskolin affinity-purified adenylate cyclase (AC). All analogs of forskolin significantly activated AC. However, in the presence of 0.1 to 0.3 microM forskolin, the less active forskolin photoaffinity probes at 100 microM caused inhibition. This inhibition was dose-dependent for PF, suggesting that PF may complete with F for the same binding site(s). After cross-linking (125I)PF-M to either membrane or Lubrol-solubilized AC preparations by photolysis, a radiolabeled 100-110 kDa protein band was observed after autoradiography followingmore » SDS-PAGE. F at 100 microM blocked the photoradiolabeling of this protein. Radioiodination of forskolin-affinity purified AC showed several protein bands on autoradiogram, however, only one band (Mr = 100-110 kDa) was specifically labeled by (125I)PF-M following photolysis. The photoaffinity-labeled protein of 100-110 kDa of AC preparation of rat adipocyte may be the catalytic unit of adenylate cyclase of rat adipocyte itself as supported by the facts that (a) no other AC-regulatory proteins are known to be of this size, (b) the catalytic unit of bovine brain enzyme is in the same range and (c) this PF specifically stimulates AC activity when assayed alone, and weekly inhibits forskolin-activation of cyclase. These studies indicate that radiolabeled PF probes may be useful for photolabeling and detecting the catalytic unit of adenylate cyclase.« less

  11. A Systematic Evaluation of Analogs and Automated Read ...

    EPA Pesticide Factsheets

    Read-across is a data gap filling technique widely used within category and analog approaches to predict a biological property for a data-poor (target) chemical using known information from similar (source analog) chemical(s). Potential source analogs are typically identified based on structural similarity. Although much guidance has been published for read-across, practical principles for the identification and evaluation of the scientific validity of source analogs remains lacking. This case study explores how well 3 structure descriptor sets (Pubchem, Chemotyper and MoSS) are able to identify analogs for read-across and predict Estrogen Receptor (ER) binding activity for a specific class of chemicals: hindered phenols. For each target chemical, analogs were selected using each descriptor set with two cut-offs: (1) Minimum Tanimoto similarity (range 0.1 - 0.9), and (2) Closest N analogs (range 1 - 10). Each target-analog pair was then evaluated for its agreement with measured ER binding and agonism. The analogs were subsequently filtered using: (1) physchem properties (LogKow & Molecular Volume), and (2) number of literature sources as a marker for the quality of the experimental data. A majority vote prediction was made for each target phenol by reading-across from the closest N analogs. The data set comprised 462 hindered phenols and 257 non-hindered phenols. The results demonstrate that: (1) The concordance in ER activity rises with increasing similarity,

  12. Matrix-addressed analog ferroelectric memory

    NASA Astrophysics Data System (ADS)

    Lemons, R. A.; Grogan, J. K.; Thompson, J. S.

    1980-08-01

    A matrix addressed analog memory which uses multiple ferroelectric domain walls to address columns of words, is demonstrated. It is shown that the analog information is stored as a pattern in the metallization on the surface of the crystal, making a read-only memory. The pattern is done photolithographically in a way compatible with the simultaneous fabrication of many devices. Attention is given to the performance results, noting that the advantage of the device is that analog information can be stored with a high density in a single mask step. Finally, it is shown that potential applications are in systems which require repetitive output from a limited vocabulary of spoken words.

  13. Conjecturing via Reconceived Classical Analogy

    ERIC Educational Resources Information Center

    Lee, Kyeong-Hwa; Sriraman, Bharath

    2011-01-01

    Analogical reasoning is believed to be an efficient means of problem solving and construction of knowledge during the search for and the analysis of new mathematical objects. However, there is growing concern that despite everyday usage, learners are unable to transfer analogical reasoning to learning situations. This study aims at facilitating…

  14. Pharmaceutical analysis of synthetic lipid A-based vaccine adjuvants in poly (D,L-lactic-co-glycolic acid) nanoparticle formulations.

    PubMed

    Hamdy, Samar; Haddadi, Azita; Somayaji, Vishwa; Ruan, David; Samuel, John

    2007-08-15

    The present study had two main objectives. First, was to compare the immune stimulatory effect of two synthetic lipid A analogues (7-acyl lipid A and pentaerythritol-based lipid A (PET lipid A)) on maturation/stimulation of bone marrow derived dendritic cells (DCs). Our second objective was to develop a liquid chromatography/mass spectrometry (LC-MS) method for the quantitative analysis of lipid A-based vaccine adjuvants. Treatment of immature DCs with 7-acyl lipid A and PET lipid A up regulated the surface expression of CD86 and CD40 molecules, and also induced similar profile of pro-inflammatory cytokine secretion. LC-MS analyses were performed using a Waters Micromass ZQ 4000 spectrometer, coupled to a Waters 2795 separations module with an autosampler. Calibration curves with R(2)>0.999 were constructed over the concentration range of 1.25-20 microg/ml for the solution of 7-acyl lipid A and PET lipid A. The method was tested in a 3 day validation protocol. The accuracy of the assay at different concentrations tested ranged from 89 to 108% and from 92 to 107% for 7-acyl lipid A and PET lipid A, respectively. The limit of quantification for both 7-acyl lipid A and PET lipid A was 1.25 microg/ml (signal/noise (S/N)) ratio >15:1. The sensitivity of the method (the limit of detection) was 0.35 and 0.15 ng for 7-acyl lipid A and PET lipid A, respectively (S/N ratio between 4:1 or 3:1). As a preliminary application, this method has been successfully applied to the determination of 7-acyl lipid A and PET lipid A content in poly (D,L-lactic-co-glycolic acid) nanoparticles (PLGA-NP).

  15. Baseline and premining geochemical characterization of mined sites

    USGS Publications Warehouse

    Nordstrom, D. Kirk

    2015-01-01

    A rational goal for environmental restoration of new, active, or inactive mine sites would be ‘natural background’ or the environmental conditions that existed before any mining activities or other related anthropogenic activities. In a strictly technical sense, there is no such thing as natural background (or entirely non-anthropogenic) existing today because there is no part of the planet earth that has not had at least some chemical disturbance from anthropogenic activities. Hence, the terms ‘baseline’ and ‘pre-mining’ are preferred to describe these conditions. Baseline conditions are those that existed at the time of the characterization which could be pre-mining, during mining, or post-mining. Protocols for geochemically characterizing pre-mining conditions are not well-documented for sites already mined but there are two approaches that seem most direct and least ambiguous. One is characterization of analog sites along with judicious application of geochemical modeling. The other is reactive-transport modeling (based on careful synoptic sampling with tracer-injection) and subtracting inputs from known mining and mineral processing. Several examples of acidic drainage are described from around the world documenting the range of water compositions produced from pyrite oxidation in the absence of mining. These analog sites provide insight to the processes forming mineralized waters in areas untouched by mining. Natural analog water-chemistry data is compared with the higher metal concentrations, metal fluxes, and weathering rates found in mined areas in the few places where comparisons are possible. The differences are generally 1–3 orders of magnitude higher for acid mine drainage.

  16. Optical domain analog to digital conversion methods and apparatus

    DOEpatents

    Vawter, Gregory A

    2014-05-13

    Methods and apparatus for optical analog to digital conversion are disclosed. An optical signal is converted by mapping the optical analog signal onto a wavelength modulated optical beam, passing the mapped beam through interferometers to generate analog bit representation signals, and converting the analog bit representation signals into an optical digital signal. A photodiode receives an optical analog signal, a wavelength modulated laser coupled to the photodiode maps the optical analog signal to a wavelength modulated optical beam, interferometers produce an analog bit representation signal from the mapped wavelength modulated optical beam, and sample and threshold circuits corresponding to the interferometers produce a digital bit signal from the analog bit representation signal.

  17. Playing with a double-edged sword: Analogies in biochemistry

    NASA Astrophysics Data System (ADS)

    Orgill, Marykay

    Analogy pervades our everyday reasoning. No situation we encounter is exactly like a situation we have encountered previously, and our ability to learn and survive in the world is based on our ability to find similarities between past and present situations and use the knowledge we have gained from past situations to manage current situations. Analogies can be powerful teaching tools because they can make new material intelligible to students by comparing it to material that is already familiar. It is clear, though, that not all analogies are good and that not all good analogies are useful to all students. In this study, I have used textbook analysis, classroom observations, student interviews and instructor interviews to determine the role that analogies play in biochemistry learning. Analogies are an important teaching technique in biochemistry classes, being used more often in both biochemistry classes and textbooks than they are in high school chemistry classes and textbooks. Most biochemistry students like, pay particular attention to, and remember the analogies their instructors provide; and they use these analogies to understand, visualize, and recall information from class. Even though students like and use analogies, they do not understand what analogies are or the mechanism by which they improve learning. For the students, analogies are simply any teaching technique that eases understanding, visualization, or recall. Instructors, on the other hand, have a good understanding of what analogies are and of how they should be presented in class; but they do not use analogies as effectively as they should. They do not plan, explain or identify the limitations of the analogies they use in class. However, regardless of how effectively instructors present analogies in class, this study indicates that, in general, analogies are useful in promoting understanding, visualization, recall, and motivation in biochemistry students at all levels. They would be even more

  18. The Pennies-as-Electrons Analogy

    ERIC Educational Resources Information Center

    Ashmann, Scott

    2009-01-01

    Everyday experiences familiarize students with the ways in which electricity is used, but often the underlying concepts remain a mystery. Teachers often use analogies to help students relate the flow of electrons to other common systems, but many times these analogies are incomplete and lead to more student misconceptions. However, the "pass the…

  19. Dose and Chemical Modification Considerations for Continuous Cyclic AMP Analog Delivery to the Injured CNS

    PubMed Central

    Fouad, Karim; Ghosh, Mousumi; Vavrek, Romana; Tse, Arthur D.

    2009-01-01

    Abstract In this investigation, two cell-permeable synthetic analogs of cAMP, dibutyryl-cAMP (db-cAMP) and 8-bromo-cAMP, which are widely used to elevate intracellular cAMP levels under experimental conditions, were investigated for their ability to dose-dependently improve histological and functional outcomes following continuous delivery in two models of incomplete spinal cord injury (SCI). The cAMP analogs were delivered via osmotic minipumps at 1–250 mM through an indwelling cortical cannula or by intrathecal infusion for up to 4 weeks after either a T8 unilateral over-hemisection or a C2-3 dorsolateral quadrant lesion, respectively. In both SCI models, continuous db-cAMP delivery was associated with histopathological changes that included sporadic micro-hemorrhage formation and cavitation, enhanced macrophage infiltration and tissue damage at regions beyond the immediate application site; no deleterious or beneficial effect of agent delivery was observed at the spinal injury site. Furthermore, these changes were accompanied by pronounced behavioral deficits that included an absence of progressive locomotor recovery, increased extensor tone, paralysis, and sensory abnormalities. These deleterious effects were not observed in saline-treated animals, in animals in which the db-cAMP dose did not exceed 1 mM, or in those animals that received a high dose (250 mM) of the alternative cAMP analog, 8-bromo-cAMP. These results demonstrate that, for continuous intraparenchymal or intrathecal administration of cAMP analogs for the study of biological or therapeutic effects within the central nervous system (CNS), consideration of the effective concentration applied as well as the potential toxicity of chemical moieties on the parent molecule and/or their activity needs to be taken into account. PMID:19397425

  20. Design and characterization of α-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination

    PubMed Central

    Giblin, Michael F.; Wang, Nannan; Hoffman, Timothy J.; Jurisson, Silvia S.; Quinn, Thomas P.

    1998-01-01

    α-Melanocyte stimulating hormone (α-MSH) analogs, cyclized through site-specific rhenium (Re) and technetium (Tc) metal coordination, were structurally characterized and analyzed for their abilities to bind α-MSH receptors present on melanoma cells and in tumor-bearing mice. Results from receptor-binding assays conducted with B16 F1 murine melanoma cells indicated that receptor-binding affinity was reduced to approximately 1% of its original levels after Re incorporation into the cyclic Cys4,10, d-Phe7–α-MSH4-13 analog. Structural analysis of the Re–peptide complex showed that the disulfide bond of the original peptide was replaced by thiolate–metal–thiolate cyclization. A comparison of the metal-bound and metal-free structures indicated that metal complexation dramatically altered the structure of the receptor-binding core sequence. Redesign of the metal binding site resulted in a second-generation Re–peptide complex (ReCCMSH) that displayed a receptor-binding affinity of 2.9 nM, 25-fold higher than the initial Re–α-MSH analog. Characterization of the second-generation Re–peptide complex indicated that the peptide was still cyclized through Re coordination, but the structure of the receptor-binding sequence was no longer constrained. The corresponding 99mTc- and 188ReCCMSH complexes were synthesized and shown to be stable in phosphate-buffered saline and to challenges from diethylenetriaminepentaacetic acid (DTPA) and free cysteine. In vivo, the 99mTcCCMSH complex exhibited significant tumor uptake and retention and was effective in imaging melanoma in a murine-tumor model system. Cyclization of α-MSH analogs via 99mTc and 188Re yields chemically stable and biologically active molecules with potential melanoma-imaging and therapeutic properties. PMID:9788997

  1. Producing and Recognizing Analogical Relations

    ERIC Educational Resources Information Center

    Lipkens, Regina; Hayes, Steven C.

    2009-01-01

    Analogical reasoning is an important component of intelligent behavior, and a key test of any approach to human language and cognition. Only a limited amount of empirical work has been conducted from a behavior analytic point of view, most of that within Relational Frame Theory (RFT), which views analogy as a matter of deriving relations among…

  2. Role of the Zn1 and Zn2 sites in metallo-β-lactamase L1

    PubMed Central

    Hu, Zhenxin; Periyannan, Gopalraj; Bennett, Brian; Crowder, Michael W.

    2009-01-01

    In an effort to probe the role of the Zn(II) sites in metallo-β-lactamase L1, mononuclear metal ion containing and heterobimetallic analogs of the enzyme were generated and characterized using kinetic and spectroscopic studies. Mononuclear Zn(II)-containing L1, which binds Zn(II) in the consensus Zn1 site, was shown to be slightly active; however, this enzyme did not stabilize a nitrocefin-derived reaction intermediate that had been previously detected. Mononuclear Co(II)- and Fe(III)-containing L1 were essentially inactive, and NMR and EPR studies suggest that these metal ions bind to the consensus Zn2 site in L1. Heterobimetallic analogs (ZnCo and ZnFe) analogs of L1 were generated, and stopped-flow kinetic studies revealed that these enzymes rapidly hydrolyze nitrocefin and that there are large amounts of the reaction intermediate formed during the reaction. The heterobimetallic analogs were reacted with nitrocefin, and the reactions were rapidly freeze quenched. EPR studies on these samples demonstrate that Co(II) is five-coordinate in the resting state, proceeds through a four-coordinate species during the reaction, and is five-coordinate in the enzyme-product complex. These studies demonstrate that the metal ion in the Zn1 site is essential for catalysis in L1 and that the metal ion in the Zn2 site is crucial for stabilization of the nitrocefin-derived reaction intermediate. PMID:18831550

  3. Enantioselective Reduction of Citral Isomers in NCR Ene Reductase: Analysis of an Active-Site Mutant Library.

    PubMed

    Kress, Nico; Rapp, Johanna; Hauer, Bernhard

    2017-04-18

    A deeper understanding of the >99 % S-selective reduction of both isomers of citral catalyzed by NCR ene reductase was achieved by active-site mutational studies and docking simulation. Though structurally similar, the E/Z isomers of citral showed a significantly varying selectivity response to introduced mutations. Although it was possible to invert (E)-citral reduction enantioselectivity to ee 46 % (R) by introducing mutation W66A, for (Z)-citral it remained ≥88 % (S) for all single-residue variants. Residue 66 seems to act as a lever for opposite binding modes. This was underlined by a W66A-based double-mutant library that enhanced the (E)-citral derived enantioselectivity to 63 % (R) and significantly lowered the S selectivity for (Z)-citral to 44 % (S). Formation of (R)-citronellal from an (E/Z)-citral mixture is a desire in industrial (-)-menthol synthesis. Our findings pave the way for a rational enzyme engineering solution. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. 10 CFR 960.3-1-4-2 - Site nomination for characterization.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-1-4-2 Site nomination for... types under expected repository conditions; evaluations of natural and man-made analogs of the repository and its subsystems, such as geothermally active areas, underground excavations, and case histories...

  5. The binding of analogs of porphyrins and chlorins with elongated side chains to albumin

    PubMed Central

    Ben Dror, Shimshon; Bronshtein, Irena; Weitman, Hana; Smith, Kevin M.; O’Neal, William G.; Jacobi, Peter A.; Ehrenberg, Benjamin

    2012-01-01

    In previous studies, we demonstrated that elongation of side chains of several sensitizers endowed them with higher affinity for artificial and natural membranes and caused their deeper localization in membranes. In the present study, we employed eight hematoporphyrin and protoporphyrin analogs and four groups containing three chlorin analogs each, all synthesized with variable numbers of methylenes in their alkyl carboxylic chains. We show that these tetrapyrroles’ affinity for bovine serum albumin (BSA) and their localization in the binding site are also modulated by chain lengths. The binding constants of the hematoporphyrins and protoporphyrins to BSA increased as the number of methylenes was increased. The binding of the chlorins depended on the substitution at the meso position opposite to the chains. The quenching of the sensitizers’ florescence by external iodide ions decreased as the side chains became longer, indicating to deeper insertion of the molecules into the BSA binding pocket. To corroborate this conclusion, we studied the efficiency of photodamage caused to tryptophan in BSA upon illumination of the bound sensitizers. The efficiency was found to depend on the side-chain lengths of the photosensitizer. We conclude that the protein site that hosts these sensitizers accommodates different analogs at positions that differ slightly from each other. These differences are manifested in the ease of access of iodide from the external aqueous phase, and in the proximity of the photosensitizers to the tryptophan. In the course of this study, we developed the kinetic equations that have to be employed when the sensitizer itself is being destroyed. PMID:19330323

  6. Radiolabeled gastrin/CCK analogs in tumor diagnosis: towards higher stability and improved tumor targeting.

    PubMed

    Kaloudi, A; Nock, B A; Krenning, E P; Maina, T; De Jong, M

    2015-09-01

    Cholecystokinin subtype 2 receptors (CCK2R) are overexpressed in several human cancers, including medullary thyroid carcinoma. Gastrin and cholecystokinin (CCK) peptides that bind with high affinity and specificity to CCK2R can be used as carriers of radioactivity to CCK2R-expressing tumor sites. Several gastrin and CCK related peptides have been proposed for diagnostic imaging and radionuclide therapy of primary and metastatic CCK2R-positive human tumors. Their clinical application has been restricted to a great extent by their fast in vivo degradation that eventually compromises tumor uptake. This problem has been addressed by structural modifications of gastrin and CCK motifs, which, however, often lead to suboptimal pharmacokinetic profiles. A major enzyme implicated in the catabolism of gastrin and CCK based peptides is neutral endopeptidase (NEP), which is widely distributed in the body. Coinjection of the NEP inhibitor phosphoramidon (PA) with radiolabeled gastrin and other peptide analogs has been recently proposed as a new promising strategy to increase bioavailability and tumor-localization of radiopeptides in tumor sites. Specifically, co-administration of PA with the truncated gastrin analog [(111)In-DOTA]MG11 ([((111)In-DOTA)DGlu(10)]gastrin(10-17)) impressively enhanced the levels of intact radiopeptide in mouse circulation and has led to an 8-fold increase of CCK2R-positive tumor uptake in SCID mice. This increased tumor uptake, visualized also by SPECT/CT imaging, is expected to eventually translate into higher diagnostic sensitivity and improved therapeutic efficacy of radiolabeled gastrin analogs in CCK2R-expressing cancer patients.

  7. Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs.

    PubMed

    Talaat, Roba; El-Sayed, Waheba; Agwa, Hussein S; Gamal-Eldeen, Amira M; Moawia, Shaden; Zahran, Magdy A H

    2015-08-05

    Thalidomide has anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It has been used to treat a variety of cancers and autoimmune diseases. This study aimed to characterize anti-inflammatory activities of novel thalidomide analogs by exploring their effects on splenocytes proliferation and macrophage functions and their antioxidant activity. MTT assay was used to assess the cytotoxic effect of thalidomide analogs against splenocytes. Tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB-P65) were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was estimated by colorimetric assay. Antioxidant activity was examined by ORAC assay. Our results demonstrated that thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 produced a slight increase in splenocyte proliferation compared with thalidomide. Thalidomide dithiocarbamate analog 1 is a potent inhibitor of TNF-α production, whereas thalidomide dithiocarbamate analog 5 is a potent inhibitor of both TNF-α and NO. Analog 2 has a pronounced inhibitory effect on NF-κB-P65 production level. All thalidomide analogs showed prooxidant activity against hydroxyl (OH) radical. Analog 1 and thalidomide dithioate analog 3 have prooxidant activity against peroxyl (ROO) radical in relation to thalidomide. On the other hand, analog 4 has a potent scavenging capacity against peroxyl (ROO) radical compared with thalidomide. Taken together, the results of this study suggest that thalidomide analogs might have valuable anti-inflammatory activities with more pronounced effect than thalidomide itself. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Oxidized Base Damage and Single-Strand Break Repair in Mammalian Genomes: Role of Disordered Regions and Posttranslational Modifications in Early Enzymes

    PubMed Central

    Hegde, Muralidhar L.; Izumi, Tadahide; Mitra, Sankar

    2012-01-01

    Oxidative genome damage induced by reactive oxygen species includes oxidized bases, abasic (AP) sites, and single-strand breaks, all of which are repaired via the evolutionarily conserved base excision repair/single-strand break repair (BER/SSBR) pathway. BER/SSBR in mammalian cells is complex, with preferred and backup sub-pathways, and is linked to genome replication and transcription. The early BER/SSBR enzymes, namely, DNA glycosylases (DGs) and the end-processing proteins such as abasic endonuclease 1 (APE1), form complexes with downstream repair (and other noncanonical) proteins via pairwise interactions. Furthermore, a unique feature of mammalian early BER/ SSBR enzymes is the presence of a disordered terminal extension that is absent in their Escherichia coli prototypes. These nonconserved segments usually contain organelle-targeting signals, common interaction interfaces, and sites of posttranslational modifications that may be involved in regulating their repair function including lesion scanning. Finally, the linkage of BER/SSBR deficiency to cancer, aging, and human neurodegenerative diseases, and therapeutic targeting of BER/SSBR are discussed. PMID:22749145

  9. Detection of DNA Sequences Refractory to PCR Amplification Using a Biophysical SERRS Assay (Surface Enhanced Resonant Raman Spectroscopy)

    PubMed Central

    Feuillie, Cécile; Merheb, Maxime M.; Gillet, Benjamin; Montagnac, Gilles; Daniel, Isabelle; Hänni, Catherine

    2014-01-01

    The analysis of ancient or processed DNA samples is often a great challenge, because traditional Polymerase Chain Reaction – based amplification is impeded by DNA damage. Blocking lesions such as abasic sites are known to block the bypass of DNA polymerases, thus stopping primer elongation. In the present work, we applied the SERRS-hybridization assay, a fully non-enzymatic method, to the detection of DNA refractory to PCR amplification. This method combines specific hybridization with detection by Surface Enhanced Resonant Raman Scattering (SERRS). It allows the detection of a series of double-stranded DNA molecules containing a varying number of abasic sites on both strands, when PCR failed to detect the most degraded sequences. Our SERRS approach can quickly detect DNA molecules without any need for DNA repair. This assay could be applied as a pre-requisite analysis prior to enzymatic reparation or amplification. A whole new set of samples, both forensic and archaeological, could then deliver information that was not yet available due to a high degree of DNA damage. PMID:25502338

  10. Detection of DNA sequences refractory to PCR amplification using a biophysical SERRS assay (Surface Enhanced Resonant Raman Spectroscopy).

    PubMed

    Feuillie, Cécile; Merheb, Maxime M; Gillet, Benjamin; Montagnac, Gilles; Daniel, Isabelle; Hänni, Catherine

    2014-01-01

    The analysis of ancient or processed DNA samples is often a great challenge, because traditional Polymerase Chain Reaction - based amplification is impeded by DNA damage. Blocking lesions such as abasic sites are known to block the bypass of DNA polymerases, thus stopping primer elongation. In the present work, we applied the SERRS-hybridization assay, a fully non-enzymatic method, to the detection of DNA refractory to PCR amplification. This method combines specific hybridization with detection by Surface Enhanced Resonant Raman Scattering (SERRS). It allows the detection of a series of double-stranded DNA molecules containing a varying number of abasic sites on both strands, when PCR failed to detect the most degraded sequences. Our SERRS approach can quickly detect DNA molecules without any need for DNA repair. This assay could be applied as a pre-requisite analysis prior to enzymatic reparation or amplification. A whole new set of samples, both forensic and archaeological, could then deliver information that was not yet available due to a high degree of DNA damage.

  11. Mars: Periglacial Morphology and Implications for Future Landing Sites

    NASA Technical Reports Server (NTRS)

    Heldmann, Jennifer L.; Schurmeier, Lauren; McKay, Christopher; Davila, Alfonso; Stoker, Carol; Marinova, Margarita; Wilhelm, Mary Beth

    2015-01-01

    At the Mars Phoenix landing site and in much of the Martian northern plains, there is ice-cemented ground beneath a layer of dry permafrost. Unlike most permafrost on Earth, though, this ice is not liquid at any time of year. However, in past epochs at higher obliquity the surface conditions during summer may have resulted in warmer conditions and possible melting. This situation indicates that the ice-cemented ground in the north polar plains is likely to be a candidate for the most recently habitable place on Mars as near-surface ice likely provided adequate water activity approximately 5 Myr ago. The high elevation Dry Valleys of Antarctica provide the best analog on Earth of Martian ground ice. These locations are the only places on Earth where ice-cemented ground is found beneath dry permafrost. The Dry Valleys are a hyper-arid polar desert environment and in locations above 1500 m elevation, such as University Valley, air temperatures do not exceed 0 C. Thus, similarly to Mars, liquid water is largely absent here and instead the hydrologic cycle is dominated by frozen ice and vapor phase processes such as sublimation. These conditions make the high elevation Dry Valleys a key Mars analog location where periglacial processes and geomorphic features can be studied in situ. This talk will focus on studies of University Valley as a Mars analog for periglacial morphology and ice stability. We will review a landing site selection study encompassing this information gleaned from the Antarctic terrestrial analog studies plus Mars spacecraft data analysis to identify candidate landing sites for a future mission to search for life on Mars.

  12. Piperazine-based nucleic acid analogs

    DOEpatents

    Schmidt, Jurgen; Silks, Louis A.; Michalczyk, Ryszard

    2005-01-11

    A novel nucleoside analog is disclosed which comprises a piperazine ring in the place of the ring ribose or deoxyribose sugar. Monomers utilizing a broad variety of nucleobases are disclosed, as well as oligomers comprising the monomers disclosed herein linked by a variety of linkages, including amide, phosphonamide, and sulfonamide linkages. A method of synthesizing the nucleoside analogs is also disclosed.

  13. Heat Flow vs. Cash Flow: A Banking Analogy

    NASA Astrophysics Data System (ADS)

    Wynn, Charles M., Sr.

    1997-04-01

    An analogy is drawn between the withdrawal of money from an automated teller machine (ATM) and an exothermic chemical reaction. In the analogy the amount in an individual's account is regarded as the system and the money withdrawn is regarded as part of the surroundings. Diagrams are used to present the analogy. An analogy can be drawn also between a deposit into an account and an endothermic chemical reaction.

  14. Analog detection for cavity lifetime spectroscopy

    DOEpatents

    Zare, Richard N.; Harb, Charles C.; Paldus, Barbara A.; Spence, Thomas G.

    2001-05-15

    An analog detection system for determining a ring-down rate or decay rate 1/.tau. of an exponentially decaying ring-down beam issuing from a lifetime or ring-down cavity during a ring-down phase. Alternatively, the analog detection system determines a build-up rate of an exponentially growing beam issuing from the cavity during a ring-up phase. The analog system can be employed in continuous wave cavity ring-down spectroscopy (CW CRDS) and pulsed CRDS (P CRDS) arrangements utilizing any type of ring-down cavity including ring-cavities and linear cavities.

  15. Analog detection for cavity lifetime spectroscopy

    DOEpatents

    Zare, Richard N.; Harb, Charles C.; Paldus, Barbara A.; Spence, Thomas G.

    2003-01-01

    An analog detection system for determining a ring-down rate or decay rate 1/.tau. of an exponentially decaying ring-down beam issuing from a lifetime or ring-down cavity during a ring-down phase. Alternatively, the analog detection system determines a build-up rate of an exponentially growing beam issuing from the cavity during a ring-up phase. The analog system can be employed in continuous wave cavity ring-down spectroscopy (CW CRDS) and pulsed CRDS (P CRDS) arrangements utilizing any type of ring-down cavity including ring-cavities and linear cavities.

  16. Hypersusceptibility to substrate analogs conferred by mutations in human immunodeficiency virus type 1 reverse transcriptase.

    PubMed

    Smith, Robert A; Anderson, Donovan J; Preston, Bradley D

    2006-07-01

    Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) contains four structural motifs (A, B, C, and D) that are conserved in polymerases from diverse organisms. Motif B interacts with the incoming nucleotide, the template strand, and key active-site residues from other motifs, suggesting that motif B is an important determinant of substrate specificity. To examine the functional role of this region, we performed "random scanning mutagenesis" of 11 motif B residues and screened replication-competent mutants for altered substrate analog sensitivity in culture. Single amino acid replacements throughout the targeted region conferred resistance to lamivudine and/or hypersusceptibility to zidovudine (AZT). Substitutions at residue Q151 increased the sensitivity of HIV-1 to multiple nucleoside analogs, and a subset of these Q151 variants was also hypersusceptible to the pyrophosphate analog phosphonoformic acid (PFA). Other AZT-hypersusceptible mutants were resistant to PFA and are therefore phenotypically similar to PFA-resistant variants selected in vitro and in infected patients. Collectively, these data show that specific amino acid replacements in motif B confer broad-spectrum hypersusceptibility to substrate analog inhibitors. Our results suggest that motif B influences RT-deoxynucleoside triphosphate interactions at multiple steps in the catalytic cycle of polymerization.

  17. The effect of somatostatin analogs on secretion of growth, pancreatic, and gastrointestinal hormones in man.

    PubMed

    Adrian, T E; Barnes, A J; Long, R G; O'Shaughnessy, D J; Brown, M R; Rivier, J; Vale, W; Blackburn, A M; Bloom, S R

    1981-10-01

    The potency and specificity of somatostatin (SS) and four of its analogs were compared in seven patients with pancreatic endocrine tumors. The analogs tested were [D-Trp8]-SS, [D-Trp8, D-Cys14]-SS, Des-Asn5-[D-Trp8, D-Ser13]-SS, and Des (AA)1,2,4,5,12,13, [D-Trp8]-SS, and they did not show selective effects on the suppression of basal concentrations of GH, insulin, glucagon, pancreatic polypeptide, gastrin, gastric inhibitory peptide, motilin, enteroglucagon, or neurotensin. The observation that the potency of these analogs is similar to that of the parent molecule throws considerable light on the structure/activity relationship of the somatostatin molecule. Des-AA1,2,4,5,12,13, [D-Trp8]-Ss has been reported to have a prolonged action when administered sc. When administered iv, however, this octapeptide analog ws not long acting, suggesting that the prolonged action seen in the previous study was a result of delayed uptake from the injection site. An increment in plasma SS concentrations of 19 +/- 3 pmol/liter suppressed basal concentrations of GH, insulin, glucagon, and several gastrointestinal hormones by more than 50%, suggesting that even small changes in plasma SS levels may be physiologically important.

  18. NASA HRP Immunology Discipline - Use of Terrestrial Analogs

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2014-01-01

    Due to the cost and operational constraints, as well as technical implementation limitations, it is desirous to perform relevant space physiology investigations first in terrestrial 'space analogs'. This is particularly true for initial investigations, which may then provide appropriate focus for subsequent flight investigations, or for mechanistic investigations that simply cannot be performed during spaceflight. Appropriate analog choice is extremely important. There are a wide variety of terrestrial space analogs, each relevant to a particular physiological discipline (or disciplines) and each with a particular fidelity (or lack thereof) to spaceflight, and each with unique operational constraints. The HRP Immunology Discipline is tasked with managing the HRP Risk concerning clinical risk for Astronaut crews related to spaceflight-associated immune dysregulation. Such dysregulation has been documented to occur during spaceflight, and found to persist for the duration of a 6-month ISS mission. Studies continue to characterize the onorbit phenomenon, but it generally consists of diminished immunocyte function, dysregulated cytokine profiles, and persistent herpesvirus reactivation. Causes are thought to synergistically include microgravity, psychological or physiological stress, radiation, and/or circadian misalignment. An appropriate terrestrial analog for immune dysregulation would replicate as many of these influences as possible. Such analogs may include clinostat or bioreactor cell culture (microgravity), hindlimb suspension (stress, fluid shifts, hypokinesis), or human deployment to remote or extreme environments (isolation, stress, circadian). Also, the laboratory setting may be used as an analog, or to augment analogs, such as sleep deprivation/misalignment or human centrifugation to replicate gravitational stress. As an appropriate example of a NASA Disciplines use of Terrestrial space analogs, this talk will discuss spaceflight associated immune

  19. Drug binding to the acetylcholine receptor: Nitroxide analogs of phencyclidine and a local anesthetic

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

    Palma, A.L.

    1988-01-01

    The interaction of noncompetitive inhibitors (NCIs) with Torpedo californica native nicotinic acetylcholine receptor (nAChR) membranes was examined primarily by the technique of electron paramagnetic resonance (EPR) spectroscopy. The goal of this work being to define some of the physical characteristics for the site(s) of association between an NCI and the nAChR membrane. A nitroxide labeled analog of a quaternary amine local anesthetic, 2-(N,N-dimethyl-N-4-(2,2,6,6-tetramethylpiperidinoxyl)amino)-ethyl 4-hexyloxybenzoate iodide (C6SLMeI), displays a strongly immobilized EPR component when added to nAChR membranes in the presence of carbamylcholine (carb). To further this work, a nitroxide labeled analog of phencyclidine (PCP), a potent NCI, was synthesized. 4-phenyl-4-(1-piperidinyl)-2,2,6,6-tetramethylpiperidinoxylmore » (PPT) exhibited one-third the potency of PCP in inhibiting nAChR mediated ion flux, and from competition binding studies with ({sup 3}H)PCP displayed a K{sub D} of 0.21 {mu}M towards a carb desensitized nAChR and a K{sub 0.5} of 18 {mu}M for a resting {alpha}-bungarotoxin treated nAChR.« less

  20. Developing Analogy Cost Estimates for Space Missions

    NASA Technical Reports Server (NTRS)

    Shishko, Robert

    2004-01-01

    The analogy approach in cost estimation combines actual cost data from similar existing systems, activities, or items with adjustments for a new project's technical, physical or programmatic differences to derive a cost estimate for the new system. This method is normally used early in a project cycle when there is insufficient design/cost data to use as a basis for (or insufficient time to perform) a detailed engineering cost estimate. The major limitation of this method is that it relies on the judgment and experience of the analyst/estimator. The analyst must ensure that the best analogy or analogies have been selected, and that appropriate adjustments have been made. While analogy costing is common, there is a dearth of advice in the literature on the 'adjustment methodology', especially for hardware projects. This paper discusses some potential approaches that can improve rigor and repeatability in the analogy costing process.

  1. Photoaffinity labeling and partial purification of the beta cell sulfonylurea receptor using a novel, biologically active glyburide analog

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

    Aguilar-Bryan, L.; Nelson, D.A.; Vu, Q.A.

    1990-05-15

    An iodinated analog of the sulfonylurea, glyburide, has been synthesized which can be labeled to high specific activity and used to photolabel the sulfonylurea receptor. 5-Iodo-2-hydroxy-glyburide, has an iodo group replacing the chlorine at position 5 and a methoxy residue replacing the hydroxy group at position 2 on the benzamido ring. This analog retains biologic activity stimulating insulin secretion from a hamster beta cell line (HIT cells) at the same ED50 (0.4 nM) as glyburide. Scatchard analysis demonstrated high and low affinity binding sites on HIT cell membranes (Kd values of 0.36 nM and 277 nM and Bmax values ofmore » 1.6 and 100 pmol/mg of membrane protein, respectively). Competitive binding assays with unlabeled glyburide or 5-iodo-2-hydroxyglyburide yield Ki values of 0.5 and 1.0 nM, respectively. The analog can be covalently linked by ultraviolet irradiation to a membrane protein of Mr = 140,000. The photolabeling is completely blocked by unlabeled glyburide or the analog. Two other species of Mr = 65,000 and 43,000 are also photolabeled; these may be the low affinity sites. After photolabeling, the receptor has been purified partially by chromatographic procedures and is suitable for obtaining peptide sequence. The 140,000 molecular weight protein is identified as the sulfonylurea receptor since its binding constant, 0.36 nM, is closely correlated with its ability to stimulate insulin secretion (ED50 congruent to 0.4 nM).« less

  2. Crows spontaneously exhibit analogical reasoning.

    PubMed

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Perceptions of Rebuttal Analogy: Politeness and Implications for Persuasion.

    ERIC Educational Resources Information Center

    Whaley, Bryan B.

    1997-01-01

    States that recent theorizing about the role of analogy in persuasion suggests that "rebuttal" analogy addresses two communicative functions by serving as argument and a method of social attack. Examines message receivers' perceptions of rebuttal analogy and rebuttal analogy users. Finds that participants perceived the communicator using…

  4. Elucidating the neurotoxic effects of MDMA and its analogs.

    PubMed

    Karuppagounder, Senthilkumar S; Bhattacharya, Dwipayan; Ahuja, Manuj; Suppiramaniam, Vishnu; Deruiter, Jack; Clark, Randall; Dhanasekaran, Muralikrishnan

    2014-04-17

    There is a rapid increase in the use of methylenedioxymethamphetamine (MDMA) and its structural congeners/analogs globally. MDMA and MDMA-analogs have been synthesized illegally in furtive dwellings and are abused due to its addictive potential. Furthermore, MDMA and MDMA-analogs have shown to have induced several adverse effects. Hence, understanding the mechanisms mediating this neurotoxic insult of MDMA-analogs is of immense importance for the public health in the world. We synthesized and investigated the neurotoxic effects of MDMA and its analogs [4-methylenedioxyamphetamine (MDA), 2, 6-methylenedioxyamphetamine (MDMA), and N-ethyl-3, 4-methylenedioxyamphetamine (MDEA)]. The stimulatory or the dopaminergic agonist effects of MDMA and MDMA-analogs were elucidated using the established 6-hydroxydopamine lesioned animal model. Additionally, we also investigated the neurotoxic mechanisms of MDMA and MDMA-analogs on mitochondrial complex-I activity and reactive oxygen species generation. MDMA and MDMA-analogs exhibited stimulatory activity as compared to amphetamines and also induced several behavioral changes in the rodents. MDMA and MDMA-analogs enhanced the reactive oxygen generation and inhibited mitochondrial complex-I activity which can lead to neurodegeneration. Hence the mechanism of neurotoxicity, MDMA and MDMA-analogs can enhance the release of monoamines, alter the monoaminergic neurotransmission, and augment oxidative stress and mitochondrial abnormalities leading to neurotoxicity. Thus, our study will help in developing effective pharmacological and therapeutic approaches for the treatment of MDMA and MDMA-analog abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Structural basis for 18-β-glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor.

    PubMed

    Zhang, Hong; Huang, Qiang; Zhai, Jing; Zhao, Yi-ning; Zhang, Li-ping; Chen, Yun-yun; Zhang, Ren-wei; Li, Qing; Hu, Xiao-peng

    2015-09-01

    Glyoxalase I (GLOI), a glutathione (GSH)-dependent enzyme, is overexpressed in tumor cells and related to multi-drug resistance in chemotherapy, making GLOI inhibitors as potential anti-tumor agents. But the most studied GSH analogs exhibit poor pharmacokinetic properties. The aim of this study was to discover novel non-GSH analog GLOI inhibitors and analyze their binding mechanisms. Mouse GLOI (mGLOI) was expressed in BL21 (DE3) pLysS after induction with isopropyl-β-D-1-thiogalactopyranoside and purified using AKTA FPLC system. An in vitro mGLOI enzyme assay was used to screen a small pool of compounds containing carboxyl groups. Crystal structure of the mGLOI-inhibitor complex was determined at 2.3 Å resolution. Molecular docking study was performed using Discovery Studio 2.5 software package. A natural compound 18-β-glycyrrhetinic acid (GA) and its derivative carbenoxolone were identified as potent competitive non-GSH analog mGLOI inhibitors with Ki values of 0.29 μmol/L and 0.93 μmol/L, respectively. Four pentacyclic triterpenes (ursolic acid, oleanolic acid, betulic acid and tripterine) showed weak activities (mGLOI inhibition ratio <25% at 10 μmol/L) and other three (maslinic acid, corosolic acid and madecassic acid) were inactive. The crystal structure of the mGLOI-GA complex showed that the carboxyl group of GA mimicked the γ-glutamyl residue of GSH by hydrogen bonding to the glutamyl sites (residues Arg38B, Asn104B and Arg123A) in the GSH binding site of mGLOI. The extensive van der Waals interactions between GA and the surrounding residues also contributed greatly to the binding of GA and mGLOI. This work demonstrates a carboxyl group to be an important functional feature of non-GSH analog GLOI inhibitors.

  6. Alteration in substrate specificity of horse liver alcohol dehydrogenase by an acyclic nicotinamide analog of NAD(+).

    PubMed

    Malver, Olaf; Sebastian, Mina J; Oppenheimer, Norman J

    2014-11-01

    A new, acyclic NAD-analog, acycloNAD(+) has been synthesized where the nicotinamide ribosyl moiety has been replaced by the nicotinamide (2-hydroxyethoxy)methyl moiety. The chemical properties of this analog are comparable to those of β-NAD(+) with a redox potential of -324mV and a 341nm λmax for the reduced form. Both yeast alcohol dehydrogenase (YADH) and horse liver alcohol dehydrogenase (HLADH) catalyze the reduction of acycloNAD(+) by primary alcohols. With HLADH 1-butanol has the highest Vmax at 49% that of β-NAD(+). The primary deuterium kinetic isotope effect is greater than 3 indicating a significant contribution to the rate limiting step from cleavage of the carbon-hydrogen bond. The stereochemistry of the hydride transfer in the oxidation of stereospecifically deuterium labeled n-butanol is identical to that for the reaction with β-NAD(+). In contrast to the activity toward primary alcohols there is no detectable reduction of acycloNAD(+) by secondary alcohols with HLADH although these alcohols serve as competitive inhibitors. The net effect is that acycloNAD(+) has converted horse liver ADH from a broad spectrum alcohol dehydrogenase, capable of utilizing either primary or secondary alcohols, into an exclusively primary alcohol dehydrogenase. This is the first example of an NAD analog that alters the substrate specificity of a dehydrogenase and, like site-directed mutagenesis of proteins, establishes that modifications of the coenzyme distance from the active site can be used to alter enzyme function and substrate specificity. These and other results, including the activity with α-NADH, clearly demonstrate the promiscuity of the binding interactions between dehydrogenases and the riboside phosphate of the nicotinamide moiety, thus greatly expanding the possibilities for the design of analogs and inhibitors of specific dehydrogenases. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Learning Plate Tectonics Using a Pre-Analogy Step

    NASA Astrophysics Data System (ADS)

    Glesener, G. B.; Sandoval, W. A.

    2011-12-01

    Previous research has shown that children tend to demonstrate lower performance on analogical reasoning tasks at a causal relations level compared to most adults (Gentner & Toupin, 1986). This tendency is an obstacle that geoscience educators must overcome because of the high frequency of analogies used in geoscience pedagogy. In particular, analog models are used to convey complex systems of non-everyday/non-observable events found in nature, such as plate tectonics. Key factors in successful analogical reasoning that have been suggested by researchers include knowledge of the causal relations in the base analog (Brown & Kane, 1988; Gentner, 1988; Gentner & Toupin, 1986), and development of learning strategies and metaconceptual competence(Brown & Kane, 1988). External factors, such as guiding cues and hints have been useful cognitive supports that help students reason through analogical problems (Gick & Holyoak, 1980). Cognitive supports have been seen by researchers to decrease processing demands on retrieval and working memory (Richland, Zur, & Holyoak, 2007). We observed third and fourth graders learning about plate tectonics beginning with a pre-analogy step-a cognitive support activity a student can do before working with an analogy to understand the target. This activity was designed to aid students in developing their understanding of object attributes and relations within an analog model so that more focus can be placed on mapping the corresponding higher-order relations between the base and target. Students learned targeted concepts of plate tectonics, as measured by pre to post gains on items adapted from the Geosciences Concept Inventory. Analyses of classroom interaction showed that students used the object attributes and higher-order relations highlighted in the pre-analogy activity as resources to reason about plate boundaries and plate movement during earthquakes.

  8. Assessment of Mars Pathfinder landing site predictions

    USGS Publications Warehouse

    Golombek, M.P.; Moore, H.J.; Haldemann, A.F.C.; Parker, T.J.; Schofield, J.T.

    1999-01-01

    Remote sensing data at scales of kilometers and an Earth analog were used to accurately predict the characteristics of the Mars Pathfinder landing site at a scale of meters. The surface surrounding the Mars Pathfinder lander in Ares Vallis appears consistent with orbital interpretations, namely, that it would be a rocky plain composed of materials deposited by catastrophic floods. The surface and observed maximum clast size appears similar to predictions based on an analogous surface of the Ephrata Fan in the Channeled Scabland of Washington state. The elevation of the site measured by relatively small footprint delay-Doppler radar is within 100 m of that determined by two-way ranging and Doppler tracking of the spacecraft. The nearly equal elevations of the Mars Pathfinder and Viking Lander 1 sites allowed a prediction of the atmospheric conditions with altitude (pressure, temperature, and winds) that were well within the entry, descent, and landing design margins. High-resolution (~38 m/pixel) Viking Orbiter 1 images showed a sparsely cratered surface with small knobs with relatively low slopes, consistent with observations of these features from the lander. Measured rock abundance is within 10% of that expected from Viking orbiter thermal observations and models. The fractional area covered by large, potentially hazardous rocks observed is similar to that estimated from model rock distributions based on data from the Viking landing sites, Earth analog sites, and total rock abundance. The bulk and fine-component thermal inertias measured from orbit are similar to those calculated from the observed rock size-frequency distribution. A simple radar echo model based on the reflectivity of the soil (estimated from its bulk density), and the measured fraction of area covered by rocks was used to approximate the quasi-specular and diffuse components of the Earth-based radar echos. Color and albedo orbiter data were used to predict the relatively dust free or unweathered

  9. Digital plus analog output encoder

    NASA Technical Reports Server (NTRS)

    Hafle, R. S. (Inventor)

    1976-01-01

    The disclosed encoder is adapted to produce both digital and analog output signals corresponding to the angular position of a rotary shaft, or the position of any other movable member. The digital signals comprise a series of binary signals constituting a multidigit code word which defines the angular position of the shaft with a degree of resolution which depends upon the number of digits in the code word. The basic binary signals are produced by photocells actuated by a series of binary tracks on a code disc or member. The analog signals are in the form of a series of ramp signals which are related in length to the least significant bit of the digital code word. The analog signals are derived from sine and cosine tracks on the code disc.

  10. An alkaline spring system within the Del Puerto ophiolite (California USA): A Mars analog site

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

    Blank, J.G.; Green, S.; Blake, D.

    2008-10-01

    Mars appears to have experienced little compositional differentiation of primitive lithosphere, and thus much of the surface of Mars is covered by mafic lavas. On Earth, mafic and ultramafic rocks present in ophiolites, oceanic crust and upper mantle that have been obducted onto land, are therefore good analogs for Mars. The characteristic mineralogy, aqueous geochemistry, and microbial communities of cold-water alkaline springs associated with these mafic and ultramafic rocks represent a particularly compelling analog for potential life-bearing systems. Serpentinization, the reaction of water with mafic minerals such as olivine and pyroxene, yields fluids with unusual chemistry (Mg-OH and Ca-OH watersmore » with pH values up to {approx}12), as well as heat and hydrogen gas that can sustain subsurface, chemosynthetic ecosystems. The recent observation of seeps from pole-facing crater and canyon walls in the higher Martian latitudes supports the hypothesis that even present conditions might allow for a rockhosted chemosynthetic biosphere in near-surface regions of the Martian crust. The generation of methane within a zone of active serpentinization, through either abiogenic or biogenic processes, could account for the presence of methane detected in the Martian atmosphere. For all of these reasons, studies of terrestrial alkaline springs associated with mafic and ultramafic rocks are particularly timely. This study focuses on the alkaline Adobe Springs, emanating from mafic and ultramafic rocks of the California Coast Range, where a community of novel bacteria is associated with the precipitation of Mg-Ca carbonate cements. The carbonates may serve as a biosignature that could be used in the search for evidence of life on Mars.« less

  11. Analogy-Enhanced Instruction: Effects on Reasoning Skills in Science

    ERIC Educational Resources Information Center

    Remigio, Krisette B.; Yangco, Rosanelia T.; Espinosa, Allen A.

    2014-01-01

    The study examined the reasoning skills of first year high school students after learning general science concepts through analogies. Two intact heterogeneous sections were randomly assigned to Analogy-Enhanced Instruction (AEI) group and Non Analogy-Enhanced (NAEI) group. Various analogies were incorporated in the lessons of the AEI group for…

  12. Substance P analogs displace sigma binding differentially in the brain and spinal cord of the adult mouse.

    PubMed

    Mousseau, D D; Larson, A A

    1994-09-01

    We have previously observed similarities in the behavioral effects produced by the NH2-terminus of the undecapeptide substance P (SP) and by 1,3-di(2-tolyl)-guanidine (DTG) in the adult mouse. The present series of experiments indicate differences in the rank-order of potency of sigma ligands [DTG; haloperidol (HAL)], SP analogs [SP; SP(1-7); SP(5-11); [D-Pro2, D-Phe7]-SP(1-7) (D-SP(1-7))] and miscellaneous compounds [morphine (MOR), naloxone (NAL)] at competing for [3H]-DTG binding sites in the mouse brain and spinal cord in vitro: Brain; DTG = HAL > SP = MOR = NAL > SP(1-7) > D-SP(1-7) > SP(5-11): Spinal cord; DTG = HAL > SP(1-7) = MOR = NAL > SP > D-SP(1-7) = SP(5-11). The observed difference in the rank-order potencies of the displacing ligands at these same binding sites supports the notion of two distinct populations of sigma binding sites in these tissues in the adult mouse. Given the low (micromolar) potency of SP analogs at displacing [3H]-DTG binding in the present series of experiments, it is unlikely that the similar behavioral effects we have previously observed elicited by SP(1-7) and DTG in the adult mouse are a result of a direct action of SP(1-7) at the sigma binding site.

  13. A Systematic Evaluation of Analogs for the Read-across ...

    EPA Pesticide Factsheets

    Read-across is a data gap filling technique widely used within category and analog approaches to predict a biological property for a target data-poor chemical using known information from similar (source analog) chemical(s). Potential source analogs are typically identified based on structural similarity. Although much guidance has been published for read-across, practical guiding principles for the identification and evaluation of the scientific validity of source analogs, which is a critical step in deriving a robust read-across prediction, remains largely lacking.This case study explores the extent to which 3 structure descriptor sets (Pubchem, Chemotyper and MoSS) and their combinations are able to identify valid analogs for reading across Estrogen Receptor (ER) activity for a specific class of chemicals: hindered phenols. For each target chemical, two sets of analogs (hindered and non-hindered phenols) were selected using each descriptor set with two cut-offs: (1). Minimum Tanimoto similarity (range 0.1 - 0.9), and (2). Closest N analogs (range 1 - 10). Each target-analog pair was then evaluated for its agreement with measured ER binding and agonism. Subsequently, the analogs were filtered using physchem properties (LogKow & Molecular Volume) and the resultant agreement between each target-analog pair was evaluated. The data set comprised 462 hindered phenols and 296 non-hindered phenols. The results demonstrate that: (1). The concordance in ER activity r

  14. Analogy, explanation, and proof

    PubMed Central

    Hummel, John E.; Licato, John; Bringsjord, Selmer

    2014-01-01

    People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic) whose truth was not even known prior to the existence of the explanation (proof). What do the cognitive operations underlying the inference that the milk is sour have in common with the proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This seemingly small difference poses a challenge to the task of marshaling our understanding of analogical reasoning to understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence. PMID:25414655

  15. Insulin analogs with improved pharmacokinetic profiles.

    PubMed

    Brange; Vølund

    1999-02-01

    The aim of insulin replacement therapy is to normalize blood glucose in order to reduce the complications of diabetes. The pharmacokinetics of the traditional insulin preparations, however, do not match the profiles of physiological insulin secretion. The introduction of the rDNA technology 20 years ago opened new ways to create insulin analogs with altered properties. Fast-acting analogs are based on the idea that an insulin with less tendency to self-association than human insulin would be more readily absorbed into the systemic circulation. Protracted-acting analogs have been created to mimic the slow, steady rate of insulin secretion in the fasting state. The present paper provides a historical review of the efforts to change the physicochemical and pharmacological properties of insulin in order to improve insulin therapy. The available clinical studies of the new insulins are surveyed and show, together with modeling results, that new strategies for optimal basal-bolus treatment are required for utilization of the new fast-acting analogs.

  16. Monocarbonyl Curcumin Analogs: Heterocyclic Pleiotropic Kinase Inhibitors that Mediate Anti-Cancer Properties

    PubMed Central

    Brown, Andrew; Shi, Qi; Moore, Terry W.; Yoon, Younghyoun; Prussia, Andrew; Maddox, Clinton; Liotta, Dennis C.; Shim*, Hyunsuk; Snyder*, James P.

    2014-01-01

    Curcumin is a biologically active component of curry powder. A structurally-related class of mimetics possesses similar anti-inflammatory and anticancer properties. Mechanism has been examined by exploring kinase inhibition trends. In a screen of 50 kinases relevant to many forms of cancer, one member of the series (4, EF31) showed ≥85% inhibition for ten of the enzymes at 5 μM, while twenty-two of the proteins were blocked at ≥40%. IC50’s for an expanded set of curcumin analogs established a rank order of potencies, and analyses of IKKβ and AKT2 enzyme kinetics for 4 revealed a mixed inhibition model, ATP competition dominating. Our curcumin mimetics are generally selective for Ser/Thr kinases. Both selectivity and potency trends are compatible with protein sequence comparisons, while modeled kinase binding site geometries deliver a reasonable correlation with mixed inhibition. Overall, these analogs are shown to be pleiotropic inhibitors that operate at multiple points along cell signaling pathways. PMID:23550937

  17. How the creative use of analogies can shape medical practice.

    PubMed

    Prasad, G V Ramesh

    2015-06-01

    Analogical reasoning is central to medical progress, and is either creative or conservative. According to Hofmann et al., conservative analogy relates concepts from old technology to new technologies with emphasis on preservation of comprehension and conduct. Creative analogy however brings new understanding to new technology, brings similarities existing in the source domain to a target domain where they previously had no bearing, and imports something entirely different from the content of the analogy itself. I defend the claim that while conservative analogies are useful by virtue of being comfortable to use from familiarity and experience, and are more easily accepted by society, they only lead to incremental advances in medicine. However, creative analogies are more exciting and productive because they generate previously unexpected associations across widely separated domains, emphasize relations over physical similarities, and structure over superficiality. I use kidney transplantation and anti-rejection medication development as an exemplar of analogical reasoning used to improve medical practice. Anti-rejection medication has not helped highly sensitized patients because of their propensity to rejecting most organs. I outline how conservative analogical reasoning led to anti-rejection medication development, but creative analogical reasoning helped highly sensitized and blood type incompatible patients through domino transplants, by which they obtain a kidney to which they are not sensitized. Creative analogical reasoning is more likely than conservative analogical reasoning to lead to revolutionary progress. While these analogies overlap and creative analogies eventually become conservative, progress is best facilitated by combining conservative and creative analogical reasoning. © 2015 John Wiley & Sons, Ltd.

  18. Bayesian analogy with relational transformations.

    PubMed

    Lu, Hongjing; Chen, Dawn; Holyoak, Keith J

    2012-07-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy problems. We introduce Bayesian analogy with relational transformations (BART) and apply the model to the task of learning first-order comparative relations (e.g., larger, smaller, fiercer, meeker) from a set of animal pairs. Inputs are coded by vectors of continuous-valued features, based either on human magnitude ratings, normed feature ratings (De Deyne et al., 2008), or outputs of the topics model (Griffiths, Steyvers, & Tenenbaum, 2007). Bootstrapping from empirical priors, the model is able to induce first-order relations represented as probabilistic weight distributions, even when given positive examples only. These learned representations allow classification of novel instantiations of the relations and yield a symbolic distance effect of the sort obtained with both humans and other primates. BART then transforms its learned weight distributions by importance-guided mapping, thereby placing distinct dimensions into correspondence. These transformed representations allow BART to reliably solve 4-term analogies (e.g., larger:smaller::fiercer:meeker), a type of reasoning that is arguably specific to humans. Our results provide a proof-of-concept that structured analogies can be solved with representations induced from unstructured feature vectors by mechanisms that operate in a largely bottom-up fashion. We discuss potential implications for algorithmic and neural models of relational thinking, as well as for the evolution of abstract thought. Copyright 2012 APA, all rights reserved.

  19. Can Pupils Use Taught Analogies for Electric Current?

    ERIC Educational Resources Information Center

    Black, David; Solomon, Joan

    1987-01-01

    Discusses the use of analogies and models for teaching about electric current. Reports on a study in which one group of students used analogies to learn about electric current and one did not. Results indicate that, in this case, analogies did not play a significant role in student understanding. (TW)

  20. Analog Techniques in CEBAF's RF Control System

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

    Hovater, J.; Fugitt, Jock

    1988-01-01

    Recent developments in high-speed analog technology have progressed into the areas of traditional RF technology.Diode-related devices are being replaced by analog IC's in the CEBAF RF control system.Complex phase modulators and attenuators have been successfully tested at 70 MHz.They have three advantages over existing technology: lower cost, less temperature sensitivity, and more linearity.RF signal conditioning components and how to implement the new analog IC's will be covered in this paper.

  1. CRC handbook of neurohypophyseal hormone analogs. Volume 2

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

    Jost, K.; Lebl, M.; Brtnik, F.

    1987-01-01

    This book is discussed in two parts. The Part 1 discusses the: Prohormones and Hormonogens of Neuro-hypophyseal Hormones, Analogs with Inhibitory properties. Analogs with Dissociated and/or High activities. Introduction. Uterotonic Activity. Galactogogic Activity. Pressor Activity. Antidiuretic Activity. References. Part 2 discusses the Other Important Activities. CNS Activities. Corticotropin- and ..beta..-Entriuretic Action. Natriferic Action. References. Practical Use in Human and Veterinary Medicine. Introduction. Methyloxytocin. Deamino-Oxytocin. Cargutocin. Glypressin. Octapressin. Desmopressin. Analogs Clinically Tried But Not Introduced into Production and Routine Clinical Practice. References. Tables of Analogs and Index.

  2. Analogical Matrices in Young Children and Students with Intellectual Disability: Reasoning by Analogy or Reasoning by Association?

    ERIC Educational Resources Information Center

    Denaes, Caroline

    2012-01-01

    Background: Analogical reasoning (AR) is renowned for being a complex activity. Young children tend to reason by association, rather by analogy, and people with intellectual disability present problems of memorization. Both these populations usually show low performances in AR. The present author investigated whether familiar material and external…

  3. Phosphorylation of Dopamine Transporter Serine 7 Modulates Cocaine Analog Binding*

    PubMed Central

    Moritz, Amy E.; Foster, James D.; Gorentla, Balachandra K.; Mazei-Robison, Michelle S.; Yang, Jae-Won; Sitte, Harald H.; Blakely, Randy D.; Vaughan, Roxanne A.

    2013-01-01

    As an approach to elucidating dopamine transporter (DAT) phosphorylation characteristics, we examined in vitro phosphorylation of a recombinant rat DAT N-terminal peptide (NDAT) using purified protein kinases. We found that NDAT becomes phosphorylated at single distinct sites by protein kinase A (Ser-7) and calcium-calmodulin-dependent protein kinase II (Ser-13) and at multiple sites (Ser-4, Ser-7, and Ser-13) by protein kinase C (PKC), implicating these residues as potential sites of DAT phosphorylation by these kinases. Mapping of rat striatal DAT phosphopeptides by two-dimensional thin layer chromatography revealed basal and PKC-stimulated phosphorylation of the same peptide fragments and comigration of PKC-stimulated phosphopeptide fragments with NDAT Ser-7 phosphopeptide markers. We further confirmed by site-directed mutagenesis and mass spectrometry that Ser-7 is a site for PKC-stimulated phosphorylation in heterologously expressed rat and human DATs. Mutation of Ser-7 and nearby residues strongly reduced the affinity of rat DAT for the cocaine analog (−)-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (CFT), whereas in rat striatal tissue, conditions that promote DAT phosphorylation caused increased CFT affinity. Ser-7 mutation also affected zinc modulation of CFT binding, with Ala and Asp substitutions inducing opposing effects. These results identify Ser-7 as a major site for basal and PKC-stimulated phosphorylation of native and expressed DAT and suggest that Ser-7 phosphorylation modulates transporter conformational equilibria, shifting the transporter between high and low affinity cocaine binding states. PMID:23161550

  4. Molecular Hybridization of Potent and Selective γ-Hydroxybutyric Acid (GHB) Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3-Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and trans-γ-Hydroxycrotonic Acid (T-HCA) Analogs.

    PubMed

    Krall, Jacob; Jensen, Claus Hatt; Bavo, Francesco; Falk-Petersen, Christina Birkedahl; Haugaard, Anne Stæhr; Vogensen, Stine Byskov; Tian, Yongsong; Nittegaard-Nielsen, Mia; Sigurdardóttir, Sara Björk; Kehler, Jan; Kongstad, Kenneth Thermann; Gloriam, David E; Clausen, Rasmus Prætorius; Harpsøe, Kasper; Wellendorph, Petrine; Frølund, Bente

    2017-11-09

    γ-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high-affinity binding sites. To facilitate target identification and ligand optimization, we herein report a comprehensive structure-affinity relationship study for novel ligands targeting these binding sites. A molecular hybridization strategy was used based on the conformationally restricted 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar K i ) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the basis for a three-dimensional pharmacophore model for GHB ligands, which identified molecular features important for high-affinity binding, with high predictive validity. These findings will be valuable in the further processes of both target characterization and ligand identification for the high-affinity GHB binding sites.

  5. Spaceflight Sensorimotor Analogs: Simulating Acute and Adaptive Effects

    NASA Technical Reports Server (NTRS)

    Taylor, Laura C.; Harm, Deborah L.; Kozlovskaya, Inessa; Reschke, Millard F.; Wood, Scott J.

    2009-01-01

    Adaptive changes in sensorimotor function during spaceflight are reflected by spatial disorientation, motion sickness, gaze destabilization and decrements in balance, locomotion and eye-hand coordination that occur during and following transitions between different gravitational states. The purpose of this study was to conduct a meta-synthesis of data from spaceflight analogs to evaluate their effectiveness in simulating adaptive changes in sensorimotor function. METHODS. The analogs under review were categorized as either acute analogs used to simulate performance decrements accompanied with transient changes, or adaptive analogs used to drive sensorimotor learning to altered sensory feedback. The effectiveness of each analog was evaluated in terms of mechanisms of action, magnitude and time course of observed deficits compared to spaceflight data, and the effects of amplitude and exposure duration. RESULTS. Parabolic flight has been used extensively to examine effects of acute variation in gravitational loads, ranging from hypergravity to microgravity. More recently, galvanic vestibular stimulation has been used to elicit acute postural, locomotor and gaze dysfunction by disrupting vestibular afferents. Patient populations, e.g., with bilateral vestibular loss or cerebellar dysfunction, have been proposed to model acute sensorimotor dysfunction. Early research sponsored by NASA involved living onboard rotating rooms, which appeared to approximate the time course of adaptation and post-exposure recovery observed in astronauts following spaceflight. Exposure to different bed-rest paradigms (6 deg head down, dry immersion) result in similar motor deficits to that observed following spaceflight. Shorter adaptive analogs have incorporated virtual reality environments, visual distortion paradigms, exposure to conflicting tilt-translation cues, and exposure to 3Gx centrifugation. As with spaceflight, there is considerable variability in responses to most of the analogs

  6. Functional DNA: Teaching Infinite Series through Genetic Analogy

    ERIC Educational Resources Information Center

    Kowalski, R. Travis

    2011-01-01

    This article presents an extended analogy that connects infinite sequences and series to the science of genetics, by identifying power series as "DNA for a function." This analogy allows standard topics such as convergence tests or Taylor approximations to be recast in a "forensic" light as mathematical analogs of genetic concepts such as DNA…

  7. The importance of explicitly mapping instructional analogies in science education

    NASA Astrophysics Data System (ADS)

    Asay, Loretta Johnson

    Analogies are ubiquitous during instruction in science classrooms, yet research about the effectiveness of using analogies has produced mixed results. An aspect seldom studied is a model of instruction when using analogies. The few existing models for instruction with analogies have not often been examined quantitatively. The Teaching With Analogies (TWA) model (Glynn, 1991) is one of the models frequently cited in the variety of research about analogies. The TWA model outlines steps for instruction, including the step of explicitly mapping the features of the source to the target. An experimental study was conducted to examine the effects of explicitly mapping the features of the source and target in an analogy during computer-based instruction about electrical circuits. Explicit mapping was compared to no mapping and to a control with no analogy. Participants were ninth- and tenth-grade biology students who were each randomly assigned to one of three conditions (no analogy module, analogy module, or explicitly mapped analogy module) for computer-based instruction. Subjects took a pre-test before the instruction, which was used to assign them to a level of previous knowledge about electrical circuits for analysis of any differential effects. After the instruction modules, students took a post-test about electrical circuits. Two weeks later, they took a delayed post-test. No advantage was found for explicitly mapping the analogy. Learning patterns were the same, regardless of the type of instruction. Those who knew the least about electrical circuits, based on the pre-test, made the most gains. After the two-week delay, this group maintained the largest amount of their gain. Implications exist for science education classrooms, as analogy use should be based on research about effective practices. Further studies are suggested to foster the building of research-based models for classroom instruction with analogies.

  8. Fatty acid analogs

    DOEpatents

    Elmaleh, David R.; Livni, Eli

    1985-01-01

    In one aspect, a radioactively labeled analog of a fatty acid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fatty acid.

  9. Organics-bearing Clays from the Rio Tinto (spain): A Novel Analog for the Phyllosilicates Outcrops Seen By Omega-mex

    NASA Astrophysics Data System (ADS)

    Bonaccorsi, Rosalba

    2007-12-01

    The Rio Tinto (RT) is considered an important analog of Sinus Meridiani on Mars and an ideal model analog for a subsurface Martian setting [1]. The RT system comprises the upper sequence of an acid rock drainage system where weathered iron -rich rocks, overlain a massive-pyrite deposit. The RT analog site is ideal for testing on the preservation of organics in hematite-rich vs. phyllosilicates-rich environments [3]. It is suggested here that RT near-surface rocks, which embed pockets of Clays, represent also a potential new model analog for the phyllosilicates-rich outcrops seen by OMEGA-MEx on the surface of Mars [5]. Results from the analysis of cores drilled under the 2005 Robotic experiment of the MARTE project (Borehole#7 Site 607cm) [2-3] are presented in this paper. Primary mineral assemblages include hematite, goethite, and Phyllosilicates e.g.,smectite, kaolinite, as quantified by X-ray diffraction [4]. Organic carbon is at low concentration (<0.05%) beneath the soil horizon in most cores dominated by iron minerals but is considerably higher in Phyllosilicate-rich levels i.e., 0.2-0.3Wt% at 385 -550 cm-depth [2-3]. Phyllosilicate-rich terrains have been identified OMEGA/MEx in the Nili Fossae, Mawrth Valles and Candor Chasma regions [e.g., 5]. These outcrops are surrounded by hematite-rich deposits, which are potentially barren in organics [6]. The potential of phyllosilicates to preserve higher amounts of organics/ biosignatures is well known for several Earth environments as well as the RT near subsurface. This potential brings a relevant element for the selection of candidate sites for the MSL mission [e.g., 1]. References: [1]Fernandez-Remolar et al.,2005 EPSL, 240,149-167; [2]Stoker et al., 2007; [3] Bonaccorsi et al., 2007; [4] Sutter et al., 2007 in Astrobiology,MARTE Spec. Issue; [5] Bibring et al., 2006, Science 312, 400-404; [6] Sumner, 2004, JGR 109. Anknowlegments: NASA-Postdoctoral-Program/C.Stoker, B.Sutter, A.F Davila and the MARTE team for

  10. A CCD Monolithic LMS Adaptive Analog Signal Processor Integrated Circuit.

    DTIC Science & Technology

    1980-03-01

    adaptive filter with electrically- reprogrammable MOS analog conductance weights. I The analog and digital peripheral MOS on-chip circuits are provided with...electrically reprogrammable analog weights at tap positions along a CCD analog delay line in order to form a basic linear combiner for adaptive filtering...electrically reprogrammable analog conductance weights was introduced with the use of non-volatile MNOS memory 6-7 transistors biased in their triode

  11. In Pursuit of Analogs for Europa's Dynamics & Potential Habitats

    NASA Astrophysics Data System (ADS)

    Schmidt, Britney E.; Blankenship, D. D.; Greenbaum, J. S.; Young, D. A.

    2010-10-01

    Future Europa exploration will seek to characterize the distribution of shallow subsurface water as well as to understand the formation of surface features through dynamic ice-shell processes. Radar sounding will be a critical tool for imaging these features, and should be of primary interest to the astrobiology community for understanding how and where life might arise on Europa. To develop successful instrumentation and data interpretation techniques for exploring Europa, we must leverage analogous terrestrial environments and processes. Airborne ice penetrating radar is now a mature tool in terrestrial studies of Earth's ice sheets, and orbital examples have been successfully deployed at Earth's Moon and Mars. It is a distinct possibility that water within or just below the ice on Europa has played a role in forming some of its dynamic terrain. Observations of rotated blocks and dark floor materials may suggest that brines existed in the near subsurface and enabled the formation of such features. The University of Texas High Capability Airborne Radar Sounder (HiCARS) developed to study Antarctic ice sheet dynamics has been configured to test observation scenarios for Europa. We discuss recent results from the 60 MHz HiCARS system over brine infiltrated Antarctic marine ice as an analog for processes affecting the formation of pits and chaos. Basal melt occurring below terrestrial marine ice is directly analogous to processes that may operate on Europa if the shell is "thin,” and will be similar to processes occurring instead within the ice sheet in the case of a thicker, multi-layer ice sheet where enriched brines may remain liquid within the shell. A key site for further investigation of conductive and "convective” ices is found in the polythermal glaciers in the Arctic, and the case for this exploration will be illuminated.

  12. A structure-function study of PACAP using conformationally-restricted analogs: identification of PAC1 receptor-selective PACAP agonists

    PubMed Central

    Ramos-Álvarez, Irene; Mantey, Samuel A.; Nakamura, Taichi; Nuche-Berenguer, Bernardo; Moreno, Paola; Moody, Terry W.; Maderdrut, Jerome L.; Coy, David H.; Jensen, Robert T.

    2015-01-01

    Pituitary adenylate-cyclase-activating polypeptide (PACAP) has widespread physiological/pathophysiological actions and there is increased interest for its use therapeutically, especially in the CNS (neuroprotection). Unfortunately, no selective PACAP-analogs exist for PACAP-preferring PAC1-receptors, primarily because of its high sequence identity to VIP and particularly, because of the inability of structure-function studies to separate the pharmacophore of PAC1-R from VPAC1-R, which has high affinity for PACAP and VIP. The present study attempted to develop PAC1-R-selective agonists primarily by making conformationally-restricted PACAP -analogs in positions important for receptor-selectivity/affinity. Forty-six PACAP-related-analogs were synthesized with substitutions in positions 1–4, 14–17, 20–22 ,28,34,38 and receptor-selectivity determined in PAC1-R,VPAC1-R,VPAC2-R-transfected or native cells from binding or cAMP-generation experiments. Fifteen PACAP-analogs had 6–78-fold higher affinities for PAC1-R than VPAC1-R and 13 were agonists. Although binding-affinities correlated significantly with agonist potency, the degree of receptor-spareness varied markedly for the different PACAP-analogs, resulting in selective potencies for activating the PAC1 receptor over the VPAC1 receptor from 0- to-103-fold. In addition, a number of PACAP-analogs were identified that had high selectivity for PAC1-R over VPAC2-R as well as PACAP-analogs that could prove more useful therapeutically because of substitutions known to extend their half-lives (substitutions at potential sites of proteolysis and attachment of long-chain fatty acids). This study provides for the first time a separation of the pharmacophores for PAC1-R and VPAC1-R, resulting in PACAP-related analogs that are PAC1-R-preferring. Some of these analogs, or their modifications, could prove useful as therapeutic agents for various diseases. PMID:25698233

  13. ANALOG-TO-DIGITAL DATA CONVERTER

    DOEpatents

    Rodgers, G.W.; Althouse, J.E.; Anderson, D.P.; Bussey, G.R.; Minnear, L.H.

    1960-09-01

    Electrical apparatus is described, particularly useful in telemetry work, for converting analog signals into electrical pulses and recording them. An electronic editor commands the taking of signal readings at a frequency which varies according to linearity of the analog signal being converted. Readings of information signals are recorded, along with time base readings and serial numbering, if desired, on magnetic tape and the latter may be used to operate a computer or the like. Magnetic tape data may be transferred to punched cards.

  14. Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2.

    PubMed

    Lister, M D; Hancock, A J

    1988-10-01

    Six isomers of dipalmitoylcyclopentanetriol phosphocholine (cyclopentano-lecithin) were tested as potential substrates for phospholipase A2. Since each of these analogs possesses a configuration that mimics a narrow range of conformations of a glycerophospholipid molecule, the analogs were used to assess the enzyme's conformational requirements. Studies showed that all of the analogs containing the phosphocholine at the C-1 (or C-3) position could be hydrolyzed, while only one of the three analogs that contains the polar head group at the C-2 position was susceptible. Kinetic studies, however, revealed that only the all-trans-(1,3/2-1P)-cyclopentano-lecithin gave initial rates of hydrolysis that were measurable by pH-stat. Acyl group specificity of the enzyme towards the all-trans isomer was determined with an analog was acyl groups were distinguishable. The synthesis of this mixed-acid-cyclopentano-PC is described herein. When this analog was enzymatically assayed, results unequivocally showed the enzyme to be specific for C-2 acyl hydrolysis. This specificity, and data showing that the all-trans analog is stereospecifically hydrolyzed, indicate that it is acted on in an analogous manner to dipalmitoylphosphatidylcholine. These studies indicate that although the configuration of the analog is not necessarily a prerequisite for hydrolysis, there does appear to be an optimal spatial orientation for enzymatic activity. The analogy between the susceptibilities of all-trans-(1,3/2-1P)-cyclopentano-lecithin and glycero-lecithin suggests that the conformation of the glycero-lecithin during phospholipase A2-mediated hydrolysis may be best simulated by the all-trans orientation of C-O bonds in the artificial substrate.

  15. Analogy, higher order thinking, and education.

    PubMed

    Richland, Lindsey Engle; Simms, Nina

    2015-01-01

    Analogical reasoning, the ability to understand phenomena as systems of structured relationships that can be aligned, compared, and mapped together, plays a fundamental role in the technology rich, increasingly globalized educational climate of the 21st century. Flexible, conceptual thinking is prioritized in this view of education, and schools are emphasizing 'higher order thinking', rather than memorization of a cannon of key topics. The lack of a cognitively grounded definition for higher order thinking, however, has led to a field of research and practice with little coherence across domains or connection to the large body of cognitive science research on thinking. We review literature on analogy and disciplinary higher order thinking to propose that relational reasoning can be productively considered the cognitive underpinning of higher order thinking. We highlight the utility of this framework for developing insights into practice through a review of mathematics, science, and history educational contexts. In these disciplines, analogy is essential to developing expert-like disciplinary knowledge in which concepts are understood to be systems of relationships that can be connected and flexibly manipulated. At the same time, analogies in education require explicit support to ensure that learners notice the relevance of relational thinking, have adequate processing resources available to mentally hold and manipulate relations, and are able to recognize both the similarities and differences when drawing analogies between systems of relationships. © 2015 John Wiley & Sons, Ltd.

  16. Analog hardware implementation of neocognitron networks

    NASA Astrophysics Data System (ADS)

    Inigo, Rafael M.; Bonde, Allen, Jr.; Holcombe, Bradford

    1990-08-01

    This paper deals with the analog implementation of neocognitron based neural networks. All of Fukushima''s and related work on the neocognitron is based on digital computer simulations. To fully take advantage of the power of this network paradigm an analog electronic approach is proposed. We first implemented a 6-by-6 sensor network with discrete analog components and fixed weights. The network was given weight values to recognize the characters U L and F. These characters are recognized regardless of their location on the sensor and with various levels of distortion and noise. The network performance has also shown an excellent correlation with software simulation results. Next we implemented a variable weight network which can be trained to recognize simple patterns by means of self-organization. The adaptable weights were implemented with PETs configured as voltage-controlled resistors. To implement a variable weight there must be some type of " memory" to store the weight value and hold it while the value is reinforced or incremented. Two methods were evaluated: an analog sample-hold circuit and a digital storage scheme using binary counters. The latter is preferable for VLSI implementation because it uses standard components and does not require the use of capacitors. The analog design and implementation of these small-scale networks demonstrates the feasibility of implementing more complicated ANNs in electronic hardware. The circuits developed can also be designed for VLSI implementation. 1.

  17. Hints of Habitable Environments on Mars Challenge Our Studies of Mars-Analog Sites on Earth

    NASA Technical Reports Server (NTRS)

    desMarais, David J

    2009-01-01

    Life as we know it requires water with a chemical activity (alpha) >or approx.0.6 and sources of nutrients and useful energy. Some biota can survive even if favorable conditions occur only intermittently, but the minimum required frequency of occurrences is poorly understood. Recent discoveries have vindicated the Mars exploration strategy to follow the water. Mars Global Surveyor s Thermal Emission Spectrometer (TES) found coarse-grained hematite at Meridiani Planum. Opportunity rover confirmed this and also found evidence of ancient sulfate-rich playa lakes and near-surface groundwater. Elsewhere, TES found evidence of evaporitic halides in topographic depressions. But alpha might not have approached 0.6 in these evaporitic sulfate- and halide-bearing waters. Mars Express (MEX) and Mars Reconnaissance Orbiter (MRO) found extensive sulfate evaporites in Meridiani and Valles Marineris. MEX found phyllosilicates at several sites, most notably Mawrth Valles and Nili Fossae. MRO's CRISM near-IR mapper extended the known diversity and geographic distribution of phyllosilicates to include numerous Noachian craters. Phyllosilicates typically occur at the base of exposed ancient rock sections or in sediments in early Hesperian craters. It is uncertain whether the phyllosilicates developed in surface or subsurface aqueous environments and how long aqueous conditions persisted. Spirit rover found remarkably pure ferric sulfate, indicating oxidation and transport of Fe and S, perhaps in fumaroles or hot springs. Spirit also found opaline silica, consistent with hydrothermal activity. CRISM mapped extensive silica deposits in the Valles Marineris region, consistent with aqueous weathering and deposition. CRISM also found ultramafic rocks and magnesite at Nili Fossae, consistent with serpentinization, a process that can sustain habitable environments on Earth. The report of atmospheric methane implies subsurface aqueous conditions. A working hypothesis is that aqueous

  18. High-affinity cannabinoid binding site in brain: A possible marijuana receptor

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

    Nye, J.S.

    The mechanism by which delta{sup 9} tetrahydrocannabinol (delta{sup 9}THC), the major psychoactive component of marijuana or hashish, produces its potent psychological and physiological effects is unknown. To find receptor binding sites for THC, we designed a water-soluble analog for use as a radioligand. 5{prime}-Trimethylammonium-delta{sup 8}THC (TMA) is a positively charged analog of delta-{sup 8}THC modified on the 5{prime} carbon, a portion of the molecule not important for its psychoactivity. We have studied the binding of ({sup 3}H)-5{prime}-trimethylammonium-delta-{sup 8}THC (({sup 3}H)TMA) to rat neuronal membranes. ({sup 3}H)TMA binds saturably and reversibly to brain membranes with high affinity to apparently one classmore » of sites. Highest binding site density occurs in brain, but several peripheral organs also display specific binding. Detergent solubilizes the sites without affecting their pharmacologial properties. Molecular sieve chromatography reveals a bimodal peak of ({sup 3}H)TMA binding activity of approximately 60,000 daltons apparent molecular weight.« less

  19. Chromomycin SA analogs from a marine-derived Streptomyces sp.

    PubMed Central

    Hu, Youcai; Espindola, Ana Paula D. M; Stewart, Nathan A.; Wei, Shuguang; Posner, Bruce A.; MacMillan, John B.

    2011-01-01

    Two chromomycin SA analogs, chromomycin SA3 and chromomycin SA2, along with deacetylchromomycin A3 and five previously reported chromomycin analogs were isolated from a marine-derived Streptomyces sp. The structures of the new compounds were determined by spectroscopic methods including 1D and 2D NMR techniques, HRMS and chemical methods. Chromomycin SA3 and chromomycin SA2 are the first naturally occuring chromomycin analogs with truncated side-chains. Biological evaluation of chromomycin analogs for cytotoxicity against two non-small cell lung cancer (NSCLC) cell-lines, A549 and HCC44, demonstrated a decrease in cytotoxicity for the truncated sides chain chromomycin analogs. PMID:21807523

  20. Simple Electronic Analog of a Josephson Junction.

    ERIC Educational Resources Information Center

    Henry, R. W.; And Others

    1981-01-01

    Demonstrates that an electronic Josephson junction analog constructed from three integrated circuits plus an external reference oscillator can exhibit many of the circuit phenomena of a real Josephson junction. Includes computer and other applications of the analog. (Author/SK)

  1. Arguing by analogy in the fetal tissue debate.

    PubMed

    Gillam, Lynn

    1997-10-01

    In the debate over fetal tissue use, an analogy is often drawn between removing organs from the body of a person who has been murdered to use for transplantation, and collecting tissue from an aborted fetus to use for the same purpose. The murder victim analogy is taken by its proponents to show that even if abortion is the moral equivalent of murder, there is still no good reason to refrain from using the fetal tissue, since as a society we do not see any problem about using organs from murder victims. However, I argue that the analogy between murder victims and aborted fetuses does not hold -- the two situations are not the same in all morally relevant respects. Thus the murder victim analogy does not provide an argument in favour of fetal tissue transplant. In conclusion, I point to some of the potential pitfalls of using analogies in ethical argument.

  2. Antarctic analogs for Enceladus

    NASA Astrophysics Data System (ADS)

    Murray, A. E.; Andersen, D. T.; McKay, C. P.

    2014-12-01

    Enceladus is a new world for Astrobiology. The Cassini discovery of the icy plume emanating from the South Polar region indicates an active world, where detection of water, organics, sodium, and nano-particle silica in the plume strongly suggests that the source is a subsurface salty ocean reservoir. Recent gravity data from Cassini confirms the presence of a regional sea extending north to 50°S. An ocean habitat under a thick ice cover is perhaps a recurring theme in the Outer Solar System, but what makes Enceladus unique is that the plume jetting out into space is carrying samples of this ocean. Therefore, through the study of Enceladus' plumes we can gain new insights not only of a possible habitable world in the Solar Systems, but also about the formation and evolution of other icy-satellites. Cassini has been able to fly through this plume - effectively sampling the ocean. It is time to plan for future missions that do more detailed analyses, possibly return samples back to Earth and search for evidence of life. To help prepare for such missions, the need for earth-based analog environments is essential for logistical, methodological (life detection) and theoretical development. We have undertaken studies of two terrestrial environments that are close analogs to Enceladus' ocean: Lake Vida and Lake Untersee - two ice-sealed Antarctic lakes that represent physical, chemical and possibly biological analogs for Enceladus. By studying the diverse biology and physical and chemical constraints to life in these two unique lakes we will begin to understand the potential habitability of Enceladus and other icy moons, including possible sources of nutrients and energy, which together with liquid water are the key ingredients for life. Analog research such as this will also enable us to develop and test new strategies to search for evidence of life on Enceladus.

  3. Digitally Controlled Analog Signal Processing

    DTIC Science & Technology

    1988-04-01

    each analog switch. The third is the parasiti - capacitance at the output (the capacitor side) of each analog switch. This last is of concern only when a...21) where fk (x) tf H(wk) -H(wk) for k = 1, 2,... n, and x denotes the vector containing n-+ I transfer function coefficients, a, a2 ,... am, and bl...b2, .... bt that are non-zero. We wish to solve this system of equations for x, the vector of unknown transfer function coefficients. The modified

  4. Binary/Analog CCD Correlator Development.

    DTIC Science & Technology

    1981-07-01

    architecture , design and performance of a general purpose, 1,024-stage, programmable transversal filter implemented in CCD/NMOS technology is described. The device features programmability of the reference signal, the filter length and weighting coefficient resolution. Off-ship circuitry is minimized by incorporating both analog and digital support circuitry, on-chip. This results in a monolithic analog signal processing system that has the flexibility to be operated in nine programmable configurations, from 1,024-stages by 1-bit, to 128-stages by 8-bits. The versatility

  5. Analogical Reasoning: What Develops? A Review of Research and Theory.

    ERIC Educational Resources Information Center

    Goswami, Usha

    1991-01-01

    Children's analogical reasoning has traditionally been measured by classical four-term analogy tasks or problem-solving tasks. Current theories of analogical development and the evidence on which they are based are reviewed. It is concluded that structural views of analogical development are wrong, and knowledge-based accounts of what develops are…

  6. N-mustard analogs of S-adenosyl-L-methionine as biochemical probes of protein arginine methylation.

    PubMed

    Hymbaugh Bergman, Sarah J; Comstock, Lindsay R

    2015-08-01

    Nucleosomes, the fundamental building blocks of eukaryotic chromatin, undergo post-synthetic modifications and play a major role in the regulation of transcriptional processes. Combinations of these modifications, including methylation, regulate chromatin structure, determining its different functional states and playing a central role in differentiation. The biological significance of cellular methylation, particularly on chromatin, is widely recognized, yet we know little about the mechanisms that link biological methylation events. To characterize and fully understand protein methylation, we describe here novel N-mustard analogs of S-adenosyl-l-methionine (SAM) as biochemical tools to better understand protein arginine methylation events using protein arginine methyltransferase 1 (PRMT1). Specifically, azide- and alkyne-functionalized N-mustard analogs serve as cofactor mimics of SAM and are enzymatically transferred to a model peptide substrate in a PRMT1-dependent fashion. Once incorporated, the resulting alkynes and azides can be modified through chemoselective ligations, including click chemistry and the Staudinger ligation. These results readily demonstrate the feasibility of utilizing N-mustard analogs as biochemical tools to site-specifically label substrates of PRMT1 and serve as an alternative approach to study protein methylation events. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. A Transiting Jupiter Analog

    NASA Astrophysics Data System (ADS)

    Kipping, D. M.; Torres, G.; Henze, C.; Teachey, A.; Isaacson, H.; Petigura, E.; Marcy, G. W.; Buchhave, L. A.; Chen, J.; Bryson, S. T.; Sandford, E.

    2016-04-01

    Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of (0.91+/- 0.02) {R}{{J}}, a low orbital eccentricity ({0.06}-0.04+0.10), and an equilibrium temperature of (131+/- 3) K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric coverage, we are able to uniquely and precisely measure the orbital period of this post snow-line planet (1071.2323 ± 0.0006d), paving the way for follow-up of this K = 11.8 mag target.

  8. An Analog Computer for Electronic Engineering Education

    ERIC Educational Resources Information Center

    Fitch, A. L.; Iu, H. H. C.; Lu, D. D. C.

    2011-01-01

    This paper describes a compact analog computer and proposes its use in electronic engineering teaching laboratories to develop student understanding of applications in analog electronics, electronic components, engineering mathematics, control engineering, safe laboratory and workshop practices, circuit construction, testing, and maintenance. The…

  9. The interplay of conflict and analogy in multidisciplinary teams.

    PubMed

    Paletz, Susannah B F; Schunn, Christian D; Kim, Kevin H

    2013-01-01

    Creative teamwork in multidisciplinary teams is a topic of interest to cognitive psychologists on the one hand, and to both social and organizational psychologists on the other. However, the interconnections between cognitive and social layers have been rarely explored. Drawing on mental models and dissonance theories, the current study takes a central variable studied by cognitive psychologists-analogy-and examines its relationship to a central variable examined by social psychologists-conflict. In an observational, field study, over 11h of audio-video data from conversations of the Mars Exploration Rover scientists were coded for different types of analogy and micro-conflicts that reveal the character of underlying psychological mechanisms. Two different types of time-lagged logistic models applied to these data revealed asymmetric patterns of associations between analogy and conflict. Within-domain analogies, but not within-discipline or outside-discipline analogies, preceded science and work process conflicts, suggesting that in multidisciplinary teams, representational gaps in very close domains will be more likely to spark conflict. But analogies also occurred in reaction to conflict: Process and negative conflicts, but not task conflicts, preceded within-discipline analogies, but not to within-domain or outside-discipline analogies. This study demonstrates ways in which cognition can be bidirectionally tied to social processes and discourse. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Fluorinated analogs of malachite green: synthesis and toxicity.

    PubMed

    Kraus, George A; Jeon, Insik; Nilsen-Hamilton, Marit; Awad, Ahmed M; Banerjee, Jayeeta; Parvin, Bahram

    2008-04-27

    A series of fluorinated analogs of malachite green (MG) have been synthesized and their toxicity to Saccharomyces cerevisiae and a human ovarian epithelial cell line examined. The toxicity profiles were found to be different for these two species. Two analogs, one with 2,4-difluoro substitution and the other with 2-fluoro substitution seem to be the most promising analogs because they showed the lowest toxicity to the human cells.

  11. Reconfigurable Analog PDE computation for Baseband and RFComputation

    DTIC Science & Technology

    2017-03-01

    waveguiding PDEs. One-dimensional ladder topologies enable linear delays, linear-phase analog filters , as well as analog beamforming, potentially at RF...performance. This discussion focuses on ODE / PDE analog computation available in SoC FPAA structures. One such computation is a ladder filter (Fig...Implementation of a one-dimensional ladder filter for computing inductor (L) and capacitor (C) lines. These components can be implemented in CABs or as

  12. Dopamine transporter-dependent and -independent striatal binding of the benztropine analog JHW 007, a cocaine antagonist with low abuse liability

    USDA-ARS?s Scientific Manuscript database

    The benztropine analog JHW 007 displays high affinity for the dopamine transporter (DAT), but unlike typical DAT ligands, has relatively low abuse liability and blocks effects of cocaine,including its self-administration. To determine sites responsible for the cocaine-antagonist effects of JHW 007, ...

  13. Synthetic heparin-binding growth factor analogs

    DOEpatents

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  14. Immune Function Changes during a Spaceflight-Analog Undersea Mission

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Stowe, Raymond; Mehta, Satish; Quiniarte, Heather; Yetman, Deborah; Pierson, Duane; Sams, Clarence

    2008-01-01

    There is ample evidence to suggest that space flight leads to immune system dysregulation. This may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. It is attractive to utilize ground-based spaceflight analogs as appropriate to investigate this phenomenon. For spaceflight-associated immune dysregulation (SAID), the authors believe the most appropriate analogs might be NEEMO (short duration, Shuttle analog), Antarctic winter-over (long-duration, ISS analog) and the Haughton Mars Project in the Canadian Arctic (intermediate-duration). Each of these analogs replicate isolation, mission-associated stress, disrupted circadian rhythms, and other aspects of flight thought to contribute to SAID. To validate NEEMO as a flight analog with respect to SAID, a pilot study was conducted during the NEEMO-12 and 13 missions during 2007. Assays were performed that assessed immune status, physiological stress and latent viral reactivation. Blood and saliva samples were collected at pre-, mid-, and post-mission timepoints.

  15. Synthetic heparin-binding factor analogs

    DOEpatents

    Pena, Louis A [Poquott, NY; Zamora, Paul O [Gaithersburg, MD; Lin, Xinhua [Plainview, NY; Glass, John D [Shoreham, NY

    2010-04-20

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  16. In vivo evidence for translesion synthesis by the replicative DNA polymerase δ

    PubMed Central

    Hirota, Kouji; Tsuda, Masataka; Mohiuddin; Tsurimoto, Toshiki; Cohen, Isadora S.; Livneh, Zvi; Kobayashi, Kaori; Narita, Takeo; Nishihara, Kana; Murai, Junko; Iwai, Shigenori; Guilbaud, Guillaume; Sale, Julian E.; Takeda, Shunichi

    2016-01-01

    The intolerance of DNA polymerase δ (Polδ) to incorrect base pairing contributes to its extremely high accuracy during replication, but is believed to inhibit translesion synthesis (TLS). However, chicken DT40 cells lacking the POLD3 subunit of Polδ are deficient in TLS. Previous genetic and biochemical analysis showed that POLD3 may promote lesion bypass by Polδ itself independently of the translesion polymerase Polζ of which POLD3 is also a subunit. To test this hypothesis, we have inactivated Polδ proofreading in pold3 cells. This significantly restored TLS in pold3 mutants, enhancing dA incorporation opposite abasic sites. Purified proofreading-deficient human Polδ holoenzyme performs TLS of abasic sites in vitro much more efficiently than the wild type enzyme, with over 90% of TLS events resulting in dA incorporation. Furthermore, proofreading deficiency enhances the capability of Polδ to continue DNA synthesis over UV lesions both in vivo and in vitro. These data support Polδ contributing to TLS in vivo and suggest that the mutagenesis resulting from loss of Polδ proofreading activity may in part be explained by enhanced lesion bypass. PMID:27185888

  17. An analog silicon retina with multichip configuration.

    PubMed

    Kameda, Seiji; Yagi, Tetsuya

    2006-01-01

    The neuromorphic silicon retina is a novel analog very large scale integrated circuit that emulates the structure and the function of the retinal neuronal circuit. We fabricated a neuromorphic silicon retina, in which sample/hold circuits were embedded to generate fluctuation-suppressed outputs in the previous study [1]. The applications of this silicon retina, however, are limited because of a low spatial resolution and computational variability. In this paper, we have fabricated a multichip silicon retina in which the functional network circuits are divided into two chips: the photoreceptor network chip (P chip) and the horizontal cell network chip (H chip). The output images of the P chip are transferred to the H chip with analog voltages through the line-parallel transfer bus. The sample/hold circuits embedded in the P and H chips compensate for the pattern noise generated on the circuits, including the analog communication pathway. Using the multichip silicon retina together with an off-chip differential amplifier, spatial filtering of the image with an odd- and an even-symmetric orientation selective receptive fields was carried out in real time. The analog data transfer method in the present multichip silicon retina is useful to design analog neuromorphic multichip systems that mimic the hierarchical structure of neuronal networks in the visual system.

  18. Reynolds analogy for the Rayleigh problem at various flow modes.

    PubMed

    Abramov, A A; Butkovskii, A V

    2016-07-01

    The Reynolds analogy and the extended Reynolds analogy for the Rayleigh problem are considered. For a viscous incompressible fluid we derive the Reynolds analogy as a function of the Prandtl number and the Eckert number. We show that for any positive Eckert number, the Reynolds analogy as a function of the Prandtl number has a maximum. For a monatomic gas in the transitional flow regime, using the direct simulation Monte Carlo method, we investigate the extended Reynolds analogy, i.e., the relation between the shear stress and the energy flux transferred to the boundary surface, at different velocities and temperatures. We find that the extended Reynolds analogy for a rarefied monatomic gas flow with the temperature of the undisturbed gas equal to the surface temperature depends weakly on time and is close to 0.5. We show that at any fixed dimensionless time the extended Reynolds analogy depends on the plate velocity and temperature and undisturbed gas temperature mainly via the Eckert number. For Eckert numbers of the order of unity or less we generalize an extended Reynolds analogy. The generalized Reynolds analogy depends mainly only on dimensionless time for all considered Eckert numbers of the order of unity or less.

  19. Two analogy strategies: the cases of mind metaphors and introspection

    NASA Astrophysics Data System (ADS)

    Fischer, Eugen

    2018-04-01

    Analogical reasoning is often employed in problem-solving and metaphor interpretation. This paper submits that, as a default, analogical reasoning addressing these different tasks employs different mapping strategies. In problem-solving, it employs analogy-maximising strategies (like structure mapping, Gentner, D., & Markman, A. B. (1997). Structure mapping in analogy and similarity. American Psychologist, 52, 45-56); in metaphor interpretation, analogy-minimising strategies (like ATT-Meta, Barnden, J. A. (2015). Open-ended elaborations in creative metaphor. In T. R. Besold, M. Schorlemmer, & A. Smaill (Eds.), Computational creativity research: Towards creative machines (pp. 217-242). Berlin: Springer). The two strategies interact in analogical reasoning with conceptual metaphors. This interaction leads to predictable fallacies. The paper supports these hypotheses through case-studies on "mind" metaphors from ordinary discourse, and abstract problem-solving in the philosophy of mind, respectively. It shows that (1) default metaphorical interpretations for vision- and space-cognition metaphors can be derived with a variant of the analogy-minimising ATT-Meta approach, (2) philosophically influential introspective conceptions of the mind can be derived with conceptual metaphors only through an analogy-maximising strategy, and (3) the interaction of these strategies leads to hitherto unrecognised fallacies in analogical reasoning with metaphors. This yields a debunking explanation of introspective conceptions.

  20. Licancabur Volcano, Bolivia and life in the Atacama: Environmental physics and analogies to Mars

    NASA Astrophysics Data System (ADS)

    Hock, Andrew Nelson

    Although there is no perfect environmental analog to Mars on Earth, quantitative study of relevant terrestrial field sites can serve as the basis for physical models and technology development to aid future exploration. This dissertation describes original field and laboratory research on two terrestrial analog sites: Licancabur Volcano, Bolivia, and the Atacama Desert, Chile. Atop Licancabur, at an elevation of nearly 6,000 meters above sea level, sits the highest volcanic lake on Earth. Prior to this work, little was known about the lake, its waters, the role of volcanism or its potential relationship to locales on Mars. In the first part of this work, I describe observations of the lake resulting from several years of field study, including data on meteorological conditions and solar irradiance. These and other measurements provide the basis for (1) the first quantitative mass and energy balance model of the lake, and (2) the first determination of the altitude effect on solar visible and ultraviolet flux from the high altitude summit. Under the observed conditions, model results indicate: lake waters are primarily meteoric in origin and evaporating rapidly; volcanic input is not required to explain observations of lake water temperature or year-end model results. Nearby, Chile's Atacama Desert is known to be one of the driest, most inhospitable environments on Earth. There, environmental similarities to Mars provide an apt testing ground for new astrobiological exploration technologies. In the latter part of this work, I present results from my work with the Life In The Atacama (LITA) Mars rover field experiment. In particular, I report on the development of a new data analysis tool named the LITA Data Scoring System (DSS). Subject to the user-defined constraints, the DSS was used to facilitate targeting, analysis and mapping of rover science results relevant to potential habitability and evidence for life at three desert field sites. Although experimental in

  1. Analog Nonvolatile Computer Memory Circuits

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd

    2007-01-01

    In nonvolatile random-access memory (RAM) circuits of a proposed type, digital data would be stored in analog form in ferroelectric field-effect transistors (FFETs). This type of memory circuit would offer advantages over prior volatile and nonvolatile types: In a conventional complementary metal oxide/semiconductor static RAM, six transistors must be used to store one bit, and storage is volatile in that data are lost when power is turned off. In a conventional dynamic RAM, three transistors must be used to store one bit, and the stored bit must be refreshed every few milliseconds. In contrast, in a RAM according to the proposal, data would be retained when power was turned off, each memory cell would contain only two FFETs, and the cell could store multiple bits (the exact number of bits depending on the specific design). Conventional flash memory circuits afford nonvolatile storage, but they operate at reading and writing times of the order of thousands of conventional computer memory reading and writing times and, hence, are suitable for use only as off-line storage devices. In addition, flash memories cease to function after limited numbers of writing cycles. The proposed memory circuits would not be subject to either of these limitations. Prior developmental nonvolatile ferroelectric memories are limited to one bit per cell, whereas, as stated above, the proposed memories would not be so limited. The design of a memory circuit according to the proposal must reflect the fact that FFET storage is only partly nonvolatile, in that the signal stored in an FFET decays gradually over time. (Retention times of some advanced FFETs exceed ten years.) Instead of storing a single bit of data as either a positively or negatively saturated state in a ferroelectric device, each memory cell according to the proposal would store two values. The two FFETs in each cell would be denoted the storage FFET and the control FFET. The storage FFET would store an analog signal value

  2. Synthesis, biological evaluation, and docking studies of gigantol analogs as calmodulin inhibitors.

    PubMed

    Reyes-Ramírez, Adelfo; Leyte-Lugo, Martha; Figueroa, Mario; Serrano-Alba, Trinidad; González-Andrade, Martín; Mata, Rachel

    2011-07-01

    Several analogs of gigantol (1) were synthesized to evaluate their effect on the complexes Ca(2+)-calmodulin (CaM) and Ca(2+)-CaM-CaM sensitive phosphodiesterase 1 (PDE1). The compounds belong to four structural groups including, 1,2-diphenylethanes (2-11), diphenylmethanes (13-15), 1,3-diphenylpropenones (16-18), and 1,3-diphenylpropanes (20-22). In vitro enzymatic studies showed that all compounds except 11 inhibited the complex Ca(2+)-CaM-PDE1 with IC(50) values ranging from 9 to 146 μM. On the other hand, all analogs but 11, 12 and 15 quenched the extrinsic fluorescence of the CaM biosensor hCaM-M124C-mBBr to different extent, then revealing different affinities to CaM; their affinity constants (K(m)) values were in the range of 3-80 μM. Molecular modeling studies indicated that all these compounds bound to CaM at the same site that the classical inhibitors trifluoperazine (TFP) and chlorpromazine (CPZ). Some of these analogs could be worthy candidates for developing new anti-tumor, local anesthetics, antidepressants, antipsychotic, or smooth muscle relaxant drugs, with anti-CaM properties due to their good affinity to CaM and the straightforwardness of their synthesis. In addition they could be valuable tools for the study of Ca(2+)-CaM functions. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  3. Arterial Pressure Analog.

    ERIC Educational Resources Information Center

    Heusner, A. A.; Tracy, M. L.

    1980-01-01

    Describes a simple hydraulic analog which allows students to explore some physical aspects of the cardiovascular system and provides them with a means to visualize and conceptualize these basic principles. Simulates the behavior of arterial pressure in response to changes in heart rate, stroke volume, arterial compliance, and peripheral…

  4. Pathways of Metabolite-related Damage to A Synthetic p53 Gene Exon 7 Oligonucleotide using Magnetic Enzyme Bioreactor Beads and LC-MS/MS Sequencing.

    PubMed

    Malla, Spundana; Kadimisetty, Karteek; Jiang, Di; Choudhary, Dharamainder; Rusling, James F

    2018-05-11

    Reactive metabolites of environmental chemicals and drugs can cause site-specific damage to p53 tumor suppressor gene in a major pathway for genotoxicity. We report here a high throughput, cell-free, 96-well plate magnetic bead-enzyme system interfaced with LC-MS/MS sequencing to bioactivate test chemicals and identify resulting adduction sites on genes. Bioactivated aflatoxin B1 was reacted with a 32 bp exon 7 fragment of the p53 gene using 8 microsomal cyt P450 enzymes from different organs coated on magnetic beads. All cyt P450s converted aflatoxin B1 to aflatoxin B1-8,9-epoxide that adducts guanine (G) in codon 249, with subsequent depurination to give abasic sites, then strand breaks. This is the first demonstration in a cell-free medium that aflatoxin B1 metabolite selectively causes abasic site formation and strand breaks at codon 249 of the p53 probe, corresponding to the chemical pathway and mutations of p53 in human liver cells and tumors. Molecular modeling supports the view that binding of aflatoxin B1-8,9-epoxide to G in codon 249 precedes the SN2 adduction reaction. Among a range of metabolic enzymes characteristic of different organs, human liver microsomes and cyt P450 3A5 supersomes showed the highest bioactivation rate for p53 exon 7 damage. This method to identify metabolite-related gene damage sites may facilitate predictions of organ-specific cancers for test chemicals via correlations with mutation sites.

  5. 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

  6. Rotanone analogs: method of preparation and use

    DOEpatents

    VanBrocklin, Henry F; O& #x27; Neil, James P; Gibbs, Andrew R; Erathodiyil, Nandanan

    2013-10-08

    The present invention provides rotenone analogs and methods of making and using them. Labeled with single photon and positron emitting isotopes, the rotenone analogs of the present invention are useful in, for example, clinical imaging applications as tracers to measure cardiac blood flow and detect regions of ischemia.

  7. Analogical Instruction in Statistics: Implications for Social Work Educators

    ERIC Educational Resources Information Center

    Thomas, Leela

    2008-01-01

    This paper examines the use of analogies in statistics instruction. Much has been written about the difficulty social work students have with statistics. To address this concern, Glisson and Fischer (1987) called for the use of analogies. Understanding of analogical problem solving has surged in the last few decades with the integration of…

  8. Modern Communication: Exploring Physiological Transmission through Tech-Savvy Analogies

    ERIC Educational Resources Information Center

    Hollabaugh, Christopher R.; Milanick, Mark A.

    2014-01-01

    Analogies are often helpful for students to grasp key physiological concepts; sometimes the technical jargon makes the concept seem more complex than it actually is. In this article the authors provide several analogies for information transfer processes that sometimes confuse students. For an analogy to be useful, of course, it needs to be…

  9. Analogical acts as conceptual strategies in science, engineering and the humanities

    NASA Technical Reports Server (NTRS)

    Winkler, V. M.

    1981-01-01

    The composing models which operate by means of analogy are identified. The importance of analogical acts in the prewriting stage of the composing process is discussed. The relations between analogical acts and concept formation are explored. A basic correspondence between the analogical thinking employed in successful learning and analogical thinking as a composing strategy is discussed. Teaching analogical acts as conceptual strategies for exploring problems and generating the form and content of discourse is presented in support of the contention that writing is a unique mode of learning.

  10. Synthetic Biology: A Unifying View and Review Using Analog Circuits.

    PubMed

    Teo, Jonathan J Y; Woo, Sung Sik; Sarpeshkar, Rahul

    2015-08-01

    We review the field of synthetic biology from an analog circuits and analog computation perspective, focusing on circuits that have been built in living cells. This perspective is well suited to pictorially, symbolically, and quantitatively representing the nonlinear, dynamic, and stochastic (noisy) ordinary and partial differential equations that rigorously describe the molecular circuits of synthetic biology. This perspective enables us to construct a canonical analog circuit schematic that helps unify and review the operation of many fundamental circuits that have been built in synthetic biology at the DNA, RNA, protein, and small-molecule levels over nearly two decades. We review 17 circuits in the literature as particular examples of feedforward and feedback analog circuits that arise from special topological cases of the canonical analog circuit schematic. Digital circuit operation of these circuits represents a special case of saturated analog circuit behavior and is automatically incorporated as well. Many issues that have prevented synthetic biology from scaling are naturally represented in analog circuit schematics. Furthermore, the deep similarity between the Boltzmann thermodynamic equations that describe noisy electronic current flow in subthreshold transistors and noisy molecular flux in biochemical reactions has helped map analog circuit motifs in electronics to analog circuit motifs in cells and vice versa via a `cytomorphic' approach. Thus, a body of knowledge in analog electronic circuit design, analysis, simulation, and implementation may also be useful in the robust and efficient design of molecular circuits in synthetic biology, helping it to scale to more complex circuits in the future.

  11. Hygroscopicity of Early Earth and Titan Laboratory Aerosol Analogs

    NASA Astrophysics Data System (ADS)

    Hasenkopf, C. A.; Beaver, M. R.; Freedman, M. A.; Toon, O. B.; Tolbert, M. A.

    2009-12-01

    We have explored the ability of organic hazes, known to exist in the atmosphere of Titan and postulated to have existed in the Archean Earth atmosphere, to act as cloud condensation nuclei (CCN). These laboratory aerosol analogs are generated via UV-photolysis of early Earth and Titan analog gas mixtures and are designed to mimic the present day atmospheric conditions on Titan and the early Earth atmosphere before the rise of oxygen. Water uptake is observed to occur on the early Earth and Titan aerosol analogs at relative humidities of 80% - 90% via optical growth measurements using cavity ring-down aerosol extinction spectroscopy. We find the optical growth of these aerosols is similar to known slightly-soluble organic acids, such as phthalic and pyromellitic acids. On average, the optical growth of the early Earth analog is slightly larger than the Titan analog. In order to translate our measurements obtained in a subsaturated regime into the CCN ability of these particles, we rely on the hygroscopicity parameter κ, developed by Petters & Kreidenweis (2007). We retrieve κ = 0.17±0.03 and 0.06±0.01 for the early Earth and Titan analogs, respectively. This early Earth analog hygroscopicity value indicates that the aerosol could activate at reasonable water vapor supersaturations. We use previous aerosol mass spectrometry results to correlate the chemical structure of the two types of analog with their hygroscopicity. The hygroscopicity of the early Earth aerosol analog, coupled with the apparent lack of other good CCN during the Archean, helps explain the role of the organic haze in the indirect effect of clouds on the early Earth and indicates that it may have had a significant impact on the hydrological cycle.

  12. Abstract analogical reasoning in high-functioning children with autism spectrum disorders.

    PubMed

    Green, Adam E; Kenworthy, Lauren; Mosner, Maya G; Gallagher, Natalie M; Fearon, Edward W; Balhana, Carlos D; Yerys, Benjamin E

    2014-12-01

    Children with autism spectrum disorders (ASD) exhibit a deficit in spontaneously recognizing abstract similarities that are crucial for generalizing learning to new situations. This may contribute to deficits in the development of appropriate schemas for navigating novel situations, including social interactions. Analogical reasoning is the central cognitive mechanism that enables typically developing children to understand abstract similarities between different situations. Intriguingly, studies of high-functioning children with ASD point to a relative cognitive strength in basic, nonabstract forms of analogical reasoning. If this analogical reasoning ability extends to abstract analogical reasoning (i.e., between superficially dissimilar situations), it may provide a bridge between a cognitive capability and core ASD deficits in areas such as generalization and categorization. This study tested whether preserved analogical reasoning abilities in ASD can be extended to abstract analogical reasoning, using photographs of real-world items and situations. Abstractness of the analogies was determined via a quantitative measure of semantic distance derived from latent semantic analysis. Children with ASD performed as well as typically developing children at identifying abstract analogical similarities when explicitly instructed to apply analogical reasoning. Individual differences in abstract analogical reasoning ability predicted individual differences in a measure of social function in the ASD group. Preliminary analyses indicated that children with ASD, but not typically developing children, showed an effect of age on abstract analogical reasoning. These results provide new evidence that children with ASD are capable of identifying abstract similarities through analogical reasoning, pointing to abstract analogical reasoning as a potential lever for improving generalization skills and social function in ASD. © 2014 International Society for Autism Research, Wiley

  13. Quantum Analog Computing

    NASA Technical Reports Server (NTRS)

    Zak, M.

    1998-01-01

    Quantum analog computing is based upon similarity between mathematical formalism of quantum mechanics and phenomena to be computed. It exploits a dynamical convergence of several competing phenomena to an attractor which can represent an externum of a function, an image, a solution to a system of ODE, or a stochastic process.

  14. Predicting Naming Latencies with an Analogical Model

    ERIC Educational Resources Information Center

    Chandler, Steve

    2008-01-01

    Skousen's (1989, Analogical modeling of language, Kluwer Academic Publishers, Dordrecht) Analogical Model (AM) predicts behavior such as spelling pronunciation by comparing the characteristics of a test item (a given input word) to those of individual exemplars in a data set of previously encountered items. While AM and other exemplar-based models…

  15. Phonological Priming and Orthographic Analogies in Reading.

    ERIC Educational Resources Information Center

    Goswami, Usha

    1990-01-01

    Findings of two experiments involving young children at a reading level of six years to six years, nine months suggest that phonological priming is an insufficient explanation of the analogy effect at the single word level. Phonological priming plays no role in the use of analogies in story reading. (RH)

  16. Triptycene analogs

    NASA Technical Reports Server (NTRS)

    Hua, Duy (Inventor); Perchellet, Jean-Pierre (Inventor)

    2004-01-01

    This invention provides analogs of triptycene which are useful as anticancer drugs, as well as for other uses. The potency of these compounds is in a similar magnitude as daunomycin, a currently used anticancer drug. Each compound of the invention produces one or more desired effects (blocking nucleoside transport, inhibiting nucleic acid or protein syntheses, decreasing the proliferation and viability of cancer cells, inducing DNA fragmentation or retaining their effectiveness against multidrug-resistant tumor cells).

  17. Gravitoelectromagnetic analogy based on tidal tensors

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

    Costa, L. Filipe O.; Herdeiro, Carlos A. R.

    2008-07-15

    We propose a new approach to a physical analogy between general relativity and electromagnetism, based on tidal tensors of both theories. Using this approach we write a covariant form for the gravitational analogues of the Maxwell equations, which makes transparent both the similarities and key differences between the two interactions. The following realizations of the analogy are given. The first one matches linearized gravitational tidal tensors to exact electromagnetic tidal tensors in Minkowski spacetime. The second one matches exact magnetic gravitational tidal tensors for ultrastationary metrics to exact magnetic tidal tensors of electromagnetism in curved spaces. In the third wemore » show that our approach leads to a two-step exact derivation of Papapetrou's equation describing the force exerted on a spinning test particle. Analogous scalar invariants built from tidal tensors of both theories are also discussed.« less

  18. ENGINEERING APPLICATIONS OF ANALOG COMPUTERS

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

    Bryant, L.T.; Janicke, M.J.; Just, L.C.

    1963-10-31

    Six experiments from the fields of reactor engineering, heat transfer, and dynamics are presented to illustrate the engineering applications of analog computers. The steps required for producing the analog solution are shown, as well as complete information for duplicating the solution. Graphical results are provided. The experiments include: deceleration of a reactor control rod, pressure variations through a packed bed, reactor kinetics over many decades with thermal feedback, a vibrating system with two degrees of freedom, temperature distribution in a radiating fin, temperature distribution in an infinite slab considering variable thermal properties, and iodine -xenon buildup in a reactor. (M.C.G.)

  19. Transistor analogs of emergent iono-neuronal dynamics.

    PubMed

    Rachmuth, Guy; Poon, Chi-Sang

    2008-06-01

    Neuromorphic analog metal-oxide-silicon (MOS) transistor circuits promise compact, low-power, and high-speed emulations of iono-neuronal dynamics orders-of-magnitude faster than digital simulation. However, their inherently limited input voltage dynamic range vs power consumption and silicon die area tradeoffs makes them highly sensitive to transistor mismatch due to fabrication inaccuracy, device noise, and other nonidealities. This limitation precludes robust analog very-large-scale-integration (aVLSI) circuits implementation of emergent iono-neuronal dynamics computations beyond simple spiking with limited ion channel dynamics. Here we present versatile neuromorphic analog building-block circuits that afford near-maximum voltage dynamic range operating within the low-power MOS transistor weak-inversion regime which is ideal for aVLSI implementation or implantable biomimetic device applications. The fabricated microchip allowed robust realization of dynamic iono-neuronal computations such as coincidence detection of presynaptic spikes or pre- and postsynaptic activities. As a critical performance benchmark, the high-speed and highly interactive iono-neuronal simulation capability on-chip enabled our prompt discovery of a minimal model of chaotic pacemaker bursting, an emergent iono-neuronal behavior of fundamental biological significance which has hitherto defied experimental testing or computational exploration via conventional digital or analog simulations. These compact and power-efficient transistor analogs of emergent iono-neuronal dynamics open new avenues for next-generation neuromorphic, neuroprosthetic, and brain-machine interface applications.

  20. Analog Building Blocks for Communications Modems.

    DTIC Science & Technology

    1977-01-01

    x*—*- A0-A039 82b ELECTRONIC COMMUNICATIONS INC ST PETERSBURG FLA F/6 9/5 ANALOG BUILDING BLOCKS FOR COMMUNICATIONS MODEMS .(U) JAN 77 B BLACK...F33615-7<t-C-1120 UNCLASSIFIED AFAL-TR-76-29 NL ANALOG BUILDING BLOCKS FOR COMMUNICATIONS MODEMS ELECTRONIC COMMUNICATIONS INC. A SUBSIDIARY OF...Idantltr Or Mac* numb*,; Avionics Building-Block modules Frequency Synthesize* Costas Demodulator Amplifier Modem Frequency Multiplier ’ -^ « TRACT

  1. A MEDL Collection Showcase: A Collection of Hands-on Physical Analog Models and Demonstrations From the Department of Geosciences MEDL at Virginia Tech

    NASA Astrophysics Data System (ADS)

    Glesener, G. B.

    2017-12-01

    The Geosciences Modeling and Educational Demonstrations Laboratory (MEDL) will present a suite of hands-on physical analog models from our curriculum materials collection used to teach about a wide range of geoscience processes. Many of the models will be equipped with Vernier data collection sensors, which visitors will be encouraged to explore on-site. Our goal is to spark interest and discussion around the affordances of these kinds of curriculum materials. Important topics to discuss will include: (1) How can having a collection of hands-on physical analog models be used to effectively produce successful broader impacts activities for research proposals? (2) What kinds of learning outcomes have instructors observed when teaching about temporally and spatially challenging concepts using physical analog models? (3) What does it take for an institution to develop their own MEDL collection? and (4) How can we develop a community of individuals who provide on-the-ground support for instructors who use physical analog models in their classroom.

  2. Mathematical Analogs and the Teaching of Fractions.

    ERIC Educational Resources Information Center

    Charles, Kathy; Nason, Rod; Cooper, Tom

    The literature has noted that some mathematical analogs are more effective than others for the teaching of fractions. This study aimed to evaluate the efficacy of seven mathematical analogs commonly used in the teaching of the partitive quotient fraction construct. A sample of twelve purposively selected Year Three children were presented with…

  3. Young Children's Analogical Reasoning in Science Domains

    ERIC Educational Resources Information Center

    Haglund, Jesper; Jeppsson, Fredrik; Andersson, Johanna

    2012-01-01

    This exploratory study in a classroom setting investigates first graders' (age 7-8 years, N = 25) ability to perform analogical reasoning and create their own analogies for two irreversible natural phenomena: mixing and heat transfer. We found that the children who contributed actively to a full-class discussion were consistently successful at…

  4. Children's Use of Analogy during Collaborative Reasoning

    ERIC Educational Resources Information Center

    Lin, Tzu-Jung; Anderson, Richard C.; Hummel, John E.; Jadallah, May; Miller, Brian W.; Nguyen-Jahiel, Kim; Morris, Joshua A.; Kuo, Li-Jen; Kim, Il-Hee; Wu, Xiaoying; Dong, Ting

    2012-01-01

    This microgenetic study examined social influences on children's development of analogical reasoning during peer-led small-group discussions of stories about controversial issues. A total of 277 analogies were identified among 7,215 child turns for speaking during 54 discussions from 18 discussion groups in 6 fourth-grade classrooms (N = 120; age…

  5. Self-Generated Analogical Models of Respiratory Pathways

    ERIC Educational Resources Information Center

    Lee, Yeung Chung

    2015-01-01

    Self-generated analogical models have emerged recently as alternatives to teacher-supplied analogies and seem to have good potential to promote deep learning and scientific thinking. However, studies of the ways and contexts in which students generate these models are still too limited to allow a fuller appraisal of these models' effectiveness in…

  6. A Mechanical Analogy for the Photoelectric Effect

    ERIC Educational Resources Information Center

    Kovacevic, Milan S.; Djordjevich, Alexandar

    2006-01-01

    Analogy is a potent tool in the teacher's repertoire. It has been particularly well recognized in the teaching of science. However, careful planning is required for its effective application to prevent documented drawbacks when analogies are stretched too far. Befitting the occasion of the World Year of Physics commemorating Albert Einstein's 1905…

  7. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, M.M.; Shoup, T.

    1998-09-15

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

  8. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, M.M.; Shoup, T.

    1998-10-06

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

  9. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, Mark M.; Shoup, Timothy

    1998-09-15

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

  10. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, Mark M.; Shoup, Timothy

    1998-10-06

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

  11. Design of an Insulin Analog with Enhanced Receptor Binding Selectivity

    PubMed Central

    Zhao, Ming; Wan, Zhu-li; Whittaker, Linda; Xu, Bin; Phillips, Nelson B.; Katsoyannis, Panayotis G.; Ismail-Beigi, Faramarz; Whittaker, Jonathan; Weiss, Michael A.

    2009-01-01

    Insulin binds with high affinity to the insulin receptor (IR) and with low affinity to the type 1 insulin-like growth factor (IGF) receptor (IGFR). Such cross-binding, which reflects homologies within the insulin-IGF signaling system, is of clinical interest in relation to the association between hyperinsulinemia and colorectal cancer. Here, we employ nonstandard mutagenesis to design an insulin analog with enhanced affinity for the IR but reduced affinity for the IGFR. Unnatural amino acids were introduced by chemical synthesis at the N- and C-capping positions of a recognition α-helix (residues A1 and A8). These sites adjoin the hormone-receptor interface as indicated by photocross-linking studies. Specificity is enhanced more than 3-fold on the following: (i) substitution of GlyA1 by d-Ala or d-Leu, and (ii) substitution of ThrA8 by diaminobutyric acid (Dab). The crystal structure of [d-AlaA1,DabA8]insulin, as determined within a T6 zinc hexamer to a resolution of 1.35 Å, is essentially identical to that of human insulin. The nonstandard side chains project into solvent at the edge of a conserved receptor-binding surface shared by insulin and IGF-I. Our results demonstrate that modifications at this edge discriminate between IR and IGFR. Because hyperinsulinemia is typically characterized by a 3-fold increase in integrated postprandial insulin concentrations, we envisage that such insulin analogs may facilitate studies of the initiation and progression of cancer in animal models. Future development of clinical analogs lacking significant IGFR cross-binding may enhance the safety of insulin replacement therapy in patients with type 2 diabetes mellitus at increased risk of colorectal cancer. PMID:19773552

  12. Analogical Reasoning in the Engineering Design Process and Technology Education Applications

    ERIC Educational Resources Information Center

    Daugherty, Jenny; Mentzer, Nathan

    2008-01-01

    This synthesis paper discusses the research exploring analogical reasoning, the role of analogies in the engineering design process, and educational applications for analogical reasoning. Researchers have discovered that analogical reasoning is often a fundamental cognitive tool in design problem solving. Regarding the possible role of analogical…

  13. Pyrochlore-rich titanate ceramics for the immobilization of plutonium: redox effects on phase equilibria in cerium- and thorium- substituted analogs

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

    Ryerson, F J; Ebbinghaus, B

    2000-05-25

    Three compositions representing plutonium-free analogs of a proposed Ca-Ti-Gd-Hf-U-PU oxide ceramic for the immobilization of plutonium were equilibrated at 1 atm, 1350 C over a range of oxygen fugacities between air and that equivalent to the iron-wuestite buffer. The cerium analog replaces Pu on a mole-per-mole basic with Ce; the thorium analog replaces Pu with Th. A third material has 10 wt% Al{sub 2}O{sub 3} added to the cerium analog to encourage the formation of a Hf-analog of, CaHfTi{sub 2}O{sub 7}, zirconolite, which is referred to as hafnolite. The predominant phase produced in each formulation under all conditions is pyrochlore,more » A{sub 2}T{sub 2}O{sub 7}, where the T site is filled by Ti, and Ca, the lanthanides, Hf, U and Pu are accommodated on the A-site. Other lanthanide and uranium-bearing phases encountered include brannerite (UTi{sub 2}O{sub 6}), hafnolite (CaHfTi{sub 2}O{sub 7}), perovskite (CaTiO{sub 3}) and a calcium-lanthanide aluminotitanate with nominal stoichiometry (Ca,Ln)Ti{sub 2}Al{sub 9}O{sub 19}, where Ln is a lanthanide. The phase compositions show progressive shifts with decreasing oxygen fugacity. All of the phases observed have previously been identified in titanate-based high-level radioactive waste ceramics and demonstrate the flexibility of these ceramics to variations in processing parameters. The main variation is an increase in the uranium concentrations of pyrochlore and brannerite which must be accommodated by variations in modal abundance. Pyrochlore compositions are consistent with existing spectroscopic data suggesting that uranium is predominantly pentavalent in samples synthesized in air. A simple model based on ideal stoichiometry suggests the U{sup +4}/{Sigma}U varies linearly with log fO{sub 2} and that all of the uranium is quadravalent at the iron-wuestite buffer.« less

  14. The formation of double-strand breaks at multiply damaged sites is driven by the kinetics of excision/incision at base damage in eukaryotic cells

    PubMed Central

    Kozmin, Stanislav G.; Sedletska, Yuliya; Reynaud-Angelin, Anne; Gasparutto, Didier; Sage, Evelyne

    2009-01-01

    It has been stipulated that repair of clustered DNA lesions may be compromised, possibly leading to the formation of double-strand breaks (DSB) and, thus, to deleterious events. Using a variety of model multiply damaged sites (MDS), we investigated parameters that govern the formation of DSB during the processing of MDS. Duplexes carrying MDS were inserted into replicative or integrative vectors, and used to transform yeast Saccharomyces cerevisiae. Formation of DSB was assessed by a relevant plasmid survival assay. Kinetics of excision/incision and DSB formation at MDS was explored using yeast cell extracts. We show that MDS composed of two uracils or abasic sites, were rapidly incised and readily converted into DSB in yeast cells. In marked contrast, none of the MDS carrying opposed oG and hU separated by 3–8 bp gave rise to DSB, despite the fact that some of them contained preexisting single-strand break (a 1-nt gap). Interestingly, the absence of DSB formation in this case correlated with slow excision/incision rates of lesions. We propose that the kinetics of the initial repair steps at MDS is a major parameter that direct towards the conversion of MDS into DSB. Data provides clues to the biological consequences of MDS in eukaryotic cells. PMID:19174565

  15. FOLLITROPIN RECEPTORS CONTAIN CRYPTIC LIGAND BINDING SITES1

    PubMed Central

    Lin, Win; Bernard, Michael P.; Cao, Donghui; Myers, Rebecca V.; Kerrigan, John E.; Moyle, William R.

    2007-01-01

    Human choriogonadotropin (hCG) and follitropin (hFSH) have been shown to contact different regions of the extracellular domains of G-protein coupled lutropin (LHR) and follitropin (FSHR) receptors. We report here that hCG and hFSH analogs interact with an FSHR/LHR chimera having only two unique LHR residues similar to the manners in which they dock with LHR and FSHR, respectively. This shows that although the FSHR does not normally bind hCG, it contains a cryptic lutropin binding site that has the potential to recognize hCG in a manner similar to the LHR. The presence of this cryptic site may explain why equine lutropins bind many mammalian FSHR and why mutations in the transmembrane domain distant from the extracellular domain enable the FSHR to bind hCG. The leucine-rich repeat domain (LRD) of the FSHR also appears to contain a cryptic FSH binding site that is obscured by other parts of the extracellular domain. This will explain why contacts seen in crystals of hFSH complexed with an LRD fragment of the human FSHR are hard to reconcile with the abilities of FSH analogs to interact with membrane G-protein coupled FSHR. We speculate that cryptic lutropin binding sites in the FSHR, which are also likely to be present in thyrotropin receptors (TSHR), permit the physiological regulation of ligand binding specificity. Cryptic FSH binding sites in the LRD may enable alternate spliced forms of the FSHR to interact with FSH. PMID:17059863

  16. A Study on Analogies Used in New Ninth Grade Biology Textbook

    ERIC Educational Resources Information Center

    Dikmenli, Musa

    2015-01-01

    Analogies have many advantages for students such as concretizing abstract concepts and enabling motivation. Analogies are frequently used in textbooks. Research shows that the analogies in textbooks are not used based on certain directives and sometimes lead to misconceptions for students. Therefore, analysing the analogies in textbooks on several…

  17. Analog hardware for learning neural networks

    NASA Technical Reports Server (NTRS)

    Eberhardt, Silvio P. (Inventor)

    1991-01-01

    This is a recurrent or feedforward analog neural network processor having a multi-level neuron array and a synaptic matrix for storing weighted analog values of synaptic connection strengths which is characterized by temporarily changing one connection strength at a time to determine its effect on system output relative to the desired target. That connection strength is then adjusted based on the effect, whereby the processor is taught the correct response to training examples connection by connection.

  18. On Lovelock analogs of the Riemann tensor

    NASA Astrophysics Data System (ADS)

    Camanho, Xián O.; Dadhich, Naresh

    2016-03-01

    It is possible to define an analog of the Riemann tensor for Nth order Lovelock gravity, its characterizing property being that the trace of its Bianchi derivative yields the corresponding analog of the Einstein tensor. Interestingly there exist two parallel but distinct such analogs and the main purpose of this note is to reconcile both formulations. In addition we will introduce a simple tensor identity and use it to show that any pure Lovelock vacuum in odd d=2N+1 dimensions is Lovelock flat, i.e. any vacuum solution of the theory has vanishing Lovelock-Riemann tensor. Further, in the presence of cosmological constant it is the Lovelock-Weyl tensor that vanishes.

  19. Mutagenicity, Stable DNA Adducts, and Abasic Sites Induced in Salmonella by Phananthro[3,4-b]- and Phenanthro[4,3-b]thiophenes, Sulfur Analogs of Benzo[c]phenanthrene

    EPA Science Inventory

    Sulfur-containing polycyclic aromatic hydrocarbons (thia-PAHs or thiaarenes) are common constituents of air pollution and cigarette smoke, yet little is known of the biological significance of exposure to these compounds. Some are mutagenic and carcinogenic, but only a few have ...

  20. Combining H/D exchange mass spectroscopy and computational docking reveals extended DNA-binding surface on uracil-DNA glycosylase

    PubMed Central

    Roberts, Victoria A.; Pique, Michael E.; Hsu, Simon; Li, Sheng; Slupphaug, Geir; Rambo, Robert P.; Jamison, Jonathan W.; Liu, Tong; Lee, Jun H.; Tainer, John A.; Ten Eyck, Lynn F.; Woods, Virgil L.

    2012-01-01

    X-ray crystallography provides excellent structural data on protein–DNA interfaces, but crystallographic complexes typically contain only small fragments of large DNA molecules. We present a new approach that can use longer DNA substrates and reveal new protein–DNA interactions even in extensively studied systems. Our approach combines rigid-body computational docking with hydrogen/deuterium exchange mass spectrometry (DXMS). DXMS identifies solvent-exposed protein surfaces; docking is used to create a 3-dimensional model of the protein–DNA interaction. We investigated the enzyme uracil-DNA glycosylase (UNG), which detects and cleaves uracil from DNA. UNG was incubated with a 30 bp DNA fragment containing a single uracil, giving the complex with the abasic DNA product. Compared with free UNG, the UNG–DNA complex showed increased solvent protection at the UNG active site and at two regions outside the active site: residues 210–220 and 251–264. Computational docking also identified these two DNA-binding surfaces, but neither shows DNA contact in UNG–DNA crystallographic structures. Our results can be explained by separation of the two DNA strands on one side of the active site. These non-sequence-specific DNA-binding surfaces may aid local uracil search, contribute to binding the abasic DNA product and help present the DNA product to APE-1, the next enzyme on the DNA-repair pathway. PMID:22492624

  1. The Discourse on Printed and Electronic Books: Analogies, Oppositions, and Perspectives

    ERIC Educational Resources Information Center

    Velagic, Zoran

    2014-01-01

    Introduction: The point of departure for this paper is the twofold analogy (analogy of content, analogy of medium) between printed and electronic books, the aim being to draw attention to the usual perception of their capacities and relationships, to provide a rather detailed analysis of the outcome and sustainability of such analogies and…

  2. Agonist properties of a stable hexapeptide analog of neurotensin, N alpha MeArg-Lys-Pro-Trp-tLeu-Leu (NT1).

    PubMed

    Akunne, H C; Demattos, S B; Whetzel, S Z; Wustrow, D J; Davis, D M; Wise, L D; Cody, W L; Pugsley, T A; Heffner, T G

    1995-04-18

    The major signal transduction pathway for neurotensin (NT) receptors is the G-protein-dependent stimulation of phospholipase C, leading to the mobilization of intracellular free Ca2+ ([Ca2+]i) and the stimulation of cyclic GMP. We investigated the functional actions of an analog of NT(8-13), N alpha MeArg-Lys-Pro-Trp-tLeu-Leu (NT1), and other NT related analogs by quantitative measurement of the cytosolic free Ca2+ concentration in HT-29 (human colonic adenocarcinoma) cells using the Ca(2+)-sensitive dye fura-2/AM and by effects on cyclic GMP levels in rat cerebellar slices. The NT receptor binding affinities for these analogs to HT-29 cell membranes and newborn (10-day-old) mouse brain membranes were also investigated. Data obtained from HT-29 cell and mouse brain membrane preparations showed saturable single high-affinity sites and binding densities (Bmax) of 130.2 and 87.5 fmol/mg protein, respectively. The respective KD values were 0.47 and 0.39 nM, and the Hill coefficients were 0.99 and 0.92. The low-affinity levocabastine-sensitive site was not present (K1 > 10,000) in either membrane preparation. Although the correlation of binding between HT-29 cell membranes and mouse brain membranes was quite significant (r = 0.92), some of the reference agents had lower binding affinities in the HT-29 cell membranes. The metabolically stable compound NT1 plus other NT analogs and related peptides [NT, NT(8-13), xenopsin, neuromedin N, NT(9-13), kinetensin and (D-Trp11)-NT] increased intracellular Ca2+ levels in HT-29 cells, indicating NT receptor agonist properties. The effect of NT1 in mobilizing [Ca2+]i blocked by SR 48692, a non-peptide NT antagonist. Receptor binding affinities of NT analogs to HT-29 cell membranes were positively correlated with potencies for mobilizing intracellular calcium in the same cells. In addition, NT1 increased cyclic GMP levels in rat cerebellar slices, confirming the latter findings of its NT agonist action. These results substantiate

  3. Carvedilol analog modulates both basal and stimulated sinoatrial node automaticity.

    PubMed

    Shinohara, Tetsuji; Kim, Daehyeok; Joung, Boyoung; Maruyama, Mitsunori; Vembaiyan, Kannan; Back, Thomas G; Wayne Chen, S R; Chen, Peng-Sheng; Lin, Shien-Fong

    2014-05-01

    The membrane voltage clock and calcium (Ca(2+)) clock jointly regulate sinoatrial node (SAN) automaticity. VK-II-36 is a novel carvedilol analog that suppresses sarcoplasmic reticulum (SR) Ca(2+) release but does not block the β-receptor. The effect of VK-II-36 on SAN function remains unclear. The purpose of this study was to evaluate whether VK-II-36 can influence SAN automaticity by inhibiting the Ca(2+) clock. We simultaneously mapped intracellular Ca(2+) and membrane potential in 24 isolated canine right atriums using previously described criteria of the timing of late diastolic intracellular Ca elevation (LDCAE) relative to the action potential upstroke to detect the Ca(2+) clock. Pharmacological interventions with isoproterenol (ISO), ryanodine, caffeine, and VK-II-36 were performed after baseline recordings. VK-II-36 caused sinus rate downregulation and reduced LDCAE in the pacemaking site under basal conditions (P < 0.01). ISO induced an upward shift of the pacemaking site in SAN and augmented LDCAE in the pacemaking site. ISO also significantly and dose-dependently increased the sinus rate. The treatment of VK-II-36 (30 μmol/l) abolished both the ISO-induced shift of the pacemaking site and augmentation of LDCAE (P < 0.01), and it suppressed the ISO-induced increase in sinus rate (P = 0.02). Our results suggest that the sinus rate may be partly controlled by the Ca(2+) clock via SR Ca(2+) release during β-adrenergic stimulation.

  4. Characterization of (/sup 3/H)forskolin binding sites in the iris-ciliary body of the albino rabbit

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

    Goldman, M.E.; Mallorga, P.; Pettibone, D.J.

    1988-01-01

    (/sup 3/H)forskolin binding sites were identified using membranes prepared from the iris-ciliary body of adult, albino rabbits. Scatchard analysis of saturation binding experiments demonstrated that (/sup 3/H)forskolin bound to a single population of high affinity sites. The K/sub d/ and B/sub max/ values were 8.7 +- 0.9 nM and 119.0 +- 30.9 fmolmg prot. using membranes prepared from frozen tissue and 17.0 +- 6.2 nM and 184.4 +- 47.2 fmolmg prot. using fresh tissue. The binding of (/sup 3/H)forskolin was magnesium-dependent. The B/sub max/ was enhanced by sodium fluoride and Gpp(NH)p, a nonhydrolyzable guanine nucleotide analog. Forskolin was the mostmore » potent inhibitor of (/sup 3/H)forskolin binding; two commercially-available analogs were weaker inhibitors. In an adenylate cyclase assay, there was the same rank order of potency to enhance enzyme activity. Based upon binding affinities, magnesium-dependence, sensitivity to sodium fluoride and Gpp(NH)p, rank order of potencies of analogs and correlation of binding with adenylate cyclase activity, these studies suggest that the (/sup 3/H)forskolin binding site in the iris-ciliary body is similar to the binding site in other tissues« less

  5. Nitrate analogs as attractants for soybean cyst nematode.

    PubMed

    Hosoi, Akito; Katsuyama, Tsutomu; Sasaki, Yasuyuki; Kondo, Tatsuhiko; Yajima, Shunsuke; Ito, Shinsaku

    2017-08-01

    Soybean cyst nematode (SCN) Heterodera glycines Ichinohe, a plant parasite, is one of the most serious pests of soybean. In this paper, we report that SCN is attracted to nitrate and its analogs. We performed attraction assays to screen for novel attractants for SCN and found that nitrates were attractants for SCN and SCN recognized nitrate gradients. However, attraction of SCN to nitrates was not observed on agar containing nitrate. To further elucidate the attraction mechanism in SCN, we performed attraction assays using nitrate analogs ([Formula: see text], [Formula: see text], [Formula: see text]). SCN was attracted to all nitrate analogs; however, attraction of SCN to nitrate analogs was not observed on agar containing nitrate. In contrast, SCN was attracted to azuki root, irrespective of presence or absence of nitrate in agar media. Our results suggest that the attraction mechanisms differ between plant-derived attractant and nitrate.

  6. Sulfur Mineralogy at the Mars Phoenix Landing Site

    NASA Technical Reports Server (NTRS)

    Ming, Douglas W.; Morris, R.V.; Golden, D.C.; Sutter, B.; Clark, B.C.; Boynton, W.V.; Hecht, M.H.; Kounaves, S.P.

    2009-01-01

    The Mars Phoenix Scout mission landed at the northernmost location (approx.68deg N) of any lander or rover on the martian surface. This paper compares the S mineralogy at the Phoenix landing site with S mineralogy of soils studied by previous Mars landers. S-bearing phases were not directly detected by the payload onboard the Phoenix spacecraft. Our objective is to derive the possible mineralogy of S-bearing phases at the Phoenix landing site based upon Phoenix measurements in combination with orbital measurements, terrestrial analog and Martian meteorite studies, and telescopic observations.

  7. NASA's Analog Missions: Driving Exploration Through Innovative Testing

    NASA Technical Reports Server (NTRS)

    Reagan, Marcum L.; Janoiko, Barbara A.; Parker, Michele L.; Johnson, James E.; Chappell, Steven P.; Abercromby, Andrew F.

    2012-01-01

    Human exploration beyond low-Earth orbit (LEO) will require a unique collection of advanced, innovative technologies and the precise execution of complex and challenging operational concepts. One tool we in the Analog Missions Project at the National Aeronautics and Space Administration (NASA) utilize to validate exploration system architecture concepts and conduct technology demonstrations, while gaining a deeper understanding of system-wide technical and operational challenges, is our analog missions. Analog missions are multi-disciplinary activities that test multiple features of future spaceflight missions in an integrated fashion to gain a deeper understanding of system-level interactions and integrated operations. These missions frequently occur in remote and extreme environments that are representative in one or more ways to that of future spaceflight destinations. They allow us to test robotics, vehicle prototypes, habitats, communications systems, in-situ resource utilization, and human performance as it relates to these technologies. And they allow us to validate architectural concepts, conduct technology demonstrations, and gain a deeper understanding of system-wide technical and operational challenges needed to support crewed missions beyond LEO. As NASA develops a capability driven architecture for transporting crew to a variety of space environments, including the moon, near-Earth asteroids (NEA), Mars, and other destinations, it will use its analog missions to gather requirements and develop the technologies that are necessary to ensure successful human exploration beyond LEO. Currently, there are four analog mission platforms: Research and Technology Studies (RATS), NASA s Extreme Environment Mission Operations (NEEMO), In-Situ Resource Utilization (ISRU), and International Space Station (ISS) Test bed for Analog Research (ISTAR).

  8. User-friendly design approach for analog layout design

    NASA Astrophysics Data System (ADS)

    Li, Yongfu; Lee, Zhao Chuan; Tripathi, Vikas; Perez, Valerio; Ong, Yoong Seang; Hui, Chiu Wing

    2017-03-01

    Analog circuits are sensitives to the changes in the layout environment conditions, manufacturing processes, and variations. This paper presents analog verification flow with five types of analogfocused layout constraint checks to assist engineers in identifying any potential device mismatch and layout drawing mistakes. Compared to several solutions, our approach only requires layout design, which is sufficient to recognize all the matched devices. Our approach simplifies the data preparation and allows seamless integration into the layout environment with minimum disruption to the custom layout flow. Our user-friendly analog verification flow provides the engineer with more confident with their layouts quality.

  9. Synthesis and Biological Evaluation of Neopeltolide and Analogs

    PubMed Central

    Cui, Yubo; Balachandran, Raghavan

    2012-01-01

    The synthesis of neopeltolide analogs that contain variations in the oxazole-containing side chain and in the macrolide core are reported along with the GI50 values for these compounds against MCF7, HCT-116, and p53 knockout HCT-116 cell lines. Although biological activity is sensitive to changes in the macrocycle and the side chain, several analogs displayed GI50 values of <25 nM. Neopeltolide and several of the more potent analogs were significantly less potent against p53 knockout cells, suggesting that p53 plays an auxiliary role in the activity of these compounds. PMID:22329423

  10. Spanish Velar-Insertion and Analogy: A Usage-Based Diachronic Analysis

    ERIC Educational Resources Information Center

    Fondow, Steven Richard

    2010-01-01

    The theory of Analogical and Exemplar Modeling (AEM) suggests renewed discussion of the formalization of analogy and its possible incorporation in linguistic theory. AEM is a usage-based model founded upon Exemplar Modeling (Bybee 2007, Pierrehumbert 2001) that utilizes several principles of the Analogical Modeling of Language (Skousen 1992, 1995,…

  11. Multilateral Research Opportunities in Ground Analogs

    NASA Technical Reports Server (NTRS)

    Corbin, Barbara J.

    2015-01-01

    The global economy forces many nations to consider their national investments and make difficult decisions regarding their investment in future exploration. International collaboration provides an opportunity to leverage other nations' investments to meet common goals. The Humans In Space Community shares a common goal to enable safe, reliable, and productive human space exploration within and beyond Low Earth Orbit. Meeting this goal requires efficient use of limited resources and International capabilities. The International Space Station (ISS) is our primary platform to conduct microgravity research targeted at reducing human health and performance risks for exploration missions. Access to ISS resources, however, is becoming more and more constrained and will only be available through 2020 or 2024. NASA's Human Research Program (HRP) is actively pursuing methods to effectively utilize the ISS and appropriate ground analogs to understand and mitigate human health and performance risks prior to embarking on human exploration of deep space destinations. HRP developed a plan to use ground analogs of increasing fidelity to address questions related to exploration missions and is inviting International participation in these planned campaigns. Using established working groups and multilateral panels, the HRP is working with multiple Space Agencies to invite International participation in a series of 30- day missions that HRP will conduct in the US owned and operated Human Exploration Research Analog (HERA) during 2016. In addition, the HRP is negotiating access to Antarctic stations (both US and non-US), the German :envihab and Russian NEK facilities. These facilities provide unique capabilities to address critical research questions requiring longer duration simulation or isolation. We are negotiating release of international research opportunities to ensure a multilateral approach to future analog research campaigns, hoping to begin multilateral campaigns in the

  12. Digital computer technique for setup and checkout of an analog computer

    NASA Technical Reports Server (NTRS)

    Ambaruch, R.

    1968-01-01

    Computer program technique, called Analog Computer Check-Out Routine Digitally /ACCORD/, generates complete setup and checkout data for an analog computer. In addition, the correctness of the analog program implementation is validated.

  13. SSERVI Analog Regolith Simulant Testbed Facility

    NASA Astrophysics Data System (ADS)

    Minafra, J.; Schmidt, G. K.

    2016-12-01

    SSERVI's goals include supporting planetary researchers within NASA, other government agencies; private sector and hardware developers; competitors in focused prize design competitions; and academic sector researchers. The SSERVI Analog Regolith Simulant Testbed provides opportunities for research scientists and engineers to study the effects of regolith analog testbed research in the planetary exploration field. This capability is essential to help to understand the basic effects of continued long-term exposure to a simulated analog test environment. The current facility houses approximately eight tons of JSC-1A lunar regolith simulant in a test bin consisting of a 4 meter by 4 meter area. SSERVI provides a bridge between several groups, joining together researchers from: 1) scientific and exploration communities, 2) multiple disciplines across a wide range of planetary sciences, and 3) domestic and international communities and partnerships. This testbed provides a means of consolidating the tasks of acquisition, storage and safety mitigation in handling large quantities of regolith simulant Facility hardware and environment testing scenarios include, but are not limited to the following; Lunar surface mobility, Dust exposure and mitigation, Regolith handling and excavation, Solar-like illumination, Lunar surface compaction profile, Lofted dust, Mechanical properties of lunar regolith, and Surface features (i.e. grades and rocks) Numerous benefits vary from easy access to a controlled analog regolith simulant testbed, and planetary exploration activities at NASA Research Park, to academia and expanded commercial opportunities in California's Silicon Valley, as well as public outreach and education opportunities.

  14. Neuroscientific Insights into the Development of Analogical Reasoning

    ERIC Educational Resources Information Center

    Whitaker, Kirstie J.; Vendetti, Michael S.; Wendelken, Carter; Bunge, Silvia A.

    2018-01-01

    Analogical reasoning, or the ability to find correspondences between entities based on shared relationships, supports knowledge acquisition. As such, the development of this ability during childhood is thought to promote learning. Here, we sought to better understand the mechanisms by which analogical reasoning about semantic relations improves…

  15. Cross-Domain Analogies as Relating Derived Relations among Two Separate Relational Networks

    PubMed Central

    Ruiz, Francisco J; Luciano, Carmen

    2011-01-01

    Contemporary behavior analytic research is making headway in analyzing analogy as the establishment of a relation of coordination among common types of trained or derived relations. Previous studies have been focused on within-domain analogy. The current study expands previous research by analyzing cross-domain analogy as relating relations among separate relational networks and by correlating participants' performance with a standard measure of analogical reasoning. In two experiments, adult participants first completed general intelligence and analogical reasoning tests. Subsequently, they were exposed to a computerized conditional discrimination training procedure designed to create two relational networks, each consisting of two 3-member equivalence classes. The critical test was a two-part analogical test in which participants had to relate combinatorial relations of coordination and distinction between the two relational networks. In Experiment 1, combinatorial relations for each network were individually tested prior to analogical testing, but in Experiment 2 they were not. Across both experiments, 65% of participants passed the analogical test on the first attempt. Moreover, results from the training procedure were strongly correlated with the standard measure of analogical reasoning. PMID:21547072

  16. Microbial diversity and iron oxidation at Okuoku-hachikurou Onsen, a Japanese hot spring analog of Precambrian iron formations.

    PubMed

    Ward, L M; Idei, A; Terajima, S; Kakegawa, T; Fischer, W W; McGlynn, S E

    2017-11-01

    Banded iron formations (BIFs) are rock deposits common in the Archean and Paleoproterozoic (and regionally Neoproterozoic) sedimentary successions. Multiple hypotheses for their deposition exist, principally invoking the precipitation of iron via the metabolic activities of oxygenic, photoferrotrophic, and/or aerobic iron-oxidizing bacteria. Some isolated environments support chemistry and mineralogy analogous to processes involved in BIF deposition, and their study can aid in untangling the factors that lead to iron precipitation. One such process analog system occurs at Okuoku-hachikurou (OHK) Onsen in Akita Prefecture, Japan. OHK is an iron- and CO 2 -rich, circumneutral hot spring that produces a range of precipitated mineral textures containing fine laminae of aragonite and iron oxides that resemble BIF fabrics. Here, we have performed 16S rRNA gene amplicon sequencing of microbial communities across the range of microenvironments in OHK to describe the microbial diversity present and to gain insight into the cycling of iron, oxygen, and carbon in this ecosystem. These analyses suggest that productivity at OHK is based on aerobic iron-oxidizing Gallionellaceae. In contrast to other BIF analog sites, Cyanobacteria, anoxygenic phototrophs, and iron-reducing micro-organisms are present at only low abundances. These observations support a hypothesis where low growth yields and the high stoichiometry of iron oxidized per carbon fixed by aerobic iron-oxidizing chemoautotrophs like Gallionellaceae result in accumulation of iron oxide phases without stoichiometric buildup of organic matter. This system supports little dissimilatory iron reduction, further setting OHK apart from other process analog sites where iron oxidation is primarily driven by phototrophic organisms. This positions OHK as a study area where the controls on primary productivity in iron-rich environments can be further elucidated. When compared with geological data, the metabolisms and mineralogy at

  17. ANALOG: a program for estimating paleoclimate parameters using the method of modern analogs

    USGS Publications Warehouse

    Schweitzer, Peter N.

    1994-01-01

    Beginning in the 1970s with CLIMAP, paleoclimatologists have been trying to derive quantitative estimates of climatic parameters from the sedimentary record. In general the procedure is to observe the modern distribution of some component of surface sediment that depends on climate, find an empirical relationship between climate and the character of sediments, then extrapolate past climate by studying older sediments in the same way. Initially the empirical relationship between climate and components of the sediment was determined using a multiple regression technique (Imbrie and Kipp, 1971). In these studies sea-floor sediments were examined to determine the percentage of various species of planktonic foraminifera present in them. Supposing that the distribution of foraminiferal assemblages depended strongly on the extremes of annual sea-surface temperature (SST), the foraminiferal assemblages (refined through use of varimax factor analysis) were regressed against the average SST during the coolest and warmest months of the year. The result was a set of transfer functions, equations that could be used to estimate cool and warm SST from the faunal composition of a sediment sample. Assuming that the ecological preference of the species had remained constant throughout the last several hundred thousand years, these transfer functions could be used to estimate SSTs during much of the late Pleistocene. Hutson (1980) and Overpeck, Webb, and Prentice (1985) proposed an alternative approach to estimating paleoclimatic parameters. Their 'method of modern analogs' revolved not around the existence of a few climatically-sensitive faunal assemblages but rather on the expectation that similar climatic regimes should foster similar faunal and floral assemblages. From a large pool of modern samples, those few are selected whose faunal compositions are most similar to a given fossil sample. Paleoclimate estimates are derived using the climatic character of only the most similar

  18. Workshop on Geology of the Apollo 17 Landing Site

    NASA Technical Reports Server (NTRS)

    Ryder, G. (Editor); Schmitt, H. H. (Editor); Spudis, P. D. (Editor)

    1992-01-01

    The topics covered include the following: petrology, lithology, lunar rocks, lunar soil, geochemistry, lunar geology, lunar resources, oxygen production, ilmenite, volcanism, highlands, lunar maria, massifs, impact melts, breccias, lunar crust, Taurus-Littrow, minerals, site selection, regolith, glasses, geomorphology, basalts, tectonics, planetary evolution, anorthosite, titanium oxides, chemical composition, and the Sudbury-Serenitatis analogy.

  19. NMR Structural Studies of Antimicrobial Peptides: LPcin Analogs.

    PubMed

    Jeong, Ji-Ho; Kim, Ji-Sun; Choi, Sung-Sub; Kim, Yongae

    2016-01-19

    Lactophoricin (LPcin), a component of proteose peptone (113-135) isolated from bovine milk, is a cationic amphipathic antimicrobial peptide consisting of 23 amino acids. We designed a series of N- or C-terminal truncated variants, mutated analogs, and truncated mutated analogs using peptide-engineering techniques. Then, we selected three LPcin analogs of LPcin-C8 (LPcin-YK1), LPcin-T2WT6W (LPcin-YK2), and LPcin-T2WT6W-C8 (LPcin-YK3), which may have better antimicrobial activities than LPcin, and successfully expressed them in E. coli with high yield. We elucidated the 3D structures and topologies of the three LPcin analogs in membrane environments by conducting NMR structural studies. We investigated the purity of the LPcin analogs and the α-helical secondary structures by performing (1)H-(15)N 2D HSQC and HMQC-NOESY liquid-state NMR spectroscopy using protein-containing micelle samples. We measured the 3D structures and tilt angles in membranes by conducting (15)N 1D and 2D (1)H-(15)N SAMMY type solid-state NMR spectroscopy with an 800 MHz in-house-built (1)H-(15)N double-resonance solid-state NMR probe with a strip-shield coil, using protein-containing large bicelle samples aligned and confirmed by molecular-dynamics simulations. The three LPcin analogs were found to be curved α-helical structures, with tilt angles of 55-75° for normal membrane bilayers, and their enhanced activities may be correlated with these topologies. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Aseptically Sampled Organics in Subsurface Rocks From the Mars Analog Rio Tinto Experiment: An Analog For The Search for Deep Subsurface Life on Mars.}

    NASA Astrophysics Data System (ADS)

    Bonaccorsi, R.; Stoker, C. R.

    2005-12-01

    The subsurface is the key environment for searching for life on planets lacking surface life. Subsurface ecosystems are of great relevance to astrobiology including the search for past/present life on Mars. The surface of Mars has conditions preventing current life but the subsurface might preserve organics and even host some life [1]. The Mars-Analog-Rio-Tinto-Experiment (MARTE) is performing a simulation of a Mars drilling experiment. This comprises conventional and robotic drilling of cores in a volcanically-hosted-massive-pyrite deposit [2] from the Iberian Pyritic Belt (IBP) and life detection experiments applying anti-contamination protocols (e.g., ATP Luminometry assay). The RT is considered an important analog of the Sinus Meridiani site on Mars and an ideal model analog for a deep subsurface Martian environment. Former results from MARTE suggest the existence of a relatively complex subsurface life including aerobic and anaerobic chemoautotrophs and strict anaerobic methanogens sustained by Fe and S minerals in anoxic conditions. A key requirement for the analysis of a subsurface sample on Mars is a set of simple tests that can help determine if the sample contains organic material of biological origin, and its potential for retaining definitive biosignatures. We report here on the presence of bulk organic matter Corg (0.03-0.05 Wt%), and Ntot (0.01-0.04 Wt%) and amount of measured ATP (Lightning MVP, Biocontrol) in weathered rocks (tuffs, gossan, pyrite stockwork from Borehole #8; >166m). This provides key insight on the type of trophic system sustaining the subsurface biosphere (i.e., heterotrophs vs. autotrophs) at RT. ATP data (Relative-Luminosity-Units, RLU) provide information on possible contamination and distribution of viable biomass with core depth (BH#8, and BH#7, ~3m). Avg. 153 RLU, i.e., surface vs. center of core, suggest that cleaness/sterility can be maintained when using a simple sterile protocol under field conditions. Results from this

  1. Examining the cognitive demands of analogy instructions compared to explicit instructions.

    PubMed

    Tse, Choi Yeung Andy; Wong, Andus; Whitehill, Tara; Ma, Estella; Masters, Rich

    2016-10-01

    In many learning domains, instructions are presented explicitly despite high cognitive demands associated with their processing. This study examined cognitive demands imposed on working memory by different types of instruction to speak with maximum pitch variation: visual analogy, verbal analogy and explicit verbal instruction. Forty participants were asked to memorise a set of 16 visual and verbal stimuli while reading aloud a Cantonese paragraph with maximum pitch variation. Instructions about how to achieve maximum pitch variation were presented via visual analogy, verbal analogy, explicit rules or no instruction. Pitch variation was assessed off-line, using standard deviation of fundamental frequency. Immediately after reading, participants recalled as many stimuli as possible. Analogy instructions resulted in significantly increased pitch variation compared to explicit instructions or no instructions. Explicit instructions resulted in poorest recall of stimuli. Visual analogy instructions resulted in significantly poorer recall of visual stimuli than verbal stimuli. The findings suggest that non-propositional instructions presented via analogy may be less cognitively demanding than instructions that are presented explicitly. Processing analogy instructions that are presented as a visual representation is likely to load primarily visuospatial components of working memory rather than phonological components. The findings are discussed with reference to speech therapy and human cognition.

  2. The Effectiveness of Teaching Science with Pictorial Analogies.

    ERIC Educational Resources Information Center

    Lin, Huann-shyang; And Others

    1996-01-01

    This study uses a conceptual problem-solving test to investigate the effect of a series of pictorial analogies on the concepts of density, pressure, and atmospheric pressure in Year Eight classrooms. Findings indicate that students taught with the pictorial analogies scored significantly higher than their counterparts. Low achievers were the most…

  3. Substrate mimicry: HIV-1 reverse transcriptase recognizes 6-modified-3′-azido-2′,3′-dideoxyguanosine-5′-triphosphates as adenosine analogs

    PubMed Central

    Herman, Brian D.; Schinazi, Raymond F.; Zhang, Hong-wang; Nettles, James H.; Stanton, Richard; Detorio, Mervi; Obikhod, Aleksandr; Pradère, Ugo; Coats, Steven J.; Mellors, John W.; Sluis-Cremer, Nicolas

    2012-01-01

    β-D-3′-Azido-2′,3′-dideoxyguanosine (3′-azido-ddG) is a potent inhibitor of HIV-1 replication with a superior resistance profile to zidovudine. Recently, we identified five novel 6-modified-3′-azido-ddG analogs that exhibit similar or superior anti-HIV-1 activity compared to 3′-azido-ddG in primary cells. To gain insight into their structure–activity–resistance relationships, we synthesized their triphosphate (TP) forms and assessed their ability to inhibit HIV-1 reverse transcriptase (RT). Steady-state and pre-steady-state kinetic experiments show that the 6-modified-3′-azido-ddGTP analogs act as adenosine rather than guanosine mimetics in DNA synthesis reactions. The order of potency of the TP analogs against wild-type RT was: 3′-azido-2,6-diaminopurine >3′-azido-6-chloropurine; 3′-azido-6-N-allylaminopurine > 2-amino-6-N,N-dimethylaminopurine; 2-amino-6-methoxypurine. Molecular modeling studies reveal unique hydrogen-bonding interactions between the nucleotide analogs and the template thymine base in the active site of RT. Surprisingly, the structure–activity relationship of the analogs differed in HIV-1 RT ATP-mediated excision assays of their monophosphate forms, suggesting that it may be possible to rationally design a modified base analog that is efficiently incorporated by RT but serves as a poor substrate for ATP-mediated excision reactions. Overall, these studies identify a promising strategy to design novel nucleoside analogs that exert profound antiviral activity against both WT and drug-resistant HIV-1. PMID:21914723

  4. A dark business, full of shadows: analogy and theology in William Harvey.

    PubMed

    Goldberg, Benjamin

    2013-09-01

    In a short work called De conceptione appended to the end of his Exercitationes de generatione animalium (1651), William Harvey developed a rather strange analogy. To explain how such marvelous productions as living beings were generated from the rather inauspicious ingredients of animal reproduction, Harvey argued that conception in the womb was like conception in the brain. It was mostly rejected at the time; it now seems a ludicrous theory based upon homonymy. However, this analogy offers insight into the structure and function of analogies in early modern natural philosophy. In this essay I hope to not only describe the complex nature of Harvey's analogy, but also offer a novel interpretation of his use of analogical reasoning, substantially revising the account offered by Guido Giglioni (1993). I discuss two points of conceptual change and negotiation in connection with Harvey's analogy, understanding it as both a confrontation between the border of the natural and the supernatural, as well as a moment in the history of psychology. My interpretation touches upon a number of important aspects, including why the analogy was rejected, how Harvey systematically deployed analogies according to his notions of natural philosophical method, how the analogy fits into contemporary discussions of analogies in science, and finally, how the analogy must be seen in the context of changing Renaissance notions of the science of the soul, ultimately confronting the problem of how to understand final causality in Aristotelian science. In connection with the last, I conclude the essay by turning to how Harvey embeds the analogy within a natural theological cosmology. Copyright © 2013. Published by Elsevier Ltd.

  5. Overview of the Human Exploration Research Analog (HERA)

    NASA Technical Reports Server (NTRS)

    Neigut, J.

    2015-01-01

    In 2013, the Human Research Program at NASA began developing a new confinement analog specifically for conducting research to investigate the effects of confinement on the human system. The HERA (Human Exploration Research Analog) habitat has been used for both 7 and 14 day missions to date to examine and mitigate exploration risks to enable safe, reliable and productive human space exploration. This presentation will describe how the Flight Analogs Project developed the HERA facility and the infrastructure to suit investigator requirements for confinement research and in the process developed a new approach to analog utilization and a new state of the art analog facility. Details regarding HERA operations will be discussed including specifics on the mission simulation utilized for the current 14-day campaign, the specifics of the facility (total volume, overall size, hardware), and the capabilities available to researchers. The overall operational philosophy, mission fidelity including timeline, schedule pressures and cadence, and development and implementation of mission stressors will be presented. Research conducted to date in the HERA has addressed risks associated with behavioral health and performance, human physiology, as well as human factors. This presentation will conclude with a discussion of future research plans for the HERA, including infrastructure improvements and additional research capabilities planned for the upcoming 30-day missions in 2016.

  6. Evaluation of Different Oligonucleotide Base Substitutions at CpG Binding sites in Multiplex Bisulfite-PCR sequencing.

    PubMed

    Lu, Jennifer; Ru, Kelin; Candiloro, Ida; Dobrovic, Alexander; Korbie, Darren; Trau, Matt

    2017-03-22

    Multiplex bisulfite-PCR sequencing is a convenient and scalable method for the quantitative determination of the methylation state of target DNA regions. A challenge of this application is the presence of CpGs in the same region where primers are being placed. A common solution to the presence of CpGs within a primer-binding region is to substitute a base degeneracy at the cytosine position. However, the efficacy of different substitutions and the extent to which bias towards methylated or unmethylated templates may occur has never been evaluated in bisulfite multiplex sequencing applications. In response, we examined the performance of four different primer substitutions at the cytosine position of CpG's contained within the PCR primers. In this study, deoxyinosine-, 5-nitroindole-, mixed-base primers and primers with an abasic site were evaluated across a series of methylated controls. Primers that contained mixed- or deoxyinosine- base modifications performed most robustly. Mixed-base primers were further selected to determine the conditions that induce bias towards methylated templates. This identified an optimized set of conditions where the methylated state of bisulfite DNA templates can be accurately assessed using mixed-base primers, and expands the scope of bisulfite resequencing assays when working with challenging templates.

  7. Analogs of diadenosine tetraphosphate (Ap4A).

    PubMed

    Guranowski, Andrzej

    2003-01-01

    This review summarizes our knowledge of analogs and derivatives of diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A), the most extensively studied member of the dinucleoside 5',5"'-P1,Pn-polyphosphate (NpnN) family. After a short discussion of enzymes that may be responsible for the accumulation and degradation of Np4)N's in the cell, this review focuses on chemically and/or enzymatically produced analogs and their practical applications. Particular attention is paid to compounds that have aided the study of enzymes involved in the metabolism of Ap4A (Np4N'). Certain Ap4A analogs were alternative substrates of Ap4A-degrading enzymes and/or acted as enzyme inhibitors, some other helped to establish enzyme mechanisms, increased the sensitivity of certain enzyme assays or produced stable enzyme:ligand complexes for structural analysis.

  8. Terrestrial Spaceflight Analogs: Antarctica

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2013-01-01

    Alterations in immune cell distribution and function, circadian misalignment, stress and latent viral reactivation appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Others are unique to the Concordia analog. Based on some initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune system changes and mission stress effects. An ongoing smaller control study at Neumayer III will address the influence of the hypoxic variable. Changes were observed in the peripheral blood leukocyte distribution consistent with immune mobilization, and similar to those observed during spaceflight. Alterations in cytokine production profiles were observed during winterover that are distinct from those observed during spaceflight, but potentially consistent with those observed during persistent hypobaric hypoxia. The reactivation of latent herpesviruses was observed during overwinter/isolation, that is consistently associated with dysregulation in immune function.

  9. Using Analogies to Prevent Misconceptions about Chemical Equilibrium

    ERIC Educational Resources Information Center

    Sahin Pekmez, Esin

    2010-01-01

    The main purpose of this study was to find the effectiveness of using analogies to prevent misconceptions about chemical equilibrium. Nineteen analogies, which were based on dynamic aspects of chemical equilibrium and application of Le Chatelier's principle, were developed. The participations of this study consisted of 11th grade students (n: 151)…

  10. The Role of Writing in Learning from Analogies

    ERIC Educational Resources Information Center

    Klein, Perry D.; Piacente-Cimini, Sabrina; Williams, Laura A.

    2007-01-01

    This study examines the role of writing in learning scientific principles through analogy. Seventy-two university students observed two demonstrations concerning one of three topics: buoyant force of a fluid, projectile motion or forces internal to a system. Each composed an analogy on one of the topics through speaking-only, writing-only, or…

  11. Promoting interdomain analogical transfer: When creating a problem helps to solve a problem.

    PubMed

    Minervino, Ricardo A; Olguín, Valeria; Trench, Máximo

    2017-02-01

    Research on analogical thinking has devised several ways of promoting an abstract encoding of base analogs, thus rendering them more retrievable during later encounters with similar situations lacking surface similarities. Recent studies have begun to explore ways of facilitating transfer at retrieval time, which could facilitate the retrieval of distant analogs learned within contexts that were not specially directed to emphasize their abstract structure. Such studies demonstrate that comparing a target problem to an analogous problem helps students retrieve base analogs that lack surface similarities. To devise more portable ways of enhancing analogical transfer, Experiment 1 replicated Kurtz and Loewenstein's (Memory & Cognition, 35, 334-341, 2007) target-comparison procedure with an additional condition in which participants compared the target to a nonanalogous problem before attempting to reach its solution. Although comparing two analogous targets outperformed the standard transfer condition in promoting analogical transfer, comparing nonanalogous problems did not yield a transfer advantage. Based on prior studies that showed that the activity of creating analogous problems during their initial encoding elicits a more abstract representation of base analogs, in Experiment 2 we assessed whether constructing a second analogous target problem at retrieval time helps participants retrieve superficially dissimilar base analogs. As predicted, target invention increased the retrieval of distant sources. In both experiments we found an association between the quality of the generated schemas and the probability of retrieving a distant base analog from memory.

  12. Insulin analogs for the treatment of diabetes mellitus: therapeutic applications of protein engineering.

    PubMed

    Berenson, Daniel F; Weiss, Allison R; Wan, Zhu-Li; Weiss, Michael A

    2011-12-01

    The engineering of insulin analogs represents a triumph of structure-based protein design. A framework has been provided by structures of insulin hexamers. Containing a zinc-coordinated trimer of dimers, such structures represent a storage form of the active insulin monomer. Initial studies focused on destabilization of subunit interfaces. Because disassembly facilitates capillary absorption, such targeted destabilization enabled development of rapid-acting insulin analogs. Converse efforts were undertaken to stabilize the insulin hexamer and promote higher-order self-assembly within the subcutaneous depot toward the goal of enhanced basal glycemic control with reduced risk of hypoglycemia. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus(®); Sanofi-Aventis) or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir(®); Novo-Nordisk). To further improve pharmacokinetic properties, modified approaches are presently under investigation. Novel strategies have recently been proposed based on subcutaneous supramolecular assembly coupled to (a) large-scale allosteric reorganization of the insulin hexamer (the TR transition), (b) pH-dependent binding of zinc ions to engineered His-X(3)-His sites at hexamer surfaces, or (c) the long-range vision of glucose-responsive polymers for regulated hormone release. Such designs share with wild-type insulin and current insulin products a susceptibility to degradation above room temperature, and so their delivery, storage, and use require the infrastructure of an affluent society. Given the global dimensions of the therapeutic supply chain, we envisage that concurrent engineering of ultra-stable protein analog formulations would benefit underprivileged patients in the developing world.

  13. Letter box line blackener for the HDTV/conventional-analog hybrid system

    DOEpatents

    Wysocki, Frederick J.; Nickel, George H.

    2006-07-18

    A blackener for letter box lines associated with a HDTV/conventional-analog hybrid television transmission where the blackener counts horizontal sync pulses contained in the HDTV/conventional-analog hybrid television transmission and determines when the HDTV/conventional-analog hybrid television transmission is in letter-box lines: if it is, then the blackener sends substitute black signal to an output; and if it is not, then the blackener sends the HDTV/conventional-analog hybrid television transmission to the output.

  14. Novel C-1 Substituted Cocaine Analogs Unlike Cocaine or Benztropine

    PubMed Central

    Ali, Solav; Hashim, Audrey; Sheikh, Imran S.; Theddu, Naresh; Gaddiraju, Narendra V.; Mehrotra, Suneet; Schmitt, Kyle C.; Murray, Thomas F.; Sershen, Henry; Unterwald, Ellen M.; Davis, Franklin A.

    2012-01-01

    Despite a wealth of information on cocaine-like compounds, there is no information on cocaine analogs with substitutions at C-1. Here, we report on (R)-(−)-cocaine analogs with various C-1 substituents: methyl (2), ethyl (3), n-propyl (4), n-pentyl (5), and phenyl (6). Analog 2 was equipotent to cocaine as an inhibitor of the dopamine transporter (DAT), whereas 3 and 6 were 3- and 10-fold more potent, respectively. None of the analogs, however, stimulated mouse locomotor activity, in contrast to cocaine. Pharmacokinetic assays showed compound 2 occupied mouse brain rapidly, as cocaine itself; moreover, 2 and 6 were behaviorally active in mice in the forced-swim test model of depression and the conditioned place preference test. Analog 2 was a weaker inhibitor of voltage-dependent Na+ channels than cocaine, although 6 was more potent than cocaine, highlighting the need to assay future C-1 analogs for this activity. Receptorome screening indicated few significant binding targets other than the monoamine transporters. Benztropine-like “atypical” DAT inhibitors are known to display reduced cocaine-like locomotor stimulation, presumably by their propensity to interact with an inward-facing transporter conformation. However, 2 and 6, like cocaine, but unlike benztropine, exhibited preferential interaction with an outward-facing conformation upon docking in our DAT homology model. In summary, C-1 cocaine analogs are not cocaine-like in that they are not stimulatory in vivo. However, they are not benztropine-like in binding mechanism and seem to interact with the DAT similarly to cocaine. The present data warrant further consideration of these novel cocaine analogs for antidepressant or cocaine substitution potential. PMID:22895898

  15. Active site dynamics of ribonuclease.

    PubMed Central

    Brünger, A T; Brooks, C L; Karplus, M

    1985-01-01

    The stochastic boundary molecular dynamics method is used to study the structure, dynamics, and energetics of the solvated active site of bovine pancreatic ribonuclease A. Simulations of the native enzyme and of the enzyme complexed with the dinucleotide substrate CpA and the transition-state analog uridine vanadate are compared. Structural features and dynamical couplings for ribonuclease residues found in the simulation are consistent with experimental data. Water molecules, most of which are not observed in crystallographic studies, are shown to play an important role in the active site. Hydrogen bonding of residues with water molecules in the free enzyme is found to mimic the substrate-enzyme interactions of residues involved in binding. Networks of water stabilize the cluster of positively charged active site residues. Correlated fluctuations between the uridine vanadate complex and the distant lysine residues are mediated through water and may indicate a possible role for these residues in stabilizing the transition state. Images PMID:3866234

  16. Analog graphic display method and apparatus

    DOEpatents

    Kronberg, J.W.

    1991-08-13

    Disclosed are an apparatus and method for using an output device such as an LED to show the approximate analog level of a variable electrical signal wherein a modulating AC waveform is superimposed either on the signal or a reference voltage, both of which are then fed to a comparator which drives the output device. Said device flashes at a constant perceptible rate with a duty cycle which varies in response to variations in the level of the input signal. The human eye perceives these variations in duty cycle as analogous to variations in the level of the input signal. 21 figures.

  17. Analog graphic display method and apparatus

    DOEpatents

    Kronberg, James W.

    1991-01-01

    An apparatus and method for using an output device such as an LED to show the approximate analog level of a variable electrical signal wherein a modulating AC waveform is superimposed either on the signal or a reference voltage, both of which are then fed to a comparator which drives the output device. Said device flashes at a constant perceptible rate with a duty cycle which varies in response to variations in the level of the input signal. The human eye perceives these variations in duty cycle as analogous to variations in the level of the input signal.

  18. Analogy Mapping Development for Learning Programming

    NASA Astrophysics Data System (ADS)

    Sukamto, R. A.; Prabawa, H. W.; Kurniawati, S.

    2017-02-01

    Programming skill is an important skill for computer science students, whereas nowadays, there many computer science students are lack of skills and information technology knowledges in Indonesia. This is contrary with the implementation of the ASEAN Economic Community (AEC) since the end of 2015 which is the qualified worker needed. This study provided an effort for nailing programming skills by mapping program code to visual analogies as learning media. The developed media was based on state machine and compiler principle and was implemented in C programming language. The state of every basic condition in programming were successful determined as analogy visualization.

  19. Terrestrial analogs to Mars

    NASA Technical Reports Server (NTRS)

    Farr, T. G.; Arcone, S.; Arvidson, R.; Baker, V.; Barlow, N.; Beaty, D.; Bell, M.; Blankenship, D.; Bridges, N.; Briggs, G.; hide

    2002-01-01

    It is well recognized that interpretations of Mars must begin with the Earth as a reference. The most successful comparisons have focused on understanding geologic processes on the Earth well enough to extrapolate to Mars' environment. Several facets of terrestrial analog studies have been pursued and are continuing.

  20. The scattering analog for infiltration in porous media

    NASA Astrophysics Data System (ADS)

    Philip, J. R.

    1989-11-01

    This review takes the form of a set of Chinese boxes. The outermost box gives a brief general account of modem developments in the mathematical physics of unsaturated flow in soils and porous media. This provides the necessary foundations for the second box, which describes the quasi-linear analysis of steady multidimensional unsaturated flow, which is an essential prerequisite to the analog. Only then can we proceed to the innermost box, devoted to our major theme. An exact analog exists between steady quasi-linear flow in unsaturated soils and porous media and the scattering of plane pulses, and the analog carries over to the scattering of plane harmonic waves. Numerous established results, and powerful techniques such as Watson transforms, far-field scattering functions, and optical theorems, become available for the solution and understanding of problems of multidimensional infiltration. These are needed, in particular, to provide the asymptotics of the physically interesting and practically important limit of flows strongly dominated by gravity, with capillary effects weak but nonzero. This is the limit of large s, where s is a characteristic length of the water supply surface normalized with respect to the sorptive length of the soil. These problems are singular in the sense that ignoring capillarity gives a totally incorrect picture of the wetted region. In terms of the optical analog, neglecting capillarity is equivalent to using geometrical optics, with coherent shadows projected to infinity. When exact solutions involve exotic functions, difficulties of both analysis and series summation may be avoided through use of small-s and large-s expansions provided by the analog. Numerous examples are given of solutions obtained through the analog. The scope for extending the application to flows from surface sources, to anisotropic and heterogeneous media, to unsteady flows, and to linear convection-diffusion processes in general is described briefly.

  1. Analogical Processes in Children's Understanding of Spatial Representations

    ERIC Educational Resources Information Center

    Yuan, Lei; Uttal, David; Gentner, Dedre

    2017-01-01

    We propose that map reading can be construed as a form of analogical mapping. We tested 2 predictions that follow from this claim: First, young children's patterns of performance in map reading tasks should parallel those found in analogical mapping tasks; and, second, children will benefit from guided alignment instructions that help them see the…

  2. Electrostatic analogy for symmetron gravity

    NASA Astrophysics Data System (ADS)

    Ogden, Lillie; Brown, Katherine; Mathur, Harsh; Rovelli, Kevin

    2017-12-01

    The symmetron model is a scalar-tensor theory of gravity with a screening mechanism that suppresses the effect of the symmetron field at high densities characteristic of the Solar System and laboratory scales but allows it to act with gravitational strength at low density on the cosmological scale. We elucidate the screening mechanism by showing that in the quasistatic Newtonian limit there are precise analogies between symmetron gravity and electrostatics for both strong and weak screening. For strong screening we find that large dense bodies behave in a manner analogous to perfect conductors in electrostatics. Based on this analogy we find that the symmetron field exhibits a lightning rod effect wherein the field gradients are enhanced near the ends of pointed or elongated objects. An ellipsoid placed in a uniform symmetron gradient is shown to experience a torque. By symmetry there is no gravitational torque in this case. Hence this effect unmasks the symmetron and might serve as the basis for future laboratory experiments. The symmetron force between a point mass and a large dense body includes a component corresponding to the interaction of the point mass with its image in the larger body. None of these effects have counterparts in the Newtonian limit of Einstein gravity. We discuss the similarities between symmetron gravity and the chameleon model as well as the differences between the two.

  3. Hardware Evolution of Analog Speed Controllers for a DC Motor

    NASA Technical Reports Server (NTRS)

    Gwaltney, David A.; Ferguson, Michael I.

    2003-01-01

    Evolvable hardware provides the capability to evolve analog circuits to produce amplifier and filter functions. Conventional analog controller designs employ these same functions. Analog controllers for the control of the shaft speed of a DC motor are evolved on an evolvable hardware platform utilizing a Field Programmable Transistor Array (FPTA). The performance of these evolved controllers is compared to that of a conventional proportional-integral (PI) controller.

  4. Synthesis and biological evaluation of ranitidine analogs as multiple-target-directed cognitive enhancers for the treatment of Alzheimer's disease.

    PubMed

    Gao, Jie; Midde, Narasimha; Zhu, Jun; Terry, Alvin V; McInnes, Campbell; Chapman, James M

    2016-11-15

    Using molecular modeling and rationally designed structural modifications, the multi-target structure-activity relationship for a series of ranitidine analogs has been investigated. Incorporation of a variety of isosteric groups indicated that appropriate aromatic moieties provide optimal interactions with the hydrophobic and π-π interactions with the peripheral anionic site of the AChE active site. The SAR of a series of cyclic imides demonstrated that AChE inhibition is increased by additional aromatic rings, where 1,8-naphthalimide derivatives were the most potent analogs and other key determinants were revealed. In addition to improving AChE activity and chemical stability, structural modifications allowed determination of binding affinities and selectivities for M1-M4 receptors and butyrylcholinesterase (BuChE). These results as a whole indicate that the 4-nitropyridazine moiety of the JWS-USC-75IX parent ranitidine compound (JWS) can be replaced with other chemotypes while retaining effective AChE inhibition. These studies allowed investigation into multitargeted binding to key receptors and warrant further investigation into 1,8-naphthalimide ranitidine derivatives for the treatment of Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Acoustic Analogy and Alternative Theories for Jet Noise Prediction

    NASA Technical Reports Server (NTRS)

    Morris, Philip J.; Farassat, F.

    2002-01-01

    Several methods for the prediction of jet noise are described. All but one of the noise prediction schemes are based on Lighthill's or Lilley's acoustic analogy, whereas the other is the jet noise generation model recently proposed by Tam and Auriault. In all of the approaches, some assumptions must be made concerning the statistical properties of the turbulent sources. In each case the characteristic scales of the turbulence are obtained from a solution of the Reynolds-averaged Navier-Stokes equation using a kappa-sigma turbulence model. It is shown that, for the same level of empiricism, Tam and Auriault's model yields better agreement with experimental noise measurements than the acoustic analogy. It is then shown that this result is not because of some fundamental flaw in the acoustic analogy approach, but instead is associated with the assumptions made in the approximation of the turbulent source statistics. If consistent assumptions are made, both the acoustic analogy and Tam and Auriault's model yield identical noise predictions. In conclusion, a proposal is presented for an acoustic analogy that provides a clearer identification of the equivalent source mechanisms, as is a discussion of noise prediction issues that remain to be resolved.

  6. Associative memory in an analog iterated-map neural network

    NASA Astrophysics Data System (ADS)

    Marcus, C. M.; Waugh, F. R.; Westervelt, R. M.

    1990-03-01

    The behavior of an analog neural network with parallel dynamics is studied analytically and numerically for two associative-memory learning algorithms, the Hebb rule and the pseudoinverse rule. Phase diagrams in the parameter space of analog gain β and storage ratio α are presented. For both learning rules, the networks have large ``recall'' phases in which retrieval states exist and convergence to a fixed point is guaranteed by a global stability criterion. We also demonstrate numerically that using a reduced analog gain increases the probability of recall starting from a random initial state. This phenomenon is comparable to thermal annealing used to escape local minima but has the advantage of being deterministic, and therefore easily implemented in electronic hardware. Similarities and differences between analog neural networks and networks with two-state neurons at finite temperature are also discussed.

  7. Synthesis and structure-activity relationships of fenbufen amide analogs.

    PubMed

    Lin, Kun-I; Yang, Chao-Hsun; Huang, Chia-Wen; Jian, Jhen-Yi; Huang, Yu-Chun; Yu, Chung-Shan

    2010-12-02

    The previous discoveries of butyl fenbufen amide analogs with antitumor effects were further examined. The amide analogs with 1, 3, 4 and 8 carbons chains were prepared in 70-80% yield. Fenbufen had no cytotoxic effects at concentrations ranging from 10 to 100 μM. Methyl fenbufen amide had significant cytotoxic effects at a concentration of 100 μM. As the length of the alkyl amide side chain increased, the cytotoxic effects increased, and the octyl fenbufen amide had the greatest cytotoxic effect. After treatment with 30 μM octyl fenbufen amide, nearly seventy percent of the cells lost their viability. At the concentration of 10 μM, fenbufen amide analogs did not show cytotoxicity according to the MTT assay results. The NO scavenging activities of the fenbufen amide analogs were not significantly different from those of fenbufen.

  8. Quantifying Uncertainty of Wind Power Production Through an Analog Ensemble

    NASA Astrophysics Data System (ADS)

    Shahriari, M.; Cervone, G.

    2016-12-01

    The Analog Ensemble (AnEn) method is used to generate probabilistic weather forecasts that quantify the uncertainty in power estimates at hypothetical wind farm locations. The data are from the NREL Eastern Wind Dataset that includes more than 1,300 modeled wind farms. The AnEn model uses a two-dimensional grid to estimate the probability distribution of wind speed (the predictand) given the values of predictor variables such as temperature, pressure, geopotential height, U-component and V-component of wind. The meteorological data is taken from the NCEP GFS which is available on a 0.25 degree grid resolution. The methodology first divides the data into two classes: training period and verification period. The AnEn selects a point in the verification period and searches for the best matching estimates (analogs) in the training period. The predictand value at those analogs are the ensemble prediction for the point in the verification period. The model provides a grid of wind speed values and the uncertainty (probability index) associated with each estimate. Each wind farm is associated with a probability index which quantifies the degree of difficulty to estimate wind power. Further, the uncertainty in estimation is related to other factors such as topography, land cover and wind resources. This is achieved by using a GIS system to compute the correlation between the probability index and geographical characteristics. This study has significant applications for investors in renewable energy sector especially wind farm developers. Lower level of uncertainty facilitates the process of submitting bids into day ahead and real time electricity markets. Thus, building wind farms in regions with lower levels of uncertainty will reduce the real-time operational risks and create a hedge against volatile real-time prices. Further, the links between wind estimate uncertainty and factors such as topography and wind resources, provide wind farm developers with valuable

  9. Children's Use of Analogy in Learning to Read.

    ERIC Educational Resources Information Center

    Goswami, Usha C.

    Two experiments were conducted in order to determine whether children are able to make analogies in learning to read. In the first experiment, 24 children from a primary school were taught three types of word pairs--only one pair of which was analogies--and then tested. Results showed not only that children are aware that consistency of spelling…

  10. Using Self-Generated Analogies in Teaching of Thermodynamics

    ERIC Educational Resources Information Center

    Haglund, Jesper; Jeppsson, Fredrik

    2012-01-01

    Using self-generated analogies has been proposed as a method in a constructivist tradition for students to learn about a new subject, by use of what they previously know. We report on a group exercise on using self-generated analogies to make sense of two thermodynamic processes, reversible adiabatic expansion and free adiabatic expansion of an…

  11. Sleep promotes analogical transfer in problem solving.

    PubMed

    Monaghan, Padraic; Sio, Ut Na; Lau, Sum Wai; Woo, Hoi Kei; Linkenauger, Sally A; Ormerod, Thomas C

    2015-10-01

    Analogical problem solving requires using a known solution from one problem to apply to a related problem. Sleep is known to have profound effects on memory and information restructuring, and so we tested whether sleep promoted such analogical transfer, determining whether improvement was due to subjective memory for problems, subjective recognition of similarity across related problems, or by abstract generalisation of structure. In Experiment 1, participants were exposed to a set of source problems. Then, after a 12-h period involving sleep or wake, they attempted target problems structurally related to the source problems but with different surface features. Experiment 2 controlled for time of day effects by testing participants either in the morning or the evening. Sleep improved analogical transfer, but effects were not due to improvements in subjective memory or similarity recognition, but rather effects of structural generalisation across problems. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Analogy as a strategy for supporting complex problem solving under uncertainty.

    PubMed

    Chan, Joel; Paletz, Susannah B F; Schunn, Christian D

    2012-11-01

    Complex problem solving in naturalistic environments is fraught with uncertainty, which has significant impacts on problem-solving behavior. Thus, theories of human problem solving should include accounts of the cognitive strategies people bring to bear to deal with uncertainty during problem solving. In this article, we present evidence that analogy is one such strategy. Using statistical analyses of the temporal dynamics between analogy and expressed uncertainty in the naturalistic problem-solving conversations among scientists on the Mars Rover Mission, we show that spikes in expressed uncertainty reliably predict analogy use (Study 1) and that expressed uncertainty reduces to baseline levels following analogy use (Study 2). In addition, in Study 3, we show with qualitative analyses that this relationship between uncertainty and analogy is not due to miscommunication-related uncertainty but, rather, is primarily concentrated on substantive problem-solving issues. Finally, we discuss a hypothesis about how analogy might serve as an uncertainty reduction strategy in naturalistic complex problem solving.

  13. Analogy motor learning by young children: a study of rope skipping.

    PubMed

    Tse, Andy C Y; Fong, Shirley S M; Wong, Thomson W L; Masters, Rich

    2017-03-01

    Research in psychology suggests that provision of an instruction by analogy can enhance acquisition and understanding of knowledge. Limited research has been conducted to test this proposition in motor learning by children. The purpose of the present study was to examine the feasibility of analogy instructions in motor skill acquisition by children. Thirty-two children were randomly assigned to one of the two instruction protocols: analogy and explicit instruction protocols for a two-week rope skipping training. Each participant completed a pretest (Lesson 1), three practice sessions (Lesson 2-4), a posttest and a secondary task test (Lesson 5). Children in the analogy protocol displayed better rope skip performance than those in the explicit instruction protocol (p < .001). Moreover, a cognitive secondary task test indicated that children in the analogy protocol performed more effectively, whereas children in the explicit protocol displayed decrements in performance. Analogy learning may aid children to acquire complex motor skills, and have potential benefits related to reduced cognitive processing requirements.

  14. Analogical processes in children's understanding of spatial representations.

    PubMed

    Yuan, Lei; Uttal, David; Gentner, Dedre

    2017-06-01

    We propose that map reading can be construed as a form of analogical mapping. We tested 2 predictions that follow from this claim: First, young children's patterns of performance in map reading tasks should parallel those found in analogical mapping tasks; and, second, children will benefit from guided alignment instructions that help them see the relational correspondences between the map and the space. In 4 experiments, 3-year-olds completed a map reading task in which they were asked to find hidden objects in a miniature room, using a corresponding map. We manipulated the availability of guided alignment (showing children the analogical mapping between maps and spaces; Experiments 1, 2, and 3a), the format of guided alignment (gesture or relational language; Experiment 2), and the iconicity of maps (Experiments 3a and 3b). We found that (a) young children's difficulties in map reading follow from known patterns of analogical development-for example, focusing on object similarity over relational similarity; and (b) guided alignment based on analogical reasoning led to substantially better performance. Results also indicated that children's map reading performance was affected by the format of guided alignment, the iconicity of the maps, and the order of tasks. The results bear on the developmental mechanisms underlying young children's learning of spatial representations and also suggest ways to support this learning. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  15. Reliable absolute analog code retrieval approach for 3D measurement

    NASA Astrophysics Data System (ADS)

    Yu, Shuang; Zhang, Jing; Yu, Xiaoyang; Sun, Xiaoming; Wu, Haibin; Chen, Deyun

    2017-11-01

    The wrapped phase of phase-shifting approach can be unwrapped by using Gray code, but both the wrapped phase error and Gray code decoding error can result in period jump error, which will lead to gross measurement error. Therefore, this paper presents a reliable absolute analog code retrieval approach. The combination of unequal-period Gray code and phase shifting patterns at high frequencies are used to obtain high-frequency absolute analog code, and at low frequencies, the same unequal-period combination patterns are used to obtain the low-frequency absolute analog code. Next, the difference between the two absolute analog codes was employed to eliminate period jump errors, and a reliable unwrapped result can be obtained. Error analysis was used to determine the applicable conditions, and this approach was verified through theoretical analysis. The proposed approach was further verified experimentally. Theoretical analysis and experimental results demonstrate that the proposed approach can perform reliable analog code unwrapping.

  16. FITPix COMBO—Timepix detector with integrated analog signal spectrometric readout

    NASA Astrophysics Data System (ADS)

    Holik, M.; Kraus, V.; Georgiev, V.; Granja, C.

    2016-02-01

    The hybrid semiconductor pixel detector Timepix has proven a powerful tool in radiation detection and imaging. Energy loss and directional sensitivity as well as particle type resolving power are possible by high resolution particle tracking and per-pixel energy and quantum-counting capability. The spectrometric resolving power of the detector can be further enhanced by analyzing the analog signal of the detector common sensor electrode (also called back-side pulse). In this work we present a new compact readout interface, based on the FITPix readout architecture, extended with integrated analog electronics for the detector's common sensor signal. Integrating simultaneous operation of the digital per-pixel information with the common sensor (called also back-side electrode) analog pulse processing circuitry into one device enhances the detector capabilities and opens new applications. Thanks to noise suppression and built-in electromagnetic interference shielding the common hardware platform enables parallel analog signal spectroscopy on the back side pulse signal with full operation and read-out of the pixelated digital part, the noise level is 600 keV and spectrometric resolution around 100 keV for 5.5 MeV alpha particles. Self-triggering is implemented with delay of few tens of ns making use of adjustable low-energy threshold of the particle analog signal amplitude. The digital pixelated full frame can be thus triggered and recorded together with the common sensor analog signal. The waveform, which is sampled with frequency 100 MHz, can be recorded in adjustable time window including time prior to the trigger level. An integrated software tool provides control, on-line display and read-out of both analog and digital channels. Both the pixelated digital record and the analog waveform are synchronized and written out by common time stamp.

  17. Method of pedestal and common-mode noise correction for switched-capacitor analog memories

    DOEpatents

    Britton, C.L.

    1997-09-23

    A method and apparatus are disclosed for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential dement is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits. 4 figs.

  18. Method of pedestal and common-mode noise correction for switched-capacitor analog memories

    DOEpatents

    Britton, C.L.

    1996-12-31

    A method and apparatus are disclosed for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential element is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits. 4 figs.

  19. Method of pedestal and common-mode noise correction for switched-capacitor analog memories

    DOEpatents

    Britton, Charles L.

    1997-01-01

    A method and apparatus for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential dement is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits.

  20. Method of pedestal and common-mode noise correction for switched-capacitor analog memories

    DOEpatents

    Britton, Charles L.

    1996-01-01

    A method and apparatus for correcting common-mode noise and pedestal noise in a multichannel array of switched-capacitor analog memories wherein each analog memory is connected to an associated analog-to-digital converter. The apparatus comprises a single differential element in two different embodiments. In a first embodiment, the differential element is a reference analog memory connected to a buffer. In the second embodiment, the differential element is a reference analog memory connected to a reference analog-to-digital connected to an array of digital summing circuits.

  1. Effects of elevated CO2 concentrations on denitrifying and nitrifying popualtions at terrestrial CO2 leakeage analogous sites

    NASA Astrophysics Data System (ADS)

    Christine, Dictor Marie; Catherine, Joulian; Valerie, Laperche; Stephanie, Coulon; Dominique, Breeze

    2010-05-01

    CO2 capture and geological storage (CCS) is recognized to be an important option for carbon abatement in Europe. One of the risks of CCS is the leakage from storage site. A laboratory was conducted on soil samples sampled near-surface from a CO2 leakage analogous site (Latera, Italy) in order to evaluate the impact of an elevated soil CO2 concentration on terrestrial bacterial ecosystems form near surface terrestrial environments and to determine a potential bacterial indicator of CO2 leakage from storage site. Surveys were conducted along a 50m long transect across the vent centre, providing a spectrum of CO2 flux rates, soil gas concentrations and compositions (Beaubien et al., 2007). A bacterial diversity studies, performed by CE-SSCP technique, on a soil profile with increasing CO2 soil concentrations (from 0.3% to 100%) showed that a change on bacterial diversity was noted when CO2 concentration was above 50 % of CO2. From this result, 3 soil samples were taken at 70 cm depth in 3 distinct zones (background soil CO2 content, soil CO2 content of 20% and soil CO2 content of 50%). Then theses soil samples were incubated under closed jars flushed with different air atmospheres (20, 50 and 90 % of CO2) during 18 months. At initial, 3, 6, 12 and 18 months, some soil samples were collected in order to estimate the denitrifying, nitrifying activities as a function of CO2 concentration content and times. Theses enzymatic activities were chosen because one occurs under anaerobic conditions (denitrification) and the other occurs under aerobic conditions (nitrification). Both of them were involved in the nitrogen cycle and are major actors of soil function and groundwater quality preservation. Metabolic diversity using BIOLOG Ecoplates was determined on every soil samples. Physico-chemical parameters (e.g. pH, bulk chemistry, mineralogy) were analyzed to have some information about the evolution of the soil during the incubation with increasing soil CO2 concentrations

  2. Conference Report: Biosignature Preservation and Detection in Mars Analog Environments.

    PubMed

    Hays, Lindsay; Beaty, David

    2017-01-01

    The Conference on Biosignature Preservation and Detection in Mars Analog Environments held in May 2016 brought together scientists to discuss microbial biosignatures in Mars analog habitable environments. Five analog environments were discussed: (1) hydrothermal spring systems, (2) subaqueous environments, (3) subaerial environments, (4) subsurface environments, and (5) iron-rich systems. This paper details the major messages that resulted from the discussions and will be followed by a review paper that adds significant detail from the published literature and interpretations from the writing committee of the workshop for future research and application to astrobiological exploration missions. Key Words: Biosignature preservation-Biosignature detection-Mars analog environments-Conference report-Astrobiological exploration. Astrobiology 17, 1-2.

  3. Where Concepts Meet Percepts: Stimulating Analogical Thought in Children.

    ERIC Educational Resources Information Center

    Flick, Larry

    1991-01-01

    Reports an instructional application of a theory of analogical reasoning. Uses the grinding of a sugar cube as an explanatory-predictive analogy for state transitions of water as a stimulus for promoting associations with other appropriate experiences in elementary school students. (PR)

  4. 21 CFR 582.5477 - Methionine hydroxy analog and its calcium salts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methionine hydroxy analog and its calcium salts... Nutrients and/or Dietary Supplements 1 § 582.5477 Methionine hydroxy analog and its calcium salts. (a) Product. Methionine hydroxy analog and its calcium salts. (b) [Reserved] (c) Limitations, restrictions, or...

  5. 21 CFR 582.5477 - Methionine hydroxy analog and its calcium salts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Methionine hydroxy analog and its calcium salts... Nutrients and/or Dietary Supplements 1 § 582.5477 Methionine hydroxy analog and its calcium salts. (a) Product. Methionine hydroxy analog and its calcium salts. (b) [Reserved] (c) Limitations, restrictions, or...

  6. Analog "neuronal" networks in early vision.

    PubMed Central

    Koch, C; Marroquin, J; Yuille, A

    1986-01-01

    Many problems in early vision can be formulated in terms of minimizing a cost function. Examples are shape from shading, edge detection, motion analysis, structure from motion, and surface interpolation. As shown by Poggio and Koch [Poggio, T. & Koch, C. (1985) Proc. R. Soc. London, Ser. B 226, 303-323], quadratic variational problems, an important subset of early vision tasks, can be "solved" by linear, analog electrical, or chemical networks. However, in the presence of discontinuities, the cost function is nonquadratic, raising the question of designing efficient algorithms for computing the optimal solution. Recently, Hopfield and Tank [Hopfield, J. J. & Tank, D. W. (1985) Biol. Cybern. 52, 141-152] have shown that networks of nonlinear analog "neurons" can be effective in computing the solution of optimization problems. We show how these networks can be generalized to solve the nonconvex energy functionals of early vision. We illustrate this approach by implementing a specific analog network, solving the problem of reconstructing a smooth surface from sparse data while preserving its discontinuities. These results suggest a novel computational strategy for solving early vision problems in both biological and real-time artificial vision systems. PMID:3459172

  7. Investigational parathyroid hormone receptor analogs for the treatment of osteoporosis.

    PubMed

    Polyzos, Stergios A; Makras, Polyzois; Efstathiadou, Zoe; Anastasilakis, Athanasios D

    2015-02-01

    Intermittent parathyroid hormone (PTH) administration, acting through multiple signaling pathways, exerts an osteoanabolic effect on the skeleton that surpasses the effect of other antiosteoporotic agents. However, its efficacy is limited by the coupling effect and relatively common adverse events. Thus, the development of more sophisticated PTH receptor analogs seems imperative. In this review, the authors summarize the role of PTH signaling pathway in bone remodeling. The authors also summarize investigational analogs targeting this pathway, which may be potential treatments for osteoporosis. β-arrestins are multifunctional cytoplasmic molecules that are decisive for regulating intracellular PTH signaling. Recently, in preclinical studies, arrestin analogs have achieved the anabolic bone effect of PTH without an accompanying increase in bone resorption. However, it is not yet known whether these analogs have adverse effects and there are no clinical data for their efficacy to date. On the other hand, several molecules derived either from PTH and PTH-related protein (PTHrP) molecules have been developed. Alternative routes of PTH 1 - 34 delivery (oral, transdermal), the PTH analog ostabolin and the N-terminal PTHrP analogs PTHrP 1 - 36 and abaloparatide, have recently been or are currently being tested in clinical trials and are more likely to become available for use in the near future.

  8. Heterobimetallic [NiFe] Complexes Containing Mixed CO/CN- Ligands: Analogs of the Active Site of the [NiFe] Hydrogenases.

    PubMed

    Perotto, Carlo U; Sodipo, Charlene L; Jones, Graham J; Tidey, Jeremiah P; Blake, Alexander J; Lewis, William; Davies, E Stephen; McMaster, Jonathan; Schröder, Martin

    2018-03-05

    The development of synthetic analogs of the active sites of [NiFe] hydrogenases remains challenging, and, in spite of the number of complexes featuring a [NiFe] center, those featuring CO and CN - ligands at the Fe center are under-represented. We report herein the synthesis of three bimetallic [NiFe] complexes [Ni( N 2 S 2 )Fe(CO) 2 (CN) 2 ], [Ni( S 4 )Fe(CO) 2 (CN) 2 ], and [Ni( N 2 S 3 )Fe(CO) 2 (CN) 2 ] that each contain a Ni center that bridges through two thiolato S donors to a {Fe(CO) 2 (CN) 2 } unit. X-ray crystallographic studies on [Ni( N 2 S 3 )Fe(CO) 2 (CN) 2 ], supported by DFT calculations, are consistent with a solid-state structure containing distinct molecules in the singlet ( S = 0) and triplet ( S = 1) states. Each cluster exhibits irreversible reduction processes between -1.45 and -1.67 V vs Fc + /Fc and [Ni( N 2 S 3 )Fe(CO) 2 (CN) 2 ] possesses a reversible oxidation process at 0.17 V vs Fc + /Fc. Spectroelectrochemical infrared (IR) and electron paramagnetic resonance (EPR) studies, supported by density functional theory (DFT) calculations, are consistent with a Ni III Fe II formulation for [Ni( N 2 S 3 )Fe(CO) 2 (CN) 2 ] + . The singly occupied molecular orbital (SOMO) in [Ni( N 2 S 3 )Fe(CO) 2 (CN) 2 ] + is based on Ni 3d z 2 and 3p S with the S contributions deriving principally from the apical S-donor. The nature of the SOMO corresponds to that proposed for the Ni-C state of the [NiFe] hydrogenases for which a Ni III Fe II formulation has also been proposed. A comparison of the experimental structures, and the electrochemical and spectroscopic properties of [Ni( N 2 S 3 )Fe(CO) 2 (CN) 2 ] and its [Ni( N 2 S 3 )] precursor, together with calculations on the oxidized [Ni( N 2 S 3 )Fe(CO) 2 (CN) 2 ] + and [Ni( N 2 S 3 )] + forms suggests that the binding of the {Fe(CO)(CN) 2 } unit to the {Ni(CysS) 4 } center at the active site of the [NiFe] hydrogenases suppresses thiolate-based oxidative chemistry involving the bridging thiolate S donors

  9. Recent Synthesis and Discovery of Brefeldin A Analogs

    PubMed Central

    Paek, Seung-Mann

    2018-01-01

    The recent development of analogs of brefeldin A (BFA), a fungal metabolite, for the improvement of BFA apoptosis-inducing activity is described. BFA has been isolated from various soil or, more recently, marine fungi and has shown versatile beneficial activities. More importantly, the apoptosis-inducing activity of BFA in cancer cells highlights the possibility of further developing this natural product as an anticancer agent. Besides its biological importance, its structural features have also gathered tremendous interest from both medicinal and synthetic chemists. By a medicinal chemistry and total synthesis approach, numerous analogs from BFA have been developed to improve its inferior bioavailability and its antiproliferative ability. In this review, the recent medicinal chemistry efforts in relation to the production of BFA analogs are extensively presented. PMID:29670019

  10. Spontaneous nucleotide exchange in low molecular weight GTPases by fluorescently labeled γ-phosphate-linked GTP analogs

    PubMed Central

    Korlach, Jonas; Baird, Daniel W.; Heikal, Ahmed A.; Gee, Kyle R.; Hoffman, Gregory R.; Webb, Watt W.

    2004-01-01

    Regulated guanosine nucleotide exchange and hydrolysis constitute the fundamental activities of low molecular weight GTPases. We show that three guanosine 5′-triphosphate analogs with BODIPY fluorophores coupled via the gamma phosphate bind to the GTPases Cdc42, Rac1, RhoA, and Ras and displace guanosine 5′-diphosphate with high intrinsic exchange rates in the presence of Mg2+ ions, thereby acting as synthetic, low molecular weight guanine nucleotide exchange factors. The accompanying large fluorescence enhancements (as high as 12-fold), caused by a reduction in guanine quenching of the environmentally sensitive BODIPY dye fluorescence on protein binding, allow for real-time monitoring of this spontaneous nucleotide exchange in the visible spectrum with high signal-to-noise ratios. Binding affinities increased with longer aliphatic linkers connecting the nucleotide and BODIPY fluorophore and were in the 10–100 nM range. Steady-state and time-resolved fluorescence spectroscopy showed an inverse relationship between linker length and fluorescence enhancement factors and differences in protein-bound fluorophore mobilities, providing optimization criteria for future applications of such compounds as efficient elicitors and reporters of nucleotide exchange. EDTA markedly enhanced nucleotide exchange, enabling rapid loading of GTPases with these probes. Differences in active site geometries, in the absence of Mg2+, caused qualitatively different reporting of the bound state by the different analogs. The BODIPY analogs also prevented the interaction of Cdc42 with p21 activated kinase. Together, these results validate the use of these analogs as valuable tools for studying GTPase functions and for developing potent synthetic nucleotide exchange factors for this important class of signaling molecules. PMID:14973186

  11. Mechanisms of Glucagon Degradation at Alkaline pH

    PubMed Central

    Caputo, Nicholas; Castle, Jessica R.; Bergstrom, Colin P.; Carroll, Julie M.; Bakhtiani, Parkash A.; Jackson, Melanie A.; Roberts, Charles T.; David, Larry L.; Ward, W. Kenneth

    2014-01-01

    Glucagon is unstable and undergoes degradation and aggregation in aqueous solution. For this reason, its use in portable pumps for closed loop management of diabetes is limited to very short periods. In this study, we sought to identify the degradation mechanisms and the bioactivity of specific degradation products. We studied degradation in the alkaline range, a range at which aggregation is minimized. Native glucagon and analogs identical to glucagon degradation products were synthesized. To quantify biological activity in glucagon and in the degradation peptides, a protein kinase A-based bioassay was used. Aged, fresh, and modified peptides were analyzed by liquid chromatography with mass spectrometry (LCMS). Oxidation of glucagon at the Met residue was common but did not reduce bioactivity. Deamidation and isomerization were also common and were more prevalent at pH 10 than 9. The biological effects of deamidation and isomerization were unpredictable; deamidation at some sites did not reduce bioactivity. Deamidation of Gln 3, isomerization of Asp 9, and deamidation with isomerization at Asn 28 all caused marked potency loss. Studies with molecular-weight-cutoff membranes and LCMS revealed much greater fibrillation at pH 9 than 10. Further work is necessary to determine formulations of glucagon that minimize degradation and fibrillation. PMID:23651991

  12. Mechanisms of glucagon degradation at alkaline pH.

    PubMed

    Caputo, Nicholas; Castle, Jessica R; Bergstrom, Colin P; Carroll, Julie M; Bakhtiani, Parkash A; Jackson, Melanie A; Roberts, Charles T; David, Larry L; Ward, W Kenneth

    2013-07-01

    Glucagon is unstable and undergoes degradation and aggregation in aqueous solution. For this reason, its use in portable pumps for closed loop management of diabetes is limited to very short periods. In this study, we sought to identify the degradation mechanisms and the bioactivity of specific degradation products. We studied degradation in the alkaline range, a range at which aggregation is minimized. Native glucagon and analogs identical to glucagon degradation products were synthesized. To quantify biological activity in glucagon and in the degradation peptides, a protein kinase A-based bioassay was used. Aged, fresh, and modified peptides were analyzed by liquid chromatography with mass spectrometry (LCMS). Oxidation of glucagon at the Met residue was common but did not reduce bioactivity. Deamidation and isomerization were also common and were more prevalent at pH 10 than 9. The biological effects of deamidation and isomerization were unpredictable; deamidation at some sites did not reduce bioactivity. Deamidation of Gln 3, isomerization of Asp 9, and deamidation with isomerization at Asn 28 all caused marked potency loss. Studies with molecular-weight-cutoff membranes and LCMS revealed much greater fibrillation at pH 9 than 10. Further work is necessary to determine formulations of glucagon that minimize degradation and fibrillation. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Varieties of noise: analogical reasoning in synthetic biology.

    PubMed

    Knuuttila, Tarja; Loettgers, Andrea

    2014-12-01

    The picture of synthetic biology as a kind of engineering science has largely created the public understanding of this novel field, covering both its promises and risks. In this paper, we will argue that the actual situation is more nuanced and complex. Synthetic biology is a highly interdisciplinary field of research located at the interface of physics, chemistry, biology, and computational science. All of these fields provide concepts, metaphors, mathematical tools, and models, which are typically utilized by synthetic biologists by drawing analogies between the different fields of inquiry. We will study analogical reasoning in synthetic biology through the emergence of the functional meaning of noise, which marks an important shift in how engineering concepts are employed in this field. The notion of noise serves also to highlight the differences between the two branches of synthetic biology: the basic science-oriented branch and the engineering-oriented branch, which differ from each other in the way they draw analogies to various other fields of study. Moreover, we show that fixing the mapping between a source domain and the target domain seems not to be the goal of analogical reasoning in actual scientific practice.

  14. The Nitty Gritty: How We Make Analogs Work

    NASA Technical Reports Server (NTRS)

    Self, A. L.; Huppman, S. R.; Spence, L. A.

    2017-01-01

    NASA's Human Research Program (HRP) is becoming increasingly reliant on Isolated, Confined and Controlled (ICC) analogs to accomplish many of its research objectives. Compared to other research platforms, ICC analogs present a unique set of operational challenges that must be addressed in order to ensure a high fidelity research environment. In particular, the Human Exploration Research Analog (HERA) habitat, which is classified as an ICC environment, has been developed over the past three years to accommodate the operational needs of research investigations from each of the HRP Elements. During the development period, various types of requirements have contributed to the current operational model, which strives to achieve the highest possible level of mission fidelity with limited resources. This presentation will focus on the operational aspects of the HERA habitat, with emphasis on how we develop the analog research environment to meet researchers' needs. Specific discussion topics include mission scenario development, operational tasks, mission timeline integration, stressor implementation, console support, and improvements based on lessons learned. The information is intended to help investigators better understand the details behind HERA operations and the benefits to their research goals.

  15. Further evaluation of the tropane analogs of haloperidol.

    PubMed

    Sampson, Dinithia; Bricker, Barbara; Zhu, Xue Y; Peprah, Kwakye; Lamango, Nazarius S; Setola, Vincent; Roth, Bryan L; Ablordeppey, Seth Y

    2014-09-01

    Previous work from our labs has indicated that a tropane analog of haloperidol with potent D2 binding but designed to avoid the formation of MPP(+)-like metabolites, such as 4-(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)pyridin-1-ium (BCPP(+)) still produced catalepsy, suggesting a strong role for the D2 receptor in the production of catalepsy in rats, and hence EPS in humans. This study tested the hypothesis that further modifications of the tropane analog to produce compounds with less potent binding to the D2 receptor than haloperidol, would produce less catalepsy. These tests have now revealed that while haloperidol produced maximum catalepsy, these compounds produced moderate to low levels of catalepsy. Compound 9, with the least binding affinity to the D2R, produced the least catalepsy and highest Minimum Adverse Effective Dose (MAED) of the analogs tested regardless of their affinities at other receptors including the 5-HT1AR. These observations support the hypothesis that moderation of the D2 binding of the tropane analogs could reduce catalepsy potential in rats and consequently EPS in man. Published by Elsevier Ltd.

  16. Metabolomic Discovery of Novel Urinary Galabiosylceramide Analogs as Fabry Disease Biomarkers

    NASA Astrophysics Data System (ADS)

    Boutin, Michel; Auray-Blais, Christiane

    2015-03-01

    Fabry disease is an X-linked, complex, multisystemic lysosomal storage disorder presenting marked phenotypic and genotypic variability among affected male and female patients. Glycosphingolipids, mainly globotriaosylceramide (Gb3) isoforms/analogs, globotriaosylsphingosine (lyso-Gb3) and analogs, as well as galabiosylceramide (Ga2) isoforms/analogs accumulate in the vascular endothelium, nerves, cardiomyocytes, renal glomerular and tubular epithelial cells, and biological fluids. The search for biomarkers reflecting disease severity and progression is still on-going. A metabolomic study using quadrupole time-of-flight mass spectrometry has revealed 22 galabiosylceramide isoforms/analogs in urine of untreated Fabry patients classified in seven groups according to their chemical structure: (1) Saturated fatty acid; (2) one extra double bond; (3) two extra double bonds; (4) hydroxylated saturated fatty acid; (5) hydroxylated fatty acid and one extra double bond; (6) hydrated sphingosine and hydroxylated fatty acid; (7) methylated amide linkage. Relative quantification of both Ga2 and Gb3 isoforms/analogs was performed. All these biomarkers are significantly more abundant in urine samples from untreated Fabry males compared with healthy male controls. A significant amount of Ga2 isoforms/analogs, accounting for 18% of all glycosphingolipids analyzed (Ga2 + Gb3 and respective isoforms/analogs), were present in urine of Fabry patients. Gb3 isoforms containing saturated fatty acids are the most abundant (60.9%) compared with 26.3% for Ga2. A comparison between Ga2 isoforms/analogs and their Gb3 counterparts also showed that the proportion of analogs with hydroxylated fatty acids is significantly greater for Ga2 (35.8%) compared with Gb3 (1.9%). These results suggest different biological pathways involved in the synthesis and/or degradation of Gb3 and Ga2 metabolites.

  17. Systematic Functional Analysis of Active-Site Residues in l-Threonine Dehydrogenase from Thermoplasma volcanium

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

    Desjardins, Morgan; Mak, Wai Shun; O’Brien, Terrence E.

    Enzymes have been through millions of years of evolution during which their active-site microenvironments are fine-tuned. Active-site residues are commonly conserved within protein families, indicating their importance for substrate recognition and catalysis. In this work, we systematically mutated active-site residues of l-threonine dehydrogenase from Thermoplasma volcanium and characterized the mutants against a panel of substrate analogs. Our results demonstrate that only a subset of these residues plays an essential role in substrate recognition and catalysis and that the native enzyme activity can be further enhanced roughly 4.6-fold by a single point mutation. Kinetic characterization of mutants on substrate analogs showsmore » that l-threonine dehydrogenase possesses promiscuous activities toward other chemically similar compounds not previously observed. Quantum chemical calculations on the hydride-donating ability of these substrates also reveal that this enzyme did not evolve to harness the intrinsic substrate reactivity for enzyme catalysis. Our analysis provides insights into connections between the details of enzyme active-site structure and specific function. Finally, these results are directly applicable to rational enzyme design and engineering.« less

  18. Systematic Functional Analysis of Active-Site Residues in l-Threonine Dehydrogenase from Thermoplasma volcanium

    DOE PAGES

    Desjardins, Morgan; Mak, Wai Shun; O’Brien, Terrence E.; ...

    2017-07-07

    Enzymes have been through millions of years of evolution during which their active-site microenvironments are fine-tuned. Active-site residues are commonly conserved within protein families, indicating their importance for substrate recognition and catalysis. In this work, we systematically mutated active-site residues of l-threonine dehydrogenase from Thermoplasma volcanium and characterized the mutants against a panel of substrate analogs. Our results demonstrate that only a subset of these residues plays an essential role in substrate recognition and catalysis and that the native enzyme activity can be further enhanced roughly 4.6-fold by a single point mutation. Kinetic characterization of mutants on substrate analogs showsmore » that l-threonine dehydrogenase possesses promiscuous activities toward other chemically similar compounds not previously observed. Quantum chemical calculations on the hydride-donating ability of these substrates also reveal that this enzyme did not evolve to harness the intrinsic substrate reactivity for enzyme catalysis. Our analysis provides insights into connections between the details of enzyme active-site structure and specific function. Finally, these results are directly applicable to rational enzyme design and engineering.« less

  19. Method and apparatus for low power analog-to-digital conversion

    DOEpatents

    De Geronimo, Gianluigi; Nambiar, Neena

    2013-10-01

    A method and apparatus for analog-to-digital conversion. An Analog-to-Digital Converter (ADC) includes M ADC.sub.j, j=1, 2, . . . , M. Each ADC.sub.j comprises a number of cells each of which comprises a first switch, a second switch, a current sink and an inverter. An inverter of a cell in an ADC.sub.j changes state in response to a current associate with an input signal of the ADC.sub.j exceeding a threshold, thus switching on the next cell. Each ADC.sub.j is enabled to perform analog-to-digital conversion on a residual current of a previous ADC.sub.j-1 after the previous ADC.sub.j-1 has completed its analog-to-digital conversion and has been disabled.

  20. Stereoselective synthesis of nicotinamide beta-riboside and nucleoside analogs.

    PubMed

    Franchetti, Palmarisa; Pasqualini, Michela; Petrelli, Riccardo; Ricciutelli, Massimo; Vita, Patrizia; Cappellacci, Loredana

    2004-09-20

    The beta-anomers of N-ribofuranosylnicotine-3-carboxamide (beta-NAR) and its nicotinic acid analog (beta-NaR) were obtained by stereoselective synthesis via glycosylation of the presilylated bases under Vorbruggen's protocol. A NAR analog, methylated in position 3 of the ribosylic moiety, is also reported.

  1. Analogy-Integrated e-Learning Module: Facilitating Students' Conceptual Understanding

    ERIC Educational Resources Information Center

    Florida, Jennifer

    2012-01-01

    The study deals with the development of an analogy-integrated e-learning module on Cellular Respiration, which is intended to facilitate conceptual understanding of students with different brain hemisphere dominance and learning styles. The module includes eight analogies originally conceptualized following the specific steps used to prepare…

  2. Emergent Verbal Behavior and Analogy: Skinnerian and Linguistic Approaches

    PubMed Central

    Matos, Maria Amelia; de Lourdes Passos, Maria

    2010-01-01

    The production of verbal operants not previously taught is an important aspect of language productivity. For Skinner, new mands, tacts, and autoclitics result from the recombination of verbal operants. The relation between these mands, tacts, and autoclitics is what linguists call analogy, a grammatical pattern that serves as a foundation on which a speaker might emit new linguistic forms. Analogy appears in linguistics as a regularity principle that characterizes language and has been related to how languages change and also to creativity. The approaches of neogrammarians like Hermann Paul, as well as those of Jespersen and Bloomfield, appear to have influenced Skinner's understanding of verbal creativity. Generalization and stimulus equivalence are behavioral processes related to the generative grammatical behavior described in the analogy model. Linguistic forms and grammatical patterns described in analogy are part of the contingencies of reinforcement that produce generalization and stimulus equivalence. The analysis of verbal behavior needs linguistic analyses of the constituents of linguistic forms and their combination patterns. PMID:22479127

  3. Inhibition of Delta-induced Notch signaling using fucose analogs

    PubMed Central

    Schneider, Michael; Kumar, Vivek; Nordstrøm, Lars Ulrik; Feng, Lei; Takeuchi, Hideyuki; Hao, Huilin; Luca, Vincent C.; Garcia, K. Christopher; Stanley, Pamela; Wu, Peng; Haltiwanger, Robert S.

    2017-01-01

    Notch is a cell-surface receptor that controls cell fate decisions and is regulated by O-glycans attached to epidermal growth factor-like (EGF) repeats in its extracellular domain. Protein O-fucosyltransferase 1 (Pofut1) modifies EGF repeats with O-fucose and is essential for Notch signaling. Constitutive activation of Notch signaling has been associated with a variety of human malignancies. Therefore, tools for inhibiting Notch activity are being developed as cancer therapeutics. Towards this end, we screened L-fucose analogs for their effects on Notch signaling. Two analogs, 6-alkynyl and 6-alkenyl fucose, were substrates of Pofut1 and were incorporated directly into Notch EGF repeats in cells. Both analogs were potent inhibitors of binding to and activation of Notch1 by Notch ligands Dll1 and Dll4, but not by Jag1. Mutagenesis and modeling studies suggest that incorporation of the analogs into EGF8 of Notch1 markedly reduces the ability of Delta ligands to bind and activate Notch1. PMID:29176671

  4. Concept Confusion and Concept Discernment in Basic Magnetism Using Analogical Reasoning

    ERIC Educational Resources Information Center

    Lemmer, Miriam; Morabe, Olebogeng Nicodimus

    2017-01-01

    Analogical reasoning is central to all learning, whether in daily life situations, in the classroom or while doing research. Although analogies can aid the learning process of making sense of phenomena and understanding new ideas in terms of known ideas, these should be used with care. This article reports a study of the use of analogies and the…

  5. Connecting long distance: semantic distance in analogical reasoning modulates frontopolar cortex activity.

    PubMed

    Green, Adam E; Kraemer, David J M; Fugelsang, Jonathan A; Gray, Jeremy R; Dunbar, Kevin N

    2010-01-01

    Solving problems often requires seeing new connections between concepts or events that seemed unrelated at first. Innovative solutions of this kind depend on analogical reasoning, a relational reasoning process that involves mapping similarities between concepts. Brain-based evidence has implicated the frontal pole of the brain as important for analogical mapping. Separately, cognitive research has identified semantic distance as a key characteristic of the kind of analogical mapping that can support innovation (i.e., identifying similarities across greater semantic distance reveals connections that support more innovative solutions and models). However, the neural substrates of semantically distant analogical mapping are not well understood. Here, we used functional magnetic resonance imaging (fMRI) to measure brain activity during an analogical reasoning task, in which we parametrically varied the semantic distance between the items in the analogies. Semantic distance was derived quantitatively from latent semantic analysis. Across 23 participants, activity in an a priori region of interest (ROI) in left frontopolar cortex covaried parametrically with increasing semantic distance, even after removing effects of task difficulty. This ROI was centered on a functional peak that we previously associated with analogical mapping. To our knowledge, these data represent a first empirical characterization of how the brain mediates semantically distant analogical mapping.

  6. Crystal structures of two new low-symmetry calcium-deficient analogs of eudialyte

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

    Rastsvetaeva, R. K.; Rozenberg, K. A.; Pekov, I. V.

    2006-03-15

    The crystal structures of two new low-symmetry (sp. gr. R3) representatives of the eudialyte group from Mont Saint-Hilaire (Quebec, Canada) and the Lovozero massif (Kola Peninsula, Russia) were studied by single-crystal X-ray diffraction analysis and refined to R = 0.068 and 0.054 using 2899 reflections with F > 5{sigma}(F) and 2927 reflections with F > 3{sigma}(F), respectively. The idealized formulas of these representatives are Na{sub 13}(Ca{sub 3}Mn{sub 3})Zr{sub 3}(Fe, Mn){sub 3}({open_square})(Si)[Si{sub 3}O{sub 9}]{sub 2}[Si{sub 9}O{sub 27}]{sub 2}(O, OH, Cl){sub 3} . 2H{sub 2}O and Na{sub 15}(Ca{sub 3}Mn{sub 3})Zr{sub 3}(Fe, Zr){sub 3}(Si)(Si) . [Si{sub 3}O{sub 9}]{sub 2}[Si{sub 9}O{sub 27}]{sub 2}O{sub 2}(OH,more » F, Cl){sub 2} . 2H{sub 2}O. Both minerals are analogs of oneillite and are characterized by a low Ca content. The distinguishing features of the mineral from Quebec are that the M(4) site is essentially vacant (>50%) and Ca atoms occupy one independent site in the six-membered ring, whereas another site is occupied by Mn along with a small impurity of Na. In the mineral from the Lovozero massif, both the M(3) and M(4) sites are occupied predominantly by silicon, while Ca atoms are distributed between both octahedral sites of the six-membered ring, one of these sites being occupied predominantly by Mn.« less

  7. Inhibition of rat prostate tumor growth by an octapeptide analog of somatostatin.

    PubMed

    Murphy, W A; Lance, V A; Moreau, S; Moreau, J P; Coy, D H

    1987-06-29

    Analogs of a potent octapeptide analog of somatostatin (SRIF) H-(D)Phe-Cys-Tyr-(D)Trp-Lys-Val-Cys-Thr(NH2) were synthesized. Aromatic substitutions for Tyr resulted in little change in inhibitory potency on growth hormone (GH) secretion in the rat. Substitutions for Val or (D)Trp resulted in analogs with diminished activity. Substitution of (D)Nal for (D)Phe increased duration of GH inhibition. Final weights of subcutaneously implanted prostate tumors (R3327) were 41% lower in rats treated with an N-terminal 4-chloro-(D)phenylalanyl analog as compared to vehicle treated controls. The analog had no effect on testicular weight or final plasma testosterone levels. SRIF analogs may represent an alternative treatment for prostate cancer that would be free of the untoward reproductive effects of other treatments (e.g. LH-RH or castration).

  8. Noise Analysis of Spatial Phase coding in analog Acoustooptic Processors

    NASA Technical Reports Server (NTRS)

    Gary, Charles K.; Lum, Henry, Jr. (Technical Monitor)

    1994-01-01

    Optical beams can carry information in their amplitude and phase; however, optical analog numerical calculators such as an optical matrix processor use incoherent light to achieve linear operation. Thus, the phase information is lost and only the magnitude can be used. This limits such processors to the representation of positive real numbers. Many systems have been devised to overcome this deficit through the use of digital number representations, but they all operate at a greatly reduced efficiency in contrast to analog systems. The most widely accepted method to achieve sign coding in analog optical systems has been the use of an offset for the zero level. Unfortunately, this results in increased noise sensitivity for small numbers. In this paper, we examine the use of spatially coherent sign coding in acoustooptical processors, a method first developed for digital calculations by D. V. Tigin. This coding technique uses spatial coherence for the representation of signed numbers, while temporal incoherence allows for linear analog processing of the optical information. We show how spatial phase coding reduces noise sensitivity for signed analog calculations.

  9. Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity

    PubMed Central

    Jha, Narendra Nath; Ghosh, Dhiman; Das, Subhadeep; Anoop, Arunagiri; Jacob, Reeba S.; Singh, Pradeep K.; Ayyagari, Narasimham; Namboothiri, Irishi N. N.; Maji, Samir K.

    2016-01-01

    Alpha-synuclein (α-Syn) aggregation into oligomers and fibrils is associated with dopaminergic neuron loss occurring in Parkinson’s disease (PD) pathogenesis. Compounds that modulate α-Syn aggregation and interact with preformed fibrils/oligomers and convert them to less toxic species could have promising applications in the drug development efforts against PD. Curcumin is one of the Asian food ingredient which showed promising role as therapeutic agent against many neurological disorders including PD. However, the instability and low solubility makes it less attractive for the drug development. In this work, we selected various curcumin analogs and studied their toxicity, stability and efficacy to interact with different α-Syn species and modulation of their toxicity. We found a subset of curcumin analogs with higher stability and showed that curcumin and its various analogs interact with preformed fibrils and oligomers and accelerate α-Syn aggregation to produce morphologically different amyloid fibrils in vitro. Furthermore, these curcumin analogs showed differential binding with the preformed α-Syn aggregates. The present data suggest the potential role of curcumin analogs in modulating α-Syn aggregation. PMID:27338805

  10. A 4 μW/Ch analog front-end module with moderate inversion and power-scalable sampling operation for 3-D neural microsystems.

    PubMed

    Al-Ashmouny, Khaled M; Chang, Sun-Il; Yoon, Euisik

    2012-10-01

    We report an analog front-end prototype designed in 0.25 μm CMOS process for hybrid integration into 3-D neural recording microsystems. For scaling towards massive parallel neural recording, the prototype has investigated some critical circuit challenges in power, area, interface, and modularity. We achieved extremely low power consumption of 4 μW/channel, optimized energy efficiency using moderate inversion in low-noise amplifiers (K of 5.98 × 10⁸ or NEF of 2.9), and minimized asynchronous interface (only 2 per 16 channels) for command and data capturing. We also implemented adaptable operations including programmable-gain amplification, power-scalable sampling (up to 50 kS/s/channel), wide configuration range (9-bit) for programmable gain and bandwidth, and 5-bit site selection capability (selecting 16 out of 128 sites). The implemented front-end module has achieved a reduction in noise-energy-area product by a factor of 5-25 times as compared to the state-of-the-art analog front-end approaches reported to date.

  11. Using Analogies in Teaching Physics: A Study on Latvian Teachers' Views and Experience

    ERIC Educational Resources Information Center

    Jonane, Lolita

    2015-01-01

    The role of analogies as tools for teaching difficult science concepts has been widely discussed in science education. The application of analogies in the context of sustainable education involves richer potential. The purposeful use of appropriate analogies can facilitate analogical thinking and transfer skills, as well as develop abilities which…

  12. When Are Analogies the Right Tool? A Look at the Strategic Use of Analogies in Teaching Cellular Respiration to Middle-School Students.

    ERIC Educational Resources Information Center

    Else, Mary Jane; Ramirez, Mary Anne; Clement, John

    In this paper, the ways in which analogies are used in the Energy and the Human Body curriculum will be examined and some preliminary assessments of successes and difficulties will be discussed. Also investigated will be what the first year's study trials suggest about the effective use of analogies in the middle-school classroom. Characteristics…

  13. In vitro blood-brain barrier permeability predictions for GABAA receptor modulating piperine analogs.

    PubMed

    Eigenmann, Daniela Elisabeth; Dürig, Carmen; Jähne, Evelyn Andrea; Smieško, Martin; Culot, Maxime; Gosselet, Fabien; Cecchelli, Romeo; Helms, Hans Christian Cederberg; Brodin, Birger; Wimmer, Laurin; Mihovilovic, Marko D; Hamburger, Matthias; Oufir, Mouhssin

    2016-06-01

    The alkaloid piperine from black pepper (Piper nigrum L.) and several synthetic piperine analogs were recently identified as positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors. In order to reach their target sites of action, these compounds need to enter the brain by crossing the blood-brain barrier (BBB). We here evaluated piperine and five selected analogs (SCT-66, SCT-64, SCT-29, LAU397, and LAU399) regarding their BBB permeability. Data were obtained in three in vitro BBB models, namely a recently established human model with immortalized hBMEC cells, a human brain-like endothelial cells (BLEC) model, and a primary animal (bovine endothelial/rat astrocytes co-culture) model. For each compound, quantitative UHPLC-MS/MS methods in the range of 5.00-500ng/mL in the corresponding matrix were developed, and permeability coefficients in the three BBB models were determined. In vitro predictions from the two human BBB models were in good agreement, while permeability data from the animal model differed to some extent, possibly due to protein binding of the screened compounds. In all three BBB models, piperine and SCT-64 displayed the highest BBB permeation potential. This was corroborated by data from in silico prediction. For the other piperine analogs (SCT-66, SCT-29, LAU397, and LAU399), BBB permeability was low to moderate in the two human BBB models, and moderate to high in the animal BBB model. Efflux ratios (ER) calculated from bidirectional permeability experiments indicated that the compounds were likely not substrates of active efflux transporters. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Clustered DNA damages induced by high and low LET radiation, including heavy ions

    NASA Technical Reports Server (NTRS)

    Sutherland, B. M.; Bennett, P. V.; Schenk, H.; Sidorkina, O.; Laval, J.; Trunk, J.; Monteleone, D.; Sutherland, J.; Lowenstein, D. I. (Principal Investigator)

    2001-01-01

    Clustered DNA damages--here defined as two or more lesions (strand breaks, oxidized purines, oxidized pyrimidines or abasic sites) within a few helical turns--have been postulated as difficult to repair accurately, and thus highly significant biological lesions. Further, attempted repair of clusters may produce double strand breaks (DSBs). However, until recently, there was no way to measure ionizing radiation-induced clustered damages, except DSB. We recently described an approach for measuring classes of clustered damages (oxidized purine clusters, oxidized pyrimidine clusters, abasic clusters, along with DSB). We showed that ionizing radiation (gamma rays and Fe ions, 1 GeV/amu) does induce such clusters in genomic DNA in solution and in human cells. These studies also showed that each damage cluster results from one radiation hit (and its track), thus indicating that they can be induced by very low doses of radiation, i.e. two independent hits are not required for cluster induction. Further, among all complex damages, double strand breaks comprise--at most-- 20%, with the other clustered damages being at least 80%.

  15. High school students' views of learning chemistry concepts with analogies

    NASA Astrophysics Data System (ADS)

    Mathews, Jeffrey A.

    Analogies are often used in teaching abstract chemistry concepts, however few studies are concerned with how students actually view learning with analogies. An eight-member focus group, consisting of high school students, described the process of learning with analogies and how aware they were of their own learning. The students attended four analogy presentations and completed written responses, attended focus groups, and participated in repeated individual interview sessions throughout this eight-week, emic, phenomenological study. This study utilized an interpretive, qualitative methodology using a constant comparative, inductive analysis design. Students from a suburban high school in the southeastern United States were selected by purposeful sampling involving a concepts pre-test and an analogy presentation used to determine an eight member focus group. The focus group meetings were videotaped and emergent, semi-structured individual interviews were audio taped, transcribed and coded. Personal student journals, field notes, and a reflective journal were used to triangulate the study. Open, axial, and selective coding were used for data analysis and interpretation. Students described the process of learning with analogies as being able to visually see connections or picture mental images of familiar and unfamiliar concepts. Students pointed out the significance of investigating analogy breakdowns and described accommodation of new information as either automatic, which according to students resulted in memorization and hard learning, or quite laborious, which resulted in understanding and soft learning. Results indicated that students gave themselves more permission to ask questions and be critical of the teaching they are experiencing when their views were given merit. Implications for teachers include insight on students' views of learning and students' self-awareness.

  16. Design by Analogy: Achieving More Patentable Ideas from One Creative Design

    NASA Astrophysics Data System (ADS)

    Jia, Li-Zhen; Wu, Chun-Long; Zhu, Xue-Hong; Tan, Run-Hua

    2018-12-01

    A patent is a kind of technical document to protect intellectual property for individuals or enterprises. Patentable idea generation is a crucial step for patent application and analogy is confirmed to be an effective technique to inspire creative ideas. Analogy-based design usually starts from representation of an analogy source and is followed by the retrieval of appropriate analogs, mapping of design knowledge and adaptation of target solution. To diffuse one core idea into other new contexts and achieve more patentable ideas, this paper mainly centered on the first two stages of analogy-based design and proposed a patentable ideation framework. The analogical information of the source system, including source design problems and solution, was mined comprehensively through International Patent Classification analysis and represented in the form of function, behavior and structure. Three heuristics were suggested for searching the set of candidate target systems with a similar design problem, where the source design could be transferred. To systematize the process of source representation, analogs retrieval, idea transfer, and solution generation, an ideation model was put forward. Finally, the bladeless fan was selected as a source design to illustrate the application of this work. The design output shows that the representation and heuristics are beneficial, and this systematic ideation method can help the engineer or designer enhance creativity and discover more patentable opportunities.

  17. UV IRRADIATION OF AROMATIC NITROGEN HETEROCYCLES IN INTERSTELLAR ICE ANALOGS

    NASA Technical Reports Server (NTRS)

    Elsila, J. E.; Bernstein, M. P.; Sanford, S. A.

    2005-01-01

    Here, we present information on the properties of the ANH quinoline frozen in interstellar water-ice analogs. Quinoline is a two-ring compound structurally analogous to the PAH naphthalene. In this work, binary mixtures of water and quinoline were frozen to create interstellar ice analogs, which were then subjected to ultraviolet photolysis. We will present the infrared spectra of the resulting ices at various temperatures, as well as chromatographic analysis of the residues remaining upon warm-up of these ices to room temperature.

  18. The optical analogy for vector fields

    NASA Technical Reports Server (NTRS)

    Parker, E. N. (Editor)

    1991-01-01

    This paper develops the optical analogy for a general vector field. The optical analogy allows the examination of certain aspects of a vector field that are not otherwise readily accessible. In particular, in the cases of a stationary Eulerian flow v of an ideal fluid and a magnetostatic field B, the vectors v and B have surface loci in common with their curls. The intrinsic discontinuities around local maxima in absolute values of v and B take the form of vortex sheets and current sheets, respectively, the former playing a fundamental role in the development of hydrodyamic turbulence and the latter playing a major role in heating the X-ray coronas of stars and galaxies.

  19. Space flight nutrition research: platforms and analogs

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Uchakin, Peter N.; Tobin, Brian W.

    2002-01-01

    Conducting research during actual or simulated weightlessness is a challenging endeavor, where even the simplest activities may present significant challenges. This article reviews some of the potential obstacles associated with performing research during space flight and offers brief descriptions of current and previous space research platforms and ground-based analogs, including those for human, animal, and cell-based research. This review is intended to highlight the main issues of space flight research analogs and leave the specifics for each physiologic system for the other papers in this section.

  20. Kinematics and age of 15 stars-photometric solar analogs

    NASA Astrophysics Data System (ADS)

    Galeev, A. I.; Shimansky, V. V.

    2008-03-01

    The radial and space velocities are inferred for 15 stars that are photometric analogs of the Sun. The space velocity components (U, V, W) of most of these stars lie within the 10-60 km/s interval. The star HD 225239, which in our previous papers we classified as a subgiant, has a space velocity exceeding 100 km/s, and belongs to the thick disk. The inferred fundamental parameters of the atmospheres of solar analogs are combined with published evolutionary tracks to estimate the masses and ages of the stars studied. The kinematics of photometric analogs is compared to the data for a large group of solar-type stars.

  1. Analogical Reasoning in the Classroom: Insights from Cognitive Science

    ERIC Educational Resources Information Center

    Vendetti, Michael S.; Matlen, Bryan J.; Richland, Lindsey E.; Bunge, Silvia A.

    2015-01-01

    Applying knowledge from one context to another is a notoriously difficult problem, both for children and adults, but lies at the heart of educational endeavors. Analogical reasoning is a cognitive underpinning of the ability to notice and draw similarities across contexts. Reasoning by analogy is especially challenging for students, who must…

  2. Young Children's Analogical Reasoning across Cultures: Similarities and Differences

    ERIC Educational Resources Information Center

    Richland, Lindsey Engle; Chan, Tsz-Kit; Morrison, Robert G.; Au, Terry Kit-Fong

    2010-01-01

    A cross-cultural comparison between U.S. and Hong Kong preschoolers examined factors responsible for young children's analogical reasoning errors. On a scene analogy task, both groups had adequate prerequisite knowledge of the key relations, were the same age, and showed similar baseline performance, yet Chinese children outperformed U.S. children…

  3. The MARS2013 Mars analog mission.

    PubMed

    Groemer, Gernot; Soucek, Alexander; Frischauf, Norbert; Stumptner, Willibald; Ragonig, Christoph; Sams, Sebastian; Bartenstein, Thomas; Häuplik-Meusburger, Sandra; Petrova, Polina; Evetts, Simon; Sivenesan, Chan; Bothe, Claudia; Boyd, Andrea; Dinkelaker, Aline; Dissertori, Markus; Fasching, David; Fischer, Monika; Föger, Daniel; Foresta, Luca; Fritsch, Lukas; Fuchs, Harald; Gautsch, Christoph; Gerard, Stephan; Goetzloff, Linda; Gołebiowska, Izabella; Gorur, Paavan; Groemer, Gerhard; Groll, Petra; Haider, Christian; Haider, Olivia; Hauth, Eva; Hauth, Stefan; Hettrich, Sebastian; Jais, Wolfgang; Jones, Natalie; Taj-Eddine, Kamal; Karl, Alexander; Kauerhoff, Tilo; Khan, Muhammad Shadab; Kjeldsen, Andreas; Klauck, Jan; Losiak, Anna; Luger, Markus; Luger, Thomas; Luger, Ulrich; McArthur, Jane; Moser, Linda; Neuner, Julia; Orgel, Csilla; Ori, Gian Gabriele; Paternesi, Roberta; Peschier, Jarno; Pfeil, Isabella; Prock, Silvia; Radinger, Josef; Ramirez, Barbara; Ramo, Wissam; Rampey, Mike; Sams, Arnold; Sams, Elisabeth; Sandu, Oana; Sans, Alejandra; Sansone, Petra; Scheer, Daniela; Schildhammer, Daniel; Scornet, Quentin; Sejkora, Nina; Stadler, Andrea; Stummer, Florian; Taraba, Michael; Tlustos, Reinhard; Toferer, Ernst; Turetschek, Thomas; Winter, Egon; Zanella-Kux, Katja

    2014-05-01

    We report on the MARS2013 mission, a 4-week Mars analog field test in the northern Sahara. Nineteen experiments were conducted by a field crew in Morocco under simulated martian surface exploration conditions, supervised by a Mission Support Center in Innsbruck, Austria. A Remote Science Support team analyzed field data in near real time, providing planning input for the management of a complex system of field assets; two advanced space suit simulators, four robotic vehicles, an emergency shelter, and a stationary sensor platform in a realistic work flow were coordinated by a Flight Control Team. A dedicated flight planning group, external control centers for rover tele-operations, and a biomedical monitoring team supported the field operations. A 10 min satellite communication delay and other limitations pertinent to human planetary surface activities were introduced. The fields of research for the experiments were geology, human factors, astrobiology, robotics, tele-science, exploration, and operations research. This paper provides an overview of the geological context and environmental conditions of the test site and the mission architecture, in particular the communication infrastructure emulating the signal travel time between Earth and Mars. We report on the operational work flows and the experiments conducted, including a deployable shelter prototype for multiple-day extravehicular activities and contingency situations.

  4. Individual differences in spontaneous analogical transfer.

    PubMed

    Kubricht, James R; Lu, Hongjing; Holyoak, Keith J

    2017-05-01

    Research on analogical problem solving has shown that people often fail to spontaneously notice the relevance of a semantically remote source analog when solving a target problem, although they are able to form mappings and derive inferences when given a hint to recall the source. Relatively little work has investigated possible individual differences that predict spontaneous transfer, or how such differences may interact with interventions that facilitate transfer. In this study, fluid intelligence was measured for participants in an analogical problem-solving task, using an abridged version of the Raven's Progressive Matrices (RPM) test. In two experiments, we systematically compared the effect of augmenting verbal descriptions of the source with animations or static diagrams. Solution rates to Duncker's radiation problem were measured across varying source presentation conditions, and participants' understanding of the relevant source material was assessed. The pattern of transfer was best fit by a moderated mediation model: the positive impact of fluid intelligence on spontaneous transfer was mediated by its influence on source comprehension; however, this path was in turn modulated by provision of a supplemental animation via its influence on comprehension of the source. Animated source depictions were most beneficial in facilitating spontaneous transfer for those participants with low scores on the fluid intelligence measure.

  5. Synthetic analog computation in living cells.

    PubMed

    Daniel, Ramiz; Rubens, Jacob R; Sarpeshkar, Rahul; Lu, Timothy K

    2013-05-30

    A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications. Digital logic has been used to build small-scale circuits, but other frameworks may be needed for efficient computation in the resource-limited environments of cells. Here we demonstrate that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. Such synthetic analog gene circuits exploit feedback to implement logarithmically linear sensing, addition, ratiometric and power-law computations. The circuits exhibit Weber's law behaviour as in natural biological systems, operate over a wide dynamic range of up to four orders of magnitude and can be designed to have tunable transfer functions. Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions. By exploiting analog building-block functions that are already naturally present in cells, this approach efficiently implements arithmetic operations and complex functions in the logarithmic domain. Such circuits may lead to new applications for synthetic biology and biotechnology that require complex computations with limited parts, need wide-dynamic-range biosensing or would benefit from the fine control of gene expression.

  6. 47 CFR 25.211 - Analog video transmissions in the Fixed-Satellite Services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Analog video transmissions in the Fixed...) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Technical Standards § 25.211 Analog video transmissions in the Fixed-Satellite Services. (a) Downlink analog video transmissions in the band 3700-4200 MHz...

  7. 47 CFR 25.211 - Analog video transmissions in the Fixed-Satellite Services.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Analog video transmissions in the Fixed...) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Technical Standards § 25.211 Analog video transmissions in the Fixed-Satellite Services. (a) Downlink analog video transmissions in the band 3700-4200 MHz...

  8. 47 CFR 25.211 - Analog video transmissions in the Fixed-Satellite Services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Analog video transmissions in the Fixed...) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Technical Standards § 25.211 Analog video transmissions in the Fixed-Satellite Services. (a) Downlink analog video transmissions in the band 3700-4200 MHz...

  9. 47 CFR 25.211 - Analog video transmissions in the Fixed-Satellite Services.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Analog video transmissions in the Fixed...) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Technical Standards § 25.211 Analog video transmissions in the Fixed-Satellite Services. (a) Downlink analog video transmissions in the band 3700-4200 MHz...

  10. 47 CFR 25.211 - Analog video transmissions in the Fixed-Satellite Services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Analog video transmissions in the Fixed...) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Technical Standards § 25.211 Analog video transmissions in the Fixed-Satellite Services. (a) Downlink analog video transmissions in the band 3700-4200 MHz...

  11. Maxwell's contrived analogy: An early version of the methodology of modeling

    NASA Astrophysics Data System (ADS)

    Hon, Giora; Goldstein, Bernard R.

    2012-11-01

    The term "analogy" stands for a variety of methodological practices all related in one way or another to the idea of proportionality. We claim that in his first substantial contribution to electromagnetism James Clerk Maxwell developed a methodology of analogy which was completely new at the time or, to borrow John North's expression, Maxwell's methodology was a "newly contrived analogue". In his initial response to Michael Faraday's experimental researches in electromagnetism, Maxwell did not seek an analogy with some physical system in a domain different from electromagnetism as advocated by William Thomson; rather, he constructed an entirely artificial one to suit his needs. Following North, we claim that the modification which Maxwell introduced to the methodology of analogy has not been properly appreciated. In view of our examination of the evidence, we argue that Maxwell gave a new meaning to analogy; in fact, it comes close to modeling in current usage.

  12. Concept confusion and concept discernment in basic magnetism using analogical reasoning

    NASA Astrophysics Data System (ADS)

    Lemmer, Miriam; Nicodimus Morabe, Olebogeng

    2017-07-01

    Analogical reasoning is central to all learning, whether in daily life situations, in the classroom or while doing research. Although analogies can aid the learning process of making sense of phenomena and understanding new ideas in terms of known ideas, these should be used with care. This article reports a study of the use of analogies and the consequences of this use in the teaching of magnetism with special reference to misconceptions. We begin by identifying concept confusion and associated misconceptions in magnetism due to in-service physics teachers’ spontaneous analogical reasoning. Two analogy-based experiments that can be used to convert such concept confusion to discernment are then described. These experiments focus on understanding basic principles about sources and interactions of magnetic fields and implement the constructivist learning processes of discrimination and generalization. Lastly, recommendations towards reinforcement of conceptual understanding of basic magnetism in its relation to electricity are proposed.

  13. Synthetic Curcumin Analogs as Inhibitors of β -Amyloid Peptide Aggregation: Potential Therapeutic and Diagnostic Agents for Alzheimer's Disease.

    PubMed

    Bukhari, Syed Nasir Abbas; Jantan, Ibrahim

    2015-01-01

    There is a crucial need to develop new effective drugs for Alzheimer's disease (AD) as the currently available AD treatments provide only momentary and incomplete symptomatic relief. Amongst natural products, curcumin, a major constituent of turmeric, has been intensively investigated for its neuroprotective effect against β-amyloid (Aβ)-induced toxicity in cultured neuronal cells. The ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three structural characteristics such as the presence of two aromatic end groups and their co-planarity, the length and rigidity of the linker region and the substitution conformation of these aromatics. However, curcumin failed to reach adequate brain levels after oral absorption in AD clinical trials due to its low water solubility and poor oral bioavailability. A number of new curcumin analogs that mimic the active site of the compound along with analogs that mimic the curcumin anti-amyloid effect combined with anticholinesterase effect have been developed to enhance the bioavailability, pharmacokinetics, water solubility, stability at physiological conditions and delivery of curcumin. In this article, we have summarized all reported synthetic analogs of curcumin showing effects on β-amyloid and discussed their potential as therapeutic and diagnostic agents for AD.

  14. Using Analogy to Overcome Misconceptions about Conservation of Matter.

    ERIC Educational Resources Information Center

    Stavy, Ruth

    1991-01-01

    This study (n=192) examined the use of analogical instruction to overcome misconceptions about conservation of matter. Students who understood the concept conservation of matter when iodine was evaporated were able to transfer their understanding to the evaporation of acetone. This indicates that teaching by analogy can be an effective tool in…

  15. Sensing Methods for Detecting Analog Television Signals

    NASA Astrophysics Data System (ADS)

    Rahman, Mohammad Azizur; Song, Chunyi; Harada, Hiroshi

    This paper introduces a unified method of spectrum sensing for all existing analog television (TV) signals including NTSC, PAL and SECAM. We propose a correlation based method (CBM) with a single reference signal for sensing any analog TV signals. In addition we also propose an improved energy detection method. The CBM approach has been implemented in a hardware prototype specially designed for participating in Singapore TV white space (WS) test trial conducted by Infocomm Development Authority (IDA) of the Singapore government. Analytical and simulation results of the CBM method will be presented in the paper, as well as hardware testing results for sensing various analog TV signals. Both AWGN and fading channels will be considered. It is shown that the theoretical results closely match with those from simulations. Sensing performance of the hardware prototype will also be presented in fading environment by using a fading simulator. We present performance of the proposed techniques in terms of probability of false alarm, probability of detection, sensing time etc. We also present a comparative study of the various techniques.

  16. Biological Characterization of Microenvironments in a Hypersaline Cold Spring Mars Analog

    PubMed Central

    Sapers, Haley M.; Ronholm, Jennifer; Raymond-Bouchard, Isabelle; Comrey, Raven; Osinski, Gordon R.; Whyte, Lyle G.

    2017-01-01

    with distinct microbial communities in the Canadian high arctic. The finding that these surficial complex microbial communities exist in close proximity to perennial springs demonstrates the existence of a transiently habitable niche in an important Mars analog site. PMID:29312221

  17. Biological Characterization of Microenvironments in a Hypersaline Cold Spring Mars Analog.

    PubMed

    Sapers, Haley M; Ronholm, Jennifer; Raymond-Bouchard, Isabelle; Comrey, Raven; Osinski, Gordon R; Whyte, Lyle G

    2017-01-01

    with distinct microbial communities in the Canadian high arctic. The finding that these surficial complex microbial communities exist in close proximity to perennial springs demonstrates the existence of a transiently habitable niche in an important Mars analog site.

  18. Analog Computer Laboratory with Biological Examples.

    ERIC Educational Resources Information Center

    Strebel, Donald E.

    1979-01-01

    The use of biological examples in teaching applications of the analog computer is discussed and several examples from mathematical ecology, enzyme kinetics, and tracer dynamics are described. (Author/GA)

  19. Mutagen Synergy: Hypermutability Generated by Specific Pairs of Base Analogs

    PubMed Central

    Ang, Jocelyn; Song, Lisa Yun; D'Souza, Sara; Hong, Irene L.; Luhar, Rohan; Yung, Madeline

    2016-01-01

    ABSTRACT We tested pairwise combinations of classical base analog mutagens in Escherichia coli to study possible mutagen synergies. We examined the cytidine analogs zebularine (ZEB) and 5-azacytidine (5AZ), the adenine analog 2-aminopurine (2AP), and the uridine/thymidine analog 5-bromodeoxyuridine (5BrdU). We detected a striking synergy with the 2AP plus ZEB combination, resulting in hypermutability, a 35-fold increase in mutation frequency (to 53,000 × 10−8) in the rpoB gene over that with either mutagen alone. A weak synergy was also detected with 2AP plus 5AZ and with 5BrdU plus ZEB. The pairing of 2AP and 5BrdU resulted in suppression, lowering the mutation frequency of 5BrdU alone by 6.5-fold. Sequencing the mutations from the 2AP plus ZEB combination showed the predominance of two new hot spots for A·T→G·C transitions that are not well represented in either single mutagen spectrum, and one of which is not found even in the spectrum of a mismatch repair-deficient strain. The strong synergy between 2AP and ZEB could be explained by changes in the dinucleoside triphosphate (dNTP) pools. IMPORTANCE Although mutagens have been widely studied, the mutagenic effects of combinations of mutagens have not been fully researched. Here, we show that certain pairwise combinations of base analog mutagens display synergy or suppression. In particular, the combination of 2-aminopurine and zebularine, analogs of adenine and cytidine, respectively, shows a 35-fold increased mutation frequency compared with that of either mutagen alone. Understanding the mechanism of synergy can lead to increased understanding of mutagenic processes. As combinations of base analogs are used in certain chemotherapy regimens, including those involving ZEB and 5AZ, these results indicate that testing the mutagenicity of all drug combinations is prudent. PMID:27457718

  20. Cometabolism of DDT analogs by a Pseudomonas sp.

    PubMed Central

    Francis, A J; Spanggord, R J; Ouchi, G I; Bohonos, N

    1978-01-01

    A Pseudomonas sp. capable of growth on several nonchlorinated and mono-p-chloro-substituted analogs of DDT as a sole carbon source degraded bis(p-chlorophenyl)methane and 1,1-bis(p-chlorophenyl)ethane only in the presence of diphenylethane. The products p-chlorophenylacetic acid and 2-(p-chlorophenyl)-propionic acid were not further metabolized by the bacterium. Other chlorinated analogs of DDT were found to be recalcitrant to cometabolic degradation with diphenylethane. PMID:637537

  1. System and method for linearly amplifying optical analog signals by backward Raman scattering

    DOEpatents

    Lin, Cheng-Heui

    1988-01-01

    A system for linearly amplifying an optical analog signal by backward stimulated Raman scattering comprises a laser source for generating a pump pulse; and an optic fiber having two opposed apertures, a first aperture for receiving the pump pulse and a second aperture for receiving the optical analog signal, wherein the optical analog signal is linearly amplified to an amplified optical analog signal.

  2. System and method for linearly amplifying optical analog signals by backward Raman scattering

    DOEpatents

    Lin, Cheng-Heui

    1988-07-05

    A system for linearly amplifying an optical analog signal by backward stimulated Raman scattering comprises a laser source for generating a pump pulse; and an optic fiber having two opposed apertures, a first aperture for receiving the pump pulse and a second aperture for receiving the optical analog signal, wherein the optical analog signal is linearly amplified to an amplified optical analog signal.

  3. The Acoustic Analogy and Alternative Theories for Jet Noise Prediction

    NASA Technical Reports Server (NTRS)

    Morris, Philip J.; Farassat, F.; Morris, Philip J.

    2002-01-01

    This paper describes several methods for the prediction of jet noise. All but one of the noise prediction schemes are based on Lighthill's or Lilley's acoustic analogy while the other is the jet noise generation model recently proposed by Tam and Auriault. In all the approaches some assumptions must be made concerning the statistical properties of the turbulent sources. In each case the characteristic scales of the turbulence are obtained from a solution of the Reynolds-averaged Navier Stokes equation using a k-epsilon turbulence model. It is shown that, for the same level of empiricism, Tam and Auriault's model yields better agreement with experimental noise measurements than the acoustic analogy. It is then shown that this result is not because of some fundamental flaw in the acoustic analogy approach: but, is associated with the assumptions made in the approximation of the turbulent source statistics. If consistent assumptions are made, both the acoustic analogy and Tam and Auriault's model yield identical noise predictions. The paper concludes with a proposal for an acoustic analogy that provides a clearer identification of the equivalent source mechanisms and a discussion of noise prediction issues that remain to be resolved.

  4. The Acoustic Analogy and Alternative Theories for Jet Noise Prediction

    NASA Technical Reports Server (NTRS)

    Morris, Philip J.; Farassat, F.

    2002-01-01

    This paper describes several methods for the prediction of jet noise. All but one of the noise prediction schemes are based on Lighthill's or Lilley's acoustic analogy while the other is the jet noise generation model recently proposed by Tam and Auriault. In all the approaches some assumptions must be made concerning the statistical properties of the turbulent sources. In each case the characteristic scales of the turbulence are obtained from a solution of the Reynolds-averaged Navier Stokes equation using a k - epsilon turbulence model. It is shown that, for the same level of empiricism, Tam and Auriault's model yields better agreement with experimental noise measurements than the acoustic analogy. It is then shown that this result is not because of some fundamental flaw in the acoustic analogy approach: but, is associated with the assumptions made in the approximation of the turbulent source statistics. If consistent assumptions are made, both the acoustic analogy and Tam and Auriault's model yield identical noise predictions. The paper concludes with a proposal for an acoustic analogy that provides a clearer identification of the equivalent source mechanisms and a discussion of noise prediction issues that remain to be resolved.

  5. Drawing Analogies to Deepen Learning

    ERIC Educational Resources Information Center

    Fava, Michelle

    2017-01-01

    This article offers examples of how drawing can facilitate thinking skills that promote analogical reasoning to enable deeper learning. The instructional design applies cognitive principles, briefly described here. The workshops were developed iteratively, through feedback from student and teacher participants. Elements of the UK National…

  6. Algicidal Activity of Stilbene Analogs

    USDA-ARS?s Scientific Manuscript database

    As part of our continuing search for natural product and natural product-based compounds for the control of off-flavor in catfish, a total of twenty nine stilbene analogs were synthesized and evaluated for algicidal activity against the 2-methylisoborneol (MIB)-producing cyanobacterium Oscillatoria ...

  7. Configurable analog-digital conversion using the neural engineering framework

    PubMed Central

    Mayr, Christian G.; Partzsch, Johannes; Noack, Marko; Schüffny, Rene

    2014-01-01

    Efficient Analog-Digital Converters (ADC) are one of the mainstays of mixed-signal integrated circuit design. Besides the conventional ADCs used in mainstream ICs, there have been various attempts in the past to utilize neuromorphic networks to accomplish an efficient crossing between analog and digital domains, i.e., to build neurally inspired ADCs. Generally, these have suffered from the same problems as conventional ADCs, that is they require high-precision, handcrafted analog circuits and are thus not technology portable. In this paper, we present an ADC based on the Neural Engineering Framework (NEF). It carries out a large fraction of the overall ADC process in the digital domain, i.e., it is easily portable across technologies. The analog-digital conversion takes full advantage of the high degree of parallelism inherent in neuromorphic networks, making for a very scalable ADC. In addition, it has a number of features not commonly found in conventional ADCs, such as a runtime reconfigurability of the ADC sampling rate, resolution and transfer characteristic. PMID:25100933

  8. Extension of analog network coding in wireless information exchange

    NASA Astrophysics Data System (ADS)

    Chen, Cheng; Huang, Jiaqing

    2012-01-01

    Ever since the concept of analog network coding(ANC) was put forward by S.Katti, much attention has been focused on how to utilize analog network coding to take advantage of wireless interference, which used to be considered generally harmful, to improve throughput performance. Previously, only the case of two nodes that need to exchange information has been fully discussed while the issue of extending analog network coding to more than three nodes remains undeveloped. In this paper, we propose a practical transmission scheme to extend analog network coding to more than two nodes that need to exchange information among themselves. We start with the case of three nodes that need to exchange information and demonstrate that through utilizing our algorithm, the throughput can achieve 33% and 20% increase compared with that of traditional transmission scheduling and digital network coding, respectively. Then, we generalize the algorithm so that it can fit for occasions with any number of nodes. We also discuss some technical issues and throughput analysis as well as the bit error rate.

  9. The Nature of Analogical Explanations: High School Physics Teachers Use in Kenya

    ERIC Educational Resources Information Center

    Nashon, Samson Madera

    2004-01-01

    This paper is about a study into the nature of analogies recorded from three Form 2 (Grade 10) classes in Kenya, instructed by three physics teachers. Through a case study method involving classroom observation, several analogies were recorded and analysed. These analogies were predominantly "environmental" (drawn from students'…

  10. Flow cytomeric measurement of DNA and incorporated nucleoside analogs

    DOEpatents

    Dolbeare, Frank A.; Gray, Joe W.

    1989-01-01

    A method is provided for simultaneously measuring total cellular DNA and incorporated nucleoside analog. The method entails altering the cellular DNA of cells grown in the presence of a nucleoside analog so that single stranded and double stranded portions are present. Separate stains are used against the two portions. An immunochemical stain is used against the single stranded portion to provide a measure of incorporated nucleoside analog, and a double strand DNA-specific stain is used against the double stranded portion to simultaneously provide a measure of total cellular DNA. The method permits rapid flow cytometric analysis of cell populations, rapid identification of cycling and noncycling subpopulations, and determination of the efficacy of S phase cytotoxic anticancer agents.

  11. Induction of Abasic Sites by the Drinking-Water Mutagen MX in Salmonella TA100

    EPA Science Inventory

    Mutagen X (MX) is a chlorinated furanone that accounts for more of the mutagenic activity of drinking water than any other disinfection by-product. It is one of the most potent base-substitution mutagens in the Salmonella (Ames) mutagenicity assay, producing primarily GC to TA mu...

  12. Relation Between the Generalized Acoustic Analogy and Lilley's Contributions to Aeroacoustics

    NASA Technical Reports Server (NTRS)

    Goldstein, M. E.

    2010-01-01

    This paper reviews Lilley s reformulation of Lighthill s equation and shows that it can be obtained as a special case of a much more general acoustic analogy. It also shows how this generalized analogy can be used to eliminate some of the difficulties that arise when more conventional parallel flow analogies are applied to high speed jets. And, finally, some recent applications of these ideas are discussed.

  13. Qualitative Differences in Real-Time Solution of Standardized Figural Analogies.

    ERIC Educational Resources Information Center

    Schiano, Diane J.; And Others

    Performance on standardized figural analogy tests is considered highly predictive of academic success. While information-processing models of analogy solution attribute performance differences to quantitative differences in processing parameters, the problem-solving literature suggests that qualitative differences in problem representation and…

  14. Promoting Learning through the Use of Analogies in High School Biology Textbooks.

    ERIC Educational Resources Information Center

    Radford, David L.

    A model for developing instructional analogies was used to produce experimental treatments that included text from a high school biology textbook to which was added extended verbal analogies written by the researcher linking each of two biology concepts to analogous familiar concepts. The control treatment was text from the biology textbook…

  15. The Role of Prior Knowledge in Learning from Analogies in Science Texts

    ERIC Educational Resources Information Center

    Braasch, Jason L. G.; Goldman, Susan R.

    2010-01-01

    Two experiments examined whether inconsistent effects of analogies in promoting new content learning from text are related to prior knowledge of the analogy "per se." In Experiment 1, college students who demonstrated little understanding of weather systems and different levels of prior knowledge (more vs. less) of an analogous everyday…

  16. Digital redesign of anti-wind-up controller for cascaded analog system.

    PubMed

    Chen, Y S; Tsai, J S H; Shieh, L S; Moussighi, M M

    2003-01-01

    The cascaded conventional anti-wind-up (CAW) design method for integral controller is discussed. Then, the prediction-based digital redesign methodology is utilized to find the new pulse amplitude modulated (PAM) digital controller for effective digital control of the analog plant with input saturation constraint. The desired digital controller is determined from existing or pre-designed CAW analog controller. The proposed method provides a novel methodology for indirect digital design of a continuous-time unity output-feedback system with a cascaded analog controller as in the case of PID controllers for industrial control processes with the presence of actuator saturations. It enables us to implement an existing or pre-designed cascaded CAW analog controller via a digital controller effectively.

  17. Reduced repair capacity of a DNA clustered damage site comprised of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 2-deoxyribonolactone results in an increased mutagenic potential of these lesions

    DOE PAGES

    Cunniffe, Siobhan; O’Neill, Peter; Greenberg, Marc M.; ...

    2014-04-01

    A signature of ionizing radiation is the induction of DNA clustered damaged sites. Non-double strand break (DSB) clustered damage has been shown to compromise the base excision repair pathway, extending the lifetimes of the lesions within the cluster, compared to isolated lesions. This increases the likelihood the lesions persist to replication and thus increasing the mutagenic potential of the lesions within the cluster. Lesions formed by ionizing radiation include 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 2-deoxyribonolactone (dL). dL poses an additional challenge to the cell as it is not repaired by the short-patch base excision repair pathway. Here we show recalcitrant dL repairmore » is reflected in mutations observed when DNA containing it and a proximal 8-oxodGuo is replicated in Escherichia coli. 8-oxodGuo in close proximity to dL on the opposing DNA strand results in an enhanced frequency of mutation of the lesions within the cluster and a 20 base sequence flanking the clustered damage site in an E. coli based plasmid assay. In vitro repair of a dL lesion is reduced when compared to the repair of an abasic (AP) site and a tetrahydrofuran (THF), and this is due mainly to a reduction in the activity of polymerase β, leading to retarded FEN1 and ligase 1 activities. This study has given insights in to the biological effects of clusters containing dL.« less

  18. Novel anticancer polymeric conjugates of activated nucleoside analogs

    PubMed Central

    Senanayake, Thulani H.; Warren, Galya; Vinogradov, Serguei V.

    2011-01-01

    Inherent or therapy-induced drug resistance is a major clinical setback in cancer treatment. The extensive usage of cytotoxic nucleobases and nucleoside analogs in chemotherapy also results in the development of specific mechanisms of drug resistance; such as nucleoside transport or activation deficiencies. These drugs are prodrugs; and being converted into the active mono-, di- and triphosphates inside cancer cells following administration, they affect nucleic acid synthesis, nucleotide metabolism, or sensitivity to apoptosis. Previously, we have actively promoted the idea that the nanodelivery of active nucleotide species, e.g. 5′-triphosphates of nucleoside analogs, can enhance drug efficacy and reduce nonspecific toxicity. In this study we report the development of a novel type of drug nanoformulations, polymeric conjugates of nucleoside analogs, which are capable of the efficient transport and sustained release of phosphorylated drugs. These drug conjugates have been synthesized, starting from cholesterol-modified mucoadhesive polyvinyl alcohol or biodegradable dextrin, by covalent attachment of nucleoside analogs through a tetraphosphate linker. Association of cholesterol moieties in aqueous media resulted in intramolecular polymer folding and the formation of small nanogel particles containing 0.5 mmol/g of a 5′-phosphorylated nucleoside analog, e.g. 5-fluoro-2′-deoxyuridine (floxuridine, FdU), an active metabolite of anticancer drug 5-fluorouracyl (5-FU). The polymeric conjugates demonstrated rapid enzymatic release of floxuridine 5′-phosphate and much slower drug release under hydrolytic conditions (pH 1.0–7.4). Among the panel of cancer cell lines, all studied polymeric FdU-conjugates demonstrated an up to 50 times increased cytotoxicity in human prostate cancer PC-3, breast cancer MCF-7 and MDA-MB-231 cells, and more than 100 times higher efficacy against cytarabine-resistant human T-lymphoma (CEM/araC/8) and gemcitabine-resistant follicular

  19. Analog Input Data Acquisition Software

    NASA Technical Reports Server (NTRS)

    Arens, Ellen

    2009-01-01

    DAQ Master Software allows users to easily set up a system to monitor up to five analog input channels and save the data after acquisition. This program was written in LabVIEW 8.0, and requires the LabVIEW runtime engine 8.0 to run the executable.

  20. The GMO-Nanotech (Dis)Analogy?

    ERIC Educational Resources Information Center

    Sandler, Ronald; Kay, W. D.

    2006-01-01

    The genetically-modified-organism (GMO) experience has been prominent in motivating science, industry, and regulatory communities to address the social and ethical dimensions of nanotechnology. However, there are some significant problems with the GMO-nanotech analogy. First, it overstates the likelihood of a GMO-like backlash against…

  1. Analogy between Thermodynamics and Mechanics.

    ERIC Educational Resources Information Center

    Peterson, Mark A.

    1979-01-01

    Establishes and illustrates a formal analogy between the motion of a particle and the "motion" of the equilibrium state of a homogeneous system in a quasistatic process. The purpose is to show that there is a much larger set of natural coordinate transformations in thermodynamics. (GA)

  2. Morphometry of Left Frontal and Temporal Poles Predicts Analogical Reasoning Abilities.

    PubMed

    Aichelburg, Clarisse; Urbanski, Marika; Thiebaut de Schotten, Michel; Humbert, Frederic; Levy, Richard; Volle, Emmanuelle

    2016-03-01

    Analogical reasoning is critical for making inferences and adapting to novelty. It can be studied experimentally using tasks that require creating similarities between situations or concepts, i.e., when their constituent elements share a similar organization or structure. Brain correlates of analogical reasoning have mostly been explored using functional imaging that has highlighted the involvement of the left rostrolateral prefrontal cortex (rlPFC) in healthy subjects. However, whether inter-individual variability in analogical reasoning ability in a healthy adult population is related to differences in brain architecture is unknown. We investigated this question by employing linear regression models of performance in analogy tasks and voxel-based morphometry in 54 healthy subjects. Our results revealed that the ability to reason by analogy was associated with structural variability in the left rlPFC and the anterior part of the inferolateral temporal cortex. Tractography of diffusion-weighted images suggested that these 2 regions have a different set of connections but may exchange information via the arcuate fasciculus. These results suggest that enhanced integrative and semantic abilities supported by structural variation in these areas (or their connectivity) may lead to more efficient analogical reasoning. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Processing-optimised imaging of analog geological models by electrical capacitance tomography

    NASA Astrophysics Data System (ADS)

    Ortiz Alemán, C.; Espíndola-Carmona, A.; Hernández-Gómez, J. J.; Orozco Del Castillo, MG

    2017-06-01

    In this work, the electrical capacitance tomography (ECT) technique is applied in monitoring internal deformation of geological analog models, which are used to study structural deformation mechanisms, in particular for simulating migration and emplacement of allochtonous salt bodies. A rectangular ECT sensor was used for internal visualization of analog geologic deformation. The monitoring of analog models consists in the reconstruction of permittivity images from the capacitance measurements obtained by introducing the model inside the ECT sensor. A simulated annealing (SA) algorithm is used as a reconstruction method, and is optimized by taking full advantage of some special features in a linearized version of this inverse approach. As a second part of this work our SA image reconstruction algorithm is applied to synthetic models, where its performance is evaluated in comparison to other commonly used algorithms such as linear back-projection and iterative Landweber methods. Finally, the SA method is applied to visualise two simple geological analog models. Encouraging results were obtained in terms of the quality of the reconstructed images, as interfaces corresponding to main geological units in the analog model were clearly distinguishable in them. We found reliable results quite useful for real time non-invasive monitoring of internal deformation of analog geological models.

  4. C-Glycosyl Analogs of Oligosaccharides

    NASA Astrophysics Data System (ADS)

    Vauzeilles, Boris; Urban, Dominique; Doisneau, Gilles; Beau, Jean-Marie

    This chapter covers the synthesis of a large collection of "C-oligosaccharides ", synthetic analogs of naturally occurring oligosaccharides in which a carbon atom replaces the anomeric, interglycosidic oxygen atom. These non-natural constructs are stable to chemical and enzymatic degradation, and are primarily devised to probe carbohydrate-based biological processes. These mainly target carbohydrate-protein interactions such as the modulation of glycoenzyme (glycosylhydrolases and transferases) activities or the design of ligands for lectin Carbohydrate Recognition Domains. The discussion is based on the key carbon-carbon bond assembling steps on carbohydrate templates: ionic (anionic and cationic chemistries, sigmatropic rearrangements) or radical assemblage, and olefin metathesis. Synthetic schemes in which at least one of the monosaccharide units is constructed by total synthesis or by cyclization of acyclic chiral chains are presented separately in a "partial de novo synthesis" section. The review also provides comments, when they are known, on the conformational and binding properties of these synthetic analogs, as well as their biological behavior when tested.

  5. [Synthesis and biological activity of substance P analogs].

    PubMed

    Liu, S Y; Zhong, M N; Dong, Y X; Li, Y L; Yuan, X M

    1997-12-01

    Substance P (SP) and its three analogs were synthesized through solid-phase procedure. The fully-protected peptide-resin was cleaved with anhydrous HF.--SH of Cys in [Cys5,9] SP(4-11) was protected with Acm, then deprotected through Iodine oxidation method, the disulfide bridge cyclization was formed subsequently. The crude product was purified on C18 RP-HPLC. The results of guinea-pig isolated ileum test (GPI) showed that the potency of the analogs was as follows: [AcGln5, Pro9] SP(5-11) > SP > SP(4-11) > [Cys5,9] SP(4-11). They induced GPI to contract very fast and showed the characteristics of tachykinin. On the writing test in mice, the results showed: [Cys5,9] SP(4-11) > SP > SP(4-11) > [AcGln5, Pro9] SP(5-11). The biological tests showed that the SP analogs have some extent of selectivity.

  6. The Human DNA glycosylases NEIL1 and NEIL3 Excise Psoralen-Induced DNA-DNA Cross-Links in a Four-Stranded DNA Structure.

    PubMed

    Martin, Peter R; Couvé, Sophie; Zutterling, Caroline; Albelazi, Mustafa S; Groisman, Regina; Matkarimov, Bakhyt T; Parsons, Jason L; Elder, Rhoderick H; Saparbaev, Murat K

    2017-12-12

    Interstrand cross-links (ICLs) are highly cytotoxic DNA lesions that block DNA replication and transcription by preventing strand separation. Previously, we demonstrated that the bacterial and human DNA glycosylases Nei and NEIL1 excise unhooked psoralen-derived ICLs in three-stranded DNA via hydrolysis of the glycosidic bond between the crosslinked base and deoxyribose sugar. Furthermore, NEIL3 from Xenopus laevis has been shown to cleave psoralen- and abasic site-induced ICLs in Xenopus egg extracts. Here we report that human NEIL3 cleaves psoralen-induced DNA-DNA cross-links in three-stranded and four-stranded DNA substrates to generate unhooked DNA fragments containing either an abasic site or a psoralen-thymine monoadduct. Furthermore, while Nei and NEIL1 also cleave a psoralen-induced four-stranded DNA substrate to generate two unhooked DNA duplexes with a nick, NEIL3 targets both DNA strands in the ICL without generating single-strand breaks. The DNA substrate specificities of these Nei-like enzymes imply the occurrence of long uninterrupted three- and four-stranded crosslinked DNA-DNA structures that may originate in vivo from DNA replication fork bypass of an ICL. In conclusion, the Nei-like DNA glycosylases unhook psoralen-derived ICLs in various DNA structures via a genuine repair mechanism in which complex DNA lesions can be removed without generation of highly toxic double-strand breaks.

  7. 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

  8. DNA polymerase θ contributes to the generation of C/G mutations during somatic hypermutation of Ig genes

    PubMed Central

    Masuda, Keiji; Ouchida, Rika; Takeuchi, Arata; Saito, Takashi; Koseki, Haruhiko; Kawamura, Kiyoko; Tagawa, Masatoshi; Tokuhisa, Takeshi; Azuma, Takachika; O-Wang, Jiyang

    2005-01-01

    Somatic hypermutation of Ig variable region genes is initiated by activation-induced cytidine deaminase; however, the activity of multiple DNA polymerases is required to ultimately introduce mutations. DNA polymerase η (Polη) has been implicated in mutations at A/T, but polymerases involved in C/G mutations have not been identified. We have generated mutant mice expressing DNA polymerase (Polθ) specifically devoid of polymerase activity. Compared with WT mice, Polq-inactive (Polq, the gene encoding Polθ) mice exhibited a reduced level of serum IgM and IgG1. The mutant mice mounted relatively normal primary and secondary immune responses to a T-dependent antigen, but the production of high-affinity specific antibodies was partially impaired. Analysis of the JH4 intronic sequences revealed a slight reduction in the overall mutation frequency in Polq-inactive mice. Remarkably, although mutations at A/T were unaffected, mutations at C/G were significantly decreased, indicating an important, albeit not exclusive, role for Polθ activity. The reduction of C/G mutations was particularly focused on the intrinsic somatic hypermutation hotspots and both transitions and transversions were similarly reduced. These findings, together with the recent observation that Polθ efficiently catalyzes the bypass of abasic sites, lead us to propose that Polθ introduces mutations at C/G by replicating over abasic sites generated via uracil-DNA glycosylase. PMID:16172387

  9. In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.

    PubMed

    Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom

    2013-11-26

    Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.

  10. Basalt: Biologic Analog Science Associated with Lava Terrains

    NASA Astrophysics Data System (ADS)

    Lim, D. S. S.; Abercromby, A.; Kobs-Nawotniak, S. E.; Kobayashi, L.; Hughes, S. S.; Chappell, S.; Bramall, N. E.; Deans, M. C.; Heldmann, J. L.; Downs, M.; Cockell, C. S.; Stevens, A. H.; Caldwell, B.; Hoffman, J.; Vadhavk, N.; Marquez, J.; Miller, M.; Squyres, S. W.; Lees, D. S.; Fong, T.; Cohen, T.; Smith, T.; Lee, G.; Frank, J.; Colaprete, A.

    2015-12-01

    This presentation will provide an overview of the BASALT (Biologic Analog Science Associated with Lava Terrains) program. BASALT research addresses Science, Science Operations, and Technology. Specifically, BASALT is focused on the investigation of terrestrial volcanic terrains and their habitability as analog environments for early and present-day Mars. Our scientific fieldwork is conducted under simulated Mars mission constraints to evaluate strategically selected concepts of operations (ConOps) and capabilities with respect to their anticipated value for the joint human and robotic exploration of Mars. a) Science: The BASALT science program is focused on understanding habitability conditions of early and present-day Mars in two relevant Mars-analog locations (the Southwest Rift Zone (SWRZ) and the East Rift Zone (ERZ) flows on the Big Island of Hawai'i and the eastern Snake River Plain (ESRP) in Idaho) to characterize and compare the physical and geochemical conditions of life in these environments and to learn how to seek, identify, and characterize life and life-related chemistry in basaltic environments representing these two epochs of martian history. b) Science Operations: The BASALT team will conduct real (non-simulated) biological and geological science at two high-fidelity Mars analogs, all within simulated Mars mission conditions (including communication latencies and bandwidth constraints) that are based on current architectural assumptions for Mars exploration missions. We will identify which human-robotic ConOps and supporting capabilities enable science return and discovery. c) Technology: BASALT will incorporate and evaluate technologies in to our field operations that are directly relevant to conducting the scientific investigations regarding life and life-related chemistry in Mars-analogous terrestrial environments. BASALT technologies include the use of mobile science platforms, extravehicular informatics, display technologies, communication

  11. CMOS analog switches for adaptive filters

    NASA Technical Reports Server (NTRS)

    Dixon, C. E.

    1980-01-01

    Adaptive active low-pass filters incorporate CMOS (Complimentary Metal-Oxide Semiconductor) analog switches (such as 4066 switch) that reduce variation in switch resistance when filter is switched to any selected transfer function.

  12. Biostable beta-Amino Acid PK/PBAN Analogs: Agonist and Antagonist Properties

    DTIC Science & Technology

    2009-01-01

    peptidases neprilysin and angiotensin converting enzyme that are shown to degrade the natural peptides . Despite the changes to the PK core, analog PK-bA-4...bound peptidase - resistant analogs of the insect allatostatins. Peptides 1999;20:23–9. [21] Nachman RJ, Holman GM, Cook BJ. Active fragments and...pheromonotropic activity of peptidase -resistant topical amphiphilic analogs of pyrokinin/PBAN insect neuropeptides. Peptides 2002;23:2035–43. [28] Nachman RJ

  13. Identification and characterization of a NBS–LRR class resistance gene analog in Pistacia atlantica subsp. Kurdica

    PubMed Central

    Bahramnejad, Bahman

    2014-01-01

    P. atlantica subsp. Kurdica, with the local name of Baneh, is a wild medicinal plant which grows in Kurdistan, Iran. The identification of resistance gene analogs holds great promise for the development of resistant cultivars. A PCR approach with degenerate primers designed according to conserved NBS-LRR (nucleotide binding site-leucine rich repeat) regions of known disease-resistance (R) genes was used to amplify and clone homologous sequences from P. atlantica subsp. Kurdica. A DNA fragment of the expected 500-bp size was amplified. The nucleotide sequence of this amplicon was obtained through sequencing and the predicted amino acid sequence compared to the amino acid sequences of known R-genes revealed significant sequence similarity. Alignment of the deduced amino acid sequence of P. atlantica subsp. Kurdica resistance gene analog (RGA) showed strong identity, ranging from 68% to 77%, to the non-toll interleukin receptor (non-TIR) R-gene subfamily from other plants. A P-loop motif (GMMGGEGKTT), a conserved and hydrophobic motif GLPLAL, a kinase-2a motif (LLVLDDV), when replaced by IAVFDDI in PAKRGA1 and a kinase-3a (FGPGSRIII) were presented in all RGA. A phylogenetic tree, based on the deduced amino-acid sequences of PAKRGA1 and RGAs from different species indicated that they were separated in two clusters, PAKRGA1 being on cluster II. The isolated NBS analogs can be eventually used as guidelines to isolate numerous R-genes in Pistachio. PMID:27843981

  14. European Forest Cover During the Past 12,000 Years: A Palynological Reconstruction Based on Modern Analogs and Remote Sensing

    PubMed Central

    Zanon, Marco; Davis, Basil A. S.; Marquer, Laurent; Brewer, Simon; Kaplan, Jed O.

    2018-01-01

    Characterization of land cover change in the past is fundamental to understand the evolution and present state of the Earth system, the amount of carbon and nutrient stocks in terrestrial ecosystems, and the role played by land-atmosphere interactions in influencing climate. The estimation of land cover changes using palynology is a mature field, as thousands of sites in Europe have been investigated over the last century. Nonetheless, a quantitative land cover reconstruction at a continental scale has been largely missing. Here, we present a series of maps detailing the evolution of European forest cover during last 12,000 years. Our reconstructions are based on the Modern Analog Technique (MAT): a calibration dataset is built by coupling modern pollen samples with the corresponding satellite-based forest-cover data. Fossil reconstructions are then performed by assigning to every fossil sample the average forest cover of its closest modern analogs. The occurrence of fossil pollen assemblages with no counterparts in modern vegetation represents a known limit of analog-based methods. To lessen the influence of no-analog situations, pollen taxa were converted into plant functional types prior to running the MAT algorithm. We then interpolate site-specific reconstructions for each timeslice using a four-dimensional gridding procedure to create continuous gridded maps at a continental scale. The performance of the MAT is compared against methodologically independent forest-cover reconstructions produced using the REVEALS method. MAT and REVEALS estimates are most of the time in good agreement at a trend level, yet MAT regularly underestimates the occurrence of densely forested situations, requiring the application of a bias correction procedure. The calibrated MAT-based maps draw a coherent picture of the establishment of forests in Europe in the Early Holocene with the greatest forest-cover fractions reconstructed between ∼8,500 and 6,000 calibrated years BP. This

  15. European Forest Cover During the Past 12,000 Years: A Palynological Reconstruction Based on Modern Analogs and Remote Sensing.

    PubMed

    Zanon, Marco; Davis, Basil A S; Marquer, Laurent; Brewer, Simon; Kaplan, Jed O

    2018-01-01

    Characterization of land cover change in the past is fundamental to understand the evolution and present state of the Earth system, the amount of carbon and nutrient stocks in terrestrial ecosystems, and the role played by land-atmosphere interactions in influencing climate. The estimation of land cover changes using palynology is a mature field, as thousands of sites in Europe have been investigated over the last century. Nonetheless, a quantitative land cover reconstruction at a continental scale has been largely missing. Here, we present a series of maps detailing the evolution of European forest cover during last 12,000 years. Our reconstructions are based on the Modern Analog Technique (MAT): a calibration dataset is built by coupling modern pollen samples with the corresponding satellite-based forest-cover data. Fossil reconstructions are then performed by assigning to every fossil sample the average forest cover of its closest modern analogs. The occurrence of fossil pollen assemblages with no counterparts in modern vegetation represents a known limit of analog-based methods. To lessen the influence of no-analog situations, pollen taxa were converted into plant functional types prior to running the MAT algorithm. We then interpolate site-specific reconstructions for each timeslice using a four-dimensional gridding procedure to create continuous gridded maps at a continental scale. The performance of the MAT is compared against methodologically independent forest-cover reconstructions produced using the REVEALS method. MAT and REVEALS estimates are most of the time in good agreement at a trend level, yet MAT regularly underestimates the occurrence of densely forested situations, requiring the application of a bias correction procedure. The calibrated MAT-based maps draw a coherent picture of the establishment of forests in Europe in the Early Holocene with the greatest forest-cover fractions reconstructed between ∼8,500 and 6,000 calibrated years BP. This

  16. Analog Video Authentication and Seal Verification Equipment Development

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

    Gregory Lancaster

    Under contract to the US Department of Energy in support of arms control treaty verification activities, the Savannah River National Laboratory in conjunction with the Pacific Northwest National Laboratory, the Idaho National Laboratory and Milagro Consulting, LLC developed equipment for use within a chain of custody regime. This paper discussed two specific devices, the Authentication Through the Lens (ATL) analog video authentication system and a photographic multi-seal reader. Both of these devices have been demonstrated in a field trial, and the experience gained throughout will also be discussed. Typically, cryptographic methods are used to prove the authenticity of digital imagesmore » and video used in arms control chain of custody applications. However, in some applications analog cameras are used. Since cryptographic authentication methods will not work on analog video streams, a simple method of authenticating analog video was developed and tested. A photographic multi-seal reader was developed to image different types of visual unique identifiers for use in chain of custody and authentication activities. This seal reader is unique in its ability to image various types of seals including the Cobra Seal, Reflective Particle Tags, and adhesive seals. Flicker comparison is used to compare before and after images collected with the seal reader in order to detect tampering and verify the integrity of the seal.« less

  17. Cryoprotective ability of betaine-type metabolite analogs during freezing denaturation of enzymes.

    PubMed

    Nakagawa, Yuichi; Sota, Masahiro; Koumoto, Kazuya

    2015-08-01

    To evaluate an analog library of betaine-type cellular metabolites, which are naturally found in polar fish for survival in subzero temperatures, for preventing denaturation of enzymes during freezing. Comparison of the cryoprotective ability of reported cryoprotectants, such as dimethylsulfoxide, glycerol, ectoine, hydroxyectoine, and trehalose, with betaine-type analogs using α-glucosidase revealed that analogs introducing C3-C6 alkyl chains into an ammonium cation retained 20 % higher activity than the control cryoprotectants at the same concentration. In particular, the analog possessing triplicate n-butyl chains showed a profound effect. It allowed retention of enzyme activity to 95 % even after 100 freeze-thaw cycles, while addition of the control cryoprotectants decreased the activity to 10-20 %. The cryoprotective ability of betaine-type analogs can be applied not only to α-glucosidase but also other enzymes such as β-glucosidase, alkaline phosphatase, lactose dehydrogenase, sulfatase, and horseradish peroxidase. Synthetic betaine-type metabolite analogs possess practicable cryoprotective ability for various enzymes, and are considerably superior to previously reported cryoprotectants.

  18. Mathematical Analogy and Metaphorical Insight

    ERIC Educational Resources Information Center

    Zwicky, Jan

    2010-01-01

    How are we to understand the power of certain literary metaphors? The author argues that the apprehension of good metaphors is importantly similar to the apprehension of fruitful mathematical analogies: both involve a structural realignment of vision. The author then explores consequences of this claim, drawing conceptually significant parallels…

  19. Bayesian Analogy with Relational Transformations

    ERIC Educational Resources Information Center

    Lu, Hongjing; Chen, Dawn; Holyoak, Keith J.

    2012-01-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy…

  20. Exploring the use of multiple analogical models when teaching and learning chemical equilibrium

    NASA Astrophysics Data System (ADS)

    Harrison, Allan G.; de Jong, Onno

    2005-12-01

    This study describes the multiple analogical models used to introduce and teach Grade 12 chemical equilibrium. We examine the teacher's reasons for using models, explain each model's development during the lessons, and analyze the understandings students derived from the models. A case study approach was used and the data were drawn from the observation of three consecutive Grade 12 lessons on chemical equilibrium, pre- and post-lesson interviews, and delayed student interviews. The key analogical models used in teaching were: the school dance; the sugar in a teacup; the pot of curry; and the busy highway. The lesson and interview data were subject to multiple, independent analyses and yielded the following outcomes: The teacher planned to use the students' prior knowledge wherever possible and he responded to student questions with stories and extended and enriched analogies. He planned to discuss where each analogy broke down but did not. The students enjoyed the teaching but built variable mental models of equilibrium and some of their analogical mappings were unreliable. A female student disliked masculine analogies, other students tended to see elements of the multiple models in isolation, and some did not recognize all the analogical mappings embedded in the teaching plan. Most students learned that equilibrium reactions are dynamic, occur in closed systems, and the forward and reverse reactions are balanced. We recommend the use of multiple analogies like these and insist that teachers always show where the analogy breaks down and carefully negotiate the conceptual outcomes.

  1. Analog and digital transport of RF channels over converged 5G wireless-optical networks

    NASA Astrophysics Data System (ADS)

    Binh, Le Nguyen

    2016-02-01

    Under the exponential increase demand by the emerging 5G wireless access networking and thus data-center based Internet, novel and economical transport of RF channels to and from wireless access systems. This paper presents the transport technologies of RF channels over the analog and digital domain so as to meet the demands of the transport capacity reaching multi-Tbps, in the followings: (i) The convergence of 5G broadband wireless and optical networks and its demands on capacity delivery and network structures; (ii) Analog optical technologies for delivery of both the information and RF carriers to and from multiple-input multiple-output (MIMO) antenna sites so as to control the beam steering of MIMO antenna in the mmW at either 28.6 GHz and 56.8 GHz RF carrier and delivery of channels of aggregate capacity reaching several Tbps; (ii) Transceiver employing advanced digital modulation formats and digital signal processing (DSP) so as to provide 100G and beyond transmission rate to meet the ultra-high capacity demands with flexible spectral grids, hence pay-on-demand services. The interplay between DSP-based and analog transport techniques is examined; (iii) Transport technologies for 5G cloud access networks and associate modulation and digital processing techniques for capacity efficiency; and (iv) Finally the integrated optic technologies with novel lasers, comb generators and simultaneous dual function photonic devices for both demultiplexing/multiplexing and modulation are proposed, hence a system on chip structure can be structured. Quantum dot lasers and matrixes of micro ring resonators are integrated on the same Si-on-Silica substrate are proposed and described.

  2. Reasoning by analogy as an aid to heuristic theorem proving.

    NASA Technical Reports Server (NTRS)

    Kling, R. E.

    1972-01-01

    When heuristic problem-solving programs are faced with large data bases that contain numbers of facts far in excess of those needed to solve any particular problem, their performance rapidly deteriorates. In this paper, the correspondence between a new unsolved problem and a previously solved analogous problem is computed and invoked to tailor large data bases to manageable sizes. This paper outlines the design of an algorithm for generating and exploiting analogies between theorems posed to a resolution-logic system. These algorithms are believed to be the first computationally feasible development of reasoning by analogy to be applied to heuristic theorem proving.

  3. Low-power analog integrated circuits for wireless ECG acquisition systems.

    PubMed

    Tsai, Tsung-Heng; Hong, Jia-Hua; Wang, Liang-Hung; Lee, Shuenn-Yuh

    2012-09-01

    This paper presents low-power analog ICs for wireless ECG acquisition systems. Considering the power-efficient communication in the body sensor network, the required low-power analog ICs are developed for a healthcare system through miniaturization and system integration. To acquire the ECG signal, a low-power analog front-end system, including an ECG signal acquisition board, an on-chip low-pass filter, and an on-chip successive-approximation analog-to-digital converter for portable ECG detection devices is presented. A quadrature CMOS voltage-controlled oscillator and a 2.4 GHz direct-conversion transmitter with a power amplifier and upconversion mixer are also developed to transmit the ECG signal through wireless communication. In the receiver, a 2.4 GHz fully integrated CMOS RF front end with a low-noise amplifier, differential power splitter, and quadrature mixer based on current-reused folded architecture is proposed. The circuits have been implemented to meet the specifications of the IEEE 802.15.4 2.4 GHz standard. The low-power ICs of the wireless ECG acquisition systems have been fabricated using a 0.18 μm Taiwan Semiconductor Manufacturing Company (TSMC) CMOS standard process. The measured results on the human body reveal that ECG signals can be acquired effectively by the proposed low-power analog front-end ICs.

  4. Automatic Generation of Analogy Questions for Student Assessment: An Ontology-Based Approach

    ERIC Educational Resources Information Center

    Alsubait, Tahani; Parsia, Bijan; Sattler, Uli

    2012-01-01

    Different computational models for generating analogies of the form "A is to B as C is to D" have been proposed over the past 35 years. However, analogy generation is a challenging problem that requires further research. In this article, we present a new approach for generating analogies in Multiple Choice Question (MCQ) format that can be used…

  5. Analog cosmological particle generation in a superconducting circuit

    NASA Astrophysics Data System (ADS)

    Tian, Zehua; Jing, Jiliang; Dragan, Andrzej

    2017-06-01

    We propose the use of a waveguidelike transmission line based on direct-current superconducting quantum interference devices (dc-SQUID) and demonstrate that the node flux in this transmission line behaves in the same way as quantum fields in an expanding (or contracting) universe. We show how to detect the analog cosmological particle generation and analyze its feasibility with current circuit quantum electrodynamics (cQED) technology. Our setup in principle paves a new way for the exploration of analog quantum gravitational effects.

  6. Stabilometer Computerized Analog Recording System for Studying Gross Motor Skill Learning

    ERIC Educational Resources Information Center

    Chasey, William C., Jr.; And Others

    1976-01-01

    The stabilometer computerized analog recording system (SCARS) provides for storing analog and digital information on a single channel audio tape recorder at lower cost and greater versatility than other systems. (MB)

  7. GABAA receptor activity modulating piperine analogs: In vitro metabolic stability, metabolite identification, CYP450 reaction phenotyping, and protein binding.

    PubMed

    Zabela, Volha; Hettich, Timm; Schlotterbeck, Götz; Wimmer, Laurin; Mihovilovic, Marko D; Guillet, Fabrice; Bouaita, Belkacem; Shevchenko, Bénédicte; Hamburger, Matthias; Oufir, Mouhssin

    2018-01-01

    In a screening of natural products for allosteric modulators of GABA A receptors (γ-aminobutyric acid type A receptor), piperine was identified as a compound targeting a benzodiazepine-independent binding site. Given that piperine is also an activator of TRPV1 (transient receptor potential vanilloid type 1) receptors involved in pain signaling and thermoregulation, a series of piperine analogs were prepared in several cycles of structural optimization, with the aim of separating GABA A and TRPV1 activating properties. We here investigated the metabolism of piperine and selected analogs in view of further cycles of lead optimization. Metabolic stability of the compounds was evaluated by incubation with pooled human liver microsomes, and metabolites were analyzed by UHPLC-Q-TOF-MS. CYP450 isoenzymes involved in metabolism of compounds were identified by reaction phenotyping with Silensomes™. Unbound fraction in whole blood was determined by rapid equilibrium dialysis. Piperine was the metabolically most stable compound. Aliphatic hydroxylation, and N- and O-dealkylation were the major routes of oxidative metabolism. Piperine was exclusively metabolized by CYP1A2, whereas CYP2C9 contributed significantly in the oxidative metabolism of all analogs. Extensive binding to blood constituents was observed for all compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Reasoning by analogy requires the left frontal pole: lesion-deficit mapping and clinical implications.

    PubMed

    Urbanski, Marika; Bréchemier, Marie-Laure; Garcin, Béatrice; Bendetowicz, David; Thiebaut de Schotten, Michel; Foulon, Chris; Rosso, Charlotte; Clarençon, Frédéric; Dupont, Sophie; Pradat-Diehl, Pascale; Labeyrie, Marc-Antoine; Levy, Richard; Volle, Emmanuelle

    2016-06-01

    SEE BURGESS DOI101093/BRAIN/AWW092 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE  : Analogical reasoning is at the core of the generalization and abstraction processes that enable concept formation and creativity. The impact of neurological diseases on analogical reasoning is poorly known, despite its importance in everyday life and in society. Neuroimaging studies of healthy subjects and the few studies that have been performed on patients have highlighted the importance of the prefrontal cortex in analogical reasoning. However, the critical cerebral bases for analogical reasoning deficits remain elusive. In the current study, we examined analogical reasoning abilities in 27 patients with focal damage in the frontal lobes and performed voxel-based lesion-behaviour mapping and tractography analyses to investigate the structures critical for analogical reasoning. The findings revealed that damage to the left rostrolateral prefrontal region (or some of its long-range connections) specifically impaired the ability to reason by analogies. A short version of the analogy task predicted the existence of a left rostrolateral prefrontal lesion with good accuracy. Experimental manipulations of the analogy tasks suggested that this region plays a role in relational matching or integration. The current lesion approach demonstrated that the left rostrolateral prefrontal region is a critical node in the analogy network. Our results also suggested that analogy tasks should be translated to clinical practice to refine the neuropsychological assessment of patients with frontal lobe lesions. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Periglacial and glacial analogs for Martian landforms

    NASA Technical Reports Server (NTRS)

    Rossbacher, Lisa A.

    1992-01-01

    The list of useful terrestrial analogs for Martian landforms has been expanded to include: features developed by desiccation processes; catastrophic flood features associated with boulder-sized materials; and sorted ground developed at a density boundary. Quantitative analytical techniques developed for physical geography have been adapted and applied to planetary studies, including: quantification of the patterns of polygonally fractured ground to describe pattern randomness independent of pattern size, with possible correlation to the mechanism of origin and quantification of the relative area of a geomorphic feature or region in comparison to planetary scale. Information about Martian geomorphology studied in this project was presented at professional meetings world-wide, at seven colleges and universities, in two interactive televised courses, and as part of two books. Overall, this project has expanded the understanding of the range of terrestrial analogs for Martian landforms, including identifying several new analogs. The processes that created these terrestrial features are characterized by both cold temperatures and low humidity, and therefore both freeze-thaw and desiccation processes are important. All these results support the conclusion that water has played a significant role in the geomorphic history of Mars.

  10. Protocol Analysis of Aptitude Differences in Figural Analogy Problem Representation.

    ERIC Educational Resources Information Center

    Schiano, Diane J.

    Individual differences in performance on figural analogy tests are usually attributed to quantitative differences in processing parameters rather than to qualitative differences in the formation and use of representations. Yet aptitude-related differences in categorizing standardized figural analogy problems between high and low scorers have been…

  11. Neural underpinnings of divergent production of rules in numerical analogical reasoning.

    PubMed

    Wu, Xiaofei; Jung, Rex E; Zhang, Hao

    2016-05-01

    Creativity plays an important role in numerical problem solving. Although the neural underpinnings of creativity have been studied over decades, very little is known about neural mechanisms of the creative process that relates to numerical problem solving. In the present study, we employed a numerical analogical reasoning task with functional Magnetic Resonance Imaging (fMRI) to investigate the neural correlates of divergent production of rules in numerical analogical reasoning. Participants performed two tasks: a multiple solution analogical reasoning task and a single solution analogical reasoning task. Results revealed that divergent production of rules involves significant activations at Brodmann area (BA) 10 in the right middle frontal cortex, BA 40 in the left inferior parietal lobule, and BA 8 in the superior frontal cortex. The results suggest that right BA 10 and left BA 40 are involved in the generation of novel rules, and BA 8 is associated with the inhibition of initial rules in numerical analogical reasoning. The findings shed light on the neural mechanisms of creativity in numerical processing. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Satellite analog FDMA/FM to digital TDMA conversion

    NASA Technical Reports Server (NTRS)

    Driggers, T.; Nguyen, T.; Kolavennu, V.

    1987-01-01

    The results of a study which investigated design issues regarding the use of analog to digital (A/D) conversion on board a satellite are presented. The need for A/D, and of course D/A as well, conversion arose from a satellite design which required analog FDMA/FM up and down links to/from a digitally modulated intersatellite link. There are also some advantages when one must interconnect a large number of various spot beams which are using analog, and therefore cannot take advantage of SS/TDMA switching among the beams, thus resulting in low fill factors. Various tradeoffs were performed regarding the implementation of on-board A/D processing, including mass, power, and costs. The various technologies which were considered included flash ADCs, surface acoustic wave (SAW) devices, and digital signal processing (DSP) chips. Impact analyses were also performed to determine the effect on ground stations to convert to digital if the A/D approach were not implemented.

  13. Analog to digital workflow improvement: a quantitative study.

    PubMed

    Wideman, Catherine; Gallet, Jacqueline

    2006-01-01

    This study tracked a radiology department's conversion from utilization of a Kodak Amber analog system to a Kodak DirectView DR 5100 digital system. Through the use of ProModel Optimization Suite, a workflow simulation software package, significant quantitative information was derived from workflow process data measured before and after the change to a digital system. Once the digital room was fully operational and the radiology staff comfortable with the new system, average patient examination time was reduced from 9.24 to 5.28 min, indicating that a higher patient throughput could be achieved. Compared to the analog system, chest examination time for modality specific activities was reduced by 43%. The percentage of repeat examinations experienced with the digital system also decreased to 8% vs. the level of 9.5% experienced with the analog system. The study indicated that it is possible to quantitatively study clinical workflow and productivity by using commercially available software.

  14. Stretched Analogies and School Reform.

    ERIC Educational Resources Information Center

    Hesse, Joseph J., III

    1997-01-01

    Develops a "theory of stretched analogies" to explain limitations of student-as-customer and athletic motivational notions. Schools are neither shopping malls nor knowledge factories; for unengaged students, there will be nothing to purchase. Also, caring teacher-coaches must decide how high to set the bar. The goal is helping all…

  15. New size-expanded RNA nucleobase analogs: a detailed theoretical study.

    PubMed

    Zhang, Laibin; Zhang, Zhenwei; Ren, Tingqi; Tian, Jianxiang; Wang, Mei

    2015-04-05

    Fluorescent nucleobase analogs have attracted much attention in recent years due to their potential applications in nucleic acids research. In this work, four new size-expanded RNA base analogs were computationally designed and their structural, electronic, and optical properties are investigated by means of DFT calculations. The results indicate that these analogs can form stable Watson-Crick base pairs with natural counterparts and they have smaller ionization potentials and HOMO-LUMO gaps than natural ones. Particularly, the electronic absorption spectra and fluorescent emission spectra are calculated. The calculated excitation maxima are greatly red-shifted compared with their parental and natural bases, allowing them to be selectively excited. In gas phase, the fluorescence from them would be expected to occur around 526, 489, 510, and 462 nm, respectively. The influences of water solution and base pairing on the relevant absorption spectra of these base analogs are also examined. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Associative Pattern Recognition In Analog VLSI Circuits

    NASA Technical Reports Server (NTRS)

    Tawel, Raoul

    1995-01-01

    Winner-take-all circuit selects best-match stored pattern. Prototype cascadable very-large-scale integrated (VLSI) circuit chips built and tested to demonstrate concept of electronic associative pattern recognition. Based on low-power, sub-threshold analog complementary oxide/semiconductor (CMOS) VLSI circuitry, each chip can store 128 sets (vectors) of 16 analog values (vector components), vectors representing known patterns as diverse as spectra, histograms, graphs, or brightnesses of pixels in images. Chips exploit parallel nature of vector quantization architecture to implement highly parallel processing in relatively simple computational cells. Through collective action, cells classify input pattern in fraction of microsecond while consuming power of few microwatts.

  17. Use of the "Tree" Analogy in Evolution Teaching by Biology Teachers

    NASA Astrophysics Data System (ADS)

    Marcelos, Maria Fátima; Nagem, Ronaldo Luiz

    2012-04-01

    This work discusses the use of Darwin's `Tree of Life' as a didactic analogy and metaphor in teaching evolution. It investigates whether biology teachers of pupils from 17 to 18 years old know Darwin's text `Tree of Life'. In addition, it examines whether those teachers systematically employ either the analogies present in that text or other analogies between the tree and evolution, and whether they adopt a specific methodology for teaching with analogies and metaphors (A&M). The academic training of teachers regarding use of A&M is review briefly. A diagnostic study was carried out with biology teachers in a public school in the town of Contagem in the state of Minas Gerais in Brazil. The data were obtained through direct observation, questionnaires and a focus group. The teachers pointed out in the questionnaires that some details of Darwin's analogy are utilized as a resource. However, analysis of the data indicates that the `Tree of Life' text is not known or utilized in class. At the same time, the teachers state that they use aspects of the tree as a didactic resource to teach evolution and that its use facilitates the learning of content. The teachers have little knowledge of specific methodologies of teaching with analogies and metaphors, revealing that their training is incomplete in this area.

  18. A Systematic Evaluation of Analogs for the Read-across Prediction of Estrogenicity (SOT)

    EPA Science Inventory

    Read-across is a data gap filling technique widely used within category and analog approaches to predict a biological property for a target data-poor chemical using known information from similar (source analog) chemical(s). Potential source analogs are typically identified base...

  19. A family of chaotic pure analog coding schemes based on baker's map function

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Li, Jing; Lu, Xuanxuan; Yuen, Chau; Wu, Jun

    2015-12-01

    This paper considers a family of pure analog coding schemes constructed from dynamic systems which are governed by chaotic functions—baker's map function and its variants. Various decoding methods, including maximum likelihood (ML), minimum mean square error (MMSE), and mixed ML-MMSE decoding algorithms, have been developed for these novel encoding schemes. The proposed mirrored baker's and single-input baker's analog codes perform a balanced protection against the fold error (large distortion) and weak distortion and outperform the classical chaotic analog coding and analog joint source-channel coding schemes in literature. Compared to the conventional digital communication system, where quantization and digital error correction codes are used, the proposed analog coding system has graceful performance evolution, low decoding latency, and no quantization noise. Numerical results show that under the same bandwidth expansion, the proposed analog system outperforms the digital ones over a wide signal-to-noise (SNR) range.

  20. Extensional flow of blood analog solutions in microfluidic devices

    PubMed Central

    Sousa, P. C.; Pinho, F. T.; Oliveira, M. S. N.; Alves, M. A.

    2011-01-01

    In this study, we show the importance of extensional rheology, in addition to the shear rheology, in the choice of blood analog solutions intended to be used in vitro for mimicking the microcirculatory system. For this purpose, we compare the flow of a Newtonian fluid and two well-established viscoelastic blood analog polymer solutions through microfluidic channels containing both hyperbolic and abrupt contractions∕expansions. The hyperbolic shape was selected in order to impose a nearly constant strain rate at the centerline of the microchannels and achieve a quasihomogeneous and strong extensional flow often found in features of the human microcirculatory system such as stenoses. The two blood analog fluids used are aqueous solutions of a polyacrylamide (125 ppm w∕w) and of a xanthan gum (500 ppm w∕w), which were characterized rheologically in steady-shear flow using a rotational rheometer and in extension using a capillary breakup extensional rheometer (CaBER). Both blood analogs exhibit a shear-thinning behavior similar to that of whole human blood, but their relaxation times, obtained from CaBER experiments, are substantially different (by one order of magnitude). Visualizations of the flow patterns using streak photography, measurements of the velocity field using microparticle image velocimetry, and pressure-drop measurements were carried out experimentally for a wide range of flow rates. The experimental results were also compared with the numerical simulations of the flow of a Newtonian fluid and a generalized Newtonian fluid with shear-thinning behavior. Our results show that the flow patterns of the two blood analog solutions are considerably different, despite their similar shear rheology. Furthermore, we demonstrate that the elastic properties of the fluid have a major impact on the flow characteristics, with the polyacrylamide solution exhibiting a much stronger elastic character. As such, these properties must be taken into account in the