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Sample records for riboswitch ligand analogs

  1. Ligand design for riboswitches, an emerging target class for novel antibiotics.

    Science.gov (United States)

    Rekand, Illimar Hugo; Brenk, Ruth

    2017-09-01

    Riboswitches are cis-acting gene regulatory elements and constitute potential targets for new antibiotics. Recent studies in this field have started to explore these targets for drug discovery. New ligands found by fragment screening, design of analogs of the natural ligands or serendipitously by phenotypic screening have shown antibacterial effects in cell assays against a range of bacteria strains and in animal models. In this review, we highlight the most advanced drug design work of riboswitch ligands and discuss the challenges in the field with respect to the development of antibiotics with a new mechanism of action.

  2. Atomic resolution mechanistic studies of ribocil: A highly selective unnatural ligand mimic of the E. coli FMN riboswitch

    Energy Technology Data Exchange (ETDEWEB)

    Howe, John A.; Xiao, Li; Fischmann, Thierry O.; Wang, Hao; Tang, Haifeng; Villafania, Artjohn; Zhang, Rumin; Barbieri, Christopher M.; Roemer, Terry (Merck)

    2016-08-02

    Bacterial riboswitches are non-coding RNA structural elements that direct gene expression in numerous metabolic pathways. The key regulatory roles of riboswitches, and the urgent need for new classes of antibiotics to treat multi-drug resistant bacteria, has led to efforts to develop small-molecules that mimic natural riboswitch ligands to inhibit metabolic pathways and bacterial growth. Recently, we reported the results of a phenotypic screen targeting the riboflavin biosynthesis pathway in the Gram-negative bacteria Escherichia coli that led to the identification of ribocil, a small molecule inhibitor of the flavin mononucleotide (FMN) riboswitch controlling expression of this biosynthetic pathway. Although ribocil is structurally distinct from FMN, ribocil functions as a potent and highly selective synthetic mimic of the natural ligand to repress riboswitch-mediated ribB gene expression and inhibit bacterial growth both in vitro and in vivo. Herein, we expand our analysis of ribocil; including mode of binding in the FMN binding pocket of the riboswitch, mechanisms of resistance and structure-activity relationship guided efforts to generate more potent analogs.

  3. Challenges of ligand identification for the second wave of orphan riboswitch candidates.

    Science.gov (United States)

    Greenlee, Etienne B; Stav, Shira; Atilho, Ruben M; Brewer, Kenneth I; Harris, Kimberly A; Malkowski, Sarah N; Mirihana Arachchilage, Gayan; Perkins, Kevin R; Sherlock, Madeline E; Breaker, Ronald R

    2018-03-04

    Orphan riboswitch candidates are noncoding RNA motifs whose representatives are believed to function as genetic regulatory elements, but whose target ligands have yet to be identified. The study of certain orphans, particularly classes that have resisted experimental validation for many years, has led to the discovery of important biological pathways and processes once their ligands were identified. Previously, we highlighted details for four of the most common and intriguing orphan riboswitch candidates. This facilitated the validation of riboswitches for the signaling molecules c-di-AMP, ZTP, and ppGpp, the metal ion Mn 2+ , and the metabolites guanidine and PRPP. Such studies also yield useful linkages between the ligands sensed by the riboswitches and numerous biochemical pathways. In the current report, we describe the known characteristics of 30 distinct classes of orphan riboswitch candidates - some of which have remained unsolved for over a decade. We also discuss the prospects for uncovering novel biological insights via focused studies on these RNAs. Lastly, we make recommendations for experimental objectives along the path to finding ligands for these mysterious RNAs.

  4. Heterogeneity and dynamics of the ligand recognition mode in purine-sensing riboswitches.

    Science.gov (United States)

    Jain, Niyati; Zhao, Liang; Liu, John D; Xia, Tianbing

    2010-05-04

    High-resolution crystal structures and biophysical analyses of purine-sensing riboswitches have revealed that a network of hydrogen bonding interactions appear to be largey responsible for discrimination of cognate ligands against structurally related compounds. Here we report that by using femtosecond time-resolved fluorescence spectroscopy to capture the ultrafast decay dynamics of the 2-aminopurine base as the ligand, we have detected the presence of multiple conformations of the ligand within the binding pockets of one guanine-sensing and two adenine-sensing riboswitches. All three riboswitches have similar conformational distributions of the ligand-bound state. The known crystal structures represent the global minimum that accounts for 50-60% of the population, where there is no significant stacking interaction between the ligand and bases of the binding pocket, but the hydrogen-bonding cage collectively provides an electronic environment that promotes an ultrafast ( approximately 1 ps) charge transfer pathway. The ligand also samples multiple conformations in which it significantly stacks with either the adenine or the uracil bases of the A21-U75 and A52-U22 base pairs that form the ceiling and floor of the binding pocket, respectively, but favors the larger adenine bases. These alternative conformations with well-defined base stacking interactions are approximately 1-1.5 kcal/mol higher in DeltaG degrees than the global minimum and have distinct charge transfer dynamics within the picosecond to nanosecond time regime. Inside the pocket, the purine ligand undergoes dynamic motion on the low nanosecond time scale, sampling the multiple conformations based on time-resolved anisotropy decay dynamics. These results allowed a description of the energy landscape of the bound ligand with intricate details and demonstrated the elastic nature of the ligand recognition mode by the purine-sensing riboswitches, where there is a dynamic balance between hydrogen bonding

  5. Integrating and Amplifying Signal from Riboswitch Biosensors

    Science.gov (United States)

    2014-08-01

    promoter is only activated in the presence of both hrpR and hrpS. RSA : Riboswitch to ligand A; RSB: Riboswitch to ligand B. Figure 2: Plasmid...binding to the purine riboswitch aptamers domain. J. Mol. Biol. 359: 754- 768 Guet, C. C., Elowitz, M. B., Hsing, W., and Leibler, S. (2002

  6. Design principles for riboswitch function.

    Directory of Open Access Journals (Sweden)

    Chase L Beisel

    2009-04-01

    Full Text Available Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence-function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands.

  7. Co-Transcriptional Folding and Regulation Mechanisms of Riboswitches

    Directory of Open Access Journals (Sweden)

    Sha Gong

    2017-07-01

    Full Text Available Riboswitches are genetic control elements within non-coding regions of mRNA. These self-regulatory elements have been found to sense a range of small metabolites, ions, and other physical signals to exert regulatory control of transcription, translation, and splicing. To date, more than a dozen riboswitch classes have been characterized that vary widely in size and secondary structure. Extensive experiments and theoretical studies have made great strides in understanding the general structures, genetic mechanisms, and regulatory activities of individual riboswitches. As the ligand-dependent co-transcriptional folding and unfolding dynamics of riboswitches are the key determinant of gene expression, it is important to investigate the thermodynamics and kinetics of riboswitches both in the presence and absence of metabolites under the transcription. This review will provide a brief summary of the studies about the regulation mechanisms of the pbuE, SMK, yitJ, and metF riboswitches based on the ligand-dependent co-transcriptional folding of the riboswitches.

  8. Computational Methods for Modeling Aptamers and Designing Riboswitches

    Directory of Open Access Journals (Sweden)

    Sha Gong

    2017-11-01

    Full Text Available Riboswitches, which are located within certain noncoding RNA region perform functions as genetic “switches”, regulating when and where genes are expressed in response to certain ligands. Understanding the numerous functions of riboswitches requires computation models to predict structures and structural changes of the aptamer domains. Although aptamers often form a complex structure, computational approaches, such as RNAComposer and Rosetta, have already been applied to model the tertiary (three-dimensional (3D structure for several aptamers. As structural changes in aptamers must be achieved within the certain time window for effective regulation, kinetics is another key point for understanding aptamer function in riboswitch-mediated gene regulation. The coarse-grained self-organized polymer (SOP model using Langevin dynamics simulation has been successfully developed to investigate folding kinetics of aptamers, while their co-transcriptional folding kinetics can be modeled by the helix-based computational method and BarMap approach. Based on the known aptamers, the web server Riboswitch Calculator and other theoretical methods provide a new tool to design synthetic riboswitches. This review will represent an overview of these computational methods for modeling structure and kinetics of riboswitch aptamers and for designing riboswitches.

  9. Secondary structural entropy in RNA switch (Riboswitch) identification.

    Science.gov (United States)

    Manzourolajdad, Amirhossein; Arnold, Jonathan

    2015-04-28

    RNA regulatory elements play a significant role in gene regulation. Riboswitches, a widespread group of regulatory RNAs, are vital components of many bacterial genomes. These regulatory elements generally function by forming a ligand-induced alternative fold that controls access to ribosome binding sites or other regulatory sites in RNA. Riboswitch-mediated mechanisms are ubiquitous across bacterial genomes. A typical class of riboswitch has its own unique structural and biological complexity, making de novo riboswitch identification a formidable task. Traditionally, riboswitches have been identified through comparative genomics based on sequence and structural homology. The limitations of structural-homology-based approaches, coupled with the assumption that there is a great diversity of undiscovered riboswitches, suggests the need for alternative methods for riboswitch identification, possibly based on features intrinsic to their structure. As of yet, no such reliable method has been proposed. We used structural entropy of riboswitch sequences as a measure of their secondary structural dynamics. Entropy values of a diverse set of riboswitches were compared to that of their mutants, their dinucleotide shuffles, and their reverse complement sequences under different stochastic context-free grammar folding models. Significance of our results was evaluated by comparison to other approaches, such as the base-pairing entropy and energy landscapes dynamics. Classifiers based on structural entropy optimized via sequence and structural features were devised as riboswitch identifiers and tested on Bacillus subtilis, Escherichia coli, and Synechococcus elongatus as an exploration of structural entropy based approaches. The unusually long untranslated region of the cotH in Bacillus subtilis, as well as upstream regions of certain genes, such as the sucC genes were associated with significant structural entropy values in genome-wide examinations. Various tests show that there

  10. Role of riboswitches in gene regulation and their potential for algal biotechnology.

    Science.gov (United States)

    Nguyen, Ginnie T D T; Scaife, Mark A; Helliwell, Katherine E; Smith, Alison G

    2016-06-01

    Riboswitches are regulatory elements in messenger RNA to which specific ligands can bind directly in the absence of proteins. Ligand binding alters the mRNA secondary structure, thereby affecting expression of the encoded protein. Riboswitches are widespread in prokaryotes, with over 20 different effector ligands known, including amino acids, cofactors, and Mg(2+) ions, and gene expression is generally regulated by affecting translation or termination of transcription. In plants, fungi, and microalgae, riboswitches have been found, but only those that bind thiamine pyrophosphate. These eukaryotic riboswitches operate by causing alternative splicing of the transcript. Here, we review the current status of riboswitch research with specific emphasis on microalgae. We discuss new riboswitch discoveries and insights into the underlying mechanism of action, and how next generation sequencing technology provides the motivation and opportunity to improve our understanding of these rare but important regulatory elements. We also highlight the potential of microalgal riboswitches as a tool for synthetic biology and industrial biotechnology. © 2016 Phycological Society of America.

  11. Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems.

    Science.gov (United States)

    Sherlock, Madeline E; Sudarsan, Narasimhan; Breaker, Ronald R

    2018-05-21

    Riboswitches are noncoding portions of certain mRNAs that bind metabolite, coenzyme, signaling molecule, or inorganic ion ligands and regulate gene expression. Most known riboswitches sense derivatives of RNA monomers. This bias in ligand chemical composition is consistent with the hypothesis that widespread riboswitch classes first emerged during the RNA World, which is proposed to have existed before proteins were present. Here we report the discovery and biochemical validation of a natural riboswitch class that selectively binds guanosine tetraphosphate (ppGpp), a widespread signaling molecule and bacterial "alarmone" derived from the ribonucleotide GTP. Riboswitches for ppGpp are predicted to regulate genes involved in branched-chain amino acid biosynthesis and transport, as well as other gene classes that previously had not been implicated to be part of its signaling network. This newfound riboswitch-alarmone partnership supports the hypothesis that prominent RNA World signaling pathways have been retained by modern cells to control key biological processes. Copyright © 2018 the Author(s). Published by PNAS.

  12. An excited state underlies gene regulation of a transcriptional riboswitch

    Science.gov (United States)

    Zhao, Bo; Guffy, Sharon L.; Williams, Benfeard; Zhang, Qi

    2017-01-01

    Riboswitches control gene expression through ligand-dependent structural rearrangements of the sensing aptamer domain. However, we found that the Bacillus cereus fluoride riboswitch aptamer adopts identical tertiary structures in solution with and without ligand. Using chemical exchange saturation transfer (CEST) NMR spectroscopy, we revealed that the structured ligand-free aptamer transiently accesses a low-populated (~1%) and short-lived (~3 ms) excited conformational state that unravels a conserved ‘linchpin’ base pair to signal transcription termination. Upon fluoride binding, this highly localized fleeting process is allosterically suppressed to activate transcription. We demonstrated that this mechanism confers effective fluoride-dependent gene activation over a wide range of transcription rates, which is essential for robust toxicity response across diverse cellular conditions. These results unveil a novel switching mechanism that employs ligand-dependent suppression of an aptamer excited state to coordinate regulatory conformational transitions rather than adopting distinct aptamer ground-state tertiary architectures, exemplifying a new mode of ligand-dependent RNA regulation. PMID:28719589

  13. Dynamic energy landscapes of riboswitches help interpret conformational rearrangements and function.

    Directory of Open Access Journals (Sweden)

    Giulio Quarta

    Full Text Available Riboswitches are RNAs that modulate gene expression by ligand-induced conformational changes. However, the way in which sequence dictates alternative folding pathways of gene regulation remains unclear. In this study, we compute energy landscapes, which describe the accessible secondary structures for a range of sequence lengths, to analyze the transcriptional process as a given sequence elongates to full length. In line with experimental evidence, we find that most riboswitch landscapes can be characterized by three broad classes as a function of sequence length in terms of the distribution and barrier type of the conformational clusters: low-barrier landscape with an ensemble of different conformations in equilibrium before encountering a substrate; barrier-free landscape in which a direct, dominant "downhill" pathway to the minimum free energy structure is apparent; and a barrier-dominated landscape with two isolated conformational states, each associated with a different biological function. Sharing concepts with the "new view" of protein folding energy landscapes, we term the three sequence ranges above as the sensing, downhill folding, and functional windows, respectively. We find that these energy landscape patterns are conserved in various riboswitch classes, though the order of the windows may vary. In fact, the order of the three windows suggests either kinetic or thermodynamic control of ligand binding. These findings help understand riboswitch structure/function relationships and open new avenues to riboswitch design.

  14. Monovalent cation and amiloride analog modulation of adrenergic ligand binding to the unglycosylated alpha 2B-adrenergic receptor subtype

    International Nuclear Information System (INIS)

    Wilson, A.L.; Seibert, K.; Brandon, S.; Cragoe, E.J. Jr.; Limbird, L.E.

    1991-01-01

    The unglycosylated alpha 2B subtype of the alpha 2-adrenergic receptor found in NG-108-15 cells possesses allosteric regulation of adrenergic ligand binding by monovalent cations and 5-amino-substituted amiloride analogs. These findings demonstrate that allosteric modulation of adrenergic ligand binding is not a property unique to the alpha 2A subtype. The observation that amiloride analogs as well as monovalent cations can modulate adrenergic ligand binding to the nonglycosylated alpha 2B subtype indicates that charge shielding due to carbohydrate moieties does not play a role in this allosteric modulation but, rather, these regulatory effects result from interactions of cations and amiloride analogs with the protein moiety of the receptor. Furthermore, the observation that both alpha 2A and alpha 2B receptor subtypes are modulated by amiloride analogs suggests that structural domains that are conserved between the two are likely to be involved in this allosteric modulation

  15. Crystal structures of the SAM-III/S[subscript MK] riboswitch reveal the SAM-dependent translation inhibition mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Lu, C.; Smith, A.M.; Fuchs, R.T.; Ding, F.; Rajashankar, K.; Henkin, T.M.; Ke, A. (Cornell); (OSU)

    2010-01-07

    Three distinct classes of S-adenosyl-L-methionine (SAM)-responsive riboswitches have been identified that regulate bacterial gene expression at the levels of transcription attenuation or translation inhibition. The SMK box (SAM-III) translational riboswitch has been identified in the SAM synthetase gene in members of the Lactobacillales. Here we report the 2.2-{angstrom} crystal structure of the Enterococcus faecalis SMK box riboswitch. The Y-shaped riboswitch organizes its conserved nucleotides around a three-way junction for SAM recognition. The Shine-Dalgarno sequence, which is sequestered by base-pairing with the anti-Shine-Dalgarno sequence in response to SAM binding, also directly participates in SAM recognition. The riboswitch makes extensive interactions with the adenosine and sulfonium moieties of SAM but does not appear to recognize the tail of the methionine moiety. We captured a structural snapshot of the SMK box riboswitch sampling the near-cognate ligand S-adenosyl-L-homocysteine (SAH) in which SAH was found to adopt an alternative conformation and fails to make several key interactions.

  16. Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography

    Science.gov (United States)

    Stagno, J. R.; Liu, Y.; Bhandari, Y. R.; Conrad, C. E.; Panja, S.; Swain, M.; Fan, L.; Nelson, G.; Li, C.; Wendel, D. R.; White, T. A.; Coe, J. D.; Wiedorn, M. O.; Knoska, J.; Oberthuer, D.; Tuckey, R. A.; Yu, P.; Dyba, M.; Tarasov, S. G.; Weierstall, U.; Grant, T. D.; Schwieters, C. D.; Zhang, J.; Ferré-D'Amaré, A. R.; Fromme, P.; Draper, D. E.; Liang, M.; Hunter, M. S.; Boutet, S.; Tan, K.; Zuo, X.; Ji, X.; Barty, A.; Zatsepin, N. A.; Chapman, H. N.; Spence, J. C. H.; Woodson, S. A.; Wang, Y.-X.

    2017-01-01

    Riboswitches are structural RNA elements that are generally located in the 5‧ untranslated region of messenger RNA. During regulation of gene expression, ligand binding to the aptamer domain of a riboswitch triggers a signal to the downstream expression platform. A complete understanding of the structural basis of this mechanism requires the ability to study structural changes over time. Here we use femtosecond X-ray free electron laser (XFEL) pulses to obtain structural measurements from crystals so small that diffusion of a ligand can be timed to initiate a reaction before diffraction. We demonstrate this approach by determining four structures of the adenine riboswitch aptamer domain during the course of a reaction, involving two unbound apo structures, one ligand-bound intermediate, and the final ligand-bound conformation. These structures support a reaction mechanism model with at least four states and illustrate the structural basis of signal transmission. The three-way junction and the P1 switch helix of the two apo conformers are notably different from those in the ligand-bound conformation. Our time-resolved crystallographic measurements with a 10-second delay captured the structure of an intermediate with changes in the binding pocket that accommodate the ligand. With at least a 10-minute delay, the RNA molecules were fully converted to the ligand-bound state, in which the substantial conformational changes resulted in conversion of the space group. Such notable changes in crystallo highlight the important opportunities that micro- and nanocrystals may offer in these and similar time-resolved diffraction studies. Together, these results demonstrate the potential of ‘mix-and-inject’ time-resolved serial crystallography to study biochemically important interactions between biomacromolecules and ligands, including those that involve large conformational changes.

  17. A magnesium-induced triplex pre-organizes the SAM-II riboswitch.

    Directory of Open Access Journals (Sweden)

    Susmita Roy

    2017-03-01

    Full Text Available Our 13C- and 1H-chemical exchange saturation transfer (CEST experiments previously revealed a dynamic exchange between partially closed and open conformations of the SAM-II riboswitch in the absence of ligand. Here, all-atom structure-based molecular simulations, with the electrostatic effects of Manning counter-ion condensation and explicit magnesium ions are employed to calculate the folding free energy landscape of the SAM-II riboswitch. We use this analysis to predict that magnesium ions remodel the landscape, shifting the equilibrium away from the extended, partially unfolded state towards a compact, pre-organized conformation that resembles the ligand-bound state. Our CEST and SAXS experiments, at different magnesium ion concentrations, quantitatively confirm our simulation results, demonstrating that magnesium ions induce collapse and pre-organization. Agreement between theory and experiment bolsters microscopic interpretation of our simulations, which shows that triplex formation between helix P2b and loop L1 is highly sensitive to magnesium and plays a key role in pre-organization. Pre-organization of the SAM-II riboswitch allows rapid detection of ligand with high selectivity, which is important for biological function.

  18. Identification and cloning of four riboswitches from Burkholderia pseudomallei strain K96243

    Science.gov (United States)

    Munyati-Othman, Noor; Fatah, Ahmad Luqman Abdul; Piji, Mohd Al Akmarul Fizree Bin Md; Ramlan, Effirul Ikhwan; Raih, Mohd Firdaus

    2015-09-01

    Structured RNAs referred as riboswitches have been predicted to be present in the genome sequence of Burkholderia pseudomallei strain K96243. Four of the riboswitches were identified and analyzed through BLASTN, Rfam search and multiple sequence alignment. The RNA aptamers belong to the following riboswitch classifications: glycine riboswitch, cobalamin riboswitch, S-adenosyl-(L)-homocysteine (SAH) riboswitch and flavin mononucleotide (FMN) riboswitch. The conserved nucleotides for each aptamer were identified and were marked on the secondary structure generated by RNAfold. These riboswitches were successfully amplified and cloned for further study.

  19. Comparison of a PreQ1 Riboswitch Aptamer in Metabolite-bound and Free States with Implications for Gene Regulation*

    OpenAIRE

    Jenkins, Jermaine L.; Krucinska, Jolanta; McCarty, Reid M.; Bandarian, Vahe; Wedekind, Joseph E.

    2011-01-01

    Riboswitches are RNA regulatory elements that govern gene expression by recognition of small molecule ligands via a high affinity aptamer domain. Molecular recognition can lead to active or attenuated gene expression states by controlling accessibility to mRNA signals necessary for transcription or translation. Key areas of inquiry focus on how an aptamer attains specificity for its effector, the extent to which the aptamer folds prior to encountering its ligand, and how ligand binding alters...

  20. Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chunhua [College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124 (China); Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108 (United States); Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin [College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124 (China); Su, Jiguo, E-mail: jiguosu@ysu.edu.cn, E-mail: zhng@umich.edu [College of Science, Yanshan University, Qinhuangdao 066004 (China); Zhang, Yang, E-mail: jiguosu@ysu.edu.cn, E-mail: zhng@umich.edu [Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108 (United States)

    2016-07-07

    Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.

  1. Monitoring lysin motif-ligand interactions via tryptophan analog fluorescence spectroscopy

    NARCIS (Netherlands)

    Petrovic, Dejan M.; Leenhouts, Kees; van Roosmalen, Maarten L.; KleinJan, Fenneke; Broos, Jaap

    2012-01-01

    The lysin motif (LysM) is a peptidoglycan binding protein domain found in a wide range of prokaryotes and eukaryotes. Various techniques have been used to study the LysM-ligand interaction, but a sensitive spectroscopic method to directly monitor this interaction has not been reported. Here a

  2. T box riboswitches in Actinobacteria: Translational regulation via novel tRNA interactions

    Science.gov (United States)

    Sherwood, Anna V.; Grundy, Frank J.; Henkin, Tina M.

    2015-01-01

    The T box riboswitch regulates many amino acid-related genes in Gram-positive bacteria. T box riboswitch-mediated gene regulation was shown previously to occur at the level of transcription attenuation via structural rearrangements in the 5′ untranslated (leader) region of the mRNA in response to binding of a specific uncharged tRNA. In this study, a novel group of isoleucyl-tRNA synthetase gene (ileS) T box leader sequences found in organisms of the phylum Actinobacteria was investigated. The Stem I domains of these RNAs lack several highly conserved elements that are essential for interaction with the tRNA ligand in other T box RNAs. Many of these RNAs were predicted to regulate gene expression at the level of translation initiation through tRNA-dependent stabilization of a helix that sequesters a sequence complementary to the Shine–Dalgarno (SD) sequence, thus freeing the SD sequence for ribosome binding and translation initiation. We demonstrated specific binding to the cognate tRNAIle and tRNAIle-dependent structural rearrangements consistent with regulation at the level of translation initiation, providing the first biochemical demonstration, to our knowledge, of translational regulation in a T box riboswitch. PMID:25583497

  3. Dual-Targeting Small-Molecule Inhibitors of the Staphylococcus aureus FMN Riboswitch Disrupt Riboflavin Homeostasis in an Infectious Setting.

    Science.gov (United States)

    Wang, Hao; Mann, Paul A; Xiao, Li; Gill, Charles; Galgoci, Andrew M; Howe, John A; Villafania, Artjohn; Barbieri, Christopher M; Malinverni, Juliana C; Sher, Xinwei; Mayhood, Todd; McCurry, Megan D; Murgolo, Nicholas; Flattery, Amy; Mack, Matthias; Roemer, Terry

    2017-05-18

    Riboswitches are bacterial-specific, broadly conserved, non-coding RNA structural elements that control gene expression of numerous metabolic pathways and transport functions essential for cell growth. As such, riboswitch inhibitors represent a new class of potential antibacterial agents. Recently, we identified ribocil-C, a highly selective inhibitor of the flavin mononucleotide (FMN) riboswitch that controls expression of de novo riboflavin (RF, vitamin B2) biosynthesis in Escherichia coli. Here, we provide a mechanistic characterization of the antibacterial effects of ribocil-C as well as of roseoflavin (RoF), an antimetabolite analog of RF, among medically significant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis. We provide genetic, biophysical, computational, biochemical, and pharmacological evidence that ribocil-C and RoF specifically inhibit dual FMN riboswitches, separately controlling RF biosynthesis and uptake processes essential for MRSA growth and pathogenesis. Such a dual-targeting mechanism is specifically required to develop broad-spectrum Gram-positive antibacterial agents targeting RF metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Coenzyme Recognition and Gene Regulation by a Flavin Mononucleotide Riboswitch

    Energy Technology Data Exchange (ETDEWEB)

    Serganov, A.; Huang, L; Patel, D

    2009-01-01

    The biosynthesis of several protein cofactors is subject to feedback regulation by riboswitches. Flavin mononucleotide (FMN)-specific riboswitches also known as RFN elements, direct expression of bacterial genes involved in the biosynthesis and transport of riboflavin (vitamin B2) and related compounds. Here we present the crystal structures of the Fusobacterium nucleatum riboswitch bound to FMN, riboflavin and antibiotic roseoflavin. The FMN riboswitch structure, centred on an FMN-bound six-stem junction, does not fold by collinear stacking of adjacent helices, typical for folding of large RNAs. Rather, it adopts a butterfly-like scaffold, stapled together by opposingly directed but nearly identically folded peripheral domains. FMN is positioned asymmetrically within the junctional site and is specifically bound to RNA through interactions with the isoalloxazine ring chromophore and direct and Mg{sup 2+}-mediated contacts with the phosphate moiety. Our structural data, complemented by binding and footprinting experiments, imply a largely pre-folded tertiary RNA architecture and FMN recognition mediated by conformational transitions within the junctional binding pocket. The inherent plasticity of the FMN-binding pocket and the availability of large openings make the riboswitch an attractive target for structure-based design of FMN-like antimicrobial compounds. Our studies also explain the effects of spontaneous and antibiotic-induced deregulatory mutations and provided molecular insights into FMN-based control of gene expression in normal and riboflavin-overproducing bacterial strains.

  5. Analogies and surprising differences between recombinant nitric oxide synthase-like proteins from Staphylococcus aureus and Bacillus anthracis in their interactions with l-arginine analogs and iron ligands.

    Science.gov (United States)

    Salard, Isabelle; Mercey, Emilie; Rekka, Eleni; Boucher, Jean-Luc; Nioche, Pierre; Mikula, Ivan; Martasek, Pavel; Raman, C S; Mansuy, Daniel

    2006-12-01

    Genome sequencing has recently shown the presence of genes coding for NO-synthase (NOS)-like proteins in bacteria. The roles of these proteins remain unclear. The interactions of a series of l-arginine (l-arg) analogs and iron ligands with two recombinant NOS-like proteins from Staphylococcus aureus (saNOS) and Bacillus anthracis (baNOS) have been studied by UV-visible spectroscopy. SaNOS and baNOS in their ferric native state, as well as their complexes with l-arg analogs and with various ligands, exhibit spectral characteristics highly similar to the corresponding complexes of heme-thiolate proteins such as cytochromes P450 and NOSs. However, saNOS greatly differs from baNOS at the level of three main properties: (i) native saNOS mainly exists under an hexacoordinated low-spin ferric state whereas native baNOS is mainly high-spin, (ii) the addition of tetrahydrobiopterin (H4B) or H4B analogs leads to an increase of the affinity of l-arg for saNOS but not for baNOS, and (iii) saNOS Fe(II), contrary to baNOS, binds relatively bulky ligands such as nitrosoalkanes and tert-butylisocyanide. Thus, saNOS exhibits properties very similar to those of the oxygenase domain of inducible NOS (iNOS(oxy)) not containing H4B, as expected for a NOSoxy-like protein that does not contain H4B. By contrast, the properties of baNOS which look like those of H4B-containing iNOS(oxy) are unexpected for a NOS-like protein not containing H4B. The origin of these surprising properties of baNOS remains to be determined.

  6. Evaluation of tricine and EDDA as Co-ligands for 99mTc-labeled HYNIC-MSH analogs for melanoma imaging.

    Science.gov (United States)

    Garcia, Maria Fernanda; Zhang, Xiuli; Gallazzi, Fabio; Fernandez, Marcelo; Moreno, Maria; Gambini, Juan Pablo; Porcal, Williams; Cabral, Pablo; Quinn, Thomas P

    2015-01-01

    Several radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs have been studied for their abilities to target melanoma tumor cells through specific recognition and binding to the melanocortin receptor 1 (MCR1). In this work, a lactam bridgecyclized α-MSH analog was labeled with (99m) via the hydrazinonicotinamide (HYNIC) chelator and characterized for its melanoma tumor targeting properties. The bifunctional chelating agent HYNIC-Boc was attached to the N-terminus of the MSH peptide followed by the lactam cyclization, resulting in the HYNIC-cyc-MSH analog. The lactam cyclized peptide displayed high affinity and specificity for MC1-receptors present on B16/F1 melanoma tumor cells, exhibiting an IC50 of 6.48 nM. HYNIC-cyc-MSH was radiolabeled with (99m)Tc using two common co-ligands, tricine and EDDA. In vitro, the radiochemical stability, cell binding and efflux properties were similar between the peptides radiolabeled with tricine and EDDA as co-ligands. In vivo, biodistribution studies (n=4) demonstrated that (99m)Tc- HYNIC-cyc-MSH/tricine had superior tumor to muscle and tumor to blood ratios than (99m)Tc-HYNIC-cyc-MSH/EDDA at early time points. Planar gamma imaging of melanoma bearing mice showed that 99mTc-HYNIC-cyc-MSH/tricine was able to clearly visualize tumors, underscoring the potential utility of (99m)Tc labeled lactam cyclized MSH molecules as melanoma imaging agents.

  7. Novel aza-analogous ergoline derived scaffolds as potent serotonin 5-HT6 and dopamine D2 receptor ligands

    DEFF Research Database (Denmark)

    Krogsgaard-Larsen, Niels; Jensen, Anders A.; Schrøder, T.J.

    2014-01-01

    By introducing distal substituents on a tetracyclic scaffold resembling the ergoline structure, two series of analogues were achieved exhibiting subnanomolar receptor binding affinities for the dopamine D2 and serotonin 5-HT6 receptor subtype, respectively. While the 5-HT6 ligands were antagonists......, the D2 ligands displayed intrinsic activities ranging from full agonism to partial agonism with low intrinsic activity. These structures could potentially be interesting for treatment of neurological diseases such as schizophrenia, Parkinson’s disease, and cognitive deficits....

  8. Mutagenic activity of a fluorinated analog of the beta-adrenoceptor ligand carazolol in the Ames test

    NARCIS (Netherlands)

    Doze, P; Elsinga, PH; de Vries, EFJ; Van Waarde, A; Vaalburg, W

    S-1'[F-18]-Fluorocarazolol (FCAR) is a fluorinated analog of the nonmutagenic beta-blocker carazolol (CAR). Tn former studies FCAR proved to be suitable for quantification of beta-adrenoceptors in vivo with positron emission tomography (PET). We report here that FCAR displays no acute toxicity in

  9. Comparison of a preQ1 riboswitch aptamer in metabolite-bound and free states with implications for gene regulation.

    Science.gov (United States)

    Jenkins, Jermaine L; Krucinska, Jolanta; McCarty, Reid M; Bandarian, Vahe; Wedekind, Joseph E

    2011-07-15

    Riboswitches are RNA regulatory elements that govern gene expression by recognition of small molecule ligands via a high affinity aptamer domain. Molecular recognition can lead to active or attenuated gene expression states by controlling accessibility to mRNA signals necessary for transcription or translation. Key areas of inquiry focus on how an aptamer attains specificity for its effector, the extent to which the aptamer folds prior to encountering its ligand, and how ligand binding alters expression signal accessibility. Here we present crystal structures of the preQ(1) riboswitch from Thermoanaerobacter tengcongensis in the preQ(1)-bound and free states. Although the mode of preQ(1) recognition is similar to that observed for preQ(0), surface plasmon resonance revealed an apparent K(D) of 2.1 ± 0.3 nm for preQ(1) but a value of 35.1 ± 6.1 nm for preQ(0). This difference can be accounted for by interactions between the preQ(1) methylamine and base G5 of the aptamer. To explore conformational states in the absence of metabolite, the free-state aptamer structure was determined. A14 from the ceiling of the ligand pocket shifts into the preQ(1)-binding site, resulting in "closed" access to the metabolite while simultaneously increasing exposure of the ribosome-binding site. Solution scattering data suggest that the free-state aptamer is compact, but the "closed" free-state crystal structure is inadequate to describe the solution scattering data. These observations are distinct from transcriptional preQ(1) riboswitches of the same class that exhibit strictly ligand-dependent folding. Implications for gene regulation are discussed.

  10. Macromolecular competition titration method accessing thermodynamics of the unmodified macromolecule-ligand interactions through spectroscopic titrations of fluorescent analogs.

    Science.gov (United States)

    Bujalowski, Wlodzimierz; Jezewska, Maria J

    2011-01-01

    Analysis of thermodynamically rigorous binding isotherms provides fundamental information about the energetics of the ligand-macromolecule interactions and often an invaluable insight about the structure of the formed complexes. The Macromolecular Competition Titration (MCT) method enables one to quantitatively obtain interaction parameters of protein-nucleic acid interactions, which may not be available by other methods, particularly for the unmodified long polymer lattices and specific nucleic acid substrates, if the binding is not accompanied by adequate spectroscopic signal changes. The method can be applied using different fluorescent nucleic acids or fluorophores, although the etheno-derivatives of nucleic acid are especially suitable as they are relatively easy to prepare, have significant blue fluorescence, their excitation band lies far from the protein absorption spectrum, and the modification eliminates the possibility of base pairing with other nucleic acids. The MCT method is not limited to the specific size of the reference nucleic acid. Particularly, a simple analysis of the competition titration experiments is described in which the fluorescent, short fragment of nucleic acid, spanning the exact site-size of the protein-nucleic acid complex, and binding with only a 1:1 stoichiometry to the protein, is used as a reference macromolecule. Although the MCT method is predominantly discussed as applied to studying protein-nucleic acid interactions, it can generally be applied to any ligand-macromolecule system by monitoring the association reaction using the spectroscopic signal originating from the reference macromolecule in the presence of the competing macromolecule, whose interaction parameters with the ligand are to be determined. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors.

    Science.gov (United States)

    Frett, Brendan; McConnell, Nick; Smith, Catherine C; Wang, Yuanxiang; Shah, Neil P; Li, Hong-yu

    2015-04-13

    The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. Mutagenic activity of a fluorinated analog of the beta-adrenoceptor ligand carazolol in the Ames test

    Energy Technology Data Exchange (ETDEWEB)

    Doze, P. E-mail: P.Doze@pet.azg.nl; Elsinga, P.H.; Vries, E.F.J. de; Waarde, A. van; Vaalburg, W

    2000-04-01

    S-1'[{sup 18}F]-Fluorocarazolol (FCAR) is a fluorinated analog of the nonmutagenic beta-blocker carazolol (CAR). In former studies FCAR proved to be suitable for quantification of beta-adrenoceptors in vivo with positron emission tomography (PET). We report here that FCAR displays no acute toxicity in either rats or mice. However, FCAR induces a strong dose-related increase in the number of revertants in the Ames test. We conclude that FCAR yields mutagenic activity as measured by the Ames test.

  13. Structural basis for recognition of S-adenosylhomocysteine by riboswitches

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, A.L.; Heroux, A.; Reyes, F. E.; Batey, R. T.

    2010-11-01

    S-adenosyl-(L)-homocysteine (SAH) riboswitches are regulatory elements found in bacterial mRNAs that up-regulate genes involved in the S-adenosyl-(L)-methionine (SAM) regeneration cycle. To understand the structural basis of SAH-dependent regulation by RNA, we have solved the structure of its metabolite-binding domain in complex with SAH. This structure reveals an unusual pseudoknot topology that creates a shallow groove on the surface of the RNA that binds SAH primarily through interactions with the adenine ring and methionine main chain atoms and discriminates against SAM through a steric mechanism. Chemical probing and calorimetric analysis indicate that the unliganded RNA can access bound-like conformations that are significantly stabilized by SAH to direct folding of the downstream regulatory switch. Strikingly, we find that metabolites bearing an adenine ring, including ATP, bind this aptamer with sufficiently high affinity such that normal intracellular concentrations of these compounds may influence regulation of the riboswitch.

  14. Structural Basis for Recognition of S-adenosylhomocysteine by Riboswitches

    Energy Technology Data Exchange (ETDEWEB)

    A Edwards; F Reyes; A Heroux; R Batey

    2011-12-31

    S-adenosyl-(L)-homocysteine (SAH) riboswitches are regulatory elements found in bacterial mRNAs that up-regulate genes involved in the S-adenosyl-(L)-methionine (SAM) regeneration cycle. To understand the structural basis of SAH-dependent regulation by RNA, we have solved the structure of its metabolite-binding domain in complex with SAH. This structure reveals an unusual pseudoknot topology that creates a shallow groove on the surface of the RNA that binds SAH primarily through interactions with the adenine ring and methionine main chain atoms and discriminates against SAM through a steric mechanism. Chemical probing and calorimetric analysis indicate that the unliganded RNA can access bound-like conformations that are significantly stabilized by SAH to direct folding of the downstream regulatory switch. Strikingly, we find that metabolites bearing an adenine ring, including ATP, bind this aptamer with sufficiently high affinity such that normal intracellular concentrations of these compounds may influence regulation of the riboswitch.

  15. Using riboswitches to regulate gene expression and define gene function in mycobacteria.

    Science.gov (United States)

    Van Vlack, Erik R; Seeliger, Jessica C

    2015-01-01

    Mycobacteria include both environmental species and many pathogenic species such as Mycobacterium tuberculosis, an intracellular pathogen that is the causative agent of tuberculosis in humans. Inducible gene expression is a powerful tool for examining gene function and essentiality, both in in vitro culture and in host cell infections. The theophylline-inducible artificial riboswitch has recently emerged as an alternative to protein repressor-based systems. The riboswitch is translationally regulated and is combined with a mycobacterial promoter that provides transcriptional control. We here provide methods used by our laboratory to characterize the riboswitch response to theophylline in reporter strains, recombinant organisms containing riboswitch-regulated endogenous genes, and in host cell infections. These protocols should facilitate the application of both existing and novel artificial riboswitches to the exploration of gene function in mycobacteria. © 2015 Elsevier Inc. All rights reserved.

  16. Macromolecular Competition Titration Method: Accessing Thermodynamics of the Unmodified Macromolecule–Ligand Interactions Through Spectroscopic Titrations of Fluorescent Analogs

    Science.gov (United States)

    Bujalowski, Wlodzimierz; Jezewska, Maria J.

    2011-01-01

    Analysis of thermodynamically rigorous binding isotherms provides fundamental information about the energetics of the ligand–macromolecule interactions and often an invaluable insight about the structure of the formed complexes. The Macromolecular Competition Titration (MCT) method enables one to quantitatively obtain interaction parameters of protein–nucleic acid interactions, which may not be available by other methods, particularly for the unmodified long polymer lattices and specific nucleic acid substrates, if the binding is not accompanied by adequate spectroscopic signal changes. The method can be applied using different fluorescent nucleic acids or fluorophores, although the etheno-derivatives of nucleic acid are especially suitable as they are relatively easy to prepare, have significant blue fluorescence, their excitation band lies far from the protein absorption spectrum, and the modification eliminates the possibility of base pairing with other nucleic acids. The MCT method is not limited to the specific size of the reference nucleic acid. Particularly, a simple analysis of the competition titration experiments is described in which the fluorescent, short fragment of nucleic acid, spanning the exact site-size of the protein–nucleic acid complex, and binding with only a 1:1 stoichiometry to the protein, is used as a reference macromolecule. Although the MCT method is predominantly discussed as applied to studying protein–nucleic acid interactions, it can generally be applied to any ligand–macromolecule system by monitoring the association reaction using the spectroscopic signal originating from the reference macromolecule in the presence of the competing macromolecule, whose interaction parameters with the ligand are to be determined. PMID:21195223

  17. PoSSuM v.2.0: data update and a new function for investigating ligand analogs and target proteins of small-molecule drugs.

    Science.gov (United States)

    Ito, Jun-ichi; Ikeda, Kazuyoshi; Yamada, Kazunori; Mizuguchi, Kenji; Tomii, Kentaro

    2015-01-01

    PoSSuM (http://possum.cbrc.jp/PoSSuM/) is a database for detecting similar small-molecule binding sites on proteins. Since its initial release in 2011, PoSSuM has grown to provide information related to 49 million pairs of similar binding sites discovered among 5.5 million known and putative binding sites. This enlargement of the database is expected to enhance opportunities for biological and pharmaceutical applications, such as predictions of new functions and drug discovery. In this release, we have provided a new service named PoSSuM drug search (PoSSuMds) at http://possum.cbrc.jp/PoSSuM/drug_search/, in which we selected 194 approved drug compounds retrieved from ChEMBL, and detected their known binding pockets and pockets that are similar to them. Users can access and download all of the search results via a new web interface, which is useful for finding ligand analogs as well as potential target proteins. Furthermore, PoSSuMds enables users to explore the binding pocket universe within PoSSuM. Additionally, we have improved the web interface with new functions, including sortable tables and a viewer for visualizing and downloading superimposed pockets. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Efficient computation of co-transcriptional RNA-ligand interaction dynamics.

    Science.gov (United States)

    Wolfinger, Michael T; Flamm, Christoph; Hofacker, Ivo L

    2018-05-04

    Riboswitches form an abundant class of cis-regulatory RNA elements that mediate gene expression by binding a small metabolite. For synthetic biology applications, they are becoming cheap and accessible systems for selectively triggering transcription or translation of downstream genes. Many riboswitches are kinetically controlled, hence knowledge of their co-transcriptional mechanisms is essential. We present here an efficient implementation for analyzing co-transcriptional RNA-ligand interaction dynamics. This approach allows for the first time to model concentration-dependent metabolite binding/unbinding kinetics. We exemplify this novel approach by means of the recently studied I-A 2 ' -deoxyguanosine (2 ' dG)-sensing riboswitch from Mesoplasma florum. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Heterobimetallic [NiFe] Complexes Containing Mixed CO/CN- Ligands: Analogs of the Active Site of the [NiFe] Hydrogenases.

    Science.gov (United States)

    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

  20. Structural stability, acidity, and halide selectivity of the fluoride riboswitch recognition site

    KAUST Repository

    Chawla, Mohit; Credendino, Raffaele; Poater, Albert; Oliva, Romina M.; Cavallo, Luigi

    2015-01-01

    Using static and dynamics DFT methods we show that the Mg2+/F-/phosphate/water cluster at the center of the fluoride riboswitch is stable by its own and, once assembled, does not rely on any additional factor from the overall RNA fold. Further, we predict that the pKa of the water molecule bridging two Mg cations is around 8.4. We also demonstrate that the halide selectivity of the fluoride riboswitch is determined by the stronger Mg-F bond, which is capable of keeping together the cluster. Replacing F- with Cl- results in a cluster that is unstable under dynamic conditions. Similar conclusions on the structure and energetics of the cluster in the binding pocket of fluoride-inhibited pyrophosphatase suggest that the peculiarity of fluoride is in its ability to establish much stronger metal-halide bonds.

  1. Structural stability, acidity, and halide selectivity of the fluoride riboswitch recognition site

    KAUST Repository

    Chawla, Mohit

    2015-01-14

    Using static and dynamics DFT methods we show that the Mg2+/F-/phosphate/water cluster at the center of the fluoride riboswitch is stable by its own and, once assembled, does not rely on any additional factor from the overall RNA fold. Further, we predict that the pKa of the water molecule bridging two Mg cations is around 8.4. We also demonstrate that the halide selectivity of the fluoride riboswitch is determined by the stronger Mg-F bond, which is capable of keeping together the cluster. Replacing F- with Cl- results in a cluster that is unstable under dynamic conditions. Similar conclusions on the structure and energetics of the cluster in the binding pocket of fluoride-inhibited pyrophosphatase suggest that the peculiarity of fluoride is in its ability to establish much stronger metal-halide bonds.

  2. Cooperation between Magnesium and Metabolite Controls Collapse of the SAM-I Riboswitch.

    Science.gov (United States)

    Roy, Susmita; Onuchic, José N; Sanbonmatsu, Karissa Y

    2017-07-25

    The S-adenosylmethionine (SAM)-I riboswitch is a noncoding RNA that regulates the transcription termination process in response to metabolite (SAM) binding. The aptamer portion of the riboswitch may adopt an open or closed state depending on the presence of metabolite. Although the transition between the open and closed states is critical for the switching process, its atomistic details are not well understood. Using atomistic simulations, we calculate the effect of SAM and magnesium ions on the folding free energy landscape of the SAM-I riboswitch. These molecular simulation results are consistent with our previous wetlab experiments and aid in interpreting the SHAPE probing measurements. Here, molecular dynamics simulations explicitly identify target RNA motifs sensitive to magnesium ions and SAM. In the simulations, we observe that, whereas the metabolite mostly stabilizes the P1 and P3 helices, magnesium serves an important role in stabilizing a pseudoknot interaction between the P2 and P4 helices, even at high metabolite concentrations. The pseudoknot stabilization by magnesium, in combination with P1 stabilization by SAM, explains the requirement of both SAM and magnesium to form the fully collapsed metabolite-bound closed state of the SAM-I riboswitch. In the absence of SAM, frequent open-to-closed conformational transitions of the pseudoknot occur, akin to breathing. These pseudoknot fluctuations disrupt the binding site by facilitating fluctuations in the 5'-end of helix P1. Magnesium biases the landscape toward a collapsed state (preorganization) by coordinating pseudoknot and 5'-P1 fluctuations. The cooperation between SAM and magnesium in stabilizing important tertiary interactions elucidates their functional significance in transcription regulation. Published by Elsevier Inc.

  3. Direct modulation of T-box riboswitch-controlled transcription by protein synthesis inhibitors.

    Science.gov (United States)

    Stamatopoulou, Vassiliki; Apostolidi, Maria; Li, Shuang; Lamprinou, Katerina; Papakyriakou, Athanasios; Zhang, Jinwei; Stathopoulos, Constantinos

    2017-09-29

    Recently, it was discovered that exposure to mainstream antibiotics activate numerous bacterial riboregulators that control antibiotic resistance genes including metabolite-binding riboswitches and other transcription attenuators. However, the effects of commonly used antibiotics, many of which exhibit RNA-binding properties, on the widespread T-box riboswitches, remain unknown. In Staphylococcus aureus, a species-specific glyS T-box controls the supply of glycine for both ribosomal translation and cell wall synthesis, making it a promising target for next-generation antimicrobials. Here, we report that specific protein synthesis inhibitors could either significantly increase T-box-mediated transcription antitermination, while other compounds could suppress it, both in vitro and in vivo. In-line probing of the full-length T-box combined with molecular modelling and docking analyses suggest that the antibiotics that promote transcription antitermination stabilize the T-box:tRNA complex through binding specific positions on stem I and the Staphylococcal-specific stem Sa. By contrast, the antibiotics that attenuate T-box transcription bind to other positions on stem I and do not interact with stem Sa. Taken together, our results reveal that the transcription of essential genes controlled by T-box riboswitches can be directly modulated by commonly used protein synthesis inhibitors. These findings accentuate the regulatory complexities of bacterial response to antimicrobials that involve multiple riboregulators. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Analog computing

    CERN Document Server

    Ulmann, Bernd

    2013-01-01

    This book is a comprehensive introduction to analog computing. As most textbooks about this powerful computing paradigm date back to the 1960s and 1970s, it fills a void and forges a bridge from the early days of analog computing to future applications. The idea of analog computing is not new. In fact, this computing paradigm is nearly forgotten, although it offers a path to both high-speed and low-power computing, which are in even more demand now than they were back in the heyday of electronic analog computers.

  5. Engineering a vitamin B12 high-throughput screening system by riboswitch sensor in Sinorhizobium meliloti.

    Science.gov (United States)

    Cai, Yingying; Xia, Miaomiao; Dong, Huina; Qian, Yuan; Zhang, Tongcun; Zhu, Beiwei; Wu, Jinchuan; Zhang, Dawei

    2018-05-11

    As a very important coenzyme in the cell metabolism, Vitamin B 12 (cobalamin, VB 12 ) has been widely used in food and medicine fields. The complete biosynthesis of VB 12 requires approximately 30 genes, but overexpression of these genes did not result in expected increase of VB 12 production. High-yield VB 12 -producing strains are usually obtained by mutagenesis treatments, thus developing an efficient screening approach is urgently needed. By the help of engineered strains with varied capacities of VB 12 production, a riboswitch library was constructed and screened, and the btuB element from Salmonella typhimurium was identified as the best regulatory device. A flow cytometry high-throughput screening system was developed based on the btuB riboswitch with high efficiency to identify positive mutants. Mutation of Sinorhizobium meliloti (S. meliloti) was optimized using the novel mutation technique of atmospheric and room temperature plasma (ARTP). Finally, the mutant S. meliloti MC5-2 was obtained and considered as a candidate for industrial applications. After 7 d's cultivation on a rotary shaker at 30 °C, the VB 12 titer of S. meliloti MC5-2 reached 156 ± 4.2 mg/L, which was 21.9% higher than that of the wild type strain S. meliloti 320 (128 ± 3.2 mg/L). The genome of S. meliloti MC5-2 was sequenced, and gene mutations were identified and analyzed. To our knowledge, it is the first time that a riboswitch element was used in S. meliloti. The flow cytometry high-throughput screening system was successfully developed and a high-yield VB 12 producing strain was obtained. The identified and analyzed gene mutations gave useful information for developing high-yield strains by metabolic engineering. Overall, this work provides a useful high-throughput screening method for developing high VB 12 -yield strains.

  6. Molecular Mechanism of preQ(1) Riboswitch Action: A Molecular Dynamics Study

    Czech Academy of Sciences Publication Activity Database

    Banáš, Pavel; Sklenovský, P.; Wedekind, J.E.; Šponer, Jiří; Otyepka, Michal

    2012-01-01

    Roč. 116, č. 42 (2012), s. 12721-12734 ISSN 1520-6106 R&D Projects: GA ČR(CZ) GD203/09/H046; GA ČR(CZ) GA203/09/1476; GA ČR(CZ) GAP208/12/1878; GA ČR(CZ) GBP305/12/G034 Grant - others:GA ČR(CZ) GBP208/12/G016 Program:GB Institutional support: RVO:68081707 Keywords : HEPATITIS -DELTA VIRUS * PARTICLE MESH EWALD * SAM-II RIBOSWITCH Subject RIV: BO - Biophysics; BO - Biophysics (BFU-R) Impact factor: 3.607, year: 2012

  7. Development of a 2,4-Dinitrotoluene-Responsive Synthetic Riboswitch in E. coli cells

    Science.gov (United States)

    2012-09-01

    INTRODUCTION Riboswitches are naturally-occurring genetic regulatory elements found in the 5′ untranslated region of some mRNA. They provide a method...Industrial Genetics at the University of Stuttgart, Germany, respectively. The plasmid pSAL8.1 was kindly provided by Dr. Justin Gallivan from Emory...vol. 252: Ribozymes and siRNA Protocols, 2nd ed. Humana Press, Inc.; 2004, 145-164. (9) Suess, B., and Weigand, J.E. RNA Biology 2008, 5(1), 1-6

  8. Molecular modeling of fentanyl analogs

    Directory of Open Access Journals (Sweden)

    LJILJANA DOSEN-MICOVIC

    2004-11-01

    Full Text Available Fentanyl is a highly potent and clinically widely used narcotic analgesic. A large number of its analogs have been synthesized, some of which (sufentanil and alfentanyl are also in clinical use. Theoretical studies, in recent years, afforded a better understanding of the structure-activity relationships of this class of opiates and allowed insight into the molecular mechanism of the interactions of fentanyl analogs with their receptors. An overview of the current computational techniques for modeling fentanyl analogs, their receptors and ligand-receptor interactions is presented in this paper.

  9. SAM-VI RNAs selectively bind S-adenosylmethionine and exhibit similarities to SAM-III riboswitches.

    Science.gov (United States)

    Mirihana Arachchilage, Gayan; Sherlock, Madeline E; Weinberg, Zasha; Breaker, Ronald R

    2018-03-04

    Five distinct riboswitch classes that regulate gene expression in response to the cofactor S-adenosylmethionine (SAM) or its metabolic breakdown product S-adenosylhomocysteine (SAH) have been reported previously. Collectively, these SAM- or SAH-sensing RNAs constitute the most abundant collection of riboswitches, and are found in nearly every major bacterial lineage. Here, we report a potential sixth member of this pervasive riboswitch family, called SAM-VI, which is predominantly found in Bifidobacterium species. SAM-VI aptamers selectively bind the cofactor SAM and strongly discriminate against SAH. The consensus sequence and structural model for SAM-VI share some features with the consensus model for the SAM-III riboswitch class, whose members are mainly found in lactic acid bacteria. However, there are sufficient differences between the two classes such that current bioinformatics methods separately cluster representatives of the two motifs. These findings highlight the abundance of RNA structures that can form to selectively recognize SAM, and showcase the ability of RNA to utilize diverse strategies to perform similar biological functions.

  10. Analog earthquakes

    International Nuclear Information System (INIS)

    Hofmann, R.B.

    1995-01-01

    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. A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository

  11. Naringenin-responsive riboswitch-based fluorescent biosensor module for Escherichia coli co-cultures.

    Science.gov (United States)

    Xiu, Yu; Jang, Sungho; Jones, J Andrew; Zill, Nicholas A; Linhardt, Robert J; Yuan, Qipeng; Jung, Gyoo Yeol; Koffas, Mattheos A G

    2017-10-01

    The ability to design and construct combinatorial synthetic metabolic pathways has far exceeded our capacity for efficient screening and selection of the resulting microbial strains. The need for high-throughput rapid screening techniques is of upmost importance for the future of synthetic biology and metabolic engineering. Here we describe the development of an RNA riboswitch-based biosensor module with dual fluorescent reporters, and demonstrate a high-throughput flow cytometry-based screening method for identification of naringenin over producing Escherichia coli strains in co-culture. Our efforts helped identify a number of key operating parameters that affect biosensor performance, including the selection of promoter and linker elements within the sensor-actuator domain, and the effect of host strain, fermentation time, and growth medium on sensor dynamic range. The resulting biosensor demonstrates a high correlation between specific fluorescence of the biosensor strain and naringenin titer produced by the second member of the synthetic co-culture system. This technique represents a novel application for synthetic microbial co-cultures and can be expanded from naringenin to any metabolite if a suitable riboswitch is identified. The co-culture technique presented here can be applied to a variety of target metabolites in combination with the SELEX approach for aptamer design. Due to the compartmentalization of the two genetic constructs responsible for production and detection into separate cells and application as independent modules of a synthetic microbial co-culture we have subsequently reduced the need for re-optimization of the producer module when the biosensor is replaced or removed. Biotechnol. Bioeng. 2017;114: 2235-2244. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. A Tyrosine-Dependent Riboswitch Controls the Expression of a Tyrosyl-tRNA Synthetase from Acidithiobacillus ferrooxidans

    Directory of Open Access Journals (Sweden)

    Paula Bustamante

    2016-06-01

    Full Text Available Expression of aminoacyl-tRNA synthetases is regulated by a variety of mechanisms at the level of transcription or translation. A T-box dependent transcription termination / antitermination riboswitch system that responds to charged / uncharged tRNA regulates expression of aminoacyl tRNA synthetase genes in Gram-positive bacteria. TyrZ, the gene encoding tyrosyl-tRNA synthetase from Acidithiobacillus ferrooxidans, a Gram-negative acidophilic bacterium that participates in bioleaching of minerals, resembles the gene from Bacillus subtilis including the 5´-untranslated region encoding the riboswitch. Transcription of A. ferrooxidans tyrZ is induced by the presence of tyrosine by a mechanism involving antitermination of transcription. This mechanism is probably adapted to the low supply of amino acids of acidic environments of autotrophic bioleaching microorganisms. This work is licensed under a Creative Commons Attribution 4.0 International License.

  13. The multi-state energy landscape of the SAM-I riboswitch: A single-molecule Förster resonance energy transfer spectroscopy study

    Science.gov (United States)

    Manz, Christoph; Kobitski, Andrei Yu.; Samanta, Ayan; Jäschke, Andres; Nienhaus, G. Ulrich

    2018-03-01

    RNA (ribonucleic acid) molecules are highly flexible biopolymers fluctuating at physiological temperatures among many different conformations that are represented by minima in a hierarchical conformational free energy landscape. Here we have employed single-molecule FRET (smFRET) to explore the energy landscape of the B. subtilis yitJ SAM-I riboswitch (RS). In this small RNA molecule, specific binding of an S-adenosyl-L-methionine (SAM) ligand in the aptamer domain regulates gene expression by inducing structural changes in another domain, the expression platform, causing transcription termination by the RNA polymerase. We have measured smFRET histograms over wide ranges of Mg2+ concentration for three RS variants that were specifically labeled with fluorescent dyes on different sites. In the analysis, different conformations are associated with discrete Gaussian model distributions, which are typically fairly broad on the FRET efficiency scale and thus can be extremely challenging to unravel due to their mutual overlap. Our earlier work on two SAM-I RS variants revealed four major conformations. By introducing a global fitting procedure which models both the Mg2+ concentration dependencies of the fractional populations and the average FRET efficiencies of the individual FRET distributions according to Mg2+ binding isotherms, we were able to consistently describe the histogram data of both variants at all studied Mg2+ concentrations. With the third FRET-labeled variant, however, we found significant deviations when applying the four-state model to the data. This can arise because the different FRET labeling of the new variant allows two states to be distinguished that were previously not separable due to overlap. Indeed, the resulting five-state model presented here consistently describes the smFRET histograms of all three variants as well as their variations with Mg2+ concentration. We also performed a triangulation of the donor position for two of the constructs

  14. Melatonin: functions and ligands.

    Science.gov (United States)

    Singh, Mahaveer; Jadhav, Hemant R

    2014-09-01

    Melatonin is a chronobiotic substance that acts as synchronizer by stabilizing bodily rhythms. Its synthesis occurs in various locations throughout the body, including the pineal gland, skin, lymphocytes and gastrointestinal tract (GIT). Its synthesis and secretion is controlled by light and dark conditions, whereby light decreases and darkness increases its production. Thus, melatonin is also known as the 'hormone of darkness'. Melatonin and analogs that bind to the melatonin receptors are important because of their role in the management of depression, insomnia, epilepsy, Alzheimer's disease (AD), diabetes, obesity, alopecia, migraine, cancer, and immune and cardiac disorders. In this review, we discuss the mechanism of action of melatonin in these disorders, which could aid in the design of novel melatonin receptor ligands. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Science Teachers' Analogical Reasoning

    Science.gov (United States)

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-08-01

    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 introduce analogies in their lessons. Both aspects have been discussed in the literature in the last few decades. However, almost nothing is known about how teachers draw their own analogies for instructional purposes or, in other words, about how they reason analogically when planning and conducting teaching. This is the focus of this paper. Six secondary teachers were individually interviewed; the aim was to characterize how they perform each of the analogical reasoning subprocesses, as well as to identify their views on analogies and their use in science teaching. The results were analyzed by considering elements of both theories about analogical reasoning: the structural mapping proposed by Gentner and the analogical mechanism described by Vosniadou. A comprehensive discussion of our results makes it evident that teachers' content knowledge on scientific topics and on analogies as well as their pedagogical content knowledge on the use of analogies influence all their analogical reasoning subprocesses. Our results also point to the need for improving teachers' knowledge about analogies and their ability to perform analogical reasoning.

  16. Intuitive analog circuit design

    CERN Document Server

    Thompson, Marc

    2013-01-01

    Intuitive Analog Circuit Design outlines ways of thinking about analog circuits and systems that let you develop a feel for what a good, working analog circuit design should be. This book reflects author Marc Thompson's 30 years of experience designing analog and power electronics circuits and teaching graduate-level analog circuit design, and is the ideal reference for anyone who needs a straightforward introduction to the subject. In this book, Dr. Thompson describes intuitive and ""back-of-the-envelope"" techniques for designing and analyzing analog circuits, including transistor amplifi

  17. Rhetoric and analogies

    OpenAIRE

    Aragonès, Enriqueta; Gilboa, Itzhak; Postlewaite, Andrew; Schmeidler, David; Universitat Autònoma de Barcelona. Unitat de Fonaments de l'Anàlisi Econòmica; Universitat Autònoma de Barcelona. Institut d'Anàlisi Econòmica

    2013-01-01

    The art of rhetoric may be defined as changing other people's minds (opinions, beliefs) without providing them new information. One tech- nique heavily used by rhetoric employs analogies. Using analogies, one may draw the listener's attention to similarities between cases and to re-organize existing information in a way that highlights certain reg- ularities. In this paper we offer two models of analogies, discuss their theoretical equivalence, and show that finding good analogies is a com- p...

  18. Analog and hybrid computing

    CERN Document Server

    Hyndman, D E

    2013-01-01

    Analog and Hybrid Computing focuses on the operations of analog and hybrid computers. The book first outlines the history of computing devices that influenced the creation of analog and digital computers. The types of problems to be solved on computers, computing systems, and digital computers are discussed. The text looks at the theory and operation of electronic analog computers, including linear and non-linear computing units and use of analog computers as operational amplifiers. The monograph examines the preparation of problems to be deciphered on computers. Flow diagrams, methods of ampl

  19. Structured Analog CMOS Design

    CERN Document Server

    Stefanovic, Danica

    2008-01-01

    Structured Analog CMOS Design describes a structured analog design approach that makes it possible to simplify complex analog design problems and develop a design strategy that can be used for the design of large number of analog cells. It intentionally avoids treating the analog design as a mathematical problem, developing a design procedure based on the understanding of device physics and approximations that give insight into parameter interdependences. The proposed transistor-level design procedure is based on the EKV modeling approach and relies on the device inversion level as a fundament

  20. Detecting analogies unconsciously

    Directory of Open Access Journals (Sweden)

    Thomas Peter Reber

    2014-01-01

    Full Text Available 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 reflects 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.

  1. Analog circuit design

    CERN Document Server

    Dobkin, Bob

    2012-01-01

    Analog circuit and system design today is more essential than ever before. With the growth of digital systems, wireless communications, complex industrial and automotive systems, designers are being challenged to develop sophisticated analog solutions. This comprehensive source book of circuit design solutions aids engineers with elegant and practical design techniques that focus on common analog challenges. The book's in-depth application examples provide insight into circuit design and application solutions that you can apply in today's demanding designs. <

  2. Alkylsulfanyl analogs as potent α2δ ligands.

    Science.gov (United States)

    Shimada, Kousei; Ohata, Yasuo; Kobayashi, Jun; Onishi, Yoshiyuki; Kawamura, Asuka; Domon, Yuki; Arakawa, Naohisa; Inoue, Tatsuya; Kitano, Yutaka; Matsuda, Fumihiko; Abe, Yuki; Deguchi, Tsuneo

    2018-06-15

    We identified novel (3R, 5S)-3-aminomethyl-5-methanesulfanyl hexanoic acid (5a: DS75091588) and (3R, 5S)-3-aminomethyl-5-ethanesulfanyl hexanoic acid (6a: DS18430756) as sulfur-containing γ-amino acid derivatives that were useful for the treatment of neuropathic pain. These two compounds exhibited a potent analgesic effect in animal models of both type I diabetes and type II diabetes, and good pharmacokinetics. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Analog synthetic biology.

    Science.gov (United States)

    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.

  4. Challenges in Using Analogies

    Science.gov (United States)

    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. Hydraulic Capacitor Analogy

    Science.gov (United States)

    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…

  6. Optical analogy. Synthesis report

    International Nuclear Information System (INIS)

    1965-01-01

    The authors report the study of conditions under which light attenuation (reflection, diffusion, absorption) and the attenuation of some radiations (notably thermal neutrons) can be described with analogical calculations. The analogy between light physical properties and neutron properties is not searched for, but the analogy between their attenuation characteristics. After having discussed this possible analogy, they propose a mathematical formulation of neutron and optical phenomena which could theoretically justify the optical analogy. The second part reports a more practical study of optics problems such as the study of simple optics materials and illumination measurements, or more precisely the study of angular distributions of optical reflections, a determination of such angular distributions, and an experimental determination of the albedo

  7. Ammonia formation by metal-ligand cooperative hydrogenolysis of a nitrido ligand

    Science.gov (United States)

    Askevold, Bjorn; Nieto, Jorge Torres; Tussupbayev, Samat; Diefenbach, Martin; Herdtweck, Eberhardt; Holthausen, Max C.; Schneider, Sven

    2011-07-01

    Bioinspired hydrogenation of N2 to ammonia at ambient conditions by stepwise nitrogen protonation/reduction with metal complexes in solution has experienced remarkable progress. In contrast, the highly desirable direct hydrogenation with H2 remains difficult. In analogy to the heterogeneously catalysed Haber-Bosch process, such a reaction is conceivable via metal-centred N2 splitting and unprecedented hydrogenolysis of the nitrido ligands to ammonia. We report the synthesis of a ruthenium(IV) nitrido complex. The high nucleophilicity of the nitrido ligand is demonstrated by unusual N-C coupling with π-acidic CO. Furthermore, the terminal nitrido ligand undergoes facile hydrogenolysis with H2 at ambient conditions to produce ammonia in high yield. Kinetic and quantum chemical examinations of this reaction suggest cooperative behaviour of a phosphorus-nitrogen-phosphorus pincer ligand in rate-determining heterolytic hydrogen splitting.

  8. Meat analog: a review.

    Science.gov (United States)

    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.

  9. Troubleshooting analog circuits

    CERN Document Server

    Pease, Robert A

    1991-01-01

    Troubleshooting Analog Circuits is a guidebook for solving product or process related problems in analog circuits. The book also provides advice in selecting equipment, preventing problems, and general tips. The coverage of the book includes the philosophy of troubleshooting; the modes of failure of various components; and preventive measures. The text also deals with the active components of analog circuits, including diodes and rectifiers, optically coupled devices, solar cells, and batteries. The book will be of great use to both students and practitioners of electronics engineering. Other

  10. Reduction of dinitrogen ligands

    International Nuclear Information System (INIS)

    Richards, R.L.

    1983-01-01

    Processes of dinitrogen ligand reduction in complexes of transition metals are considered. The basic character of the dinitrogen ligand is underlined. Data on X-ray photoelectronic spectroscopy and intensities of bands ν (N 2 ) in IR-spectra of nitrogen complexes are given. The mechanism of protonation of an edge dinitrogen ligand is discussed. Model systems and mechanism of nitrogenogenase are compared

  11. Analog circuits cookbook

    CERN Document Server

    Hickman, Ian

    2013-01-01

    Analog Circuits Cookbook presents articles about advanced circuit techniques, components and concepts, useful IC for analog signal processing in the audio range, direct digital synthesis, and ingenious video op-amp. The book also includes articles about amplitude measurements on RF signals, linear optical imager, power supplies and devices, and RF circuits and techniques. Professionals and students of electrical engineering will find the book informative and useful.

  12. FGF growth factor analogs

    Science.gov (United States)

    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.

  13. Ligands in PSI structures

    International Nuclear Information System (INIS)

    Kumar, Abhinav; Chiu, Hsiu-Ju; Axelrod, Herbert L.; Morse, Andrew; Elsliger, Marc-André; Wilson, Ian A.; Deacon, Ashley

    2010-01-01

    A survey of the types and frequency of ligands that are bound to PSI structures is analyzed as well as their utility in functional annotation of previously uncharacterized proteins. Approximately 65% of PSI structures report some type of ligand(s) that is bound in the crystal structure. Here, a description is given of how such ligands are handled and analyzed at the JCSG and a survey of the types, variety and frequency of ligands that are observed in the PSI structures is also compiled and analyzed, including illustrations of how these bound ligands have provided functional clues for annotation of proteins with little or no previous experimental characterization. Furthermore, a web server was developed as a tool to mine and analyze the PSI structures for bound ligands and other identifying features

  14. Electrical Circuits and Water Analogies

    Science.gov (United States)

    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)

  15. CMOS analog circuit design

    CERN Document Server

    Allen, Phillip E

    1987-01-01

    This text presents the principles and techniques for designing analog circuits to be implemented in a CMOS technology. The level is appropriate for seniors and graduate students familiar with basic electronics, including biasing, modeling, circuit analysis, and some familiarity with frequency response. Students learn the methodology of analog integrated circuit design through a hierarchically-oriented approach to the subject that provides thorough background and practical guidance for designing CMOS analog circuits, including modeling, simulation, and testing. The authors' vast industrial experience and knowledge is reflected in the circuits, techniques, and principles presented. They even identify the many common pitfalls that lie in the path of the beginning designer--expert advice from veteran designers. The text mixes the academic and practical viewpoints in a treatment that is neither superficial nor overly detailed, providing the perfect balance.

  16. Analogical Reasoning in Geometry Education

    Science.gov (United States)

    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…

  17. Digital and analog communication systems

    Science.gov (United States)

    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.

  18. Analogs for transuranic elements

    International Nuclear Information System (INIS)

    Weimer, W.C.; Laul, J.C.; Kutt, J.C.

    1981-01-01

    A combined theoretical and experimental approach is being used to estimate the long-term environmental and biogeochemical behaviors of selected transuranic elements. The objective of this research is to estimate the effect that long-term (hundreds of years) environmental weathering has on the behavior of the transuranic elements americium and curium. This is achieved by investigating the actual behavior of naturally occurring rare earth elements, especially neodymium, that serve as transuranic analogs. Determination of the analog element behavior provides data that can be used to estimate the ultimate availability to man of transuranic materials released into the environment

  19. Terrestrial Analogs to Mars

    Science.gov (United States)

    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.

  20. Reasoning through Instructional Analogies

    Science.gov (United States)

    Kapon, Shulamit; diSessa, Andrea A.

    2012-01-01

    This article aims to account for students' assessments of the plausibility and applicability of analogical explanations, and individual differences in these assessments, by analyzing properties of students' underlying knowledge systems. We developed a model of explanation and change in explanation focusing on knowledge elements that provide a…

  1. The Paradox of Analogy

    Directory of Open Access Journals (Sweden)

    David Botting

    2012-03-01

    Full Text Available I will show that there is a type of analogical reasoning that instantiates a pattern of reasoning in confirmation theory that is considered at best paradoxical and at worst fatal to the entire syntactical approach to confirmation and explanation. However, I hope to elaborate conditions under which this is a sound (although not necessarily strong method of reasoning.

  2. Analogy, explanation, and proof

    Science.gov (United States)

    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

  3. How Analogy Drives Physics

    International Nuclear Information System (INIS)

    Hofstadter, Doug

    2004-01-01

    Many new ideas in theoretical physics come from analogies to older ideas in physics. For instance, the abstract notion of 'isospin' (or isotopic spin) originated in the prior concept of 'spin' (quantized angular momentum); likewise, the concept of 'phonon' (quantum of sound, or quantized collective excitation of a crystal) was based on the prior concept of 'photon' (quantum of light, or quantized element of the electromagnetic field). But these two examples, far from being exceptions, in fact represent the bread and butter of inventive thinking in physics. In a nutshell, intraphysics analogy-making -- borrowing by analogy with something already known in another area of physics -- is central to the progress of physics. The aim of this talk is to reveal the pervasiveness -- indeed, the indispensability -- of this kind of semi-irrational, wholly intuitive type of thinking (as opposed to more deductive mathematical inference) in the mental activity known as 'doing physics'. Speculations as to why wild analogical leaps are so crucial to the act of discovery in physics (as opposed to other disciplines) will be offered.

  4. Quantum Analog Computing

    Science.gov (United States)

    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.

  5. Selective high-affinity polydentate ligands and methods of making such

    Energy Technology Data Exchange (ETDEWEB)

    Denardo, Sally J.; Denardo, Gerald L.; Balhorn, Rodney L.

    2018-02-06

    This invention provides novel polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each bind different region son the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

  6. Schiff base ligand

    Indian Academy of Sciences (India)

    Unknown

    Low-temperature stoichiometric Schiff base reaction in air in 3 : 1 mole ratio between benz- aldehyde and triethylenetetramine (trien) in methanol yields a novel tetraaza µ-bis(bidentate) acyclic ligand L. It was .... electrochemical work was performed as reported in ..... change in ligand shape through change in oxidation.

  7. Supramolecular architectures constructed using angular bipyridyl ligands

    International Nuclear Information System (INIS)

    Barnett, Sarah Ann

    2003-01-01

    This work details the synthesis and characterization of a series of coordination frameworks that are formed using bidentate angular N-donor ligands. Pyrimidine was reacted with metal(ll) nitrate salts. Reactions using Cd(NO 3 ) 2 receive particular focus and the analogous reactions using the linear ligand, pyrazine, were studied for comparison. In all cases, two-dimensional coordination networks were prepared. Structural diversity is observed for the Cd(ll) centres including metal-nitrate bridging. In contrast, first row transition metal nitrates form isostructural one-dimensional chains with only the bridging N-donor ligands generating polymeric propagation. The angular ligand, 2,4-bis(4-pyridyl)-1,3,5-triazine (dpt), was reacted with Cd(NO 3 ) 2 and Zn(NO 3 ) 2 . Whereas Zn(NO 3 ) 2 compounds exhibit solvent mediated polymorphism, a range of structures were obtained for the reactions with Cd(NO 3 ) 2 , including the first example of a doubly parallel interpenetrated 4.8 2 net. 4,7-phenanthroline, was reacted with various metal(ll) nitrates as well as cobalt(ll) and copper(ll) halides. The ability of 4,7-phenanthroline to act as both a N-donor ligand and a hydrogen bond acceptor has been discussed. Reactions of CuSCN with pyrimidine yield an unusual three-dimensional structure in which polymeric propagation is not a result of ligand bridging. The reaction of CuSCN with dpt yielded structural supramolecular isomers. (author)

  8. Terrestrial Spaceflight Analogs: Antarctica

    Science.gov (United States)

    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. Analog storage integrated circuit

    Science.gov (United States)

    Walker, J.T.; Larsen, R.S.; Shapiro, S.L.

    1989-03-07

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks. 6 figs.

  10. Analogy, Explanation, and Proof

    Directory of Open Access Journals (Sweden)

    John eHummel

    2014-11-01

    Full Text Available 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 (inductive inference that the milk is sour have in common with the (deductive 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 small-seeming difference poses a challenge to the task of marshaling our understanding of analogical reasoning in the service of 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.

  11. Ligand Exchange Kinetics of Environmentally Relevant Metals

    Energy Technology Data Exchange (ETDEWEB)

    Panasci, Adele Frances [Univ. of California, Davis, CA (United States)

    2014-07-15

    The interactions of ground water with minerals and contaminants are of broad interest for geochemists but are not well understood. Experiments on the molecular scale can determine reaction parameters (i.e. rates of ligand exchange, activation entropy, activation entropy, and activation volume) that can be used in computations to gain insight into reactions that occur in natural groundwaters. Experiments to determine the rate of isotopic ligand exchange for three environmentally relevant metals, rhodium (Rh), iron (Fe), and neptunium (Np), are described. Many environmental transformations of metals (e.g. reduction) in soil occur at trivalent centers, Fe(III) in particular. Contaminant ions absorb to mineral surfaces via ligand exchange, and the reversal of this reaction can be dangerous, releasing contaminants into the environment. Ferric iron is difficult to study spectroscopically because most of its complexes are paramagnetic and are generally reactive toward ligand exchange; therefore, Rh(III), which is diamagnetic and less reactive, was used to study substitution reactions that are analogous to those that occur on mineral oxide surfaces. Studies on both Np(V) and Np(VI) are important in their own right, as 237Np is a radioactive transuranic element with a half-life of 2 million years.

  12. Ligand modeling and design

    Energy Technology Data Exchange (ETDEWEB)

    Hay, B.P. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-10-01

    The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used in the cost-effective removal of specific radionuclides from nuclear waste streams. Organic ligands with metal ion specificity are critical components in the development of solvent extraction and ion exchange processes that are highly selective for targeted radionuclides. The traditional approach to the development of such ligands involves lengthy programs of organic synthesis and testing, which in the absence of reliable methods for screening compounds before synthesis, results in wasted research effort. The author`s approach breaks down and simplifies this costly process with the aid of computer-based molecular modeling techniques. Commercial software for organic molecular modeling is being configured to examine the interactions between organic ligands and metal ions, yielding an inexpensive, commercially or readily available computational tool that can be used to predict the structures and energies of ligand-metal complexes. Users will be able to correlate the large body of existing experimental data on structure, solution binding affinity, and metal ion selectivity to develop structural design criteria. These criteria will provide a basis for selecting ligands that can be implemented in separations technologies through collaboration with other DOE national laboratories and private industry. The initial focus will be to select ether-based ligands that can be applied to the recovery and concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium.

  13. Identification of VDR Antagonists among Nuclear Receptor Ligands Using Virtual Screening

    Directory of Open Access Journals (Sweden)

    Kelly Teske

    2014-04-01

    Full Text Available Herein, we described the development of two virtual screens to identify new vitamin D receptor (VDR antagonists among nuclear receptor (NR ligands. Therefore, a database of 14330 nuclear receptor ligands and their NR affinities was assembled using the online available “Binding Database.” Two different virtual screens were carried out in conjunction with a reported VDR crystal structure applying a stringent and less stringent pharmacophore model to filter docked NR ligand conformations. The pharmacophore models were based on the spatial orientation of the hydroxyl functionalities of VDR's natural ligands 1,25(OH2D3 and 25(OH2D3. The first virtual screen identified 32 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. All but nordihydroguaiaretic acid (NDGA are VDR ligands, which inhibited the interaction between VDR and coactivator peptide SRC2-3 with an IC50 value of 15.8 μM. The second screen identified 162 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. More than half of these ligands were developed to bind VDR followed by ERα/β ligands (26%, TRα/β ligands (7%, and LxRα/β ligands (7%. The binding between VDR and ERα ligand H6036 as well as TRα/β ligand triiodothyronine and a homoserine analog thereof was confirmed by fluorescence polarization.

  14. Component Processes in Analogical Reasoning

    Science.gov (United States)

    Sternberg, Robert J.

    1977-01-01

    Describes alternative theoretical positions regarding (a) the component information processes used in analogical reasoning and (b) strategies for combining these processes. Also presents results from three experiments on analogical reasoning. (Author/RK)

  15. Inductive, Analogical, and Communicative Generalization

    Directory of Open Access Journals (Sweden)

    Adri Smaling

    2003-03-01

    Full Text Available Three forms of inductive generalization - statistical generalization, variation-based generalization and theory-carried generalization - are insufficient concerning case-to-case generalization, which is a form of analogical generalization. The quality of case-to-case generalization needs to be reinforced by setting up explicit analogical argumentation. To evaluate analogical argumentation six criteria are discussed. Good analogical reasoning is an indispensable support to forms of communicative generalization - receptive and responsive (participative generalization — as well as exemplary generalization.

  16. Analogical Reasoning and Computer Programming.

    Science.gov (United States)

    Clement, Catherine A.; And Others

    1986-01-01

    A study of correlations between analogical reasoning and Logo programming mastery among female high school students related the results of pretests of analogical reasoning to posttests of programming mastery. A significant correlation was found between analogical reasoning and the ability to write subprocedures for use in several different…

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

    Science.gov (United States)

    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.

  18. Discrete Calculus by Analogy

    CERN Document Server

    Izadi, F A; Bagirov, G

    2009-01-01

    With its origins stretching back several centuries, discrete calculus is now an increasingly central methodology for many problems related to discrete systems and algorithms. The topics covered here usually arise in many branches of science and technology, especially in discrete mathematics, numerical analysis, statistics and probability theory as well as in electrical engineering, but our viewpoint here is that these topics belong to a much more general realm of mathematics; namely calculus and differential equations because of the remarkable analogy of the subject to this branch of mathemati

  19. ESD analog circuits and design

    CERN Document Server

    Voldman, Steven H

    2014-01-01

    A comprehensive and in-depth review of analog circuit layout, schematic architecture, device, power network and ESD design This book will provide a balanced overview of analog circuit design layout, analog circuit schematic development, architecture of chips, and ESD design.  It will start at an introductory level and will bring the reader right up to the state-of-the-art. Two critical design aspects for analog and power integrated circuits are combined. The first design aspect covers analog circuit design techniques to achieve the desired circuit performance. The second and main aspect pres

  20. Albert Einstein, Analogizer Extraordinaire

    CERN Multimedia

    CERN. Geneva

    2007-01-01

    Where does deep insight in physics come from? It is tempting to think that it comes from the purest and most precise of reasoning, following ironclad laws of thought that compel the clear mind completely rigidly. And yet the truth is quite otherwise. One finds, when one looks closely at any major discovery, that the greatest of physicists are, in some sense, the most crazily daring and irrational of all physicists. Albert Einstein exemplifies this thesis in spades. In this talk I will describe the key role, throughout Albert Einstein's fabulously creative life, played by wild guesses made by analogy lacking any basis whatsoever in pure reasoning. In particular, in this year of 2007, the centenary of 1907, I will describe how over the course of two years (1905 through 1907) of pondering, Einstein slowly came, via analogy, to understand the full, radical consequences of the equation that he had first discovered and published in 1905, arguably the most famous equation of all time: E = mc2.

  1. Detecting analogical resemblance without retrieving the source analogy.

    Science.gov (United States)

    Kostic, Bogdan; Cleary, Anne M; Severin, Kaye; Miller, Samuel W

    2010-06-01

    We examined whether people can detect analogical resemblance to an earlier experimental episode without being able to recall the experimental source of the analogical resemblance. We used four-word analogies (e.g., robin-nest/beaver-dam), in a variation of the recognition-without-cued-recall method (Cleary, 2004). Participants studied word pairs (e.g., robin-nest) and were shown new word pairs at test, half of which analogically related to studied word pairs (e.g., beaver-dam) and half of which did not. For each test pair, participants first attempted to recall an analogically similar pair from the study list. Then, regardless of whether successful recall occurred, participants were prompted to rate the familiarity of the test pair, which was said to indicate the likelihood that a pair that was analogically similar to the test pair had been studied. Across three experiments, participants demonstrated an ability to detect analogical resemblance without recalling the source analogy. Findings are discussed in terms of their potential relevance to the study of analogical reasoning and insight, as well as to the study of familiarity and recognition memory.

  2. Feedback in analog circuits

    CERN Document Server

    Ochoa, Agustin

    2016-01-01

    This book describes a consistent and direct methodology to the analysis and design of analog circuits with particular application to circuits containing feedback. The analysis and design of circuits containing feedback is generally presented by either following a series of examples where each circuit is simplified through the use of insight or experience (someone else’s), or a complete nodal-matrix analysis generating lots of algebra. Neither of these approaches leads to gaining insight into the design process easily. The author develops a systematic approach to circuit analysis, the Driving Point Impedance and Signal Flow Graphs (DPI/SFG) method that does not require a-priori insight to the circuit being considered and results in factored analysis supporting the design function. This approach enables designers to account fully for loading and the bi-directional nature of elements both in the feedback path and in the amplifier itself, properties many times assumed negligible and ignored. Feedback circuits a...

  3. Spectrophotometric method for determination of bifunctional macrocyclic ligands in macrocyclic ligand-protein conjugates

    International Nuclear Information System (INIS)

    Dadachova, E.; Chappell, L.L.; Brechbiel, M.W.

    1999-01-01

    A simple spectrophotometric assay for determination of bifunctional polyazacarboxylate-macrocyclic ligands of different sizes that are conjugated to proteins has been developed for: 12-membered macrocycle DOTA (2-[4-nitrobenzyl]-1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) and analogs, the 15-membered PEPA macrocycle (2-[4-nitrobenzyl]-1,4,7,10,13-pentaazacyclopentadecane-N,N',N'',N''',N'''' -pentaacetic acid), and the large 18-membered macrocycle HEHA (1,4,7,10,13,16-hexaazacyclooctadecane-N,N',N'',N''',N''''-hexaacetic acid). The method is based on titration of the blue-colored 1:1 Pb(II)-Arsenazo III (AAIII) complex with the polyazacarboxylate macrocyclic ligand in the concentration range of 0-2.5 μM, wherein color change occurring upon transchelation of the Pb(II) from the AAIII to the polyazamacrocyclic ligand is monitored at 656 nm. The assay is performed at ambient temperature within 20 min without any interfering interaction between the protein and Pb(II)-AA(III) complex. Thus, this method also provides a ligand-to-protein ratio (L/P ratio) that reflects the effective number of ligands per protein molecule available to radiolabeling. The method is not suitable for 14-membered TETA macrocycle (2-[4-nitrobenzyl]-1, 4, 8, 11-tetraazacyclotetradecane N,N',N'',N'''-tetraacetic acid) because of low stability constant of Pb(II)-TETA complex. The method is rapid, simple and may be customized for other polyazacarboxylate macrocyclic ligands

  4. Beginning analog electronics through projects

    CERN Document Server

    Singmin, Andrew

    2001-01-01

    Analog electronics is the simplest way to start a fun, informative, learning program. Beginning Analog Electronics Through Projects, Second Edition was written with the needs of beginning hobbyists and students in mind. This revision of Andrew Singmin's popular Beginning Electronics Through Projects provides practical exercises, building techniques, and ideas for useful electronics projects. Additionally, it features new material on analog and digital electronics, and new projects for troubleshooting test equipment.Published in the tradition of Beginning Electronics Through Projects an

  5. Children's Development of Analogical Reasoning: Insights from Scene Analogy Problems

    Science.gov (United States)

    Richland, Lindsey E.; Morrison, Robert G.; Holyoak, Keith J.

    2006-01-01

    We explored how relational complexity and featural distraction, as varied in scene analogy problems, affect children's analogical reasoning performance. Results with 3- and 4-year-olds, 6- and 7-year-olds, 9- to 11-year-olds, and 13- and 14-year-olds indicate that when children can identify the critical structural relations in a scene analogy…

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

    Science.gov (United States)

    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.

  7. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  8. Optical analog transmission device

    International Nuclear Information System (INIS)

    Ikawa, Shinji.

    1994-01-01

    The present invention concerns a device such as electro-optical conversion elements, optoelectric-electric elements and optical transmission channel, not undergoing deleterious effects on the efficiency of conversion and transmission due to temperature, and aging change. That is, a sine wave superposing means superposes, on a detector signal to be transmitted, a sine-wave signal having a predetermined amplitude and at a frequency lower than that of the detector signal. An optoelectric conversion means converts the electric signal as the signal of the sine-wave signal superposing means into an optical signal and outputs the same to an optical transmitting channel. The optoelectric conversion means converts the transmitted signal to an electric signal. A discriminating means discriminates the electric signal into a detector signal and a sine-wave signal. A calculating means calculates an optical transmitting efficiency of the transmitting channel based on the amplitude of the discriminated sine-wave signal. A processing means compensates an amplitude value of the detector signals discriminated by the discriminating means based on the optical transmission efficiency. As a result, an optical analog transmission device can be attained, which conducts optical transmission at a high accuracy without undergoing the defective effects of the optical transmission efficiency. (I.S.)

  9. Conjecturing via Reconceived Classical Analogy

    Science.gov (United States)

    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…

  10. Musik som analogi og metafor

    DEFF Research Database (Denmark)

    Bonde, Lars Ole

    2014-01-01

    Indeholder underkapitlerne: 2.5.1 Musik som analogi 2.5.2 Musik som metafor 2.5.3 Musikkens psykologiske funktioner - en taxonomi og metaforisk lytning til fire baroksatser......Indeholder underkapitlerne: 2.5.1 Musik som analogi 2.5.2 Musik som metafor 2.5.3 Musikkens psykologiske funktioner - en taxonomi og metaforisk lytning til fire baroksatser...

  11. Drawing Analogies in Environmental Education

    Science.gov (United States)

    Affifi, Ramsey

    2014-01-01

    Reconsidering the origin, process, and outcomes of analogy-making suggests practices for environmental educators who strive to disengage humans from the isolating illusions of dichotomizing frameworks. We can view analogies as outcomes of developmental processes within which human subjectivity is but an element, threading our sense of self back…

  12. An Analogy Using Pennies and Dimes to Explain Chemical Kinetics Concepts

    Science.gov (United States)

    Cortes-Figueroa, Jose E.; Perez, Wanda I.; Lopez, Jose R.; Moore-Russo, Deborah A.

    2011-01-01

    In this article, the authors present an analogy that uses coins and graphical analysis to teach kinetics concepts and resolve pseudo-first-order rate constants related to transition-metal complexes ligand-solvent exchange reactions. They describe an activity that is directed to upper-division undergraduate and graduate students. The activity…

  13. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J M

    2010-01-01

    The design of an analog-to-digital converter or digital-to-analog converter is one of the most fascinating tasks in micro-electronics. In a converter the analog world with all its intricacies meets the realm of the formal digital abstraction. Both disciplines must be understood for an optimum conversion solution. In a converter also system challenges meet technology opportunities. Modern systems rely on analog-to-digital converters as an essential part of the complex chain to access the physical world. And processors need the ultimate performance of digital-to-analog converters to present the results of their complex algorithms. The same progress in CMOS technology that enables these VLSI digital systems creates new challenges for analog-to-digital converters: lower signal swings, less power and variability issues. Last but not least, the analog-to-digital converter must follow the cost reduction trend. These changing boundary conditions require micro-electronics engineers to consider their design choices for...

  14. Analog fourier transform channelizer and OFDM receiver

    OpenAIRE

    2007-01-01

    An OFDM receiver having an analog multiplier based I-Q channelizing filter, samples and holds consecutive analog I-Q samples of an I-Q baseband, the I-Q basebands having OFDM sub-channels. A lattice of analog I-Q multipliers and analog I-Q summers concurrently receives the held analog I-Q samples, performs analog I-Q multiplications and analog I-Q additions to concurrently generate a plurality of analog I-Q output signals, representing an N-point discrete Fourier transform of the held analog ...

  15. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

  16. Radiobiology with DNA ligands

    International Nuclear Information System (INIS)

    Weinreich, R.; Argentini, M.; Guenther, I.; Koziorowski, J.; Larsson, B.; Nievergelt-Egido, M.C.; Salt, C.; Wyer, L.; Dos Santos, D.F.; Hansen, H.J.

    1997-01-01

    The paper deals with the following topics: labelling of DNA ligands and other tumour-affinic compounds with 4.15-d 124 I, radiotoxicity of Hoechst 33258 and 33342 and of iodinated Hoechst 33258 in cell cultures, preparation of 76 Br-, 123 I-, and 221 At-labelled 5-halo-2'-deoxyuridine, chemical syntheses of boron derivatives of Hoechst 33258.III., Gadolinium neutron capture therapy

  17. Gemini analogs of vitamin D.

    Science.gov (United States)

    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.

  18. Analog filters in nanometer CMOS

    CERN Document Server

    Uhrmann, Heimo; Zimmermann, Horst

    2014-01-01

    Starting from the basics of analog filters and the poor transistor characteristics in nanometer CMOS 10 high-performance analog filters developed by the authors in 120 nm and 65 nm CMOS are described extensively. Among them are gm-C filters, current-mode filters, and active filters for system-on-chip realization for Bluetooth, WCDMA, UWB, DVB-H, and LTE applications. For the active filters several operational amplifier designs are described. The book, furthermore, contains a review of the newest state of research on low-voltage low-power analog filters. To cover the topic of the book comprehensively, linearization issues and measurement methods for the characterization of advanced analog filters are introduced in addition. Numerous elaborate illustrations promote an easy comprehension. This book will be of value to engineers and researchers in industry as well as scientists and Ph.D students at universities. The book is also recommendable to graduate students specializing on nanoelectronics, microelectronics ...

  19. Analog elements for transuranic chemistries

    International Nuclear Information System (INIS)

    Weimer, W.C.

    1982-01-01

    The analytical technique for measuring trace concentrations of the analog rare earth elements has been refined for optimal detection. The technique has been used to determine the rare earth concentrations in a series of geological and biological materials, including samples harvested from controlled lysimeter investigations. These studies have demonstrated that any of the trivalent rare earth elements may be used as analog elements for the trivalent transuranics, americium and curium

  20. CMOS Analog IC Design: Fundamentals

    OpenAIRE

    Bruun, Erik

    2018-01-01

    This book is intended for use as the main textbook for an introductory course in CMOS analog integrated circuit design. It is aimed at electronics engineering students who have followed basic courses in mathematics, physics, circuit theory, electronics and signal processing. It takes the students directly from a basic level to a level where they can start working on simple analog IC design projects or continue their studies using more advanced textbooks in the field. A distinct feature of thi...

  1. Analogical proportions: another logical view

    Science.gov (United States)

    Prade, Henri; Richard, Gilles

    This paper investigates the logical formalization of a restricted form of analogical reasoning based on analogical proportions, i.e. statements of the form a is to b as c is to d. Starting from a naive set theoretic interpretation, we highlight the existence of two noticeable companion proportions: one states that a is to b the converse of what c is to d (reverse analogy), while the other called paralogical proportion expresses that what a and b have in common, c and d have it also. We identify the characteristic postulates of the three types of proportions and examine their consequences from an abstract viewpoint. We further study the properties of the set theoretic interpretation and of the Boolean logic interpretation, and we provide another light on the understanding of the role of permutations in the modeling of the three types of proportions. Finally, we address the use of these proportions as a basis for inference in a propositional setting, and relate it to more general schemes of analogical reasoning. The differences between analogy, reverse-analogy, and paralogy is still emphasized in a three-valued setting, which is also briefly presented.

  2. Synthesis and characterization of an iron complex bearing a cyclic tetra-N-heterocyclic carbene ligand: An artifical heme analogue?

    KAUST Repository

    Anneser, Markus R.

    2015-04-20

    An iron(II) complex with a cyclic tetradentate ligand containing four N-heterocyclic carbenes was synthesized and characterized by means of NMR and IR spectroscopies, as well as by single-crystal X-ray structure analysis. The iron center exhibits an octahedral coordination geometry with two acetonitrile ligands in axial positions, showing structural analogies with porphyrine-ligated iron complexes. The acetonitrile ligands can readily be substituted by other ligands, for instance, dimethyl sulfoxide, carbon monoxide, and nitric oxide. Cyclic voltammetry was used to examine the electronic properties of the synthesized compounds. © 2015 American Chemical Society.

  3. Bexarotene ligand pharmaceuticals.

    Science.gov (United States)

    Hurst, R E

    2000-12-01

    Bexarotene (LGD-1069), from Ligand, was the first retinoid X receptor (RXR)-selective, antitumor retinoid to enter clinical trials. The company launched the drug for the treatment of cutaneous T-cell lymphoma (CTCL), as Targretin capsules, in the US in January 2000 [359023]. The company filed an NDA for Targretin capsules in June 1999, and for topical gel in December 1999 [329011], [349982] specifically for once-daily oral administration for the treatment of patients with early-stage CTCL who have not tolerated other therapies, patients with refractory or persistent early stage CTCL and patients with refractory advanced stage CTCL. The FDA approved Targretin capsules at the end of December 1999 for once-daily oral treatment of all stages of CTCL in patients refractory to at least one prior systemic therapy, at an initial dose of 300 mg/m2/day. After an NDA was submitted in December 1999 for Targretin gel, the drug received Priority Review status for use as a treatment of cutaneous lesions in patients with stage IA, IB or IIA CTCL [354836]. The FDA issued an approvable letter in June 2000, and granted marketing clearance for CTCL in the same month [370687], [372768], [372769], [373279]. Ligand had received Orphan Drug designation for this indication [329011]. At the request of the FDA, Ligand agreed to carry out certain post-approval phase IV and pharmacokinetic studies [351604]. The company filed an MAA with the EMEA for Targretin Capsules to treat lymphoma in November 1999 [348944]. The NDA for Targretin gel is based on a multicenter phase III trial that was conducted in the US, Canada, Europe and Australia involving 50 patients and a multicenter phase I/II clinical program involving 67 patients. Targretin gel was evaluated for the treatment of patients with early stage CTCL (IA-IIA) who were refractory to, intolerant to, or reached a response plateau for at least 6 months on at least two prior therapies. Efficacy results exceeded the protocol-defined response

  4. Dramatic improvement in photostability of luminescent Eu(III) complexes with tetraphenylimidodiphosphinate ligand

    International Nuclear Information System (INIS)

    Zheng, Wei; Li, Shu-Jing; Li, Cheng-Hui; Zheng, You-Xuan; You, Xiao-Zeng

    2014-01-01

    In this paper, we synthesized and characterized a new Eu(III) tetraphenylimidodiphosphinate complex with dimethyl sulfoxide (DMSO) as co-ligand. Moreover, we compared the photostability of a series of Eu(III) complexes containing tetraphenylimidodiphosphinate ligands, Eu(tpip) 3 , Eu(tpip) 3 Phen, Eu(tpip) 3 DMSO, with their analogs of 1,3-dibenzoylmethanate, Eu(dbm) 3 ∙2H 2 O, Eu(dbm) 3 Phen, Eu(dbm) 3 (DMSO) 2 . We found that the photostability of the luminescent Eu(III) complexes was significantly improved upon substitution of the 1,3-diketones with tetraphenylimidodiphosphinate ligands. -- Highlights: • We synthesized and characterized a new Eu(III) tetraphenylimidodiphosphinate complexes with dimethyl sulfoxide. • We compared the photostability of Eu(III) complex with tetraphenylimidodiphosphinate and 1,3-dibenzoylmethanate ligands. • The photostability is significantly improved in Eu(III) complexes with tetraphenylimidodiphosphinate ligands

  5. Producing and Recognizing Analogical Relations

    Science.gov (United States)

    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 relations. The present series of four studies expands previous work by exploring the applicability of this model of analogy to topography-based rather than merely selection-based responses and by extending the work into additional relations, including nonsymmetrical ones. In each of the four studies participants pretrained in contextual control over nonarbitrary stimulus relations of sameness and opposition, or of sameness, smaller than, and larger than, learned arbitrary stimulus relations in the presence of these relational cues and derived analogies involving directly trained relations and derived relations of mutual and combinatorial entailment, measured using a variety of productive and selection-based measures. In Experiment 1 participants successfully recognized analogies among stimulus networks containing same and opposite relations; in Experiment 2 analogy was successfully used to extend derived relations to pairs of novel stimuli; in Experiment 3 the procedure used in Experiment 1 was extended to nonsymmetrical comparative relations; in Experiment 4 the procedure used in Experiment 2 was extended to nonsymmetrical comparative relations. Although not every participant showed the effects predicted, overall the procedures occasioned relational responses consistent with an RFT account that have not yet been demonstrated in a behavior-analytic laboratory setting, including productive responding on the basis of analogies. PMID:19230515

  6. Fast multichannel analog storage system

    International Nuclear Information System (INIS)

    Freytag, D.R.

    1982-11-01

    A Multichannel Analog Storage System based on a commercial 32-channel parallel in/serial out (PISO) analog shift register is described. The basic unit is a single width CAMAC module containing 512 analog cells and the associated logic for data storage and subsequent readout. At sampling rates of up to 30 MHz the signals are strobed directly into the PISO. At higher rates signals are strobed into a fast presampling stage and subsequently transferred in block form into an array of PISO's. Sampling rates of 300 MHz have been achieved with the present device and 1000 MHz are possible with improved signal drivers. The system is well suited for simultaneous handling of many signal channels with moderate numbers of samples in each channel. RMS noise over full scale signal has been measured as 1:3000 (approx. = 11 bit). However, nonlinearities in the response and differences in sensitivity of the analog cells require an elaborate calibration system in order to realize 11 bit accuracy for the analog information

  7. Structural and Electrochemical Consequences of [Cp*] Ligand Protonation.

    Science.gov (United States)

    Peng, Yun; Ramos-Garcés, Mario V; Lionetti, Davide; Blakemore, James D

    2017-09-05

    There are few examples of the isolation of analogous metal complexes bearing [η 5 -Cp*] and [η 4 -Cp*H] (Cp* = pentamethylcyclopentadienyl) complexes within the same metal/ligand framework, despite the relevance of such structures to catalytic applications. Recently, protonation of Cp*Rh(bpy) (bpy = 2,2'-bipyridyl) has been shown to yield a complex bearing the uncommon [η 4 -Cp*H] ligand, rather than generating a [Rh III -H] complex. We now report the purification and isolation of this protonated species, as well as characterization of analogous complexes of 1,10-phenanthroline (phen). Specifically, reaction of Cp*Rh(bpy) or Cp*Rh(phen) with 1 equiv of Et 3 NH + Br - affords rhodium compounds bearing endo-η 4 -pentamethylcyclopentadiene (η 4 -Cp*H) as a ligand. NMR spectroscopy and single-crystal X-ray diffraction studies confirm protonation of the Cp* ligand, rather than formation of metal hydride complexes. Analysis of new structural data and electronic spectra suggests that phen is significantly reduced in Cp*Rh(phen), similar to the case of Cp*Rh(bpy). Backbonding interactions with olefinic motifs are activated by formation of [η 4 -Cp*H]; protonation of [Cp*] stabilizes the low-valent metal center and results in loss of reduced character on the diimine ligands. In accord with these changes in electronic structure, electrochemical studies reveal a distinct manifold of redox processes that are accessible in the [Cp*H] complexes in comparison with their [Cp*] analogues; these processes suggest new applications in catalysis for the complexes bearing endo-η 4 -Cp*H.

  8. Analog electronics for radiation detection

    CERN Document Server

    2016-01-01

    Analog Electronics for Radiation Detection showcases the latest advances in readout electronics for particle, or radiation, detectors. Featuring chapters written by international experts in their respective fields, this authoritative text: Defines the main design parameters of front-end circuitry developed in microelectronics technologies Explains the basis for the use of complementary metal oxide semiconductor (CMOS) image sensors for the detection of charged particles and other non-consumer applications Delivers an in-depth review of analog-to-digital converters (ADCs), evaluating the pros and cons of ADCs integrated at the pixel, column, and per-chip levels Describes incremental sigma delta ADCs, time-to-digital converter (TDC) architectures, and digital pulse-processing techniques complementary to analog processing Examines the fundamental parameters and front-end types associated with silicon photomultipliers used for single visible-light photon detection Discusses pixel sensors ...

  9. Natural analogs for Yucca Mountain

    International Nuclear Information System (INIS)

    Murphy, W.M.

    1995-01-01

    High-level radioactive waste in the US, spent fuels from commercial reactors and nuclear materials generated by defense activities, will remain potentially hazardous for thousands of years. Demonstrable long-term stability of certain geologic and geochemical systems motivates and sustains the concept that high-level waste can be safely isolated in geologic repositories for requisite periods of time. Each geologic repository is unique in its properties and performance with reguard to isolation of nuclear wastes. Studies of processes analogous to waste-form alteration and radioelement transport in environments analogous to Yucca Mountain are being conducted at two sites, described in this article to illustrate uses of natural analog data: the Nopal I uranium deposit in the Sierra Pena Blanca, Mexico, and the Akrotiri archaeological site on the island of Santorini, Greece

  10. Synthetic Analogs of Phospholipid Metabolites as Antimalarials.

    Science.gov (United States)

    1979-07-01

    phosphatidic acid analogs containing ether and phosphonate groups; completely non- hydrolyzable lecithin analogs containing phosphinate and ether groups...substance is a completely non- hydrolyzable analog of lecithin containing ether and phosphonate moieties instead of the normally labile carboxylic and...and also ant-i-phospholipase C (clostridial enzyme) activity. This substance Is a completely non- hydrolyzable analog of lecithin containing ether

  11. Ligand Depot: a data warehouse for ligands bound to macromolecules.

    Science.gov (United States)

    Feng, Zukang; Chen, Li; Maddula, Himabindu; Akcan, Ozgur; Oughtred, Rose; Berman, Helen M; Westbrook, John

    2004-09-01

    Ligand Depot is an integrated data resource for finding information about small molecules bound to proteins and nucleic acids. The initial release (version 1.0, November, 2003) focuses on providing chemical and structural information for small molecules found as part of the structures deposited in the Protein Data Bank. Ligand Depot accepts keyword-based queries and also provides a graphical interface for performing chemical substructure searches. A wide variety of web resources that contain information on small molecules may also be accessed through Ligand Depot. Ligand Depot is available at http://ligand-depot.rutgers.edu/. Version 1.0 supports multiple operating systems including Windows, Unix, Linux and the Macintosh operating system. The current drawing tool works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.

  12. Metal-ligand interactions

    Science.gov (United States)

    Ervin, Kent M.

    Experimental studies of the interactions of small transition-metal cluster anions with carbonyl ligands are reviewed and compared with neutral and cationic clusters. Under thermal conditions, the reaction rates of transition-metal clusters with carbon monoxide are measured as a function of cluster size. Saturation limits for carbon monoxide addition can be related to the geometric structures of the clusters. Both energy-resolved threshold collision-induced dissociation experiments and time-resolved photodissociation experiments are used to measure metal-carbonyl binding energies. For platinum and palladium trimer anions, the carbonyl binding energies are assigned to different geometric binding sites. Platinum and palladium cluster anions catalyse the oxidation of carbon monoxide to carbon dioxide in a full catalytic cycle at thermal energies.

  13. Macrocyclic G-quadruplex ligands

    DEFF Research Database (Denmark)

    Nielsen, M C; Ulven, Trond

    2010-01-01

    are macrocyclic structures which have been modeled after the natural product telomestatin or from porphyrin-based ligands discovered in the late 1990s. These two structural classes of G-quadruplex ligands are reviewed here with special attention to selectivity and structure-activity relationships, and with focus...

  14. Multichannel analog temperature sensing system

    International Nuclear Information System (INIS)

    Gribble, R.

    1985-08-01

    A multichannel system that protects the numerous and costly water-cooled magnet coils on the translation section of the FRX-C/T magnetic fusion experiment is described. The system comprises a thermistor for each coil, a constant current circuit for each thermistor, and a multichannel analog-to-digital converter interfaced to the computer

  15. 49205 ANALOGE OG DIGITALE FILTRE

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    1997-01-01

    Theese lecture notes treats the fundamental theory and the most commonly used design methods for passive- active and digital filters with special emphasis on microelectronic realizations. The lecture notes covers 75% of the material taught in the course 49205 Analog and Digital Filters...

  16. Drawing Analogies to Deepen Learning

    Science.gov (United States)

    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…

  17. Bayesian analogy with relational transformations.

    Science.gov (United States)

    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.

  18. Crows spontaneously exhibit analogical reasoning.

    Science.gov (United States)

    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.

  19. Water oxidation catalyzed by mononuclear ruthenium complexes with a 2,2'-bipyridine-6,6'-dicarboxylate (bda) ligand: how ligand environment influences the catalytic behavior.

    Science.gov (United States)

    Staehle, Robert; Tong, Lianpeng; Wang, Lei; Duan, Lele; Fischer, Andreas; Ahlquist, Mårten S G; Sun, Licheng; Rau, Sven

    2014-02-03

    A new water oxidation catalyst [Ru(III)(bda)(mmi)(OH2)](CF3SO3) (2, H2bda = 2,2'-bipyridine-6,6'-dicarboxylic acid; mmi = 1,3-dimethylimidazolium-2-ylidene) containing an axial N-heterocyclic carbene ligand and one aqua ligand was synthesized and fully characterized. The kinetics of catalytic water oxidation by 2 were measured using stopped-flow technique, and key intermediates in the catalytic cycle were probed by density functional theory calculations. While analogous Ru-bda water oxidation catalysts [Ru(bda)L2] (L = pyridyl ligands) are supposed to catalyze water oxidation through a bimolecular coupling pathway, our study points out that 2, surprisingly, undergoes a single-site water nucleophilic attack (acid-base) pathway. The diversion of catalytic mechanisms is mainly ascribed to the different ligand environments, from nonaqua ligands to an aqua ligand. Findings in this work provide some critical proof for our previous hypothesis about how alternation of ancillary ligands of water oxidation catalysts influences their catalytic efficiency.

  20. Enhanced efficacy (intrinsic activity) of cyclic opioid peptide analogs at the μ-receptor

    International Nuclear Information System (INIS)

    Schiller, P.W.; Lemieux, C.; Nguyen, T.M.D.; Maziak, L.A.

    1986-01-01

    Side-chain to end group cyclized enkephalin analogs (e.g. H-Tyr-cyclo[-D-Lys-Gly-Phe-Leu-] and cyclic opioid peptide analogs obtained through covalent linkage of two side-chains (e.g. H-Tyr-D-Cys-Gly-Phe-Cys-NH 2 or H-Tyr-D-Lys-Gly-Phe-Glu-NH 3 ) were tested in the μ-receptor-representative guinea pig ileum (GPI) bioassay and in a binding assay based on displacement of the μ-ligand [ 3 H]DAGO from rat brain membranes. The cyclic analogs were 5 to 70 times more potent in the GPI assay than in the binding assay, whereas linear analogs showed equal potency in the two assays. These results suggest that the efficacy (intrinsic activity) of cyclic opioid peptide analogs at the μ-receptor is increased as a consequence of the conformation constraint imposed through ring closure. This effect was most pronounced in analogs containing a long hydrophobic sidechain as part of the ring structure in the 2-position of the peptide sequence. Further experimental evidence ruled out the possibilities that these potency discrepancies may be due to differences in enzymatic degradation, dissimilar exposure of the receptors in their lipid environment or interaction with different receptor types in the two assay systems. It can be hypothesized that the semi-rigid cyclic analogs may induce a more productive conformational change in the receptor protein than the linear peptides

  1. Analog circuit design art, science and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    This book is far more than just another tutorial or reference guide - it's a tour through the world of analog design, combining theory and applications with the philosophies behind the design process. Readers will learn how leading analog circuit designers approach problems and how they think about solutions to those problems. They'll also learn about the `analog way' - a broad, flexible method of thinking about analog design tasks.A comprehensive and useful guide to analog theory and applications. Covers visualizing the operation of analog circuits. Looks at how to rap

  2. Two novel mixed-ligand complexes containing organosulfonate ligands.

    Science.gov (United States)

    Li, Mingtian; Huang, Jun; Zhou, Xuan; Fang, Hua; Ding, Liyun

    2008-07-01

    The structures reported herein, viz. bis(4-aminonaphthalene-1-sulfonato-kappaO)bis(4,5-diazafluoren-9-one-kappa(2)N,N')copper(II), [Cu(C(10)H(8)NO(3)S)(2)(C(11)H(6)N(2)O)(2)], (I), and poly[[[diaquacadmium(II)]-bis(mu-4-aminonaphthalene-1-sulfonato)-kappa(2)O:N;kappa(2)N:O] dihydrate], {[Cd(C(10)H(8)NO(3)S)(2)(H(2)O)(2)].2H(2)O}(n), (II), are rare examples of sulfonate-containing complexes where the anion does not fulfill a passive charge-balancing role, but takes an active part in coordination as a monodentate and/or bridging ligand. Monomeric complex (I) possesses a crystallographic inversion center at the Cu(II) atom, and the asymmetric unit contains one-half of a Cu atom, one complete 4-aminonaphthalene-1-sulfonate (ans) ligand and one 4,5-diazafluoren-9-one (DAFO) ligand. The Cu(II) atom has an elongated distorted octahedral coordination geometry formed by two O atoms from two monodentate ans ligands and by four N atoms from two DAFO molecules. Complex (II) is polymeric and its crystal structure is built up by one-dimensional chains and solvent water molecules. Here also the cation (a Cd(II) atom) lies on a crystallographic inversion center and adopts a slightly distorted octahedral geometry. Each ans anion serves as a bridging ligand linking two Cd(II) atoms into one-dimensional infinite chains along the [010] direction, with each Cd(II) center coordinated by four ans ligands via O and N atoms and by two aqua ligands. In both structures, there are significant pi-pi stacking interactions between adjacent ligands and hydrogen bonds contribute to the formation of two- and three-dimensional networks.

  3. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel

    2017-01-01

    This textbook is appropriate for use in graduate-level curricula in analog-to-digital conversion, as well as for practicing engineers in need of a state-of-the-art reference on data converters. It discusses various analog-to-digital conversion principles, including sampling, quantization, reference generation, nyquist architectures and sigma-delta modulation. This book presents an overview of the state of the art in this field and focuses on issues of optimizing accuracy and speed, while reducing the power level. This new, third edition emphasizes novel calibration concepts, the specific requirements of new systems, the consequences of 22-nm technology and the need for a more statistical approach to accuracy. Pedagogical enhancements to this edition include additional, new exercises, solved examples to introduce all key, new concepts and warnings, remarks and hints, from a practitioner’s perspective, wherever appropriate. Considerable background information and practical tips, from designing a PCB, to lay-o...

  4. Synthesis of novel '4+1' Tc(III)/Re(III) mixed-ligand complexes with dendritically modified ligands

    International Nuclear Information System (INIS)

    Gniazdowska, E.; Kuenstler, J.U.; Stephan, H.; Pietzsch, H.J.

    2006-01-01

    Coordination chemistry of technetium and rhenium attracts a considerable interest due to the nuclear medicine applications of their radionuclides. Inert, so-called '3+1' or '4+1' technetium/rhenium mixed-ligand complexes open a new way to application of 99 mTc/ 188 Re labeled compounds in tumor diagnosis and therapy. In the presented paper, authors describe the synthesis and study of novel 99 mTc/ 188 Re complexes with dendritically functionalized tetradentate (tripodal chelator 2,2',2''-nitrilotris(ethanethiol), NS 3 and carboxyl group-bearing ligand, NS 3 (COOH) 3 ) and monodentate (dendritically modified isocyanide, CN-R(COOMe) 3 and isocyanide-modified peptide, CN-GGY) ligands. To verify the identity of the prepared n.c.a. complexes, non-radioactive analogous '4+1' Re compounds were synthesized. The experimental data show that a dendritic modification of the tetradentate/monodentate ligands changes the complex lipophilicity and does not influence its stability

  5. Analogies between antiferromagnets and antiferroelectrics

    International Nuclear Information System (INIS)

    Enz, C.P.; Matthias, B.T.

    1980-01-01

    Ferro- and antiferromagnetism in the Laves phase TiBesub(2-x) Cusub(x) occurs for 0.1 4 H 2 PO 4 and its solid solutions with TlH 2 PO 4 and with the ferroelectric KH 2 PO 4 are discussed as function of deuteration and of pressure. Another analogy as function of pressure is established with the antiferroelectric perovskite PbZrO 3 . (author)

  6. Novel phosphanucleoside analogs of dideoxynucleosides

    Czech Academy of Sciences Publication Activity Database

    Páv, Ondřej; Buděšínský, Miloš; Rosenberg, Ivan

    2017-01-01

    Roč. 73, č. 34 (2017), s. 5220-5228 ISSN 0040-4020 R&D Projects: GA ČR(CZ) GA17-12703S; GA ČR GA13-26526S; GA MZd NV15-31604A Institutional support: RVO:61388963 Keywords : phosphanucleoside * nucleoside analog * ring-closing metathesis * stereoselective hydroboration * chiral resolution Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 2.651, year: 2016

  7. Electrostatic analogy for symmetron gravity

    Science.gov (United States)

    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.

  8. Correcting ligands, metabolites, and pathways

    NARCIS (Netherlands)

    Ott, M.A.; Vriend, G.

    2006-01-01

    BACKGROUND: A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases,

  9. The Development of Analogical Reasoning Processes.

    Science.gov (United States)

    Sternberg, Robert J.; Rifkin, Bathsheva

    1979-01-01

    Two experiments were conducted to test the generalizability to children of a theory of analogical reasoning processes, originally proposed for adults, and to examine the development of analogical reasoning processes in terms of five proposed sources of cognitive development. (MP)

  10. 16-channel analog store and multiplexer unit

    Energy Technology Data Exchange (ETDEWEB)

    Brossard, M; Kulka, Z [Clermont-Ferrand-2 Univ., 63 - Aubiere (France). Lab. de Physique Corpusculaire

    1979-03-15

    A 16-channel analog store and multiplexer unit is described. The unit enables storing and selection of analog information which is then digitally encoded by single ADC. This solution becomes economically attractive particularly in multidetector pulse height analysis systems.

  11. Atheism and Analogy: Aquinas Against the Atheists

    OpenAIRE

    Linford, Daniel J.

    2014-01-01

    In the 13th century, Thomas Aquinas developed two models for how humans may speak of God - either by the analogy of proportion or by the analogy of proportionality. Aquinas's doctrines initiated a theological debate concerning analogy that spanned several centuries. In the 18th century, there appeared two closely related arguments for atheism which both utilized analogy for their own purposes. In this thesis, I show that one argument, articulated by the French materialist Paul-Henri Thiry Bar...

  12. Enhancing programming logic thinking using analogy mapping

    Science.gov (United States)

    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.

  13. Electrochemistry of oxo-technetium(V) complexes containing Schiff base and 8-quinolinol ligands

    International Nuclear Information System (INIS)

    Refosco, F.; Mazzi, U.; Deutsch, E.; Kirchhoff, J.R.; Heineman, W.R.; Seeber, R.

    1988-01-01

    The electrochemistry of six-coordinate, monooxo technetium(V) complexes containing Schiff base ligands has been studied in acetonitrile and N,N'-dimethylformamide solutions. The complexes have the general formula TcOCl(L B ) 2 or TcO(L T )(L B ), where L B represents a bidentate-N,O Schiff base ligand or a bidentate-N,O 8-quinolinol ligand and L T represents a tridentate-O,N,O Schiff base ligand. Cyclic voltammetry at a platinum-disk electrode, controlled-potential coulometry, and thin-layer spectroelectrochemistry were used to probe both the oxidation and the reduction of these complexes. The results of these studies, and previously reported results on the analogous Re(V) complexes, can be understood within a single general reaction scheme. The salient features of this scheme are (i) one-electron reduction of Tc(V) to Tc(IV), (ii) subsequent loss of a ligand situated cis to the Tc≡O linkage, and (iii) subsequent isomerization of this unstable Tc(IV) product to more stable complex in which the site trans to the Tc≡O linkage is vacant. The Tc(IV) complexes can also be reduced to analogous Tc(III) species, which appear to undergo the same ligand loss and isomerization reactions. The technetium complexes are 400-500 mV easier to reduce than are their rhenium analogues. The 8-quinolinol ligands, and especially the 5-nitro derivative, both thermodynamically and kinetically stabilize the Tc(IV) and Tc(III) oxidation states. These electrogenerated species are unusual in that they constitute the bulk of the known examples of monomeric Tc(IV) and Tc(III) complexes containing only N- and O-donating ligands. 34 refs., 9 figs., 1 tab

  14. Analogies and the 5E Model

    Science.gov (United States)

    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…

  15. Science Teachers' Analogical Reasoning

    Science.gov (United States)

    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…

  16. The Micro-Category Account of Analogy

    Science.gov (United States)

    Green, Adam E.; Fugelsang, Jonathan A.; Kraemer, David J. M.; Dunbar, Kevin N.

    2008-01-01

    Here, we investigate how activation of mental representations of categories during analogical reasoning influences subsequent cognitive processing. Specifically, we present and test the central predictions of the "Micro-Category" account of analogy. This account emphasizes the role of categories in aligning terms for analogical mapping. In a…

  17. Redox non-innocent bis(2,6-diimine-pyridine) ligand-iron complexes as anolytes for flow battery applications.

    Science.gov (United States)

    Duarte, Gabriel M; Braun, Jason D; Giesbrecht, Patrick K; Herbert, David E

    2017-12-21

    Diiminepyridines are a well-known class of "non-innocent" ligands that confer additional redox activity to coordination complexes beyond metal-centred oxidation/reduction. Here, we demonstrate that metal coordination complexes (MCCs) of diiminepyridine (DIP) ligands with iron are suitable anolytes for redox-flow battery applications, with enhanced capacitance and stability compared with bipyridine analogs, and access to storage of up to 1.6 electron equivalents. Substitution of the ligand is shown to be a key factor in the cycling stability and performance of MCCs based on DIP ligands, opening the door to further optimization.

  18. Theoretic investigation into polytopic rearrangements mechanism of molecules of sulfurans and their analogs

    International Nuclear Information System (INIS)

    Minkin, V.I.; Minyaev, R.M.

    1975-01-01

    The energy characteristics and electron distributions were calculated for the fundamental and transitional states in topomerization of configuration of sulfo-, selenium and tellurium-uranium compounds of the AX 4 type. Also mapping of the potential energies was made for the predominant topomerization mechanisms. The mechanisms were classified into rearrangement types according to exchange-responsible apical and equatorial ligands. The physical mechanisms of the topomerization were determined on the basis of symmetry requirements for transitional configuration with respect to non-interchanging ligands. The lowest activation barrier was characteristic for the Berry mechanism of pseudorotation; however, other mechanism (the lever and pyramidal type) can compete with the Berry mechanisms. The expanded method of Hukkel does not give correct values for the relative energy of the fundamental and transitional configurations for sulfouranium molecules and their analogs for two of the three exchange mechanisms examined. Tunnel ligand-exchange mechanism cannot compete with the kinetic path of psudorotation reaction even at very low temperatures

  19. Are all analogies created equal? Prefrontal cortical functioning may predict types of analogical reasoning.

    Science.gov (United States)

    Chrysikou, Evangelia G; Thompson-Schill, Sharon L

    2010-06-01

    Abstract The proposed theory can account for analogies based on learned relationships between elements in the source and target domains. However, its explanatory power regarding the discovery of new relationships during analogical reasoning is limited. We offer an alternative perspective for the role of PFC in analogical thought that may better address different types of analogical mappings.

  20. Practical analog electronics for technicians

    CERN Document Server

    Kimber, W A

    2013-01-01

    'Practical Analog Electronics for Technicians' not only provides an accessible introduction to electronics, but also supplies all the problems and practical activities needed to gain hands-on knowledge and experience. This emphasis on practice is surprisingly unusual in electronics texts, and has already gained Will Kimber popularity through the companion volume, 'Practical Digital Electronics for Technicians'. Written to cover the Advanced GNVQ optional unit in electronics, this book is also ideal for BTEC National, A-level electronics and City & Guilds courses. Together with 'Practical Digit

  1. Resistive RAMs as analog trimming elements

    Science.gov (United States)

    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.

  2. Analog and mixed-signal electronics

    CERN Document Server

    Stephan, Karl

    2015-01-01

    A practical guide to analog and mixed-signal electronics, with an emphasis on design problems and applications This book provides an in-depth coverage of essential analog and mixed-signal topics such as power amplifiers, active filters, noise and dynamic range, analog-to-digital and digital-to-analog conversion techniques, phase-locked loops, and switching power supplies. Readers will learn the basics of linear systems, types of nonlinearities and their effects, op-amp circuits, the high-gain analog filter-amplifier, and signal generation. The author uses system design examples to motivate

  3. Analog circuit design art, science, and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    Analog Circuit Design: Art, Science, and Personalities discusses the many approaches and styles in the practice of analog circuit design. The book is written in an informal yet informative manner, making it easily understandable to those new in the field. The selection covers the definition, history, current practice, and future direction of analog design; the practice proper; and the styles in analog circuit design. The book also includes the problems usually encountered in analog circuit design; approach to feedback loop design; and other different techniques and applications. The text is

  4. Analogical reasoning in schizophrenic delusions.

    Science.gov (United States)

    Simpson, Jane; Done, D John

    2004-09-01

    Reasoning ability has often been argued to be impaired in people with schizophrenic delusions, although evidence for this is far from convincing. This experiment examined the analogical reasoning abilities of several groups of patients, including non-deluded and deluded schizophrenics, to test the hypothesis that performance by the deluded schizophrenic group would be impaired. Eleven deluded schizophrenics, 10 depressed subjects, seven non-deluded schizophrenics and 16 matched non-psychiatric controls, who were matched on a number of key variables, were asked to solve an analogical reasoning task. Performance by the deluded schizophrenic group was certainly impaired when compared with the depressed and non-psychiatric control groups though less convincingly so when compared with the non-deluded schizophrenic group. The impairment shown by the deluded schizophrenic group seemed to occur at the initial stage of the reasoning task. The particular type of impairment shown by the deluded subjects was assessed in relation to other cognitive problems already researched and the implications of these problems on reasoning tasks and theories of delusions was discussed.

  5. Reliability of analog quantum simulation

    Energy Technology Data Exchange (ETDEWEB)

    Sarovar, Mohan [Sandia National Laboratories, Digital and Quantum Information Systems, Livermore, CA (United States); Zhang, Jun; Zeng, Lishan [Shanghai Jiao Tong University, Joint Institute of UMich-SJTU, Key Laboratory of System Control and Information Processing (MOE), Shanghai (China)

    2017-12-15

    Analog quantum simulators (AQS) will likely be the first nontrivial application of quantum technology for predictive simulation. However, there remain questions regarding the degree of confidence that can be placed in the results of AQS since they do not naturally incorporate error correction. Specifically, how do we know whether an analog simulation of a quantum model will produce predictions that agree with the ideal model in the presence of inevitable imperfections? At the same time there is a widely held expectation that certain quantum simulation questions will be robust to errors and perturbations in the underlying hardware. Resolving these two points of view is a critical step in making the most of this promising technology. In this work we formalize the notion of AQS reliability by determining sensitivity of AQS outputs to underlying parameters, and formulate conditions for robust simulation. Our approach naturally reveals the importance of model symmetries in dictating the robust properties. To demonstrate the approach, we characterize the robust features of a variety of quantum many-body models. (orig.)

  6. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J. M

    2013-01-01

    This textbook is appropriate for use in graduate-level curricula in analog to digital conversion, as well as for practicing engineers in need of a state-of-the-art reference on data converters.  It discusses various analog-to-digital conversion principles, including sampling, quantization, reference generation, nyquist architectures and sigma-delta modulation.  This book presents an overview of the state-of-the-art in this field and focuses on issues of optimizing accuracy and speed, while reducing the power level. This new, second edition emphasizes novel calibration concepts, the specific requirements of new systems, the consequences of 45-nm technology and the need for a more statistical approach to accuracy.  Pedagogical enhancements to this edition include more than twice the exercises available in the first edition, solved examples to introduce all key, new concepts and warnings, remarks and hints, from a practitioner’s perspective, wherever appropriate.  Considerable background information and pr...

  7. DockoMatic: automated peptide analog creation for high throughput virtual screening.

    Science.gov (United States)

    Jacob, Reed B; Bullock, Casey W; Andersen, Tim; McDougal, Owen M

    2011-10-01

    The purpose of this manuscript is threefold: (1) to describe an update to DockoMatic that allows the user to generate cyclic peptide analog structure files based on protein database (pdb) files, (2) to test the accuracy of the peptide analog structure generation utility, and (3) to evaluate the high throughput capacity of DockoMatic. The DockoMatic graphical user interface interfaces with the software program Treepack to create user defined peptide analogs. To validate this approach, DockoMatic produced cyclic peptide analogs were tested for three-dimensional structure consistency and binding affinity against four experimentally determined peptide structure files available in the Research Collaboratory for Structural Bioinformatics database. The peptides used to evaluate this new functionality were alpha-conotoxins ImI, PnIA, and their published analogs. Peptide analogs were generated by DockoMatic and tested for their ability to bind to X-ray crystal structure models of the acetylcholine binding protein originating from Aplysia californica. The results, consisting of more than 300 simulations, demonstrate that DockoMatic predicts the binding energy of peptide structures to within 3.5 kcal mol(-1), and the orientation of bound ligand compares to within 1.8 Å root mean square deviation for ligand structures as compared to experimental data. Evaluation of high throughput virtual screening capacity demonstrated that Dockomatic can collect, evaluate, and summarize the output of 10,000 AutoDock jobs in less than 2 hours of computational time, while 100,000 jobs requires approximately 15 hours and 1,000,000 jobs is estimated to take up to a week. Copyright © 2011 Wiley Periodicals, Inc.

  8. Rational Ligand Design for U(VI) and Pu(IV)

    International Nuclear Information System (INIS)

    Szigethy, Geza

    2009-01-01

    ligands exhibited increased uranyl affinity compared to bis-Me-3,2-HOPO ligands. This result is due in part to their increased denticity, but is primarily the result of the presence of the TAM moiety. In an effort to explore the relatively unexplored coordination chemistry of Pu(IV) with bidentate moieties, a series of Pu(IV) complexes were also crystallized using bidentate hydroxypyridinone and hydroxypyrone ligands. The geometries of these complexes are compared to that of the analogous Ce(IV) complexes. While in some cases these showed the expected structural similarities, some ligand systems led to significant coordination changes. A series of crystal structure analyses with Ce(IV) indicated that these differences are most likely the result of crystallization condition differences and solvent inclusion effects.

  9. Rational Ligand Design for U(VI) and Pu(IV)

    Energy Technology Data Exchange (ETDEWEB)

    Szigethy, Geza [Univ. of California, Berkeley, CA (United States)

    2009-08-12

    saturation, these ligands exhibited increased uranyl affinity compared to bis-Me-3,2-HOPO ligands. This result is due in part to their increased denticity, but is primarily the result of the presence of the TAM moiety. In an effort to explore the relatively unexplored coordination chemistry of Pu(IV) with bidentate moieties, a series of Pu(IV) complexes were also crystallized using bidentate hydroxypyridinone and hydroxypyrone ligands. The geometries of these complexes are compared to that of the analogous Ce(IV) complexes. While in some cases these showed the expected structural similarities, some ligand systems led to significant coordination changes. A series of crystal structure analyses with Ce(IV) indicated that these differences are most likely the result of crystallization condition differences and solvent inclusion effects.

  10. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng; Huang, Jianhua Z; Gao, Xin

    2014-01-01

    Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction

  11. Pan-pathway based interaction profiling of FDA-approved nucleoside and nucleobase analogs with enzymes of the human nucleotide metabolism.

    Science.gov (United States)

    Egeblad, Louise; Welin, Martin; Flodin, Susanne; Gräslund, Susanne; Wang, Liya; Balzarini, Jan; Eriksson, Staffan; Nordlund, Pär

    2012-01-01

    To identify interactions a nucleoside analog library (NAL) consisting of 45 FDA-approved nucleoside analogs was screened against 23 enzymes of the human nucleotide metabolism using a thermal shift assay. The method was validated with deoxycytidine kinase; eight interactions known from the literature were detected and five additional interactions were revealed after the addition of ATP, the second substrate. The NAL screening gave relatively few significant hits, supporting a low rate of "off target effects." However, unexpected ligands were identified for two catabolic enzymes guanine deaminase (GDA) and uridine phosphorylase 1 (UPP1). An acyclic guanosine prodrug analog, valaciclovir, was shown to stabilize GDA to the same degree as the natural substrate, guanine, with a ΔT(agg) around 7°C. Aciclovir, penciclovir, ganciclovir, thioguanine and mercaptopurine were also identified as ligands for GDA. The crystal structure of GDA with valaciclovir bound in the active site was determined, revealing the binding of the long unbranched chain of valaciclovir in the active site of the enzyme. Several ligands were identified for UPP1: vidarabine, an antiviral nucleoside analog, as well as trifluridine, idoxuridine, floxuridine, zidovudine, telbivudine, fluorouracil and thioguanine caused concentration-dependent stabilization of UPP1. A kinetic study of UPP1 with vidarabine revealed that vidarabine was a mixed-type competitive inhibitor with the natural substrate uridine. The unexpected ligands identified for UPP1 and GDA imply further metabolic consequences for these nucleoside analogs, which could also serve as a starting point for future drug design.

  12. Automatic activation of categorical and abstract analogical relations in analogical reasoning.

    Science.gov (United States)

    Green, Adam E; Fugelsang, Jonathan A; Dunbar, Kevin N

    2006-10-01

    We examined activation of concepts during analogical reasoning. Subjects made either analogical judgments or categorical judgments about four-word sets. After each four-word set, they named the ink color of a single word in a modified Stroop task. Words that referred to category relations were primed (as indicated by longer response times on Stroop color naming) subsequent to analogical judgments and categorical judgments. This finding suggests that activation of category concepts plays a fundamental role in analogical thinking. When colored words referred to analogical relations, priming occurred subsequent to analogical judgments, but not to categorical judgments, even though identical four-word stimuli were used for both types of judgments. This finding lends empirical support to the hypothesis that, when people comprehend the analogy between two items, they activate an abstract analogical relation that is distinct from the specific content items that compose the analogy.

  13. The Young Solar Analogs Project

    Science.gov (United States)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Fuller, V.; Kahvaz, Y.; Lambert, R.; Newsome, I.; Seeds, M.

    2013-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using facilities at the Dark Sky Observatory (DSO - Appalachian State University) and the Vatican Advanced Technology Telescope (VATT). These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in the 6th year of spectroscopic measurements of these stars: these data include Ca II H & K chromospheric flux measurements, and narrow-band measurements in the photospheric G-band, both obtained with the G/M spectrograph on the DSO 32-inch telescope. We will present evidence of activity cycles in a number of our stars, as well as periods determined from rotational modulation of the spectroscopic indices. The relationship between the Ca II activity index and the G-band index will be explored. NSF support for our project has provided funds for the construction of a robotic photometric telescope to monitor the program stars in a 5-passband system (Strömgren-v, Johnson-Cousins B, V, and R, and a 3-nm wide Hα filter). The robotic telescope has been functional since April 2012 and observes the program stars on every clear night; combined with the Piggy-back telescope attached to the DSO 32-inch, we now have photometric observations on over 130 nights stretching over nearly 2 years. We will examine the relationships between variations in the Ca II H & K index, the G-band index and the photometric bands. This project is supported by the National Science Foundation, grant AST-1109158.

  14. The Young Solar Analogs Project

    Science.gov (United States)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Seeds, M. F.; Morrison, S. S.

    2012-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using the Dark Sky Observatory (DSO -- Appalachian State University) 32-inch telescope and the G/M spectrograph. These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in our 5th year of obtaining Ca II K & H chromospheric flux measurements, and are beginning to see signs of long-term activity cycles in a number of our stars. In addition, rotational modulation of the chromospheric fluxes is detectable in our data, and we have determined rotational periods for many of our stars. Short timescale increases in the K & H fluxes have been observed in a number of our stars; these events may be related to stellar flares. VATTSpec, a new moderate-resolution spectrograph on the 1.8-m Vatican Telescope in Arizona, has recently become involved with the project. This spectrograph will increase our ability to detect short-term changes in stellar activity on timescales of hours to minutes. We have been monitoring the program stars for one year in a multi-band photometric system consisting of Stromgren-v, and Johnson B, V, and R filters. We will soon add a narrow-band H-alpha filter to the system. Photometry is being carried out with a small piggy-back telescope on the 32-inch, but a robotic photometric telescope is currently being installed at DSO for this purpose. This project is supported by the National Science Foundation.

  15. Synthesis and complexation of acyclic dithiolate ligands

    International Nuclear Information System (INIS)

    Ashford, L.

    1999-11-01

    Four approaches to ring substituted and unsubstituted N,N'-bis(o-mercaptobenzyliden)propylenediaminate ligands are described using N,N-dimethylcarbamate as a thiolate protecting group. Of the four basic methods, substitution, reduction, rearrangement and oxidation, the latter two successfully synthesise the aldehyde precursor. Rearrangement of the thiocarbamoyl group to the protected thiophenol is shown to be facilitated by a para-nitro substiuent. Ni(II) and Cu(II) complexes of N,N'-bis(p-nitro-o-mercaptobenzyliden)-propylenediaminate are synthesised by reaction of 2-formyl-4-nitro-N,N-dimethylcarbamoyI thiophenol, [Ni(OAc) 2 ].4(H 2 O) and 1,3-diaminopropane. The para-unsubstituted Ni(II) complex, Nickel-[N,N'-bis(o-mercaptobenzyliden) propylenediaminate] is prepared via reaction of the aldehyde, 2-formyl-N,N-dimethylcarbamoyl thiophenol with [Ni(OAc) 2 ].4(H 2 O) and 1,3-diaminopropane. The analogous carbamoyl-protected amine ligands, N,N'-dimethyl-N.N'-di[2-(N'',N''-dimethylcarbamyl)mercapto] benzyl-1,3-propane-diamine and N,N'-dimethyl-N,N'-di[2-(N'',N''-dimethylcarbamyl)mercapto] benzyl-1,2-ethane-diamine are also studied. The tertiary-butyl-protected diimine ligand, N,N'-bis-(o-mercaptobenzylidene)-propylenediaminate is prepared from 2-(tert-butylsulfanyl)benzaldehyde and 1,3-diaminopropane. Reaction with [Ni(H 2 O) 6 ]Cl 2 gives Nickel-[N,N'-bis(o-mercaptobenzyliden)-propylenediaminate], the crystal structure showing a distorted square-planar Ni(II) centre. Reaction with ZnCl 2 gives Zinc-[N,N'-bis(o-mercaptobenzyliden)propylenediaminate]dichloride. The crystal structure shows the thiolate donors remain protected and uncoordinated. The Zn(II) ion is coordinated by two imine donors and two chloride ions in a tetrahedral environment. In reactions with Ag(I) and Hg(II), N,N'-bis-(o-mercaptobenzylidene)-propylenediaminate acts as a reductant giving the free metals. Structural data and NMR and IR spectroscopic data for Nickel

  16. Rosetta Ligand docking with flexible XML protocols.

    Science.gov (United States)

    Lemmon, Gordon; Meiler, Jens

    2012-01-01

    RosettaLigand is premiere software for predicting how a protein and a small molecule interact. Benchmark studies demonstrate that 70% of the top scoring RosettaLigand predicted interfaces are within 2Å RMSD from the crystal structure [1]. The latest release of Rosetta ligand software includes many new features, such as (1) docking of multiple ligands simultaneously, (2) representing ligands as fragments for greater flexibility, (3) redesign of the interface during docking, and (4) an XML script based interface that gives the user full control of the ligand docking protocol.

  17. Priming analogical reasoning with false memories.

    Science.gov (United States)

    Howe, Mark L; Garner, Sarah R; Threadgold, Emma; Ball, Linden J

    2015-08-01

    Like true memories, false memories are capable of priming answers to insight-based problems. Recent research has attempted to extend this paradigm to more advanced problem-solving tasks, including those involving verbal analogical reasoning. However, these experiments are constrained inasmuch as problem solutions could be generated via spreading activation mechanisms (much like false memories themselves) rather than using complex reasoning processes. In three experiments we examined false memory priming of complex analogical reasoning tasks in the absence of simple semantic associations. In Experiment 1, we demonstrated the robustness of false memory priming in analogical reasoning when backward associative strength among the problem terms was eliminated. In Experiments 2a and 2b, we extended these findings by demonstrating priming on newly created homonym analogies that can only be solved by inhibiting semantic associations within the analogy. Overall, the findings of the present experiments provide evidence that the efficacy of false memory priming extends to complex analogical reasoning problems.

  18. Neural correlates of creativity in analogical reasoning.

    Science.gov (United States)

    Green, Adam E; Kraemer, David J M; Fugelsang, Jonathan A; Gray, Jeremy R; Dunbar, Kevin N

    2012-03-01

    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 determinant of the creativity of analogical mapping (i.e., more distant analogies are generally more creative). Here, we used functional magnetic resonance imaging to assess brain activity during an analogy generation task in which we varied the semantic distance of analogical mapping (as derived quantitatively from a latent semantic analysis). Data indicated that activity within an a priori region of interest in left frontopolar cortex covaried parametrically with increasing semantic distance, even after removing effects of task difficulty. Results implicate increased recruitment of frontopolar cortex as a mechanism for integrating semantically distant information to generate solutions in creative analogical reasoning. 2012 APA, all rights reserved

  19. An emergent approach to analogical inference

    Science.gov (United States)

    Thibodeau, Paul H.; Flusberg, Stephen J.; Glick, Jeremy J.; Sternberg, Daniel A.

    2013-03-01

    In recent years, a growing number of researchers have proposed that analogy is a core component of human cognition. According to the dominant theoretical viewpoint, analogical reasoning requires a specific suite of cognitive machinery, including explicitly coded symbolic representations and a mapping or binding mechanism that operates over these representations. Here we offer an alternative approach: we find that analogical inference can emerge naturally and spontaneously from a relatively simple, error-driven learning mechanism without the need to posit any additional analogy-specific machinery. The results also parallel findings from the developmental literature on analogy, demonstrating a shift from an initial reliance on surface feature similarity to the use of relational similarity later in training. Variants of the model allow us to consider and rule out alternative accounts of its performance. We conclude by discussing how these findings can potentially refine our understanding of the processes that are required to perform analogical inference.

  20. Analog techniques in CEBAF's RF control system

    International Nuclear Information System (INIS)

    Hovater, C.; Fugitt, J.

    1989-01-01

    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. 4 refs., 5 figs

  1. Analog techniques in CEBAF'S RF control system

    International Nuclear Information System (INIS)

    Hovater, C.; Fugitt, J.

    1989-01-01

    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. 4 refs., 5 figs

  2. Design and Analysis of Reconfigurable Analog System

    Science.gov (United States)

    2011-02-01

    34010010" �" �" �" �" �" �" �±" N3 N2 N± P1 P2 P3 * Current sources $RR = 1; *Ramp Rate (slope of the...2008/12/12/31e83bac-500f-4182- acca -4d360295fd9c.pdf, Analog Devices, Analog Dialogue 39-06, June 2005. [15] D. A. Johns, K. Martin "Analog Integrated

  3. Fermilab accelerator control system: Analog monitoring facilities

    International Nuclear Information System (INIS)

    Seino, K.; Anderson, L.; Smedinghoff, J.

    1987-10-01

    Thousands of analog signals are monitored in different areas of the Fermilab accelerator complex. For general purposes, analog signals are sent over coaxial or twinaxial cables with varying lengths, collected at fan-in boxes and digitized with 12 bit multiplexed ADCs. For higher resolution requirements, analog signals are digitized at sources and are serially sent to the control system. This paper surveys ADC subsystems that are used with the accelerator control systems and discusses practical problems and solutions, and it describes how analog data are presented on the console system

  4. Relations as transformations: implications for analogical reasoning.

    Science.gov (United States)

    Leech, Robert; Mareschal, Denis; Cooper, Richard P

    2007-07-01

    We present two experiments assessing whether the size of a transformation instantiating a relation between two states of the world (e.g., shrinks) is a performance factor affecting analogical reasoning. The first experiment finds evidence of transformation size as a significant factor in adolescent analogical problem solving while the second experiment finds a similar effect on adult analogical reasoning using a markedly different analogical completion paradigm. The results are interpreted as providing evidence for the more general framework that cognitive representations of relations are best understood as mental transformations.

  5. Epistemology of analogy: Knowledge, society and expression

    Directory of Open Access Journals (Sweden)

    Mauricio Beuchot

    2017-06-01

    Full Text Available In this article we expose the bases of analog epistemology. This theory of knowledge is between an extreme subjectivism and an extreme objectivism. Analog hermeneutics is a realistic hermeneutics. She seeks the truth, but incorporates the meaning and emotion. We have separated the reason from the experience, the praxis theory, the mind or the soul of the body. We have to get them back together, if we do not get lost in the rational (which says little of the human being, or we lose ourselves in the emotional (without logical consistency. The analogical hermeneutic realism is able, thanks to the analogy itself, to mediate in this way of union.

  6. Crystallization of protein–ligand complexes

    International Nuclear Information System (INIS)

    Hassell, Anne M.; An, Gang; Bledsoe, Randy K.; Bynum, Jane M.; Carter, H. Luke III; Deng, Su-Jun J.; Gampe, Robert T.; Grisard, Tamara E.; Madauss, Kevin P.; Nolte, Robert T.; Rocque, Warren J.; Wang, Liping; Weaver, Kurt L.; Williams, Shawn P.; Wisely, G. Bruce; Xu, Robert; Shewchuk, Lisa M.

    2007-01-01

    Methods presented for growing protein–ligand complexes fall into the categories of co-expression of the protein with the ligands of interest, use of the ligands during protein purification, cocrystallization and soaking the ligands into existing crystals. Obtaining diffraction-quality crystals has long been a bottleneck in solving the three-dimensional structures of proteins. Often proteins may be stabilized when they are complexed with a substrate, nucleic acid, cofactor or small molecule. These ligands, on the other hand, have the potential to induce significant conformational changes to the protein and ab initio screening may be required to find a new crystal form. This paper presents an overview of strategies in the following areas for obtaining crystals of protein–ligand complexes: (i) co-expression of the protein with the ligands of interest, (ii) use of the ligands during protein purification, (iii) cocrystallization and (iv) soaks

  7. Expert analogy use in a naturalistic setting

    Science.gov (United States)

    Kretz, Donald R.; Krawczyk, Daniel C.

    2014-01-01

    The use of analogy is an important component of human cognition. The type of analogy we produce and communicate depends heavily on a number of factors, such as the setting, the level of domain expertise present, and the speaker's goal or intent. In this observational study, we recorded economics experts during scientific discussion and examined the categorical distance and structural depth of the analogies they produced. We also sought to characterize the purpose of the analogies that were generated. Our results supported previous conclusions about the infrequency of superficial similarity in subject-generated analogs, but also showed that distance and depth characteristics were more evenly balanced than in previous observational studies. This finding was likely due to the nature of the goals of the participants, as well as the broader nature of their expertise. An analysis of analogical purpose indicated that the generation of concrete source examples of more general target concepts was most prevalent. We also noted frequent instances of analogies intended to form visual images of source concepts. Other common purposes for analogies were the addition of colorful speech, inclusion (i.e., subsumption) of a target into a source concept, or differentiation between source and target concepts. We found no association between depth and either of the other two characteristics, but our findings suggest a relationship between purpose and distance; i.e., that visual imagery typically entailed an outside-domain source whereas exemplification was most frequently accomplished using within-domain analogies. Overall, we observed a rich and diverse set of spontaneously produced analogical comparisons. The high degree of expertise within the observed group along with the richly comparative nature of the economics discipline likely contributed to this analogical abundance. PMID:25505437

  8. Expert Analogy Use in a Naturalistic Setting

    Directory of Open Access Journals (Sweden)

    Donald R Kretz

    2014-11-01

    Full Text Available The use of analogy is an important component of human cognition. The type of analogy we produce and communicate depends heavily on a number of factors, such as the setting, the level of domain expertise present, and the speaker’s goal or intent. In this observational study, we recorded economics experts during scientific discussion and examined the categorical distance and structural depth of the analogies they produced. We also sought to characterize the purpose of the analogies that were generated. Our results supported previous conclusions about the infrequency of superficial similarity in subject-generated analogs, but also showed that distance and depth characteristics were more evenly balanced than in previous observational studies. This finding was likely due to the nature of the goals of the participants, as well as the broader nature of their expertise. An analysis of analogical purpose indicated that the generation of concrete source examples of more general target concepts was most prevalent. We also noted frequent instances of analogies intended to form visual images of source concepts. Other common purposes for analogies were the addition of colorful speech, inclusion (i.e., subsumption of a target into a source concept, or differentiation between source and target concepts. We found no association between depth and either of the other two characteristics, but our findings suggest a relationship between purpose and distance; i.e., that visual imagery typically entailed an outside-domain source whereas exemplification was most frequently accomplished using within-domain analogies. Overall, we observed a rich and diverse set of spontaneously produced analogical comparisons. The high degree of expertise within the observed group along with the richly comparative nature of the economics discipline likely contributed to this analogical abundance.

  9. -Pincer Ligand Family through Ligand Post-Modification

    KAUST Repository

    Huang, Mei-Hui; Hu, Jinsong; Huang, Kuo-Wei

    2017-01-01

    A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

  10. -Pincer Ligand Family through Ligand Post-Modification

    KAUST Repository

    Huang, Mei-Hui

    2017-10-02

    A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

  11. Reactivity of halide and pseudohalide ligands

    International Nuclear Information System (INIS)

    Kukushkin, Yu.N.

    1987-01-01

    Reactivity of halide and pseudohalide (cyanide, azide, thiocyanate, cyanate) ligands tending to form bridge bonds in transition metal (Re, Mo, W) complexes is considered. Complexes where transition metal salts are ligands of other, complex-forming ion, are described. Transformation of innerspheric pseudohalide ligands is an important way of directed synthesis of these metal coordination compounds

  12. Energy transfer processes in Tb(III)-dibenzoylmethanate complexes with phosphine oxide ligands

    International Nuclear Information System (INIS)

    Silva Junior, Francisco A.; Nascimento, Helenise A.; Pereira, Dariston K.S.; Teotonio, Ercules E.S.; Espinola, Jose Geraldo P.; Faustino, Wagner M.; Sa, Gilberto F.

    2013-01-01

    The Tb 3+ -β-diketonate complexes [Tb(DBM) 3 L], [Tb(DBM) 2 (NO 3 )L 2 ] and [Tb(DBM)(NO 3 ) 2 (HMPA) 2 ] (DBM = dibenzoylmethanate; L: TPPO triphenylphosphine oxide or HMPA=hexamethylphosphine oxide) were prepared and characterized by elemental analysis (CHN), complexometric titration with EDTA and Fourier transform infrared (FTIR) spectroscopy, and the photoluminescence properties evaluated. The triplet state energies of the coordinated DBM ligands were determined using time-resolved phosphorescence spectra of analogous Gd 3+ complexes. The results show that the energies increase along with the number of coordinated nitrate anions replacing the DBM ligand in the complexes. The luminescence spectra and emission lifetime measurements revealed that the ligand-to-metal energy transfer efficiency follows the same tendency. Unlike the tris-DBM complexes, bis- and mono-DBM presented high luminescence, and may act as promising candidates for preparation of the emitting layer of light converting molecular devices (LCMDs). (author)

  13. Young Children's Analogical Reasoning in Science Domains

    Science.gov (United States)

    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…

  14. Children's Use of Analogy during Collaborative Reasoning

    Science.gov (United States)

    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…

  15. Patterns of Analogical Reasoning among Beginning Readers

    Science.gov (United States)

    Farrington-Flint, Lee; Wood, Clare; Canobi, Katherine H.; Faulkner, Dorothy

    2004-01-01

    Despite compelling evidence that analogy skills are available to beginning readers, few studies have actually explored the possibility of identifying individual differences in young children's analogy skills in early reading. The present study examined individual differences in children's use of orthographic and phonological relations between…

  16. ANALOGICAL REASONING USING TRANSFORMATIONS OF RULES

    OpenAIRE

    Haraguchi, Makoto; 原口, 誠

    1986-01-01

    A formalism of analogical reasoning is presented. The analogical reasoning can be considered as a deduction with a function of transforming logical rules. From this viewpoint, the reasoning is defined in terms of deduction, and is therefore realized in a logic programming system. The reasoning system is described as an extension of Prolog interpreter.

  17. Analogies in high school Brazilian chemistry textbooks

    Directory of Open Access Journals (Sweden)

    Rosária Justi

    2000-05-01

    Full Text Available This paper presents and discusses an analysis of the analogies presented by Brazilian chemistry textbooks for the medium level. The main aim of the analysis is to discuss whether such analogies can be said good teaching models. From the results, some aspects concerning with teachers' role are discussed. Finally, some new research questions are emphasised.

  18. Spectrometric analog-to-digital converter

    International Nuclear Information System (INIS)

    Ormandzhiev, S.I.; Jordanov, V.T.

    1988-01-01

    Converter of digit-by-digit counterbalancing with slipping dial with number of channels equal to total number of states of the main digital-to-analog converter of digit-by-digit counterbalancing systems is presented. Algorithm for selection of digital-to-analog converters, which must be used by means of computer is suggested

  19. An Analog Computer for Electronic Engineering Education

    Science.gov (United States)

    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…

  20. PEMETAAN ANALOGI PADA KONSEP ABSTRAK FISIKA

    Directory of Open Access Journals (Sweden)

    Nyoto Suseno

    2014-11-01

    Full Text Available The research of any where founded majority students have common difficulties in abstract physics concept. The result of observation, lecturers have problem  in teaching implementation of abstract concepts on physics learning. The objective of this research is to find out the ways how to overcome this problem. The research place of  physics education programs and senior high school. The data are colected by quetionere, observation and interview. The lecturer behavior to making out this case is use of analogy to make concrete a abstract concept. This action is true, because the analogies are dynamic tools that facilitate understanding, rather than representations of the correct and static explanations. Using analogies not only promoted profound understanding of abstract concept, but also helped students overcome their misconceptions. However used analogy in teaching not yet planed with seriousness, analogy used spontanously with the result that less optimal. By planing and selecting right analogy, the role of analogy can be achieved the optimal result. Therefore, it is important to maping analogies of abstract consepts on physics learning.

  1. Computational approaches to analogical reasoning current trends

    CERN Document Server

    Richard, Gilles

    2014-01-01

    Analogical reasoning is known as a powerful mode for drawing plausible conclusions and solving problems. It has been the topic of a huge number of works by philosophers, anthropologists, linguists, psychologists, and computer scientists. As such, it has been early studied in artificial intelligence, with a particular renewal of interest in the last decade. The present volume provides a structured view of current research trends on computational approaches to analogical reasoning. It starts with an overview of the field, with an extensive bibliography. The 14 collected contributions cover a large scope of issues. First, the use of analogical proportions and analogies is explained and discussed in various natural language processing problems, as well as in automated deduction. Then, different formal frameworks for handling analogies are presented, dealing with case-based reasoning, heuristic-driven theory projection, commonsense reasoning about incomplete rule bases, logical proportions induced by similarity an...

  2. Structure problems in the analog computation

    International Nuclear Information System (INIS)

    Braffort, P.L.

    1957-01-01

    The recent mathematical development showed the importance of elementary structures (algebraic, topological, etc.) in abeyance under the great domains of classical analysis. Such structures in analog computation are put in evidence and possible development of applied mathematics are discussed. It also studied the topological structures of the standard representation of analog schemes such as additional triangles, integrators, phase inverters and functions generators. The analog method gives only the function of the variable: time, as results of its computations. But the course of computation, for systems including reactive circuits, introduces order structures which are called 'chronological'. Finally, it showed that the approximation methods of ordinary numerical and digital computation present the same structure as these analog computation. The structure analysis permits fruitful comparisons between the several domains of applied mathematics and suggests new important domains of application for analog method. (M.P.)

  3. Ligand-regulated peptide aptamers.

    Science.gov (United States)

    Miller, Russell A

    2009-01-01

    The peptide aptamer approach employs high-throughput selection to identify members of a randomized peptide library displayed from a scaffold protein by virtue of their interaction with a target molecule. Extending this approach, we have developed a peptide aptamer scaffold protein that can impart small-molecule control over the aptamer-target interaction. This ligand-regulated peptide (LiRP) scaffold, consisting of the protein domains FKBP12, FRB, and GST, binds to the cell-permeable small-molecule rapamycin and the binding of this molecule can prevent the interaction of the randomizable linker region connecting FKBP12 with FRB. Here we present a detailed protocol for the creation of a peptide aptamer plasmid library, selection of peptide aptamers using the LiRP scaffold in a yeast two-hybrid system, and the screening of those peptide aptamers for a ligand-regulated interaction.

  4. A Fluid Membrane-Based Soluble Ligand Display System for Live CellAssays

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Jwa-Min; Nair, Pradeep N.; Neve, Richard M.; Gray, Joe W.; Groves, Jay T.

    2005-10-14

    Cell communication modulates numerous biological processes including proliferation, apoptosis, motility, invasion and differentiation. Correspondingly, there has been significant interest in the development of surface display strategies for the presentation of signaling molecules to living cells. This effort has primarily focused on naturally surface-bound ligands, such as extracellular matrix components and cell membranes. Soluble ligands (e.g. growth factors and cytokines) play an important role in intercellular communications, and their display in a surface-bound format would be of great utility in the design of array-based live cell assays. Recently, several cell microarray systems that display cDNA, RNAi, or small molecules in a surface array format were proven to be useful in accelerating high-throughput functional genetic studies and screening therapeutic agents. These surface display methods provide a flexible platform for the systematic, combinatorial investigation of genes and small molecules affecting cellular processes and phenotypes of interest. In an analogous sense, it would be an important advance if one could display soluble signaling ligands in a surface assay format that allows for systematic, patterned presentation of soluble ligands to live cells. Such a technique would make it possible to examine cellular phenotypes of interest in a parallel format with soluble signaling ligands as one of the display parameters. Herein we report a ligand-modified fluid supported lipid bilayer (SLB) assay system that can be used to functionally display soluble ligands to cells in situ (Figure 1A). By displaying soluble ligands on a SLB surface, both solution behavior (the ability to become locally enriched by reaction-diffusion processes) and solid behavior (the ability to control the spatial location of the ligands in an open system) could be combined. The method reported herein benefits from the naturally fluid state of the supported membrane, which allows

  5. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    , for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...... as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context....

  6. Bitopic Ligands and Metastable Binding Sites

    DEFF Research Database (Denmark)

    Fronik, Philipp; Gaiser, Birgit I; Sejer Pedersen, Daniel

    2017-01-01

    of orthosteric binding sites. Bitopic ligands have been employed to address the selectivity problem by combining (linking) an orthosteric ligand with an allosteric modulator, theoretically leading to high-affinity subtype selective ligands. However, it remains a challenge to identify suitable allosteric binding...... that have been reported to date, this type of bitopic ligands would be composed of two identical pharmacophores. Herein, we outline the concept of bitopic ligands, review metastable binding sites, and discuss their potential as a new source of allosteric binding sites....

  7. Radioiodinated ligands for dopamine receptors

    International Nuclear Information System (INIS)

    Kung, H.F.

    1994-01-01

    The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

  8. Generating explanations via analogical comparison.

    Science.gov (United States)

    Hoyos, Christian; Gentner, Dedre

    2017-10-01

    Generating explanations can be highly effective in promoting learning in both adults and children. Our interest is in the mechanisms that underlie this effect and in whether and how they operate in early learning. In adult reasoning, explanation may call on many subprocesses-including comparison, counterfactual reasoning, and reasoning by exclusion; but it is unlikely that all these processes are available to young children. We propose that one process that may serve both children and adults is comparison. In this study, we asked whether children would use the results of a comparison experience when asked to explain why a model skyscraper was stable. We focused on a challenging principle-that diagonal cross-bracing lends stability to physical structures (Gentner et al., Cognitive Science, 40, 224-240, 2016). Six-year-olds either received no training or interacted with model skyscrapers in one of three different conditions, designed to vary in their potential to invite and support comparison. In the Single Model condition, children interacted with a single braced model. In the comparison conditions (Low Alignability and High Alignability), children compared braced and unbraced models. Following experience with the models, children were asked to explain why the braced model was stable. They then received two transfer tasks. We found that children who received highly alignable pairs were most likely to (a) produce brace-based explanations and (b) transfer the brace principle to a dissimilar context. This provides evidence that children can benefit from analogical comparison in generating explanations and also suggests limitations on this ability.

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

    Science.gov (United States)

    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, ...

  10. Frontopolar cortex mediates abstract integration in analogy.

    Science.gov (United States)

    Green, Adam E; Fugelsang, Jonathan A; Kraemer, David J M; Shamosh, Noah A; Dunbar, Kevin N

    2006-06-22

    Integration of abstractly similar relations during analogical reasoning was investigated using functional magnetic resonance imaging. Activation elicited by an analogical reasoning task that required both complex working memory and integration of abstractly similar relations was compared to activation elicited by a non-analogical task that required complex working memory in the absence of abstract relational integration. A left-sided region of the frontal pole of the brain (BA 9/10) was selectively active for the abstract relational integration component of analogical reasoning. Analogical reasoning also engaged a left-sided network of parieto-frontal regions. Activity in this network during analogical reasoning is hypothesized to reflect categorical alignment of individual component terms that make up analogies. This parieto-frontal network was also engaged by the complex control task, which involved explicit categorization, but not by a simpler control task, which did not involve categorization. We hypothesize that frontopolar cortex mediates abstract relational integration in complex reasoning while parieto-frontal regions mediate working memory processes, including manipulation of terms for the purpose of categorical alignment, that facilitate this integration.

  11. Advances in Analog Circuit Design 2015

    CERN Document Server

    Baschirotto, Andrea; Harpe, Pieter

    2016-01-01

    This book is based on the 18 tutorials presented during the 24th workshop on Advances in Analog Circuit Design. Expert designers present readers with information about a variety of topics at the frontier of analog circuit design, including low-power and energy-efficient analog electronics, with specific contributions focusing on the design of efficient sensor interfaces and low-power RF systems. This book serves as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development. ·         Provides a state-of-the-art reference in analog circuit design, written by experts from industry and academia; ·         Presents material in a tutorial-based format; ·         Includes coverage of high-performance analog-to-digital and digital to analog converters, integrated circuit design in scaled technologies, and time-domain signal processing.

  12. The force of dissimilar analogies in bioethics.

    Science.gov (United States)

    Mertes, Heidi; Pennings, Guido

    2011-04-01

    Although analogical reasoning has long been a popular method of reasoning in bioethics, current literature does not sufficiently grasp its variety. We assert that the main shortcoming is the fact that an analogy's value is often judged on the extent of similarity between the source situation and the target situation, while in (bio)ethics, analogies are often used because of certain dissimilarities rather than in spite of them. We make a clear distinction between dissimilarities that aim to reinforce a similar approach in the source situation and the target situation and dissimilarities that aim to undermine or denounce a similar approach. The former kind of dissimilarity offers the analogy more normative force than if there were no dissimilarities present; this is often overlooked by authors who regard all relevant dissimilarities as detrimental to the analogy's strength. Another observation is that an evaluation of the normative force of an analogy cannot be made independently of moral principles or theories. Without these, one cannot select which elements in an analogy are morally relevant nor determine how they should be interpreted.

  13. The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via σ1 receptor activation: comparison with the effects of dextromethorphan

    OpenAIRE

    Shin, Eun-Joo; Nah, Seung-Yeol; Kim, Won-Ki; Ko, Kwang Ho; Jhoo, Wang-Kee; Lim, Yong-Kwang; Cha, Joo Young; Chen, Chieh-Fu; Kim, Hyoung-Chun

    2005-01-01

    In a previous study, we demonstrated that a dextromethorphan analog, dimemorfan, has neuroprotective effects.Dextromethorphan and dimemorfan are high-affinity ligands at σ1 receptors. Dextromethorphan has moderate affinities for phencyclidine sites, while dimemorfan has very low affinities for such sites, suggesting that these sites are not essential for the anticonvulsant actions of dimemorfan.Kainate (KA) administration (10 mg kg−1, i.p.) produced robust convulsions lasting 4–6 h in rats. P...

  14. Selective termination, fetal reduction and analogical reasoning.

    Science.gov (United States)

    Pennings, G

    2013-06-01

    Analogical reasoning is a basic method in bioethics. Its main purpose is to transfer the rule from an existing or known situation to a new and problematic situation. This commentary applies the lifeboat analogy to the context of selective termination and fetal reduction. It turns out that the analogy is only partially helpful as the main principle in the case of selective termination is the procreative beneficence principle. However, the wide person-affecting form of this principle doubly justifies selective termination: i.e. one prevents the harm caused by the birth of an affected child and one increases the life chances of the remaining fetuses. I conclude, however, that all analogies are basically flawed since they assume that fetuses as such have interests. I argue that fetuses only have interests to the extent that they are potential future persons. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  15. An Electrical Analog Computer for Poets

    Science.gov (United States)

    Bruels, Mark C.

    1972-01-01

    Nonphysics majors are presented with a direct current experiment beyond Ohms law and series and parallel laws. This involves construction of an analog computer from common rheostats and student-assembled voltmeters. (Author/TS)

  16. Pentagastrin analogs containing α-aminooxy acids

    International Nuclear Information System (INIS)

    Balaspiri, L.; Kovacs, L.; Kovacs, K.; Varga, L.; Varro, V.; Schoen, I.; Kisfaludy, L.

    1982-01-01

    Two 14 C-labelled pentagastrin analogs of different specific radioactivities, containing α-aminooxy acids, have been synthesised to study their biological effects in the gastro-intestinal tract. (U.K.)

  17. Quantum States Transfer by Analogous Bell States

    International Nuclear Information System (INIS)

    Mei Di; Li Chong; Yang Guohui; Song Heshan

    2008-01-01

    Transmitting quantum states by channels of analogous Bell states is studied in this paper. We analyze the transmitting process, constructed the probabilitic unitary operator, and gain the largest successful transfer quantum state probability.

  18. MCD spectroscopy and TD-DFT calculations of low symmetry subnaphthalocyanine analogs.

    Science.gov (United States)

    Mack, John; Otaki, Tatsuya; Durfee, William S; Kobayashi, Nagao; Stillman, Martin J

    2014-07-01

    Magnetic circular dichroism (MCD) spectroscopy and time-dependent density functional theory (TD-DFT) calculations are used to analyze the electronic structure and optical properties of low-symmetry subnaphthalocyanine analogs with AAB and ABB structures formed during mixed condensations of tetrafluorophthalonitrile and 2,3-naphthalenedicarbonitrile. The results demonstrate that trends observed in the properties of phthalocyanine analogs can be used to fine tune the optical properties so that the Q(0,0) bands lie in the red region, in a manner that does not significantly destabilize the highest occupied molecular orbital (HOMO) energy relative to that of the parent subphthalocyanine ligand. Attempts to study the spectroscopy of anion radical species proved unsuccessful, since they proved to be unstable. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. High-frequency analog integrated circuit design

    CERN Document Server

    1995-01-01

    To learn more about designing analog integrated circuits (ICs) at microwave frequencies using GaAs materials, turn to this text and reference. It addresses GaAs MESFET-based IC processing. Describes the newfound ability to apply silicon analog design techniques to reliable GaAs materials and devices which, until now, was only available through technical papers scattered throughout hundred of articles in dozens of professional journals.

  20. Emergent Explorations: Analog and Digital Scripting

    OpenAIRE

    Worden, Alexander

    2011-01-01

    This book documents an exploration of emergent and linear modes of defining space, form, and structure. The thesis highlights a dialog between analog and digital modeling techniques, in concept and project development. It identifies that analog modeling techniques, coupled with judgment, can be used to develop complex forms. The thesis project employs critical judgment and the textile techniques of crochet as a vehicle generate form. Crochet lends itself to this investigation because it ...

  1. An analog integrated circuit design laboratory

    OpenAIRE

    Mondragon-Torres, A.F.; Mayhugh, Jr.; Pineda de Gyvez, J.; Silva-Martinez, J.; Sanchez-Sinencio, E.

    2003-01-01

    We present the structure of an analog integrated circuit design laboratory to instruct at both, senior undergraduate and entry graduate levels. The teaching material includes: a laboratory manual with analog circuit design theory, pre-laboratory exercises and circuit design specifications; a reference web page with step by step instructions and examples; the use of mathematical tools for automation and analysis; and state of the art CAD design tools in use by industry. Upon completion of the ...

  2. HAPS, a Handy Analog Programming System

    DEFF Research Database (Denmark)

    Højberg, Kristian Søe

    1975-01-01

    HAPS (Hybrid Analog Programming System) is an analog compiler that can be run on a minicomputer in an interactive mode. Essentially HAPS is written in FORTRAN. The equations to be programmed for an ana log computer are read in by using a FORTRAN-like notation. The input must contain maximum...... and emphasizes the limitations HAPS puts on equation structure, types of computing circuit, scaling, and static testing....

  3. Children's analogical reasoning about natural phenomena.

    Science.gov (United States)

    Pauen, S; Wilkening, F

    1997-10-01

    This report investigates children's analogical reasoning in a physics task, using an analogy generated by the children rather than by the experimenter. A total of 127 elementary school children took part in three related studies. Children learned to predict the behavior of a balance scale. Later, they were asked to solve a force interaction problem. Two versions of the balance scale training were devised: version A suggested an incorrect solution to the target problem (negative analogy), and version B suggested a correct solution to the target problem (positive analogy). In Study 1, 9- to 10-year-olds showed spontaneous transfer in both training conditions. In Study 2, 7-year-olds did not show any transfer in the positive analogy condition. Study 3 revealed that the lack of transfer in younger children was not due to a failure either to notice the analogy or to perform the mapping. Instead, 7-year-olds transferred only selected aspects of the correct solution. Copyright 1997 Academic Press.

  4. Working memory predicts children's analogical reasoning.

    Science.gov (United States)

    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.

  5. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Directory of Open Access Journals (Sweden)

    Stéphanie Pérot

    Full Text Available Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely

  6. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Science.gov (United States)

    Pérot, Stéphanie; Regad, Leslie; Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A; Villoutreix, Bruno O; Camproux, Anne-Claude

    2013-01-01

    Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket

  7. Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

    Directory of Open Access Journals (Sweden)

    Tino Wolter

    Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

  8. Development of immobilized ligands for actinide separations

    International Nuclear Information System (INIS)

    Paine, R.T.

    1994-01-01

    Primary goals during this grant period were to (1) synthesize new bifunctional chelating ligands, (2) characterize the structural features of the Ln and An coordination complexes formed by these ligands, (3) use structural data to iteratively design new classes of multifunctional ligands, and (4) explore additional routes for attachment of key ligands to solid supports that could be useful for chromatographic separations. Some highlights of recently published work as well as a summary of submitted, unpublished and/or still in progress research are outlined

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

    Science.gov (United States)

    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.

  10. Anti-Plasmodium activity of ceramide analogs

    Directory of Open Access Journals (Sweden)

    Gatt Shimon

    2004-12-01

    Full Text Available Abstract Background Sphingolipids are key molecules regulating many essential functions in eukaryotic cells and ceramide plays a central role in sphingolipid metabolism. A sphingolipid metabolism occurs in the intraerythrocytic stages of Plasmodium falciparum and is associated with essential biological processes. It constitutes an attractive and potential target for the development of new antimalarial drugs. Methods The anti-Plasmodium activity of a series of ceramide analogs containing different linkages (amide, methylene or thiourea linkages between the fatty acid part of ceramide and the sphingoid core was investigated in culture and compared to the sphingolipid analog PPMP (d,1-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. This analog is known to inhibit the parasite sphingomyelin synthase activity and block parasite development by preventing the formation of the tubovesicular network that extends from the parasitophorous vacuole to the red cell membrane and delivers essential extracellular nutrients to the parasite. Results Analogs containing methylene linkage showed a considerably higher anti-Plasmodium activity (IC50 in the low nanomolar range than PPMP and their counterparts with a natural amide linkage (IC50 in the micromolar range. The methylene analogs blocked irreversibly P. falciparum development leading to parasite eradication in contrast to PPMP whose effect is cytostatic. A high sensitivity of action towards the parasite was observed when compared to their effect on the human MRC-5 cell growth. The toxicity towards parasites did not correlate with the inhibition by methylene analogs of the parasite sphingomyelin synthase activity and the tubovesicular network formation, indicating that this enzyme is not their primary target. Conclusions It has been shown that ceramide analogs were potent inhibitors of P. falciparum growth in culture. Interestingly, the nature of the linkage between the fatty acid part and the

  11. The future of vitamin D analogs

    Directory of Open Access Journals (Sweden)

    Carlien eLeyssens

    2014-04-01

    Full Text Available The active form of vitamin D3, 1,25-dihydroxyvitamin D3, is a major regulator of bone and calcium homeostasis. In addition, this hormone also inhibits the proliferation and stimulates the differentiation of normal as well as malignant cells. Supraphysiological doses of 1,25-dihydroxyvitamin D3 are required to reduce cancer cell proliferation. However, these doses will lead in vivo to calcemic side effects such as hypercalcemia and hypercalciuria. During the last 25 years, many structural analogs of 1,25-dihydroxyvitamin D3 have been synthesized by the introduction of chemical modifications in the A-ring, central CD-ring region or side chain of 1,25-dihydroxyvitamin D3 in the hope to find molecules with a clear dissociation between the beneficial antiproliferative effects and adverse calcemic side effects. One example of such an analog with a good dissociation ratio is calcipotriol (DaivonexR, which is clinically used to treat the hyperproliferative skin disease psoriasis. Other vitamin D analogs were clinically approved for the treatment of osteoporosis or secondary hyperparathyroidism. No vitamin D analog is currently used in the clinic for the treatment of cancer although several analogs have been shown to be potent drugs in animal models of cancer. Omics studies as well as in vitro cell biological experiments unraveled basic mechanisms involved in the antineoplastic effects of vitamin D and its analogs. 1,25-dihydroxyvitamin D3 and analogs act in a cell type- and tissue-specific manner. Moreover, a blockade in the transition of the G0/1 towards S phase of the cell cycle, induction of apoptosis, inhibition of migration and invasion of tumor cells together with effects on angiogenesis and inflammation have been implicated in the pleiotropic effects of 1,25-dihydroxyvitamin D3 and its analogs. In this review we will give an overview of the action of vitamin D analogs in tumor cells and look forward how these compounds could be introduced in the

  12. NaturAnalogs for the Unsaturated Zone

    Energy Technology Data Exchange (ETDEWEB)

    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 Unsaturated 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.

  13. Analog forecasting with dynamics-adapted kernels

    Science.gov (United States)

    Zhao, Zhizhen; Giannakis, Dimitrios

    2016-09-01

    Analog forecasting is a nonparametric technique introduced by Lorenz in 1969 which predicts the evolution of states of a dynamical system (or observables defined on the states) by following the evolution of the sample in a historical record of observations which most closely resembles the current initial data. Here, we introduce a suite of forecasting methods which improve traditional analog forecasting by combining ideas from kernel methods developed in harmonic analysis and machine learning and state-space reconstruction for dynamical systems. A key ingredient of our approach is to replace single-analog forecasting with weighted ensembles of analogs constructed using local similarity kernels. The kernels used here employ a number of dynamics-dependent features designed to improve forecast skill, including Takens’ delay-coordinate maps (to recover information in the initial data lost through partial observations) and a directional dependence on the dynamical vector field generating the data. Mathematically, our approach is closely related to kernel methods for out-of-sample extension of functions, and we discuss alternative strategies based on the Nyström method and the multiscale Laplacian pyramids technique. We illustrate these techniques in applications to forecasting in a low-order deterministic model for atmospheric dynamics with chaotic metastability, and interannual-scale forecasting in the North Pacific sector of a comprehensive climate model. We find that forecasts based on kernel-weighted ensembles have significantly higher skill than the conventional approach following a single analog.

  14. Analogy, higher order thinking, and education.

    Science.gov (United States)

    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.

  15. An analog silicon retina with multichip configuration.

    Science.gov (United States)

    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.

  16. A fast multichannel analog storage system

    International Nuclear Information System (INIS)

    Freytag, D.R.

    1983-01-01

    A Multichannel Analog Storage System based on a commercial 32-channel parallel in/serial out (PISO) analog shift register is described. The basic unit is a single width CAMAC module containing 512 analog cells and the associated logic for data storage and subsequent readout. At sampling rates of up to 30 MHz the signals are strobed directly into the PISO. At higher rates signals are strobed into a fast presampling stage and subsequently transferred in block form into an array of PISO's. Sampling rates of 300 MHz have been achieved with the present device and 1000 MHz are possible with improved signal drivers. The system is well suited for simultaneous handling of many signal channels with moderate numbers of samples in each channel. RMS noise over full scale signal has been measured as 1:3000 (approx. =11 bit). However, nonlinearities in the response and differences in sensitivity of the analog cells require an elaborate calibration system in order to realize 11 bit accuracy for the analog information

  17. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    Directory of Open Access Journals (Sweden)

    Troco K. Mihali

    2010-07-01

    Full Text Available Saxitoxin (STX and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs. PSTs are the causative agents of paralytic shellfish poisoning (PSP and are mostly associated with marine dinoflagellates (eukaryotes and freshwater cyanobacteria (prokaryotes, which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

  18. Natural Analogs for the Unsaturated Zone

    International Nuclear Information System (INIS)

    Simmons, A.; Unger, A.; Murrell, M.

    2000-01-01

    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 Unsaturated 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

  19. Macrocyclic ligands for uranium complexation

    International Nuclear Information System (INIS)

    Potts, K.T.

    1991-04-01

    A highly preorganized 24-macrocycle containing biuret, thiobiuret and pyridine subunits has been prepared by high dilution ring-closure procedures. Intermediate products to this macrocycle have been utilized to extend this synthetic route to include further representatives where solubility and stability will be influenced by substituent variation. A 1:1 complex has been formed from uranyl acetate and a quinquepyridine derivative, this representing a new type of ligand for the uranyl ion. A very convenient synthetic procedure that will allow the incorporation of these macrocycles into polymeric systems has been developed for the introduction of a vinyl substituent into the 4-position of the pyridine ring. Using triflate, vinyltributyltin and Pd 0 chemistry, this procedure should make a variety of substituted 4-vinylpyridines available for the first time. 3 refs

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

    Science.gov (United States)

    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…

  1. CXCR4 Ligands : The Next Big Hit?

    NARCIS (Netherlands)

    Walenkamp, Annemiek M. E.; Lapa, Constantin; Herrmann, Ken; Wester, Hans-Juergen

    2017-01-01

    The G protein-coupled protein receptor C-X-C chemokine receptor 4 (CXCR4) is an attractive target for cancer diagnosis and treatment, as it is overexpressed in many solid and hematologic cancers. Binding of its ligand, C-X-C chemokine ligand 12 (CXCL12), results in receptor internalization and

  2. Ligand-receptor Interactions by NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Novak. P.

    2008-04-01

    Full Text Available Today NMR spectroscopy is a method of choice for elucidation of interactions between biomolecules and the potential ligands. Knowledge on these interactions is an essential prerequisite for the rational drug design. The most important contribution of NMR to drug design a few years ago was the 3D structure determination of proteins. Besides delivering the 3D structures of the free proteins as a raw material for the modeling studies on ligand binding, NMR can directly yield valuable experimental data on the biologically important protein-ligand complexes. In addition to X-ray diffraction, NMR spectroscopy can provide information on the internal protein dynamics ordynamics of intermolecular interactions. Changes in NMR parameters allow us to detect ("SAR by NMR" and quantitatively determine binding affinities (titration, diffusion NMR experiments, etc. of potential ligands. Also, it is possible to determine the binding site and conformations of ligands, receptors and receptor-ligand complexes with the help of NMR methods such as tr-NOESY. Epitopes or functional groups responsible for binding of ligands to the receptor can be identified by employing STD or WaterLOGSY experiments. In this review are described some of the most frequent NMR methods for the characterization of the interactions between biomolecules and ligands, together with their advantages and disadvantages.

  3. Autocrine signal transmission with extracellular ligand degradation

    Science.gov (United States)

    Muratov, C B; Posta, F; Shvartsman, S Y

    2009-03-01

    Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand-receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers.

  4. Organotellurium ligands – designing and complexation reactions

    Indian Academy of Sciences (India)

    Unknown

    membered rings it is negative and ~30 ppm only. Keywords. Organotellurium ligands; hybrid telluroether; platinum metal complexes; tellurium-125 NMR. 1. Introduction. Tellurium is the noblest metalloid which may act as a Lewis acid as well as Lewis base. The ligand chemistry of tellurium, which acts as a 'soft' donor, was ...

  5. Changes in analogical reasoning in adulthood.

    Science.gov (United States)

    Clark, E; Gardner, M K; Brown, G; Howell, R J

    1990-01-01

    This study sought to investigate adult intellectual development through an analysis of a particular type of cognitive ability, verbal analogical reasoning. The performance of 60 individuals between the ages of 20 and 79 was compared on 100 verbal analogies. The subjects consisted of six groups of ten individuals each (five males and five females), matched as a group for education and gender. Solution times and error rates served as the dependent measures. Results showed that there was a significant trend for the older subjects (60- and 70-year-olds) to be slower than the young subjects (20-, 30-, 40-, and 50-year-olds), but not necessarily more error prone. These data suggest that verbal analogical reasoning changes with age. Supplemental data demonstrated a change in other abilities as well (i.e., decline in perceptual-motor speed and spatial skill).

  6. Electronic devices for analog signal processing

    CERN Document Server

    Rybin, Yu K

    2012-01-01

    Electronic Devices for Analog Signal Processing is intended for engineers and post graduates and considers electronic devices applied to process analog signals in instrument making, automation, measurements, and other branches of technology. They perform various transformations of electrical signals: scaling, integration, logarithming, etc. The need in their deeper study is caused, on the one hand, by the extension of the forms of the input signal and increasing accuracy and performance of such devices, and on the other hand, new devices constantly emerge and are already widely used in practice, but no information about them are written in books on electronics. The basic approach of presenting the material in Electronic Devices for Analog Signal Processing can be formulated as follows: the study with help from self-education. While divided into seven chapters, each chapter contains theoretical material, examples of practical problems, questions and tests. The most difficult questions are marked by a diamon...

  7. Electrical analog of a Josephson junction

    International Nuclear Information System (INIS)

    Goldman, A.M.

    1979-01-01

    It is noted that a mathematical description of the phase-coupling of two oscillators synchronized by a phase-lock-loop under the influence of thermal white noise is analogous to that of the phase coupling of two superconductors in a Josephson junction also under the influence of noise. This analogy may be useful in studying threshold instabilities of the Josephson junction in regimes not restricted to the case of large damping. This is of interest because the behavior of the mean voltage near the threshold current can be characterized by critical exponents which resemble those exhibited by an order parameter of a continuous phase transition. As it is possible to couple a collection of oscillators together in a chain, the oscillator analogy may also be useful in exploring the dynamics and statistical mechanics of coupled junctions

  8. On Lovelock analogs of the Riemann tensor

    Science.gov (United States)

    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.

  9. Analogical reasoning for reliability analysis based on generic data

    Energy Technology Data Exchange (ETDEWEB)

    Kozin, Igor O

    1996-10-01

    The paper suggests using the systemic concept 'analogy' for the foundation of an approach to analyze system reliability on the basis of generic data, describing the method of structuring the set that defines analogical models, an approach of transition from the analogical model to a reliability model and a way of obtaining reliability intervals of analogous objects.

  10. Analogical reasoning for reliability analysis based on generic data

    International Nuclear Information System (INIS)

    Kozin, Igor O.

    1996-01-01

    The paper suggests using the systemic concept 'analogy' for the foundation of an approach to analyze system reliability on the basis of generic data, describing the method of structuring the set that defines analogical models, an approach of transition from the analogical model to a reliability model and a way of obtaining reliability intervals of analogous objects

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

    Science.gov (United States)

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

    Science.gov (United States)

    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…

  13. Conformation driven complexation of two analogous benzimidazole ...

    Indian Academy of Sciences (India)

    metal-organic framework involving Ag(I) and a neutral, semirigid, tripodal ligand, 1 .... tion quality single crystals of the complex, suitable for single crystal diffraction ..... Mohanty J S, Baksi A, Leeb H and Pradeep T 2015 RSC. Adv. 5 48039. 14.

  14. Words, Concepts, and the Geometry of Analogy

    Directory of Open Access Journals (Sweden)

    Stephen McGregor

    2016-08-01

    Full Text Available This paper presents a geometric approach to the problem of modelling the relationship between words and concepts, focusing in particular on analogical phenomena in language and cognition. Grounded in recent theories regarding geometric conceptual spaces, we begin with an analysis of existing static distributional semantic models and move on to an exploration of a dynamic approach to using high dimensional spaces of word meaning to project subspaces where analogies can potentially be solved in an online, contextualised way. The crucial element of this analysis is the positioning of statistics in a geometric environment replete with opportunities for interpretation.

  15. Analogical reasoning abilities of recovering alcoholics.

    Science.gov (United States)

    Gardner, M K; Clark, E; Bowman, M A; Miller, P J

    1989-08-01

    This study investigated analogical reasoning abilities of alcoholics who had been abstinent from alcohol for at least 1 year. Their performance was compared to that of nonalcoholic controls matched as a group for education, age, and gender. Solution times and error rates were modeled using a regression model. Results showed a nonsignificant trend for alcoholics to be faster, but more error prone, than controls. The same componential model applied to both groups, and fit them equally well. Although differences have been found in analogical reasoning ability between controls and alcoholics immediately following detoxification, we find no evidence of differences after extended periods of sobriety.

  16. Analogy in systems management: a theoretical inquiry

    Energy Technology Data Exchange (ETDEWEB)

    Silverman, B.G.

    1983-11-01

    This theoretical analysis of the intuitive and diffuse characteristics of analogical reasoning processes is the first step in a research effort intended to lead to: understanding of common (and possibly costly) errors, pitfalls, travails, and problem-solving impediments; possible recommendations for improvements to organizational structures, control and coordination processes, and management information flows, and guidelines for a generalized analogical reasoning support framework (e.g., a handbook, a knowledge bank design, and/or even a software package/artificial intelligence program). 233 references.

  17. Analysis of Recurrent Analog Neural Networks

    Directory of Open Access Journals (Sweden)

    Z. Raida

    1998-06-01

    Full Text Available In this paper, an original rigorous analysis of recurrent analog neural networks, which are built from opamp neurons, is presented. The analysis, which comes from the approximate model of the operational amplifier, reveals causes of possible non-stable states and enables to determine convergence properties of the network. Results of the analysis are discussed in order to enable development of original robust and fast analog networks. In the analysis, the special attention is turned to the examination of the influence of real circuit elements and of the statistical parameters of processed signals to the parameters of the network.

  18. Analogy Mapping Development for Learning Programming

    Science.gov (United States)

    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. Design of analog integrated circuits and systems

    CERN Document Server

    Laker, Kenneth R

    1994-01-01

    This text is designed for senior or graduate level courses in analog integrated circuits or design of analog integrated circuits. This book combines consideration of CMOS and bipolar circuits into a unified treatment. Also included are CMOS-bipolar circuits made possible by BiCMOS technology. The text progresses from MOS and bipolar device modelling to simple one and two transistor building block circuits. The final two chapters present a unified coverage of sample-data and continuous-time signal processing systems.

  20. High-speed and high-resolution analog-to-digital and digital-to-analog converters

    NARCIS (Netherlands)

    van de Plassche, R.J.

    1989-01-01

    Analog-to-digital and digital-to-analog converters are important building blocks connecting the analog world of transducers with the digital world of computing, signal processing and data acquisition systems. In chapter two the converter as part of a system is described. Requirements of analog

  1. Process and circuiting arrangement for the conversion of analog signals to digital signals and digital signals to analog signals

    International Nuclear Information System (INIS)

    Wintzer, K.

    1977-01-01

    Process for analog-to-digital and digital-to-analog conversion in telecommunication systems whose outstations each have an analog transmitter and an analog receiver. The invention illustrates a method of reducing the power demand of the converters at times when no conversion processes take place. (RW) [de

  2. Binuclear trivalent and tetravalent uranium halides and cyanides supported by cyclooctatetraene ligands

    International Nuclear Information System (INIS)

    Wang, Cong-Zhi; Wu, Qun-Yan; Lan, Jian-Hui; Shi, Wei-Qun; Gibson, John K.

    2017-01-01

    Although the first organoactinide chloride Cp_3UCl (Cp = η"5-C_5H_5) was synthesized more than 50 years ago, binuclear uranium halides remain very rare in organoactinide chemistry. Herein, a series of binuclear trivalent and tetravalent uranium halides and cyanides with cyclooctatetraene ligands, (COT)_2U_2X_n (COT = η"8-C_8H_8; X=F, Cl, CN; n=2, 4), have been systematically studied using scalar-relativistic density functional theory (DFT). The structures with bridging halide or cyanide ligands were predicted to be the most stable complexes of (COT)_2U_2X_n, and all the complexes show weak antiferromagnetic interactions between the uranium centers. However, for each species, there is no significant uranium-uranium bonding interaction. The bonding between the metal and the ligands shows some degree of covalent character, especially between the metal and terminal halide or cyanide ligands. The U-5f and 6d orbitals are predominantly involved in the metal-ligand bonding. All the (COT)_2U_2X_n species were predicted to be more stable compared to the mononuclear half-sandwich complexes at room temperature in the gas phase such that (COT)_2U_2X_4 might be accessible through the known (COT)_2U complex. The tetravalent derivatives (COT)_2U_2X_4 are more energetically favorable than the trivalent (COT)_2U_2X_2 analogs, which may be attributed to the greater number of strong metal-ligand bonds in the former complexes.

  3. Binuclear trivalent and tetravalent uranium halides and cyanides supported by cyclooctatetraene ligands

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cong-Zhi; Wu, Qun-Yan; Lan, Jian-Hui; Shi, Wei-Qun [Chinese Academy of Sciences, Beijing (China). Laboratory of Nuclear Energy Chemistry and Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety; Chai, Zhi-Fang [Chinese Academy of Sciences, Beijing (China). Laboratory of Nuclear Energy Chemistry and Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety; Soochow Univ., Suzhou (China). School of Radiological and Interdisciplinary Sciences (RAD-X); Gibson, John K. [Lawrence Berkeley National Laboratory, CA (United States). Chemical Sciences Division

    2017-03-01

    Although the first organoactinide chloride Cp{sub 3}UCl (Cp = η{sup 5}-C{sub 5}H{sub 5}) was synthesized more than 50 years ago, binuclear uranium halides remain very rare in organoactinide chemistry. Herein, a series of binuclear trivalent and tetravalent uranium halides and cyanides with cyclooctatetraene ligands, (COT){sub 2}U{sub 2}X{sub n} (COT = η{sup 8}-C{sub 8}H{sub 8}; X=F, Cl, CN; n=2, 4), have been systematically studied using scalar-relativistic density functional theory (DFT). The structures with bridging halide or cyanide ligands were predicted to be the most stable complexes of (COT){sub 2}U{sub 2}X{sub n}, and all the complexes show weak antiferromagnetic interactions between the uranium centers. However, for each species, there is no significant uranium-uranium bonding interaction. The bonding between the metal and the ligands shows some degree of covalent character, especially between the metal and terminal halide or cyanide ligands. The U-5f and 6d orbitals are predominantly involved in the metal-ligand bonding. All the (COT){sub 2}U{sub 2}X{sub n} species were predicted to be more stable compared to the mononuclear half-sandwich complexes at room temperature in the gas phase such that (COT){sub 2}U{sub 2}X{sub 4} might be accessible through the known (COT){sub 2}U complex. The tetravalent derivatives (COT){sub 2}U{sub 2}X{sub 4} are more energetically favorable than the trivalent (COT){sub 2}U{sub 2}X{sub 2} analogs, which may be attributed to the greater number of strong metal-ligand bonds in the former complexes.

  4. Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands.

    Science.gov (United States)

    Hubin, Timothy J; Amoyaw, Prince N-A; Roewe, Kimberly D; Simpson, Natalie C; Maples, Randall D; Carder Freeman, TaRynn N; Cain, Amy N; Le, Justin G; Archibald, Stephen J; Khan, Shabana I; Tekwani, Babu L; Khan, M O Faruk

    2014-07-01

    Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal complexes of the dibenzyl cross-bridged cyclam ligand exhibited potent antimalarial activity. The Mn(2+) complex of this ligand was the most potent with IC50s of 0.127 and 0.157μM against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) P. falciparum strains, respectively. In general, the dibenzyl hydrophobic ligands showed better anti-malarial activity compared to the activity of monobenzyl ligands, potentially because of their higher lipophilicity and thus better cell penetration ability. The higher antimalarial activity displayed by the manganese complex for the cyclam ligand in comparison to that of the cyclen, correlates with the larger pocket of cyclam compared to that of cyclen which produces a more stable complex with the Mn(2+). Few of the Cu(2+) and Fe(2+) complexes also showed improvement in activity but Ni(2+), Co(2+) and Zn(2+) complexes did not show any improvement in activity upon the metal-free ligands for anti-malarial development. Published by Elsevier Ltd.

  5. Ligand-selective activation of heterologously-expressed mammalian olfactory receptor.

    Science.gov (United States)

    Ukhanov, K; Bobkov, Y; Corey, E A; Ache, B W

    2014-10-01

    Mammalian olfactory receptors (ORs) appear to have the capacity to couple to multiple G protein-coupled signaling pathways in a ligand-dependent selective manner. To better understand the mechanisms and molecular range of such ligand selectivity, we expressed the mouse eugenol OR (mOR-EG) in HEK293T cells together with Gα15 to monitor activation of the phospholipase-C (PLC) signaling pathway and/or Gαolf to monitor activation of the adenylate cyclase (AC) signaling pathway, resulting in intracellular Ca(2+) release and/or Ca(2+) influx through a cyclic nucleotide-gated channel, respectively. PLC-dependent responses differed dynamically from AC-dependent responses, allowing them to be distinguished when Gα15 and Gαolf were co-expressed. The dynamic difference in readout was independent of the receptor, the heterologous expression system, and the ligand concentration. Of 17 reported mOR-EG ligands tested, including eugenol, its analogs, and structurally dissimilar compounds (mousse cristal, nootkatone, orivone), some equally activated both signaling pathways, some differentially activated both signaling pathways, and some had no noticeable effect even at 1-5mM. Our findings argue that mOR-EG, when heterologously expressed, can couple to two different signaling pathways in a ligand selective manner. The challenge now is to determine the potential of mOR-EG, and perhaps other ORs, to activate multiple signaling pathways in a ligand selective manner in native ORNs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Correcting ligands, metabolites, and pathways

    Directory of Open Access Journals (Sweden)

    Vriend Gert

    2006-11-01

    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  7. Methane. [biosynthesis from manure or analogous substance

    Energy Technology Data Exchange (ETDEWEB)

    Ducellier, G L.R.; Isman, M A

    1949-04-19

    CH/sub 4/ is produced by the fermentation of manure or analogous substances in a vat having a dome covering the vat, the lower edge of the dome being immersed in a liquid seal, and the dome being arranged to rise vertically in order to hold the CH/sub 4/ produced.

  8. Analog voicing detector responds to pitch

    Science.gov (United States)

    Abel, R. S.; Watkins, H. E.

    1967-01-01

    Modified electronic voice encoder /Vocoder/ includes an independent analog mode of operation in addition to the conventional digital mode. The Vocoder is a bandwidth compression equipment that permits voice transmission over channels, having only a fraction of the bandwidth required for conventional telephone-quality speech transmission.

  9. Invention through Form and Function Analogy

    Science.gov (United States)

    Rule, Audrey C.

    2015-01-01

    "Invention through Form and Function Analogy" is an invention book for teachers and other leaders working with youth who are involving students in the invention process. The book consists of an introduction and set of nine learning cycle formatted lessons for teaching the principles of invention through the science and engineering design…

  10. Formal analogies in physics teacher education

    DEFF Research Database (Denmark)

    Avelar Sotomaior Karam, Ricardo; Ricardo, Elio

    2012-01-01

    the exact same appearance. Coulomb’s law’s similarity with Newton’s, Maxwell’s application of fluid theory to electromagnetism and Hamilton’s optical mechanical analogy are some among many other examples. These cases illustrate the power of mathematics in providing unifying structures for physics. Despite...

  11. An iconic, analogical approach to grammaticalization

    NARCIS (Netherlands)

    Fischer, O.; Conradie, C.J.; Johl, R.; Beukes, M.; Fischer, O.; Ljungberg, C.

    2010-01-01

    This paper addresses a number of problems connected with the ‘apparatus’ used in grammaticalization theory. It will be argued that we get a better grip on what happens in processes of grammaticalization (and its ‘opposite’, lexicalization) if the process is viewed in terms of analogical processes,

  12. Analog and digital dividers for mass spectrometers

    International Nuclear Information System (INIS)

    Osipov, A.K.

    1980-01-01

    Errors of four different types of stress dividers used in statical mass-spectrometers for determination of mass number by accelerating stress are analyzed. The simplest flowsheet of the analog divider comprises operation amplifier, in the chain of the negative feedback of which a multiplication device on differential cascade is switched- in. This analog divider has high sensitivity to temperature and high error approximately 5%. Application of the multiplier on differential cascade with normalization permits to increase temperature stability and decrease the error up to 1%. Another type of the analog divider is a logarithmic divider the error of which is constant within the whole operation range and it constitutes 1-5%. The digital divider with a digital-analog transformer (DAT) has the error of +-0.015% which is determined by the error of detectors and resistance of keys in the locked state. Considered is the design of a divider based on transformation of the inlet stress into the time period. The error of the divider is determined in this case mainly by stress of the zero shift of the operation amplifier (it should be compensated) and relative threshold stability of the comparator triggering which equals (2-3)x10 -4 . It is noted that the divider with DAT application and the divider with the use of stress transformation within the time period are most perspective ones for statical mass-spectrometers [ru

  13. Analog Experiment for rootless cone eruption

    Science.gov (United States)

    Noguchi, R.; Hamada, A.; Suzuki, A.; Kurita, K.

    2017-09-01

    Rootless cone is a unique geomorphological landmark to specify igneous origin of investigated terrane, which is formed by magma-water interaction. To understand its formation mechanism we conducted analog experiment for heat-induced vesiculation by using hot syrup and sodium bicarbonate solution.

  14. SSERVI Analog Regolith Simulant Testbed Facility

    Science.gov (United States)

    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.

  15. A physical analogy to fuzzy clustering

    DEFF Research Database (Denmark)

    Jantzen, Jan

    2004-01-01

    This tutorial paper provides an interpretation of the membership assignment in the fuzzy clustering algorithm fuzzy c-means. The membership of a data point to several clusters is shown to be analogous to the gravitational forces between bodies of mass. This provides an alternative way to explain...

  16. A high-speed analog neural processor

    NARCIS (Netherlands)

    Masa, P.; Masa, Peter; Hoen, Klaas; Hoen, Klaas; Wallinga, Hans

    1994-01-01

    Targeted at high-energy physics research applications, our special-purpose analog neural processor can classify up to 70 dimensional vectors within 50 nanoseconds. The decision-making process of the implemented feedforward neural network enables this type of computation to tolerate weight

  17. C4913 ANALOGE OG DIGITALE FILTRE

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    1996-01-01

    Theese lecture notes treats the fundamental theory and the most commonly used design methods for passive- active and digital filters with special emphasis on microelectronic realizations. The lecture notes covers 75% of the material taught in the course C4913 Analog and Digital Filters...

  18. Analog circuit design automation for performance

    NARCIS (Netherlands)

    Ning, Zhen-Qiu; Ning, Zhen-Qiu; Kole, Marq; Kole, M.E.; Mouthaan, A.J.; Wallinga, Hans

    1992-01-01

    This paper describes an improved version of the program SEAS (a Simulated Evolution approach for Analog circuit Synthesis), in which an approach for selection of alternatives based on the evaluation of mutation values is developed, and design automafion for high performance comparators is covered.

  19. Hands Together! An Analog Clock Problem

    Science.gov (United States)

    Earnest, Darrell; Radtke, Susan; Scott, Siri

    2017-01-01

    In this article, the authors first present the Hands Together! task. The mathematics in this problem concerns the relationship of hour and minute durations as reflected in the oft-overlooked proportional movements of the two hands of an analog clock. The authors go on to discuss the importance of problem solving in general. They then consider…

  20. Analog subsystem for the plutonium protection system

    International Nuclear Information System (INIS)

    Arlowe, H.D.

    1978-12-01

    An analog subsystem is described which monitors certain functions in the Plutonium Protection System. Rotary and linear potentiometer output signals are digitized, as are the outputs from thermistors and container ''bulge'' sensors. This work was sponsored by the Department of Energy/Office of Safeguards and Security (DOE/OSS) as part of the overall Sandia Fixed Facility Physical Protection Program

  1. The GMO-Nanotech (Dis)Analogy?

    Science.gov (United States)

    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…

  2. A Mechanical Analogy for Ohm's Law.

    Science.gov (United States)

    do Couto Tavares, Milton; And Others

    1991-01-01

    A mechanical analogy between the microscopic motion of a charged carrier in an ordinary resistor and the macroscopic motion of a ball falling along a slanted board covered with a lattice of nails is introduced. The Drude model is also introduced to include the case of inelastic collisions. Computer simulation of the motion is described. (KR)

  3. Plasma analog of particle-pair production

    International Nuclear Information System (INIS)

    Tsidulko, Yu.A.; Berk, H.L.

    1996-09-01

    It is shown that the plasma axial shear flow instability satisfies the Klein-Gordon equation. The plasma instability is then shown to be analogous to spontaneous particle-pair production when a potential energy is present that is greater than twice the particle rest mass energy. Stability criteria can be inferred based on field theoretical conservation laws

  4. Performance of the Analog Moving Window Detector

    DEFF Research Database (Denmark)

    Hansen, V. Gregers

    1970-01-01

    A type of analog integrating moving window detector for use with a scanning pulse radar is examined. A performance analysis is carried out, which takes into account both the radiation pattern of the antenna and the dynamic character of the detection process due to the angular scanning...

  5. Insulin analogs with improved pharmacokinetic profiles.

    Science.gov (United States)

    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.

  6. Bootstrapped Low-Voltage Analog Switches

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper

    1999-01-01

    Novel low-voltage constant-impedance analog switch circuits are proposed. The switch element is a single MOSFET, and constant-impedance operation is obtained using simple circuits to adjust the gate and bulk voltages relative to the switched signal. Low-voltage (1-volt) operation is made feasible...

  7. Design of ligands for the nicotinic acetylcholine receptors: the quest for selectivity.

    Science.gov (United States)

    Bunnelle, William H; Dart, Michael J; Schrimpf, Michael R

    2004-01-01

    In the last decade, nicotinic acetylcholine receptors (nAChRs) have emerged as important targets for drug discovery. The therapeutic potential of nicotinic agonists depends substantially on the ability to selectively activate certain receptor subtypes that mediate beneficial effects. The design of such compounds has proceeded in spite of a general shortage of data pertaining to subtype selectivity. Medicinal chemistry efforts have been guided principally by binding affinities to the alpha4beta2 and/or alpha7 subtypes, even though these are not predictive of agonist activity at either subtype. Nevertheless, a diverse family of nAChR ligands has been developed, and several analogs with promising therapeutic potential have now advanced to human clinical trials. This paper provides an overview of the structure-affinity relationships that continue to drive development of new nAChR ligands.

  8. Comparison of the kinetics of different Markov models for ligand binding under varying conditions

    International Nuclear Information System (INIS)

    Martini, Johannes W. R.; Habeck, Michael

    2015-01-01

    We recently derived a Markov model for macromolecular ligand binding dynamics from few physical assumptions and showed that its stationary distribution is the grand canonical ensemble [J. W. R. Martini, M. Habeck, and M. Schlather, J. Math. Chem. 52, 665 (2014)]. The transition probabilities of the proposed Markov process define a particular Glauber dynamics and have some similarity to the Metropolis-Hastings algorithm. Here, we illustrate that this model is the stochastic analog of (pseudo) rate equations and the corresponding system of differential equations. Moreover, it can be viewed as a limiting case of general stochastic simulations of chemical kinetics. Thus, the model links stochastic and deterministic approaches as well as kinetics and equilibrium described by the grand canonical ensemble. We demonstrate that the family of transition matrices of our model, parameterized by temperature and ligand activity, generates ligand binding kinetics that respond to changes in these parameters in a qualitatively similar way as experimentally observed kinetics. In contrast, neither the Metropolis-Hastings algorithm nor the Glauber heat bath reflects changes in the external conditions correctly. Both converge rapidly to the stationary distribution, which is advantageous when the major interest is in the equilibrium state, but fail to describe the kinetics of ligand binding realistically. To simulate cellular processes that involve the reversible stochastic binding of multiple factors, our pseudo rate equation model should therefore be preferred to the Metropolis-Hastings algorithm and the Glauber heat bath, if the stationary distribution is not of only interest

  9. Comparison of the kinetics of different Markov models for ligand binding under varying conditions

    Energy Technology Data Exchange (ETDEWEB)

    Martini, Johannes W. R., E-mail: jmartin2@gwdg.de [Max Planck Institute for Developmental Biology, Tübingen (Germany); Felix Bernstein Institute for Mathematical Statistics in the Biosciences, University of Göttingen, Göttingen (Germany); Habeck, Michael, E-mail: mhabeck@gwdg.de [Felix Bernstein Institute for Mathematical Statistics in the Biosciences, University of Göttingen, Göttingen (Germany); Max Planck Institute for Biophysical Chemistry, Göttingen (Germany)

    2015-03-07

    We recently derived a Markov model for macromolecular ligand binding dynamics from few physical assumptions and showed that its stationary distribution is the grand canonical ensemble [J. W. R. Martini, M. Habeck, and M. Schlather, J. Math. Chem. 52, 665 (2014)]. The transition probabilities of the proposed Markov process define a particular Glauber dynamics and have some similarity to the Metropolis-Hastings algorithm. Here, we illustrate that this model is the stochastic analog of (pseudo) rate equations and the corresponding system of differential equations. Moreover, it can be viewed as a limiting case of general stochastic simulations of chemical kinetics. Thus, the model links stochastic and deterministic approaches as well as kinetics and equilibrium described by the grand canonical ensemble. We demonstrate that the family of transition matrices of our model, parameterized by temperature and ligand activity, generates ligand binding kinetics that respond to changes in these parameters in a qualitatively similar way as experimentally observed kinetics. In contrast, neither the Metropolis-Hastings algorithm nor the Glauber heat bath reflects changes in the external conditions correctly. Both converge rapidly to the stationary distribution, which is advantageous when the major interest is in the equilibrium state, but fail to describe the kinetics of ligand binding realistically. To simulate cellular processes that involve the reversible stochastic binding of multiple factors, our pseudo rate equation model should therefore be preferred to the Metropolis-Hastings algorithm and the Glauber heat bath, if the stationary distribution is not of only interest.

  10. NMR studies of DNA oligomers and their interactions with minor groove binding ligands

    Energy Technology Data Exchange (ETDEWEB)

    Fagan, Patricia A. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    1996-05-01

    The cationic peptide ligands distamycin and netropsin bind noncovalently to the minor groove of DNA. The binding site, orientation, stoichiometry, and qualitative affinity of distamycin binding to several short DNA oligomers were investigated by NMR spectroscopy. The oligomers studied contain A,T-rich or I,C-rich binding sites, where I = 2-desaminodeoxyguanosine. I•C base pairs are functional analogs of A•T base pairs in the minor groove. The different behaviors exhibited by distamycin and netropsin binding to various DNA sequences suggested that these ligands are sensitive probes of DNA structure. For sites of five or more base pairs, distamycin can form 1:1 or 2:1 ligand:DNA complexes. Cooperativity in distamycin binding is low in sites such as AAAAA which has narrow minor grooves, and is higher in sites with wider minor grooves such as ATATAT. The distamycin binding and base pair opening lifetimes of I,C-containing DNA oligomers suggest that the I,C minor groove is structurally different from the A,T minor groove. Molecules which direct chemistry to a specific DNA sequence could be used as antiviral compounds, diagnostic probes, or molecular biology tools. The author studied two ligands in which reactive groups were tethered to a distamycin to increase the sequence specificity of the reactive agent.

  11. Autocrine signal transmission with extracellular ligand degradation

    International Nuclear Information System (INIS)

    Muratov, C B; Posta, F; Shvartsman, S Y

    2009-01-01

    Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand–receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers

  12. Radiation induced ligand loss from cobalt complexes

    International Nuclear Information System (INIS)

    Funston, A. M.; McFadyen, W.D.; Tregloan, P.A.

    2000-01-01

    Full text: Due to the rapid nature of ligand dissociation from cobalt(II) complexes the study of the rate of ligand dissociation necessitates the use of a technique such as pulse radiolysis. This allows the rapid reduction of the corresponding cobalt(III) complex by a reducing radical, such as the aquated electron, to form the cobalt(II) complex. However, to date, no systematic study of either the mechanism of reduction or the influence of the electronic structure on the rate of ligand dissociation has been carried out. In order to understand these processes more fully the mechanism of reduction of a range of related cobalt(III) complexes by the aquated electron and the subsequent rate of ligand dissociation from the resulting cobalt(II) complexes is being investigated. It has been found that a number of processes are observed following the initial rapid reaction of the cobalt(III) complex with the aquated electron. Ultimately ligand loss is observed. Depending upon the complex, the initial processes observed may include the formation of coordinated radicals and electron transfer within the complex. For complexes containing aromatic ligands such as 2,2'-bipyridine, 1,10-phenanthroline and dipyrido[3,2-a:2',3'-c]phenazine the formation of a coordinated radical is observed as the initial reduction step. The kinetics of ligand dissociation of these complexes has been determined. The loss of monodentate ligands is fast and has been indistinguishable from the reduction processes when aromatic ligands are also present in the complex. However, for diamine chelates and diimine chelates spectra of the transient species can be resolved

  13. Analog-to-digital conversion using custom CMOS analog memory for the EOS time projection chamber

    International Nuclear Information System (INIS)

    Lee, K.L.; Arthur, A.A.; Jones, R.W.; Matis, H.S.; Nakamura, M.; Kleinfelder, S.A.; Ritter, H.G.; Wienman, H.H.

    1990-01-01

    This paper describes the multiplexing scheme of custom CMOS analog memory integrated circuits, 16 channels x 256 cells, into analog to digital converters (ADC's) to handle 15,360 signal channels of a time projection, chamber detector system. Primary requirements of this system are high density, low power and large dynamic range. The analog memory device multiplexing scheme was designed to digitize the information stored in the memory cells. The digitization time of the ADC's and the settling times for the memory unit were carefully interleaved to optimize the performance and timing during the multiplexing operation. This kept the total number of ADC's, a costly and power dissipative component, to an acceptable minimum

  14. Labeled receptor ligands for spect

    International Nuclear Information System (INIS)

    Kung, H.F.

    1989-01-01

    Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

  15. A Versatile Dinucleating Ligand Containing Sulfonamide Groups

    DEFF Research Database (Denmark)

    Sundberg, Jonas; Witt, Hannes; Cameron, Lisa

    2014-01-01

    ligand can be prepared in aqueous solutions using only divalent metal ions. Two of the copper(II) complexes, [Cu2(psmp)(OH)] and [Cu2(psmp)(OAc)2]-, demonstrate the anticipated 1:2 ligand/metal stoichiometry and show that the dimetallic binding site created for exogenous ligands possesses high inherent...... of antiferromagnetic coupling. This is corroborated computationally by broken-symmetry density functional theory, which for isotropic modeling of the coupling predicts an antiferromagnetic coupling strength of J = 70.5 cm-1....

  16. Targeting nanoparticles to M cells with non-peptidic ligands for oral vaccination

    OpenAIRE

    Fievez, Virginie; Plapied, Laurence; des Rieux, Anne; Pourcelle, Vincent; Freichels, Hélène; Wascotte, Valentine; Vanderhaegen, Marie-Lyse; Jérôme, Christine; Vanderplasschen, Alain; Marchand-Brynaert, Jacqueline; Préat, Véronique

    2009-01-01

    The presence of RGD on nanoparticles allows the targeting of β1 integrins at the apical surface of human M cells and the enhancement of an immune response after oral immunization. To check the hypothesis that non-peptidic ligands targeting intestinal M cells or APCs would be more efficient for oral immunization than RGD, novel non-peptidic and peptidic analogs (RGD peptidomimitic (RGDp), LDV derivative (LDVd) and LDV peptidomimetic (LDVp)) as well as mannose were grafted on the PEG chain of P...

  17. Preliminary studies of 99mTc labeled fatty acid analogs for myocardial imaging

    International Nuclear Information System (INIS)

    Guo Yuzhi; Kung, H.F.; Mack, R.H.

    1988-01-01

    Radio iodine labelled fatty acid analogs are potential myocardial imaging agents for SPECT. In this paper are reported three new 99m Tc labbeled fatty acid analogs: 9 '9 m Tc-BAT-TDA, 99m Tc-BAT-PDA and 99m Tc-BAT-H x DA. Ligand exchange reaction with 99m Tc stannous glucoheptonate in 50% aqueous ethanol is used for labelling. The yield of reactions is 87%, 70%, 49% respectively. 99m Tc-fatty acid is purified by extraction into chloroform and the purity as determined by reverse phase HPLC is 98%. In order to determine the structure of Tc-BAT-fatty acid, 99 Tc-BAT-PDA is synthesized with 99 Tc ammonium pertechnetate in 50% citric acid buffer (pH=6)/ethanol using stannous chloride as the reducing agent. 99 Tc-BAT-PDA displays the expected Tc=O UV absorption at 420nm and strong peak at 900cm -1 in the FTIR spectrum. Biodistribution studies of three 99m Tc-fatty acid analogs are conducted in rats using 125 I-ω- (p-iodophenyl) -penta-decanoic acid (IPPDA) as internal standard. The initial heart uptake of them is significantly lower than that of 125 I-IPPDA

  18. Riboflavin analogs as antiinfectives: occurrence, mode of action, metabolism and resistance.

    Science.gov (United States)

    Pedrolli, Danielle Biscaro; Jankowitsch, Frank; Schwarz, Julia; Langer, Simone; Nakanishi, Shinobu; Frei, Eva; Mack, Matthias

    2013-01-01

    Antimetabolites are molecules, which are structurally similar to molecules needed to carry out primary metabolic reactions.The inhibitory activity of an antimetabolite depends on its successful competition with the natural substrate, ligand, modulator or cofactor of a given biomolecule. Antimetabolites are indispensable as molecular tools in order to understand biological processes. Beyond that,antimetabolites have a large variety of applications in the pharmaceutical and food industries. The identification of the structural riboflavin(vitamin B2) analog roseoflavin in Streptomyces davawensis demonstrates that anti-vitamins/cofactor analogs may serve as lead structures for the development of novel antibiotics. The latter is supported by the recent finding that roseoflavin had a profound inhibiting effect on the growth and infectivity of the human bacterial pathogen Listeria monocytogenes at very low concentrations. Roseoflavin is studied in our laboratory as a model compound. We investigate the biosynthesis, the possible large-scale production, the metabolization,the mechanism of action and the resistance mechanism of the producer organism in order to pave the way for the structured analysis of other vitamin analogs yet to be discovered. These compounds hopefully will help to replenish the arsenal of antimicrobials urgently needed to fight multiresistant bacterial pathogens.

  19. Resveratrol, piceatannol and analogs inhibit activation of both wild-type and T877A mutant androgen receptor.

    Science.gov (United States)

    Lundqvist, Johan; Tringali, Corrado; Oskarsson, Agneta

    2017-11-01

    Prostate cancer growth and progression are mainly dependent on androgens and many current prostate cancer treatment options target the synthesis or function of androgens. We have previously reported that resveratrol and synthetic analogs of resveratrol with a higher bioavailability inhibit the synthesis of androgens in human adrenocortical H295R cells. Now we have studied the antiandrogenic properties of resveratrol, piceatannol and analogs in two different prostate cell lines; LNCaP and RWPE. LNCaP carry a T877A mutation in the androgen receptor while RWPE has a wild-type androgen receptor. We found that resveratrol, piceatannol and all studied analogs were able to inhibit a dihydrotestosterone-induced activation of the androgen receptor, showing that they act as antiandrogens. In LNCaP cells, all studied compounds were able to statistically significantly decrease the androgenic signaling in concentrations ≥1μM and the synthetic analogs trimethylresveratrol (RSVTM) and tetramethylpiceatannol (PICTM) were the most potent compounds. RWPE cells were not as responsive to the studied compounds as the LNCaP cells. A statistically significant decrease in the androgenic signaling was observed at concentrations ≤5μM for most compounds and RSVTM was found to be the most potent compound. Further, we studied the effects of resveratrol, piceatannol and analogs on the levels of prostate-specific antigen (PSA) in LNCaP cells and found that all studied compounds decreased the level of PSA and that the synthetic analogs diacetylresveratrol (RSVDA), triacetylresveratrol (RSVTA) and RSVTM were the most potent compounds, decreasing the PSA level by approx. 50% at concentrations ≥10μM. In a cell-free receptor binding assay we were unable to show binding of resveratrol or analogs to the ligand binding domain of the androgen receptor, indicating that the observed effects are mediated via other mechanisms than direct ligand competition. We conclude that the resveratrol

  20. Multilateral Research Opportunities in Ground Analogs

    Science.gov (United States)

    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

  1. Ligand based pharmacophore modelling of anticancer histone ...

    African Journals Online (AJOL)

    USER

    2010-06-21

    Jun 21, 2010 ... The study was carried out using the software Ligand Scout (version .... Computer Science, for his great help and support. We are also grateful to Faculty of Engineering and applied. Sciences, Mohammad .... Aided Mol. Design ...

  2. Synthesis and characterization β-ketoamine ligands

    Science.gov (United States)

    Zaid, Nurzati Amani Mohamed; Hassan, Nur Hasyareeda; Karim, Nurul Huda Abd

    2018-04-01

    β-ketoamine ligands are important members of heterodonor ligand because of their ease of preparation and modification of both steric and/or electronic effects. Complexes with β-ketoamine has received much less attention and there has been no study about this complex with β-ketoamine in ionic liquid reported. Two type of β-ketoamine ligands which are 4-amino-3-pentene-2-onato (A) and 3-amino-2-butenoic acid methyl ester (B) have been synthesized in this work. The resulting compound formed was characterized using standard spectroscopic and structural techniques which includes 1H and 13C, NMR spectroscopy and FTIR spectroscopy. The 1H and 13C NMR spectrum displayed all the expected signals with correct integration and multiplicity. And it is proved that there are some differences between two ligands as observed in NMR and FTIR spectrum.

  3. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S

    2006-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During cogenesis in Drosophila melanogaster local Egfr activation by the spatially-restricted TGFalpha-like ligand Gurken (Grk...

  4. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S

    2005-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During oogenesis in Drosophila melanogaster, local EGFR activation by the spatially restricted TGF alpha-like ligand, Gurken (Grk...

  5. Using Visual Analogies To Teach Introductory Statistical Concepts

    Directory of Open Access Journals (Sweden)

    Jessica S. Ancker

    2017-07-01

    Full Text Available Introductory statistical concepts are some of the most challenging to convey in quantitative literacy courses. Analogies supplemented by visual illustrations can be highly effective teaching tools. This literature review shows that to exploit the power of analogies, teachers must select analogies familiar to the audience, explicitly link the analog with the target concept, and avert misconceptions by explaining where the analogy fails. We provide guidance for instructors and a series of visual analogies for use in teaching medical and health statistics.

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

    Science.gov (United States)

    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. Cell-specific targeting by heterobivalent ligands.

    Science.gov (United States)

    Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

    2011-07-20

    Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

  8. Semiconductor Quantum Dots with Photoresponsive Ligands.

    Science.gov (United States)

    Sansalone, Lorenzo; Tang, Sicheng; Zhang, Yang; Thapaliya, Ek Raj; Raymo, Françisco M; Garcia-Amorós, Jaume

    2016-10-01

    Photochromic or photocaged ligands can be anchored to the outer shell of semiconductor quantum dots in order to control the photophysical properties of these inorganic nanocrystals with optical stimulations. One of the two interconvertible states of the photoresponsive ligands can be designed to accept either an electron or energy from the excited quantum dots and quench their luminescence. Under these conditions, the reversible transformations of photochromic ligands or the irreversible cleavage of photocaged counterparts translates into the possibility to switch luminescence with external control. As an alternative to regulating the photophysics of a quantum dot via the photochemistry of its ligands, the photochemistry of the latter can be controlled by relying on the photophysics of the former. The transfer of excitation energy from a quantum dot to a photocaged ligand populates the excited state of the species adsorbed on the nanocrystal to induce a photochemical reaction. This mechanism, in conjunction with the large two-photon absorption cross section of quantum dots, can be exploited to release nitric oxide or to generate singlet oxygen under near-infrared irradiation. Thus, the combination of semiconductor quantum dots and photoresponsive ligands offers the opportunity to assemble nanostructured constructs with specific functions on the basis of electron or energy transfer processes. The photoswitchable luminescence and ability to photoinduce the release of reactive chemicals, associated with the resulting systems, can be particularly valuable in biomedical research and can, ultimately, lead to the realization of imaging probes for diagnostic applications as well as to therapeutic agents for the treatment of cancer.

  9. Designer TGFβ superfamily ligands with diversified functionality.

    Directory of Open Access Journals (Sweden)

    George P Allendorph

    Full Text Available Transforming Growth Factor--beta (TGFβ superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs, and Bone Morphogenetic Proteins (BMPs, are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer, to engineer chemically-refoldable TGFβ superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-βA and BMP-2 sequences, exhibits the refolding characteristics of BMP-2 while possessing Activin-like signaling attributes. Further, we find several additional ligands, AB204, AB211, and AB215, which initiate the intracellular Smad1-mediated signaling pathways more strongly than BMP-2 but show no sensitivity to the natural BMP antagonist Noggin unlike natural BMP-2. In another design, incorporation of a short N-terminal segment from BMP-2 was sufficient to enable chemical refolding of BMP-9, without which was never produced nor refolded. Our studies show that the RASCH strategy enables us to expand the functional repertoire of TGFβ superfamily ligands through development of novel chimeric TGFβ ligands with diverse biological and clinical values.

  10. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng

    2014-12-03

    Background Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction for protein-ligand binding sites, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. Results In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. We propose a combination technique to reduce the effects of different sliding residue windows in the process of encoding input feature vectors. Moreover, due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we construct several balanced data sets, for each of which a random forest (RF)-based classifier is trained. The ensemble of these RF classifiers forms a sequence-based protein-ligand binding site predictor. Conclusions Experimental results on CASP9 and CASP8 data sets demonstrate that our method compares favorably with the state-of-the-art protein-ligand binding site prediction methods.

  11. Analog data transmission via fiber optics

    International Nuclear Information System (INIS)

    Cisneros, E.L.; Burgueno, G.F.

    1986-10-01

    In the SLAC Linear Collider Detector (SLD), as in most high-energy particle detectors, the electromagnetic noise environment is the limiting factor in electronic readout performance. Front-end electronics are particulary susceptible to electromagnetic interference (EMI), and great care has been taken to minimize its effects. The transfer of preprocessed analog signals from the detector environs, to the remote digital processing electronics, by conventional means (via metal conductors), may ultimately limit the performance of the system. Because it is highly impervious to EMI and ground loops, a fiber-optic medium has been chosen for the transmission of these signals. This paper describes several fiber-optic transmission schemes which satisfy the requirements of the SLD analog data transmission

  12. Analog data transmission via fiber optics

    International Nuclear Information System (INIS)

    Cisneros, E.L.; Burgueno, G.F.

    1987-01-01

    In the SLAC Linear Collider Detector (SLD), as in most high-energy particle detectors, the electromagnetic noise environment is the limiting factor in electronic readout performance. Front-end electronics are particularly susceptible to electromagnetic interference (EMI), and great care has been taken to minimize its effects. The transfer of preprocessed analog signals from the detector environs, to the remote digital processing electronics, by conventional means (via metal conductors), may ultimately limit the performance of the system. Because it is highly impervious to EMI and ground loops, a fiber-optic medium has been chosen for the transmission of these signals. This paper describes several fiber-optic transmission schemes which satisfy the requirements of the SLD analog data transmission

  13. An analogy strategy for transformation optics

    International Nuclear Information System (INIS)

    Yao, Kan; Liu, Yongmin; Chen, Huanyang; Jiang, Xunya

    2014-01-01

    We introduce an analogy strategy to design transformation optical devices. Based on the similarities between field lines in different physical systems, the trajectories of light can be intuitively determined to curve in a gentle manner, and the resulting materials are isotropic and nonmagnetic. Furthermore, the physical meaning of the analogue problems plays a key role in the removal of dielectric singularities. We illustrate this approach by creating two designs of carpet cloak and a collimating lens as representative examples in two- and three-dimensional spaces, respectively. The analogy strategy not only reveals the intimate connections between different physical disciplines, such as optics, fluid mechanics and electrostatics, but also provides a heuristic pathway to designing advanced photonic systems

  14. The optical analogy for vector fields

    Science.gov (United States)

    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.

  15. High resolution tomography using analog coding

    International Nuclear Information System (INIS)

    Brownell, G.L.; Burnham, C.A.; Chesler, D.A.

    1985-01-01

    As part of a 30-year program in the development of positron instrumentation, the authors have developed a high resolution bismuth germanate (BGO) ring tomography (PCR) employing 360 detectors and 90 photomultiplier tubes for one plane. The detectors are shaped as trapezoid and are 4 mm wide at the front end. When assembled, they form an essentially continuous cylindrical detector. Light from a scintillation in the detector is viewed through a cylindrical light pipe by the photomultiplier tubes. By use of an analog coding scheme, the detector emitting light is identified from the phototube signals. In effect, each phototube can identify four crystals. PCR is designed as a static device and does not use interpolative motion. This results in considerable advantage when performing dynamic studies. PCR is the positron tomography analog of the γ-camera widely used in nuclear medicine

  16. Analog fault diagnosis by inverse problem technique

    KAUST Repository

    Ahmed, Rania F.

    2011-12-01

    A novel algorithm for detecting soft faults in linear analog circuits based on the inverse problem concept is proposed. The proposed approach utilizes optimization techniques with the aid of sensitivity analysis. The main contribution of this work is to apply the inverse problem technique to estimate the actual parameter values of the tested circuit and so, to detect and diagnose single fault in analog circuits. The validation of the algorithm is illustrated through applying it to Sallen-Key second order band pass filter and the results show that the detecting percentage efficiency was 100% and also, the maximum error percentage of estimating the parameter values is 0.7%. This technique can be applied to any other linear circuit and it also can be extended to be applied to non-linear circuits. © 2011 IEEE.

  17. Optimal neural computations require analog processors

    Energy Technology Data Exchange (ETDEWEB)

    Beiu, V.

    1998-12-31

    This paper discusses some of the limitations of hardware implementations of neural networks. The authors start by presenting neural structures and their biological inspirations, while mentioning the simplifications leading to artificial neural networks. Further, the focus will be on hardware imposed constraints. They will present recent results for three different alternatives of parallel implementations of neural networks: digital circuits, threshold gate circuits, and analog circuits. The area and the delay will be related to the neurons` fan-in and to the precision of their synaptic weights. The main conclusion is that hardware-efficient solutions require analog computations, and suggests the following two alternatives: (i) cope with the limitations imposed by silicon, by speeding up the computation of the elementary silicon neurons; (2) investigate solutions which would allow the use of the third dimension (e.g. using optical interconnections).

  18. Ligand-induced internalization of neurotensin in transfected COS-7 cells: differential intracellular trafficking of ligand and receptor.

    Science.gov (United States)

    Vandenbulcke, F; Nouel, D; Vincent, J P; Mazella, J; Beaudet, A

    2000-09-01

    The neuropeptide neurotensin (NT) is known to be internalized in a receptor-mediated fashion into its target cells. To gain insight into the mechanisms underlying this process, we monitored in parallel the migration of the NT1 neurotensin receptor subtype and a fluorescent analog of NT (fluo-NT) in COS-7 cells transfected with a tagged NT1 construct. Fluo-NT internalization was prevented by hypertonic sucrose, potassium depletion and cytosol acidification, demonstrating that it proceeded via clathrin-coated pits. Within 0-30 minutes, fluo-NT accumulated together with its receptor in Acridine Orange-positive, acidic organelles. These organelles concentrated transferrin and immunostained positively for rab 5A, therefore they were early endosomes. After 30-45 minutes, the ligand and its receptor no longer colocalized. Fluo-NT was first found in rab 7-positive late endosomes and later in a nonacidic juxtanuclear compartment identified as the Trans-Golgi Network (TGN) by virtue of its staining for syntaxin 6. This juxtanuclear compartment also stained positively for rab 7 and for the TGN/pericentriolar recycling endosome marker rab 11, suggesting that the ligand could have been recruited to the TGN from either late or recycling endosomes. By that time, internalized receptors were detected in Lamp-1-immunoreactive lysosomes. These results demonstrate that neurotensin/NT1 receptor complexes follow a recycling cycle that is unique among the G protein-coupled receptors studied to date, and provide the first evidence for the targeting of a nonendogenous protein from endosomes to the TGN.

  19. An introduction to analog and digital communications

    CERN Document Server

    Haykin, Simon

    2012-01-01

    The second edition of this accessible book provides readers with an introductory treatment of communication theory as applied to the transmission of information-bearing signals. While it covers analog communications, the emphasis is placed on digital technology. It begins by presenting the functional blocks that constitute the transmitter and receiver of a communication system. Readers will next learn about electrical noise and then progress to multiplexing and multiple access techniques.

  20. Pyrrolidine nucleotide analogs with a tunable conformation

    Czech Academy of Sciences Publication Activity Database

    Poštová Slavětínská, Lenka; Rejman, Dominik; Pohl, Radek

    2014-01-01

    Roč. 10, Aug 22 (2014), s. 1967-1980 ISSN 1860-5397 R&D Projects: GA ČR GA13-24880S Institutional support: RVO:61388963 Keywords : conformation * NMR * nucleic acids * nucleotide analog * phosphonic acid * pseudorotation * pyrrolidine Subject RIV: CC - Organic Chemistry Impact factor: 2.762, year: 2014 http://www.beilstein-journals.org/bjoc/single/articleFullText.htm?publicId=1860-5397-10-205

  1. Combined analog-to-digital converter

    International Nuclear Information System (INIS)

    Zhukov, A.V.; Rzhendinskaya, S.N.

    1983-01-01

    A 10-bit analog-to-digital converter (ADC) designed for operating in spectrometers with time-dependent filters is described. The ADC operation is based on combining the parallel reading and sequential counting methods. At maximum conversion time of 12 μs, timing series frequency of 25 MHz and foUr reference levels the differential nonlinearity withoUt statistical smoothing (maximum relative channel width deviation from average value) is not more than 4%

  2. Performance of MSGC with analog pipeline readout

    International Nuclear Information System (INIS)

    Gomez, F.; Adeva, B.; Gracia, G.; Lopez, M.A.; Nunez, T.; Pazos, A.; Plo, M.; Rodriguez, A.; Santamarina, C.; Vazquez, P.

    1997-01-01

    We analyse some of the performance characteristics of a chromium MSGC operated with Ar-DME 50%-50% in a test beam at CERN. Excellent signal-to-noise ratio and efficiency has been achieved with this gas mixture using cathode analog pipeline readout. We also determine optimal parameters for the sampling algorithm in order to work in a random trigger experiment (fixed target). (orig.)

  3. Biomedical sensor design using analog compressed sensing

    Science.gov (United States)

    Balouchestani, Mohammadreza; Krishnan, Sridhar

    2015-05-01

    The main drawback of current healthcare systems is the location-specific nature of the system due to the use of fixed/wired biomedical sensors. Since biomedical sensors are usually driven by a battery, power consumption is the most important factor determining the life of a biomedical sensor. They are also restricted by size, cost, and transmission capacity. Therefore, it is important to reduce the load of sampling by merging the sampling and compression steps to reduce the storage usage, transmission times, and power consumption in order to expand the current healthcare systems to Wireless Healthcare Systems (WHSs). In this work, we present an implementation of a low-power biomedical sensor using analog Compressed Sensing (CS) framework for sparse biomedical signals that addresses both the energy and telemetry bandwidth constraints of wearable and wireless Body-Area Networks (BANs). This architecture enables continuous data acquisition and compression of biomedical signals that are suitable for a variety of diagnostic and treatment purposes. At the transmitter side, an analog-CS framework is applied at the sensing step before Analog to Digital Converter (ADC) in order to generate the compressed version of the input analog bio-signal. At the receiver side, a reconstruction algorithm based on Restricted Isometry Property (RIP) condition is applied in order to reconstruct the original bio-signals form the compressed bio-signals with high probability and enough accuracy. We examine the proposed algorithm with healthy and neuropathy surface Electromyography (sEMG) signals. The proposed algorithm achieves a good level for Average Recognition Rate (ARR) at 93% and reconstruction accuracy at 98.9%. In addition, The proposed architecture reduces total computation time from 32 to 11.5 seconds at sampling-rate=29 % of Nyquist rate, Percentage Residual Difference (PRD)=26 %, Root Mean Squared Error (RMSE)=3 %.

  4. Biophysical and lipofection studies of DOTAP analogs.

    Science.gov (United States)

    Regelin, A E; Fankhaenel, S; Gürtesch, L; Prinz, C; von Kiedrowski, G; Massing, U

    2000-03-15

    In order to investigate the relationship between lipid structure and liposome-mediated gene transfer, we have studied biophysical parameters and transfection properties of monocationic DOTAP analogs, systematically modified in their non-polar hydrocarbon chains. Stability, size and (by means of anisotropy profiles) membrane fluidity of liposomes and lipoplexes were determined, and lipofection efficiency was tested in a luciferase reporter gene assay. DOTAP analogs were used as single components or combined with a helper lipid, either DOPE or cholesterol. Stability of liposomes was a precondition for formation of temporarily stable lipoplexes. Addition of DOPE or cholesterol improved liposome and lipoplex stability. Transfection efficiencies of lipoplexes based on pure DOTAP analogs could be correlated with stability data and membrane fluidity at transfection temperature. Inclusion of DOPE led to rather uniform transfection and anisotropy profiles, corresponding to lipoplex stability. Cholesterol-containing lipoplexes were generally stable, showing high transfection efficiency at low relative fluidity. Our results demonstrate that the efficiency of gene transfer mediated by monocationic lipids is greatly influenced by lipoplex biophysics due to lipid composition. The measurement of fluorescence anisotropy is an appropriate method to characterize membrane fluidity within a defined system of liposomes or lipoplexes and may be helpful to elucidate structure-activity relationships.

  5. Targeting thyroid diseases with TSH receptor analogs.

    Science.gov (United States)

    Galofré, Juan C; Chacón, Ana M; Latif, Rauf

    2013-12-01

    The thyroid-stimulating hormone (TSH) receptor (TSHR) is a major regulator of thyroid function and growth, and is the key antigen in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various effective treatment strategies are currently available for many of these clinical conditions such as antithyroid drugs or radioiodine therapy, but they are not devoid of side effects. In addition, treatment of complications of Graves' disease such as Graves' ophthalmopathy is often difficult and unsatisfactory using current methods. Recent advances in basic research on both in vitro and in vivo models have suggested that TSH analogs could be used for diagnosis and treatment of some of the thyroid diseases. The advent of high-throughput screening methods has resulted in a group of TSH analogs called small molecules, which have the potential to be developed as promising drugs. Small molecules are low molecular weight compounds with agonist, antagonist and, in some cases, inverse agonist activity on TSHR. This short review will focus on current advances in development of TSH analogs and their potential clinical applications. Rapid advances in this field may lead to the conduct of clinical trials of small molecules related to TSHR for the management of Graves' disease, thyroid cancer, and thyroid-related osteoporosis in the coming years. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  6. Synthetic analog computation in living cells.

    Science.gov (United States)

    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.

  7. Theory of analogous force on number sets

    Energy Technology Data Exchange (ETDEWEB)

    Canessa, Enrique [Abdus Salam International Centre for Theoretical Physics, Trieste (Italy)

    2003-08-01

    A general statistical thermodynamic theory that considers given sequences of x-integers to play the role of particles of known type in an isolated elastic system is proposed. By also considering some explicit discrete probability distributions p{sub x} for natural numbers, we claim that they lead to a better understanding of probabilistic laws associated with number theory. Sequences of numbers are treated as the size measure of finite sets. By considering p{sub x} to describe complex phenomena, the theory leads to derive a distinct analogous force f{sub x} on number sets proportional to ({partial_derivative}p{sub x}/{partial_derivative}x){sub T} at an analogous system temperature T. In particular, this yields to an understanding of the uneven distribution of integers of random sets in terms of analogous scale invariance and a screened inverse square force acting on the significant digits. The theory also allows to establish recursion relations to predict sequences of Fibonacci numbers and to give an answer to the interesting theoretical question of the appearance of the Benford's law in Fibonacci numbers. A possible relevance to prime numbers is also analyzed. (author)

  8. Periglacial and glacial analogs for Martian landforms

    Science.gov (United States)

    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.

  9. Sensing Methods for Detecting Analog Television Signals

    Science.gov (United States)

    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.

  10. Synthesis and characterization of mixed ligand chiral nanoclusters

    KAUST Repository

    Guven, Zekiye P.

    2016-06-22

    Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

  11. Synthesis and characterization of mixed ligand chiral nanoclusters

    KAUST Repository

    Guven, Zekiye P.; Ustbas, Burcin; Harkness, Kellen M.; Coskun, Hikmet; Joshi, Chakra Prasad; Besong, Tabot M.D.; Stellacci, Francesco; Bakr, Osman; Akbulut, Ozge

    2016-01-01

    Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

  12. Creative Analogy Use in a Heterogeneous Design Team

    DEFF Research Database (Denmark)

    Christensen, Bo; Ball, Linden J.

    2016-01-01

    the design dialogue derived from team members with highly disparate educational backgrounds. Our analyses revealed that analogies that matched (versus mismatched) educational backgrounds were generated and revisited more frequently, presumably because they were more accessible. Matching analogies were also...

  13. Scientific Analogies and Their Use in Teaching Science

    Science.gov (United States)

    Kipnis, Nahum

    Analogy in science knew its successes and failures, as illustrated by examples from the eighteenth-century physics. At times, some scientists abstained from using a certain analogy on the ground that it had not yet been demonstrated. Several false discoveries in the 18th and early 19th centuries appeared to support their caution. It is now clear that such a position reflected a methodological confusion that resulted from a failure to distinguish between particular and general analogies. Considering analogy as a hierarchical structure provides a new insight into "testing an analogy". While warning science teachers of dangers associated with use of analogy, historical cases and their analysis provided here may encourage them to use analogy more extensively while avoiding misconceptions. An argument is made that the history of science may be a better guide than philosophy of science and cognitive psychology when it concerns the role of analogy in science and in teaching science for understanding.

  14. Impact of protein and ligand impurities on ITC-derived protein-ligand thermodynamics.

    Science.gov (United States)

    Grüner, Stefan; Neeb, Manuel; Barandun, Luzi Jakob; Sielaff, Frank; Hohn, Christoph; Kojima, Shun; Steinmetzer, Torsten; Diederich, François; Klebe, Gerhard

    2014-09-01

    The thermodynamic characterization of protein-ligand interactions by isothermal titration calorimetry (ITC) is a powerful tool in drug design, giving valuable insight into the interaction driving forces. ITC is thought to require protein and ligand solutions of high quality, meaning both the absence of contaminants as well as accurately determined concentrations. Ligands synthesized to deviating purity and protein of different pureness were titrated by ITC. Data curation was attempted also considering information from analytical techniques to correct stoichiometry. We used trypsin and tRNA-guanine transglycosylase (TGT), together with high affinity ligands to investigate the effect of errors in protein concentration as well as the impact of ligand impurities on the apparent thermodynamics. We found that errors in protein concentration did not change the thermodynamic properties obtained significantly. However, most ligand impurities led to pronounced changes in binding enthalpy. If protein binding of the respective impurity is not expected, the actual ligand concentration was corrected for and the thus revised data compared to thermodynamic properties obtained with the respective pure ligand. Even in these cases, we observed differences in binding enthalpy of about 4kJ⋅mol(-1), which is considered significant. Our results indicate that ligand purity is the critical parameter to monitor if accurate thermodynamic data of a protein-ligand complex are to be recorded. Furthermore, artificially changing fitting parameters to obtain a sound interaction stoichiometry in the presence of uncharacterized ligand impurities may lead to thermodynamic parameters significantly deviating from the accurate thermodynamic signature. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Novel Chemical Strategies for Labeling Small Molecule Ligands for Androgen, Progestin, and Peroxisome Proliferator-Activated Receptors for Imaging Prostate and Breast Cancer and the Heart

    International Nuclear Information System (INIS)

    Katzenellenbogen, John A.

    2007-01-01

    Summary of Progress The specific aims of this project can be summarized as follows: Aim 1: Prepare and evaluate radiolabeled ligands for the peroxisome proliferator-activated receptor γ (PPARγ), a new nuclear hormone receptor target for tumor imaging and hormone therapy. Aim 2: Prepare steroids labeled with a cyclopentadienyl tricarbonyl technetium or rhenium unit. Aim 3: Prepare and evaluate other organometallic systems of novel design as ligand mimics and halogenated ligands for nuclear hormone receptor-based tumor imaging. As is described in detail in the report, we made excellent progress on all three of these aims; the highlights of our progress are the following: (1) we have prepared the first fluorine-18 labeled analogs of ligands for the PPARγ receptor and used these in tissue distribution studies in rats; (2) we have developed three new methods for the synthesis of cyclopentadienyltricarbonyl rhenium and technetium (CpRe(CO)3 and CpTc(CO)3) systems and we have adapted these to the synthesis of steroids labeled with these metals, as well as ligands for other receptor systems; (3) we have prepared a number of fluorine-18 labeled steroidal and non-steroidal androgens and measured their tissue distribution in rats; (4) we have prepared iodine and bromine-labeled progestins with high progesterone receptor binding affinity; and (5) we have prepared inorganic metal tricarbonyl complexes and steroid receptor ligands in which the metal tricarbonyl unit is an integral part off the ligand core

  16. Expression of nociceptive ligands in canine osteosarcoma.

    Science.gov (United States)

    Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

    2015-01-01

    Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  17. When Reasoning Modifies Memory: Schematic Assimilation Triggered by Analogical Mapping

    Science.gov (United States)

    Vendetti, Michael S.; Wu, Aaron; Rowshanshad, Ebi; Knowlton, Barbara J.; Holyoak, Keith J.

    2014-01-01

    Analogical mapping highlights shared relations that link 2 situations, potentially at the expense of information that does not fit the dominant pattern of correspondences. To investigate whether analogical mapping can alter subsequent recognition memory for features of a source analog, we performed 2 experiments with 4-term proportional analogies…

  18. Analogies in Medicine: Valuable for Learning, Reasoning, Remembering and Naming

    Science.gov (United States)

    Pena, Gil Patrus; Andrade-Filho, Jose de Souza

    2010-01-01

    Analogies are important tools in human reasoning and learning, for resolving problems and providing arguments, and are extensively used in medicine. Analogy and similarity involve a structural alignment or mapping between domains. This cognitive mechanism can be used to make inferences and learn new abstractions. Through analogies, we try to…

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

    Science.gov (United States)

    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…

  20. The design analogy : a model for moral problem solving

    NARCIS (Netherlands)

    Dorst, C.H.; Royakkers, L.M.M.

    2006-01-01

    In this paper we explore an analogy between design and ethics, first drawn by Whitbeck. We investigate her claim that such an analogy can help to understand moral problems and aid us in dealing with them by suggesting strategies for addressing moral problems. We explore the nature of analogies, and

  1. Functional DNA: Teaching Infinite Series through Genetic Analogy

    Science.gov (United States)

    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…

  2. Circuit with a successive approximation analog to digital converter

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2011-01-01

    During successive approximation analog to digital conversion a series of successive digital reference values is selected that converges towards a digital representation of an analog input signal. An analog reference signal is generated dependent on the successive digital reference values and

  3. Circuit with a successive approximation analog to digital converter

    NARCIS (Netherlands)

    Louwsma, S.M.; Vertregt, Maarten

    2010-01-01

    During successive approximation analog to digital conversion a series of successive digital reference values is selected that converges towards a digital representation of an analog input signal. An analog reference signal is generated dependent on the successive digital reference values and

  4. Immobilisation of ligands by radio-derivatized polymers; Immobilisering av ligander med radioderiverte polymerer

    Energy Technology Data Exchange (ETDEWEB)

    Varga, J.M.; Fritsch, P.

    1995-01-30

    The invention relates to radio-derivatized polymers and a method of producing them by contacting non-polymerizable conjugands with radiolysable polymers in the presence of irradiation. The resulting radio-derivatized polymers can be further linked with ligand of organic or inorganic nature to immobilize such ligands. 2 figs., 5 tabs.

  5. Quantum probability ranking principle for ligand-based virtual screening

    Science.gov (United States)

    Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

    2017-04-01

    Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

  6. Quantum probability ranking principle for ligand-based virtual screening.

    Science.gov (United States)

    Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

    2017-04-01

    Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

  7. A General Ligand Design for Gold Catalysis allowing Ligand-Directed Anti Nucleophilic Attack of Alkynes

    Science.gov (United States)

    Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

    2014-01-01

    Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding. PMID:24704803

  8. A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

    KAUST Repository

    Li, Huaifeng

    2014-12-01

    Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands\\' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

  9. A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

    KAUST Repository

    Li, Huaifeng; Zheng, Bin; Huang, Kuo-Wei

    2014-01-01

    Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

  10. Effects of PPARγ ligands on vascular tone.

    Science.gov (United States)

    Salomone, Salvatore; Drago, Filippo

    2012-06-01

    Peroxisome Proliferator-Activated Receptor γ (PPARγ), originally described as a transcription factor for genes of carbohydrate and lipid metabolism, has been more recently studied in the context of cardiovascular pathophysiology. Here, we review the available data on PPARγ ligands as modulator of vascular tone. PPARγ ligands include: thiazolidinediones (used in the treatment of type 2 diabetes mellitus), glitazars (bind and activate both PPARγ and PPARα), and other experimental drugs (still in development) that exploit the chemistry of thiazolidinediones as a scaffold for PPARγ-independent pharmacological properties. In this review, we examine both short (mostly from in vitro data)- and long (mostly from in vivo data)-term effects of PPARγ ligands that extend from PPARγ-independent vascular effects to PPARγ-dependent gene expression. Because endothelium is a master regulator of vascular tone, we have attempted to differentiate between endothelium-dependent and endothelium-independent effects of PPARγ ligands. Based on available data, we conclude that PPARγ ligands appear to influence vascular tone in different experimental paradigms, most often in terms of vasodilatation (potentially increasing blood flow to some tissues). These effects on vascular tone, although potentially beneficial, must be weighed against specific cardiovascular warnings that may apply to some drugs, such as rosiglitazone.

  11. LIBRA: LIgand Binding site Recognition Application.

    Science.gov (United States)

    Hung, Le Viet; Caprari, Silvia; Bizai, Massimiliano; Toti, Daniele; Polticelli, Fabio

    2015-12-15

    In recent years, structural genomics and ab initio molecular modeling activities are leading to the availability of a large number of structural models of proteins whose biochemical function is not known. The aim of this study was the development of a novel software tool that, given a protein's structural model, predicts the presence and identity of active sites and/or ligand binding sites. The algorithm implemented by ligand binding site recognition application (LIBRA) is based on a graph theory approach to find the largest subset of similar residues between an input protein and a collection of known functional sites. The algorithm makes use of two predefined databases for active sites and ligand binding sites, respectively, derived from the Catalytic Site Atlas and the Protein Data Bank. Tests indicate that LIBRA is able to identify the correct binding/active site in 90% of the cases analyzed, 90% of which feature the identified site as ranking first. As far as ligand binding site recognition is concerned, LIBRA outperforms other structure-based ligand binding sites detection tools with which it has been compared. The application, developed in Java SE 7 with a Swing GUI embedding a JMol applet, can be run on any OS equipped with a suitable Java Virtual Machine (JVM), and is available at the following URL: http://www.computationalbiology.it/software/LIBRAv1.zip. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Dockomatic - automated ligand creation and docking.

    Science.gov (United States)

    Bullock, Casey W; Jacob, Reed B; McDougal, Owen M; Hampikian, Greg; Andersen, Tim

    2010-11-08

    The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI) application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

  13. Dockomatic - automated ligand creation and docking

    Directory of Open Access Journals (Sweden)

    Hampikian Greg

    2010-11-01

    Full Text Available Abstract Background The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. Results DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. Conclusions DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

  14. SSERVI Analog Regolith Simulant Testbed Facility

    Science.gov (United States)

    Minafra, Joseph; Schmidt, Gregory; Bailey, Brad; Gibbs, Kristina

    2016-10-01

    The Solar System Exploration Research Virtual Institute (SSERVI) at NASA's Ames Research Center in California's Silicon Valley was founded in 2013 to act as a virtual institute that provides interdisciplinary research centered on the goals of its supporting directorates: NASA Science Mission Directorate (SMD) and the Human Exploration & Operations Mission Directorate (HEOMD).Primary research goals of the Institute revolve around the integration of science and exploration to gain knowledge required for the future of human space exploration beyond low Earth orbit. SSERVI intends to leverage existing JSC1A regolith simulant resources into the creation of a regolith simulant testbed facility. The purpose of this testbed concept is to provide the planetary exploration community with a readily available capability to test hardware and conduct research in a large simulant environment.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.SSERVI 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, including dust mitigation and safety oversight.Facility hardware and environment testing scenarios could include, 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, Surface features (i.e. grades and rocks)Numerous benefits vary from easy access to a controlled analog regolith simulant testbed, and

  15. Ligand identification using electron-density map correlations

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

    2007-01-01

    An automated ligand-fitting procedure is applied to (F o − F c )exp(iϕ c ) difference density for 200 commonly found ligands from macromolecular structures in the Protein Data Bank to identify ligands from density maps. A procedure for the identification of ligands bound in crystal structures of macromolecules is described. Two characteristics of the density corresponding to a ligand are used in the identification procedure. One is the correlation of the ligand density with each of a set of test ligands after optimization of the fit of that ligand to the density. The other is the correlation of a fingerprint of the density with the fingerprint of model density for each possible ligand. The fingerprints consist of an ordered list of correlations of each the test ligands with the density. The two characteristics are scored using a Z-score approach in which the correlations are normalized to the mean and standard deviation of correlations found for a variety of mismatched ligand-density pairs, so that the Z scores are related to the probability of observing a particular value of the correlation by chance. The procedure was tested with a set of 200 of the most commonly found ligands in the Protein Data Bank, collectively representing 57% of all ligands in the Protein Data Bank. Using a combination of these two characteristics of ligand density, ranked lists of ligand identifications were made for representative (F o − F c )exp(iϕ c ) difference density from entries in the Protein Data Bank. In 48% of the 200 cases, the correct ligand was at the top of the ranked list of ligands. This approach may be useful in identification of unknown ligands in new macromolecular structures as well as in the identification of which ligands in a mixture have bound to a macromolecule

  16. Towards PSII analogs driven by ruthenium photophysics

    International Nuclear Information System (INIS)

    Olsson, Jerry

    2002-01-01

    A number of model complexes have been prepared in an attempt to develop models for photosystem II (PSII) in green plants. As replacement for the chlorophyll photosensitizer, we have used Ru(ll) tris-2,2-bipyridyl or Ru(ll) bis-2,2';6',2 - terpyridyl complexes linked to a pendant 2,2'-bipyridyl or 2,2';6',2''-terpyridyl moieties via spacers of varying lengths. Manganese (ll) has been covalently linked to the pendant 2,2'-bipyridyl /2,2';6',2''-terpyridyl moieties. The use of different ruthenium centres and spacers has made it possible to make assumptions about the way and how easily manganese is coordinated through self-assembly to the pendant 2,2'-bipyridyl or 2,2';6',2''-terpyridyl groups. Several polynuclear complexes containing a photoactive centre (Ru(ll) tris-2,2'-bipyridine or Ru(ll) bis-2,2';6',2''-terpyridine) or other metal ions (Co 2+ , Fe 2+ , Mn 2= ) have been prepared and characterised. The main work has been focused on organic synthesis and characterisation of polypyridine ligands and coordinated to different metal centres. The complexes have been investigated electrochemically and photophysically. Several new phenol-based ligands have been prepared by organic synthetic methods and characterised by various different methods. (author)

  17. Image magnification based on similarity analogy

    International Nuclear Information System (INIS)

    Chen Zuoping; Ye Zhenglin; Wang Shuxun; Peng Guohua

    2009-01-01

    Aiming at the high time complexity of the decoding phase in the traditional image enlargement methods based on fractal coding, a novel image magnification algorithm is proposed in this paper, which has the advantage of iteration-free decoding, by using the similarity analogy between an image and its zoom-out and zoom-in. A new pixel selection technique is also presented to further improve the performance of the proposed method. Furthermore, by combining some existing fractal zooming techniques, an efficient image magnification algorithm is obtained, which can provides the image quality as good as the state of the art while greatly decrease the time complexity of the decoding phase.

  18. Probleme bei der Digitalisierung analoger Messwerte

    Science.gov (United States)

    Plaßmann, Wilfried

    Messwerte liegen häufig in analoger Form als Spannungswerte vor. Sie werden in eine digital kodierte Form umgesetzt, wenn eine (nahezu) fehlerfreie Übertragung erforderlich ist, wenn Signalverläufe gespeichert werden sollen, wenn eine Weiterverarbeitung erfolgen soll oder wenn Messungen mit sehr geringem Messfehler notwendig sind. Hier soll auf einige Probleme, die durch die Umsetzung entstehen, aus messtechnischer Sicht eingegangen werden. Stichworte: Fehler bei der Digitalisierung; Signal-Quantisierungsgeräusch-Abstand; Verbesserung des Signal-Rausch-Verhältnisses; Abtast-Halte-Glied; Aliasing; Erfassung von Momentanwerten.

  19. Bosonic analog of the Klein paradox

    International Nuclear Information System (INIS)

    Wagner, R. E.; Ware, M. R.; Su, Q.; Grobe, R.

    2010-01-01

    The standard Klein paradox describes how an incoming electron scatters off a supercritical electrostatic barrier that is so strong that it can generate electron-positron pairs. This fermionic system has been widely discussed in textbooks to illustrate some of the discrepancies between quantum mechanical and quantum field theoretical descriptions for the pair creation process. We compare the fermionic dynamics with that of the corresponding bosonic system. We point out that the direct counterpart of the Pauli exclusion principle (the central mechanism to resolve the fermionic Klein paradox) is stimulated emission, which leads to the resolution of the analogous bosonic paradox.

  20. Novel Gemini vitamin D3 analogs

    DEFF Research Database (Denmark)

    Okamoto, Ryoko; Gery, Sigal; Kuwayama, Yoshio

    2014-01-01

    anticancer potency, but similar toxicity causing hypercalcemia. We focused on the effect of these compounds on the stimulation of expression of human cathelicidin antimicrobial peptide (CAMP) whose gene has a vitamin D response element in its promoter. Expression of CAMP mRNA and protein increased in a dose......-response fashion after exposure of acute myeloid leukemia (AML) cells to the Gemini analog, BXL-01-126, in vitro. A xenograft model of AML was developed using U937 AML cells injected into NSG-immunodeficient mice. Administration of vitamin D3 compounds to these mice resulted in substantial levels of CAMP...

  1. Development of analog watch with minute repeater

    Science.gov (United States)

    Okigami, Tomio; Aoyama, Shigeru; Osa, Takashi; Igarashi, Kiyotaka; Ikegami, Tomomi

    A complementary metal oxide semiconductor with large scale integration was developed for an electronic minute repeater. It is equipped with the synthetic struck sound circuit to generate natural struck sound necessary for the minute repeater. This circuit consists of an envelope curve drawing circuit, frequency mixer, polyphonic mixer, and booster circuit made by using analog circuit technology. This large scale integration is a single chip microcomputer with motor drivers and input ports in addition to the synthetic struck sound circuit, and it is possible to make an electronic system of minute repeater at a very low cost in comparison with the conventional type.

  2. Analog to digital conversion for nuclear spectrometry

    International Nuclear Information System (INIS)

    Carvalho, P.V.R. de.

    1982-04-01

    A study of the analog to digital conversion techniques for nuclear spectrometry is presented and the main design philosophies of nuclear ADC's are compared. Among them, the most suitable for the current Brazilian conditions, concerning the specifications and components avaiability is the one that employs a statistical correction of successive approximation converters. This technique is described in full detail. A prototype has been developed an tested for the practical demonstration of the theoretical conclusions. These tests was carried on nuclear spectrometry data aquisition system whose implementation is also described. (Author) [pt

  3. Ligand sphere conversions in terminal carbide complexes

    DEFF Research Database (Denmark)

    Morsing, Thorbjørn Juul; Reinholdt, Anders; Sauer, Stephan P. A.

    2016-01-01

    Metathesis is introduced as a preparative route to terminal carbide complexes. The chloride ligands of the terminal carbide complex [RuC(Cl)2(PCy3)2] (RuC) can be exchanged, paving the way for a systematic variation of the ligand sphere. A series of substituted complexes, including the first...... example of a cationic terminal carbide complex, [RuC(Cl)(CH3CN)(PCy3)2]+, is described and characterized by NMR, MS, X-ray crystallography, and computational studies. The experimentally observed irregular variation of the carbide 13C chemical shift is shown to be accurately reproduced by DFT, which also...... demonstrates that details of the coordination geometry affect the carbide chemical shift equally as much as variations in the nature of the auxiliary ligands. Furthermore, the kinetics of formation of the sqaure pyramidal dicyano complex, trans-[RuC(CN)2(PCy3)2], from RuC has been examined and the reaction...

  4. Characteristic molecular vibrations of adenosine receptor ligands.

    Science.gov (United States)

    Chee, Hyun Keun; Yang, Jin-San; Joung, Je-Gun; Zhang, Byoung-Tak; Oh, S June

    2015-02-13

    Although the regulation of membrane receptor activation is known to be crucial for molecular signal transduction, the molecular mechanism underlying receptor activation is not fully elucidated. Here we study the physicochemical nature of membrane receptor behavior by investigating the characteristic molecular vibrations of receptor ligands using computational chemistry and informatics methods. By using information gain, t-tests, and support vector machines, we have identified highly informative features of adenosine receptor (AdoR) ligand and corresponding functional amino acid residues such as Asn (6.55) of AdoR that has informative significance and is indispensable for ligand recognition of AdoRs. These findings may provide new perspectives and insights into the fundamental mechanism of class A G protein-coupled receptor activation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  5. A bilateral frontoparietal network underlies visuospatial analogical reasoning.

    Science.gov (United States)

    Watson, Christine E; Chatterjee, Anjan

    2012-02-01

    Our ability to reason by analogy facilitates problem solving and allows us to communicate ideas efficiently. In this study, we examined the neural correlates of analogical reasoning and, more specifically, the contribution of rostrolateral prefrontal cortex (RLPFC) to reasoning. This area of the brain has been hypothesized to integrate relational information, as in analogy, or the outcomes of subgoals, as in multi-tasking and complex problem solving. Using fMRI, we compared visuospatial analogical reasoning to a control task that was as complex and difficult as the analogies and required the coordination of subgoals but not the integration of relations. We found that analogical reasoning more strongly activated bilateral RLPFC, suggesting that anterior prefrontal cortex is preferentially recruited by the integration of relational knowledge. Consistent with the need for inhibition during analogy, bilateral, and particularly right, inferior frontal gyri were also more active during analogy. Finally, greater activity in bilateral inferior parietal cortex during the analogy task is consistent with recent evidence for the neural basis of spatial relation knowledge. Together, these findings indicate that a network of frontoparietal areas underlies analogical reasoning; we also suggest that hemispheric differences may emerge depending on the visuospatial or verbal/semantic nature of the analogies. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  7. Docking Simulation of the Binding Interactions of Saxitoxin Analogs Produced by the Marine Dinoflagellate Gymnodinium catenatum to the Voltage-Gated Sodium Channel Nav1.4

    Directory of Open Access Journals (Sweden)

    Lorena M. Durán-Riveroll

    2016-05-01

    Full Text Available Saxitoxin (STX and its analogs are paralytic alkaloid neurotoxins that block the voltage-gated sodium channel pore (Nav, impeding passage of Na+ ions into the intracellular space, and thereby preventing the action potential in the peripheral nervous system and skeletal muscle. The marine dinoflagellate Gymnodinium catenatum produces an array of such toxins, including the recently discovered benzoyl analogs, for which the mammalian toxicities are essentially unknown. We subjected STX and its analogs to a theoretical docking simulation based upon two alternative tri-dimensional models of the Nav1.4 to find a relationship between the binding properties and the known mammalian toxicity of selected STX analogs. We inferred hypothetical toxicities for the benzoyl analogs from the modeled values. We demonstrate that these toxins exhibit different binding modes with similar free binding energies and that these alternative binding modes are equally probable. We propose that the principal binding that governs ligand recognition is mediated by electrostatic interactions. Our simulation constitutes the first in silico modeling study on benzoyl-type paralytic toxins and provides an approach towards a better understanding of the mode of action of STX and its analogs.

  8. Docking Simulation of the Binding Interactions of Saxitoxin Analogs Produced by the Marine Dinoflagellate Gymnodinium catenatum to the Voltage-Gated Sodium Channel Nav1.4.

    Science.gov (United States)

    Durán-Riveroll, Lorena M; Cembella, Allan D; Band-Schmidt, Christine J; Bustillos-Guzmán, José J; Correa-Basurto, José

    2016-05-06

    Saxitoxin (STX) and its analogs are paralytic alkaloid neurotoxins that block the voltage-gated sodium channel pore (Nav), impeding passage of Na⁺ ions into the intracellular space, and thereby preventing the action potential in the peripheral nervous system and skeletal muscle. The marine dinoflagellate Gymnodinium catenatum produces an array of such toxins, including the recently discovered benzoyl analogs, for which the mammalian toxicities are essentially unknown. We subjected STX and its analogs to a theoretical docking simulation based upon two alternative tri-dimensional models of the Nav1.4 to find a relationship between the binding properties and the known mammalian toxicity of selected STX analogs. We inferred hypothetical toxicities for the benzoyl analogs from the modeled values. We demonstrate that these toxins exhibit different binding modes with similar free binding energies and that these alternative binding modes are equally probable. We propose that the principal binding that governs ligand recognition is mediated by electrostatic interactions. Our simulation constitutes the first in silico modeling study on benzoyl-type paralytic toxins and provides an approach towards a better understanding of the mode of action of STX and its analogs.

  9. C-H functionalization: thoroughly tuning ligands at a metal ion, a chemist can greatly enhance catalyst's activity and selectivity.

    Science.gov (United States)

    Shul'pin, Georgiy B

    2013-09-28

    This brief essay consists of a few "exciting stories" devoted to relations within a metal-complex catalyst between a metal ion and a coordinated ligand. When, as in the case of a human couple, the rapport of the partners is cordial and a love cements these relations, a chemist finds an ideal married couple, in other words he obtains a catalyst of choice which allows him to functionalize C-H bonds very efficiently and selectively. Examples of such lucky marriages in the catalytic world of ions and ligands are discussed here. Activity of the catalyst is characterized by turnover number (TON) or turnover frequency (TOF) as well as by yield of a target product. Introducing a chelating N,N- or N,O-ligand to the catalyst molecule (this can be an iron or manganese derivative) sharply enhances its activity. However, the activity of vanadium derivatives (with additionally added to the solution pyrazinecarboxylic acid, PCA) as well as of various osmium complexes does not dramatically depend on the nature of ligands surrounding metal ions. Complexes of these metals are very efficient catalysts in oxidations with H2O2. Osmium derivatives are record-holders exhibiting extremely high TONs whereas vanadium complexes are on the second position. Finally, elegant examples of alkane functionalization on the ions of non-transition metals (aluminium, gallium etc.) are described when one ligand within the metal complex (namely, hydroperoxyl ligand HOO(-)) helps other ligand of this complex (H2O2 molecule coordinated to the metal) to disintegrate into two species, generating very reactive hydroxyl radical. Hydrogen peroxide molecule, even ligated to the metal ion, is perfectly stable without the assistance of the neighboring HOO(-) ligand. This ligand can be easily oxidized donating an electron to its partner ligand (H2O2). In an analogous case, when the central ion in the catalyst is a transition metal, this ion changing its oxidation state can donate an electron to the coordinated H2O2

  10. Searching for new aluminium chelating agents: a family of hydroxypyrone ligands.

    Science.gov (United States)

    Toso, Leonardo; Crisponi, Guido; Nurchi, Valeria M; Crespo-Alonso, Miriam; Lachowicz, Joanna I; Mansoori, Delara; Arca, Massimiliano; Santos, M Amélia; Marques, Sérgio M; Gano, Lurdes; Niclós-Gutíerrez, Juan; González-Pérez, Josefa M; Domínguez-Martín, Alicia; Choquesillo-Lazarte, Duane; Szewczuk, Zbigniew

    2014-01-01

    Attention is devoted to the role of chelating agents in the treatment of aluminium related diseases. In fact, in spite of the efforts that have drastically reduced the occurrence of aluminium dialysis diseases, they so far constitute a cause of great medical concern. The use of chelating agents for iron and aluminium in different clinical applications has found increasing attention in the last thirty years. With the aim of designing new chelators, we synthesized a series of kojic acid derivatives containing two kojic units joined by different linkers. A huge advantage of these molecules is that they are cheap and easy to produce. Previous works on complex formation equilibria of a first group of these ligands with iron and aluminium highlighted extremely good pMe values and gave evidence of the ability to scavenge iron from inside cells. On these bases a second set of bis-kojic ligands, whose linkers between the kojic chelating moieties are differentiated both in terms of type and size, has been designed, synthesized and characterized. The aluminium(III) complex formation equilibria studied by potentiometry, electrospray ionization mass spectroscopy (ESI-MS), quantum-mechanical calculations and (1)H NMR spectroscopy are here described and discussed, and the structural characterization of one of these new ligands is presented. The in vivo studies show that these new bis-kojic derivatives induce faster clearance from main organs as compared with the monomeric analog. © 2013.

  11. Energy transfer processes in Tb(III)-dibenzoylmethanate complexes with phosphine oxide ligands

    Energy Technology Data Exchange (ETDEWEB)

    Silva Junior, Francisco A.; Nascimento, Helenise A.; Pereira, Dariston K.S.; Teotonio, Ercules E.S.; Espinola, Jose Geraldo P.; Faustino, Wagner M., E-mail: teotonioees@quimica.ufpb.br [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Departamento de Quimica; Brito, Hermi F. [Universidade de Sao Paulo (USP), SP (Brazil). Instituto de Quimica. Departamento de Quimica Fundamental; Felinto, Maria Claudia F.C. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), SP (Brazil); Sa, Gilberto F. [Universidade Federal de Pernambuco (UFPE/CCEN), Recife, PE (Brazil). Centro de Ciencias Exatas e da Natureza. Departamento de Quimica Fundamental

    2013-04-15

    The Tb{sup 3+}-{beta}-diketonate complexes [Tb(DBM){sub 3}L], [Tb(DBM){sub 2}(NO{sub 3})L{sub 2}] and [Tb(DBM)(NO{sub 3}){sub 2} (HMPA){sub 2}] (DBM = dibenzoylmethanate; L: TPPO triphenylphosphine oxide or HMPA=hexamethylphosphine oxide) were prepared and characterized by elemental analysis (CHN), complexometric titration with EDTA and Fourier transform infrared (FTIR) spectroscopy, and the photoluminescence properties evaluated. The triplet state energies of the coordinated DBM ligands were determined using time-resolved phosphorescence spectra of analogous Gd{sup 3+} complexes. The results show that the energies increase along with the number of coordinated nitrate anions replacing the DBM ligand in the complexes. The luminescence spectra and emission lifetime measurements revealed that the ligand-to-metal energy transfer efficiency follows the same tendency. Unlike the tris-DBM complexes, bis- and mono-DBM presented high luminescence, and may act as promising candidates for preparation of the emitting layer of light converting molecular devices (LCMDs). (author)

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

    Science.gov (United States)

    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.

  13. Discrete stochastic analogs of Erlang epidemic models.

    Science.gov (United States)

    Getz, Wayne M; Dougherty, Eric R

    2018-12-01

    Erlang differential equation models of epidemic processes provide more realistic disease-class transition dynamics from susceptible (S) to exposed (E) to infectious (I) and removed (R) categories than the ubiquitous SEIR model. The latter is itself is at one end of the spectrum of Erlang SE[Formula: see text]I[Formula: see text]R models with [Formula: see text] concatenated E compartments and [Formula: see text] concatenated I compartments. Discrete-time models, however, are computationally much simpler to simulate and fit to epidemic outbreak data than continuous-time differential equations, and are also much more readily extended to include demographic and other types of stochasticity. Here we formulate discrete-time deterministic analogs of the Erlang models, and their stochastic extension, based on a time-to-go distributional principle. Depending on which distributions are used (e.g. discretized Erlang, Gamma, Beta, or Uniform distributions), we demonstrate that our formulation represents both a discretization of Erlang epidemic models and generalizations thereof. We consider the challenges of fitting SE[Formula: see text]I[Formula: see text]R models and our discrete-time analog to data (the recent outbreak of Ebola in Liberia). We demonstrate that the latter performs much better than the former; although confining fits to strict SEIR formulations reduces the numerical challenges, but sacrifices best-fit likelihood scores by at least 7%.

  14. Endpoint distinctiveness facilitates analogical mapping in pigeons.

    Science.gov (United States)

    Hagmann, Carl Erick; Cook, Robert G

    2015-03-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due to endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal mapping of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons' capacity for more advanced types of analogical reasoning. This article is part of a Special Issue entitled: Tribute to Tom Zentall. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Endpoint Distinctiveness Facilitates Analogical Mapping in Pigeons

    Science.gov (United States)

    Hagmann, Carl Erick; Cook, Robert G.

    2015-01-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, reassignment, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal map of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons’ capacity for more advanced types of analogical reasoning. PMID:25447511

  16. Merging Galaxy Clusters: Analysis of Simulated Analogs

    Science.gov (United States)

    Nguyen, Jayke; Wittman, David; Cornell, Hunter

    2018-01-01

    The nature of dark matter can be better constrained by observing merging galaxy clusters. However, uncertainty in the viewing angle leads to uncertainty in dynamical quantities such as 3-d velocities, 3-d separations, and time since pericenter. The classic timing argument links these quantities via equations of motion, but neglects effects of nonzero impact parameter (i.e. it assumes velocities are parallel to the separation vector), dynamical friction, substructure, and larger-scale environment. We present a new approach using n-body cosmological simulations that naturally incorporate these effects. By uniformly sampling viewing angles about simulated cluster analogs, we see projected merger parameters in the many possible configurations of a given cluster. We select comparable simulated analogs and evaluate the likelihood of particular merger parameters as a function of viewing angle. We present viewing angle constraints for a sample of observed mergers including the Bullet cluster and El Gordo, and show that the separation vectors are closer to the plane of the sky than previously reported.

  17. The gravitational analog of Faraday's induction law

    Science.gov (United States)

    Zile, Daniel; Overduin, James

    2015-04-01

    Michael Faraday, the discoverer of electromagnetic induction, was convinced that there must also be a gravitational analog of this law, and he carried out drop-tower experiments in 1849 to look for the electric current induced in a coil by changes in gravitational flux through the coil. This work, now little remembered, was in some ways the first investigation of what we would now call a unified-field theory. We revisit Faraday's experiments in the light of current knowledge and ask what might be learned if they were to be performed today. We then review the gravitational analog for Faraday's law that arises within the vector (or gravito-electromagnetic) approximation to Einstein's theory of general relativity in the weak-field, low-velocity limit. This law relates spinning masses and induced ``mass currents'' rather than spinning charges and electric currents, but is otherwise remarkably similar to its electromagnetic counterpart. The predicted effects are completely unobservable in everyday settings like those envisioned by Faraday, but are thought to be relevant in astrophysical contexts like the accretion disks around collapsed stars, thus bearing out Faraday's remarkable intuition. Undergraduate student.

  18. Strong Ligand-Protein Interactions Derived from Diffuse Ligand Interactions with Loose Binding Sites.

    Science.gov (United States)

    Marsh, Lorraine

    2015-01-01

    Many systems in biology rely on binding of ligands to target proteins in a single high-affinity conformation with a favorable ΔG. Alternatively, interactions of ligands with protein regions that allow diffuse binding, distributed over multiple sites and conformations, can exhibit favorable ΔG because of their higher entropy. Diffuse binding may be biologically important for multidrug transporters and carrier proteins. A fine-grained computational method for numerical integration of total binding ΔG arising from diffuse regional interaction of a ligand in multiple conformations using a Markov Chain Monte Carlo (MCMC) approach is presented. This method yields a metric that quantifies the influence on overall ligand affinity of ligand binding to multiple, distinct sites within a protein binding region. This metric is essentially a measure of dispersion in equilibrium ligand binding and depends on both the number of potential sites of interaction and the distribution of their individual predicted affinities. Analysis of test cases indicates that, for some ligand/protein pairs involving transporters and carrier proteins, diffuse binding contributes greatly to total affinity, whereas in other cases the influence is modest. This approach may be useful for studying situations where "nonspecific" interactions contribute to biological function.

  19. Interaction of calreticulin with CD40 ligand, TRAIL and Fas ligand

    DEFF Research Database (Denmark)

    Duus, K; Pagh, R T; Holmskov, U

    2007-01-01

    is utilized by many other functionally diverse molecules and in this work the interaction of calreticulin with C1q and structurally similar molecules was investigated. In addition to C1q and MBL, CD40 ligand (CD40L), tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) were...... found to bind calreticulin strongly. A low level or no binding was observed for adiponectin, tumour necrosis factor-alpha (TNF-alpha), CD30L, surfactant protein-A and -D and collagen VIII. The interaction with calreticulin required a conformational change in CD40L, TRAIL and FasL and showed the same...

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

    Science.gov (United States)

    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.

  1. Ligand iron catalysts for selective hydrogenation

    Science.gov (United States)

    Casey, Charles P.; Guan, Hairong

    2010-11-16

    Disclosed are iron ligand catalysts for selective hydrogenation of aldehydes, ketones and imines. A catalyst such as dicarbonyl iron hydride hydroxycyclopentadiene) complex uses the OH on the five member ring and hydrogen linked to the iron to facilitate hydrogenation reactions, particularly in the presence of hydrogen gas.

  2. Programmed Death-Ligand 1 Immunohistochemistry Testing

    DEFF Research Database (Denmark)

    Büttner, Reinhard; Gosney, John R; Skov, Birgit Guldhammer

    2017-01-01

    Purpose Three programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for treatment of non-small-cell lung cancer (NSCLC). Treatment with pembrolizumab in NSCLC requires PD-L1 immunohistochemistry (IHC) testing. Nivolumab and atezolizumab are approved without PD-L1...

  3. Versatile phosphite ligands based on silsesquioxane backbones

    NARCIS (Netherlands)

    van der Vlugt, JI; Ackerstaff, J; Dijkstra, TW; Mills, AM; Kooijman, H; Spek, AL; Meetsma, A; Abbenhuis, HCL; Vogt, D

    Silsesquioxanes are employed as ligand backbones for the synthesis of novel phosphite compounds with 3,3'-5,5'-tetrakis(tert-butyl)-2,2'-di-oxa-1,1'-biphenyl substituents. Both mono- and bidentate phosphites are prepared in good yields. Two types of silsesquioxanes are employed as starting

  4. READ - Remote Analog ASIC Design System

    Directory of Open Access Journals (Sweden)

    Michael E. Auer

    2006-11-01

    Full Text Available The scope of this work is to present a solution to implement a remote electronic laboratory for testing and designing analog ASICs (ispPAC10. The application allows users to create circuit schematics, upload the design to the device and perform measurements. The software used for designing circuits is the PAC-Designer and it runs on a Citrix server. The signals are generated and the responses are acquired by a data acquisition board controlled by LabView. The virtual instruments interact with some ActiveX controls specially designed to look like real oscilloscope and function generator devices and represent the user interface of the lab. These ActiveX give users the control over the LabView VIs and the access to its facilities in order to perform electronic exercises.

  5. Nilpotent Quantum Mechanics: Analogs and Applications

    Directory of Open Access Journals (Sweden)

    Peter Marcer

    2017-07-01

    Full Text Available The most significant characteristic of nilpotent quantum mechanics is that the quantum system (fermion state and its environment (vacuum are, in mathematical terms, mirror images of each other. So a change in one automatically leads to corresponding changes in the other. We have used this characteristic as a model for self-organization, which has applications well beyond quantum physics. The nilpotent structure has also been identified as being constructed from two commutative vector spaces. This zero square-root construction has a number of identifiable characteristics which we can expect to find in systems where self-organization is dominant, and a case presented after the publication of a paper by us on “The ‘Logic’ of Self-Organizing Systems” [1], in the organization of the neurons in the visual cortex. We expect to find many more complex systems where our general principles, based, by analogy, on nilpotent quantum mechanics, will apply.

  6. Atwood and Poggendorff: an insightful analogy

    DEFF Research Database (Denmark)

    Coelho, Ricardo; Borges, Paulo; Avelar Sotomaior Karam, Ricardo

    2016-01-01

    - librium provide us with the solution for a compound Atwood machine with the same bodies. This analogy is pedagogically useful because it illustrates a common strategy to transform a dynamic in a static situation improving stu- dents’ comprehension of Newton’s laws and equilibrium.......Atwood’s treatise, in which the Atwood machine appears, was published in 1784. About 70 years later, Poggendorff showed experimentally that the weight of an Atwood machine is reduced when it is brought to motion. In the present paper, a twofold connection between this experiment and the Atwood...... machine is established. Firstly, if the Poggendorff apparatus is taken as an ideal one, the equations of motion of the apparatus coincide with the equations of motion of the compound Atwood machine. Secondly, if the Poggendorff apparatus, which works as a lever, is rebalanced, the equations of this equi...

  7. Atwood and Poggendorff: an insightful analogy

    Science.gov (United States)

    Coelho, R. L.; Borges, P. F.; Karam, R.

    2016-11-01

    Atwood’s treatise, in which the Atwood machine appears, was published in 1784. About 70 years later, Poggendorff showed experimentally that the weight of an Atwood machine is reduced when it is brought to motion. In the present paper, a twofold connection between this experiment and the Atwood machine is established. Firstly, if the Poggendorff apparatus is taken as an ideal one, the equations of motion of the apparatus coincide with the equations of motion of the compound Atwood machine. Secondly, if the Poggendorff apparatus, which works as a lever, is rebalanced, the equations of this equilibrium provide us with the solution for a compound Atwood machine with the same bodies. This analogy is pedagogically useful because it illustrates a common strategy to transform a dynamic in a static situation improving students’ comprehension of Newton’s laws and equilibrium.

  8. Analog Electronic Filters Theory, Design and Synthesis

    CERN Document Server

    Dimopoulos, Hercules G

    2012-01-01

    Filters are essential subsystems in a huge variety of electronic systems. Filter applications are innumerable; they are used for noise reduction, demodulation, signal detection, multiplexing, sampling, sound and speech processing, transmission line equalization and image processing, to name just a few. In practice, no electronic system can exist without filters. They can be found in everything from power supplies to mobile phones and hard disk drives and from loudspeakers and MP3 players to home cinema systems and broadband Internet connections. This textbook introduces basic concepts and methods and the associated mathematical and computational tools employed in electronic filter theory, synthesis and design.  This book can be used as an integral part of undergraduate courses on analog electronic filters. Includes numerous, solved examples, applied examples and exercises for each chapter. Includes detailed coverage of active and passive filters in an independent but correlated manner. Emphasizes real filter...

  9. Large-scale digitizer system, analog converters

    International Nuclear Information System (INIS)

    Althaus, R.F.; Lee, K.L.; Kirsten, F.A.; Wagner, L.J.

    1976-10-01

    Analog to digital converter circuits that are based on the sharing of common resources, including those which are critical to the linearity and stability of the individual channels, are described. Simplicity of circuit composition is valued over other more costly approaches. These are intended to be applied in a large-scale processing and digitizing system for use with high-energy physics detectors such as drift-chambers or phototube-scintillator arrays. Signal distribution techniques are of paramount importance in maintaining adequate signal-to-noise ratio. Noise in both amplitude and time-jitter senses is held sufficiently low so that conversions with 10-bit charge resolution and 12-bit time resolution are achieved

  10. Test signal generation for analog circuits

    Directory of Open Access Journals (Sweden)

    B. Burdiek

    2003-01-01

    Full Text Available In this paper a new test signal generation approach for general analog circuits based on the variational calculus and modern control theory methods is presented. The computed transient test signals also called test stimuli are optimal with respect to the detection of a given fault set by means of a predefined merit functional representing a fault detection criterion. The test signal generation problem of finding optimal test stimuli detecting all faults form the fault set is formulated as an optimal control problem. The solution of the optimal control problem representing the test stimuli is computed using an optimization procedure. The optimization procedure is based on the necessary conditions for optimality like the maximum principle of Pontryagin and adjoint circuit equations.

  11. Principles of digital and analog communications

    CERN Document Server

    Gibson, Jerry D

    1993-01-01

    This textbook for the first course in communications covers analog and digital systems and emphasizes digital communications. It covers data transmission, signal space, optimal receivers, and pulse code modulation, and includes readable treatments of coded modulation and continuous phase modulation. Advanced mathematics is kept to a minimum-Fourier series, Fourier transforms, linear systems, random variables, and stochastic process are described thoroughly. It includes data compression of speech and images and a full chapter coverage of information theory, rate distortion theory and coded modulation. It relates digital communications theory to current practice and covers digital communications over band-width constrained channels, including pulse shaping and equilization. -- Dieser Text bezieht sich auf eine vergriffene oder nicht verfügbare Ausgabe dieses Titels.

  12. Integrated Circuits for Analog Signal Processing

    CERN Document Server

    2013-01-01

      This book presents theory, design methods and novel applications for integrated circuits for analog signal processing.  The discussion covers a wide variety of active devices, active elements and amplifiers, working in voltage mode, current mode and mixed mode.  This includes voltage operational amplifiers, current operational amplifiers, operational transconductance amplifiers, operational transresistance amplifiers, current conveyors, current differencing transconductance amplifiers, etc.  Design methods and challenges posed by nanometer technology are discussed and applications described, including signal amplification, filtering, data acquisition systems such as neural recording, sensor conditioning such as biomedical implants, actuator conditioning, noise generators, oscillators, mixers, etc.   Presents analysis and synthesis methods to generate all circuit topologies from which the designer can select the best one for the desired application; Includes design guidelines for active devices/elements...

  13. Four-gate transistor analog multiplier circuit

    Science.gov (United States)

    Mojarradi, Mohammad M. (Inventor); Blalock, Benjamin (Inventor); Cristoloveanu, Sorin (Inventor); Chen, Suheng (Inventor); Akarvardar, Kerem (Inventor)

    2011-01-01

    A differential output analog multiplier circuit utilizing four G.sup.4-FETs, each source connected to a current source. The four G.sup.4-FETs may be grouped into two pairs of two G.sup.4-FETs each, where one pair has its drains connected to a load, and the other par has its drains connected to another load. The differential output voltage is taken at the two loads. In one embodiment, for each G.sup.4-FET, the first and second junction gates are each connected together, where a first input voltage is applied to the front gates of each pair, and a second input voltage is applied to the first junction gates of each pair. Other embodiments are described and claimed.

  14. HIGH RESOLUTION ANALOG / DIGITAL POWER SUPPLY CONTROLLER

    International Nuclear Information System (INIS)

    Medvedko, Evgeny A

    2003-01-01

    Corrector magnets for the SPEAR-3 synchrotron radiation source require precision, high-speed control for use with beam-based orbit feedback. A new Controller Analog/Digital Interface card (CANDI) has been developed for these purposes. The CANDI has a 24-bit DAC for current control and three 24-bit Δ-Σ ADCs to monitor current and voltages. The ADCs can be read and the DAC updated at the 4 kHz rate needed for feedback control. A precision 16-bit DAC provides on-board calibration. Programmable multiplexers control internal signal routing for calibration, testing, and measurement. Feedback can be closed internally on current setpoint, externally on supply current, or beam position. Prototype and production tests are reported in this paper. Noise is better than 17 effective bits in a 10 mHz to 2 kHz bandwidth. Linearity and temperature stability are excellent

  15. Quantum walks based on an interferometric analogy

    International Nuclear Information System (INIS)

    Hillery, Mark; Bergou, Janos; Feldman, Edgar

    2003-01-01

    There are presently two models for quantum walks on graphs. The ''coined'' walk uses discrete-time steps, and contains, besides the particle making the walk, a second quantum system, the coin, that determines the direction in which the particle will move. The continuous walk operates with continuous time. Here a third model for quantum walks is proposed, which is based on an analogy to optical interferometers. It is a discrete-time model, and the unitary operator that advances the walk one step depends only on the local structure of the graph on which the walk is taking place. This type of walk also allows us to introduce elements, such as phase shifters, that have no counterpart in classical random walks. Several examples are discussed

  16. Estrogenic effects of several BPA analogs in the developing zebrafish brain

    Directory of Open Access Journals (Sweden)

    Joel eCano-Nicolau

    2016-03-01

    Full Text Available Important set of studies have demonstrated the endocrine disrupting activity of Bisphenol A (BPA. The present work aimed at defining estrogenic-like activity of several BPA structural analogs, including BPS, BPF, BPAF, and BPAP, on 4-day or 7-day post-fertilization (dpf zebrafish larva as an in vivo model. We measured the induction level of the estrogen-sensitive marker cyp19a1b gene (Aromatase B, expressed in the brain, using three different in situ/in vivo strategies: 1 Quantification of cyp19a1b transcripts using RT-qPCR in wild type 7-dpf larva brains exposed to bisphenols ; 2 Detection and distribution of cyp19a1b transcripts using in situ hybridization on 7-dpf brain sections (hypothalamus; and 3 Quantification of the cyp19a1b promoter activity in live cyp19a1b-GFP transgenic zebrafish (EASZY assay at 4-dpf larval stage. These three different experimental approaches demonstrated that BPS, BPF or BPAF exposure, similarly to BPA, significantly activates the expression of the estrogenic marker in the brain of developing zebrafish. In vitro experiments using both reporter gene assay in a glial cell context and competitive ligand binding assays strongly suggested that up-regulation of cyp19a1b is largely mediated by the zebrafish estrogen nuclear receptor alpha (zfERα. Importantly, and in contrast to other tested bisphenol A analogs, the bisphenol AP (BPAP did not show estrogenic activity in our model.

  17. Ultraviolet reflectance spectroscopy measurements of planetary materials and their analogs

    Science.gov (United States)

    Hibbitts, C.; Stockstill-Cahill, K.

    2017-12-01

    The compositions of airless solar system objects tell us about the origin and evolutionary processes that are responsible for the current state of our solar system and that shape our environment. Spacecraft have obtained UV reflectance measurements of the surfaces of Mercury, the Moon, asteroids, comets, icy satellites, and Pluto from which composition is being inferred. Most minerals absorb in the UV making studying surface composition both informative but also challenging [e.g. 1]. The UV region is sensitive to atomic and molecular electronic absorptions such as the ligand-metal charge transfer band that is present in oxides and silicates and the conduction band at vacuum UV wavelengths. Unfortunately, limited laboratory reflectance measurements in the ultraviolet hampers the interpretation of some of these planetary UV reflectance datasets. However, several laboratory efforts have been developed [e.g. 2,3] to fill the need for laboratory UV measurements. These are difficult measurements to make, being complicated by the absorptive nature of the atmosphere, requiring measurements to be conducted under vacuum or over very short path lengths of a N2-purged system. Also, the lack of a widely accepted UV diffuse reflectance standard is problematic. At the JHU-APL, bidirectional UV reflectance measurements are obtained under vacuum from 140 nm to 570 nm. Sample temperature can be controlled from 100K to 600K, which enables the study of the interaction of water ice and other volatiles with the refractory samples. Results from our laboratory research include the development of a correlation between the spectral nature of the OMCT band and the abundance of iron in low water content lunar analog glasses [3]. Also, the spectral signature of water in the UV has been investigated. While water-ice has a known strong absorption feature near 180 nm [e.g. 4], adsorbed molecular and disassociatively adsorbed OH apparently are not optically active in this spectral region [5]. We

  18. Automating analog design: Taming the shrew

    Science.gov (United States)

    Barlow, A.

    1990-01-01

    The pace of progress in the design of integrated circuits continues to amaze observers inside and outside of the industry. Three decades ago, a 50 transistor chip was a technological wonder. Fifteen year later, a 5000 transistor device would 'wow' the crowds. Today, 50,000 transistor chips will earn a 'not too bad' assessment, but it takes 500,000 to really leave an impression. In 1975 a typical ASIC device had 1000 transistors, took one year to first samples (and two years to production) and sold for about 5 cents per transistor. Today's 50,000 transistor gate array takes about 4 months from spec to silicon, works the first time, and sells for about 0.02 cents per transistor. Fifteen years ago, the single most laborious and error prone step in IC design was the physical layout. Today, most IC's never see the hand of a layout designer: and automatic place and route tool converts the engineer's computer captured schematic to a complete physical design using a gate array or a library of standard cells also created by software rather than by designers. CAD has also been a generous benefactor to the digital design process. The architect of today's digital systems creates the design using an RTL or other high level simulator. Then the designer pushes a button to invoke the logic synthesizer-optimizer tool. A fault analyzer checks the result for testability and suggests where scan based cells will improve test coverage. One obstinate holdout amidst this parade of progress is the automation of analog design and its reduction to semi-custom techniques. This paper investigates the application of CAD techniques to analog design.

  19. Dynamic ligand-based pharmacophore modeling and virtual ...

    Indian Academy of Sciences (India)

    Five ligand-based pharmacophore models were generated from 40 different .... the Phase module of the Schrodinger program.35 Each model consisted of six types of ... ligand preparation included the OPLS_2005 force field and to retain the ...

  20. Substrate coated with receptor and labelled ligand for assays

    International Nuclear Information System (INIS)

    1980-01-01

    Improvements in the procedures for assaying ligands are described. The assay consists of a polystyrene tube on which receptors are present for both the ligand to be assayed and a radioactively labelled form of the ligand. The receptors on the bottom portion of the tube are also coated with labelled ligands, thus eliminating the necessity for separate addition of the labelled ligand and sample during an assay. Examples of ligands to which this method is applicable include polypeptides, nucleotides, nucleosides and proteins. Specific examples are given in which the ligand to be assayed is digoxin, the labelled form of the ligand is 3-0-succinyl digoxyigenin tyrosine ( 125 I) and the receptor is digoxin antibody. (U.K.)

  1. 23rd workshop on Advances in Analog Circuit Design

    CERN Document Server

    Baschirotto, Andrea; Makinwa, Kofi

    2015-01-01

    This book is based on the 18 tutorials presented during the 23rd workshop on Advances in Analog Circuit Design.  Expert designers present readers with information about a variety of topics at the frontier of analog circuit design, serving as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development.    • Includes coverage of high-performance analog-to-digital and digital to analog converters, integrated circuit design in scaled technologies, and time-domain signal processing; • Provides a state-of-the-art reference in analog circuit design, written by experts from industry and academia; • Presents material in a tutorial-based format.

  2. Inhibition of translation by 7-methyl guanosine (m7G) nucleotide cap analogs with derivatized 5'-monophosphates

    International Nuclear Information System (INIS)

    Tahara, S.M.; Darzynkiewicz, E.; Ekiel, I.

    1986-01-01

    Recognition of the 5'-m 7 GpppN (cap) structure of eukaryote mRNA is an important step of translation initiation as shown by the potent inhibitory effect of m 7 G nucleotides on this process. A comparison of cap analogs as competitive inhibitors of initiation has allowed the authors to map probable protein-ligand contact points between the cap and cognate cap binding proteins (CBPs). Recently, several new derivatives of m 7 GMP (1) with modified phosphates were synthesized: m 7 G 5'-phosphite (2), m 7 G 5'-phosphoramidate (3), m 7 G 5'-methylphosphonate (4), and m 7 G 5'-phosphate-O-methyl ester (5). In addition, 7,8-dimethyl GMP (6) and 7-methyl 8-amino GMP (7) were synthesized. 6 and7 are primarily syn and anti respectively, relative to the glycosidic bond as shown by solution NMR studies. Inhibition by analogs on total translation in reticulocyte lysate and binding of mRNA to rabbit reticulocyte ribosomes was found to be: 1 = 3 > 5 > 4 > 2. The inhibitory activity of 3 was unexpected since it is isosteric with 4, however it suggested that electron configuration and/or the ability to form a hydrogen bond between protein and the phosphate moiety might be important for ligand binding. 7 was more inhibitory than 6. The latter two are isosteric therefore differences in electron delocalization and/or syn-anti conformation are likely to be the reason(s) for the observed difference

  3. New Ru(II) complexes for dual photoreactivity: ligand exchange and (1)O2 generation.

    Science.gov (United States)

    Knoll, Jessica D; Albani, Bryan A; Turro, Claudia

    2015-08-18

    Uncovering the factors that govern the electronic structure of Ru(II)-polypyridyl complexes is critical in designing new compounds for desired photochemical reactions, and strategies to tune excited states for ligand dissociation and (1)O2 production are discussed herein. The generally accepted mechanism for photoinduced ligand dissociation proposes that population of the dissociative triplet ligand field ((3)LF) state proceeds through thermal population from the vibrationally cooled triplet metal-to-ligand charge transfer ((3)MLCT) state; however, temperature-dependent emission spectroscopy provides varied activation energies using the emission and ligand exchange quantum yields for [Ru(bpy)2(L)2](2+) (bpy = 2,2'-bipyridine; L = CH3CN or py). This suggests that population of the (3)LF state proceeds from the vibrationally excited (3)MLCT state. Because the quantum yield of ligand dissociation for nitriles is much more efficient than that for py, steric bulk was introduced into the ligand set to distort the pseudo-octahedral geometry and lower the energy of the (3)LF state. The py dissociation quantum yield with 500 nm irradiation in a series of [Ru(tpy)(NN)(py)](2+) complexes (tpy = 2,2':6',2″-terpyridine; NN = bpy, 6,6'-dimethyl-2,2'-bipyridine (Me2bpy), 2,2'-biquinoline (biq)) increases by 2-3 orders of magnitude with the sterically bulky Me2bpy and biq ligands relative to bpy. Ultrafast transient absorption spectroscopy reveals population of the (3)LF state within 3-7 ps when NN is bulky, and density functional theory calculations support stabilized (3)LF states. Dual activity via ligand dissociation and (1)O2 production can be achieved by careful selection of the ligand set to tune the excited-state dynamics. Incorporation of an extended π system in Ru(II) complexes such as [Ru(bpy)(dppn)(CH3CN)2](2+) (dppn = benzo[i]dipyrido[3,2-a:2',3'-c]phenazine) and [Ru(tpy)(Me2dppn)(py)](2+) (Me2dppn = 3,6-dimethylbenzo[i]dipyrido[3,2-a:2',3'-c]phenazine) introduces

  4. New Ru(II) Complexes for Dual Photoreactivity: Ligand Exchange and 1O2 Generation

    Science.gov (United States)

    Knoll, Jessica D.; Albani, Bryan A.; Turro, Claudia

    2016-01-01

    CONSPECTUS Uncovering the factors that govern the electronic structure of Ru(II)–polypyridyl complexes is critical in designing new compounds for desired photochemical reactions, and strategies to tune excited states for ligand dissociation and 1O2 production are discussed herein. The generally accepted mechanism for photoinduced ligand dissociation proposes that population of the dissociative triplet ligand field (3LF) state proceeds through thermal population from the vibrationally cooled triplet metal-to-ligand charge transfer (3MLCT) state; however, temperature-dependent emission spectroscopy provides varied activation energies using the emission and ligand exchange quantum yields for [Ru(bpy)2(L)2]2+ (bpy = 2,2′-bipyridine; L = CH3CN or py). This suggests that population of the 3LF state proceeds from the vibrationally excited 3MLCT state. Because the quantum yield of ligand dissociation for nitriles is much more efficient than that for py, steric bulk was introduced into the ligand set to distort the pseudo-octahedral geometry and lower the energy of the 3LF state. The py dissociation quantum yield with 500 nm irradiation in a series of [Ru(tpy)(NN)(py)]2+ complexes (tpy = 2,2′:6′,2″-terpyridine; NN = bpy, 6,6′-dimethyl-2,2′-bipyridine (Me2bpy), 2,2′-biquinoline (biq)) increases by 2–3 orders of magnitude with the sterically bulky Me2bpy and biq ligands relative to bpy. Ultrafast transient absorption spectroscopy reveals population of the 3LF state within 3–7 ps when NN is bulky, and density functional theory calculations support stabilized 3LF states. Dual activity via ligand dissociation and 1O2 production can be achieved by careful selection of the ligand set to tune the excited-state dynamics. Incorporation of an extended π system in Ru(II) complexes such as [Ru(bpy)(dppn)(CH3CN)2]2+ (dppn = benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(tpy)(Me2dppn)(py)]2+ (Me2dppn = 3,6-dimethylbenzo[i]dipyrido[3,2-a:2′,3

  5. Role of ligand-ligand vs. core-core interactions in gold nanoclusters.

    Science.gov (United States)

    Milowska, Karolina Z; Stolarczyk, Jacek K

    2016-05-14

    The controlled assembly of ligand-coated gold nanoclusters (NCs) into larger structures paves the way for new applications ranging from electronics to nanomedicine. Here, we demonstrate through rigorous density functional theory (DFT) calculations employing novel functionals accounting for van der Waals forces that the ligand-ligand interactions determine whether stable assemblies can be formed. The study of NCs with different core sizes, symmetry forms, ligand lengths, mutual crystal orientations, and in the presence of a solvent suggests that core-to-core van der Waals interactions play a lesser role in the assembly. The dominant interactions originate from combination of steric effects, augmented by ligand bundling on NC facets, and related to them changes in electronic properties induced by neighbouring NCs. We also show that, in contrast to standard colloidal theory approach, DFT correctly reproduces the surprising experimental trends in the strength of the inter-particle interaction observed when varying the length of the ligands. The results underpin the importance of understanding NC interactions in designing gold NCs for a specific function.

  6. Analog circuit design a tutorial guide to applications and solutions

    CERN Document Server

    Williams, Jim

    2011-01-01

    * Covers the fundamentals of linear/analog circuit and system design to guide engineers with their design challenges. * Based on the Application Notes of Linear Technology, the foremost designer of high performance analog products, readers will gain practical insights into design techniques and practice. * Broad range of topics, including power management tutorials, switching regulator design, linear regulator design, data conversion, signal conditioning, and high frequency/RF design. * Contributors include the leading lights in analog design, Robert Dobkin, Jim Willia

  7. Synthesis and anti-inflammatory activity of phenylbutenoid dimer analogs

    International Nuclear Information System (INIS)

    Kim, Sung Soo; Fang, Yuan Ying; Park, Hae Eil

    2015-01-01

    Several phenylbutenoid dimer (PBD) analogs were synthesized and evaluated for their inhibitory activities against nitric oxide (NO) production and TNF-α release. The PBD analogs were synthesized via Diels–Alder and subsequent Schlosser reactions as key steps. Among the tested compounds, two analogs (8c, 8f) exhibited much stronger inhibitory activity against LPS-stimulated NO production and TNF-α release in RAW 264.7 cells than that of wogonin

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

    Science.gov (United States)

    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.

  9. Analogies between classical statistical mechanics and quantum mechanics

    International Nuclear Information System (INIS)

    Uehara, M.

    1986-01-01

    Some analogies between nonequilibrium classical statistical mechanics and quantum mechanics, at the level of the Liouville equation and at the kinetic level, are commented on. A theorem, related to the Vlasov equation applied to a plasma, is proved. The theorem presents an analogy with Ehrenfest's theorem of quantum mechanics. An analogy between the plasma kinetic theory and Bohm's quantum theory with 'hidden variables' is also shown. (Author) [pt

  10. The analogic model ''RIC'' of thermal behaviour of mass concrete

    International Nuclear Information System (INIS)

    Gonzalez Redondo, M.; Gonzalez de Posada, F.; Plana Claver, J.

    1997-01-01

    In order to study the thermal field and calorific flows in heat sources (i.e. mass concrete during setting) we have conceived, built and experimented with an analogical electric model. This model, named RIC, consists of resistors (R) and capacitors (C) in which nodes an electric current (I) has been injected. Several analogical constants were used for the mathematical approximation. Thus, this paper describes the analogical RIC model, simulating heat generation, boundary and initial conditions and concreting. (Author) 4 refs

  11. AutoSite: an automated approach for pseudo-ligands prediction—from ligand-binding sites identification to predicting key ligand atoms

    Science.gov (United States)

    Ravindranath, Pradeep Anand; Sanner, Michel F.

    2016-01-01

    Motivation: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. Results: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand. In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. Availability and Implementation: http://adfr.scripps.edu/AutoDockFR/autosite.html Contact: sanner@scripps.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354702

  12. Children's analogical reasoning in a third-grade science discussion

    Science.gov (United States)

    May, David B.; Hammer, David; Roy, Patricia

    2006-03-01

    Expert scientific inquiry involves the generation and use of analogies. How and when students might develop this aspect of expertise has implications for understanding how and when instruction might facilitate that development. In a study of K-8 student inquiry in physical science, we are examining cases of spontaneous analogy generation. In the case we present here, a third-grader generates an analogy and modifies it to reconcile his classmates' counterarguments, allowing us to identify in these third-graders specific aspects of nascent expertise in analogy use. Promoting abilities and inclinations such as these children display requires that educators recognize and respond to them.

  13. 25th workshop on Advances in Analog Circuit Design

    CERN Document Server

    Harpe, Pieter; Makinwa, Kofi

    2017-01-01

    This book is based on the 18 tutorials presented during the 25th workshop on Advances in Analog Circuit Design. Expert designers present readers with information about a variety of topics at the frontier of analog circuit design, including low-power and energy-efficient analog electronics, with specific contributions focusing on the design of continuous-time sigma-delta modulators, automotive electronics, and power management. This book serves as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development.

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

    Science.gov (United States)

    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.

  15. Non-analog Monte Carlo estimators for radiation momentum deposition

    International Nuclear Information System (INIS)

    Hykes, Joshua M.; Densmore, Jeffery D.

    2009-01-01

    The standard method for calculating radiation momentum deposition in Monte Carlo simulations is the analog estimator, which tallies the change in a particle's momentum at each interaction with the matter. Unfortunately, the analog estimator can suffer from large amounts of statistical error. In this paper, we present three new non-analog techniques for estimating momentum deposition. Specifically, we use absorption, collision, and track-length estimators to evaluate a simple integral expression for momentum deposition that does not contain terms that can cause large amounts of statistical error in the analog scheme. We compare our new non-analog estimators to the analog estimator with a set of test problems that encompass a wide range of material properties and both isotropic and anisotropic scattering. In nearly all cases, the new non-analog estimators outperform the analog estimator. The track-length estimator consistently yields the highest performance gains, improving upon the analog-estimator figure of merit by factors of up to two orders of magnitude.

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

    Science.gov (United States)

    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.

  17. A response calculus for immobilized T cell receptor ligands

    DEFF Research Database (Denmark)

    Andersen, P S; Menné, C; Mariuzza, R A

    2001-01-01

    determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated...

  18. Fullerenes as a new type of ligands for transition metals

    International Nuclear Information System (INIS)

    Sokolov, V.I.

    2007-01-01

    Fullerenes are considered as ligands in transition metal π-complexes. The following aspects are discussed: metals able to form π-complexes with fullerenes (Zr, V, Ta, Mo, W, Re, Ru, etc.); haptic numbers; homo- and hetero ligand complexes; ligand compatibility with fullerenes for different metals, including fullerenes with a disturbed structure of conjugation [ru

  19. New pinene-derived pyridines as bidentate chiral ligands

    Czech Academy of Sciences Publication Activity Database

    Malkov, A. V.; Stewart-Liddon, A.; Teplý, Filip; Kobr, L.; Muir, K. W.; Haigh, D.; Kočovský, P.

    2008-01-01

    Roč. 64, č. 18 (2008), s. 4011-4025 ISSN 0040-4020 Institutional research plan: CEZ:AV0Z40550506 Keywords : chiral ligands * transition metal catalysis * asymmetric catalysis * pyridine ligands * oxazoline ligands Subject RIV: CC - Organic Chemistry Impact factor: 2.897, year: 2008

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

    Science.gov (United States)

    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

  1. Is the link from working memory to analogy causal? No analogy improvements following working memory training gains.

    Directory of Open Access Journals (Sweden)

    J Elizabeth Richey

    Full Text Available Analogical reasoning has been hypothesized to critically depend upon working memory through correlational data, but less work has tested this relationship through experimental manipulation. 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. 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.

  2. Is the link from working memory to analogy causal? No analogy improvements following working memory training gains.

    Science.gov (United States)

    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, but less work has tested this relationship through experimental manipulation. 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. 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.

  3. Crystallographic and Spectroscopic Characterization of Americium Complexes Containing the Bis[(phosphino)methyl]pyridine-1-oxide (NOPOPO) Ligand Platform

    Energy Technology Data Exchange (ETDEWEB)

    Corbey, Jordan F. [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Rapko, Brian M. [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Wang, Zheming [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; McNamara, Bruce K. [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Surbella, Robert G. [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Pellegrini, Kristi L. [Pacific Northwest National Laboratory, Richland, Washington 99354, United States; Schwantes, Jon M. [Pacific Northwest National Laboratory, Richland, Washington 99354, United States

    2018-02-06

    Abstract The crystal structures of americium species containing a common multi-functional phosphine oxide ligand, reported for its ability to extract f elements from acidic solutions, namely 2,6-[Ph2P(O)CH2]2C5H3-NO, L, have finally been determined after over three decades of separations studies involving these species and their surrogates. The molecular compounds Am(L)(NO3)3, Am 1:1, and [Am(L)2(NO3)][NO3]2, Am 2:1, along with their neodymium and europium analogs were synthesized and characterized using single-crystal X-ray crystallography, attenuated total reflectance Fourier transform infrared (ATR) spectroscopy and luminescence spectroscopy to provide a comprehensive comparison with new and known analogous complexes.

  4. Comparative tissue distribution of conformationally restricted radioiodinated vesamicol receptor ligands

    Energy Technology Data Exchange (ETDEWEB)

    Efange, S M.N.; Khare, A B; Langason, R B

    1995-05-01

    Three conformationally restricted analogs of vesamicol, 1'-[1-(3-iodobenzyl)-4-hydroxypiperidin-3-yl]-spirol[1H-indene-1,4'- piperidine] (5), 1'-[1-(3-iodobenzyl)-4-hydroxypiperidin-3-yl]-3,4-dihydrospiro[indene-1,4'- piperidine] (6) and 1'-[1-(3-iodobenzyl)-4-hydroxypiperidin-3-yl)]-3,4-dihydrospiro[naphthalene- 1(2H),4'-piperidine] (7), were labelled with iodine-125 and evaluated as potential radioligands for mapping vesamicol receptor (VR) density and cholinergic function in vivo. All compounds showed similar kinetics in most tissues. However, differences were observed in the brain. Although comparable levels of each corresponding enantiomeric pair were obtained initially in the brain, the levels of the dextrorotatory enantiomers (+)-5, (+)-6 and (+)-7 were found to decrease by 72-82% over a period of 3 h. In contrast, the brain levels of the corresponding levorotatory isomers were maintained throughout the duration of the experiment. Among the dextrorotatory isomers, (+)-6 showed the highest brain extraction, while (+)-7 showed the lowest. In tissue dissection experiments, the levels of (+)-5, (+)-6 and (+)-7 were highest in the striatum and moderate to low in the cortex and cerebellum. Co-administration of haloperidol with (+)-6 decreased the levels of the latter in the striatum by 27%, while the levels in the cortex and cerebellum were each reduced by 60%. In addition, haloperidol failed to affect the regional distribution of (+)-7 in the brain. However, both haloperidol and spiperone increased the striatal levels of (+)-5 by 67 and 76%, respectively, suggesting that the binding of this radioligand is related to cholinergic function. Furthermore, haloperidol reduced the concentration of (+)-5 in the cortex and cerebellum by 25 and 33%, respectively, thereby implicating the sigma site as a secondary target for this ligand in the cortex.

  5. Comparative tissue distribution of conformationally restricted radioiodinated vesamicol receptor ligands

    International Nuclear Information System (INIS)

    Efange, S.M.N.; Khare, A.B.; Langason, R.B.

    1995-01-01

    Three conformationally restricted analogs of vesamicol, 1'-[1-(3-iodobenzyl)-4-hydroxypiperidin-3-yl]-spirol[1H-indene-1,4'- piperidine] (5), 1'-[1-(3-iodobenzyl)-4-hydroxypiperidin-3-yl]-3,4-dihydrospiro[indene-1,4'- piperidine] (6) and 1'-[1-(3-iodobenzyl)-4-hydroxypiperidin-3-yl)-3,4-dihydrospiro[naphthalene- 1(2H),4'-piperidine] (7), were labelled with iodine-125 and evaluated as potential radioligands for mapping vesamicol receptor (VR) density and cholinergic function in vivo. All compounds showed similar kinetics in most tissues. However, differences were observed in the brain. Although comparable levels of each corresponding enantiomeric pair were obtained initially in the brain, the levels of the dextrorotatory enantiomers (+)-5, (+)-6 and (+)-7 were found to decrease by 72-82% over a period of 3 h. In contrast, the brain levels of the corresponding levorotatory isomers were maintained throughout the duration of the experiment. Among the dextrorotatory isomers, (+)-6 showed the highest brain extraction, while (+)-7 showed the lowest. In tissue dissection experiments, the levels of (+)-5, (+)-6 and (+)-7 were highest in the striatum and moderate to low in the cortex and cerebellum. Co-administration of haloperidol with (+)-6 decreased the levels of the latter in the striatum by 27%, while the levels in the cortex and cerebellum were each reduced by 60%. In addition, haloperidol failed to affect the regional distribution of (+)-7 in the brain. However, both haloperidol and spiperone increased the striatal levels of (+)-5 by 67 and 76%, respectively, suggesting that the binding of this radioligand is related to cholinergic function. Furthermore, haloperidol reduced the concentration of (+)-5 in the cortex and cerebellum by 25 and 33%, respectively, thereby implicating the sigma site as a secondary target for this ligand in the cortex

  6. Sigma-2 receptor ligands QSAR model dataset

    Directory of Open Access Journals (Sweden)

    Antonio Rescifina

    2017-08-01

    Full Text Available The data have been obtained from the Sigma-2 Receptor Selective Ligands Database (S2RSLDB and refined according to the QSAR requirements. These data provide information about a set of 548 Sigma-2 (σ2 receptor ligands selective over Sigma-1 (σ1 receptor. The development of the QSAR model has been undertaken with the use of CORAL software using SMILES, molecular graphs and hybrid descriptors (SMILES and graph together. Data here reported include the regression for σ2 receptor pKi QSAR models. The QSAR model was also employed to predict the σ2 receptor pKi values of the FDA approved drugs that are herewith included.

  7. Metal-ligand cooperative activation of nitriles by a ruthenium complex with a de-aromatized PNN pincer ligand

    NARCIS (Netherlands)

    Eijsink, Linda E; Perdriau, Sébastien C P; de Vries, Johannes G; Otten, Edwin

    2016-01-01

    The pincer complex (PNN)RuH(CO), with a de-aromatized pyridine in the ligand backbone, is shown to react with nitriles in a metal-ligand cooperative manner. This leads to the formation of a series of complexes with new Ru-N(nitrile) and C(ligand)-C(nitrile) bonds. The initial nitrile cycloaddition

  8. EGFR Activation by Spatially Restricted Ligands

    Science.gov (United States)

    2006-06-01

    the level of ligand production, that result in human breast cancer. We have integrated genetic and biochemical methods to study (1) the effects of a...and spindle-B encode components of the RAD52 DNA repair pathway and affect meiosis and patterning in Drosophila oogenesis. Genes Dev 12, 2711-2723...findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision

  9. Selective oxoanion separation using a tripodal ligand

    Energy Technology Data Exchange (ETDEWEB)

    Custelcean, Radu; Moyer, Bruce A.; Rajbanshi, Arbin

    2016-02-16

    The present invention relates to urea-functionalized crystalline capsules self-assembled by sodium or potassium cation coordination and by hydrogen-bonding water bridges to selectively encapsulate tetrahedral divalent oxoanions from highly competitive aqueous alkaline solutions and methods using this system for selective anion separations from industrial solutions. The method involves competitive crystallizations using a tripodal tris(urea) functionalized ligand and, in particular, provides a viable approach to sulfate separation from nuclear wastes.

  10. Targeting Selectins and Their Ligands in Cancer

    Directory of Open Access Journals (Sweden)

    Alessandro eNatoni

    2016-04-01

    Full Text Available Aberrant glycosylation is a hallmark of cancer cells with increased evidence pointing to a role in tumor progression. In particular, aberrant sialylation of glycoproteins and glycolipids have been linked to increased immune cell evasion, drug evasion, drug resistance, tumor invasiveness, and vascular dissemination leading to metastases. Hypersialylation of cancer cells is largely the result of overexpression of sialyltransferases. Humans differentially express twenty different sialyltransferases in a tissue-specific manner, each of which catalyze the attachment of sialic acids via different glycosidic linkages (2-3; 2-6 or 2-8 to the underlying glycan chain. One important mechanism whereby overexpression of sialyltransferases contributes to an enhanced metastatic phenotype is via the generation of selectin ligands. Selectin ligand function requires the expression of sialyl-Lewis X and its structural-isomer sialyl-Lewis A, which are synthesized by the combined action of alpha 1-3-fucosyltransferases, 2-3-sialyltransferases, 1-4-galactosyltranferases, and N-acetyl--glucosaminyltransferases. The α2-3-sialyltransferases ST3Gal4 and ST3Gal6 are critical to the generation of functional E- and P-selectin ligands and overexpression of these sialyltransferases have been linked to increased risk of metastatic disease in solid tumors and poor outcome in multiple myeloma. Thus, targeting selectins and their ligands as well as the enzymes involved in their generation, in particular sialyltransferases, could be beneficial to many cancer patients. Potential strategies include sialyltransferase inhibition and the use of selectin antagonists, such as glycomimetic drugs and antibodies. Here, we review ongoing efforts to optimize the potency and selectivity of sialyltransferase inhibitors, including the potential for targeted delivery approaches, as well as evaluate the potential utility of selectin inhibitors, which are now in early clinical

  11. Amplifying Riboswitch Signal Output using Cellular Wiring

    Science.gov (United States)

    2017-01-30

    included in this document for any purpose other than Government procurement does not in any way obligate the U.S. Government. The fact that the...release. 88ABW-2016-3094, 23 June 2016 ACKNOWLEDGEMENTS We thank Dr. Christopher Voigt (Massachusetts Institute of Technology) for his generous gift of...plasmids, and Dr. Dimitri Deheyn (U.C. San Diego) for his generous gift of GFPa1, and Dr. Jason Micklefield (University of Manchester, UK) for

  12. Modeling visual problem solving as analogical reasoning.

    Science.gov (United States)

    Lovett, Andrew; Forbus, Kenneth

    2017-01-01

    We present a computational model of visual problem solving, designed to solve problems from the Raven's Progressive Matrices intelligence test. The model builds on the claim that analogical reasoning lies at the heart of visual problem solving, and intelligence more broadly. Images are compared via structure mapping, aligning the common relational structure in 2 images to identify commonalities and differences. These commonalities or differences can themselves be reified and used as the input for future comparisons. When images fail to align, the model dynamically rerepresents them to facilitate the comparison. In our analysis, we find that the model matches adult human performance on the Standard Progressive Matrices test, and that problems which are difficult for the model are also difficult for people. Furthermore, we show that model operations involving abstraction and rerepresentation are particularly difficult for people, suggesting that these operations may be critical for performing visual problem solving, and reasoning more generally, at the highest level. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  13. NMR analog of Bell's inequalities violation test

    International Nuclear Information System (INIS)

    Souza, A M; Oliveira, I S; Sarthour, R S; Magalhaes, A; Teles, J; Azevedo, E R de; Bonagamba, T J

    2008-01-01

    In this paper, we present an analog of Bell's inequalities violation test for N qubits to be performed in a nuclear magnetic resonance (NMR) quantum computer. This can be used to simulate or predict the results for different Bell's inequality tests, with distinct configurations and a larger number of qubits. To demonstrate our scheme, we implemented a simulation of the violation of the Clauser, Horne, Shimony and Holt (CHSH) inequality using a two-qubit NMR system and compared the results to those of a photon experiment. The experimental results are well described by the quantum mechanics theory and a local realistic hidden variables model (LRHVM) that was specifically developed for NMR. That is why we refer to this experiment as a simulation of Bell's inequality violation. Our result shows explicitly how the two theories can be compatible with each other due to the detection loophole. In the last part of this work, we discuss the possibility of testing some fundamental features of quantum mechanics using NMR with highly polarized spins, where a strong discrepancy between quantum mechanics and hidden variables models can be expected

  14. Natural Analog Studies at Pena Blanca, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    A.M. Simmons

    2005-07-11

    The significance of the Pena Blanca uranium deposits in the State of Chihuahua, Mexico as potential natural analogs for a nuclear waste repository in unsaturated welded tuff was first recognized in the 1980s. In the 1970s, the Pena Blanca region was a major target of uranium exploration and exploitation by the Mexican government. Since then the Nopal I uranium deposit has been studied extensively by researchers in the U.S., Mexico, and Europe. The Nopal I deposit represents an environment similar to that of the proposed high-level radioactive waste repository at Yucca Mountain in many ways. Both are located in semi-arid regions. Both are located in Tertiary rhyolitic tuffs overlying carbonate rocks that have been subjected to basin and range-style tectonic deformation. Both are located in a chemically oxidizing, unsaturated zone 200 m or more above the water table. The alteration of uraninite to secondary minerals at Nopal I may be similar to the alteration of uranium fuel rods in this type of setting. Investigations at Nopal I and in the surrounding Sierra Pena Blanca have included detailed outcrop mapping, hydrologic and isotopic studies of flow and transport, studies of mineral alteration, modeling, and performance assessment.

  15. Natural Analog Studies at Pena Blanca, Mexico

    International Nuclear Information System (INIS)

    A.M. Simmons

    2005-01-01

    The significance of the Pena Blanca uranium deposits in the State of Chihuahua, Mexico as potential natural analogs for a nuclear waste repository in unsaturated welded tuff was first recognized in the 1980s. In the 1970s, the Pena Blanca region was a major target of uranium exploration and exploitation by the Mexican government. Since then the Nopal I uranium deposit has been studied extensively by researchers in the U.S., Mexico, and Europe. The Nopal I deposit represents an environment similar to that of the proposed high-level radioactive waste repository at Yucca Mountain in many ways. Both are located in semi-arid regions. Both are located in Tertiary rhyolitic tuffs overlying carbonate rocks that have been subjected to basin and range-style tectonic deformation. Both are located in a chemically oxidizing, unsaturated zone 200 m or more above the water table. The alteration of uraninite to secondary minerals at Nopal I may be similar to the alteration of uranium fuel rods in this type of setting. Investigations at Nopal I and in the surrounding Sierra Pena Blanca have included detailed outcrop mapping, hydrologic and isotopic studies of flow and transport, studies of mineral alteration, modeling, and performance assessment

  16. Natural CO2 Analogs for Carbon Sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Scott H. Stevens; B. Scott Tye

    2005-07-31

    The report summarizes research conducted at three naturally occurring geologic CO{sub 2} fields in the US. The fields are natural analogs useful for the design of engineered long-term storage of anthropogenic CO{sub 2} in geologic formations. Geologic, engineering, and operational databases were developed for McElmo Dome in Colorado; St. Johns Dome in Arizona and New Mexico; and Jackson Dome in Mississippi. The three study sites stored a total of 2.4 billion t (46 Tcf) of CO{sub 2} equivalent to 1.5 years of power plant emissions in the US and comparable in size with the largest proposed sequestration projects. The three CO{sub 2} fields offer a scientifically useful range of contrasting geologic settings (carbonate vs. sandstone reservoir; supercritical vs. free gas state; normally pressured vs. overpressured), as well as different stages of commercial development (mostly undeveloped to mature). The current study relied mainly on existing data provided by the CO{sub 2} field operator partners, augmented with new geochemical data. Additional study at these unique natural CO{sub 2} accumulations could further help guide the development of safe and cost-effective design and operation methods for engineered CO{sub 2} storage sites.

  17. Heavy ion irradiation of astrophysical ice analogs

    International Nuclear Information System (INIS)

    Duarte, Eduardo Seperuelo; Domaracka, Alicja; Boduch, Philippe; Rothard, Hermann; Balanzat, Emmanuel; Dartois, Emmanuel; Pilling, Sergio; Farenzena, Lucio; Frota da Silveira, Enio

    2009-01-01

    Icy grain mantles consist of small molecules containing hydrogen, carbon, oxygen and nitrogen atoms (e.g. H 2 O, GO, CO 2 , NH 3 ). Such ices, present in different astrophysical environments (giant planets satellites, comets, dense clouds, and protoplanetary disks), are subjected to irradiation of different energetic particles: UV radiation, ion bombardment (solar and stellar wind as well as galactic cosmic rays), and secondary electrons due to cosmic ray ionization of H 2 . The interaction of these particles with astrophysical ice analogs has been the object of research over the last decades. However, there is a lack of information on the effects induced by the heavy ion component of cosmic rays in the electronic energy loss regime. The aim of the present work is to simulate of the astrophysical environment where ice mantles are exposed to the heavy ion cosmic ray irradiation. Sample ice films at 13 K were irradiated by nickel ions with energies in the 1-10 MeV/u range and analyzed by means of FTIR spectrometry. Nickel ions were used because their energy deposition is similar to that deposited by iron ions, which are particularly abundant cosmic rays amongst the heaviest ones. In this work the effects caused by nickel ions on condensed gases are studied (destruction and production of molecules as well as associated cross sections, sputtering yields) and compared with respective values for light ions and UV photons. (authors)

  18. Photometric properties of Mars soils analogs

    Science.gov (United States)

    Pommerol, A.; Thomas, N.; Jost, B.; Beck, P.; Okubo, C.; McEwen, A.S.

    2013-01-01

    We have measured the bidirectional reflectance of analogs of dry, wet, and frozen Martian soils over a wide range of phase angles in the visible spectral range. All samples were produced from two geologic samples: the standard JSC Mars-1 soil simulant and Hawaiian basaltic sand. In a first step, experiments were conducted with the dry samples to investigate the effects of surface texture. Comparisons with results independently obtained by different teams with similar samples showed a satisfying reproducibility of the photometric measurements as well as a noticeable influence of surface textures resulting from different sample preparation procedures. In a second step, water was introduced to produce wet and frozen samples and their photometry investigated. Optical microscope images of the samples provided information about their microtexture. Liquid water, even in relatively low amount, resulted in the disappearance of the backscattering peak and the appearance of a forward-scattering peak whose intensity increases with the amount of water. Specular reflections only appeared when water was present in an amount large enough to allow water to form a film at the surface of the sample. Icy samples showed a wide variability of photometric properties depending on the physical properties of the water ice. We discuss the implications of these measurements in terms of the expected photometric behavior of the Martian surface, from equatorial to circum-polar regions. In particular, we propose some simple photometric criteria to improve the identification of wet and/or icy soils from multiple observations under different geometries.

  19. MEDIA PEMBELAJARAN ANALOG OSCILLATOR VIRTUAL LABOLATORY

    Directory of Open Access Journals (Sweden)

    Aji Widhi Wibowo

    2016-01-01

    Full Text Available The purpose of this research is to design and implement a Virtual Labolatory Materials Signal Processing Sub discussion 'Oscillator' Analog as Newspapers. Developers using the model Sutopo Ariesto Hadi (2003 as a method to produce the product. Consists of six stages: concept, design, material collecting, assembly, testing and distribution. This results in the development of Virtual media Labolatory with material 'Oscillator' with the results of 4 (four practicum digital oscillator, namely (1 Oscillator Wien Bridge, (2 Colpitts oscillator, (3 Oscillator Hartley and (4 astable multivibrator. Another result is that a user be jobsheet practicum. There are two types, namely: (1 jobsheet grip lecturers and (2 jobsheet for students. In Jobsheet there is a short book that contains the Manual on procedures for the use of virtual labolatory when practical and anatomical description of the product. Virtual Labolatory consists of the initial page (flash scren, the main page (home, pages and pages about the developer's lab referring to the story board. There are four (4 test are: (1 the truth polarity capacitor, (2 the connection (wiring, (3 mode frequency and time in the meter frequency

  20. The MARS2013 Mars analog mission.

    Science.gov (United States)

    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.

  1. Amino acid analogs for tumor imaging

    International Nuclear Information System (INIS)

    Goodman, M.M.; Shoup, T.

    1998-01-01

    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 [ 18 F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an α-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of α-aminoisobutyric acid

  2. Semantics by analogy for illustrative volume visualization☆

    Science.gov (United States)

    Gerl, Moritz; Rautek, Peter; Isenberg, Tobias; Gröller, Eduard

    2012-01-01

    We present an interactive graphical approach for the explicit specification of semantics for volume visualization. This explicit and graphical specification of semantics for volumetric features allows us to visually assign meaning to both input and output parameters of the visualization mapping. This is in contrast to the implicit way of specifying semantics using transfer functions. In particular, we demonstrate how to realize a dynamic specification of semantics which allows to flexibly explore a wide range of mappings. Our approach is based on three concepts. First, we use semantic shader augmentation to automatically add rule-based rendering functionality to static visualization mappings in a shader program, while preserving the visual abstraction that the initial shader encodes. With this technique we extend recent developments that define a mapping between data attributes and visual attributes with rules, which are evaluated using fuzzy logic. Second, we let users define the semantics by analogy through brushing on renderings of the data attributes of interest. Third, the rules are specified graphically in an interface that provides visual clues for potential modifications. Together, the presented methods offer a high degree of freedom in the specification and exploration of rule-based mappings and avoid the limitations of a linguistic rule formulation. PMID:23576827

  3. Intracranial Fluid Redistribution During a Spaceflight Analog

    Science.gov (United States)

    Koppelmans, Vincent; Pasternak, Ofer; Bloomberg, Jacob J.; De Dios, Yiri E.; Wood, Scott J.; Riascos, Roy; Reuter-Lorenz, Patrica A.; Kofman, Igor S.; Mulavara, Ajitkumar P.; Seidler, Rachael D.

    2017-01-01

    The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and limb unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6 deg HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n=12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging, derived from diffusion MRI, was used to quantify the distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreased in the post-central gyrus and precuneus. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.

  4. Resonant Tunneling Analog-To-Digital Converter

    Science.gov (United States)

    Broekaert, T. P. E.; Seabaugh, A. C.; Hellums, J.; Taddiken, A.; Tang, H.; Teng, J.; vanderWagt, J. P. A.

    1995-01-01

    As sampling rates continue to increase, current analog-to-digital converter (ADC) device technologies will soon reach a practical resolution limit. This limit will most profoundly effect satellite and military systems used, for example, for electronic countermeasures, electronic and signal intelligence, and phased array radar. New device and circuit concepts will be essential for continued progress. We describe a novel, folded architecture ADC which could enable a technological discontinuity in ADC performance. The converter technology is based on the integration of multiple resonant tunneling diodes (RTD) and hetero-junction transistors on an indium phosphide substrate. The RTD consists of a layered semiconductor hetero-structure AlAs/InGaAs/AlAs(2/4/2 nm) clad on either side by heavily doped InGaAs contact layers. Compact quantizers based around the RTD offer a reduction in the number of components and a reduction in the input capacitance Because the component count and capacitance scale with the number of bits N, rather than by 2 (exp n) as in the flash ADC, speed can be significantly increased, A 4-bit 2-GSps quantizer circuit is under development to evaluate the performance potential. Circuit designs for ADC conversion with a resolution of 6-bits at 25GSps may be enabled by the resonant tunneling approach.

  5. Young Children's Analogical Problem Solving: Gaining Insights from Video Displays

    Science.gov (United States)

    Chen, Zhe; Siegler, Robert S.

    2013-01-01

    This study examined how toddlers gain insights from source video displays and use the insights to solve analogous problems. Two- to 2.5-year-olds viewed a source video illustrating a problem-solving strategy and then attempted to solve analogous problems. Older but not younger toddlers extracted the problem-solving strategy depicted in the video…

  6. 47 CFR 74.705 - TV broadcast analog station protection.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false TV broadcast analog station protection. 74.705... EXPERIMENTAL RADIO, AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Low Power TV, TV Translator, and TV Booster Stations § 74.705 TV broadcast analog station protection. (a) The TV broadcast...

  7. Using Analogies to Prevent Misconceptions about Chemical Equilibrium

    Science.gov (United States)

    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)…

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

    Science.gov (United States)

    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.

  9. Neuroscientific Insights into the Development of Analogical Reasoning

    Science.gov (United States)

    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…

  10. Analogical reasoning and aging: the processing speed and inhibition hypothesis.

    Science.gov (United States)

    Bugaiska, Aurélia; Thibaut, Jean-Pierre

    2015-01-01

    This study was designed to investigate the effect of aging on analogical reasoning by manipulating the strength of semantic association (LowAssoc or HighAssoc) and the number of distracters' semantic analogies of the A:B::C:D type and to determine which factors might be responsible for the age-related differences on analogical reasoning by testing two different theoretical frameworks: the inhibition hypothesis and the speed mediation hypothesis. We compared young adults and two groups of aging people (old and old-old) with word analogies of the A:B::C:D format. Results indicate an age-related effect on analogical reasoning, this effect being greatest with LowAssoc analogies. It was not associated with the presence of semantic distractors. Moreover, the results show that the variance part of the analogy task due to age was mainly explained by processing speed (rather than by inhibition) in the case of old participants and by both processing speed and inhibition in the old-old group. These results are discussed in relation to current models of aging and their interaction with the processes involved in analogical reasoning.

  11. Young Children's Analogical Reasoning: The Role of Immediate Feedback

    Science.gov (United States)

    Chiu, Shuhui; Alexander, Patricia A.

    2014-01-01

    In this study, a computerized measure, Interactive Analogical Measure (IAM), was developed and used to assess young children's ability to reason analogically. The IAM was equipped to provide corrective feedback and the effects of that feedback were tested for experimental and control groups. A group of 5-year-olds (N = 80) participated in the…

  12. Analogical Reasoning in Children with Specific Language Impairment

    Science.gov (United States)

    Leroy, Sandrine; Parisse, Christophe; Maillart, Christelle

    2012-01-01

    Usage-based theory considers analogical reasoning as a cognitive process required in language development. We hypothesized that difficulties with analogical reasoning could hinder the abstraction of construction schemas, thus slowing down morphosyntactic development for children with specific language impairment (SLI). We also hypothesized, in…

  13. Analysis of Attention and Analogical Reasoning in Children of Poverty

    Science.gov (United States)

    Weatherholt, Tara N.; Harris, Ruby C.; Burns, Barbara M.; Clement, Catherine

    2006-01-01

    This study examined the relationship between specific attentional aspects of processing capacity and analogical reasoning in children from low-income families. 77 children aged 48-77 (M = 56.7) months were assessed on an analogical reasoning task (matrices subtest of the Kaufman Brief Intelligence Test) and on computerized attention tasks designed…

  14. Analogical Reasoning in the Classroom: Insights from Cognitive Science

    Science.gov (United States)

    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…

  15. Some aspects of analogical reasoning in mathematical creativity

    OpenAIRE

    Pease, Alison; Guhe, Markus; Smaill, Alan

    2010-01-01

    Analogical reasoning can shed light on both of the two key processes of creativity– generation and evaluation. Hence, it is a powerful tool for creativity. We illustrate this with three historical case studies of creative mathematical conjectures which were either found or evaluated via analogies. We conclude by describing our ongoing efforts to build computational realisations of these ideas.

  16. SEAS: A simulated evolution approach for analog circuit synthesis

    NARCIS (Netherlands)

    Ning, Zhen-Qiu; Ning, Zhen-Qiu; Mouthaan, A.J.; Wallinga, Hans

    1991-01-01

    The authors present a simulated evolution approach for analog circuit synthesis based on an analogy with the natural selection process in biological environments and on the iterative improvements in solving engineering problems. A prototype framework based on this idea, called SEAS, has been

  17. New Synthetic Routes to Furocoumarins and Their Analogs: A Review

    Directory of Open Access Journals (Sweden)

    Valery F. Traven

    2004-02-01

    Full Text Available Many furocoumarins and their analogs possess a prominent photobiological activity. Some of them are successfully used as drugs in phototherapy of skin diseases. Fries rearrangement of acyloxyheteroarenes, condensation of acylhydroxyheteroarenes with α-carbonyl compounds under base catalysis and transformations of dihydrofurocoumarinones are new trends in synthesis of furocoumarins and their analogs.

  18. Young Children's Analogical Reasoning across Cultures: Similarities and Differences

    Science.gov (United States)

    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…

  19. Analogy as a means of theoretical adoption of pedagogical disciplines

    Directory of Open Access Journals (Sweden)

    Solovcova Irina A.

    2006-01-01

    Full Text Available The paper considers an application of analogy in the initial-teacher training as a tool of approaching pedagogical disciplines. The author proposes a classification of pedagogical analogies which provides choices of the most efficient model for a specific didactic situation. The article clarifies the model of the theoretical approach to pedagogical disciplines through active use of analogy, which contributes to a higher efficiency in a teacher and student interaction. The model consists of three stages: training (the stage of acquiring analogy model, the analytical stage (acquisition of pedagogical concepts, phenomena and systems through the application of analogy, and the stage of self-realization (the application of analogy method in students’ scientific-research activities considering external and internal didactic conditions which transform analogy from a teaching method into a tool for the acquisition of pedagogical disciplines. The author demonstrates that the application of analogy has a positive effect not only on the acquisition of pedagogical knowledge (especially methodic and the development of heuristic skills in students, but also on motivation for the study of pedagogical disciplines (cognitive aspect and professional pedagogical activity (formation of an individual-pedagogical attitude. .

  20. Verbal Analogical Reasoning in Children with Language-Learning Disabilities.

    Science.gov (United States)

    Masterson, Julie J.; And Others

    1993-01-01

    Children (ages 9-13) with language-learning disabilities were administered 5 types of verbal analogies: synonyms, antonyms, linear order, category membership, and functional relationship. Subjects performed worse than mental age-matched children on all types of analogies and performed worse than language age-matched children on all types except…

  1. The Development of Verbal Relations in Analogical Reasonings.

    Science.gov (United States)

    Sternberg, Robert J.; Nigro, Georgia

    A six-process theory of analogical reasoning was tested by administering verbal analogy items to students in grades 3 through college. The items were classified according to five verbal relations: synonyms, antonyms, functional, linear ordering, and class membership. A new method of componential analysis that does not require precueing was used to…

  2. Analog capacitance ROM with IGFET bucket-brigade shift register

    DEFF Research Database (Denmark)

    Bruun, Erik; Olesen, Ole

    1975-01-01

    A new type of monolithic analog read-out memory is described. It consists of a memory element and associated on-chip readout circuitry. The memory can be used for storing sample values of time-varying analog signals. The memory element is a matrix of MOS capacitors, preprogrammed in size...

  3. Molecular interactions between (--epigallocatechin gallate analogs and pancreatic lipase.

    Directory of Open Access Journals (Sweden)

    Shihui Wang

    Full Text Available 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.

  4. Modular arrangement of regulatory RNA elements.

    Science.gov (United States)

    Roßmanith, Johanna; Narberhaus, Franz

    2017-03-04

    Due to their simple architecture and control mechanism, regulatory RNA modules are attractive building blocks in synthetic biology. This is especially true for riboswitches, which are natural ligand-binding regulators of gene expression. The discovery of various tandem riboswitches inspired the design of combined RNA modules with activities not yet found in nature. Riboswitches were placed in tandem or in combination with a ribozyme or temperature-responsive RNA thermometer resulting in new functionalities. Here, we compare natural examples of tandem riboswitches with recently designed artificial RNA regulators suggesting substantial modularity of regulatory RNA elements. Challenges associated with modular RNA design are discussed.

  5. Determination of ligand binding modes in weak protein–ligand complexes using sparse NMR data

    Energy Technology Data Exchange (ETDEWEB)

    Mohanty, Biswaranjan; Williams, Martin L.; Doak, Bradley C.; Vazirani, Mansha; Ilyichova, Olga [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); Wang, Geqing [La Trobe University, La Trobe Institute for Molecular Bioscience (Australia); Bermel, Wolfgang [Bruker Biospin GmbH (Germany); Simpson, Jamie S.; Chalmers, David K. [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); King, Glenn F. [The University of Queensland, Institute for Molecular Bioscience (Australia); Mobli, Mehdi, E-mail: m.mobli@uq.edu.au [The University of Queensland, Centre for Advanced Imaging (Australia); Scanlon, Martin J., E-mail: martin.scanlon@monash.edu [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia)

    2016-11-15

    We describe a general approach to determine the binding pose of small molecules in weakly bound protein–ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of Ile, Leu, Val, Ala and Thr methyl groups using triple resonance scalar correlation data. The same sample may be used to obtain Met {sup ε}CH{sub 3} assignments using NOESY-based methods, although the superior sensitivity of NOESY using [U-{sup 13}C,{sup 15}N]-labeled protein makes the use of this second sample more efficient. We describe a structural model for a weakly binding ligand bound to its target protein, DsbA, derived from intermolecular methyl-to-ligand nuclear Overhauser enhancements, and demonstrate that the ability to assign all methyl resonances in the spectrum is essential to derive an accurate model of the structure. Once the methyl assignments have been obtained, this approach provides a rapid means to generate structural models for weakly bound protein–ligand complexes. Such weak complexes are often found at the beginning of programs of fragment based drug design and can be challenging to characterize using X-ray crystallography.

  6. The making of analog module for gamma camera interface

    International Nuclear Information System (INIS)

    Yulinarsari, Leli; Rl, Tjutju; Susila, Atang; Sukandar

    2003-01-01

    The making of an analog module for gamma camera has been conducted. For computerization of planar gamma camera 37 PMT it has been developed interface hardware technology and software between the planar gamma camera with PC. With this interface gamma camera image information (Originally analog signal) was changed to digital single, therefore processes of data acquisition, image quality increase and data analysis as well as data base processing can be conducted with the help of computers, there are three gamma camera main signals, i.e. X, Y and Z . This analog module makes digitation of analog signal X and Y from the gamma camera that conveys position information coming from the gamma camera crystal. Analog conversion to digital was conducted by 2 converters ADC 12 bit with conversion time 800 ns each, conversion procedure for each coordinate X and Y was synchronized using suitable strobe signal Z for information acceptance

  7. Learning Plate Tectonics Using a Pre-Analogy Step

    Science.gov (United States)

    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. NASA HRP Immunology Discipline - Use of Terrestrial Analogs

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  10. ProBiS-ligands: a web server for prediction of ligands by examination of protein binding sites.

    Science.gov (United States)

    Konc, Janez; Janežič, Dušanka

    2014-07-01

    The ProBiS-ligands web server predicts binding of ligands to a protein structure. Starting with a protein structure or binding site, ProBiS-ligands first identifies template proteins in the Protein Data Bank that share similar binding sites. Based on the superimpositions of the query protein and the similar binding sites found, the server then transposes the ligand structures from those sites to the query protein. Such ligand prediction supports many activities, e.g. drug repurposing. The ProBiS-ligands web server, an extension of the ProBiS web server, is open and free to all users at http://probis.cmm.ki.si/ligands. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    Science.gov (United States)

    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…

  12. Frozen orbit realization using LQR analogy

    Science.gov (United States)

    Nagarajan, N.; Rayan, H. Reno

    In the case of remote sensing orbits, the Frozen Orbit concept minimizes altitude variations over a given region using passive means. This is achieved by establishing the mean eccentricity vector at the orbital poles i.e., by fixing the mean argument of perigee at 90 deg with an appropriate eccentricity to balance the perturbations due to zonal harmonics J2 and J3 of the Earth's potential. Eccentricity vector is a vector whose magnitude is the eccentricity and direction is the argument of perigee. The launcher dispersions result in an eccentricity vector which is away from the frozen orbit values. The objective is then to formulate an orbit maneuver strategy to optimize the fuel required to achieve the frozen orbit in the presence of visibility and impulse constraints. It is shown that the motion of the eccentricity vector around the frozen perigee can be approximated as a circle. Combining the circular motion of the eccentricity vector around the frozen point and the maneuver equation, the following discrete equation is obtained. X(k+1) = AX(k) + Bu(k), where X is the state (i.e. eccentricity vector components), A the state transition matrix, u the scalar control force (i.e. dV in this case) and B the control matrix which transforms dV into eccentricity vector change. Based on this, it is shown that the problem of optimizing the fuel can be treated as a Linear Quadratic Regulator (LQR) problem in which the maneuver can be solved by using control system design tools like MATLAB by deriving an analogy LQR design.

  13. Remote Sensing and Quantization of Analog Sensors

    Science.gov (United States)

    Strauss, Karl F.

    2011-01-01

    This method enables sensing and quantization of analog strain gauges. By manufacturing a piezoelectric sensor stack in parallel (physical) with a piezoelectric actuator stack, the capacitance of the sensor stack varies in exact proportion to the exertion applied by the actuator stack. This, in turn, varies the output frequency of the local sensor oscillator. The output, F(sub out), is fed to a phase detector, which is driven by a stable reference, F(sub ref). The output of the phase detector is a square waveform, D(sub out), whose duty cycle, t(sub W), varies in exact proportion according to whether F(sub out) is higher or lower than F(sub ref). In this design, should F(sub out) be precisely equal to F(sub ref), then the waveform has an exact 50/50 duty cycle. The waveform, D(sub out), is of generally very low frequency suitable for safe transmission over long distances without corruption. The active portion of the waveform, t(sub W), gates a remotely located counter, which is driven by a stable oscillator (source) of such frequency as to give sufficient digitization of t(sub W) to the resolution required by the application. The advantage to this scheme is that it negates the most-common, present method of sending either very low level signals (viz. direct output from the sensors) across great distances (anything over one-half meter) or the need to transmit widely varying higher frequencies over significant distances thereby eliminating interference [both in terms of beat frequency generation and in-situ EMI (electromagnetic interference)] caused by ineffective shielding. It also results in a significant reduction in shielding mass.

  14. De Analogía a Digitalia

    Directory of Open Access Journals (Sweden)

    Dr. Xaime Fandiño Alonso

    2001-01-01

    ía, creatividad y contenidos.ABSTRACTThe transition towards binary-based technology has unleashed dramatic changes that in the last decade have affected the different stages involved in an audiovisual production: from scripting and creating a project, through the various technological procedures of the actual production process to its final distribution.The remains of the analogical era are finally sinking under a seemingly unstoppable wave of constantly evolving new digital environments.The new hardware devices used in this field are mainly prototypes. An ever evolving market, the constant arising of new competitors, newborn joint-ventures and a myriad of related facts force technology providers to keep a pace of constant updating in a mad race of fierce competition.The old system which implied one machine for each process is increasingly becoming a memory of the past. Today new devices are being launched at such a speed that the old technological approach which dealt with mechanical appliances like magnetoscopes, closed platforms and linear recording are already bound for extinction.It’s only natural then that the sacred cows of the industry fear for their position. Big and small are elusive concepts in this new audiovisual frenzy. Its almost daily routine to read about big audiovisual corporations announcing mergers, buy-outs or the acquisition of a stake in new and small creativity and development firms built from scratch by young entrepreneurs out of the blue.The digital era is drawing a heavy curtain that luckily leaves behind an analogical era in which the ownership of the costly means of production was the most important card in the game. The artist could only exercise its art if access to the professional team and technical equipment required for an audiovisual work was granted by its proprietors.Today, digital means new systems with far more productive environments which besides are user-friendly and cost only a small fraction of the old hardware.Right now, with

  15. Nuclease-resistant c-di-AMP derivatives that differentially recognize RNA and protein receptors

    Science.gov (United States)

    Meehan, Robert E.; Torgerson, Chad D.; Gaffney, Barbara L.; Jones, Roger A.; Strobel, Scott A.

    2016-01-01

    The ability of bacteria to sense environmental cues and adapt is essential for their survival. The use of second-messenger signaling molecules to translate these cues into a physiological response is a common mechanism employed by bacteria. The second messenger 3’-5’-cyclic diadenosine monophosphate (c-di-AMP) has been linked to a diverse set of biological processes involved in maintaining cell viability and homeostasis, as well as pathogenicity. A complex network of both protein and RNA receptors inside the cell activate specific pathways and mediate phenotypic outputs in response to c-di-AMP. Structural analysis of these RNA and protein receptors has revealed the different recognition elements employed by these effectors to bind the same small molecule. Herein, using a series of c-di-AMP analogs, we probed the interactions made with a riboswitch and a phosphodiesterase protein to identify the features important for c-di-AMP binding and recognition. We found that the ydaO riboswitch binds c-di-AMP in two discrete sites with near identical affinity and a Hill coefficient of 1.6. The ydaO riboswitch distinguishes between c-di-AMP and structurally related second messengers by discriminating against an amine at the C2 position, more than a carbonyl at the C6 position. We also identified phosphate-modified analogs that bind both the ydaO RNA and GdpP protein with high affinity, while symmetrically-modified ribose analogs exhibited a substantial decrease in ydaO affinity, but retained high affinity for GdpP. These ligand modifications resulted in increased resistance to enzyme-catalyzed hydrolysis by the GdpP enzyme. Together, these data suggest that these c-di-AMP analogs could be useful as chemical tools to specifically target subsections of the second-messenger signaling pathways. PMID:26789423

  16. Ligand cluster-based protein network and ePlatton, a multi-target ligand finder.

    Science.gov (United States)

    Du, Yu; Shi, Tieliu

    2016-01-01

    Small molecules are information carriers that make cells aware of external changes and couple internal metabolic and signalling pathway systems with each other. In some specific physiological status, natural or artificial molecules are used to interact with selective biological targets to activate or inhibit their functions to achieve expected biological and physiological output. Millions of years of evolution have optimized biological processes and pathways and now the endocrine and immune system cannot work properly without some key small molecules. In the past thousands of years, the human race has managed to find many medicines against diseases by trail-and-error experience. In the recent decades, with the deepening understanding of life and the progress of molecular biology, researchers spare no effort to design molecules targeting one or two key enzymes and receptors related to corresponding diseases. But recent studies in pharmacogenomics have shown that polypharmacology may be necessary for the effects of drugs, which challenge the paradigm, 'one drug, one target, one disease'. Nowadays, cheminformatics and structural biology can help us reasonably take advantage of the polypharmacology to design next-generation promiscuous drugs and drug combination therapies. 234,591 protein-ligand interactions were extracted from ChEMBL. By the 2D structure similarity, 13,769 ligand emerged from 156,151 distinct ligands which were recognized by 1477 proteins. Ligand cluster- and sequence-based protein networks (LCBN, SBN) were constructed, compared and analysed. For assisting compound designing, exploring polypharmacology and finding possible drug combination, we integrated the pathway, disease, drug adverse reaction and the relationship of targets and ligand clusters into the web platform, ePlatton, which is available at http://www.megabionet.org/eplatton. Although there were some disagreements between the LCBN and SBN, communities in both networks were largely the same

  17. Towards ligand docking including explicit interface water molecules.

    Directory of Open Access Journals (Sweden)

    Gordon Lemmon

    Full Text Available Small molecule docking predicts the interaction of a small molecule ligand with a protein at atomic-detail accuracy including position and conformation the ligand but also conformational changes of the protein upon ligand binding. While successful in the majority of cases, docking algorithms including RosettaLigand fail in some cases to predict the correct protein/ligand complex structure. In this study we show that simultaneous docking of explicit interface water molecules greatly improves Rosetta's ability to distinguish correct from incorrect ligand poses. This result holds true for both protein-centric water docking wherein waters are located relative to the protein binding site and ligand-centric water docking wherein waters move with the ligand during docking. Protein-centric docking is used to model 99 HIV-1 protease/protease inhibitor structures. We find protease inhibitor placement improving at a ratio of 9:1 when one critical interface water molecule is included in the docking simulation. Ligand-centric docking is applied to 341 structures from the CSAR benchmark of diverse protein/ligand complexes [1]. Across this diverse dataset we see up to 56% recovery of failed docking studies, when waters are included in the docking simulation.

  18. Eye Movements Reveal Optimal Strategies for Analogical Reasoning.

    Science.gov (United States)

    Vendetti, Michael S; Starr, Ariel; Johnson, Elizabeth L; Modavi, Kiana; Bunge, Silvia A

    2017-01-01

    Analogical reasoning refers to the process of drawing inferences on the basis of the relational similarity between two domains. Although this complex cognitive ability has been the focus of inquiry for many years, most models rely on measures that cannot capture individuals' thought processes moment by moment. In the present study, we used participants' eye movements to investigate reasoning strategies in real time while solving visual propositional analogy problems (A:B::C:D). We included both a semantic and a perceptual lure on every trial to determine how these types of distracting information influence reasoning strategies. Participants spent more time fixating the analogy terms and the target relative to the other response choices, and made more saccades between the A and B items than between any other items. Participants' eyes were initially drawn to perceptual lures when looking at response choices, but they nonetheless performed the task accurately. We used participants' gaze sequences to classify each trial as representing one of three classic analogy problem solving strategies and related strategy usage to analogical reasoning performance. A project-first strategy, in which participants first extrapolate the relation between the AB pair and then generalize that relation for the C item, was both the most commonly used strategy as well as the optimal strategy for solving visual analogy problems. These findings provide new insight into the role of strategic processing in analogical problem solving.

  19. Eye Movements Reveal Optimal Strategies for Analogical Reasoning

    Directory of Open Access Journals (Sweden)

    Michael S. Vendetti

    2017-06-01

    Full Text Available Analogical reasoning refers to the process of drawing inferences on the basis of the relational similarity between two domains. Although this complex cognitive ability has been the focus of inquiry for many years, most models rely on measures that cannot capture individuals' thought processes moment by moment. In the present study, we used participants' eye movements to investigate reasoning strategies in real time while solving visual propositional analogy problems (A:B::C:D. We included both a semantic and a perceptual lure on every trial to determine how these types of distracting information influence reasoning strategies. Participants spent more time fixating the analogy terms and the target relative to the other response choices, and made more saccades between the A and B items than between any other items. Participants' eyes were initially drawn to perceptual lures when looking at response choices, but they nonetheless performed the task accurately. We used participants' gaze sequences to classify each trial as representing one of three classic analogy problem solving strategies and related strategy usage to analogical reasoning performance. A project-first strategy, in which participants first extrapolate the relation between the AB pair and then generalize that relation for the C item, was both the most commonly used strategy as well as the optimal strategy for solving visual analogy problems. These findings provide new insight into the role of strategic processing in analogical problem solving.

  20. A hierarchical spatiotemporal analog forecasting model for count data.

    Science.gov (United States)

    McDermott, Patrick L; Wikle, Christopher K; Millspaugh, Joshua

    2018-01-01

    Analog forecasting is a mechanism-free nonlinear method that forecasts a system forward in time by examining how past states deemed similar to the current state moved forward. Previous applications of analog forecasting has been successful at producing robust forecasts for a variety of ecological and physical processes, but it has typically been presented in an empirical or heuristic procedure, rather than as a formal statistical model. The methodology presented here extends the model-based analog method of McDermott and Wikle (Environmetrics, 27, 2016, 70) by placing analog forecasting within a fully hierarchical statistical framework that can accommodate count observations. Using a Bayesian approach, the hierarchical analog model is able to quantify rigorously the uncertainty associated with forecasts. Forecasting waterfowl settling patterns in the northwestern United States and Canada is conducted by applying the hierarchical analog model to a breeding population survey dataset. Sea surface temperature (SST) in the Pacific Ocean is used to help identify potential analogs for the waterfowl settling patterns.

  1. Design rules for superconducting analog-digital transducers; Entwurfsregeln fuer Supraleitende Analog-Digital-Wandler

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Taghrid

    2015-05-29

    This Thesis is a contribution for dimensioning aspects of circuits designs in superconductor electronics. Mainly superconductor comparators inclusive Josephson comparators as well as QOJS-Comparators are investigated. Both types were investigated in terms of speed and sensitivity. The influence of the thermal noise on the decision process of the comparators represent in so called gray zone, which is analysed in this thesis. Thereby, different relations between design parameters were derived. A circuit model of the Josephson comparator was verified by experiments. Concepts of superconductor analog-to-digital converters, which are based on above called comparators, were investigated in detail. From the comparator design rules, new rules for AD-converters were derived. Because of the reduced switching energy, the signal to noise ratio (SNR) of the circuits is affected and therefore the reliability of the decision-process is affected. For special applications with very demanding requirements in terms of the speed and accuracy superconductor analog-to-digital converters offer an excellent performance. This thesis provides relations between different design paramenters and shows resulting trade-offs, This method is transparent and easy to transfer to other circuit topologies. As a main result, a highly predictive tool for dimensioning of superconducting ADC's is proved.

  2. Symmetry energy II: Isobaric analog states

    Science.gov (United States)

    Danielewicz, Pawel; Lee, Jenny

    2014-02-01

    Using excitation energies to isobaric analog states (IAS) and charge invariance, we extract nuclear symmetry coefficients, representing a mass formula, on a nucleus-by-nucleus basis. Consistently with charge invariance, the coefficients vary weakly across an isobaric chain. However, they change strongly with nuclear mass and range from aa˜10 MeV at mass A˜10 to aa˜22 MeV at A˜240. Variation with mass can be understood in terms of dependence of nuclear symmetry energy on density and the rise in importance of low densities within nuclear surface in smaller systems. At A≳30, the dependence of coefficients on mass can be well described in terms of a macroscopic volume-surface competition formula with aaV≃33.2 MeV and aaS≃10.7 MeV. Our further investigation shows, though, that the fitted surface symmetry coefficient likely significantly underestimates that for the limit of half-infinite matter. Following the considerations of a Hohenberg-Kohn functional for nuclear systems, we determine how to find in practice the symmetry coefficient using neutron and proton densities, even when those densities are simultaneously affected by significant symmetry-energy and Coulomb effects. These results facilitate extracting the symmetry coefficients from Skyrme-Hartree-Fock (SHF) calculations, that we carry out using a variety of Skyrme parametrizations in the literature. For the parametrizations, we catalog novel short-wavelength instabilities. In our further analysis, we retain only those parametrizations which yield systems that are adequately stable both in the long- and short-wavelength limits. In comparing the SHF and IAS results for the symmetry coefficients, we arrive at narrow (±2.4 MeV) constraints on the symmetry-energy values S(ρ) at 0.04≲ρ≲0.13 fm. Towards normal density the constraints significantly widen, but the normal value of energy aaV and the slope parameter L are found to be strongly correlated. To narrow the constraints, we reach for the

  3. Targeting nanoparticles to M cells with non-peptidic ligands for oral vaccination.

    Science.gov (United States)

    Fievez, Virginie; Plapied, Laurence; des Rieux, Anne; Pourcelle, Vincent; Freichels, Hélène; Wascotte, Valentine; Vanderhaeghen, Marie-Lyse; Jerôme, Christine; Vanderplasschen, Alain; Marchand-Brynaert, Jacqueline; Schneider, Yves-Jacques; Préat, Véronique

    2009-09-01

    The presence of RGD on nanoparticles allows the targeting of beta1 integrins at the apical surface of human M cells and the enhancement of an immune response after oral immunization. To check the hypothesis that non-peptidic ligands targeting intestinal M cells or APCs would be more efficient for oral immunization than RGD, novel non-peptidic and peptidic analogs (RGD peptidomimitic (RGDp), LDV derivative (LDVd) and LDV peptidomimetic (LDVp)) as well as mannose were grafted on the PEG chain of PCL-PEG and incorporated in PLGA-based nanoparticles. RGD and RGDp significantly increased the transport of nanoparticles across an in vitro model of human M cells as compared to enterocytes. RGD, LDVp, LDVd and mannose enhanced nanoparticle uptake by macrophages in vitro. The intraduodenal immunization with RGDp-, LDVd- or mannose-labeled nanoparticles elicited a higher production of IgG antibodies than the intramuscular injection of free ovalbumin or intraduodenal administration of either non-targeted or RGD-nanoparticles. Targeted formulations were also able to induce a cellular immune response. In conclusion, the in vitro transport of nanoparticles, uptake by macrophages and the immune response were positively influenced by the presence of ligands at the surface of nanoparticles. These targeted-nanoparticles could thus represent a promising delivery system for oral immunization.

  4. Analogical Arguments in Ethics and Law: A Defence of Deductivism

    Directory of Open Access Journals (Sweden)

    Fábio Perin Shecaira

    2013-09-01

    Full Text Available The paper provides a qualified defence of Bruce Waller’s deductivist schema for a priori analogical arguments in ethics and law. One crucial qualification is that the schema represents analogical arguments as complexes composed of one deductive inference (hence “deductivism” but also of one non-deductive subargument. Another important qualification is that the schema is informed by normative assumptions regarding the conditions that an analogical argument must satisfy in order for it to count as an optimal instance of its kind. Waller’s schema (in qualified form is defended from criticisms formulated by Trudy Govier, Marcello Guarini and Lilian Bermejo-Luque.

  5. Reasoning by analogy as an aid to heuristic theorem proving.

    Science.gov (United States)

    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.

  6. Source selection for analogical reasoning an empirical approach

    Energy Technology Data Exchange (ETDEWEB)

    Stubblefield, W.A. [Sandia National Labs., Albuquerque, NM (United States); Luger, G.F. [Univ. of New Mexico, Albuquerque, NM (United States)

    1996-12-31

    The effectiveness of an analogical reasoner depends upon its ability to select a relevant analogical source. In many problem domains, however, too little is known about target problems to support effective source selection. This paper describes the design and evaluation of SCAVENGER, an analogical reasoner that applies two techniques to this problem: (1) An assumption-based approach to matching that allows properties of candidate sources to match unknown target properties in the absence of evidence to the contrary. (2) The use of empirical learning to improve memory organization based on problem solving experience.

  7. Josephson junction analog and quasiparticle-pair current

    DEFF Research Database (Denmark)

    Bak, Christen Kjeldahl; Pedersen, Niels Falsig

    1973-01-01

    A close analogy exists between a Josephson junction and a phase-locked loop. A new type of electrical analog based on this principle is presented. It is shown that the inclusion in this analog of a low-pass filter gives rise to a current of the same form as the Josephson quasiparticle-pair current....... A simple picture of the quasiparticle-pair current, which gives the right dependences, is obtained by assuming a junction cutoff frequency to be at the energy gap. ©1973 American Institute of Physics...

  8. Single-event transients (SET) in analog circuits

    International Nuclear Information System (INIS)

    Chen Panxun; Zhou Kaiming

    2006-01-01

    A new phenomenon of single- event upset is introduced. The transient signal is produced in the output of analog circuits after a heavy ion strikes. The transient upset can influence the circuit connected with the output of analog circuits. For example, the output of operational amplifier can be connected with the input of a digital counter, and the pulse of sufficiently high transient output induced by an ion can increase counts of the counter. On the other hand, the transient voltage signal at the output of analog circuits can change the stage of other circuits. (authors)

  9. UV IRRADIATION OF AROMATIC NITROGEN HETEROCYCLES IN INTERSTELLAR ICE ANALOGS

    Science.gov (United States)

    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.

  10. Fast parallel-series analog-to-digital converter

    International Nuclear Information System (INIS)

    Pogosov, A.Yu.

    1987-01-01

    Fast analog-to-digital converters are used in systems for detection of rapid processes, nuclear spectroscopy. A 12-digit analog-to-digital converter with conversion time of 160 ns and conversion frequency of 8.3 MHz is described; a segmented digital-to-analog converter with differential non-linearity of < 0.01% and a differential amplifier-limiter with setting time of 80 ns at the error of 0.2% are utilized in the converter; a control device is based on the chain of flip-flop circuit

  11. Kinematics and age of 15 stars-photometric solar analogs

    Science.gov (United States)

    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.

  12. Global orbit feedback utilizing analog and digital technologies

    International Nuclear Information System (INIS)

    Singh, O.; Tang, Y.; Ramamoorthy, S.; Krinsky, S.; Yu, L.H.

    1997-01-01

    At the NSLS, an analog global orbit feedback system is used in regular operations, and a digital global orbit feedback system is available in machine physics studies on the X-Ray Ring. Here, the authors discuss the relative merits of utilizing analog and digital technology in orbit feedback. Results of experiments are reported characterizing the performance of the analog and digital systems when operated individually or together. They give their thoughts on plans for future development of the orbit feedback systems at the NSLS

  13. ASIC3 Channels Integrate Agmatine and Multiple Inflammatory Signals through the Nonproton Ligand Sensing Domain

    Directory of Open Access Journals (Sweden)

    Cao Hui

    2010-12-01

    Full Text Available Abstract Background Acid-sensing ion channels (ASICs have long been known to sense extracellular protons and contribute to sensory perception. Peripheral ASIC3 channels represent natural sensors of acidic and inflammatory pain. We recently reported the use of a synthetic compound, 2-guanidine-4-methylquinazoline (GMQ, to identify a novel nonproton sensing domain in the ASIC3 channel, and proposed that, based on its structural similarity with GMQ, the arginine metabolite agmatine (AGM may be an endogenous nonproton ligand for ASIC3 channels. Results Here, we present further evidence for the physiological correlation between AGM and ASIC3. Among arginine metabolites, only AGM and its analog arcaine (ARC activated ASIC3 channels at neutral pH in a sustained manner similar to GMQ. In addition to the homomeric ASIC3 channels, AGM also activated heteromeric ASIC3 plus ASIC1b channels, extending its potential physiological relevance. Importantly, the process of activation by AGM was highly sensitive to mild acidosis, hyperosmolarity, arachidonic acid (AA, lactic acid and reduced extracellular Ca2+. AGM-induced ASIC3 channel activation was not through the chelation of extracellular Ca2+ as occurs with increased lactate, but rather through a direct interaction with the newly identified nonproton ligand sensing domain. Finally, AGM cooperated with the multiple inflammatory signals to cause pain-related behaviors in an ASIC3-dependent manner. Conclusions Nonproton ligand sensing domain might represent a novel mechanism for activation or sensitization of ASIC3 channels underlying inflammatory pain-sensing under in vivo conditions.

  14. Predicting Nanocrystal Shape through Consideration of Surface-Ligand Interactions

    KAUST Repository

    Bealing, Clive R.

    2012-03-27

    Density functional calculations for the binding energy of oleic acid-based ligands on Pb-rich {100} and {111} facets of PbSe nanocrystals determine the surface energies as a function of ligand coverage. Oleic acid is expected to bind to the nanocrystal surface in the form of lead oleate. The Wulff construction predicts the thermodynamic equilibrium shape of the PbSe nanocrystals. The equilibrium shape is a function of the ligand surface coverage, which can be controlled by changing the concentration of oleic acid during synthesis. The different binding energy of the ligand on the {100} and {111} facets results in different equilibrium ligand coverages on the facets, and a transition in the equilibrium shape from octahedral to cubic is predicted when increasing the ligand concentration during synthesis. © 2012 American Chemical Society.

  15. Prediction of GPCR-Ligand Binding Using Machine Learning Algorithms

    Directory of Open Access Journals (Sweden)

    Sangmin Seo

    2018-01-01

    Full Text Available We propose a novel method that predicts binding of G-protein coupled receptors (GPCRs and ligands. The proposed method uses hub and cycle structures of ligands and amino acid motif sequences of GPCRs, rather than the 3D structure of a receptor or similarity of receptors or ligands. The experimental results show that these new features can be effective in predicting GPCR-ligand binding (average area under the curve [AUC] of 0.944, because they are thought to include hidden properties of good ligand-receptor binding. Using the proposed method, we were able to identify novel ligand-GPCR bindings, some of which are supported by several studies.

  16. Mixed ligand chelates of rare earths in aqueous solution

    International Nuclear Information System (INIS)

    Lakhani, S.U.; Thakur, G.S.; Sangal, S.P.

    1981-01-01

    Mixed ligand chelates of the 1:1 trivalent lanthanoids-EDTA, HEDTA and NTA chelates-1, 2-Dihydroxybenzene (Pyrocatechol) have been investigated at 35degC and 0.2 M ionic strength maintained by NaC10 4 . The formation of mixed ligand chelates has been found in all cases. The formation of mixed ligand chelates with EDTA shows the coordination number of lanthanoids to be eight, while the mixed ligand chelates with HEDTA and NTA shows the coordination number to be seven and six respectively. The stability constants of mixed ligand chelates are smaller than the binary complexes. The order of stability constants with respect to primary ligands follows the order NTA>HEDTA>EDTA. With respect to metal ions the stability constants increases with the decrease in ionic radii such as Gd< Er< Yb. (author)

  17. New ' Bucky- ligands'. Potentially Monoanionic Terdentate Diamino Aryl Pincer Ligands Anchored to C60

    NARCIS (Netherlands)

    Koten, G. van; Meijer, M.D.; Gossage, R.A.; Jastrzebski, J.T.B.H.

    1998-01-01

    Two new methanofullerenes have been prepared by the reaction of C{6}{0} with diazo substituted, potentially monoanionic, terdentate diamino aryl ligands, yielding a mixture of the open valence [5, 6]- and closed valence [6,6]-isomers. Single isomers of the pure [6,6]-methanofullerenes were obtained

  18. LASSO-ligand activity by surface similarity order: a new tool for ligand based virtual screening.

    Science.gov (United States)

    Reid, Darryl; Sadjad, Bashir S; Zsoldos, Zsolt; Simon, Aniko

    2008-01-01

    Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

  19. LASSO—ligand activity by surface similarity order: a new tool for ligand based virtual screening

    Science.gov (United States)

    Reid, Darryl; Sadjad, Bashir S.; Zsoldos, Zsolt; Simon, Aniko

    2008-06-01

    Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

  20. Variation in one residue associated with the metal ion-dependent adhesion site regulates αIIbβ3 integrin ligand binding affinity.

    Directory of Open Access Journals (Sweden)

    Joel Raborn

    Full Text Available The Asp of the RGD motif of the ligand coordinates with the β I domain metal ion dependent adhesion site (MIDAS divalent cation, emphasizing the importance of the MIDAS in ligand binding. There appears to be two distinct groups of integrins that differ in their ligand binding affinity and adhesion ability. These differences may be due to a specific residue associated with the MIDAS, particularly the β3 residue Ala(252 and corresponding Ala in the β1 integrin compared to the analogous Asp residue in the β2 and β7 integrins. Interestingly, mutations in the adjacent to MIDAS (ADMIDAS of integrins α4β7 and αLβ2 increased the binding and adhesion abilities compared to the wild-type, while the same mutations in the α2β1, α5β1, αVβ3, and αIIbβ3 integrins demonstrated decreased ligand binding and adhesion. We introduced a mutation in the αIIbβ3 to convert this MIDAS associated Ala(252 to Asp. By combination of this mutant with mutations of one or two ADMIDAS residues, we studied the effects of this residue on ligand binding and adhesion. Then, we performed molecular dynamics simulations on the wild-type and mutant αIIbβ3 integrin β I domains, and investigated the dynamics of metal ion binding sites in different integrin-RGD complexes. We found that the tendency of calculated binding free energies was in excellent agreement with the experimental results, suggesting that the variation in this MIDAS associated residue accounts for the differences in ligand binding and adhesion among different integrins, and it accounts for the conflicting results of ADMIDAS mutations within different integrins. This study sheds more light on the role of the MIDAS associated residue pertaining to ligand binding and adhesion and suggests that this residue may play a pivotal role in integrin-mediated cell rolling and firm adhesion.