Sample records for analogous hiv-p6 protein

  1. Solution structure of the Equine Infectious Anemia Virus p9 protein: a rationalization of its different ALIX binding requirements compared to the analogous HIV-p6 protein

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    Henklein Peter


    Full Text Available Abstract Background The equine infection anemia virus (EIAV p9 Gag protein contains the late (L- domain required for efficient virus release of nascent virions from the cell membrane of infected cell. Results In the present study the p9 protein and N- and C-terminal fragments (residues 1-21 and 22-51, respectively were chemically synthesized and used for structural analyses. Circular dichroism and 1H-NMR spectroscopy provide the first molecular insight into the secondary structure and folding of this 51-amino acid protein under different solution conditions. Qualitative 1H-chemical shift and NOE data indicate that in a pure aqueous environment p9 favors an unstructured state. In its most structured state under hydrophobic conditions, p9 adopts a stable helical structure within the C-terminus. Quantitative NOE data further revealed that this α-helix extends from Ser-27 to Ser-48, while the N-terminal residues remain unstructured. The structural elements identified for p9 differ substantially from that of the functional homologous HIV-1 p6 protein. Conclusions These structural differences are discussed in the context of the different types of L-domains regulating distinct cellular pathways in virus budding. EIAV p9 mediates virus release by recruiting the ALG2-interacting protein X (ALIX via the YPDL-motif to the site of virus budding, the counterpart of the YPXnL-motif found in p6. However, p6 contains an additional PTAP L-domain that promotes HIV-1 release by binding to the tumor susceptibility gene 101 (Tsg101. The notion that structures found in p9 differ form that of p6 further support the idea that different mechanisms regulate binding of ALIX to primary versus secondary L-domains types.

  2. Protein Structure Prediction with Visuospatial Analogy (United States)

    Davies, Jim; Glasgow, Janice; Kuo, Tony

    We show that visuospatial representations and reasoning techniques can be used as a similarity metric for analogical protein structure prediction. Our system retrieves pairs of α-helices based on contact map similarity, then transfers and adapts the structure information to an unknown helix pair, showing that similar protein contact maps predict similar 3D protein structure. The success of this method provides support for the notion that changing representations can enable similarity metrics in analogy.

  3. NMCP/LINC proteins: putative lamin analogs in plants? (United States)

    Ciska, Malgorzata; Moreno Diaz de la Espina, Susana


    Lamins are the main components of the metazoan lamina, and while the organization of the nuclear lamina of metazoans and plants is similar, there are apparently no genes encoding lamins or most lamin-binding proteins in plants. Thus, the plant lamina is not lamin-based and the proteins that form this structure are still to be characterized. Members of the plant NMCP/LINC/CRWN protein family share the typical tripartite structure of lamins, although the 2 exhibit no sequence similarity. However, given the many similarities between NMCP/LINC/CRWN proteins and lamins (structural organization, position of conserved regions, sub-nuclear distribution, solubility, and pattern of expression), these proteins are good candidates to carry out the functions of lamins in plants. Moreover, functional analysis of NMCP/LINC mutants has revealed their involvement in maintaining nuclear size and shape, another activity fulfilled by lamins. This review summarizes the current understanding of NMCP/LINC proteins and discusses future studies that will be required to demonstrate definitively that these proteins are plant analogs of lamins.

  4. Design of a reversible biotin analog and applications in protein labeling, detection, and isolation. (United States)

    Ying, Lai-Qiang; Branchaud, Bruce P


    To expand the applicability of the biotin-(strept)avidin system, a biotin analog with reversible binding under non-denaturing conditions has been designed, and its applications in protein labeling, detection, and isolation have been evaluated.

  5. Analog sensitive chemical inhibition of the DEAD-box protein DDX3. (United States)

    Floor, Stephen N; Barkovich, Krister J; Condon, Kendall J; Shokat, Kevan M; Doudna, Jennifer A


    Proper maintenance of RNA structure and dynamics is essential to maintain cellular health. Multiple families of RNA chaperones exist in cells to modulate RNA structure, RNA-protein complexes, and RNA granules. The largest of these families is the DEAD-box proteins, named after their catalytic Asp-Glu-Ala-Asp motif. The human DEAD-box protein DDX3 is implicated in diverse biological processes including translation initiation and is mutated in numerous cancers. Like many DEAD-box proteins, DDX3 is essential to cellular health and exhibits dosage sensitivity, such that both decreases and increases in protein levels can be lethal. Therefore, chemical inhibition would be an ideal tool to probe the function of DDX3. However, most DEAD-box protein active sites are extremely similar, complicating the design of specific inhibitors. Here, we show that a chemical genetic approach best characterized in protein kinases, known as analog-sensitive chemical inhibition, is viable for DDX3 and possibly other DEAD-box proteins. We present an expanded active-site mutant that is tolerated in vitro and in vivo, and is sensitive to chemical inhibition by a novel bulky inhibitor. Our results highlight a course towards analog sensitive chemical inhibition of DDX3 and potentially the entire DEAD-box protein family.

  6. A Proposed Model of Self-Generated Analogical Reasoning for the Concept of Translation in Protein Synthesis (United States)

    Salih, Maria


    This paper explored and described the analogical reasoning occurring in the minds of different science achievement groups for the concept of translation in protein synthesis. "What is the process of self-generated analogical reasoning?", "What types of matching was involved?" and "What are the consequences of the matching…

  7. Digital Operation of Microelectronic Circuits Analogous to Protein Hydrogen Bonding Networks

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    Elitsa Gieva


    Full Text Available Two hydrogen bonding networks with water molecules and branching residues extracted from β-lactamase protein are investigated and their proton transfer characteristics are studied by creating analogous electrical circuits consisting of block-elements. The block-elements and their proton transfer are described by polynomials that are coded in Matlab and in Verilog-A for use in the Spectre simulator of Cadence IC design system. DC and digital pulse analyses are performed to demonstrate that some circuit outputs behave as repeaters while other - behave as inverters. The results also showed that the HBN circuits might behave as a D-latch and a demultiplexer.

  8. Conjugation of extracellular matrix proteins to basal lamina analogs enhances keratinocyte attachment. (United States)

    Bush, Katie A; Downing, Brett R; Walsh, Sarah E; Pins, George D


    The dermal-epidermal junction of skin contains extracellular matrix proteins that are involved in initiating and controlling keratinocyte signaling events such as attachment, proliferation, and terminal differentiation. To characterize the relationship between extracellular matrix proteins and keratinocyte attachment, a biomimetic design approach was used to precisely tailor the surface of basal lamina analogs with biochemistries that emulate the native biochemical composition found at the dermal-epidermal junction. A high-throughput screening device was developed by our laboratory that allows for the simultaneous investigation of the conjugation of individual extracellular matrix proteins (e.g. collagen type I, collagen type IV, laminin, or fibronectin) as well as their effect on keratinocyte attachment, on the surface of an implantable collagen membrane. Fluorescence microscopy coupled with quantitative digital image analyses indicated that the extracellular matrix proteins adsorbed to the collagen-GAG membranes in a dose-dependent manner. To determine the relationship between extracellular matrix protein signaling cues and keratinocyte attachment, cells were seeded on protein-conjugated collagen-GAG membranes and a tetrazolium-based colorimetric assay was used to quantify viable keratinocyte attachment. Our results indicate that keratinocyte attachment was significantly enhanced on the surfaces of collagen membranes that were conjugated with fibronectin and type IV collagen. These findings define a set of design parameters that will enhance keratinocyte binding efficiency on the surface of collagen membranes and ultimately improve the rate of epithelialization for dermal equivalents.

  9. Chemo-informatic design of antibiotic geldenamycin analogs to target stress proteins HSP90 of pathogenic protozoan parasites. (United States)

    Singh, Chaya; Atri, Neelam


    Stress proteins HSP90 (Heat shock proteins) are essential molecular chaperones involved in signal transduction, cell cycle control, stress management, folding and degradation of proteins. HSP90 have been found in a variety of organisms including pathogens suggesting that they are ancient and conserved proteins. Here, using molecular modeling and docking protocols, antibiotic Geldenamycin and its analog are targeted to the HSP90 homolog proteins of pathogenic protozoans Plasmodium falciparum, Leishmania donovani, Trypanosoma brucei and Entamoeba Histolytica. The designed analogs of geldenamycin have shown drug like property with improved binding affinity to their targets. A decrease in insilico affinity of the analogs for the Human HSP90 target indicates that they can be used as potential drug candidates.

  10. Evidences for Cooperative Resonance-Assisted Hydrogen Bonds in Protein Secondary Structure Analogs (United States)

    Zhou, Yu; Deng, Geng; Zheng, Yan-Zhen; Xu, Jing; Ashraf, Hamad; Yu, Zhi-Wu


    Cooperative behaviors of the hydrogen bonding networks in proteins have been discovered for a long time. The structural origin of this cooperativity, however, is still under debate. Here we report a new investigation combining excess infrared spectroscopy and density functional theory calculation on peptide analogs, represented by N-methylformamide (NMF) and N-methylacetamide (NMA). Interestingly, addition of the strong hydrogen bond acceptor, dimethyl sulfoxide, to the pure analogs caused opposite effects, namely red- and blue-shift of the N-H stretching infrared absorption in NMF and NMA, respectively. The contradiction can be reconciled by the marked lowering of the energy levels of the self-associates between NMA molecules due to a cooperative effect of the hydrogen bonds. On the contrary, NMF molecules cannot form long-chain cooperative hydrogen bonds because they tend to form dimers. Even more interestingly, we found excellent linear relationships between changes on bond orders of N-H/N-C/C = O and the hydrogen bond energy gains upon the formation of hydrogen bonding multimers in NMA, suggesting strongly that the cooperativity originates from resonance-assisted hydrogen bonds. Our findings provide insights on the structures of proteins and may also shed lights on the rational design of novel molecular recognition systems.

  11. Low-Tech, Pilot Scale Purification of a Recombinant Spider Silk Protein Analog from Tobacco Leaves. (United States)

    Heppner, René; Weichert, Nicola; Schierhorn, Angelika; Conrad, Udo; Pietzsch, Markus


    Spider dragline is used by many members of the Araneae family not only as a proteinogenic safety thread but also for web construction. Spider dragline has been shown to possess high tensile strength in combination with elastic behavior. This high tensile strength can be attributed to the presence of antiparallel β-sheets within the thread; these antiparallel β-sheets are why the protein is classified as a silk. Due to the properties of spider silk and its technical and medical uses, including its use as a suture material and as a scaffold for tissue regeneration, spider dragline is a focus of the biotechnology industry. The production of sufficient amounts of spider silk is challenging, as it is difficult to produce large quantities of fibers because of the cannibalistic behavior of spiders and their large spatial requirements. In recent years, the heterologous expression of genes coding for spider silk analogs in various hosts, including plants such as Nicotiana tabacum, has been established. We developed a simple and scalable method for the purification of a recombinant spider silk protein elastin-like peptide fusion protein (Q-/K-MaSp1-100× ELP) after heterologous production in tobacco leaves involving heat and acetone precipitation. Further purification was performed using centrifugal Inverse Transition Cycling (cITC). Up to 400 mg of highly pure spider silk protein derivatives can be isolated from six kilograms of tobacco leaves, which is the highest amount of silk protein derivatives purified from plants thus far.

  12. Low-Tech, Pilot Scale Purification of a Recombinant Spider Silk Protein Analog from Tobacco Leaves

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    René Heppner


    Full Text Available Spider dragline is used by many members of the Araneae family not only as a proteinogenic safety thread but also for web construction. Spider dragline has been shown to possess high tensile strength in combination with elastic behavior. This high tensile strength can be attributed to the presence of antiparallel β-sheets within the thread; these antiparallel β-sheets are why the protein is classified as a silk. Due to the properties of spider silk and its technical and medical uses, including its use as a suture material and as a scaffold for tissue regeneration, spider dragline is a focus of the biotechnology industry. The production of sufficient amounts of spider silk is challenging, as it is difficult to produce large quantities of fibers because of the cannibalistic behavior of spiders and their large spatial requirements. In recent years, the heterologous expression of genes coding for spider silk analogs in various hosts, including plants such as Nicotiana tabacum, has been established. We developed a simple and scalable method for the purification of a recombinant spider silk protein elastin-like peptide fusion protein (Q-/K-MaSp1-100× ELP after heterologous production in tobacco leaves involving heat and acetone precipitation. Further purification was performed using centrifugal Inverse Transition Cycling (cITC. Up to 400 mg of highly pure spider silk protein derivatives can be isolated from six kilograms of tobacco leaves, which is the highest amount of silk protein derivatives purified from plants thus far.

  13. Protein conformation and disease : pathological consequences of analogous mutations in homologous proteins.

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    Stevens, F. J.; Pokkuluri, P. R.; Schiffer, M.; Biosciences Division


    The antibody light chain variable domain (V{sub L}){sup 1} and myelin protein zero (MPZ) are representatives of the functionally diverse immunoglobulin superfamily. The V{sub L} is a subunit of the antigen-binding component of antibodies, while MPZ is the major membrane-linked constituent of the myelin sheaths that coat peripheral nerves. Despite limited amino acid sequence homology, the conformations of the core structures of the two proteins are largely superimposable. Amino acid variations in V{sub L} account for various conformational disease outcomes, including amyloidosis. However, the specific amino acid changes in V{sub L} that are responsible for disease have been obscured by multiple concurrent primary structure alterations. Recently, certain demyelination disorders have been linked to point mutations and single amino acid polymorphisms in MPZ. We demonstrate here that some pathogenic variations in MPZ correspond to changes suspected of determining amyloidosis in V{sub L}. This unanticipated observation suggests that studies of the biophysical origin of conformational disease in one member of a superfamily of homologous proteins may have implications throughout the superfamily. In some cases, findings may account for overt disease; in other cases, due to the natural repertoire of inherited polymorphisms, variations in a representative protein may predict subclinical impairment of homologous proteins.

  14. Complex Assembly Behavior During the Encapsulation of Green Fluorescent Protein Analogs in Virus Derived Protein Capsules

    NARCIS (Netherlands)

    Minten, Inge J.; Nolte, Roeland J.M.; Cornelissen, Jeroen J.L.M.


    Enzymes encapsulated in nanocontainers are a better model of the conditions inside a living cell than free enzymes in solution. In a first step toward the encapsulation of multiple enzymes inside the cowpea chlorotic mottle virus (CCMV) capsid, enhanced green fluorescent protein (EGFP) was attached

  15. An amino acid depleted cell-free protein synthesis system for the incorporation of non-canonical amino acid analogs into proteins. (United States)

    Singh-Blom, Amrita; Hughes, Randall A; Ellington, Andrew D


    Residue-specific incorporation of non-canonical amino acids into proteins is usually performed in vivo using amino acid auxotrophic strains and replacing the natural amino acid with an unnatural amino acid analog. Herein, we present an efficient amino acid depleted cell-free protein synthesis system that can be used to study residue-specific replacement of a natural amino acid by an unnatural amino acid analog. This system combines a simple methodology and high protein expression titers with a high-efficiency analog substitution into a target protein. To demonstrate the productivity and efficacy of a cell-free synthesis system for residue-specific incorporation of unnatural amino acids in vitro, we use this system to show that 5-fluorotryptophan and 6-fluorotryptophan substituted streptavidin retain the ability to bind biotin despite protein-wide replacement of a natural amino acid for the amino acid analog. We envisage this amino acid depleted cell-free synthesis system being an economical and convenient format for the high-throughput screening of a myriad of amino acid analogs with a variety of protein targets for the study and functional characterization of proteins substituted with unnatural amino acids when compared to the currently employed in vivo methodologies.

  16. Nucleotide sequence analysis of the Legionella micdadei mip gene, encoding a 30-kilodalton analog of the Legionella pneumophila Mip protein

    DEFF Research Database (Denmark)

    Bangsborg, Jette Marie; Cianciotto, N P; Hindersson, P


    After the demonstration of analogs of the Legionella pneumophila macrophage infectivity potentiator (Mip) protein in other Legionella species, the Legionella micdadei mip gene was cloned and expressed in Escherichia coli. DNA sequence analysis of the L. micdadei mip gene contained in the plasmid p...... homology with the mip-like genes of several Legionella species. Furthermore, amino acid sequence comparisons revealed significant homology to two eukaryotic proteins with isomerase activity (FK506-binding proteins)....

  17. Bisubstrate analog probes for the insulin receptor protein tyrosine kinase: molecular yardsticks for analyzing catalytic mechanism and inhibitor design. (United States)

    Hines, Aliya C; Parang, Keykavous; Kohanski, Ronald A; Hubbard, Stevan R; Cole, Philip A


    Bisubstrate analogs have the potential to provide enhanced specificity for protein kinase inhibition and tools to understand catalytic mechanism. Previous efforts led to the design of a peptide-ATP conjugate bisubstrate analog utilizing aminophenylalanine in place of tyrosine and a thioacetyl linker to the gamma-phosphate of ATP which was a potent inhibitor of the insulin receptor kinase (IRK). In this study, we have examined the contributions of various electrostatic and structural elements in the bisubstrate analog to IRK binding affinity. Three types of changes (seven specific analogs in all) were introduced: a Tyr isostere of the previous aminophenylalanine moiety, modifications of the spacer between the adenine and the peptide, and deletions and substitutions within the peptide moiety. These studies allowed a direct evaluation of the hydrogen bond strength between the anilino nitrogen of the bisubstrate analog and the enzyme catalytic base Asp and showed that it contributes 2.5 kcal/mol of binding energy, in good agreement with previous predictions. Modifications of the linker length resulted in weakened inhibitory affinity, consistent with the geometric requirements of an enzyme-catalyzed dissociative transition state. Alterations in the peptide motif generally led to diminished inhibitory potency, and only some of these effects could be rationalized based on prior kinetic and structural studies. Taken together, these results suggest that a combination of mechanism-based design and empirical synthetic manipulation will be necessary in producing optimized protein kinase bisubstrate analog inhibitors.

  18. Gene families of cuticular proteins analogous to peritrophins (CPAPs in Tribolium castaneum have diverse functions.

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    Sinu Jasrapuria

    Full Text Available The functional characterization of an entire class of 17 genes from the red flour beetle, Tribolium castaneum, which encode two families of Cuticular Proteins Analogous to Peritrophins (CPAPs has been carried out. CPAP genes in T. castaneum are expressed exclusively in cuticle-forming tissues and have been classified into two families, CPAP1 and CPAP3, based on whether the proteins contain either one (CPAP1, or three copies (CPAP3 of the chitin-binding domain, ChtBD2, with its six characteristically spaced cysteine residues. Individual members of the TcCPAP1 and TcCPAP3 gene families have distinct developmental patterns of expression. Many of these proteins serve essential and non-redundant functions in maintaining the structural integrity of the cuticle in different parts of the insect anatomy. Three genes of the TcCPAP1 family and five genes of the TcCPAP3 family are essential for insect development, molting, cuticle integrity, proper locomotion or fecundity. RNA interference (RNAi targeting TcCPAP1-C, TcCPAP1-H, TcCPAP1-J or TcCPAP3-C transcripts resulted in death at the pharate adult stage of development. RNAi for TcCPAP3-A1, TcCPAP3-B, TcCPAP3-D1 or TcCPAP3-D2 genes resulted in different developmental defects, including adult/embryonic mortality, abnormal elytra or hindwings, or an abnormal 'stiff-jointed' gait. These results provide experimental support for specialization in the functions of CPAP proteins in T. castaneum and a biological rationale for the conservation of CPAP orthologs in other orders of insects. This is the first comprehensive functional analysis of an entire class of cuticular proteins with one or more ChtBD2 domains in any insect species.

  19. A Better Understanding of Protein Structure and Function by the Synthesis and Incorporation of Selenium- and Tellurium Containing Tryptophan Analogs

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    Helmey, Sherif Samir [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Belmont Univ., Nashville, TN (United States). Dept. of Chemistry and Physics; Rice, Ambrose Eugene [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Belmont Univ., Nashville, TN (United States). Dept. of Chemistry and Physics; Hatch, Duane Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Belmont Univ., Nashville, TN (United States). Dept. of Chemistry and Physics; Silks, Louis A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Marti-Arbona, Ricardo [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division


    Unnatural heavy metal-containing amino acid analogs have shown to be very important in the analysis of protein structure, using methods such as X-ray crystallography, mass spectroscopy, and NMR spectroscopy. Synthesis and incorporation of selenium-containing methionine analogs has already been shown in the literature however with some drawbacks due to toxicity to host organisms. Thus synthesis of heavy metal tryptophan analogs should prove to be more effective since the amino acid tryptophan is naturally less abundant in many proteins. For example, bioincorporation of β-seleno[3,2-b]pyrrolyl-L-alanine ([4,5]SeTrp) and β-selenolo[2,3-b]pyrrolyl-L-alanine ([6,7]SeTrp) has been shown in the following proteins without structural or catalytic perturbations: human annexin V, barstar, and dihydrofolate reductase. The reported synthesis of these Se-containing analogs is currently not efficient for commercial purposes. Thus a more efficient, concise, high-yield synthesis of selenotryptophan, as well as the corresponding, tellurotryptophan, will be necessary for wide spread use of these unnatural amino acid analogs. This research will highlight our progress towards a synthetic route of both [6,7]SeTrp and [6,7]TeTrp, which ultimately will be used to study the effect on the catalytic activity of Lignin Peroxidase (LiP).

  20. Calcimimetic and vitamin D analog use in hemodialyzed patients is associated with increased levels of vitamin K dependent proteins. (United States)

    Fusaro, Maria; Giannini, Sandro; Gallieni, Maurizio; Noale, Marianna; Tripepi, Giovanni; Rossini, Maurizio; Messa, Piergiorgio; Rigotti, Paolo; Pati, Tecla; Barbisoni, Francesco; Piccoli, Antonio; Aghi, Andrea; Alessi, Marianna; Bonfante, Luciana; Fabris, Fabrizio; Zambon, Sabina; Sella, Stefania; Iervasi, Giorgio; Plebani, Mario


    Matrix Gla protein (MGP) and bone Gla protein (BGP) are two vitamin K-dependent proteins (VKDPs) involved in the regulation of vascular calcification (VC). We carried out a secondary analysis of the VIKI study to evaluate associations between drug consumption and VKDP levels in 387 hemodialyzed patients. The VIKI study assessed the prevalence of vitamin K deficiency in hemodialysis patients. We evaluated drug consumption, determined BGP and MGP levels, and verified the presence of any vertebral fractures (VF) and VC by spine radiographs. Total BGP levels were twice as high with calcimimetics versus no calcimimetics (290 vs. 158.5 mcg/L, p vitamin D analogs (268 vs. 159 mcg/L, p vitamin D analogs (21.1 vs. 18.3 mcg/L, p = 0.43). Median Total BGP level was 29 % lower in patients with ≥1 VF (151 vs. 213 mcg/L, p = 0.0091) and 36 % lower in patients with VC (164 vs. 262.1 mcg/L, p = 0.0003). In non-survivors, median BGP and MGP were lower, but only for MGP this difference reached the statistical significance (152 vs. 191 mcg/L, p = 0.20 and 15.0 vs. 19.7 mcg/L, p = 0.02, respectively). Pending studies on vitamin K supplementation, calcimimetics, and vitamin D analogs may play a role in preserving vitamin K-dependent protein activity, thus contributing to bone and vascular health in CKD patients.

  1. Synchronized fission yeast meiosis using an ATP analog-sensitive Pat1 protein kinase


    Cipak, Lubos; Polakova, Silvia; Hyppa, Randy W.; Smith, Gerald R.; Gregan, Juraj


    Synchronous cultures are often indispensable for studying meiosis. Here, we present an optimized protocol for induction of synchronous meiosis in the fission yeast Schizosaccharomyces pombe. Chemical inactivation of an ATP analog-sensitive form of the Pat1 kinase (pat1-as2) by adding the ATP-analog 1-NM-PP1 in G1-arrested cells allows induction of synchronous meiosis at optimal temperature (25 °C). Importantly, this protocol eliminates detrimental effects of elevated temperature (34 °C) which...

  2. Rapid detection, discovery, and identification of post-translationally myristoylated proteins during apoptosis using a bio-orthogonal azidomyristate analog. (United States)

    Martin, Dale D O; Vilas, Gonzalo L; Prescher, Jennifer A; Rajaiah, Gurram; Falck, John R; Bertozzi, Carolyn R; Berthiaume, Luc G


    Myristoylation is the attachment of the 14-carbon fatty acid myristate to the N-terminal glycine residue of proteins. Typically a co-translational modification, myristoylation of proapoptotic cysteinyl-aspartyl proteases (caspase)-cleaved Bid and PAK2 was also shown to occur post-translationally and is essential for their proper localization and proapoptotic function. Progress in the identification and characterization of myristoylated proteins has been impeded by the long exposure times required to monitor incorporation of radioactive myristate into proteins (typically 1-3 months). Consequently, we developed a nonradioactive detection methodology in which a bio-orthogonal azidomyristate analog is specifically incorporated co- or post-translationally into proteins at N-terminal glycines, chemoselectively ligated to tagged triarylphosphines and detected by Western blotting with short exposure times (seconds to minutes). This represents over a million-fold signal amplification in comparison to using radioactive labeling methods. Using rational prediction analysis to recognize putative internal myristoylation sites in caspase-cleaved proteins combined with our nonradioactive chemical detection method, we identify 5 new post-translationally myristoylatable proteins (PKC epsilon, CD-IC2, Bap31, MST3, and the catalytic subunit of glutamate cysteine ligase). We also demonstrate that 15 proteins undergo post-translational myristoylation in apoptotic Jurkat T cells. This suggests that post-translational myristoylation of caspase-cleaved proteins represents a novel mechanism widely used to regulate cell death.

  3. Inhibitors of protein:farnesyl transferase and protein:geranylgeranyl transferase I : Synthesis of homologous diphosphonate analogs of isoprenylated pyrophosphate

    NARCIS (Netherlands)

    Overhand, M.; Stuivenberg, H.R.; Pieterman, E.; Cohen, L.H.; Leeuwen, R.E.W. van; Valentijn, A.R.P.M.; Overkleeft, H.S.; Marel, G.A. van der; Boom, J.H. van


    Novel diphosphonate homologs 7a-7c, and their cyclic counterparts 8a- 8c, of the previously synthesized farnesyl pyrophosphate analogs 1 and 2 were prepared and tested for their inhibition potency and specificity of the enzymes PFT and PGGT-I. Compound 2 was shown to be the most potent inhibitor of

  4. Analogs of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, as Anti-Cancer Agents. (United States)

    Li, Xiaokai; Srinivasan, Sharan R; Connarn, Jamie; Ahmad, Atta; Young, Zapporah T; Kabza, Adam M; Zuiderweg, Erik R P; Sun, Duxin; Gestwicki, Jason E


    The rhodacyanine, MKT-077, has anti-proliferative activity against cancer cell lines through its ability to inhibit members of the heat shock protein 70 (Hsp70) family of molecular chaperones. However, MKT-077 is rapidly metabolized, which limits its use as either a chemical probe or potential therapeutic. We report the synthesis and characterization of MKT-077 analogs designed for greater stability. The most potent molecules, such as 30 (JG-98), were at least 3-fold more active than MKT-077 against the breast cancer cell lines MDA-MB-231 and MCF-7 (EC50 values of 0.4 ± 0.03 μM and 0.7 ± 0.2 μM, respectively). The analogs modestly destabilized the chaperone "clients", Akt1 and Raf1, and induced apoptosis in these cells. Further, the microsomal half-life of JG-98 was improved at least 7-fold (t1/2 = 37 min) compared to MKT-077 (t1/2 MKT-077. These studies advance MKT-077 analogs as chemical probes for studying Hsp70's roles in cancer.

  5. Curcumin and synthetic analogs induce reactive oxygen species and decreases specificity protein (Sp transcription factors by targeting microRNAs

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    Gandhy Shruti U


    Full Text Available Abstract Background Curcumin inhibits growth of several cancer cell lines, and studies in this laboratory in bladder and pancreatic cancer cells show that curcumin downregulates specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 and pro-oncogenic Sp-regulated genes. In this study, we investigated the anticancer activity of curcumin and several synthetic cyclohexanone and piperidine analogs in colon cancer cells. Methods The effects of curcumin and synthetic analogs on colon cancer cell proliferation and apoptosis were determined using standardized assays. The changes in Sp proteins and Sp-regulated gene products were analysed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a, miR-20a, miR-17-5p and ZBTB10 and ZBTB4 mRNA expression. Results The IC50 (half-maximal values for growth inhibition (24 hr of colon cancer cells by curcumin and synthetic cyclohexanone and piperidine analogs of curcumin varied from 10 μM for curcumin to 0.7 μM for the most active synthetic piperidine analog RL197, which was used along with curcumin as model agents in this study. Curcumin and RL197 inhibited RKO and SW480 colon cancer cell growth and induced apoptosis, and this was accompanied by downregulation of specificity protein (Sp transcription factors Sp1, Sp3 and Sp4 and Sp-regulated genes including the epidermal growth factor receptor (EGFR, hepatocyte growth factor receptor (c-MET, survivin, bcl-2, cyclin D1 and NFκB (p65 and p50. Curcumin and RL197 also induced reactive oxygen species (ROS, and cotreatment with the antioxidant glutathione significantly attenuated curcumin- and RL197-induced growth inhibition and downregulation of Sp1, Sp3, Sp4 and Sp-regulated genes. The mechanism of curcumin-/RL197-induced repression of Sp transcription factors was ROS-dependent and due to induction of the Sp repressors ZBTB10 and ZBTB4 and downregulation of microRNAs (miR-27a, miR-20a and miR-17-5p that regulate these repressors

  6. Synchronized fission yeast meiosis using an ATP analog-sensitive Pat1 protein kinase. (United States)

    Cipak, Lubos; Polakova, Silvia; Hyppa, Randy W; Smith, Gerald R; Gregan, Juraj


    Synchronous cultures are often indispensable for studying meiosis. Here we present an optimized protocol for induction of synchronous meiosis in the fission yeast Schizosaccharomyces pombe. Chemical inactivation of an ATP analog-sensitive form of the Pat1 kinase (pat1-as2) by adding the ATP analog 1-NM-PP1 in G1-arrested cells allows the induction of synchronous meiosis at optimal temperature (25°C). Importantly, this protocol eliminates detrimental effects of elevated temperature (34°C), which is required to inactivate the commonly used temperature-sensitive Pat1 kinase mutant (pat1-114). The addition of the mat-Pc gene to a mat1-M strain further improves chromosome segregation and spore viability. Thus, our protocol offers highly synchronous meiosis at optimal temperature, with most characteristics similar to those of wild-type meiosis. The synchronization protocol can be completed in 5 d (not including strain production, which may take as long as 2 or 3 months).


    Directory of Open Access Journals (Sweden)

    Dewi Pratiwi Ambari


    Full Text Available ABSTRACTThe purpose of this study was to develop formula of sausage based on tempeh flour with the addition of oyster mushroom (Pleurotus ostreatus as functional food rich in protein and dietary fiber as healthy snack product for children. Sausage was formulated by addition of oyster mushroom used trial and error method. A selected formula was determined based on semi trained panelist preference. Acceptance of the selected sausage formula was examine by children using hedonic test. The contribution of protein and dietary fiber contained in sausage per serving size (50 g was calculated for general consumer. The accepted sausage with 20% oyster mushroom addition contained 24% of protein and can be claimed as source of protein and 7.64 g of dietary fiber per 100 g and can be claimed rich in dietary fiber.Keywords: dietary fiber, oyster mushroom, protein, sausage, tempehABSTRAKTujuan penelitian ini adalah untuk mengembangkan formula sosis berbasis tempe dengan penambahan jamur tiram sebagai pangan fungsional kaya protein dan serat pangan untuk produk camilan sehat bagi anak-anak. Sosis diformulasikan dengan penambahan jamur tiram melalui metode trial dan error. Formula terpilih ditentukan berdasarkan kesukaan panelis semi terlatih. Penerimaan sosis formula terpilih dilakukan terhadap anak-anak melalui uji hedonik. Kontribusi protein dan serat pangan pada sosis per takaran saji (50 g dihitung untuk konsumen umum. Sosis terpilih dengan penambahan 20% jamur tiram mengandung 24% protein sehingga dapat diklaim sebagai sumber protein dan 7.64 g serat pangan per 100 g sehingga dapat diklaim kaya serat pangan.Kata kunci: jamur tiram, protein, serat pangan, sosis, tempe

  8. Phosphorylation of β-actin by protein kinase C-delta in camptothecin analog-induced leukemic cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Shuang WANG; Ying ZHENG; Yun YU; Li XIA; Guo-qiang CHEN; Yong-zong YANG; Li-shun WANG


    Aim: This study was conducted to reveal new proteins involved in acute myeloid leukemia (AML) cell apoptosis. Methods: Using camptothecin analog NSC606985-induced leukemic U937 cell apoptosis as a model, this study performed a differen-tial proteomic analysis during apoptosis induction. The significantly modulated protein was underwent further investigation in the apoptotic process. Results: We found that β-actin protein presented two different spots on the two-dimen-sional electrophoresis (2-DE) map, which shared similar molecular weight and different pI. Those two spots demonstrated contrary changes (disappeared on the basic-end and increased on the acid-end spot) during apoptosis induction, although the total level of β-actin kept constant. This observation was further confirmed by immunoblot analysis on 2-DE gel. When NSC606985-treated cell iysate was incubated with alkaline phosphotase, β-actin on the basic-end spot was restored, indicating increased phosphorylation of β-actin during NSC606985-induced apoptosis. Moreover, the polymerization of actin also decreased after NSC606985 treatment. The increased β-actin phosphorylation and decreased ac-tin polymerization was antagonized by pre-treatment of rottlerin, a specific protein kinase C-delta (PKCδ) inhibitor. Conclusion: All these results indicate that β-actin was phosphorylated during apoptosis induction, which was mediated by acti-vated PKCδ.

  9. The genomic structure of the human Charcot-Leyden crystal protein gene is analogous to those of the galectin genes

    Energy Technology Data Exchange (ETDEWEB)

    Dyer, K.D. [National Inst. of Health, Bethesda, MD (United States)]|[Georgetown Univ. Medical Center, Washington, DC (United States); Handen, J.S.; Rosenberg, H.F. [National Inst. of Health, Bethesda, MD (United States)


    The Charcot-Leyden crystal (CLC) protein, or eosinophil lysophospholipase, is a characteristic protein of human eosinophils and basophils; recent work has demonstrated that the CLC protein is both structurally and functionally related to the galectin family of {beta}-galactoside binding proteins. The galectins as a group share a number of features in common, including a linear ligand binding site encoded on a single exon. In this work, we demonstrate that the intron-exon structure of the gene encoding CLC is analogous to those encoding the galectins. The coding sequence of the CLC gene is divided into four exons, with the entire {beta}-galactoside binding site encoded by exon III. We have isolated CLC {beta}-galactoside binding sites from both orangutan (Pongo pygmaeus) and murine (Mus musculus) genomic DNAs, both encoded on single exons, and noted conservation of the amino acids shown to interact directly with the {beta}-galactoside ligand. The most likely interpretation of these results suggests the occurrence of one or more exon duplication and insertion events, resulting in the distribution of this lectin domain to CLC as well as to the multiple galectin genes. 35 refs., 3 figs.

  10. Lunar Analog (United States)

    Cromwell, Ronita L.


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

  11. Identification and analysis of the acetylated status of poplar proteins reveals analogous N-terminal protein processing mechanisms with other eukaryotes.

    Directory of Open Access Journals (Sweden)

    Chang-Cai Liu

    Full Text Available BACKGROUND: The N-terminal protein processing mechanism (NPM including N-terminal Met excision (NME and N-terminal acetylation (N(α-acetylation represents a common protein co-translational process of some eukaryotes. However, this NPM occurred in woody plants yet remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: To reveal the NPM in poplar, we investigated the N(α-acetylation status of poplar proteins during dormancy by combining tandem mass spectrometry with TiO2 enrichment of acetylated peptides. We identified 58 N-terminally acetylated (N(α-acetylated proteins. Most proteins (47, >81% are subjected to N(α-acetylation following the N-terminal removal of Met, indicating that N(α-acetylation and NME represent a common NPM of poplar proteins. Furthermore, we confirm that poplar shares the analogous NME and N(α-acetylation (NPM to other eukaryotes according to analysis of N-terminal features of these acetylated proteins combined with genome-wide identification of the involving methionine aminopeptidases (MAPs and N-terminal acetyltransferase (Nat enzymes in poplar. The N(α-acetylated reactions and the involving enzymes of these poplar proteins are also identified based on those of yeast and human, as well as the subcellular location information of these poplar proteins. CONCLUSIONS/SIGNIFICANCE: This study represents the first extensive investigation of N(α-acetylation events in woody plants, the results of which will provide useful resources for future unraveling the regulatory mechanisms of N(α-acetylation of proteins in poplar.

  12. GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy.

    Directory of Open Access Journals (Sweden)

    Shvetank Sharma

    Full Text Available BACKGROUND: Nonalcoholic fatty liver disease (NAFLD is a known outcome of hepatosteatosis. Free fatty acids (FFA induce the unfolded protein response (UPR or endoplasmic reticulum (ER stress that may induce apoptosis. Recent data indicate ER stress to be a major player in the progression of fatty liver to more aggressive lesions. Autophagy on the other hand has been demonstrated to be protective against ER stress-induced cell death. We hypothesized that exendin-4 (GLP-1 analog treatment of fat loaded hepatocytes can reduce steatosis by autophagy which leads to reduced ER stress-related hepatocyte apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Primary human hepatocytes were loaded with saturated, cis- and trans-unsaturated fatty acids (palmitic, oleic and elaidic acid respectively. Steatosis, induced with all three fatty acids, was significantly resolved after exendin-4 treatment. Exendin-4 sustained levels of GRP78 expression in fat-loaded cells when compared to untreated fat-loaded cells alone. In contrast, CHOP (C/EBP homologous protein; the penultimate protein that leads to ER stress-related cell death was significantly decreased by exendin-4 in hepatocytes loaded with fatty acids. Finally, exendin-4 in fat loaded hepatocytes clearly promoted gene products associated with macroautophagy as measured by enhanced production of both Beclin-1 and LC3B-II, markers for autophagy; and visualized by transmission electron microscopy (TEM. Similar observations were made in mouse liver lysates after mice were fed with high fat high fructose diet and treated with a long acting GLP-1 receptor agonist, liraglutide. CONCLUSIONS/SIGNIFICANCE: GLP-1 proteins appear to protect hepatocytes from fatty acid-related death by prohibition of a dysfunctional ER stress response; and reduce fatty acid accumulation, by activation of both macro-and chaperone-mediated autophagy. These findings provide a novel role for GLP-1 proteins in halting the progression of more

  13. Topology of RNA-protein nucleobase-amino acid π-π interactions and comparison to analogous DNA-protein π-π contacts. (United States)

    Wilson, Katie A; Holland, Devany J; Wetmore, Stacey D


    The present work analyzed 120 high-resolution X-ray crystal structures and identified 335 RNA-protein π-interactions (154 nonredundant) between a nucleobase and aromatic (W, H, F, or Y) or acyclic (R, E, or D) π-containing amino acid. Each contact was critically analyzed (including using a visual inspection protocol) to determine the most prevalent composition, structure, and strength of π-interactions at RNA-protein interfaces. These contacts most commonly involve F and U, with U:F interactions comprising one-fifth of the total number of contacts found. Furthermore, the RNA and protein π-systems adopt many different relative orientations, although there is a preference for more parallel (stacked) arrangements. Due to the variation in structure, the strength of the intermolecular forces between the RNA and protein components (as determined from accurate quantum chemical calculations) exhibits a significant range, with most of the contacts providing significant stability to the associated RNA-protein complex (up to -65 kJ mol(-1)). Comparison to the analogous DNA-protein π-interactions emphasizes differences in RNA- and DNA-protein π-interactions at the molecular level, including the greater abundance of RNA contacts and the involvement of different nucleobase/amino acid residues. Overall, our results provide a clearer picture of the molecular basis of nucleic acid-protein binding and underscore the important role of these contacts in biology, including the significant contribution of π-π interactions to the stability of nucleic acid-protein complexes. Nevertheless, more work is still needed in this area in order to further appreciate the properties and roles of RNA nucleobase-amino acid π-interactions in nature.

  14. Identification of sucrose binding, membrane proteins using a photolyzable sucrose analog. [P. saccharophila

    Energy Technology Data Exchange (ETDEWEB)

    Ripp, K.G.; Liu, D.F.; Viitanen, P.; Hitz, W.D.


    The sucrose derivative 6'-deoxy-6'-(2-hydroxy-4-azido)benzamidosucrose (6'-HABS) was prepared from sucrose (via 6'-deoxy-6'-aminosucrose) and 4-amino-salicylic acid. 6'-HABS is a competitive inhibitor of sucrose influx into protoplasts from developing soybean cotyledons and of sucrose binding to membranes from the bacteria P. saccharophila. The Ki for inhibition in the soybean protoplasts was 6'-Deoxy-6'-(2-hydroxy-3-/sup 125/Iodo-4-azido)benzamidosucrose was prepared by lactoperoxidase iodination of 6'-HABS. Upon photolysis in the presence of membranes from P saccharophila, label from the photoprobe is incorporated into a sucrose inducible polypeptide of mass 84 KD in SDS-PAGE. The polypeptide is protected from labeling by the inclusion of sucrose in the photolysis mixture. Photolysis conditions which lead to specific labeling of the sucrose protectable polypeptide in bacterial membranes also give sucrose protectable labeling of a 66 KD polypeptide in microsomal preparations made from developing soybeans. The possibility that this is a sucrose transporting protein is being tested.

  15. Analog computing

    CERN Document Server

    Ulmann, Bernd


    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.

  16. Synthesis of Paclitaxel Analogs


    Xu, Zhibing


    Paclitaxel is one of the most successful anti-cancer drugs, particularly in the treatment of breast cancer and ovarian cancer. For the investigation of the interaction between paclitaxel and MD-2 protein, and development of new antagonists for lipopolysaccharide, several C10 A-nor-paclitaxel analogs have been synthesized and their biological activities have been evaluated. In order to reduce the myelosuppression effect of the paclitaxel, several C3â ² and C4 paclitaxel analogs have been synth...

  17. Analog earthquakes

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, R.B. [Center for Nuclear Waste Regulatory Analyses, San Antonio, TX (United States)


    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.

  18. Differential half-maximal effects of human insulin and its analogs for in situ glucose transport and protein synthesis in rat soleus muscle (United States)

    Weinstein, Randi B.; Eleid, Noura; LeCesne, Catherine; Durando, Bianca; Crawford, Julie T.; Heffner, Michelle; Layton, Christle; O'Keefe, Matthew; Robinson, Jennifer; Rudinsky, Suzy; Henriksen, Erik J.; Tischler, Marc E.


    Analogs of human insulin have been used to discriminate between responses of metabolic and mitogenic (growth-related) pathways. This study compared the stimulatory effects of human insulin (HI) and 2 analogs (X2, B-Asp(9), B-Glu(27) and H2, A-His(8),B-His(4),B-Glu(10), B-His(27)) on glucose uptake and protein synthesis in rat soleus muscle in situ. Glucose uptake, estimated by intramuscular (IM) injection of 2-deoxy[1,2-3H]glucose with or without insulin, was maximally increased at 10(-6) mol/L for HI and X2 and 10(-7) mol/L for H2. HI had a larger effect (318%) than either X2 (156%) or H2 (124%). The half-maximal effect (ED(50)) values for HI, X2, and H2 were 3.3 x10(-8) mol/L, 1.7 x 10(-7) mol/L, and 1.6 x 10(-9) mol/L, respectively. Protein synthesis, estimated by protein incorporation of [(3)H]phenylalanine injected into muscles with or without insulin, was maximally increased at 10(-5) mol/L for HI and 10(-6) for X2 and H2. HI had a larger effect in stimulating protein synthesis (34%) than either X2 (25%) or H2 (19.8%). The ED(50) values for HI, X2, and H2 were 3.0 x 10(-7) mol/L, 3.2 x 10(-7) mol/L, and 1.0 x 10(-9) mol/L, respectively. The biological potency of each analog (ED(50)insulin/ED(50)analog) showed X2 to be less potent than HI for both glucose uptake (0.2) and protein synthesis (0.9), whereas H2 is more potent than HI with ratios of 20 and 300, respectively. These data suggest that this approach for studying insulin responsiveness in a single muscle in situ may be a useful tool for investigating insulin signaling in muscle in vivo. Copyright 2002, Elsevier Science (USA). All rights reserved.

  19. Characterization of a modified ROCK2 protein that allows use of N6-ATP analogs for the identification of novel substrates


    Couzens, Amber L.; Gill, R. Montgomery; Scheid, Michael P.


    Background The Rho-associated coiled-coil kinase-2 (ROCK2) is an important signaling transducer in the transmission of extracellular signals effecting organization of the actin cytoskeleton. ROCK2 has been implicated in numerous pathologies and the current focus is on understanding the molecular events that couple ROCK2 activity to biological function. To aid in the search for new ROCK2 substrates, we have developed an analog-sensitive (AS) ROCK2 protein that allows the use of selective ATP a...

  20. Design of a modified mouse protein with ligand binding properties of its human analog by molecular dynamics simulations: the case of C3 inhibition by compstatin. (United States)

    Tamamis, Phanourios; Pierou, Panayiota; Mytidou, Chrystalla; Floudas, Christodoulos A; Morikis, Dimitrios; Archontis, Georgios


    The peptide compstatin and its derivatives inhibit the complement-component protein C3 in primate mammals and are potential therapeutic agents against the unregulated activation of complement in humans, but are inactive against C3 from lower mammals. Recent molecular dynamics (MD) simulations showed that the most potent compstatin analog comprised entirely of natural amino acids (W4A9) had a smaller affinity for rat C3, due to reproducible changes in the rat protein structure with respect to the human protein, which eliminated or weakened specific protein-ligand interactions seen in the human C3:W4A9 complex. Here, we study by MD simulations three W4A9 complexes with the mouse C3 protein, and two "transgenic" mouse derivatives, containing a small number (6-9) of human C3 substitutions. The mouse complex experiences the conformational changes and affinity reduction of the rat complex. In the "transgenic" complexes, the conformation remains closer to that of the human complex, the protein-ligand interactions are improved, and the affinity for compstatin becomes "human-like." The present work creates new avenues for a compstatin-sensitive animal model. A similar strategy, involving the comparison of a series of complexes by MD simulations, could be used to design "transgenic" sequences in other systems.

  1. The new 4-O-methylhonokiol analog GS12021 inhibits inflammation and macrophage chemotaxis: role of AMP-activated protein kinase α activation.

    Directory of Open Access Journals (Sweden)

    Sora Kim

    Full Text Available Preventing pathologic tissue inflammation is key to treating obesity-induced insulin resistance and type 2 diabetes. Previously, we synthesized a series of methylhonokiol analogs and reported that compounds with a carbamate structure had inhibitory function against cyclooxygenase-2 in a cell-free enzyme assay. However, whether these compounds could inhibit the expression of inflammatory genes in macrophages has not been investigated. Here, we found that a new 4-O-methylhonokiol analog, 3',5-diallyl-4'-methoxy-[1,1'-biphenyl]-2-yl morpholine-4-carboxylate (GS12021 inhibited LPS- or TNFα-stimulated inflammation in macrophages and adipocytes, respectively. LPS-induced phosphorylation of nuclear factor-kappa B (NF-κB/p65 was significantly decreased, whereas NF-κB luciferase activities were slightly inhibited, by GS12021 treatment in RAW 264.7 cells. Either mitogen-activated protein kinase phosphorylation or AP-1 luciferase activity was not altered by GS12021. GS12021 increased the phosphorylation of AMP-activated protein kinase (AMPK α and the expression of sirtuin (SIRT 1. Inhibition of mRNA expression of inflammatory genes by GS12021 was abolished in AMPKα1-knockdown cells, but not in SIRT1 knockout cells, demonstrating that GS12021 exerts anti-inflammatory effects through AMPKα activation. The transwell migration assay results showed that GS12021 treatment of macrophages prevented the cell migration promoted by incubation with conditioned medium obtained from adipocytes. GS12021 suppression of p65 phosphorylation and macrophage chemotaxis were preserved in AMPKα1-knockdown cells, indicating AMPK is not required for these functions of GS12021. Identification of this novel methylhonokiol analog could enable studies of the structure-activity relationship of this class of compounds and further evaluation of its in vivo potential for the treatment of insulin-resistant states and other chronic inflammatory diseases.

  2. Inhibition of mitogen activated protein kinases increases the sensitivity of A549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog. (United States)

    Warmka, Janel K; Solberg, Eric L; Zeliadt, Nicholette A; Srinivasan, Balasubramanian; Charlson, Aaron T; Xing, Chengguo; Wattenberg, Elizabeth V


    We are interested in investigating the biological activity of chalcones, a major class of compounds found in the beverage kava, in order to develop potent and selective chemopreventive candidates. Consumption of kava in the South Pacific Islands is inversely correlated with cancer incidence, even among smokers. Accordingly, chalcones have anti-cancer activities in animal and cell culture models. To investigate signaling pathways that affect chalcone action we studied a potent analog, (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (chalcone-24). Chalcone-24 was selected from a series of chalcone analogs that were synthesized based on the structures derived from flavokawain compounds found in kava, and screened in A549 lung cancer cells for induction of cytotoxicity and inhibition of NF-κB, a transcription factor associated with cell survival. Incubation of A549 cells with chalcone-24 resulted in a dose-dependent inhibition of cell viability, inhibition of NF-κB, activation of caspases, and activation of extracellular signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK); ERK1/2 and JNK are mitogen activated protein kinases that play central roles in regulating cell fate. Pharmacological inhibitors of ERK1/2 or JNK increased the sensitivity of A549 cells to chalcone-24-induced cytotoxicity, without affecting NF-κB or caspase activity. These results will help refine the synthesis of chalcone analogs to maximize the combination of actions required to prevent and treat cancer.

  3. Labeling of Oxidizable Proteins with a Photoactivatable Analog of the Antitumor Agent DMXAA: Evidence for Redox Signaling in Its Mode of Action

    Directory of Open Access Journals (Sweden)

    Romy Brauer


    Full Text Available The signaling pathway(s and molecular target(s for 5,6-dimethylxanthenone-4-acetic acid (DMXAA, a tumor vascular disrupting agent in late stages of clinical development, are still undefined. As an approach toward identifying potential targets for DMXAA, a tritiated azido-analog of DMXAA was used to probe for cellular binding proteins. More than 20 cytosolic proteins from murine splenocytes, RAW 264.7 cells, and the HECPP immortalized endothelial cells were photoaffinity-labeled. Although no protein domain, fold, or binding site for a specific ligand was found to be shared by all the candidate proteins, essentially all were noted to be oxidizable proteins, implicating a role for redox signaling in the action of DMXAA. Consistent with this hypothesis, DMXAA caused an increase in concentrations of reactive oxygen species (ROS in RAW264.7 cells during the first 2 hours. This increase in ROS was suppressed in the presence of the antioxidant, N-acetyl-L-cysteine, which also suppressed DMXAA-induced cytokine production in the RAW 264.7 cells with no effects on cell viability. Short interfering RNA (siRNA-mediated knockdown of one of the photoaffinity-labeled proteins, superoxide dismutase 1, an ROS scavenger, resulted in an increase in tumor necrosis factor-α production by RAW 264.7 cells in response to DMXAA compared with negative or positive controls transfected with nontargeting or lamin A/C-targeting siRNA molecules, respectively. The results from these lines of study all suggest that redox signaling plays a central role in cytokine induction by DMXAA.

  4. Analogs of LDL Receptor Ligand Motifs in Dengue Envelope and Capsid Proteins as Potential Codes for Cell Entry


    Juan Guevara; Jaime Romo; Troy McWhorter; Natalia Valentinova Guevara


    It is established that cell entry of low density lipoprotein particles (LLPs) containing Apo B100 and Apo E is mediated by receptors and GAGs. Receptor ligand motifs, XBBBXXBX, XBBXBX, and ΨBΨXB, and mono- and bipartite NLS sequences are abundant in Apo E and Apo B100 as well as in envelope and capsid proteins of Dengue viruses 1–4 (DENV1–4). Synthetic, fluorescence-labeled peptides of sequences in DENV2 envelope protein, and DENV3 capsid that include these motifs were used to conduct a quali...

  5. Chick intestinal cytosol binding protein for 1,25-dihydroxyvitamin D/sub 3/: a study of analog binding

    Energy Technology Data Exchange (ETDEWEB)

    Kream, B.E.; Jose, M.J.L.; DeLuca, H.F.


    The structural features of 1,25-dihydroxyvitamin D/sub 3/ that permit its high affinity binding to a 3.7 S protein from chick intestinal cytosol were determined in a series of binding and competition experiments analyzed by sucrose density gradient centrifugation. Optimal binding to the 3.7 S protein was achieved when both 1..cap alpha..- and 25-hydroxyls were present in the vitamin D/sub 3/ molecule. Modification of the side chain by the introduction of a methyl on C-24 and a double bond on C-22,23 (1,25-dihydroxyvitamin D/sub 2/) did not alter the binding of 1,25-dihydroxyvitamin D/sub 3/, but significantly diminished the binding of 25-hydroxyvitamin D/sub 3/. However, introduction of a hydroxyl on C-24 decreased the ability of either 1,25-dihydroxyvitamin D/sub 3/ or 25-hydroxyvitamin D/sub 3/ to compete, especially when the 24-hydroxyl was in the S configuration. These results reveal that the 3.7 S protein requires specific ligand structural features for binding and suggest that metabolite discrimination by the chick intestinal receptor system is likely located in the 3.7 S cytosol protein.

  6. An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein

    Energy Technology Data Exchange (ETDEWEB)

    McCready, Jessica [Department of Natural Sciences, Assumption College, Worcester, MA 01609 (United States); Wong, Daniel S. [Department of Developmental Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Cell and Molecular Physiology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States); Burlison, Joseph A.; Ying, Weiwen [Synta Pharmaceuticals, Lexington, MA 02421 (United States); Jay, Daniel G., E-mail: [Department of Developmental Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Cell and Molecular Physiology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States)


    Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital intracellular Hsp90 functions in normal cells. While some eHsp90 clients are known, it is important to establish other proteins that act outside the cell to validate eHsp90 as a drug target to limit cancer spread. Using mass spectrometry we identified two precursor proteins Galectin 3 binding protein (G3BP) and Lysyl oxidase 2-like protein (LOXL2) that associate with eHsp90 in MDA-MB231 breast cancer cell conditioned media and confirmed that LOXL2 binds to eHsp90 in immunoprecipitates. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. We used STA-12-7191 to test if LOXL2 and G3BP are potential eHsp90 clients. We showed that while LOXL2 can increase wound healing and compensate for STA-12-7191-mediated inhibition of wound closure, addition of G3BP had no affect on this assay. These findings support of role for LOXL2 in eHsp90 stimulated cancer cell migration and provide preliminary evidence for the use of STA-12-7191 to inhibit eHsp90 to limit cancer invasion.

  7. Effects of breast cancer resistance protein inhibitors and pharmaceutical excipients on decreasing gastrointestinal toxicity of camptothecin analogs

    Institute of Scientific and Technical Information of China (English)

    Xin-xin ZHANG; Wei-san PAN; Li GAN; Chun-liu ZHU; Yong GAN


    Aim: To investigate the effect of breast cancer resistance protein (BCRP) inhibitors and pharmaceutical excipients on reducing the biliary excretion of camptothecins (CPT), ameliorating delayed-type diarrhea and intestinal mucosa damage induced by CPT. Methods: The cumulative biliary excretion of irinotecan (CPT-11) and hydroxycamptothecin (HCPT) with or without BCRP inhibitors and excipients was investigated in rats. The gastrointestinal toxicity, assessed as the diarrheal score, body weight change and microscopic pathological damage was also determined in rats. Results: Breast cancer resistance protein (BCRP) exhibited important effects on the biliary excretion of CPT. Coadministration of BCRP inhibitors such as GF120918 and cyclosporin A reduced the biliary excretion of CPT-11 and HCPT. Pharmaceutical excipients such as Pluronic F68 and PEG 2000 stearate also showed inhibitory effects on BCRP and similarly reduced CPT biliary excretion. The observed gastrointestinal toxicity was ameliorated by coadministration of BCRP inhibitors and excipients compared with injection of CPT-11 and HCPT alone. Conclusion:The use of excipients as inhibitors of BCRP is safe and relatively non-toxic, and may lead to important pharmacotherapeutic benefits by decreasing the gastrointestinal toxicity of CPT.

  8. PoSSuM v.2.0: data update and a new function for investigating ligand analogs and target proteins of small-molecule drugs. (United States)

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


    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, 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.

  9. Cytotoxicity Induced by a Redox-silent Analog of Tocotrienol in Human Mesothelioma H2452 Cell Line via Suppression of Cap-dependent Protein Translation. (United States)

    Sato, Ayami; Ueno, Haruka; Takase, Akari; Ando, Akira; Sekine, Yuko; Yano, Tomohiro


    De novo synthesis of proteins is regulated by cap-dependent protein translation. Aberrant activation of the translation is a hallmark of many cancer types including malignant mesothelioma (MM). We previously reported that a redox-silent analog of α-tocotrienol, 6-O-carboxypropyl-α-tocotrienol (T3E) induces potent cytotoxicity against human MM cells. However, the detailed mechanism of cytotoxicity of T3E remains unclear. In this study, we investigated if T3E induced potent cytotoxicity aganist MM cells. T3E reduced the formation of the cap-dependent translation complex and induced inactivation of oncogene from rat sarcoma virus (RAS). These events were associated with T3E cytotoxicity in MM cells. Furthermore, atorvastatin, an inhibitor of RAS function, had similar effects on MM cells. Moreover, 4EGI-1, a specific inhibitor of the cap-dependent translation complex, induced severe cytotoxicity in MM cells. Overall, T3E had a cytotoxic effect on MM cells via disruption of the activated cap-dependent translation complex through inactivation of RAS.

  10. Learning by Analogy: Discriminating between Potential Analogs (United States)

    Richland, Lindsey E.; McDonough, Ian M.


    The ability to successfully discriminate between multiple potentially relevant source analogs when solving new problems is crucial to proficiency in a mathematics domain. Experimental findings in two different mathematical contexts demonstrate that providing cues to support comparative reasoning during an initial instructional analogy, relative to…

  11. Intuitive analog circuit design

    CERN Document Server

    Thompson, Marc


    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

  12. Structured Analog CMOS Design

    CERN Document Server

    Stefanovic, Danica


    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

  13. Analog and hybrid computing

    CERN Document Server

    Hyndman, D E


    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

  14. Analogy in CLAM


    Melis, Erica


    CL A M is a proof planner, developed by the Dream group in Edinburgh,that mainly operates for inductive proofs. This paper addresses the questionhow an analogy model that I developed independently of CL A M can beapplied to CL A M and it presents analogy-driven proof plan construction as acontrol strategy of CL A M . This strategy is realized as a derivational analogythat includes the reformulation of proof plans. The analogical replay checkswhether the reformulated justifications of the sour...

  15. Analog circuit design

    CERN Document Server

    Dobkin, Bob


    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. <

  16. Analogies of Information Security


    Sole, Amund Bauck


    In this thesis it will be tested wither analogies and metaphors would make it easier to teach the fundamental subjects of information security and hacking to people with no previous background in computer science and only basic computer skills. This will be done by conducting interview on people with no background in computer science to see what analogies work the best for different topics in information security. From the analogy getting the best response, a small game will be designed with ...

  17. Challenges in Using Analogies (United States)

    Lin, Shih-Yin; Singh, Chandralekha


    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…

  18. Hydraulic Capacitor Analogy (United States)

    Baser, Mustafa


    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…

  19. Troubleshooting analog circuits

    CERN Document Server

    Pease, Robert A


    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

  20. TV Analog Station Transmitters (United States)

    Department of Homeland Security — This file is an extract from the Consolidated Database System (CDBS) licensed by the Media Bureau. It consists of Analog Television Stations (see Rule Part47 CFR...

  1. Analog multivariate counting analyzers

    CERN Document Server

    Nikitin, A V; Armstrong, T P


    Characterizing rates of occurrence of various features of a signal is of great importance in numerous types of physical measurements. Such signal features can be defined as certain discrete coincidence events, e.g. crossings of a signal with a given threshold, or occurrence of extrema of a certain amplitude. We describe measuring rates of such events by means of analog multivariate counting analyzers. Given a continuous scalar or multicomponent (vector) input signal, an analog counting analyzer outputs a continuous signal with the instantaneous magnitude equal to the rate of occurrence of certain coincidence events. The analog nature of the proposed analyzers allows us to reformulate many problems of the traditional counting measurements, and cast them in a form which is readily addressed by methods of differential calculus rather than by algebraic or logical means of digital signal processing. Analog counting analyzers can be easily implemented in discrete or integrated electronic circuits, do not suffer fro...

  2. Challenges in Analogical Reasoning

    CERN Document Server

    Lin, Shih-Yin


    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 physics principle is involved but that is more difficult to handle. Here, we examine introductory physics students' ability to use analogies in solving problems involving Newton's second law. Students enrolled in an algebra-based introductory physics course were given a solved problem involving tension in a rope and were then asked to solve another problem for which the physics is very similar but involved a frictional force. They were asked to point out the similarities between the two problems and then use the analogy to solve the friction problem.

  3. FGF growth factor analogs (United States)

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


    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.

  4. Analog circuits cookbook

    CERN Document Server

    Hickman, Ian


    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.

  5. Electrical Circuits and Water Analogies (United States)

    Smith, Frederick A.; Wilson, Jerry D.


    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)

  6. Digital and analog communication systems (United States)

    Shanmugam, K. S.


    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.

  7. Analogical Reasoning in Geometry Education (United States)

    Magdas, Ioana


    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…

  8. 6-alkynyl fucose is a bioorthogonal analog for O-fucosylation of epidermal growth factor-like repeats and thrombospondin type-1 repeats by protein O-fucosyltransferases 1 and 2. (United States)

    Al-Shareffi, Esam; Chaubard, Jean-Luc; Leonhard-Melief, Christina; Wang, Sheng-Kai; Wong, Chi-Huey; Haltiwanger, Robert S


    Protein O-fucosyltransferase 1 (Pofut1) and protein O-fucosyltransferase 2 (Pofut2) add O-linked fucose at distinct consensus sequences in properly folded epidermal growth factor (EGF)-like repeats and thrombospondin type-1 (TSR) repeats, respectively. Glycan chain elongation past O-fucose can occur to yield a tetrasaccharide on EGF repeats and a disaccharide on TSRs. Elimination of Pofut1 in mice causes embryonic lethality with Notch-like phenotypes demonstrating that O-fucosylation of Notch is essential for its function. Similarly, elimination of Pofut2 results in an early embryonic lethal phenotype in mice, although the molecular mechanism for the lethality is unknown. The recent development of sugar analogs has revolutionized the study of glycans by providing a convenient method for labeling and tracking glycosylation. In order to study O-fucosylation, we took advantage of the recently developed reporter, 6-alkynyl fucose. Using the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC), or "click" reaction, azido-biotin allows tagging and detection of 6AF-modified proteins. Here we examine whether proteins containing EGF repeats or TSRs with O-fucose consensus sequences are specifically modified with 6AF in cell culture. Using mass spectrometry (MS), we demonstrate that 6AF is efficiently incorporated onto the appropriate consensus sequences on EGF repeats and TSRs. Furthermore, the elongation of the O-fucose monosaccharide on EGF repeats and TSRs is not hampered when 6AF is used. These results show that 6AF is efficiently utilized in a truly bioorthogonal manner by Pofut1, Pofut2 and the enzymes that elongate O-fucose, providing evidence that 6AF is a significant new tool in the study of protein O-fucosylation.

  9. 1,1-Difluoroethyl-substituted triazolothienopyrimidines as inhibitors of a human urea transport protein (UT-B): new analogs and binding model. (United States)

    Liu, Y; Esteva-Font, C; Yao, C; Phuan, P W; Verkman, A S; Anderson, M O


    The kidney urea transport protein UT-B is an attractive target for the development of small-molecule inhibitors with a novel diuretic ('urearetic') action. Previously, two compounds in the triazolothienopyrimidine scaffold (1a and 1c) were reported as UT-B inhibitors. Compound 1c incorporates a 1,1-difluoroethyl group, which affords improved microsomal stability when compared to the corresponding ethyl-substituted compound 1a. Here, a small focused library (4a-4f) was developed around lead inhibitor 1c to investigate the requirement of an amidine-linked thiophene in the inhibitor scaffold. Two compounds (4a and 4b) with nanomolar inhibitory potency (IC50≈40 nM) were synthesized. Computational docking of lead structure 1c and 4a-4f into a homology model of the UT-B cytoplasmic surface suggested binding with the core heterocycle buried deep into the hydrophobic pore region of the protein.

  10. Fluctuation of Vegetative Storage Proteins in the Seedlings of Swietenia macrophylla, Analogous to the Seasonal Changes of Those in the Shoot of the Adult Tree

    Institute of Scientific and Technical Information of China (English)

    Ya-Qin Han; Xing-Fu Yan; Hua Zhang; Zheng-Hai Hu; Bing-Zhong Hao; Wei-Min Tian


    In order to identify appropriate plant materials for studying the gene expression and biological function of vegetative storage proteins (VSPs) in woody plants, the VSPs in the seedlings of Swietenia macrophylla King were investigated by using light microscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)and Western-blotting. The seed of S. macrophylla was rich in storage proteins that accumulated in the vacuoles of cotyledon parenchyma cells in appearance of compact spherical grains. The growth and development of S.macrophylla seedlings were characterized by an obvious growth rhythm. The storage proteins in seeds disappeared during seedling growth while VSPs appeared in the stem 2 weeks after seedling leaves matured. Thereafter,the VSPs in the seedling stem almost exhausted during new shoot growth, and when the leaves of new shoot just matured, both the stem beneath the new shoot of seedlings and the stem of new shoot started to accumulate VSPs. Nitrogen application dramatically increased the level of VSPs, but had little influence on the dynamics of VSP consumption and accumulation in seedling stem. Together with these data, the fluctuation of VSPs in seedlings was very similar to that in the branches of the adult trees. In addition, seedlings are easy to be treated due to their small size. Our results suggested that S. macrophylla seedlings were suitable for investigating the biological roles of VSPs and the mechanism of nitrogen storage in trees.

  11. Analogy, explanation, and proof. (United States)

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


    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.

  12. Quantum Analog Computing (United States)

    Zak, M.


    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.

  13. Are Scientific Analogies Metaphors? (United States)


    psychospiritual processes. A more modern example of unclarified analogy is Freud’s (1973; reprinted from 1955) discussion of anal- eroticism , in which...299-304. Freud, S. On transformations of instinct as exemplified in anal eroticism . In J. Strachey (Ed.), The standard 37 edition of the complete

  14. Terrestrial Spaceflight Analogs: Antarctica (United States)

    Crucian, Brian


    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.

  15. Analogy, Explanation, and Proof

    Directory of Open Access Journals (Sweden)

    John eHummel


    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.

  16. A Transiting Jupiter Analog

    CERN Document Server

    Kipping, David M; Henze, Chris; Teachey, Alex; Isaacson, Howard T; Petigura, Erik A; Marcy, Geoffrey W; Buchhave, Lars A; Chen, Jingjing; Bryson, Steve T; Sandford, Emily


    Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of $(0.91\\pm0.02)$ $R_{\\mathrm{Jup}}$, a low orbital eccentricity ($0.06_{-0.04}^{+0.10}$) and an equilibrium temperature of $(131\\pm3)$ K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric ...

  17. Synthetic Biology: A Unifying View and Review Using Analog Circuits. (United States)

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


    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.

  18. Inductive, Analogical, and Communicative Generalization

    Directory of Open Access Journals (Sweden)

    Adri Smaling


    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.



    Haraguchi, Makoto


    This paper presents a mathematical theory of analogy, which should be a basis in developing analogical reasoning by a computer. The analogy is a partial identity between two sets of facts. In order to compare several analogies, we introduce an ordering of analogies, and we define two types of optimal analogies, maximal analogies and greatest ones. We show a condition under which the greatest analogy exists, and also present a top-down procedure to find the maximal analogies.

  20. Inhibition of a plant virus infection by analogs of melittin. (United States)

    Marcos, J F; Beachy, R N; Houghten, R A; Blondelle, S E; Pérez-Payá, E


    An approach that enables identification of specific synthetic peptide inhibitors of plant viral infection is reported. Synthetic analogs of melittin that have sequence and structural similarities to an essential domain of tobacco mosaic virus coat protein were found to possess highly specific antiviral activity. This approach involves modification of residues located at positions analogous to those that are critical for virus assembly. The degree of inhibition found correlates well with sequence similarities between the viral capsid protein and the melittin analogs studied as well as with the induced conformational changes that result upon interaction of the peptides and ribonucleic acid. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8618922

  1. ESD analog circuits and design

    CERN Document Server

    Voldman, Steven H


    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

  2. Albert Einstein, Analogizer Extraordinaire

    CERN Document Server

    CERN. Geneva


    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.

  3. The human analog of murine cystein rich protein 61 [correction of 16] is a 1alpha,25-dihydroxyvitamin D3 responsive immediate early gene in human fetal osteoblasts: regulation by cytokines, growth factors, and serum. (United States)

    Schütze, N; Lechner, A; Groll, C; Siggelkow, H; Hüfner, M; Köhrle, J; Jakob, F


    1Alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is a potent mediator of differentiation and maintenance of specific functions of osteoblasts. To detect novel targets for 1,25-(OH)2D3 action, we applied differential display PCR to human fetal osteoblast-like cells and identified the human analog of murine cystein rich protein 61 (hCYR61) as a 1,25-(OH)2D3-responsive immediate early gene in differentiated fetal osteoblast-like cells. The murine gene CYR61 is important for cell-cell and cell-matrix interactions, and it belongs to an emerging gene family of cysteine-rich proteins. hCYR61 messenger RNA (mRNA) steady-state levels were stimulated 11-fold by 10 nM 1,25-(OH)2D3 by 1 h and declined to control levels by 4 h. This transient stimulation of hCYR61 mRNA was not inhibited by cycloheximide but was prevented by actinomycin D, indicating that the 1,25-(OH)2D3 effect involves transcriptional events and does not require de novo protein synthesis. hCYR61 mRNA stability was not influenced by 1,25(OH)2D3, whereas cycloheximide treatment stabilized hCYR61 mRNA. FCS, as well as growth factors and cytokines such as basic fibroblast growth factor, epidermal growth factor, tumor necrosis factor alpha, and interleukin-1, strongly elevated hCYR61 mRNA steady-state levels within 1 h. hCYR61 mRNA was expressed also in primary human osteoblasts and osteosarcoma cell lines. Using a commercial tissue blot, hCYR61 mRNA was only observed in skeletal muscle. The fast and transient response of hCYR 61 to 1,25-(OH)2D3, serum, growth factors, and cytokines suggests an important role of hCYR61 for osteoblast function and differentiation.

  4. Vorticity in analog gravity (United States)

    Cropp, Bethan; Liberati, Stefano; Turcati, Rodrigo


    In the analog gravity framework, the acoustic disturbances in a moving fluid can be described by an equation of motion identical to a relativistic scalar massless field propagating in curved space-time. This description is possible only when the fluid under consideration is barotropic, inviscid, and irrotational. In this case, the propagation of the perturbations is governed by an acoustic metric that depends algebrically on the local speed of sound, density, and the background flow velocity, the latter assumed to be vorticity-free. In this work we provide a straightforward extension in order to go beyond the irrotational constraint. Using a charged—relativistic and nonrelativistic—Bose-Einstein condensate as a physical system, we show that in the low-momentum limit and performing the eikonal approximation we can derive a d’Alembertian equation of motion for the charged phonons where the emergent acoustic metric depends on flow velocity in the presence of vorticity.

  5. Feedback in analog circuits

    CERN Document Server

    Ochoa, Agustin


    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...

  6. Beginning analog electronics through projects

    CERN Document Server

    Singmin, Andrew


    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

  7. Mathematical problem solving by analogy. (United States)

    Novick, L R; Holyoak, K J


    We report the results of 2 experiments and a verbal protocol study examining the component processes of solving mathematical word problems by analogy. College students first studied a problem and its solution, which provided a potential source for analogical transfer. Then they attempted to solve several analogous problems. For some problems, subjects received one of a variety of hints designed to reduce or eliminate the difficulty of some of the major processes hypothesized to be involved in analogical transfer. Our studies yielded 4 major findings. First, the process of mapping the features of the source and target problems and the process of adapting the source solution procedure for use in solving the target problem were clearly distinguished: (a) Successful mapping was found to be insufficient for successful transfer and (b) adaptation was found to be a major source of transfer difficulty. Second, we obtained direct evidence that schema induction is a natural consequence of analogical transfer. The schema was found to co-exist with the problems from which it was induced, and both the schema and the individual problems facilitated later transfer. Third, for our multiple-solution problems, the relation between analogical transfer and solution accuracy was mediated by the degree of time pressure exerted for the test problems. Finally, mathematical expertise was a significant predictor of analogical transfer, but general analogical reasoning ability was not. The implications of the results for models of analogical transfer and for instruction were considered.

  8. [Analogies and analogy research in technical biology and bionics]. (United States)

    Nachtigall, Werner


    The procedural approaches of Technical Biology and Bionics are characterized, and analogy research is identified as their common basis. The actual creative aspect in bionical research lies in recognizing and exploiting technically oriented analogies underlying a specific biological prototype to indicate a specific technical application.

  9. Conjecturing via Reconceived Classical Analogy (United States)

    Lee, Kyeong-Hwa; Sriraman, Bharath


    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)


    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. Natural analog studies: Licensing perspective

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, J.W. [Nuclear Regulatory Commission, Washington, DC (United States)


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

  12. Protein (United States)

    ... Food Service Resources Additional Resources About FAQ Contact Protein Protein is found throughout the body—in muscle, ... the heart and respiratory system, and death. All Protein Isn’t Alike Protein is built from building ...

  13. Distributed Episodic and Analogical Reasoning (DEAR) (United States)


    ends analysis Carbonell 1983 Modeling of Analogy Making Structure Mapping Theory (SMT) Gentner 1984 Agent based approach to analogy making...Mapping Engine (SME) Forbus 1990 Learning by analogy with larger domains Prodigy/Analogy Veloso and Carbonell 1991 Analogical Retrieval Engine MAC/FAC

  14. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J M


    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...

  15. Molecular modeling of fentanyl analogs

    Directory of Open Access Journals (Sweden)



    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.

  16. Sulfonimidamide analogs of oncolytic sulfonylureas. (United States)

    Toth, J E; Grindey, G B; Ehlhardt, W J; Ray, J E; Boder, G B; Bewley, J R; Klingerman, K K; Gates, S B; Rinzel, S M; Schultz, R M; Weir, L C; Worzalla, J F


    A series of sulfonimidamide analogs of the oncolytic diarylsulfonylureas was synthesized and evaluated for (1) in vitro cytotoxicity against CEM cells, (2) in vivo antitumor activity against subaxillary implanted 6C3HED lymphosarcoma, and (3) metabolic breakdown to the o-sulfate of p-chloroaniline. The separated enantiomers of one sulfonimidamide analog displayed very different activities in the in vivo screening model. In general, several analogs demonstrated excellent growth inhibitory activity in the 6C3HED model when dosed orally or intraperitoneally. A correlative structure-activity relationship to the oncolytic sulfonylureas was not apparent.

  17. Analog regulation of metabolic demand

    Directory of Open Access Journals (Sweden)

    Muskhelishvili Georgi


    Full Text Available Abstract Background The 3D structure of the chromosome of the model organism Escherichia coli is one key component of its gene regulatory machinery. This type of regulation mediated by topological transitions of the chromosomal DNA can be thought of as an analog control, complementing the digital control, i.e. the network of regulation mediated by dedicated transcription factors. It is known that alterations in the superhelical density of chromosomal DNA lead to a rich pattern of differential expressed genes. Using a network approach, we analyze these expression changes for wild type E. coli and mutants lacking nucleoid associated proteins (NAPs from a metabolic and transcriptional regulatory network perspective. Results We find a significantly higher correspondence between gene expression and metabolism for the wild type expression changes compared to mutants in NAPs, indicating that supercoiling induces meaningful metabolic adjustments. As soon as the underlying regulatory machinery is impeded (as for the NAP mutants, this coherence between expression changes and the metabolic network is substantially reduced. This effect is even more pronounced, when we compute a wild type metabolic flux distribution using flux balance analysis and restrict our analysis to active reactions. Furthermore, we are able to show that the regulatory control exhibited by DNA supercoiling is not mediated by the transcriptional regulatory network (TRN, as the consistency of the expression changes with the TRN logic of activation and suppression is strongly reduced in the wild type in comparison to the mutants. Conclusions So far, the rich patterns of gene expression changes induced by alterations of the superhelical density of chromosomal DNA have been difficult to interpret. Here we characterize the effective networks formed by supercoiling-induced gene expression changes mapped onto reconstructions of E. coli's metabolic and transcriptional regulatory network. Our

  18. Analog CMOS contrastive Hebbian networks (United States)

    Schneider, Christian; Card, Howard


    CMOS VLSI circuits implementing an analog neural network with on-chip contrastive Hebbian learning and capacitive synaptic weight storage have been designed and fabricated. Weights are refreshed by periodic repetition of the training data. To evaluate circuit performance in a medium-sized system, these circuits were used to build a 132 synapse neural network. An adaptive neural system, such as the one described in this paper, can compensate for imperfections in the components from which it is constructed, and thus it is possible to build this type of system using simple, silicon area-efficient analog circuits. Because these analog VLSI circuits are far more compact than their digital counterparts, analog VLSI neural network implementations are potentially more efficient than digital ones.

  19. Solving a problem by analogy (United States)

    Easton, Don


    This note is a description of a student solution to a problem. I found the solution exciting because it exemplifies the kind of solution by analogy that Feynman describes in The Feynman Lectures on Physics.

  20. Analog filters in nanometer CMOS

    CERN Document Server

    Uhrmann, Heimo; Zimmermann, Horst


    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 ...

  1. Novel Gemini vitamin D3 analogs

    DEFF Research Database (Denmark)

    Okamoto, Ryoko; Gery, Sigal; Kuwayama, Yoshio


    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...

  2. Analog electronic neural network circuits

    Energy Technology Data Exchange (ETDEWEB)

    Graf, H.P.; Jackel, L.D. (AT and T Bell Labs., Holmdel, NJ (USA))


    The large interconnectivity and moderate precision required in neural network models present new opportunities for analog computing. This paper discusses analog circuits for a variety of problems such as pattern matching, optimization, and learning. Most of the circuits build so far are relatively small, exploratory designs. The most mature circuits are those for template matching. Chips performing this function are now being applied to pattern recognition problems.

  3. Analog approach to mixed analog-digital circuit simulation (United States)

    Ogrodzki, Jan


    Logic simulation of digital circuits is a well explored research area. Most up-to-date CAD tools for digital circuits simulation use an event driven, selective trace algorithm and Hardware Description Languages (HDL), e.g. the VHDL. This techniques enable simulation of mixed circuits, as well, where an analog part is connected to the digital one through D/A and A/D converters. The event-driven mixed simulation applies a unified, digital-circuits dedicated method to both digital and analog subsystems. In recent years HDL techniques have been also applied to mixed domains, as e.g. in the VHDL-AMS. This paper presents an approach dual to the event-driven one, where an analog part together with a digital one and with converters is treated as the analog subsystem and is simulated by means of circuit simulation techniques. In our problem an analog solver used yields some numerical problems caused by nonlinearities of digital elements. Efficient methods for overriding these difficulties have been proposed.

  4. Labeled Cocaine Analogs (United States)

    Goodman, Mark M.; Shi, Bing Zhi; Keil, Robert N.


    Novel compounds having the structure: ##STR1## where X in .beta. configuration is phenyl, naphthyl; 2,3 or 4-iodophenyl; 2,3 or 4-(trimethylsilyl)phenyl; 3,4,5 or 6-iodonaphthyl; 3,4,5 or 6-(trimethylsilyl)naphthyl; 2,3 or 4-(trialkylstannyl)phenyl; or 3,4,5 or 6-(trialkylstannyl)naphthyl Y in .beta. configuration is Y.sub.1 or Y.sub.2, where Y.sub.1 is 2-fluoroethoxy, 3-fluoropropoxy, 4-fluorobutoxy, 2-fluorocyclopropoxy, 2 or 3-fluorocyclobutoxy, R,S 1'-fluoroisopropoxy, R 1'-fluoroisopropoxy, S 1'-fluoroisopropoxy, 1',3'-difluoroisopropoxy, R,S 1'-fluoroisobutoxy, R 1'-fluoroisobutoxy, S 1'-fluoroisobutoxy, R,S 4'-fluoroisobutoxy, R 4'-fluoroisobutoxy, S 4'-fluoroisobutoxy, or 1',1'-di(fluoromethyl)isobutoxy, and Y.sub.2 is 2-methanesulfonyloxy ethoxy, 3-methanesulfonyloxy propoxy, 4-methanesulfonyloxy butoxy, 2-methanesulfonyloxy cyclopropoxy, 2 or 3-methanesulfonyloxy cyclobutoxy, 1'methanesulfonyloxy isopropoxy, 1'-fluoro, 3'-methanesulfonyloxy isopropoxy, 1'-methanesulfonyloxy, 3'-fluoro isopropoxy, 1'-methanesulfonyloxy isobutoxy, or 4'-methanesulfonyloxy isobutoxy bind dopamine transporter protein and can be labeled with .sup.18 F or .sup.123 I for imaging.

  5. Purine inhibitors of protein kinases, G proteins and polymerases

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Nathanael S. (Berkeley, CA); Schultz, Peter (Oakland, CA); Kim, Sung-Hou (Moraga, CA); Meijer, Laurent (Roscoff, FR)


    The present invention relates to purine analogs that inhibit, inter alia, protein kinases, G-proteins and polymerases. In addition, the present invention relates to methods of using such purine analogs to inhibit protein kinases, G-proteins, polymerases and other cellular processes and to treat cellular proliferative diseases.

  6. All-optical analog comparator (United States)

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


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

  7. Test Wiseness and Analogy Test Performance (United States)

    Moore, James C.


    Subjects received self instruction on how to approach analogy questions. Instruction was directed toward knowledge of the general format of analogy questions in standarized tests and the 15 types of relationships commonly asked for in analogy questions. An analogies post-test showed a significant effect for the group. (Author)

  8. Analog electronics for radiation detection

    CERN Document Server


    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. All-optical analog comparator


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


    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical device...

  10. Mathematical Analogy and Metaphorical Insight (United States)

    Zwicky, Jan


    How are we to understand the power of certain literary metaphors? The author argues that the apprehension of good metaphors is importantly similar to the apprehension of fruitful mathematical analogies: both involve a structural realignment of vision. The author then explores consequences of this claim, drawing conceptually significant parallels…

  11. Geometrical Analogies in Mathematics Lessons (United States)

    Eid, Wolfram


    A typical form of thinking to approach problem solutions humanly is thinking in analogous structures. Therefore school, especially mathematical lessons should help to form and to develop corresponding heuristic abilities of the pupils. In the contribution, a summary of possibilities of mathematics lessons regarding this shall particularly be…

  12. Schema Training in Analogical Reasoning. (United States)

    Robins, Shani; Mayer, Richard E.


    In 3 experiments, 93, 97, and 86 college students, respectively, learned how to solve 20 verbal analogy problems and took transfer and memory tests. Results are inconsistent with active responding theory and further indicate that schema induction is maximized when the schemas are made salient and the cognitive system is not overloaded. (SLD)


    DEFF Research Database (Denmark)

    Gaunholt, Hans


    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...

  14. Analog Input Data Acquisition Software (United States)

    Arens, Ellen


    DAQ Master Software allows users to easily set up a system to monitor up to five analog input channels and save the data after acquisition. This program was written in LabVIEW 8.0, and requires the LabVIEW runtime engine 8.0 to run the executable.

  15. International Alligator Rivers Analog Project

    Energy Technology Data Exchange (ETDEWEB)

    Bichard, G.F.


    The Australian Nuclear Science and Technology Organization (ANSTO), the Japan Atomic Energy Research Institute, the Swedish Nuclear Power Inspectorate, the U.K. Department of the Environment, the US Nuclear Regulatory Commission (NRC), and the Power Reactor and Nuclear Fuel Development Corporation of Japan are participating under the aegis of the Nuclear Energy Agency in the International Alligator Rivers Analog Project. The project has a duration of 3 yr, starting in 1988. The project has grown out of a research program on uranium ore bodies as analogs of high-level waste (HLW) repositories undertaken by ANSTO supported by the NRC. A primary objective of the project is to develop an approach to radionuclide transport model validation that may be used by the participants to support assessments of the safety of radioactive waste repositories. The approach involves integrating mathematical and physical modeling with hydrological and geochemical field and laboratory investigations of the analog site. The Koongarra uranium ore body has been chosen as the analog site because it has a secondary ore body that has formed over the past million years as a result of leaching by groundwater flowing through fractures in the primary ore body.

  16. Amygdalin analogs for the treatment of psoriasis. (United States)

    Perez, Juan J


    Psoriasis is one of the most prevalent immune-mediated illness worldwide. The disease can still only be managed rather than cured, so treatments are aimed at clearing skin lesions and preventing their recurrence. Several treatments are available depending on the extent of the psoriatic lesion. Among the topical treatments corticostereoids, vitamin D3 analogs and retinoids are commonly used. However, these treatments may have adverse effects in the long term. Conversely, systemic conventional treatments include immunosuppresors such as cyclosporin or methotrexate associated with high toxicity levels. Biologicals are alternative therapeutical agents introduced in the last 10 years. These include fusion proteins or monoclonal antibodies designed to inhibit the action of specific cytokines or to prevent T-lymphocyte activation. However, due to recent knowledge on the etiology of the disease, diverse new small molecules have appeared as promising alternatives for the treatment of psoriasis. Among them, inhibitors of JAK3, inhibitors of PDE 4 and amygdalin analogs. The latter are promising small molecules presently in preclinical studies which are the object of the present report.

  17. C-Glycosyl Analogs of Oligosaccharides (United States)

    Vauzeilles, Boris; Urban, Dominique; Doisneau, Gilles; Beau, Jean-Marie

    This chapter covers the synthesis of a large collection of "C-oligosaccharides ", synthetic analogs of naturally occurring oligosaccharides in which a carbon atom replaces the anomeric, interglycosidic oxygen atom. These non-natural constructs are stable to chemical and enzymatic degradation, and are primarily devised to probe carbohydrate-based biological processes. These mainly target carbohydrate-protein interactions such as the modulation of glycoenzyme (glycosylhydrolases and transferases) activities or the design of ligands for lectin Carbohydrate Recognition Domains. The discussion is based on the key carbon-carbon bond assembling steps on carbohydrate templates: ionic (anionic and cationic chemistries, sigmatropic rearrangements) or radical assemblage, and olefin metathesis. Synthetic schemes in which at least one of the monosaccharide units is constructed by total synthesis or by cyclization of acyclic chiral chains are presented separately in a "partial de novo synthesis" section. The review also provides comments, when they are known, on the conformational and binding properties of these synthetic analogs, as well as their biological behavior when tested.

  18. Analog circuit design art, science and personalities

    CERN Document Server

    Williams, Jim


    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

  19. Disease Resistance Gene Analogs (RGAs in Plants

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Sekhwal


    Full Text Available Plants have developed effective mechanisms to recognize and respond to infections caused by pathogens. Plant resistance gene analogs (RGAs, as resistance (R gene candidates, have conserved domains and motifs that play specific roles in pathogens’ resistance. Well-known RGAs are nucleotide binding site leucine rich repeats, receptor like kinases, and receptor like proteins. Others include pentatricopeptide repeats and apoplastic peroxidases. RGAs can be detected using bioinformatics tools based on their conserved structural features. Thousands of RGAs have been identified from sequenced plant genomes. High-density genome-wide RGA genetic maps are useful for designing diagnostic markers and identifying quantitative trait loci (QTL or markers associated with plant disease resistance. This review focuses on recent advances in structures and mechanisms of RGAs, and their identification from sequenced genomes using bioinformatics tools. Applications in enhancing fine mapping and cloning of plant disease resistance genes are also discussed.

  20. Holism and nonseparability by analogy (United States)

    Arageorgis, Aristidis


    This paper explores the issues of holism and nonseparability in relativistic quantum field theory (QFT) by focusing on an analog of the typical model featuring in many discussions of holism and nonseparability in nonrelativistic quantum mechanics. It is argued that the quantum field theoretic model does exhibit holism in a metaphysical sense and that there are plausible grounds to view QFT holistic in an epistemological sense. However, the complexities arising from the fact that quantum fields have infinite degrees of freedom prohibit the exploitation of the elaborated analogy toward demonstrating that the QFT model exhibits the kind of state nonseparability familiar from ordinary quantum mechanics. Still, it is argued that the QFT model does satisfy a rather weak epistemological criterion for state nonseparability.

  1. Synaptic dynamics in analog VLSI. (United States)

    Bartolozzi, Chiara; Indiveri, Giacomo


    Synapses are crucial elements for computation and information transfer in both real and artificial neural systems. Recent experimental findings and theoretical models of pulse-based neural networks suggest that synaptic dynamics can play a crucial role for learning neural codes and encoding spatiotemporal spike patterns. Within the context of hardware implementations of pulse-based neural networks, several analog VLSI circuits modeling synaptic functionality have been proposed. We present an overview of previously proposed circuits and describe a novel analog VLSI synaptic circuit suitable for integration in large VLSI spike-based neural systems. The circuit proposed is based on a computational model that fits the real postsynaptic currents with exponentials. We present experimental data showing how the circuit exhibits realistic dynamics and show how it can be connected to additional modules for implementing a wide range of synaptic properties.

  2. Mechanical Analogies of Fractional Elements

    Institute of Scientific and Technical Information of China (English)

    HU Kai-Xin; ZHU Ke-Qin


    A Fractional element model describes a special kind of viscoelastic material.Its stress is proportional to the fractional-order derivative of strain. Physically the mechanical analogies of fractional elements can be represented by spring-dashpot fractal networks. We introduce a constitutive operator in the constitutive equations of viscoelastic materials.To derive constitutive operators for spring-dashpot fractal networks, we use Heaviside operational calculus, which provides explicit answers not otherwise obtainable simply.Then the series-parallel formulas for the constitutive operator are derived. Using these formulas, a constitutive equation of fractional element with 1/2-order derivative is obtained.Finally we find the way to derive the constitutive equations with other fractional-order derivatives and their mechanical analogies.

  3. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel


    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. Shotgun protein sequencing.

    Energy Technology Data Exchange (ETDEWEB)

    Faulon, Jean-Loup Michel; Heffelfinger, Grant S.


    A novel experimental and computational technique based on multiple enzymatic digestion of a protein or protein mixture that reconstructs protein sequences from sequences of overlapping peptides is described in this SAND report. This approach, analogous to shotgun sequencing of DNA, is to be used to sequence alternative spliced proteins, to identify post-translational modifications, and to sequence genetically engineered proteins.

  5. Low Power CMOS Analog Multiplier

    Directory of Open Access Journals (Sweden)

    Shipra Sachan


    Full Text Available In this paper Low power low voltage CMOS analog multiplier circuit is proposed. It is based on flipped voltage follower. It consists of four voltage adders and a multiplier core. The circuit is analyzed and designed in 0.18um CMOS process model and simulation results have shown that, under single 0.9V supply voltage, and it consumes only 31.8µW quiescent power and 110MHZ bandwidth.

  6. A global analog of Cheshire charge

    CERN Document Server

    McGraw, P


    It is shown that a model with a spontaneously broken global symmetry can support defects analogous to Alice strings, and a process analogous to Cheshire charge exchange can take place. A possible realization in superfluid He-3 is pointed out.

  7. Investigating visual analogies for visual insight problems


    Corina Sas; Eric Luchian; Linden Ball


    Much research has focused on the impact of analogies in insight problem solving, but less work has investigated how the visual analogies for insight are actually constructed. Thus, it appears that in the search for their facilitative impact on the incubation effect, the understanding of what makes good visual analogies has somehow been lost. This paper presents preliminary work of constructing a set of 6 visual analogies and evaluating their impact on solving the visual problem of eight coins...

  8. Hegel, Analogy, and Extraterrestrial Life (United States)

    Ross, Joseph T.

    Georg Wilhelm Friedrich Hegel rejected the possibility of life outside of the Earth, according to several scholars of extraterrestrial life. Their position is that the solar system and specifically the planet Earth is the unique place in the cosmos where life, intelligence, and rationality can be. The present study offers a very different interpretation of Hegel's statements about the place of life on Earth by suggesting that, although Hegel did not believe that there were other solar systems where rationality is present, he did in fact suggest that planets in general, not the Earth exclusively, have life and possibly also intelligent inhabitants. Analogical syllogisms are superficial, according to Hegel, insofar as they try to conclude that there is life on the Moon even though there is no evidence of water or air on that body. Similar analogical arguments for life on the Sun made by Johann Elert Bode and William Herschel were considered by Hegel to be equally superficial. Analogical arguments were also used by astronomers and philosophers to suggest that life could be found on other planets in our solar system. Hegel offers no critique of analogical arguments for life on other planets, and in fact Hegel believed that life would be found on other planets. Planets, after all, have meteorological processes and therefore are "living" according to his philosophical account, unlike the Moon, Sun, and comets. Whereas William Herschel was already finding great similarities between the Sun and the stars and had extended these similarities to the property of having planets or being themselves inhabitable worlds, Hegel rejected this analogy. The Sun and stars have some properties in common, but for Hegel one cannot conclude from these similarities to the necessity that stars have planets. Hegel's arguments against the presence of life in the solar system were not directed against other planets, but rather against the Sun and Moon, both of which he said have a different

  9. Construction and characterization of an azurin analog for the purple copper site in cytochrome c oxidase.


    Hay, M; Richards, J. H.; Lu, Y.


    A protein analog of a purple copper center has been constructed from a recombinant blue copper protein (Pseudomonas aeruginosa azurin) by replacing the loop containing the three ligands to the blue copper center with the corresponding loop of the CuA center in cytochrome c oxidase (COX) from Paracoccus denitrificans. The electronic absorption in the UV and visible region (UV-vis) and electron paramagnetic resonance (EPR) spectra of this analog are remarkably similar to those of the native CuA...

  10. Analogical Reasoning: A Review of the Literature. (United States)

    Dawis, Rene V.; Siojo, Luis T.

    The mathematical and philosophical origins of "analogy" are described and their influence on the thinking of intelligence theorists is traced. Theories of intelligence and cognition bearing on analogical reasoning are examined, specifically those of Spearman, Thorndike, Guilford and Piaget. The analogy test item is shown to be a paradigm…

  11. Reasoning by Analogy in Constructing Mathematical Ideas. (United States)

    English, Lyn D.

    A powerful way of understanding something new is by analogy with something already known. An analogy is defined as a mapping from one structure, which is already known (the base or source), to another structure that is to be inferred or discovered (the target). The research community has given considerable attention to analogical reasoning in the…

  12. EscO, a Functional and Structural Analog of the Flagellar FliJ Protein, Is a Positive Regulator of EscN ATPase Activity of the Enteropathogenic Escherichia coli Injectisome


    Romo-Castillo, Mariana; Andrade, Angel; Espinosa, Norma; Monjarás Feria, Julia; Soto, Eduardo; Díaz-Guerrero, Miguel; González-Pedrajo, Bertha


    Type III secretion systems (T3SSs) are multiprotein molecular devices used by many Gram-negative bacterial pathogens to translocate effector proteins into eukaryotic cells. A T3SS is also used for protein export in flagellar assembly, which promotes bacterial motility. The two systems are evolutionarily related, possessing highly conserved components in their export apparatuses. Enteropathogenic Escherichia coli (EPEC) employs a T3SS, encoded by genes in the locus of enterocyte effacement (LE...

  13. Analog circuit design art, science, and personalities

    CERN Document Server

    Williams, Jim


    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

  14. Analog and mixed-signal electronics

    CERN Document Server

    Stephan, Karl


    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

  15. Practical analog electronics for technicians

    CERN Document Server

    Kimber, W A


    '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

  16. Transfer Between Analogies: How Solving One Analogy Problem Helps to Solve Another


    Keane, Mark T.


    This paper deals with transfer between analogies; with what people acquire from one analogy problem-solving episode that can be re-applied to a subsequent analogy, problem-solving episode. This issue must be resolved if we are to understand the nature of expertise and the appropriate use of analogy in education. There are two main explanations of what subjects acquire from an analogy problem-solving episode. The schema-induction hypothesis maintains that subjects acquire an abs...

  17. EscO, a functional and structural analog of the flagellar FliJ protein, is a positive regulator of EscN ATPase activity of the enteropathogenic Escherichia coli injectisome. (United States)

    Romo-Castillo, Mariana; Andrade, Angel; Espinosa, Norma; Monjarás Feria, Julia; Soto, Eduardo; Díaz-Guerrero, Miguel; González-Pedrajo, Bertha


    Type III secretion systems (T3SSs) are multiprotein molecular devices used by many Gram-negative bacterial pathogens to translocate effector proteins into eukaryotic cells. A T3SS is also used for protein export in flagellar assembly, which promotes bacterial motility. The two systems are evolutionarily related, possessing highly conserved components in their export apparatuses. Enteropathogenic Escherichia coli (EPEC) employs a T3SS, encoded by genes in the locus of enterocyte effacement (LEE) pathogenicity island, to colonize the human intestine and cause diarrheal disease. In the present work, we investigated the role of the LEE-encoded EscO protein (previously Orf15 or EscA) in T3SS biogenesis. We show that EscO shares similar properties with the flagellar FliJ and the Yersinia YscO protein families. Our findings demonstrate that EscO is essential for secretion of all categories of T3SS substrates. Consistent with its central role in protein secretion, it was found to interact with the ATPase EscN and its negative regulator, EscL, of the export apparatus. Moreover, we show that EscO stimulates EscN enzymatic activity; however, it is unable to upregulate ATP hydrolysis in the presence of EscL. Remarkably, EscO partially restored the swimming defect of a Salmonella flagellar fliJ mutant and was able to stimulate the ATPase activity of FliI. Overall, our data indicate that EscO is the virulence counterpart of the flagellar FliJ protein.

  18. Selective modulation of protein kinase isozymes by the site-selective analog 8-chloroadenosine 3',5'-cyclic monophosphate provides a biological means for control of human colon cancer cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Ally, S.; Tortora, G.; Clair, T.; Grieco, D.; Merlo, G.; Katsaros, D.; Ogreid, D.; Doeskeland, S.O.; Jahnsen, T.; Cho-Chung, Yoonsang


    Differential expression of type I and type II cAMP-dependent protein kinase isozymes has been linked to growth regulation and differentiation. The authors examined the expression of protein kinase isozymes in the LS 174T human colon cancer cell line during 8-chloroadenosine 3',5'-cyclic monophosphate (8-Cl-cAMP)-induced growth inhibition. Two species of R/sup II/ (the regulatory subunit of protein kinase type II) with apparent M/sub r/ 52,000 (R/sup II//sub 52/) and M/sub r/ 56,000 (R/sup II//sub 56/) and a single species of R/sup I/ (the regulatory subunit of protein kinase type I) with M/sub r/ 48,000 were identified in the cancer cells. R/sup I/ and both forms of R/sup II/ were covalently labeled with 8-azidoadenosine 3',5'-cyclic (/sup 32/P)monophosphate, and two anti-R/sup II/ antibodies that exclusively recognize either R/sup II//sub 52/ or R/sup II//sub 56/ resolved two forms of the R/sup II/ receptors. 8-Cl-cAMP caused transcriptional activation of the R/sup II//sub 52/ receptor gene and inactivation of the R/sup I/ receptor gene. Thus, differential regulation of various forms of cAMP receptor proteins is involved in 8-Cl-cAMP-induced regulation of cancer cell growth, and nuclear translocation of R/sup II//sub 52/ receptor protein appears to be an early event in such differential regulation.

  19. Synthesis of a water-soluble analog of 6-methyl-3-N-alkyl catechol labeled with carbon 13: NMR approach to the reactivity of poison ivy/oak sensitizers toward proteins. (United States)

    Goetz, G; Meschkat, E; Lepoittevin, J P


    A 13-C labeled water soluble derivative of alkylcatechol was synthesized and reacted with human serum albumin in phosphate buffer at pH 7.4 in air to allow a slow oxidation of the catechol into orthoquinone. The formation of several adducts was evidenced by a combination of 13C and 1H-13C correlation NMR. Although some adducts could result from a classical o-quinone formation - Michael type addition, our results suggest that a second pathway, involving a direct reaction of a carbon centered radical with proteins could be an important mechanism in the formation of modified proteins.

  20. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J. M


    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...

  1. Study on CCR5 analogs and affinity peptides. (United States)

    Wu, Yingping; Deng, Riqiang; Wu, Wenyan


    The G protein-coupled receptor of human chemokine receptor 5 (CCR5) is a key target in the human immunodeficiency virus (HIV) infection process due to its major involvement in binding to the HIV type 1 (HIV-1) envelope glycoprotein gp120 and facilitating virus entry into the cells. The identification of naturally occurring CCR5 mutations (especially CCR5 delta-32) has allowed us to address the CCR5 molecule as a promising target to prevent or resist HIV infection in vivo. To obtain high-affinity peptides that can be used to block CCR5, CCR5 analogs with high conformational similarity are required. In this study, two recombinant proteins named CCR5 N-Linker-E2 and CCR5 mN-E1-E2 containing the fragments of the CCR5 N-terminal, the first extracellular loop or the second extracellular loop are cloned from a full-length human CCR5 cDNA. The recombinant human CCR5 analogs with self-cleavage activity of the intein Mxe or Ssp in the vector pTwinI were then produced with a high-yield expression and purification system in Escherichia coli. Experiments of extracellular epitope-activity identification (such as immunoprecipitation and indirective/competitive enzyme-linked immunosorbent assay) confirmed the close similarity between the epitope activity of the CCR5 analogs and that of the natural CCR5, suggesting the applicability of the recombinant CCR5 analogs as antagonists of the chemokine ligands. Subsequent screening of high-affinity peptides from the phage random-peptides library acquired nine polypeptides, which could be used as CCR5 peptide antagonists. The CCR5 analogs and affinity peptides elucidated in this paper provide us with a basis for further study of the mechanism of inhibition of HIV-1 infection.

  2. Development of a stable phosphoarginine analog for producing phosphoarginine antibodies. (United States)

    Ouyang, Han; Fu, Chuan; Fu, Songsen; Ji, Zhe; Sun, Ying; Deng, Peiran; Zhao, Yufen


    Protein phosphorylation is one of the most common and extensively studied post-translational modifications (PTMs). Compared to the O-phosphorylation on Ser, Thr and Tyr residues, our understanding of arginine phosphorylation is relatively limited, both in prokaryotes and eukaryotes, due to the intrinsic instability of phosphoarginine (pArg) and the lack of a feasible method to produce anti-pArg antibodies. We report the design and synthesis of a stable pArg analog, in which the labile N-P bond is replaced with a non-hydrolyzable C-P bond. Significantly, this analog was successfully used as a hapten to raise an immune response and the first mouse polyclonal antibody that specifically recognizes pArg-containing peptides and proteins was produced using analog-KLH conjugated as the immunogen. The generated antibody shows excellent specificity towards pArg-containing peptides and proteins, and could be used for a variety of biological detection methods. This provides us an invaluable tool to unravel the mystery of the biological function of pArg.

  3. Analog computing by Brewster effect. (United States)

    Youssefi, Amir; Zangeneh-Nejad, Farzad; Abdollahramezani, Sajjad; Khavasi, Amin


    Optical computing has emerged as a promising candidate for real-time and parallel continuous data processing. Motivated by recent progresses in metamaterial-based analog computing [Science343, 160 (2014)SCIEAS0036-807510.1126/science.1242818], we theoretically investigate the realization of two-dimensional complex mathematical operations using rotated configurations, recently reported in [Opt. Lett.39, 1278 (2014)OPLEDP0146-959210.1364/OL.39.001278]. Breaking the reflection symmetry, such configurations could realize both even and odd Green's functions associated with spatial operators. Based on such an appealing theory and by using the Brewster effect, we demonstrate realization of a first-order differentiator. Such an efficient wave-based computation method not only circumvents the major potential drawbacks of metamaterials, but also offers the most compact possible device compared to conventional bulky lens-based optical signal and data processors.

  4. Priming analogical reasoning with false memories. (United States)

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


    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.

  5. Design and Analysis of Reconfigurable Analog System (United States)


    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

  6. Robust hyperchaotic synchronization via analog transmission line (United States)

    Sadoudi, S.; Tanougast, C.


    In this paper, a novel experimental chaotic synchronization technique via analog transmission is discussed. We demonstrate through Field-Programmable Gate Array (FPGA) implementation design the robust synchronization of two embedded hyperchaotic Lorenz generators interconnected with an analog transmission line. The basic idea of this work consists in combining a numerical generation of chaos and transmitting it with an analog signal. The numerical chaos allows to overcome the callback parameter mismatch problem and the analog transmission offers robust data security. As application, this technique can be applied to all families of chaotic systems including time-delayed chaotic systems.

  7. Fermilab accelerator control system: Analog monitoring facilities

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  8. Inhibition of thyrotropin-stimulated adenosine 3',5'-monophosphate formation in rat thyroid cells by an adenosine analog. Evidence that the inhibition is mediated by the putative inhibitory guanine nucleotide regulatory protein. (United States)

    Berman, M I; Thomas, C G; Nayfeh, S N


    Addition of N6-(L-2-phenylisopropyl)-adenosine (PIA) to cultured FRTL-5 rat thyroid cells led to a concentration-dependent inhibition of TSH-stimulated cAMP formation. Half-maximal inhibition was attained with approximately 0.5 nM PIA. Forskolin and cholera toxin-stimulated cAMP production were also inhibited by PIA. 3-Isobutyl-methylxanthine inhibited the effect of PIA. These results are consistent with the presence of inhibitory adenosine receptors (Ri). Ri-sites were further demonstrated by the binding of 3H-cyclohexyl-adenosine to FRTL-5 plasma membranes. High (Kd = 0.50 +/- 0.07 nM) and low affinity (Kd = 5.95 +/- 2.33 nM) binding sites were observed. Pretreatment of FRTL-5 cells with pertussis, but not cholera, toxin effectively antagonized the inhibitory effects of PIA on cAMP production. ADP-ribosylation of FRTL-5 membranes with [32P]-NAD in the presence of cholera or pertussis toxin specifically labeled a 45,000 and 41,000 Mr species, respectively, which correspond to the alpha subunit of the stimulatory and inhibitory guanine nucleotide regulatory proteins. These results demonstrate that PIA inhibits TSH-stimulated cAMP production via Ri-sites on FRTL-5 thyroid cells. PIA appears to exert its inhibitory effects through the inhibitory guanine nucleotide regulatory protein.

  9. Direct Monitoring of Nucleotide Turnover in Human Cell Extracts and Cells by Fluorogenic ATP Analogs. (United States)

    Hacker, Stephan M; Buntz, Annette; Zumbusch, Andreas; Marx, Andreas


    Nucleotides containing adenosine play pivotal roles in every living cell. Adenosine triphosphate (ATP), for example, is the universal energy currency, and ATP-consuming processes also contribute to posttranslational protein modifications. Nevertheless, detecting the turnover of adenosine nucleotides in the complex setting of a cell remains challenging. Here, we demonstrate the use of fluorogenic analogs of ATP and adenosine tetraphosphate to study nucleotide hydrolysis in lysates of human cell lines and in intact human cells. We found that the adenosine triphosphate analog is completely stable in lysates of human cell lines, whereas the adenosine tetraphosphate analog is rapidly turned over. The observed activity in human cell lysates can be assigned to a single enzyme, namely, the human diadenosine tetraphosphate hydrolase NudT2. Since NudT2 has been shown to be a prognostic factor for breast cancer, the adenosine tetraphosphate analog might contribute to a better understanding of its involvement in cancerogenesis and allow the straightforward screening for inhibitors. Studying hydrolysis of the analogs in intact cells, we found that electroporation is a suitable method to deliver nucleotide analogs into the cytoplasm and show that high FRET efficiencies can be detected directly after internalization. Time-dependent experiments reveal that adenosine triphosphate and tetraphosphate analogs are both processed in the cellular environment. This study demonstrates that these nucleotide analogs indeed bear the potential to be powerful tools for the exploration of nucleotide turnover in the context of whole cells.

  10. Synthesis and biodistribution of radioiodinated nicotine analogs

    Energy Technology Data Exchange (ETDEWEB)

    Chan, S.M.; Basmadjian, G.P.; Sadek, S.A.; Magarian, R.A.; Grunder, J.R.; Marten, D.F.


    Four /sup 125/I-labelled nicotine analogs were synthesized: 3-(methylpropylaminomethyl)-, 3-(diethylaminomethyl)-, 3-(isopropylaminomethyl)-, and 3-(diisopropylaminomethyl)-5-(/sup 125/I)-iodopyridines. 5-Bromonicotinic acid was acylated with thionyl chloride and then reacted with the appropriate primary and secondary amines to give the corresponding amides which were reduced with diborane to the desirable amines. Radioiodination was done by halogen exchange. Biodistribution studies in rats, showed that all four labelled compounds were rapidly taken up by the brain and the adrenal gland. This was followed by rapid washout of the compounds from these organs. The most promising of these compounds, 3-(diisopropylaminomethyl)-5-(/sup 125/I)-iodopyridine, showed a brain-to-blood ratio of 6.0:1 and an adrenal-to-blood ratio of 35.9:1 at 2 minutes post administration. In vitro correlation studies showed that brain uptake of these compounds depends on both protein binding and lipophilicity, whereas adrenal uptake depends only on lipophilicity.

  11. Differentiation of Keratinocytes Modulates Skin HPA Analog. (United States)

    Wierzbicka, Justyna M; Żmijewski, Michał A; Antoniewicz, Jakub; Sobjanek, Michal; Slominski, Andrzej T


    It is well established, that epidermal keratinocytes express functional equivalent of hypothalamus-pituitary-adrenal axis (HPA) in order to respond to changing environment and maintain internal homeostasis. We are presenting data indicating that differentiation of primary neonatal human keratinocytes (HPEKp), induced by prolonged incubation or calcium is accompanied by significant changes in the expression of the elements of skin analog of HPA (sHPA). Expression of CRF, UCN1-3, POMC, ACTH, CRFR1, CRFR2, MC1R, MC2R, and GR (coded by NR3C1 gene) were observed on gene/protein levels along differentiation of keratinocytes in culture with similar pattern seen by immunohistochemistry on full thickness skin biopsies. Expression of CRF was more pronounced in less differentiated keratinocytes, which corresponded to the detection of CRF immunoreactivity preferentially in the stratum basale. POMC expression was enhanced in more differentiated keratinocytes, which corresponded to detection of ACTH immunoreactivity, predominantly in the stratum spinosum and stratum granulosum. Expression of urocortins was also affected by induction of HPEKp differentiation. Immunohistochemical studies showed high prevalence of CRFR1 in well differentiated keratinocytes, while smaller keratinocytes showed predominantly CRFR2 immunoreactivity. MC2R mRNA levels were elevated from days 4 to 8 of in vitro incubation, while MC2R immunoreactivity was the highest in the upper layers of epidermis. Similar changes in mRNA/protein levels of sHPA elements were observed in HPEKp keratinocytes treated with calcium. Summarizing, preferential expression of CRF and POMC (ACTH) by populations of keratinocytes on different stage of differentiation resembles organization of central HPA axis suggesting their distinct role in physiology and pathology of the epidermis. J. Cell. Physiol. 232: 154-166, 2017. © 2016 Wiley Periodicals, Inc.

  12. Characterization of a lectin in human plasma analogous to bovine conglutinin

    DEFF Research Database (Denmark)

    Thiel, S; Baatrup, G; Friis-Christiansen, P


    The structural characteristics of a human plasma protein analogous to bovine conglutinin were studied. The protein was previously found to bind to complement-reacted IgG in a calcium-dependent and N-acetyl-D-glucosamine-inhibitable manner and it further shows cross-reactivity with anti-bovine con...

  13. A physical analogy to fuzzy clustering

    DEFF Research Database (Denmark)

    Jantzen, Jan


    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...... the algorithm to students. The analogy suggests a possible extension of the fuzzy membership assignment equation....


    Directory of Open Access Journals (Sweden)

    Nyoto Suseno


    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.

  15. An Analog Computer for Electronic Engineering Education (United States)

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


    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…

  16. A Mechanical Analogy for the Photoelectric Effect (United States)

    Kovacevic, Milan S.; Djordjevich, Alexandar


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

  17. Analogies in high school Brazilian chemistry textbooks

    Directory of Open Access Journals (Sweden)

    Rosária Justi


    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. Antibacterial and Antibiofilm Activities of Makaluvamine Analogs

    Directory of Open Access Journals (Sweden)

    Bhavitavya Nijampatnam


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

  19. Compressed Sensing of Analog Signals

    CERN Document Server

    Eldar, Yonina C


    A traditional assumption underlying most data converters is that the signal should be sampled at a rate which exceeds twice the highest frequency. This statement is based on a worst-case scenario in which the signal occupies the entire available bandwidth. In practice, many signals posses a sparse structure so that a large part of the bandwidth is not exploited. In this paper, we consider a framework for utilizing this sparsity in order to sample such analog signals at a low rate. More specifically, we consider continuous-time signals that lie in a shift-invariant (SI) space generated by m kernels, so that any signal in the space can be expressed as an infinite linear combination of the shifted kernels. If the period of the underlying SI space is equal to T, then such signals can be perfectly reconstructed from samples at a rate of m/T. Here we treat the case in which only k out of the m generators are active, meaning that the signal actually lies in a lower dimensional space spanned by k generators. However,...

  20. Novel Analog For Muscle Deconditioning (United States)

    Ploutz-Snyder, Lori; Ryder, Jeff; Buxton, Roxanne; Redd. Elizabeth; Scott-Pandorf, Melissa; Hackney, Kyle; Fiedler, James; Ploutz-Snyder, Robert; Bloomberg, Jacob


    Existing models (such as bed rest) of muscle deconditioning are cumbersome and expensive. We propose a new model utilizing a weighted suit to manipulate strength, power, or endurance (function) relative to body weight (BW). Methods: 20 subjects performed 7 occupational astronaut tasks while wearing a suit weighted with 0-120% of BW. Models of the full relationship between muscle function/BW and task completion time were developed using fractional polynomial regression and verified by the addition of pre-and postflightastronaut performance data for the same tasks. Splineregression was used to identify muscle function thresholds below which task performance was impaired. Results: Thresholds of performance decline were identified for each task. Seated egress & walk (most difficult task) showed thresholds of leg press (LP) isometric peak force/BW of 18 N/kg, LP power/BW of 18 W/kg, LP work/BW of 79 J/kg, isokineticknee extension (KE)/BW of 6 Nm/kg, and KE torque/BW of 1.9 Nm/kg.Conclusions: Laboratory manipulation of relative strength has promise as an appropriate analog for spaceflight-induced loss of muscle function, for predicting occupational task performance and establishing operationally relevant strength thresholds.

  1. An optical analog signal transmitter

    Energy Technology Data Exchange (ETDEWEB)

    Fudzita, K.; Itida, T.; Tanaka, Kh.


    An optical laser analog signal transmitter employing an amplitude modulated subcarrier is patented; this transmitter performs stable and high quality transmission of information signals over great distances. A feature of the proposed transmitter is a special transmitter operational mode in which the light emission reflected off the connection point to the fiber optic conduit is sent back to the laser diode in a transient period. As a result, the critical mode of the generated emission is not influenced by the reflected signal. The transmitter consists of a laser diode with biasing near the cutoff point, an amplitude modulator with a subcarrier frequency oscillator, a section of flexible fiber-optic cable of length L, which connects the laser diode to the primary optical fiber conduit, and the connector itself. The subcarrier frequency may vary over wide ranges to establish the necessary correlation between the length of the light conduit section L and the return propagation time of the reflected light signal from the connection point to the laser diode. The difference between the lasing time of the light signal and the return time to the laser diode of the signal reflected off the connector is determined by the relation tau equals 2nL/c - mtauc, where L is the length of the connecting section; n is the refractivity of the optical fiber; c is the velocity of light; tauc is the period of the high frequency subcarrier signal; and m is an integer.

  2. Demonstrative and non-demonstrative reasoning by analogy


    Ippoliti, Emiliano


    The paper analizes a set of issues related to analogy and analogical reasoning, namely: 1) The problem of analogy and its duplicity; 2) The role of analogy in demonstrative reasoning; 3) The role of analogy in non-demonstrative reasoning; 4) The limits of analogy; 5) The convergence, particularly in multiple analogical reasoning, of these two apparently distinct aspects and its methodological and philosophical consequences. The paper, using example from number theory, argues for an heuristc c...

  3. Computational approaches to analogical reasoning current trends

    CERN Document Server

    Richard, Gilles


    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...

  4. An Analog Earth Climate Model (United States)

    Varekamp, J. C.


    The earth climate is broadly governed by the radiative power of the sun as well as the heat retention and convective cooling of the atmosphere. I have constructed an analog earth model for an undergraduate climate class that simulates mean climate using these three parameters. The ‘earth’ is a hollow, black, bronze sphere (4 cm diameter) mounted on a thin insulated rod, and illuminated by two opposite optic fibers, with light focused on the sphere by a set of lenses. The sphere is encased in a large double-walled aluminum cylinder (34 cm diameter by 26 cm high) with separate water cooling jackets at the top, bottom, and sides. The cylinder can be filled with a gas of choice at a variety of pressures or can be run in vacuum. The exterior is cladded with insulation, and the temperature of the sphere, atmosphere and walls is monitored with thermocouples. The temperature and waterflow of the three cooling jackets can be monitored to establish the energy output of the whole system; the energy input is the energy yield of the two optic fibers. A small IR transmissive lens at the top provides the opportunity to hook up the fiber of a hyper spectrometer to monitor the emission spectrum of the black ‘earth’ sphere. A pressure gauge and gas inlet-outlet system for flushing of the cell completes it. The heat yield of the cooling water at the top is the sum of the radiative and convective components, whereas the bottom jacket only carries off the radiative heat of the sphere. Undergraduate E&ES students at Wesleyan University have run experiments with dry air, pure CO2, N2 and Ar at 1 atmosphere, and a low vacuum run was accomplished to calibrate the energy input. For each experiment, the lights are flipped on, the temperature acquisition routine is activated, and the sphere starts to warm up until an equilibrium temperature has been reached. The lights are then flipped off and the cooling sequence towards ambient is registered. The energy input is constant for a given

  5. Namibian Analogs To Titan Dunes (United States)

    Wall, Stephen D.; Lopes, R.; Kirk, R.; Stofan, E.; Farr, T.; Van der Ploeg, P.; Lorenz, R.; Radebaugh, J.


    Titan's equatorial dunes, observed in Cassini SAR, have been described as longitudinal, similar to longitudinal dunes in the Namib sand sea in southern Africa. Their "Y” junctions and the way they divert around topography are used as evidence of equatorial wind flow direction. In two instances of such diversion they exhibit overlying or crosshatched patterns in two distinct directions that have been interpreted as a transition to transverse dunes. Here we describe field observations of the Namibian dunes and these comparisons, we present images of the dunes from terrestrial SAR missions, and we discuss implications to both the Titan dunes and the wind regime that created them. Selected portions of the Namibian dunes resemble Titan's dunes in peak-to-peak distance and length. They are morphologically similar to Titan, and specific superficial analogs are common, but they also differ. For example, when Titan dunes encounter topography they either terminate abruptly, "climb” the upslope, or divert around; only the latter behavior is seen in remote sensing images of Namibia. Namib linear dunes do transition to transverse as they divert, but at considerably smaller wavelength, while at Titan the wavelengths are of the same scale. Crosshatching of similar-wavelength dunes does occur in Namibia, but not near obstacles. Many additional aeolian features that are seen at Namibia such as star dunes, serpentine ridges and scours have not been detected on Titan, although they might be below the Cassini SAR's 300-m resolution. These similarities and differences allow us to explore mechanisms of Titan dune formation, in some cases giving us clues as to what larger scale evidence to look for in SAR images. Viewed at similar resolution, they provide interesting comparisons with the Titan dunes, both in likeness and differences. A part of this work was carried out at JPL under contract with NASA.


    Directory of Open Access Journals (Sweden)

    Bayu Kanetro


    Full Text Available The aims of this research were to determine the best of local legume sprout as raw material of meat analog, based on its texture, sensory (preference properties, and the ratio of arginine/lysine, compared to meat analog from soybean. Meat analogs were made of protein of local legumes sprout, which were velvet beans, cowpeas, and winged beans that had been germinated for 48, 36 and 24 hr respectively. The protein of velvet beans, cowpeas, and winged beans sprout for meat analog production were extracted at pH 9 and precipitated at pH 4, 5, and 5 respectively. Hence their products were analyzed the texture, the sensory properties (the hedonic scales of color, texture, odor, taste, and overall, and the ratio of arginine/lysine. The characteristics of meat analog from the legumes sprout were compared to meat analog from soybean for determination of the best legume sprout as raw material of meat analog. The result of this research showed the properties of meat analog from winged bean and cowpeas sprouts were better than velvet beans sprout. The meat analog from soybean was still better than meat analog from the local legumes sprout, especially its texture. The arginine content, that was known as  hypocholesterolemic and hypoglycemic component,  of meat analog from cowpeas sprout was lower than meat analog from soybean, but its ratio of arginie/lysine was not signifi cantly different. While the ratio of arginine/lysine of meat analog from the other legumes sprout were lower than meat analog from soybean. Therefore the meat analog from cowpeas sprout was chosen as the best product and was potential as functional food especially for reducing blood cholesterol. Keywords: Meat analog, sprout, local legumes, arginine/lysine ratio   ABSTRAK Tujuan penelitian ini adalah untuk menentukan jenis kecambah kacang-kacangan lokal terbaik sebagai bahan baku kedelai berdasarkan tekstur, sifat sensoris, dan rasio arginin/lisin dibandingkan meat analog dari biji

  7. A synthetic combinatorial strategy for developing a-conotoxin analogs as potent a7 nicotinic acetylcholine receptor antagonists

    DEFF Research Database (Denmark)

    Armishaw, Christopher J; Singh, Narender; Medina-Franco, Jose L;


    ) nAChR Fluo-4/Ca2+ assay, allowing amino acids that confer antagonistic activity for this receptor to be identified. A second series of individual alpha-conotoxin analogs based on the combinations of defined active amino acid residues from positional scan synthetic combinatorial library screening...... data were synthesized. Several analogs exhibited significantly improved antagonist activity for the alpha(7) nAChR compared with WT-ImI. Binding interactions between the analogs and the alpha(7) nAChR were explored using a homology model of the amino-terminal domain based on a crystal structure...... of an acetylcholine-binding protein. Finally, a third series of refined analogs was synthesized based on modeling studies, which led to several analogs with refined pharmacological properties. Of the 96 individual alpha-conotoxin analogs synthesized, three displayed > or =10-fold increases in antagonist potency...

  8. Analogies: Explanatory Tools in Web-Based Science Instruction (United States)

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


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

  9. Advances in Analog Circuit Design 2015

    CERN Document Server

    Baschirotto, Andrea; Harpe, Pieter


    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.

  10. A computational model of analogical reasoning

    Institute of Scientific and Technical Information of China (English)

    李波; 赵沁平


    A computational model of analogical reasoning is presented, which divides analogical reasoning process into four subprocesses, i.e. reminding, elaboration, matching and transfer. For each subprocess, its role and the principles it follows are given. The model is discussed in detail, including salient feature-based reminding, relevance-directed elaboration, an improved matching model and a transfer model. And the advantages of this model are summarized based on the results of BHARS, which is an analogical reasoning system implemented by this model.

  11. Analogies in science education: contributions and challenges

    Directory of Open Access Journals (Sweden)

    Maria da Conceição Duarte


    Full Text Available An analogy is a comparison between domains of knowledge that have similarities at the levels of characteristics and relationships. Several authors highlight the importance of this tool in the teaching and learning of difficult scientific concepts. Nevertheless, some problems associated to the use of analogies have been found. This paper aims at contributing to a better understanding of the use of analogies in science education, by means of a review of the state of art regarding this matter. It will take into account its contribution to science education as well as the challenges to further research

  12. Analog to Digital Conversion in Physical Measurements

    CERN Document Server

    Kapitaniak, T; Feudel, U; Grebogi, C


    There exist measuring devices where an analog input is converted into a digital output. Such converters can have a nonlinear internal dynamics. We show how measurements with such converting devices can be understood using concepts from symbolic dynamics. Our approach is based on a nonlinear one-to-one mapping between the analog input and the digital output of the device. We analyze the Bernoulli shift and the tent map which are realized in specific analog/digital converters. Furthermore, we discuss the sources of errors that are inevitable in physical realizations of such systems and suggest methods for error reduction.


    Directory of Open Access Journals (Sweden)

    Md. Abdul Hye Khan


    Full Text Available Epoxyeicosatrienoic acids (EETs contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end-organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II-induced hypertension. EET-B was administered in drinking water for 14 days (10mg/kg/d and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

  14. The molecular mechanism of thalidomide analogs in hematologic malignancies. (United States)

    Lindner, Stefanie; Krönke, Jan


    Thalidomide was sold in the 1950s as a sedative and was also used by pregnant women to treat morning sickness. It became notorious for causing severe birth defects and was removed from the market. More than four decades later, thalidomide had a renaissance in the treatment of cancer. Thalidomide and its more potent analogs, lenalidomide and pomalidomide, are nowadays approved treatments for multiple myeloma and myelodysplastic syndrome with deletion of chromosome 5q. In addition, thalidomide and its analogs inhibit release of tumor necrosis factor-α and increase interleukin-2 (IL-2) and interferon-γ release from T cells. The underlying molecular mechanisms for these pleiotropic effects remained obscure until the identification of the cereblon (CRBN) E3 ubiquitin ligase as the primary target of thalidomide and its analogs in 2010. Binding of thalidomide or lenalidomide increases the affinity of CRBN to the transcription factors IKZF1 and IKZF3 and casein kinase 1α (CK1α). Ubiquitination and degradation of these neo-substrates results in IL-2 release and growth arrest of multiple myeloma and MDS cells. The discovery of this previously undescribed mechanism for an approved drug provides a proof-of-concept for the development of new therapeutics that exploit ubiquitin ligases for specific degradation of disease-associated proteins.

  15. Epoxyeicosatrienoic acid analog attenuates angiotensin II hypertension and kidney injury. (United States)

    Khan, Abdul Hye; Falck, John R; Manthati, Vijaya L; Campbell, William B; Imig, John D


    Epoxyeicosatrienoic acids (EETs) contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II)-induced hypertension. EET-B was administered in drinking water for 14 days (10 mg/kg/d) and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

  16. Use of analogy in learning scientific concepts. (United States)

    Donnelly, C M; McDaniel, M A


    Four experiments compared learning of scientific concepts as expressed in either traditional literal form or through an analogy. Comprehension of basic-level details and inferential implications was measured through multiple-choice testing. In Experiment 1, literal or analogical renditions were presented in textual form only. In Experiment 2, text was accompanied by a dynamic video. In Experiment 3, the video and text literal rendition was compared with a text-only analogical rendition. In Experiment 4, subjects read only about a familiar domain. Subjects consistently answered basic-level questions most accurately when concepts were expressed literally, but answered inferential questions most accurately when concepts were expressed analogically. Analysis of individual differences (Experiment 2) indicated that this interaction strongly characterized the conceptual learning of science novices. The results are discussed within the framework of schema induction.

  17. Identifying Solar Analogs in the Kepler Field (United States)

    Buzasi, Derek L.; Lezcano, Andrew; Preston, Heather L.


    Since human beings live on a planet orbiting a G2 V star, to us perhaps the most intrinsically interesting category of stars about which planets have been discovered is solar analogs. While Kepler has observed more than 26000 targets which have effective temperatures within 100K of the Sun, many of these are not true solar analogs due to activity, surface gravity, metallicity, or other considerations. Here we combine ground-based measurements of effective temperature and metallicity with data on rotational periods and surface gravities derived from 16 quarters of Kepler observations to produce a near-complete sample of solar analogs in the Kepler field. We then compare the statistical distribution of stellar physical parameters, including activity level, for subsets of solar analogs consisting of KOIs and those with no detected exoplanets. Finally, we produce a list of potential solar twins in the Kepler field.

  18. Synthesis and Biological Activity of Philanthotoxin Analogs

    Institute of Scientific and Technical Information of China (English)

    Yong An ZHANG; Ke Zhong LIU; Deng Yuan WANG; Yu Zhu WANG; Liang Jian QU; Chang Jin ZHU


    The synthesis of four analogs of philanthotoxin is described. The preliminary bioassay showed that these compounds all had good insecticidal activities, and the compound 6a had the best killing effect.

  19. Analogy betwen dislocation creep and relativistic cosmology


    J.A. Montemayor-Aldrete; J.D. Muñoz-Andrade; Mendoza-Allende, A.; Montemayor-Varela, A.


    A formal, physical analogy between plastic deformation, mainly dislocation creep, and Relativistic Cosmology is presented. The physical analogy between eight expressions for dislocation creep and Relativistic Cosmology have been obtained. By comparing the mathematical expressions and by using a physical analysis, two new equations have been obtained for dislocation creep. Also, four new expressions have been obtained for Relativistic Cosmology. From these four new equations, one may determine...

  20. The analogy between stereo depth and brightness. (United States)

    Brookes, A; Stevens, K A


    Apparent depth in stereograms exhibits various simultaneous-contrast and induction effects analogous to those reported in the luminance domain. This behavior suggests that stereo depth, like brightness, is reconstructed, ie recovered from higher-order spatial derivatives or differences of the original signal. The extent to which depth is analogous to brightness is examined. There are similarities in terms of contrast effects but dissimilarities in terms of the lateral inhibition effects traditionally attributed to underlying spatial-differentiation operators.

  1. AMiBA Wideband Analog Correlator

    CERN Document Server

    Li, Chao-Te; Wilson, Warwick; Lin, Kai-Yang; Chen, Ming-Tang; Ho, P T P; Chen, Chung-Cheng; Han, Chih-Chiang; Oshiro, Peter; Martin-Cocher, Pierre; Chang, Chia-Hao; Chang, Shu-Hao; Altamirano, Pablo; Jiang, Homin; Chiueh, Tzi-Dar; Lien, Chun-Hsien; Wang, Huei; Wei, Ray-Ming; Yang, Chia-Hsiang; Peterson, Jeffrey B; Chang, Su-Wei; Huang, Yau-De; Hwang, Yuh-Jing; Kesteven, Michael; Koch, Patrick; Liu, Guo-Chin; Nishioka, Hiroaki; Umetsu, Keiichi; Wei, Tashun; Wu, Jiun-Huei Proty


    A wideband analog correlator has been constructed for the Yuan-Tseh Lee Array for Microwave Background Anisotropy. Lag correlators using analog multipliers provide large bandwidth and moderate frequency resolution. Broadband IF distribution, backend signal processing and control are described. Operating conditions for optimum sensitivity and linearity are discussed. From observations, a large effective bandwidth of around 10 GHz has been shown to provide sufficient sensitivity for detecting cosmic microwave background variations.

  2. Analog baseband circuits for sensor systems



    This thesis is composed of six publications and an overview of the research topic, which also summarizes the work. The research presented in this thesis focuses on research into analog baseband circuits for sensor systems. The research is divided into three different topics: the integration of analog baseband circuits into a radio receiver for sensor applications; the integration of an ΔΣ modulator A/D converter into a GSM/WCDMA radio receiver for mobile phones, and the integration of algorit...

  3. Automated Integrated Analog Filter Design Issues



    An analysis of modern automated integrated analog circuits design methods and their use in integrated filter design is done. Current modern analog circuits automated tools are based on optimization algorithms and/or new circuit generation methods. Most automated integrated filter design methods are only suited to gmC and switched current filter topologies. Here, an algorithm for an active RC integrated filter design is proposed, that can be used in automated filter designs. The algorithm is t...

  4. Synthetic heparin-binding growth factor analogs (United States)

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


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

  5. Learning Domain Theories via Analogical Transfer (United States)


    Shive & Weber 1982). In the linear kinematics section of the textbook used for this study ( Giancoli 1991), there are eight worked out analogous to the dynamics of linear motion” (p. 197, Giancoli 1991). This is common practice in textbooks, and analogies between domains form the...and Worked Solution All problems and worked solutions used in this work were taken from the same physics textbook ( Giancoli 1991). Problems are

  6. Analogical Learning and Automated Rule Constructions

    Institute of Scientific and Technical Information of China (English)



    This paper describes some experiments of analogical learning and automated rule construction.The present investigation focuses on knowledge acquisition,learning by analyogy,and knowledge retention.The developed system initially learns from scratch,gradually acquires knowledge from its environment through trial-and-error interaction,incrementally augments its knowledge base,and analogically solves new tasks in a more efficient and direct manner.

  7. Development of analogical problem-solving skill. (United States)

    Holyoak, K J; Junn, E N; Billman, D O


    3 experiments were performed to assess children's ability to solve a problem by analogy to a superficially dissimilar situation. Preschoolers and fifth and sixth graders were asked to solve a problem that allowed multiple solutions. Some subjects were first read a story that included an analogous problem and its solution. When the mapping between the relations involved in the corresponding solutions was relatively simple, and the corresponding instruments were perceptually and functionally similar, even preschoolers were able to use the analogy to derive a solution to the transfer problem (Experiment 1). Furthermore, salient similarity of the instruments was neither sufficient (Experiment 2) nor necessary (Experiment 3) for success by preschool subjects. When the story analog mapped well onto the transfer problem, 4-year-olds were often able to generate a solution that required transformation of an object with little perceptual or semantic similarity to the instrument used in the base analog (Experiment 3). The older children used analogies in a manner qualitatively similar to that observed in comparable studies with adults (Experiment 1), whereas the younger children exhibited different limitations.

  8. Analog modelling of obduction processes (United States)

    Agard, P.; Zuo, X.; Funiciello, F.; Bellahsen, N.; Faccenna, C.; Savva, D.


    Obduction corresponds to one of plate tectonics oddities, whereby dense, oceanic rocks (ophiolites) are presumably 'thrust' on top of light, continental ones, as for the short-lived, almost synchronous Peri-Arabic obduction (which took place along thousands of km from Turkey to Oman in c. 5-10 Ma). Analog modelling experiments were performed to study the mechanisms of obduction initiation and test various triggering hypotheses (i.e., plate acceleration, slab hitting the 660 km discontinuity, ridge subduction; Agard et al., 2007). The experimental setup comprises (1) an upper mantle, modelled as a low-viscosity transparent Newtonian glucose syrup filling a rigid Plexiglas tank and (2) high-viscosity silicone plates (Rhodrosil Gomme with PDMS iron fillers to reproduce densities of continental or oceanic plates), located at the centre of the tank above the syrup to simulate the subducting and the overriding plates - and avoid friction on the sides of the tank. Convergence is simulated by pushing on a piston at one end of the model with velocities comparable to those of plate tectonics (i.e., in the range 1-10 cm/yr). The reference set-up includes, from one end to the other (~60 cm): (i) the piston, (ii) a continental margin containing a transition zone to the adjacent oceanic plate, (iii) a weakness zone with variable resistance and dip (W), (iv) an oceanic plate - with or without a spreading ridge, (v) a subduction zone (S) dipping away from the piston and (vi) an upper, active continental margin, below which the oceanic plate is being subducted at the start of the experiment (as is known to have been the case in Oman). Several configurations were tested and over thirty different parametric tests were performed. Special emphasis was placed on comparing different types of weakness zone (W) and the extent of mechanical coupling across them, particularly when plates were accelerated. Displacements, together with along-strike and across-strike internal deformation in all

  9. A novel effect of thalidomide and its analogs: suppression of cereblon ubiquitination enhances ubiquitin ligase function. (United States)

    Liu, Yaobin; Huang, Xiangao; He, Xian; Zhou, Yanqing; Jiang, Xiaogang; Chen-Kiang, Selina; Jaffrey, Samie R; Xu, Guoqiang


    The immunomodulatory drug (IMiD) thalidomide and its structural analogs lenalidomide and pomalidomide are highly effective in treating clinical indications. Thalidomide binds to cereblon (CRBN), a substrate receptor of the cullin-4 really interesting new gene (RING) E3 ligase complex. Here, we examine the effect of thalidomide and its analogs on CRBN ubiquitination and its functions in human cell lines. We find that the ubiquitin modification of CRBN includes K48-linked polyubiquitin chains and that thalidomide blocks the formation of CRBN-ubiquitin conjugates. Furthermore, we show that ubiquitinated CRBN is targeted for proteasomal degradation. Treatment of human myeloma cell lines such as MM1.S, OPM2, and U266 with thalidomide (100 μM) and its structural analog lenalidomide (10 μM) results in stabilization of CRBN and elevation of CRBN protein levels. This in turn leads to the reduced level of CRBN target proteins and enhances the sensitivity of human multiple myeloma cells to IMiDs. Our results reveal a novel mechanism by which thalidomide and its analogs modulate the CRBN function in cells. Through inhibition of CRBN ubiquitination, thalidomide and its analogs allow CRBN to accumulate, leading to the increased cullin-4 RING E3 ligase-mediated degradation of target proteins.

  10. Anti-Plasmodium activity of ceramide analogs

    Directory of Open Access Journals (Sweden)

    Gatt Shimon


    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


    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. Analog forecasting with dynamics-adapted kernels (United States)

    Zhao, Zhizhen; Giannakis, Dimitrios


    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.

  13. Analogy, higher order thinking, and education. (United States)

    Richland, Lindsey Engle; Simms, Nina


    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.

  14. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    Directory of Open Access Journals (Sweden)

    Troco K. Mihali


    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.

  15. Magnetic activity of seismic solar analogs

    CERN Document Server

    Salabert, D


    We present our latest results on the solar-stellar connection by studying 18 solar analogs that we identified among the Kepler seismic sample (Salabert et al., 2016a). We measured their magnetic activity properties using observations collected by the Kepler satellite and the ground-based, high-resolution Hermes spectrograph. The photospheric (Sph) and chromospheric (S) magnetic activity proxies of these seismic solar analogs are compared in relation to solar activity. We show that the activity of the Sun is actually comparable to the activity of the seismic solar analogs. Furthermore, we report on the discovery of temporal variability in the acoustic frequencies of the young (1 Gyr-old) solar analog KIC10644253 with a modulation of about 1.5 years, which agrees with the derived photospheric activity (Salabert et al., 2016b). It could actually be the signature of the short-period modulation, or quasi-biennal oscillation, of its magnetic activity as observed in the Sun and the 1-Gyr-old solar analog HD30495. In...

  16. NaturAnalogs for the Unsaturated Zone

    Energy Technology Data Exchange (ETDEWEB)

    A. Simmons; A. Unger; M. Murrell


    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.

  17. Not All Analogies Are Created Equal: Associative and Categorical Analogy Processing following Brain Damage (United States)

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


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

  18. Analogy-Enhanced Instruction: Effects on Reasoning Skills in Science (United States)

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


    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…

  19. Value and Limitations of Analogs in Teaching Mathematics. (United States)

    Halford, Graeme S.; Boulton-Lewis, Gillian M.

    Analogical reasoning is frequently used in acquisition of mathematical concepts. Concrete representations used to teach mathematics are essentially analogs of mathematical concepts, and it is argued that analogies enter into mathematical concept acquisition in numerous other ways as well. According to Gentner's theory, analogies entail a…

  20. Analog Forecasting with Dynamics-Adapted Kernels

    CERN Document Server

    Zhao, Zhizhen


    Analog forecasting is a non-parametric 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 state-space reconstruction for dynamical systems and kernel methods developed in harmonic analysis and machine learning. The first improvement is to augment the dimension of the initial data using Takens' delay-coordinate maps to recover information in the initial data lost through partial observations. Then, instead of using Euclidean distances between the states, weighted ensembles of analogs are constructed according to similarity kernels in delay-coordinate space, featuring an explicit dependence on the dynamical vector field generating the data. The eigenvalues and eigenfunctions ...

  1. On Lovelock analogs of the Riemann tensor

    Energy Technology Data Exchange (ETDEWEB)

    Camanho, Xian O. [Albert-Einstein-Institut, Max-Planck-Institut fuer Gravitationsphysik, Golm (Germany); Dadhich, Naresh [Jamia Millia Islamia, Centre for Theoretical Physics, New Delhi (India); Inter-University Centre for Astronomy and Astrophysics, Pune (India)


    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. (orig.)

  2. Formal analogies in physics teacher education

    DEFF Research Database (Denmark)

    Avelar Sotomaior Karam, Ricardo; Ricardo, Elio


    the relevance of the subject, formal analogies are rarely systematically approached in physics education. In order to discuss this issue with pre-service physics teachers, we planned a lecture and designed a questionnaire with the goal of encouraging them to think about some “coincidences” in well known......Reasoning by similarities, especially the ones associated with formal aspects, is one of the most valuable sources for the development of physical theories. The essential role of formal analogies in science can be highlighted by the fact that several equations for different physical situations have...... 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...

  3. Analog Module Placement Design Using Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)


    This paper presents a novel genetic algorithm for analog module placement based on ageneralization of the two-dimensional bin packing problem. The genetic encoding and operators assure that allproblem constraints are always satisfied. Thus the potential problems of adding penalty terms to the costfunction are eliminated so that the search configuration space is drastically decreased. The dedicated costfunction is based on the special requirements of analog integrated circuits. A fractional factorial experimentwas conducted using an orthogonal array to study the algorithm parameters. A meta GA was applied todetermine the optimal parameter values. The algorithm was tested with several local benchmark circuits. Theexperimental results show that the algorithm has better performance than the simulated annealing approachwith satisfactory results comparable to manual placement. This study demonstrates the effectiveness of thegenetic algorithm in the analog module placement problem. The algorithm has been successfully used in alayout synthesis tool.

  4. Electronic devices for analog signal processing

    CERN Document Server

    Rybin, Yu K


    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...

  5. Landauer Bound for Analog Computing Systems

    CERN Document Server

    Diamantini, M Cristina; Trugenberger, Carlo A


    By establishing a relation between information erasure and continuous phase transitions we generalise the Landauer bound to analog computing systems. The entropy production per degree of freedom during erasure of an analog variable (reset to standard value) is given by the logarithm of the configurational volume measured in units of its minimal quantum. As a consequence every computation has to be carried on with a finite number of bits and infinite precision is forbidden by the fundamental laws of physics, since it would require an infinite amount of energy.

  6. Words, Concepts, and the Geometry of Analogy

    Directory of Open Access Journals (Sweden)

    Stephen McGregor


    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.

  7. Landauer bound for analog computing systems (United States)

    Diamantini, M. Cristina; Gammaitoni, Luca; Trugenberger, Carlo A.


    By establishing a relation between information erasure and continuous phase transitions we generalize the Landauer bound to analog computing systems. The entropy production per degree of freedom during erasure of an analog variable (reset to standard value) is given by the logarithm of the configurational volume measured in units of its minimal quantum. As a consequence, every computation has to be carried on with a finite number of bits and infinite precision is forbidden by the fundamental laws of physics, since it would require an infinite amount of energy.

  8. Fungitoxicity of chemical analogs with heartwood toxins. (United States)

    Grohs, B M; Kunz, B


    Trans-stilbene and tropolone as chemical analogs with naturally occurring fungitoxic heartwood compounds were studied with respect to their fungitoxic potency. While stilbene showed no fungitoxic activity towards the fungi Aureobasidium pullulans var. melanogenum, Penicillium glabrum, and Trichoderma harzianum in the concentrations tested, the minimal inhibiting concentration of tropolone was 10(-3) M for Penicillium glabrum and Trichoderma harzianum, and 10(-5) M for Aureobasidium pullulans var. melanogenum. In all cases, the effect of tropolone was a fungistatic one. Using chemical analogs for assessing the chemical basis of the fungitoxicity of tropolone, this substance proved to be the only compound tested which possesses fungitoxic properties.

  9. Automated Integrated Analog Filter Design Issues

    Directory of Open Access Journals (Sweden)

    Karolis Kiela


    Full Text Available An analysis of modern automated integrated analog circuits design methods and their use in integrated filter design is done. Current modern analog circuits automated tools are based on optimization algorithms and/or new circuit generation methods. Most automated integrated filter design methods are only suited to gmC and switched current filter topologies. Here, an algorithm for an active RC integrated filter design is proposed, that can be used in automated filter designs. The algorithm is tested by designing an integrated active RC filter in a 65 nm CMOS technology.

  10. Synthetic heparin-binding factor analogs (United States)

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


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

  11. Analysis of Recurrent Analog Neural Networks

    Directory of Open Access Journals (Sweden)

    Z. Raida


    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.

  12. Discrete analog computing with rotor-routers. (United States)

    Propp, James


    Rotor-routing is a procedure for routing tokens through a network that can implement certain kinds of computation. These computations are inherently asynchronous (the order in which tokens are routed makes no difference) and distributed (information is spread throughout the system). It is also possible to efficiently check that a computation has been carried out correctly in less time than the computation itself required, provided one has a certificate that can itself be computed by the rotor-router network. Rotor-router networks can be viewed as both discrete analogs of continuous linear systems and deterministic analogs of stochastic processes.

  13. Analog circuit design for communication SOC

    CERN Document Server

    Tu, Steve Hung-Lung


    This e-book provides several state-of-the-art analog circuit design techniques. It presents both empirical and theoretical materials for system-on-a-chip (SOC) circuit design. Fundamental communication concepts are used to explain a variety of topics including data conversion (ADC, DAC, S-? oversampling data converters), clock data recovery, phase-locked loops for system timing synthesis, supply voltage regulation, power amplifier design, and mixer design. This is an excellent reference book for both circuit designers and researchers who are interested in the field of design of analog communic

  14. Implementing neural architectures using analog VLSI circuits (United States)

    Maher, Mary Ann C.; Deweerth, Stephen P.; Mahowald, Misha A.; Mead, Carver A.


    Analog very large-scale integrated (VLSI) technology can be used not only to study and simulate biological systems, but also to emulate them in designing artificial sensory systems. A methodology for building these systems in CMOS VLSI technology has been developed using analog micropower circuit elements that can be hierarchically combined. Using this methodology, experimental VLSI chips of visual and motor subsystems have been designed and fabricated. These chips exhibit behavior similar to that of biological systems, and perform computations useful for artificial sensory systems.

  15. Analogies between a Meniscus and a Cantilever

    Institute of Scientific and Technical Information of China (English)

    LIU Jian-Lin


    Systematic and quantitative analyses of exact analogies between a meniscus and an elastica are performed. It is shown that the two governing equations take the same style after coordinate translation and scale transformation. The morphologies of the liquid bridge and the cantilever are calculated in terms of elliptic integrations, which can be reduced to the same shape,after converting the boundary conditions. The present analyses can make us grasp the nature of this physical phenomenon deeply and show some inspiration for designing the analogy experiments. Moreover, the calculated results are helpful to engineering applications, such as design and fabrication of MEMS, and micro-manipulations in micro/nano- technology.


    Directory of Open Access Journals (Sweden)

    E. Tlelo-Cuautle


    Full Text Available A new symbollc-method is introduced to enhance the calculation of symbolic expressions of analog circults. First, the analog circuit is transformed to a nullor equivalent circuit. Second, a new method is introduced to the formulation of a compact system of equations (CSES. Third, a new method is introduced to the solution of theCSES, by avoiding multiplications by zero to Improve the evaluation of determlnants. Flnally, two eXamples are given to show the usefulness of the proposed methods to calculate fully symbolic transfer functions.

  17. An Optical Analog of a Black Holes

    CERN Document Server

    Royston, A; Royston, Andrew; Gass, Richard


    Using media with extremely low group velocities one can create an optical analog of a curved space-time. Leonhardt and Piwnicki have proposed that a vortex flow will act as an optical black hole. We show that although the Leonhardt - Piwnicki flow has an orbit of no return and an infinite red-shift surface, it is not a true black hole since it lacks a null hypersurface. However a radial flow will produce a true optical black hole that has a Hawking temperature and obeys the first law of black hole mechanics. By combining the Leonhardt - Piwnicki flow with a radial flow we obtain the analog of the Kerr black hole.

  18. HAPS, a Handy Analog Programming System

    DEFF Research Database (Denmark)

    Højberg, Kristian Søe


    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 minimum values for the variables. The output file includes potentiometer coefficients and static-test 'measuring values.' The file format is fitted to an automatic potentiometer-setting and static-test program. Patch instructions are printed by HAPS. The article describes the principles of HAPS...

  19. Associative Pattern Recognition In Analog VLSI Circuits (United States)

    Tawel, Raoul


    Winner-take-all circuit selects best-match stored pattern. Prototype cascadable very-large-scale integrated (VLSI) circuit chips built and tested to demonstrate concept of electronic associative pattern recognition. Based on low-power, sub-threshold analog complementary oxide/semiconductor (CMOS) VLSI circuitry, each chip can store 128 sets (vectors) of 16 analog values (vector components), vectors representing known patterns as diverse as spectra, histograms, graphs, or brightnesses of pixels in images. Chips exploit parallel nature of vector quantization architecture to implement highly parallel processing in relatively simple computational cells. Through collective action, cells classify input pattern in fraction of microsecond while consuming power of few microwatts.

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

    NARCIS (Netherlands)

    van de Plassche, R.J.


    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 filte

  1. Conformational analysis of Infectious bursal disease virus (IBDV derived cell penetrating peptide (CPP analogs

    Directory of Open Access Journals (Sweden)

    Vinay G. Joshi


    Full Text Available Aim: This study was designed to develop peptide analogs of Infectious Bursal Disease (IBD virus VP5 protein segment having cell penetrating ability to improve their interaction with cargo molecule (Nucleic acid without affecting the backbone conformation. Materials and Methods: IBDV VP5 protein segment designated as RATH peptide were synthesized using solid phase peptide synthesis and their solution conformation was elucidated using CD spectroscopy in polar (water and apolar (TFE solvents. Cell penetrating ability of RATH-CONH2 was observed using FITC labeled peptide internalization in to HeLa cells under fluorescent microscopy. The efficacy of RATH analog interactions with nucleic acids was evaluated using FITC labeled oligonucleotides by fluorescence spectroscopy and plasmid constructs in gel retardation assay. Results: CD spectra of RATH analogs in water and apolar trifluroethanol (TFE helped to compare their secondary structures which were almost similar with dominant beta conformations suggesting successful induction of positive charge in the analogs without affecting back bone conformation of CPP designed. Cell penetrating ability of RATH CONH2 in HeLa cell was more than 90%. The fluorescence spectroscopy and plasmid constructs in gel retardation assay demonstrated successful interaction of amide analogs with nucleic acid. Conclusion: Intentional changes made in IBDV derived peptide RATH COOH to RATH CONH2 did not showed major changes in backbone conformation and such modifications may help to improve the cationic charge in most CPPs to interact with nucleic acid. [Vet World 2013; 6(6.000: 307-312

  2. Analogies and Reconstruction of Mathematical Knowledge. (United States)

    Fast, Gerald R.

    An investigation was conducted to determine the effectiveness of utilizing analogies to effect conceptual change in mathematics. Forty-one high school seniors participated in a knowledge reconstruction process regarding their beliefs about everyday probability situations such as sports events or lotteries. These mathematics students were given…

  3. Analogy and mathematical reasoning : a survey


    Miller, C. D. F.


    We survey the literature of Artificial Intelligence, and other related work, pertaining to the modelling of mathematical reasoning and its relationship with the use of analogy. In particular, we discuss the contribution of Lenat's program AM to models of mathematical discovery and concept-formation. We consider the use of similarity measures to structure a knowledge space and their role in concept acquisition.

  4. Analog circuit design designing waveform processing circuits

    CERN Document Server

    Feucht, Dennis


    The fourth volume in the set Designing Waveform-Processing Circuits builds on the previous 3 volumes and presents a variety of analog non-amplifier circuits, including voltage references, current sources, filters, hysteresis switches and oscilloscope trigger and sweep circuitry, function generation, absolute-value circuits, and peak detectors.

  5. An iconic, analogical approach to grammaticalization

    NARCIS (Netherlands)

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


    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, w

  6. Generating Analog IC Layouts with LAYGEN II

    CERN Document Server

    Martins, Ricardo M F; Horta, Nuno C G


    This book presents an innovative methodology for the automatic generation of analog integrated circuits (ICs) layout, based on template descriptions and on evolutionary computational techniques. A design automation tool, LAYGEN II, was implemented to validate the proposed approach giving special emphasis to reusability of expert design knowledge and to efficiency on retargeting operations.

  7. CMOS circuits for analog signal processing

    NARCIS (Netherlands)

    Wallinga, Hans


    Design choices in CMOS analog signal processing circuits are presented. Special attention is focussed on continuous-time filter technologies. The basics of MOSFET-C continuous-time filters and CMOS Square Law Circuits are explained at the hand of a graphical MOST characteristics representation.

  8. Analog Acoustic Expression in Speech Communication (United States)

    Shintel, Hadas; Nusbaum, Howard C.; Okrent, Arika


    We present the first experimental evidence of a phenomenon in speech communication we call "analog acoustic expression." Speech is generally thought of as conveying information in two distinct ways: discrete linguistic-symbolic units such as words and sentences represent linguistic meaning, and continuous prosodic forms convey information about…

  9. Invention through Form and Function Analogy (United States)

    Rule, Audrey C.


    "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…


    DEFF Research Database (Denmark)

    Gaunholt, Hans


    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...

  11. The GMO-Nanotech (Dis)Analogy? (United States)

    Sandler, Ronald; Kay, W. D.


    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…

  12. Analog of Superradiance effect in BEC

    CERN Document Server

    Basak, S


    We investigate the scattering of phase oscillation of Bose-Einstein Condensate by a 'draining of bathtub' type fluid motion. We derive a relation between the reflection and transmission coefficients which exhibits existence of analog of 'Superradiance effect' in BEC vortex with sink.

  13. Classical Analog of Electromagnetically Induced Transparency

    CERN Document Server

    Alzar, C L G; Nussenzveig, P


    We present a classical analog for Electromagnetically Induced Transparency (EIT). In a system of just two coupled harmonic oscillators subject to a harmonic driving force we can reproduce the phenomenology observed in EIT. We describe a simple experiment performed with two linearly coupled RLC circuits which can be taught in an undergraduate laboratory class.

  14. Analogy between thermal convective and magnetohydrodynamic instabilities

    Energy Technology Data Exchange (ETDEWEB)

    Valdmanis, Ya.Ya.; Kukainis, O.A.


    An examination is made of the analogy between thermo-convective instability and instability produced by various electromagnetic forces both in steady and alternating thermal and electromagnetic fields. An example is given for calculating an assumed bubble instability which could occur in an alternating magnetic field. 17 references.

  15. Three optimized and validated (using accuracy profiles) LC methods for the determination of pentamidine and new analogs in rat plasma. (United States)

    Hambÿe, S; Stanicki, D; Colet, J-M; Aliouat, E M; Vanden Eynde, J J; Blankert, B


    Three novel LC-UV methods for the determination of pentamidine (PTMD) and two of its new analogs in rat plasma are described. The chromatographic conditions (wavelength, acetonitrile percentage in the mobile phase, internal standard) were optimized to have an efficient selectivity. A pre-step of extraction was simultaneously developed for each compound. For PTMD, a solid phase extraction (SPE) with Oasis(®) HLB cartridges was selected, while for the analogs we used protein precipitation with acetonitrile. SPE for PTMD gave excellent results in terms of extraction yield (99.7 ± 2.8) whereas the recoveries for the analogs were not so high but were reproducible as well (64.6 ± 2.6 and 36.8 ± 1.6 for analog 1 and 2, respectively). By means of a recent strategy based on accuracy profiles (β-expectation tolerance interval), the methods were successfully validated. β was fixed at 95% and the acceptability limits at ± 15% as recommended by the FDA. The method was successfully validated for PTMD (29.6-586.54 ng/mL), analog 1 (74.23-742.3 ng/mL) and analog 2 (178.12-890.6 ng/mL). The first concentration level tested was considered as the LLOQ (lower limit of quantification) for PTMD and analog 1 whereas for analog 2, the LLOQ was not the first level tested and was raised to 178.12 ng/mL.

  16. Antiproliferative Activity and in Vivo Toxicity of Double-Point Modified Analogs of 1,25-Dihydroxyergocalciferol. (United States)

    Trynda, Justyna; Turlej, Eliza; Milczarek, Magdalena; Pietraszek, Anita; Chodyński, Michał; Kutner, Andrzej; Wietrzyk, Joanna


    Analogs of 1,25-dihydroxyergocalciferol, modified in the side-chain and in the A-ring, were tested for their antiproliferative activity against a series of human cancer cell lines in vitro and in vivo toxicity. The proliferation inhibition caused by the analogs was higher than that of the parent compounds, while the toxicity, measured as the serum calcium level, was lower. All analogs were able to induce, in HL-60 and MV4-11 leukemic cells, G₀/G₁ cell cycle arrest and differentiation expressed as morphological signs typical for monocytes. The analogs also induced the expression of CD11b and/or CD14 cell-differentiation markers. The most potent analogs, PRI-5105, PRI-5106, PRI-5201 and PRI-5202, were also able to induce vitamin D receptor (VDR) protein expression, mainly in the cytoplasmic fraction of HL-60 or MV4-11 cells. The most active analogs were the 19-nor ones with an extended and rigidified side-chain (PRI-5201 and PRI-5202), as in the former analogs PRI-1906 and PRI-1907. Epimerization at C-24 (PRI-5101) or introduction of an additional hydroxyl at C-23 (PRI-5104) reduced the toxicity of the analog with retained antiproliferative activity.

  17. Antiproliferative Activity and in Vivo Toxicity of Double-Point Modified Analogs of 1,25-Dihydroxyergocalciferol

    Directory of Open Access Journals (Sweden)

    Justyna Trynda


    Full Text Available Analogs of 1,25-dihydroxyergocalciferol, modified in the side-chain and in the A-ring, were tested for their antiproliferative activity against a series of human cancer cell lines in vitro and in vivo toxicity. The proliferation inhibition caused by the analogs was higher than that of the parent compounds, while the toxicity, measured as the serum calcium level, was lower. All analogs were able to induce, in HL-60 and MV4-11 leukemic cells, G0/G1 cell cycle arrest and differentiation expressed as morphological signs typical for monocytes. The analogs also induced the expression of CD11b and/or CD14 cell-differentiation markers. The most potent analogs, PRI-5105, PRI-5106, PRI-5201 and PRI-5202, were also able to induce vitamin D receptor (VDR protein expression, mainly in the cytoplasmic fraction of HL-60 or MV4-11 cells. The most active analogs were the 19-nor ones with an extended and rigidified side-chain (PRI-5201 and PRI-5202, as in the former analogs PRI-1906 and PRI-1907. Epimerization at C-24 (PRI-5101 or introduction of an additional hydroxyl at C-23 (PRI-5104 reduced the toxicity of the analog with retained antiproliferative activity.

  18. Structure-based design and synthesis of a bivalent iminobiotin analog showing strong affinity toward a low immunogenic streptavidin mutant. (United States)

    Kawato, Tatsuya; Mizohata, Eiichi; Shimizu, Yohei; Meshizuka, Tomohiro; Yamamoto, Tomohiro; Takasu, Noriaki; Matsuoka, Masahiro; Matsumura, Hiroyoshi; Kodama, Tatsuhiko; Kanai, Motomu; Doi, Hirofumi; Inoue, Tsuyoshi; Sugiyama, Akira


    The streptavidin/biotin interaction has been widely used as a useful tool in research fields. For application to a pre-targeting system, we previously developed a streptavidin mutant that binds to an iminobiotin analog while abolishing affinity for natural biocytin. Here, we design a bivalent iminobiotin analog that shows 1000-fold higher affinity than before, and determine its crystal structure complexed with the mutant protein.

  19. Playing with a double-edged sword: Analogies in biochemistry (United States)

    Orgill, Marykay

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

  20. RNA fragments mimicking tRNA analogs interact with cytochrome c. (United States)

    Pawlowska, Roza; Janicka, Magdalena; Jedrzejczyk, Dominika; Chworos, Arkadiusz


    In times, when drug seeking assays focus on the natural molecular triggers and their analogs, a deeper insight into molecular mechanisms governing the initial step of intrinsic apoptosis (cytochrome c release) is essential to suppress the immortality of pathologically changed cells. In this study, we examined RNA molecules mimicking mitochondrial tRNAs interacting with cytochrome c and possibly affecting its cellular function. tRNA analogs were designed and synthesized prior to the conformational analysis and gel assays clearly stating the nucleic acid-protein complex formation. The circular dichroism spectroscopic (CD) and microscale thermophoresis examination revealed the structural and conformational differences between four tRNA analogs in their interactions with cytochrome c. Obtained CD spectra and gel studies resulted in the complex ratio estimation and conclusion that not only the complex formation may be preferential towards specific tRNAs present in the cell, but nucleobase modifications are not essential for such interaction.

  1. Application of constrained aza-valine analogs for Smac mimicry. (United States)

    Chingle, Ramesh; Ratni, Sara; Claing, Audrey; Lubell, William D


    Constrained azapeptides were designed based on the Ala-Val-Pro-Ile sequence from the second mitochondria-derived activator of caspases (Smac) protein and tested for ability to induce apoptosis in cancer cells. Diels-Alder cyclizations and Alder-ene reactions on azopeptides enabled construction of a set of constrained aza-valine dipeptide building blocks, that were introduced into mimics using effective coupling conditions to acylate bulky semicarbazide residues. Evaluation of azapeptides 7-11 in MCF-7 breast cancer cells indicated aza-cyclohexanylglycyine analog 11 induced cell death more efficiently than the parent tetrapeptide likely by a caspase-9 mediated apoptotic pathway. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 235-244, 2016.

  2. Analog Computation by DNA Strand Displacement Circuits. (United States)

    Song, Tianqi; Garg, Sudhanshu; Mokhtar, Reem; Bui, Hieu; Reif, John


    DNA circuits have been widely used to develop biological computing devices because of their high programmability and versatility. Here, we propose an architecture for the systematic construction of DNA circuits for analog computation based on DNA strand displacement. The elementary gates in our architecture include addition, subtraction, and multiplication gates. The input and output of these gates are analog, which means that they are directly represented by the concentrations of the input and output DNA strands, respectively, without requiring a threshold for converting to Boolean signals. We provide detailed domain designs and kinetic simulations of the gates to demonstrate their expected performance. On the basis of these gates, we describe how DNA circuits to compute polynomial functions of inputs can be built. Using Taylor Series and Newton Iteration methods, functions beyond the scope of polynomials can also be computed by DNA circuits built upon our architecture.

  3. Optimal neural computations require analog processors

    Energy Technology Data Exchange (ETDEWEB)

    Beiu, V.


    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).

  4. Parabolic flight as a spaceflight analog. (United States)

    Shelhamer, Mark


    Ground-based analog facilities have had wide use in mimicking some of the features of spaceflight in a more-controlled and less-expensive manner. One such analog is parabolic flight, in which an aircraft flies repeated parabolic trajectories that provide short-duration periods of free fall (0 g) alternating with high-g pullout or recovery phases. Parabolic flight is unique in being able to provide true 0 g in a ground-based facility. Accordingly, it lends itself well to the investigation of specific areas of human spaceflight that can benefit from this capability, which predominantly includes neurovestibular effects, but also others such as human factors, locomotion, and medical procedures. Applications to research in artificial gravity and to effects likely to occur in upcoming commercial suborbital flights are also possible.

  5. A new program on digitizing analog seismograms (United States)

    Wang, Maofa; Jiang, Qigang; Liu, Qingjie; Huang, Meng


    Historical seismograms contain a great variety of useful information which can be used in the study of earthquakes. It is necessary for researchers to digitize analog records and extract the information just as modern computing analysis requires. Firstly, an algorithm based on color scene filed method is presented in order to digitize analog seismograms. Secondly, an interactive software program using C# has been developed to digitize seismogram traces from raster files quickly and accurately. The program can deal with gray-scale images stored in a suitable file format and it offers two different methods: manual digitization and automatic digitization. The test result of the program shows that the methods presented in this paper can lead to good performance.

  6. Synthesis and Evaluation of Desmethyl Azumamide Analogs

    DEFF Research Database (Denmark)

    Maolanon, Alex

    the azumamide analogs; however, removal of the methyl group had a significant impact relative to the natural products. To understand this effect, the NMR structure was solved with the assistance from Casper Hoeck and Charlotte H. Gotfredsen and docked conformations were obtained from Niels J. Christensen...... and Peter Fristrup. Compared to the natural compounds, the 3Dstructure of the scaffold in the azumamide analogs were similar. Although a conclusion was not found, the preliminary docking results indicated favorable lipophilic interaction with the methyl group in the azumamides. Largazole is another...... macrocylic natural product with HDAC inhibitory activity. The compound has a thioester functionality in the side chain, which is hydrolyzed before interaction with the enzymes. In the attempt to mimic the prodrug nature of largazole, compounds containing a thiol group were designed, as it was hypothesized...

  7. Analog fault diagnosis by inverse problem technique

    KAUST Repository

    Ahmed, Rania F.


    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.

  8. Interference Alignment with Analog Channel State Feedback

    CERN Document Server

    Ayach, Omar El


    Interference alignment (IA) is a multiplexing gain optimal transmission strategy for the interference channel with an arbitrary number of users. While the achieved sum rate with IA is much higher than previously thought possible, the improvement comes at the cost of requiring network channel state information at the transmitters. This can be achieved by explicit feedback, a flexible yet costly approach that incurs large overhead and limits throughput. We propose using analog feedback as an alternative to limited feedback or reciprocity based alignment. We show that the full multiplexing gain observed with perfect channel knowledge is preserved by analog feedback and the mean loss in sum rate is bounded by a constant when signal-to-noise ratio is comparable in both forward and feedback channels. When such feedback quality is not quite possible, a fraction of the degrees of freedom is achieved. We consider the overhead of training and feedback and use this framework to optimize the system's effective throughput...

  9. Quantum Electric Circuits Analogous to Ballistic Conductors



    The conductance steps in a constricted two-dimensional electron gas and the minimum conductivity in graphene are related to a new uncertainty relation between electric charge and conductance in a quantized electric circuit that mimics the electric transport in mesoscopic systems. This uncertainty relation makes specific use of the discreteness of electric charge. Quantum electric circuits analogous to both constricted two-dimensional electron gas and graphene are introduced. In the latter cas...

  10. An introduction to analog and digital communications

    CERN Document Server

    Haykin, Simon


    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.

  11. Analog of landau Levels to Electric Dipole

    CERN Document Server

    Ribeiro, L R; Nascimento, J R; Furtado, Claudio


    In this article we discuss the analogy between the dynamics of a neutral particle with an electric dipole, in the presence of configuration of magnetic field, with Landau level quantization for charged particle. We analyze this quantization based on the He-Mckelar-Wilkens interaction developed of similar way that Ericsson and Sj\\"oqvist[Phys Rev. A {\\bf 65} 013607 (2001)] was analyzed the Landau-Aharonov-Casher effect. The energy level and eingenfuctions and eigenvalues are obtained.

  12. Neurotoxic Alkaloids: Saxitoxin and Its Analogs


    Mihali, Troco K; Moffitt, Michelle C.; Neilan, Brett A.; Maria Wiese; D’Agostino, Paul M.


    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...

  13. Analog-digital codesign using coarse quantization (United States)

    Kokkeler, Andre Bernardus Joseph

    With regards to electronic systems, two important trends can be observed. The first trend is generally known as Moore's law: the digital processing capacity per chip is increasing a factor two every 18 months. Another part of the first trend is that the performance increase of integrated linear or analog processing is slow, a factor two every 4.7 years. The second trend is that the rate of data exchange between electronic systems is increasing rapidly. Because of these high data rates especially the design of data converters from analog to digital (ADCs) is demanding. For a specific set of applications, the requirements for the ADC can be relaxed by reducing the resolution of the conversion from analog to digital. Within these specific applications, signal characteristics rather than instantaneous values of the signal are determined. Reducing the resolution to an extreme extend is called 'coarse quantization'. The design of mixed signal systems is guided by a Y-chart design methodology. Analog-Digital Codesign, guided by the Y-chart approach, leads to mixed-signal systems with reduced costs compared to systems designed with the traditional methodology. The Y-chart approach also enables the use of coarse quantization as an additional design parameter to further reduce costs. This is illustrated by two case studies. The first case study concentrates on the design of a digital predistorter for Power Amplifiers (PAs) in telecommunication transmitters. In the second case study, we reconsider the design of a part of a Radio Telescope, used for Radio Astronomy. This part is called the Tied Array Adder and it sums signals from different telescopes. Both case studies show that coarse quantization can lead to mixed-signal systems with lower costs but system parameters will change. The explicit reconsideration of functional specifications, facilitated by the Y-chart approach, is therefore essential for the introduction of coarse quantization.





    Analogies can trigger breakthrough ideas in new product development. Numerous examples demonstrate that substantial innovations often result from transferring problem solutions from one industry or domain to another. For instance, the designers of the new running show generation of Nike, "Nike SHOX", use the same suspension concept like the technologies applied for formula 1 racing cars, or the biological Lotus-effect leading to the evelopment of various self-cleaning surfaces. Academic resea...

  15. How to use analogies for breakthrough innovations


    Schild, Katharina; Herstatt, Cornelius; Lüthje, Christian


    Analogies can trigger breakthrough ideas in new product development. Numerous examples demonstrate that substantial innovations often result from transferring problem solutions from one industry or domain to another. For instance, the designers of the new running shoe generation of Nike, “Nike SHOX”, use the same suspension concept like the technologies applied for Formula 1 racing cars, or the biological Lotus-effect led to the development of various self-cleaning surfaces. Academic resea...

  16. Transition State Analog Inhibitors for Esterases. (United States)


    Propanones." SCIENTIFIC PERSONNEL SUPPORTED BY THIS PROJECT AND DEGREES AWARDED DURING THIS REPORTING PERIOD Dr. Alan Dafforn Dr. Antoon Brouwer Dr. John P...294, Raven Press, New York. 11. Hansch, C. and Leo , A., (1979) "Substituent Constants for Correlation Analysis in Chemistry and Biology," pp. 69-70...BORONIC ACIDS AS 1INSITION STATE ANALOG INHIBITORS OF ACTYLCHOLINESTERASE by Alan Dafforn and Antoon C. Brouwer Department of Chemistry Bowling Green

  17. Survey of Evaluated Isobaric Analog States

    Energy Technology Data Exchange (ETDEWEB)

    MacCormick, M., E-mail: [Institut de Physique Nucléaire, CNRS/IN2P3, Université Paris-Sud, 91406 Orsay CEDEX (France); Audi, G. [Centre de Spectrométrie Nucléaire et de Spectrométrie de Masse, CNRS/IN2P3, Université Paris-Sud, Bât. 108, F-91405 Orsay Campus (France)


    Isobaric analog states (IAS) can be used to estimate the masses of members belonging to the same isospin multiplet. Experimental and estimated IAS have been used frequently within the Atomic Mass Evaluation (AME) in the past, but the associated set of evaluated masses have been published for the first time in AME2012 and NUBASE2012. In this paper the current trends of the isobaric multiplet mass equation (IMME) coefficients are shown. The T = 2 multiplet is used as a detailed illustration.

  18. Biomedical sensor design using analog compressed sensing (United States)

    Balouchestani, Mohammadreza; Krishnan, Sridhar


    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 %.

  19. Theory of analogous force on number sets (United States)

    Canessa, Enrique


    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 px 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 px to describe complex phenomena, the theory leads to derive a distinct analogous force fx on number sets proportional to (∂ px/∂ x) T at an analogous system temperature T. In particular, this leads 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.

  20. Using Analogs for Chemistry Problem Solving: Does It Increase Understanding? (United States)

    Friedel, Arthur W.; And Others


    Discussed is the effectiveness of using analogies in chemistry instruction. Students' mathematics anxiety, spatial visualization skill, and proportional reasoning ability were found to be important aptitudes for determining chemistry achievement. The relationship between analogs and algorithms is described. (KR)

  1. Creative Analogy Use in a Heterogeneous Design Team

    DEFF Research Database (Denmark)

    Christensen, Bo; Ball, Linden J.


    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...

  2. Vitamin D analogs differentially control antimicrobial peptide/"alarmin" expression in psoriasis.

    Directory of Open Access Journals (Sweden)

    Mark Peric

    Full Text Available Antimicrobial peptides (AMPs are strongly expressed in lesional skin in psoriasis and play an important role as proinflammatory "alarmins" in this chronic skin disease. Vitamin D analogs like calcipotriol have antipsoriatic effects and might mediate this effect by changing AMP expression. In this study, keratinocytes in lesional psoriatic plaques showed decreased expression of the AMPs beta-defensin (HBD 2 and HBD3 after topical treatment with calcipotriol. At the same time, calcipotriol normalized the proinflammatory cytokine milieu and decreased interleukin (IL-17A, IL-17F and IL-8 transcript abundance in lesional psoriatic skin. In contrast, cathelicidin antimicrobial peptide expression was increased by calcipotriol while psoriasin expression remained unchanged. In cultured human epidermal keratinocytes the effect of different vitamin D analogs on the expression of AMPs was further analyzed. All vitamin D analogs tested blocked IL-17A induced HBD2 expression by increasing IkappaB-alpha protein and inhibition of NF-kappaB signaling. At the same time vitamin D analogs induced cathelicidin through activation of the vitamin D receptor and MEK/ERK signaling. These studies suggest that vitamin D analogs differentially alter AMP expression in lesional psoriatic skin and cultured keratinocytes. Balancing AMP "alarmin" expression might be a novel goal in treatment of chronic inflammatory skin diseases.

  3. A Reasoning System using Inductive Inference of Analogical Union


    Miyahara, Tetsuhiro


    Analogical reasoning derives a new fact based on the analogous facts previously known. Inductive inference is a process of gaining a general rule from examples. We propose a new reasoning system using inductive inference and analogical reasoning. which is applicable to intellectual information processing and we characterize its power. Given an enumeration of paired examples. this system inductively infers a program representing the paring and constructs an analogical union. It reasons by anal...

  4. Functional DNA: Teaching Infinite Series through Genetic Analogy (United States)

    Kowalski, R. Travis


    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…

  5. The Role of Causal Models in Analogical Inference (United States)

    Lee, Hee Seung; Holyoak, Keith J.


    Computational models of analogy have assumed that the strength of an inductive inference about the target is based directly on similarity of the analogs and in particular on shared higher order relations. In contrast, work in philosophy of science suggests that analogical inference is also guided by causal models of the source and target. In 3…

  6. Analogy Use in Eighth-Grade Mathematics Classrooms (United States)

    Richland, Lindsey E.; Holyoak, Keith J.; Stigler, James W.


    Analogical reasoning has long been believed to play a central role in mathematics learning and problem solving (see Genter, Holyoak, & Kokinov, 2001); however, little is known about how analogy is used in everyday instructional contexts. This article examines analogies produced in naturally occurring U.S. mathematics lessons to explore…

  7. Analogical Instruction in Statistics: Implications for Social Work Educators (United States)

    Thomas, Leela


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

  8. Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs. (United States)

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


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

  9. Analogies in Medicine: Valuable for Learning, Reasoning, Remembering and Naming (United States)

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


    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…

  10. Investigating and Theorizing Discourse during Analogy Writing in Chemistry (United States)

    Bellocchi, Alberto; Ritchie, Stephen M.


    Explanations of the role of analogies in learning science at a cognitive level are made in terms of creating bridges between new information and students' prior knowledge. In this empirical study of learning with analogies in an 11th grade chemistry class, we explore an alternative explanation at the "social" level where analogy shapes…

  11. Mosquitocidal properties of natural product compounds isolated from Chinese herbs and synthetic analogs of curcumin. (United States)

    Anstrom, David M; Zhou, Xia; Kalk, Cody N; Song, Baoan; Lan, Que


    Because of resistance to current insecticides and to environmental, health, and regulatory concerns, naturally occurring compounds and their derivatives are of increasing interest for the development of new insecticidal compounds against vectors of disease-causing pathogens. Fifty-eight compounds, either extracted and purified from plants native to China or synthetic analogs of curcumin, were evaluated for both their larvicidal activity against Aedes aegypti (L.) and their ability to inhibit binding of cholesterol to Ae. aegypti sterol carrier protein-2 in vitro. Of the compounds tested, curcumin analogs seem especially promising in that of 24 compounds tested five were inhibitors of Ae. aegypti sterol carrier protein-2 with EC50 values ranging from 0.65 to 62.87 microM, and three curcumin analogs exhibited larvicidal activity against fourth instar Ae. aegypti larvae with LC50 values ranging from 17.29 to 27.90 microM. Adding to the attractiveness of synthetic curcumin analogs is the relative ease of synthesizing a large diversity of compounds; only a small fraction of such diversity has been sampled in this study.

  12. Inviting Argument by Analogy: Analogical-Mapping-Based Comparison Activities as a Scaffold for Small-Group Argumentation (United States)

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


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

  13. SSERVI Analog Regolith Simulant Testbed Facility (United States)

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


    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

  14. Integrated Analogic Filter Tuning System Design

    Directory of Open Access Journals (Sweden)

    Karolis Kiela


    Full Text Available Parameters of integrated analog filters can vary due to temperatu-re change, IC process variation and therefore they should have dedicated tuning circuits that compensate these imperfections. A method is proposed that speeds up switched resistor bank design while taking into account the required tuning range and step size. A novel counter structure is used in the tuning circuit that is ba-sed on successive approximation approach. The proposed swit-ched resistor design method and tuning circuit are designed in 0.18 μm CMOS technology and verified. Results are compared to existing tuning circuit designs.

  15. Reconfiguration of Analog Electronics for Extreme Environments (United States)

    Stoica, Adrian; Zebulum, Ricardo; Keymeulen, Didier; Guo, Xin


    This paper argues in favor of adaptive reconfiguration as a technique to expand the operational envelope of analog electronics for extreme environments (EE). On a reconfigurable device, although component parameters change in EE, as long as devices still operate, albeit degraded, a new circuit design, suitable for new parameter values, may be mapped into the reconfigurable structure to recover the initial circuit function. Laboratory demonstrations of this technique were performed by JPL in several independent experiments in which bulk CMOS reconfgurable devices were exposed to, and degraded by, high temperatures (approx.300 C) or radiation (300kRad TID), and then recovered by adaptive reconfiguration using evolutionary search algorithms.

  16. An Analog VLSI Saccadic Eye Movement System



    In an effort to understand saccadic eye movements and their relation to visual attention and other forms of eye movements, we - in collaboration with a number of other laboratories - are carrying out a large-scale effort to design and build a complete primate oculomotor system using analog CMOS VLSI technology. Using this technology, a low power, compact, multi-chip system has been built which works in real-time using real-world visual inputs. We describe in this paper the performance of a...

  17. Microstore: the Stanford analog memory unit

    Energy Technology Data Exchange (ETDEWEB)

    Walker, J.T.; Chae, S.I.; Shapiro, S.; Larsen, R.S.


    An NMOS device has been developed which provides high speed analog signal storage and readout for time expansion of transient signals. This device takes advantage of HMOS-1 VLSI technology to implement an array of 256 storage cells. Sequential samples of an input waveform can be taken every 5 ns while providing an effective sampling aperture time of less than 1 ns. The design signal-to-noise ratio is 1 part in 2000. Digital control circuitry is provided on the chip for controlling the read-in and read-out processes. A reference circuit is incorporated in the chip for first order compensation of leakage drifts, sampling pedestals, and temperature effects.

  18. Bootstrapped Low-Voltage Analog Switches

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper


    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...... by employing a feedback loop. The gate oxide will not be subject to voltages exceeding the supply voltage difference.Realistic switches have been simulated with HSPICE. The simulations show that the switch circuits operate very well, even when the supply voltage approaches the technology's threshold voltage....

  19. Analogy among microfluidics, micromechanics, and microelectronics. (United States)

    Li, Sheng-Shian; Cheng, Chao-Min


    We wish to illuminate the analogous link between microfluidic-based devices, and the already established pairing of micromechanics and microelectronics to create a triangular/three-way scientific relationship as a means of interlinking familial disciplines and accomplishing two primary goals: (1) to facilitate the modeling of multidisciplinary domains; and, (2) to enable us to co-simulate the entire system within a compact circuit simulator (e.g., Cadence or SPICE). A microfluidic channel-like structure embedded in a micro-electro-mechanical resonator via our proposed CMOS-MEMS technology is used to illustrate the connections among microfluidics, micromechanics, and microelectronics.

  20. An optical analog of quantum optomechanics

    CERN Document Server

    Rodríguez-Lara, B M


    We present a two-dimensional array of nearest-neighbor coupled waveguides that is the optical analog of a quantum optomechanical system. We show that the quantum model predicts the appearance of effective column isolation, diagonal-coupling and other non-trivial couplings in the two-dimensional photonic lattice under a standard approximation from ion-trap cavity electrodynamics. We provide an approximate impulse function for the case of effective column isolation and compare it with exact numerical propagation in the photonic lattice.

  1. Analogic China map constructed by DNA

    Institute of Scientific and Technical Information of China (English)

    QIAN Lulu; HE Lin; WANG Ying; ZHANG Zhao; ZHAO Jian; PAN Dun; ZHANG Yi; LIU Qiang; FAN Chunhai; HU Jun


    In this research, a nanoscale DNA structure of analogic China map is created. The nanostructure of roughly 150 nm in diameter with a spatial resolution of 6 nm is purely constructed by folding DNA. The picture observed by atomic force microscopy (AFM) is almost identical with the designed shape. The DNA origami technology invented by Rothemund in 2006 is employed in the construction of this shape, which has proved the capability of constructing almost any complicated shape enabled by DNA origami, and provides new bottom-up method for constructing nanostructures.

  2. Analogies as categorization phenomena: Studies from scientific discourse (United States)

    Atkins, Leslie Jill

    Studies on the role of analogies in science classrooms have tended to focus on analogies that come from the teacher or curriculum, and not the analogies that students generate. Such studies are derivative of an educational system that values content knowledge over scientific creativity, and derivative of a model of teaching in which the teacher's role is to convey content knowledge. This dissertation begins with the contention that science classrooms should encourage scientific thinking and one role of the teacher is to model that behavior and identify and encourage it in her students. One element of scientific thinking is analogy. This dissertation focuses on student-generated analogies in science, and offers a model for understanding these. I provide evidence that generated analogies are assertions of categorization, and the base of an analogy is the constructed prototype of an ad hoc category. Drawing from research on categorization, I argue that generated analogies are based in schemas and cognitive models. This model allows for a clear distinction between analogy and literal similarity; prior to this research analogy has been considered to exist on a spectrum of similarity, differing from literal similarity to the degree that structural relations hold but features do not. I argue for a definition in which generated analogies are an assertion of an unexpected categorization: that is, they are asserted as contradictions to an expected schema.

  3. Analogies in medicine: valuable for learning, reasoning, remembering and naming. (United States)

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


    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 explain a knowledge to be achieved (the target), with pieces of information already familiar to the learner (the source), keeping in mind the constraints of similarity, structure and purpose. The purpose of this essay is to examine the use of analogies in medicine. We provide a brief review of the theoretical basis of analogical reasoning. This theoretical background is discussed in the light of actual examples of analogies retrieved from medical literature. In medicine, analogies have long been used to explain several physiologic and pathologic processes. Besides deeper structural relations, superficial attribute similarity is extensively used in many medical specialties. These attribute similarities are important in naming, categorizing and classifying, and play a role as learning and memorizing tools. Analogies also serve as basis for medical nomenclature. The choice of the source of analogies is highly dependent on cultural background, and may derive from ancient or diverse cultures. Learning by analogies may thus require research on culture diversity in order to establish an adequate justification and to comprehend the purpose of an analogy.

  4. Unconscious violinists and the use of analogies in moral argument. (United States)

    Wiland, E


    Analogies are the stuff out of which normative moral philosophy is made. Certainly one of the most famous analogies constructed by a philosopher in order to argue for a specific controversial moral conclusion is the one involving Judith Thomson's unconscious violinist. Reflection upon this analogy is meant to show us that abortion is generally not immoral even if the prenatal have the same moral status as the postnatal. This was and still is a controversial conclusion, and yet the analogy does seem to reveal in a very vivid way what makes abortion a reasonable response to a terrible situation. But Thomson's example has frequently been attacked on all sides for not being truly analogous to abortion. Here I develop a brand new analogy that sheds light on the issue with which Thomson was concerned, while at the same time avoiding most of the more serious objections made to her analogy.

  5. Continuous-time analog filter in CMOS nanoscale era (United States)

    Baschirotto, A.; De Matteis, M.; Pezzotta, A.; D'Amico, S.


    Analog filters are key blocks in analog signal processing. They are widely employed in many systems, like wireless transceivers, detectors read-out, sensors interfaces, etc. The IC technology choice for such systems is mainly dictated by the requirements of high speed and low power consumption of digital circuits. This pushed an impressive movement towards scaled technology and this has important consequences on the analog circuits design. The impact of technology scaling down to nanometre scale on analog filters design is here investigated. For instance, supply voltage reduction in analog filters limits circuits design solutions and could result in higher power consumption. Moreover, at the same time, innovative systems push analog filters to get higher and higher operation frequencies, due to the increasing bandwidth/speed requirements. Recent solutions for efficient low-voltage and high frequency analog filters in nanometre technology are described.

  6. Use of analogy in learning physics: The role of representations

    Directory of Open Access Journals (Sweden)

    Noah D. Finkelstein


    Full Text Available Previous studies have demonstrated that analogies can promote student learning in physics and can be productively taught to students to support their learning, under certain conditions. We build on these studies to explore the use of analogy by students in a large introductory college physics course. In the first large-scale study of its kind, we demonstrate that different analogies can lead to varied student reasoning. When different analogies were used to teach electromagnetic (EM waves, we found that students explicitly mapped characteristics either of waves on strings or sound waves to EM waves, depending upon which analogy students were taught. We extend these results by investigating how students use analogies. Our findings suggest that representational format plays a key role in the use of analogy.

  7. Molecular simulation of N-acetylneuraminic acid analogs and molecular dynamics studies of cholera toxin-Neu5Gc complex. (United States)

    Blessy, J Jino; Sharmila, D Jeya Sundara


    Cholera toxin (CT) is an AB5 protein complex secreted by the pathogen Vibrio cholera, which is responsible for cholera infection. N-acetylneuraminic acid (NeuNAc) is a derivative of neuraminic acid with nine-carbon backbone. NeuNAc is distributed on the cell surface mainly located in the terminal components of glycoconjugates, and also plays an important role in cell-cell interaction. In our current study, molecular docking and molecular dynamic (MD) simulations were implemented to identify the potent NeuNAc analogs with high-inhibitory activity against CT protein. Thirty-four NeuNAc analogs, modified in different positions C-1/C-2/C-4/C-5/C-7/C-8/C-9, were modeled and docked against the active site of CT protein. Among the 34 NeuNAc analogs, the analog Neu5Gc shows the least extra precision glide score of -9.52 and glide energy of -44.71 kcal/mol. NeuNAc analogs block the CT active site residues HIS:13, ASN:90, LYS:91, GLN:56, GLN:61, and TRP:88 through intermolecular hydrogen bonding. The MD simulation for CT-Neu5Gc docking complex was performed using Desmond. MD simulation of CT-Neu5Gc complex reveals the stable nature of docking interaction.

  8. The gravitational analog of Faraday's induction law (United States)

    Zile, Daniel; Overduin, James


    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.

  9. Developing Fluorescent Hyaluronan Analogs for Hyaluronan Studies

    Directory of Open Access Journals (Sweden)

    Shi Ke


    Full Text Available Two kinds of fluorescent hyaluronan (HA analogs, one serving as normal imaging agent and the other used as a biosensitive contrast agent, were developed for the investigation of HA uptake and degradation. Our approach of developing HA imaging agents depends on labeling HA with varying molar percentages of a near-infrared (NIR dye. At low labeling ratios, the hyaluronan uptake can be directly imaged while at high labeling ratios, the fluorescent signal is quenched and signal generation occurs only after degradation. It is found that the conjugate containing 1%–2% NIR dye can be used as a normal optical imaging agent, while bioactivable imaging agents are formed at 6% to 17% dye loading. It was determined that the conjugation of dye to HA with different loading percentages does not impact HA biodegradation by hyaluronidase (Hyal. The feasibility of using these two NIR fluorescent hyaluronan analogs for HA investigation was evaluated in vivo with optical imaging. The data demonstrates that the 1% dye loaded fluorescent HA can be used to monitor the behavior of HA and its fragments, whereas bioactivatable HA imaging agent (17% dye in HA is more suitable for detecting HA fragments.

  10. Digital and analog gene circuits for biotechnology. (United States)

    Roquet, Nathaniel; Lu, Timothy K


    Biotechnology offers the promise of valuable chemical production via microbial processing of renewable and inexpensive substrates. Thus far, static metabolic engineering strategies have enabled this field to advance industrial applications. However, the industrial scaling of statically engineered microbes inevitably creates inefficiencies due to variable conditions present in large-scale microbial cultures. Synthetic gene circuits that dynamically sense and regulate different molecules can resolve this issue by enabling cells to continuously adapt to variable conditions. These circuits also have the potential to enable next-generation production programs capable of autonomous transitioning between steps in a bioprocess. Here, we review the design and application of two main classes of dynamic gene circuits, digital and analog, for biotechnology. Within the context of these classes, we also discuss the potential benefits of digital-analog interconversion, memory, and multi-signal integration. Though synthetic gene circuits have largely been applied for cellular computation to date, we envision that utilizing them in biotechnology will enhance the efficiency and scope of biochemical production with living cells.

  11. Antarctic analog for dilational bands on Europa (United States)

    Hurford, T. A.; Brunt, K. M.


    Europa's surface shows signs of extension, which is revealed as lithospheric dilation expressed along ridges, dilational bands and ridged bands. Ridges, the most common tectonic feature on Europa, comprise a central crack flanked by two raised banks a few hundred meters high on each side. Together these three classes may represent a continuum of formation. In Tufts' Dilational Model ridge formation is dominated by daily tidal cycling of a crack, which can be superimposed with regional secular dilation. The two sources of dilation can combine to form the various band morphologies observed. New GPS data along a rift on the Ross Ice Shelf, Antarctica is a suitable Earth analog to test the framework of Tufts' Dilational Model. As predicted by Tufts' Dilational Model, tensile failures in the Ross Ice Shelf exhibit secular dilation, upon which a tidal signal can be seen. From this analog we conclude that Tufts' Dilational Model for Europan ridges and bands may be credible and that the secular dilation is most likely from a regional source and not tidally driven.

  12. Efficient Analog Circuits for Boolean Satisfiability

    CERN Document Server

    Yin, Xunzhao; Varga, Melinda; Ercsey-Ravasz, Maria; Toroczkai, Zoltan; Hu, Xiaobo Sharon


    Efficient solutions to NP-complete problems would significantly benefit both science and industry. However, such problems are intractable on digital computers based on the von Neumann architecture, thus creating the need for alternative solutions to tackle such problems. Recently, a deterministic, continuous-time dynamical system (CTDS) was proposed (Nature Physics, 7(12), 966 (2011)) to solve a representative NP-complete problem, Boolean Satisfiability (SAT). This solver shows polynomial analog time-complexity on even the hardest benchmark $k$-SAT ($k \\geq 3$) formulas, but at an energy cost through exponentially driven auxiliary variables. With some modifications to the CTDS equations, here we present a novel analog hardware SAT solver, AC-SAT, implementing the CTDS. AC-SAT is intended to be used as a co-processor, and with its modular design can be readily extended to different problem sizes. The circuit is designed and simulated based on a 32nm CMOS technology. SPICE simulation results show speedup factor...

  13. Analog IC reliability in nanometer CMOS

    CERN Document Server

    Maricau, Elie


    This book focuses on modeling, simulation and analysis of analog circuit aging. First, all important nanometer CMOS physical effects resulting in circuit unreliability are reviewed. Then, transistor aging compact models for circuit simulation are discussed and several methods for efficient circuit reliability simulation are explained and compared. Ultimately, the impact of transistor aging on analog circuits is studied. Aging-resilient and aging-immune circuits are identified and the impact of technology scaling is discussed.   The models and simulation techniques described in the book are intended as an aid for device engineers, circuit designers and the EDA community to understand and to mitigate the impact of aging effects on nanometer CMOS ICs.   ·         Enables readers to understand long-term reliability of an integrated circuit; ·         Reviews CMOS unreliability effects, with focus on those that will emerge in future CMOS nodes; ·         Provides overview of models for...

  14. Photonic analog-to-digital converters (United States)

    Valley, George C.


    This paper reviews over 30 years of work on photonic analog-to-digital converters. The review is limited to systems in which the input is a radio-frequency (RF) signal in the electronic domain and the output is a digital version of that signal also in the electronic domain, and thus the review excludes photonic systems directed towards digitizing images or optical communication signals. The state of the art in electronic ADCs, basic properties of ADCs and properties of analog optical links, which are found in many photonic ADCs, are reviewed as background information for understanding photonic ADCs. Then four classes of photonic ADCs are reviewed: 1) photonic assisted ADC in which a photonic device is added to an electronic ADC to improve performance, 2) photonic sampling and electronic quantizing ADC, 3) electronic sampling and photonic quantizing ADC, and 4) photonic sampling and quantizing ADC. It is noted, however, that all 4 classes of “photonic ADC” require some electronic sampling and quantization. After reviewing all known photonic ADCs in the four classes, the review concludes with a discussion of the potential for photonic ADCs in the future.

  15. Metaphor and analogy in everyday problem solving. (United States)

    Keefer, Lucas A; Landau, Mark J


    Early accounts of problem solving focused on the ways people represent information directly related to target problems and possible solutions. Subsequent theory and research point to the role of peripheral influences such as heuristics and bodily states. We discuss how metaphor and analogy similarly influence stages of everyday problem solving: Both processes mentally map features of a target problem onto the structure of a relatively more familiar concept. When individuals apply this structure, they use a well-known concept as a framework for reasoning about real world problems and candidate solutions. Early studies found that analogy use helped people gain insight into novel problems. More recent research on metaphor goes further to show that activating mappings has subtle, sometimes surprising effects on judgment and reasoning in everyday problem solving. These findings highlight situations in which mappings can help or hinder efforts to solve problems. WIREs Cogn Sci 2016, 7:394-405. doi: 10.1002/wcs.1407 For further resources related to this article, please visit the WIREs website.

  16. Metastatic Insulinoma Managed with Radiolabeled Somatostatin Analog (United States)

    Costa, Ricardo; Bacchi, Carlos E.; Almeida Filho, Paulo


    Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium (177LU). PMID:24455330

  17. The exoplanets analogy to the Multiverse

    CERN Document Server

    Kinouchi, Osame


    The idea of a Mutiverse is controversial, although it is a natural possible solution to particle physics and cosmological fine-tuning problems (FTPs). Here I explore the analogy between the Multiverse proposal and the proposal that there exist an infinite number of stellar systems with planets in a flat Universe, the Multiplanetverse. Although the measure problem is present in this scenario, the idea of a Multiplanetverse has predictive power, even in the absence of direct evidence for exoplanets that appeared since the 90s. We argue that the fine-tuning of Earth to life (and not only the fine-tuning of life to Earth) could predict with certainty the existence of exoplanets decades or even centuries before that direct evidence. Several other predictions can be made by studying only the Earth and the Sun, without any information about stars. The analogy also shows that theories that defend that the Earth is the unique existing planet and that, at the same time, is fine-tuned to life by pure chance (or pure phy...

  18. Isolation and characterization of soybean NBS analogs

    Institute of Scientific and Technical Information of China (English)


    Isolation of plant resistance genes is greatly helpful to crop resistance breeding and the insight of resistance mechanism. The cloned plant resistance genes are classified into four classes according to their putative structural domain, of which the majority possesses nucleotide-binding site (NBS) domain that consists of P-loop, kinase2a and kinase3a. The conservation of this domain affords the potential possibility of cloning the plant resistance genes, which is homology-based cloning technique. In the present study, the degenerate oligonucleotide primers were designed according to the tobacco N and Arabidopsis RPS2, and 358 clones were isolated from the genomic DNA of resistance soybean cultivar Kefeng1, resistant to soybean mosaic virus, and 4 open-reading NBS analogs were finally characterized and designated as KNBS1, KNBS2, KNBS3 and KNBS4. Southern hybridization suggested that they were present with multicopy in the soybean genome; KNBS4 was mapped to F linkage group and KNBS2 co-located J linkage group with the SCAR marker of Rsa resistant to soybean mosaic virus by RFLP analysis. Northern analysis suggested that KNBS2- related sequence was low and constitutively expressed in the root, stem and leaves of soybean. The detailed characterization of NBS analogs is very helpful to ultimately cloning the soybean resistance gene.

  19. Antarctic Analog for Dilational Bands on Europa (United States)

    Hurford, T. A.; Brunt, K. M.


    Europa's surface shows signs of extension, which is revealed as lithospheric dilation expressed along ridges, dilational bands and ridged bands. Ridges, the most common tectonic feature on Europa, comprise a central crack flanked by two raised banks a few hundred meters high on each side. Together these three classes may represent a continuum of formation. In Tufts' Dilational Model ridge formation is dominated by daily tidal cycling of a crack, which can be superimposed with regional secular dilation. The two sources of dilation can combine to form the various band morphologies observed. New GPS data along a rift on the Ross Ice Shelf, Antarctica is a suitable Earth analog to test the framework of Tufts' Dilational Model. As predicted by Tufts' Dilational Model, tensile failures in the Ross Ice Shelf exhibit secular dilation, upon which a tidal signal can be seen. From this analog we conclude that Tufts' Dilational Model for Europan ridges and bands may be credible and that the secular dilation is most likely from a regional source and not tidally driven.

  20. Comparison between analog and digital filters

    Directory of Open Access Journals (Sweden)

    Zoltan Erdei


    Full Text Available Digital signal processing(DSP is one of the most powerful technologies and will model science and engineering in the 21st century. Revolutionary changes have already been made in different areas of research such as communications, medical imaging, radar and sonar technology, high fidelity audio signal reproducing etc. Each of these fields developed a different signal processing technology with its own algorithms, mathematics and technology, Digital filters are used in two general directions: to separate mixed signals and to restore signals that were compromised in different modes. The objective of this paper is to compare some basic digital filters versus analog filters such as low-pass, high-pass, band-pass filters. Scientists and engineers comprehend that, in comparison with analog filters, digital filters can process the same signal in real-time with broader flexibility. This understanding is considered important to instill incentive for engineers to become interested in the field of DSP. The analysis of the results will be made using dedicated libraries in MATLAB and Simulink software, such as the Signal Processing Toolbox.

  1. Martian hillside gullies and icelandic analogs (United States)

    Hartmann, William K.; Thorsteinsson, Thorsteinn; Sigurdsson, Freysteinn


    We report observations of Icelandic hillside gully systems that are near duplicates of gullies observed on high-latitude martian hillsides. The best Icelandic analogs involve basaltic talus slopes at the angle of repose, with gully formation by debris flows initiated by ground water saturation, and/or by drainage of water from upslope cliffs. We report not only the existence of Mars analog gullies, but also an erosional sequence of morphologic forms, found both on Mars and in Iceland. The observations support hypotheses calling for creation of martian gullies by aqueous processes. Issues remain whether the water in each case comes only from surficial sources, such as melting of ground ice or snow, or from underground sources such as aquifers that gain surface access in hillsides. Iceland has many examples of the former, but the latter mechanism is not ruled out. Our observations are consistent with the martian debris flow mechanism of F. Costard et al. (2001c, Science295, 110-113), except that classic debris flows begin at midslope more frequently than on Mars. From morphologic observations, we suggest that some martian hillside gully systems not only involve significant evolution by extended erosive activity, but gully formation may occur in episodes, and the time interval since the last episode is considerably less than the time interval needed to erase the gully through normal martian obliteration processes.

  2. Palytoxin and Analogs: Biological and Ecological Effects

    Directory of Open Access Journals (Sweden)

    Vítor Ramos


    Full Text Available Palytoxin (PTX is a potent marine toxin that was originally found in soft corals from tropical areas of the Pacific Ocean. Soon after, its occurrence was observed in numerous other marine organisms from the same ecological region. More recently, several analogs of PTX were discovered, remarkably all from species of the dinoflagellate genus Ostreopsis. Since these dinoflagellates are also found in other tropical and even in temperate regions, the formerly unsuspected broad distribution of these toxins was revealed. Toxicological studies with these compounds shows repeatedly low LD50 values in different mammals, revealing an acute toxic effect on several organs, as demonstrated by different routes of exposure. Bioassays tested for some marine invertebrates and evidences from environmental populations exposed to the toxins also give indications of the high impact that these compounds may have on natural food webs. The recognition of its wide distribution coupled with the poisoning effects that these toxins can have on animals and especially on humans have concerned the scientific community. In this paper, we review the current knowledge on the effects of PTX and its analogs on different organisms, exposing the impact that these toxins may have in coastal ecosystems.

  3. Metastatic Insulinoma Managed with Radiolabeled Somatostatin Analog

    Directory of Open Access Journals (Sweden)

    Ricardo Costa


    Full Text Available Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT scans, magnetic resonance imaging (MRI, and positron emission tomography (PET/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium (177LU.

  4. Biochemical characterization and cellular imaging of a novel, membrane permeable fluorescent cAMP analog

    Directory of Open Access Journals (Sweden)

    Zaccolo Manuela


    Full Text Available Abstract Background A novel fluorescent cAMP analog (8-[Pharos-575]- adenosine-3', 5'-cyclic monophosphate was characterized with respect to its spectral properties, its ability to bind to and activate three main isoenzymes of the cAMP-dependent protein kinase (PKA-Iα, PKA-IIα, PKA-IIβ in vitro, its stability towards phosphodiesterase and its ability to permeate into cultured eukaryotic cells using resonance energy transfer based indicators, and conventional fluorescence imaging. Results The Pharos fluorophore is characterized by a Stokes shift of 42 nm with an absorption maximum at 575 nm and the emission peaking at 617 nm. The quantum yield is 30%. Incubation of the compound to RIIα and RIIβ subunits increases the amplitude of excitation and absorption maxima significantly; no major change was observed with RIα. In vitro binding of the compound to RIα subunit and activation of the PKA-Iα holoenzyme was essentially equivalent to cAMP; RII subunits bound the fluorescent analog up to ten times less efficiently, resulting in about two times reduced apparent activation constants of the holoenzymes compared to cAMP. The cellular uptake of the fluorescent analog was investigated by cAMP indicators. It was estimated that about 7 μM of the fluorescent cAMP analog is available to the indicator after one hour of incubation and that about 600 μM of the compound had to be added to intact cells to half-maximally dissociate a PKA type IIα sensor. Conclusion The novel analog combines good membrane permeability- comparable to 8-Br-cAMP – with superior spectral properties of a modern, red-shifted fluorophore. GFP-tagged regulatory subunits of PKA and the analog co-localized. Furthermore, it is a potent, PDE-resistant activator of PKA-I and -II, suitable for in vitro applications and spatial distribution evaluations in living cells.

  5. Operational Lessons Learned from NASA Analog Missions (United States)

    Arnold, Larissa S.


    vehicle and system capabilities are required to support the activities? How will the crew and the Earth-based mission control team interact? During the initial phases of manned planetary exploration, one challenge in particular is virtually the same as during the Apollo program: How can scientific return be maximized during a relatively short surface mission? Today, NASA is investigating solutions to these challenges by conducting analog missions. These Earth-based missions possess characteristics that are analogous to missions on the Moon or Mars. These missions are excellent for testing operational concepts, and the design, configuration, and functionality of spacesuits, robots, rovers, and habitats. Analog mission crews test specific techniques and procedures for surface field geology, biological sample collection, and planetary protection. The process of actually working an analog mission reveals a myriad of small details, which either contribute to or impede efficient operations, many of which would never have been thought about otherwise. It also helps to define the suite of tools, containers, and other small equipment that surface explorers will use. This paper focuses on how analog missions have addressed selected operational considerations for future planetary missions.

  6. Analog models of computations \\& Effective Church Turing Thesis: Efficient simulation of Turing machines by the General Purpose Analog Computer

    CERN Document Server

    Pouly, Amaury; Graça, Daniel S


    \\emph{Are analog models of computations more powerful than classical models of computations?} From a series of recent papers, it is now clear that many realistic analog models of computations are provably equivalent to classical digital models of computations from a \\emph{computability} point of view. Take, for example, the probably most realistic model of analog computation, the General Purpose Analog Computer (GPAC) model from Claude Shannon, a model for Differential Analyzers, which are analog machines used from 1930s to early 1960s to solve various problems. It is now known that functions computable by Turing machines are provably exactly those that are computable by GPAC. This paper is about next step: understanding if this equivalence also holds at the \\emph{complexity} level. In this paper we show that the realistic models of analog computation -- namely the General Purpose Analog Computer (GPAC) -- can simulate Turing machines in a computationally efficient manner. More concretely we show that, modulo...

  7. Design and Synthesis of Resin-Conjugated Tamiflu Analogs for Affinity Chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Yasuaki; Yamatsugu, Kenzo; Kanai, Motomu; Shibasaki, Masakatsu [The University of Tokyo, Tokyo (Japan); Echigo, Noriko; Kuzuhara, Takashi [Tokushima Bunri University, Tokushima (Japan)


    Two types of resin-conjugated Tamiflu analogs were synthesized by modifying our original synthetic route of oseltamivir phosphate (Tamiflu). The prepared resins bound to influenza virus neuraminidase, the main target of Tamiflu. The resins will be useful for isolating and identifying presumed endogenous vertebrate proteins that interact with Tamiflu, which might relate to the rarely observed abnormal behavior exhibited by some influenza patients treated with Tamiflu.

  8. Karakteristik Sensori dan Fisiko-Kimia Beras Analog Sorghum dengan Penambahan Rempah Campuran

    Directory of Open Access Journals (Sweden)

    Maya Indra Rasyid


    Full Text Available The purpose of this study was to obtain the formula of sorghum rice analogue by mixed spices addition with acceptable sensory and physico-chemical characteristics.  The selection of sorghum rice analogue formula was tested by using hedonic test with 70 untrained panelists. The addition of mixed spices powder was as follows: 30 % onion, 20 % garlic, 10 % bay leaves, 20 % ginger and 20 % lemongrass. Those mixed spices powder were added to the sorghum rice analogue at percentage of 0.25 %, 0,5 %, 1 %, 2 %, 3 % and 0 % (control  from total dough weight. The sorghum rice analogue was made using extrusion technology (a twin screw extruder. The overall sensory evaluation result showed that the addition of spice mixed had significant effect (p ≤ 0.05 on the characteristics of sorghum rice analogue. The panelists accepted the sorghum rice analogue with 1% mixed spice. The preferred formulation was the addition of 1% mixed spice which contain of  9.56 % moisture, 0.72 % ash, 0.53 % fat, 6.22 % protein, 92.53 % carbohydrate, 26.48 % amyloseand 6,67 % dietary fiber. Sorghum rice analogue enriched by spices is a potential as a rich fiber source. ABSTRAK Tujuan penelitian adalah mendapatkan formula beras analog berbahan dasar sorgum dengan penambahan rempah campuran yang dapat diterima secara sensori. Pemilihan formula dilakukan dengan uji hedonik menggunakan 70 orang panelis tidak terlatih. Rempah yang ditambahkan berupa bubuk rempah campuran yang terdiri atas bawang merah 30%, bawang putih 20 %, daun salam 10 %, jahe 20 % dan sereh 20 %. Penambahan bubuk rempah campuran untuk pembuatan beras analog sorghum berturut-turut 0,25 %, 0,5 %, 1 %, 2 %, 3 % dan kontrol (tanpa rempah dari total berat adonan diluar air. Beras analog sorghum dibuat dengan teknologi ekstrusi menggunakan ekstruder ulir ganda. Hasil uji sensori secara keseluruhan menunjukkan bahwa penambahan rempah campuran berpengaruh nyata (p <0,05 terhadap nasi beras analog yang dihasilkan

  9. Synthetic analogs of bacterial quorum sensors

    Energy Technology Data Exchange (ETDEWEB)

    Iyer, Rashi (Los Alamos, NM); Ganguly, Kumkum (Los Alamos, NM); Silks, Louis A. (Los Alamos, NM)


    Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

  10. Ultra Low-Power Analog Median Filters

    Directory of Open Access Journals (Sweden)

    A. Diaz-Sanchez


    Full Text Available The design and implementation of three analog median filter topologies, whose transistors operate in the deep weak-inversion region, is described. The first topology is a differential pairs array, in which drain currents are driven into two nodes in a differential fashion, while the second topology is based on a wide range OTA, which is used to maximize the dynamic range. Finally, the third topology uses three range-extended OTAs. The proposed weak-inversion filters were designed and fabricated in ON Semiconductor 0.5 micrometer technology through MOSIS. Experimental results of three-input fabricated prototypes for all three topologies are show, where power consumptions of 90nW in the first case, and 270nW in the other two cases can be noticed. A dual power supply +/-1.5 Volts were used.

  11. Atwood and Poggendorff: an insightful analogy

    DEFF Research Database (Denmark)

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


    - 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...

  12. Atwood and Poggendorff: an insightful analogy (United States)

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


    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.

  13. Four-gate transistor analog multiplier circuit (United States)

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


    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. On analog implementations of discrete neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Beiu, V.; Moore, K.R.


    The paper will show that in order to obtain minimum size neural networks (i.e., size-optimal) for implementing any Boolean function, the nonlinear activation function of the neutrons has to be the identity function. The authors shall shortly present many results dealing with the approximation capabilities of neural networks, and detail several bounds on the size of threshold gate circuits. Based on a constructive solution for Kolmogorov`s superpositions they will show that implementing Boolean functions can be done using neurons having an identity nonlinear function. It follows that size-optimal solutions can be obtained only using analog circuitry. Conclusions, and several comments on the required precision are ending the paper.

  15. Synthesis and biodistribution of radioiodinated nicotine analogs

    Energy Technology Data Exchange (ETDEWEB)

    Chan, S.M.; Basmadjian, G.P.; Marten, D.F.; Sadek, S.; Magarian, R.A.; Grunder, J.R.; Ice, R.D.


    The authors reported previously on the synthesis and biodistribution of radioiodinated 5-iodonicotine. In their continuous effort to search for a potential brain as well as adrenal medulla imaging agent, the authors synthesized four radioiodinated nicotine analogs. The labeled compounds were prepared by brominating nicotinic acid, and reacting the acylated product with the appropriate amines to give the respective amides which were then reduced with diborane to the amines. I-125 labeling was done by halogen exchange. Biodistribution studies performed in female Sprague-Dawley rats showed that all these compounds were taken up rapidly by the brain and the adrenal. The highest uptake of all these compounds in both organs occurred at 2 minutes after tail vein injections. The organ:blood ratios at 2 minutes and the T/sub 1/3/ (min.) of radioactivity in these organs were compared.

  16. Analog Electronic Filters Theory, Design and Synthesis

    CERN Document Server

    Dimopoulos, Hercules G


    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...

  17. Z~+(4430) and Analogous Heavy Flavor States

    Institute of Scientific and Technical Information of China (English)

    DING Gui-jun


    We have studied Z~+ (4430)as a D~* D_1 molecule from the quark model,state mixing effect is considered by solving the coupled channel Schr(o)dinger equation numerically.More precise measurements of Z~+ (4430)mass and width,partial wave analysis are helpful to understand its structure.If it lies below the D~* D_1 threshold,molecule interpretation with J~P=1~- is favored,and JP =0~- can not be ruled out.Otherwise Z~+ (4430)may be a virtual state with J~P=2~-.The analogous heavy flavor mesons Z~+_(bb) and Z~(++)_(bc) are considered as well,and the masses predicted in our model are in agreement with the predictions from the potential model and QCD sum rule.

  18. A Probabilistic Approach to Pronunciation by Analogy

    CERN Document Server

    Kujala, Janne V


    The relationship between written and spoken words is convoluted in languages with a deep orthography such as English and therefore it is difficult to devise explicit rules for generating the pronunciations for unseen words. Pronunciation by analogy (PbA) is a data-driven method of constructing pronunciations for novel words from concatenated segments of known words and their pronunciations. PbA performs relatively well with English and outperforms several other proposed methods. However, the best published word accuracy of 65.5% (for the 20,000 word NETtalk corpus) suggests there is much room for improvement in it. Previous PbA algorithms have used several different scoring strategies such as the product of the frequencies of the component pronunciations of the segments, or the number of different segmentations that yield the same pronunciation, and different combinations of these methods, to evaluate the candidate pronunciations. In this article, we instead propose to use a probabilistically justified scorin...

  19. X-Rays from Green Pea Analogs (United States)

    Brorby, Matthew


    X-rays may have contributed to the heating and reionization of the IGM in the early universe. High mass X-ray binaries (HMXB) within small, low-metallicity galaxies are expected to be the main source of X-rays at this time. Since studying these high-redshift galaxies is currently impossible, we turn to local analogs that have the same properties the galaxies in the early are expected to have. A number of recent studies have shown an enhanced number of HMXBs in nearby low metallicity galaxies. We propose to observe a sample of metal-deficient luminous compact galaxies (LCG) in order to determine if the X-ray luminosity is enhanced relative to SFR, thereby providing further evidence to the importance of X-rays in the early universe.

  20. Analog circuit for controlling acoustic transducer arrays

    Energy Technology Data Exchange (ETDEWEB)

    Drumheller, Douglas S. (Cedar Crest, NM)


    A simplified ananlog circuit is presented for controlling electromechanical transducer pairs in an acoustic telemetry system. The analog circuit of this invention comprises a single electrical resistor which replaces all of the digital components in a known digital circuit. In accordance with this invention, a first transducer in a transducer pair of array is driven in series with the resistor. The voltage drop across this resistor is then amplified and used to drive the second transducer. The voltage drop across the resistor is proportional and in phase with the current to the transducer. This current is approximately 90 degrees out of phase with the driving voltage to the transducer. This phase shift replaces the digital delay required by the digital control circuit of the prior art.

  1. Analog model for an expanding universe

    CERN Document Server

    Weinfurtner, S E C


    Over the last few years numerous papers concerning analog models for gravity have been published. It was shown that the dynamical equation of several systems (e.g. Bose-Einstein condensates with a sink or a vortex) have the same wave equation as light in a curved-space (e.g. black holes). In the last few months several papers were released which deal with simulations of the universe. In this article the de-Sitter universe will be compared with a freely expanding three-dimensional spherical Bose-Einstein condensate. Initially the condensate is in a harmonic trap, which suddenly will be switched off. At the same time a small perturbation will be injected in the center of the condensate cloud. The motion of the perturbation in the expanding condensate will be discussed, and after some transformations the similarity to an expanding universe will be shown.

  2. Analogies and metaphors in clinical medicine. (United States)

    Masukume, Gwinyai; Zumla, Alimuddin


    Medicine is traditionally known as an 'art', and not an exact 'science'. Medical images of clinical signs and pathology were communicated through 'metaphors' in the 19th and early 20th centuries to make recognition easier in anticipation of the clinical counterpart when encountered in medical practice. They have served as teaching aids, enhancing memory retention for medical students, nurses and doctors and have withstood the test of time. Standard medical textbooks contain metaphors that have become entrenched in teaching, learning and examining in medical schools and hospitals worldwide. The continued use of metaphors has given rise to an ongoing debate, particularly in Africa, due to the usage of inappropriate or unfamiliar metaphors which are not locally or culturally relevant. Despite this, medical analogies will no doubt continue to be useful for medical education, clinical practice and 'aide memoirs' for examinations, and bring light humour, for a long time to come.

  3. Analog VLSI neural network integrated circuits (United States)

    Kub, F. J.; Moon, K. K.; Just, E. A.


    Two analog very large scale integration (VLSI) vector matrix multiplier integrated circuit chips were designed, fabricated, and partially tested. They can perform both vector-matrix and matrix-matrix multiplication operations at high speeds. The 32 by 32 vector-matrix multiplier chip and the 128 by 64 vector-matrix multiplier chip were designed to perform 300 million and 3 billion multiplications per second, respectively. An additional circuit that has been developed is a continuous-time adaptive learning circuit. The performance achieved thus far for this circuit is an adaptivity of 28 dB at 300 KHz and 11 dB at 15 MHz. This circuit has demonstrated greater than two orders of magnitude higher frequency of operation than any previous adaptive learning circuit.

  4. Analog computing using reflective plasmonic metasurfaces

    CERN Document Server

    Pors, Anders; Bozhevolnyi, Sergey I


    Motivated by the recent renewed interest in compact analog computing using light and metasurfaces (Silva, A. et al., Science 2014, 343, 160-163), we suggest a practical approach to its realization that involves reflective metasurfaces consisting of arrayed gold nanobricks atop a subwavelength-thin dielectric spacer and optically-thick gold film, a configuration that supports gap-surface plasmon resonances. Using well established numerical routines, we demonstrate that these metasurfaces enable independent control of the light phase and amplitude, and design differentiator and integrator metasurfaces featuring realistic system parameters. Proof-of-principle experiments are reported along with the successful realization of a high-quality poor-man's integrator metasurface operating at the wavelength of 800 nm.

  5. Analogy between fluid cavitation and fracture mechanics (United States)

    Hendricks, R. C.; Mullen, R. L.; Braun, M. J.


    When the stresses imposed on a fluid are sufficiently large, rupture or cavitation can occur. Such conditions can exist in many two-phase flow applications, such as the choked flows, which can occur in seals and bearings. Nonspherical bubbles with large aspect ratios have been observed in fluids under rapid acceleration and high shear fields. These bubbles are geometrically similar to fracture surface patterns (Griffith crack model) existing in solids. Analogies between crack growth in solid and fluid cavitation are proposed and supported by analysis and observation (photographs). Healing phenomena (void condensation), well accepted in fluid mechanics, have been observed in some polymers and hypothesized in solid mechanics. By drawing on the strengths of the theories of solid mechanics and cavitation, a more complete unified theory can be developed.

  6. Scattering by interstellar graphite dust analog (United States)

    Ahmed, Gazi A.; Gogoi, Ankur


    The analysis of optical scattering data of interstellar carbonaceous graphite dust analog at 543.5 nm, 594.5 nm and 632.8 nm laser wavelengths by using an original laboratory light scattering setup is presented. The setup primarily consisted of a laser source, optical units, aerosol sprayer, data acquisition system and associated instrumentation. The instrument measured scattered light signals from 10° to 170° in steps of 1°. The results of the measurements of the volume scattering function β(θ) and degree of linear polarization P(θ) of the carbonaceous graphite dust particles that were sprayed in front of the laser beam by using an aerosol sprayer were subsequently compared with theoretically generated Mie plots with estimated parameters.

  7. A QCD analogy for quantum gravity

    CERN Document Server

    Holdom, Bob


    Quadratic gravity presents us with a renormalizable, asymptotically free theory of quantum gravity. When its couplings grow strong at some scale, as in QCD, then this strong scale sets the Planck mass. QCD has a gluon that does not appear in the physical spectrum. Quadratic gravity has a spin-2 ghost that we conjecture does not appear in the physical spectrum. We discuss how the QCD analogy leads to this conjecture and to the emergence of general relativity. Certain aspects of the QCD path integral and its measure could also be similar for quadratic gravity. With the addition of the Einstein-Hilbert term, quadratic gravity has a dimensionful parameter that seems to control a quantum phase transition and the size of a mass gap in the strong phase.

  8. Integrated Circuits for Analog Signal Processing

    CERN Document Server


      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...

  9. Positons: slowly diminishing analogs of solitons

    CERN Document Server

    Matveev, V B


    The introduction to the theory of positons is presented. The positons are the remote-acting analogues of solitons and represent slowly diminishing and oscillating solitons of the nonlinear integrated equations of KdV type. The positon and soliton-positon solutions of the KdV equation were for the first time obtained and analyzed about 10 years ago and thereafter designed for a number of other models: mKdV, Toda chains, NSch, sn-Gordon equation and its lattice analog. By the proper selection of the scattering data the single positon and multipositon potentials are characterized by the remarkable property: the corresponding reflection coefficient is equal to zero and the transition coefficient is equal to one (the latter property, as it is known, has no place for the standard short-acting nonreflection potentials

  10. The production of body analogs for use in radiation physics. (United States)

    Metcalfe, P E; Hoban, P W; Harper, N R; Murray, D C; Round, W H


    Bone, muscle and lung analog materials have been produced in-house, and dosimetry phantoms have been produced. A method using computed tomography (CT) has been developed to check that the analogs produced match the radiation properties of body tissues. The relative electron densities and ratio of electron cross sections are calculated from elemental compositions of the analogs. Using these data the theoretical CT numbers are calculated and these numbers are compared with experimental CT numbers for the analogs produced. The experimental CT numbers are found by scanning the samples on a Siemens DRH CT scanner. Results show the maximum difference between theoretical and experimental CT numbers for the analogs is 18 Hounsfield units, which relates to a delta NCT of less than 1%. Comparison of analog CT numbers with CT numbers for the related patient tissues also shows a close match.

  11. 23rd workshop on Advances in Analog Circuit Design

    CERN Document Server

    Baschirotto, Andrea; Makinwa, Kofi


    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.

  12. [Analogies between the thymus and epidermis]. (United States)

    De Panfilis, G


    In this paper, similarities between epidermis and thymus are reviewed. Both epidermis and thymus deal with an epithelial stroma harbouring dendritic cells, which are bone-marrow derived. Both epithelia are keratinized, and a map can be constructed illustrating histo-topographic and antigenic similarities between thymic epithelial cells distributed in various thymic zones (i.e. subcapsular cortex, outer cortex, inner cortex, medulla, outer layers of Hassall's bodies, inner layers of Hassall's bodies) and keratinocytes of different epidermal layers. By contrast, a possible similarity between thymocytes and Langerhans cells is not so easy to demonstrate, although both cell types are CD1 positive. Rather, in our opinion a comparison is preferable of thymocytes to Thy-1 positive dendritic epidermal cells, due to morphological, antigenic, functional and especially lineage similarities. Similarities between thymus and epidermis are clearly important dealing with analogous molecular interactions, namely, thymic epithelial cells/thymocytes versus keratinocytes/T-lymphocytes. Indeed, our recent investigations demonstrated that a subset of keratinocytes is ICAM-1 positive, and the whole keratinocyte population is LFA-3 positive. Since the interaction thymic epithelial cells (ICAM-1 and LFA-3 positive)/thymocytes (LFA-1 and CD2 positive) has been shown to be necessary for promotion of activation and maturation of thymocytes, the interaction keratinocytes (ICAM-1 and LFA-3 positive, as we demonstrated)/T-lymphocytes (LFA-1 and CD2 positive as well) might be, by analogy, important not only for the "homing" of T-lymphocytes within the epidermis, but also for the epidermis being considered a peripheral inductive site for T-cell activation and maturation.

  13. Optical analog-to-digital converter (United States)

    Evanchuk, Vincent L. (Inventor)


    A method and apparatus for converting the intensity of an unknown optical signal (B) into an electrical signal in digital form utilizes two elongated optical attenuators (11, 13), one for the unknown optical signal from a source (10) and one for a known optical signal (A) from a variable source (12), a plurality of photodetectors (e.g., 17, 18) along each attenuator for detecting the intensity of the optical signals, and a plurality of comparators (e.g., 21) connected to the photodetectors in pairs to determine at what points being compared the attenuated known signal equals the attenuated unknown signal. The intensity of the unknown relative to the known is thus determined by the output of a particular comparator. That output is automatically encoded to a relative intensity value in digital form through a balancing feedback control (24) and encoder (23). The digital value may be converted to analog form in a D-to-A converter (27) and used to vary the source of the known signal so that the attenuated intensity of the known signal at a predetermined point (comparator 16) equals the attenuated intensity of the unknown signal at the predetermined point of comparison. If the known signal is then equal to the unknown, there is verification of the analog-to-digital conversion being complete. Otherwise the output of the comparator indicating equality at some other point along the attenuators will provide an output which is encoded and added, through an accumulator comprised of a register (25) and an adder (26), to a previous relative intensity value thereby to further vary the intensity of the known signal source. The steps are repeated until full conversion is verified.

  14. Automating analog design: Taming the shrew (United States)

    Barlow, A.


    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.

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

    CERN Document Server

    Williams, Jim


    * 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

  16. Scalable Low-Power Deep Machine Learning with Analog Computation (United States)


    learning task. We have further designed a second more complex learning chip. We have made significant innovations to the algorithm to facilitate analog ...Paper 2.00 3.00 Junjie Lu, Steven Young, Itamar Arel, Jeremy Holleman. An analog online clustering circuit in 130nm CMOS , 2013 IEEE Asian Solid-State...further designed and fabricated a second more complex learning chip. We have made significant innovations to the algorithm to facilitate analog




    Nature has evolved highly advanced systems capable of performing complex computations, adoption and learning using analog computations. Furthermore nature has evolved techniques to deal with imprecise analog computations by using redundancy and massive connectivity. In this paper we are making use of Artificial Neural Network to demonstrate the way in which the biological system processes in analog domain. We are using 180nm CMOS VLSI technology for implementing circuits which ...

  18. Synthesis and biological activity of nifuroxazide and analogs. II. (United States)

    Tavares, L C; Chisté, J J; Santos, M G; Penna, T C


    Nifuroxazyde and six analogs were synthesized by varying the substitute from the para-position of the benzenic ring and the heteroatom of the heterocyclic ring. The MIC of seven resultant compounds was determined by serial dilutions, testing the ATCC 25923 strain of Staphylococcus aureus. A significant increase in the anti-microbial activity of thyophenic analogs, as compared with furanic and pyrrholic analogs, was observed. In addition, unlike the cyano and hydroxyl groups, the acetyl group promoted anti-microbial activity.

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


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


    Despite a wealth of information on cocaine-like compounds, there is no information on cocaine analogs with substitutions at C-1. Here, we report on (R)-(−)-cocaine analogs with various C-1 substituents: methyl (2), ethyl (3), n-propyl (4), n-pentyl (5), and phenyl (6). Analog 2 was equipotent to cocaine as an inhibitor of the dopamine transporter (DAT), whereas 3 and 6 were 3- and 10-fold more potent, respectively. None of the analogs, however, stimulated mouse locomotor activity, in contrast...

  20. Physical analogy between continuum thermodynamics and classical mechanics. (United States)

    Umantsev, Alex


    The main focus of this paper is the profound physical analogy between a continuum thermodynamical system, which evolves with relaxation under (possibly) nonisothermal conditions, and a classical mechanical system of a few interacting particles moving with dissipation in (possibly), time-dependent nonconservative fields. This analogy is applied to the problem of phase transitions in a one-dimensional thermodynamic system. The thermomechanical analogy stems from the validity of variational methods in mechanics and thermodynamics and allows for a different interpretation of the dynamical selection principle in the theory of pattern formation. This physical analogy is very helpful for understanding different nonlinear thermodynamic phenomena and for developing intuition in numerical simulations.

  1. CRC handbook of neurohypophyseal hormone analogs. Volume 2

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

    Densmore, Jeffery D [Los Alamos National Laboratory; Hykes, Joshua M [Los Alamos National Laboratory


    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.

  3. 25th workshop on Advances in Analog Circuit Design

    CERN Document Server

    Harpe, Pieter; Makinwa, Kofi


    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.

  4. Analog-digital converters for industrial applications including an introduction to digital-analog converters

    CERN Document Server

    Ohnhäuser, Frank


    This book offers students and those new to the topic of analog-to-digital converters (ADCs) a broad introduction, before going into details of the state-of-the-art design techniques for SAR and DS converters, including the latest research topics, which are valuable for IC design engineers as well as users of ADCs in applications. The book then addresses important topics, such as correct connectivity of ADCs in an application, the verification, characterization and testing of ADCs that ensure high-quality end products. Analog-to-digital converters are the central element in any data processing system and regulation loops such as modems or electrical motor drives. They significantly affect the performance and resolution of a system or end product. System development engineers need to be familiar with the performance parameters of the converters and understand the advantages and disadvantages of the various architectures. Integrated circuit development engineers have to overcome the problem of achieving high per...

  5. Comparative Study of the Effect of Baicalin and Its Natural Analogs on Neurons with Oxygen and Glucose Deprivation Involving Innate Immune Reaction of TLR2/TNFα

    Directory of Open Access Journals (Sweden)

    Hui-Ying Li


    Full Text Available This work is to study the baicalin and its three analogs, baicalin, wogonoside, and wogonin, on the protective effect of neuron from oxygen-glucose deprivation (OGD and toll-like receptor 2 (TLR2 expression in OGD damage. The results showed that baicalin and its three analogs did protect neurons from OGD damage and downregulated protein level of TLR2. D-Glucopyranosiduronic acid on site 7 in the structure played a core of cytotoxicity of these flavonoid analogs. The methoxyl group on carbon 8 of the structure had the relation with TLR2 protein expression, as well as the anti-inflammation. In addition, we detected caspase3 and antioxidation capability, to investigate the effect of four analogs on cell apoptosis and total antioxidation competence in OGD model.

  6. Partitioning, diffusion, and ligand binding of raft lipid analogs in model and cellular plasma membranes. (United States)

    Sezgin, Erdinc; Levental, Ilya; Grzybek, Michal; Schwarzmann, Günter; Mueller, Veronika; Honigmann, Alf; Belov, Vladimir N; Eggeling, Christian; Coskun, Unal; Simons, Kai; Schwille, Petra


    Several simplified membrane models featuring coexisting liquid disordered (Ld) and ordered (Lo) lipid phases have been developed to mimic the heterogeneous organization of cellular membranes, and thus, aid our understanding of the nature and functional role of ordered lipid-protein nanodomains, termed "rafts". In spite of their greatly reduced complexity, quantitative characterization of local lipid environments using model membranes is not trivial, and the parallels that can be drawn to cellular membranes are not always evident. Similarly, various fluorescently labeled lipid analogs have been used to study membrane organization and function in vitro, although the biological activity of these probes in relation to their native counterparts often remains uncharacterized. This is particularly true for raft-preferring lipids ("raft lipids", e.g. sphingolipids and sterols), whose domain preference is a strict function of their molecular architecture, and is thus susceptible to disruption by fluorescence labeling. Here, we analyze the phase partitioning of a multitude of fluorescent raft lipid analogs in synthetic Giant Unilamellar Vesicles (GUVs) and cell-derived Giant Plasma Membrane Vesicles (GPMVs). We observe complex partitioning behavior dependent on label size, polarity, charge and position, lipid headgroup, and membrane composition. Several of the raft lipid analogs partitioned into the ordered phase in GPMVs, in contrast to fully synthetic GUVs, in which most raft lipid analogs mis-partitioned to the disordered phase. This behavior correlates with the greatly enhanced order difference between coexisting phases in the synthetic system. In addition, not only partitioning, but also ligand binding of the lipids is perturbed upon labeling: while cholera toxin B binds unlabeled GM1 in the Lo phase, it binds fluorescently labeled GMI exclusively in the Ld phase. Fluorescence correlation spectroscopy (FCS) by stimulated emission depletion (STED) nanoscopy on intact

  7. Design of an active ultrastable single-chain insulin analog: synthesis, structure, and therapeutic implications. (United States)

    Hua, Qing-xin; Nakagawa, Satoe H; Jia, Wenhua; Huang, Kun; Phillips, Nelson B; Hu, Shi-quan; Weiss, Michael A


    Single-chain insulin (SCI) analogs provide insight into the inter-relation of hormone structure, function, and dynamics. Although compatible with wild-type structure, short connecting segments (design, structure, and function of a single-chain insulin analog (SCI-57) containing a 6-residue linker (GGGPRR). Native receptor-binding affinity (130 +/- 8% relative to the wild type) is achieved as hindrance by the linker is offset by favorable substitutions in the insulin moiety. The thermodynamic stability of SCI-57 is markedly increased (DeltaDeltaG(u) = 0.7 +/- 0.1 kcal/mol relative to the corresponding two-chain analog and 1.9 +/- 0.1 kcal/mol relative to wild-type insulin). Analysis of inter-residue nuclear Overhauser effects demonstrates that a native-like fold is maintained in solution. Surprisingly, the glycine-rich connecting segment folds against the insulin moiety: its central Pro contacts Val(A3) at the edge of the hydrophobic core, whereas the final Arg extends the A1-A8 alpha-helix. Comparison between SCI-57 and its parent two-chain analog reveals striking enhancement of multiple native-like nuclear Overhauser effects within the tethered protein. These contacts are consistent with wild-type crystal structures but are ordinarily attenuated in NMR spectra of two-chain analogs, presumably due to conformational fluctuations. Linker-specific damping of fluctuations provides evidence for the intrinsic flexibility of an insulin monomer. In addition to their biophysical interest, ultrastable SCIs may enhance the safety and efficacy of insulin replacement therapy in the developing world.

  8. The interplay of conflict and analogy in multidisciplinary teams. (United States)

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


    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.

  9. Analog circuit design techniques at 0.5V

    CERN Document Server

    Chatterjee, Shouri; Stanic, Nebojša


    This book tackles challenges for the design of analog integrated circuits that operate from ultra-low power supply voltages (down to 0.5V). Coverage demonstrates the signal processing circuit and circuit biasing approaches through the design of operational transconductance amplifiers (OTAs). These amplifiers are then used to build analog system functions including continuous time filter and a sample and hold amplifier.

  10. Analogical Reasoning in the Classroom: Insights from Cognitive Science (United States)

    Vendetti, Michael S.; Matlen, Bryan J.; Richland, Lindsey E.; Bunge, Silvia A.


    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…

  11. Q-Analogies: A Test of Quantitative Reasoning. (United States)

    Chase, Clinton I.; Johnson, Judith J.

    The initial steps necessary for constructing an analogies test are described. Basic mathematics being the context, the aim of the test is to predict student performance in research statistics courses characteristic of graduate education and social science programs. Items involving analogies in a quantitative context were built, sorted into two…

  12. Analog modeling of transient moisture flow in unsaturated soil

    NARCIS (Netherlands)

    Wind, G.P.


    Hydraulic and electronic analog models are developed for the simulation of moisture flow and accumulation in unsaturated soil. The analog models are compared with numerical models and checked with field observations. Application of soil physical knowledge on a soil technological problem by means of

  13. Physical properties and structure of enzymatically synthesized amylopectin analogs

    NARCIS (Netherlands)

    Ciric, Jelena; Woortman, Albert J. J.; Gordiichuk, Pavlo; Stuart, Marc C. A.; Loos, Katja


    The mechanism of the enzymatic polymerization of amylopectin analogs with phosphorylase b and glycogen branching enzyme is very intriguing. Recently, size exclusion chromatography with multi-detection of enzymatically synthesized amylopectin analogs in combination with MALDI-ToF MS analysis of enzym

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

    NARCIS (Netherlands)

    Ning, Zhen-Qiu; Mouthaan, Ton; Wallinga, Hans


    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 impleme

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

    DEFF Research Database (Denmark)

    Bruun, Erik; Olesen, Ole


    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 by a spe...

  16. Using Analogies to Prevent Misconceptions about Chemical Equilibrium (United States)

    Sahin Pekmez, Esin


    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)…

  17. Stereoselective synthesis of nicotinamide beta-riboside and nucleoside analogs. (United States)

    Franchetti, Palmarisa; Pasqualini, Michela; Petrelli, Riccardo; Ricciutelli, Massimo; Vita, Patrizia; Cappellacci, Loredana


    The beta-anomers of N-ribofuranosylnicotine-3-carboxamide (beta-NAR) and its nicotinic acid analog (beta-NaR) were obtained by stereoselective synthesis via glycosylation of the presilylated bases under Vorbruggen's protocol. A NAR analog, methylated in position 3 of the ribosylic moiety, is also reported.

  18. 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.

  19. Insulin analogs and cancer: A note of caution

    NARCIS (Netherlands)

    J.A.M.J.L. Janssen (Joseph); A.J. Varewijck (Aimee)


    textabstractIn view of the lifelong exposure and large patient populations involved, insulin analogs with an increased mitogenic effect in comparison to human insulin may potentially constitute a major health problem, since these analogs may possibly induce the growth of pre-existing neoplasms. At p

  20. 47 CFR 74.705 - TV broadcast analog station protection. (United States)


    ... 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...

  1. Radiolabeled somatostatin analogs in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, M.L.; Kolan, H.; Li, J.; Wiaderkiewicz, R.; Pallela, V.R.; Duggaraju, R.; Schally, A.V


    Vapreotide (RC-160), a somatostatin analog, was labeled with {sup 99m}Tc by a direct method and also by using CPTA [1,4,8,11-tetraazacyclotetradecane] as a bifunctional chelating agent. The labeled compounds were evaluated in nude mice bearing experimental human prostate cancers. In these studies, {sup 111}In-DTPA-D-Phe-Octreotide ({sup 111}In-DTPA-octreotide) served as a standard and {sup 99m}Tc-oxytocin as a receptor-non-specific control. {sup 99m}Tc-octreotide was also used. The 24 htumor uptake of {sup 99m}Tc-RC-160 was nearly 400% higher, (p < 0.05), than that of {sup 111}In-DTPA-octreotide and diminished upon receptor blocking. In all tissues except the kidneys, the uptake of {sup 99m}Tc-RC-160 was also higher than that of {sup 111}In-DTPA-octreotide. The uptake of {sup 99m}Tc-RC-160 was influenced by the amount of peptide injected and the best tumor/muscle and tumor/blood ratios were obtained when only one {mu}g of the peptide (200 Ci/mmol) was administered.

  2. Serial Pixel Analog-to-Digital Converter

    Energy Technology Data Exchange (ETDEWEB)

    Larson, E D


    This method reduces the data path from the counter to the pixel register of the analog-to-digital converter (ADC) from as many as 10 bits to a single bit. The reduction in data path width is accomplished by using a coded serial data stream similar to a pseudo random number (PRN) generator. The resulting encoded pixel data is then decoded into a standard hexadecimal format before storage. The high-speed serial pixel ADC concept is based on the single-slope integrating pixel ADC architecture. Previous work has described a massively parallel pixel readout of a similar architecture. The serial ADC connection is similar to the state-of-the art method with the exception that the pixel ADC register is a shift register and the data path is a single bit. A state-of-the-art individual-pixel ADC uses a single-slope charge integration converter architecture with integral registers and “one-hot” counters. This implies that parallel data bits are routed among the counter and the individual on-chip pixel ADC registers. The data path bit-width to the pixel is therefore equivalent to the pixel ADC bit resolution.

  3. The MARS2013 Mars analog mission. (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


    We report on the MARS2013 mission, a 4-week Mars analog field test in the northern Sahara. Nineteen experiments were conducted by a field crew in Morocco under simulated martian surface exploration conditions, supervised by a Mission Support Center in Innsbruck, Austria. A Remote Science Support team analyzed field data in near real time, providing planning input for the management of a complex system of field assets; two advanced space suit simulators, four robotic vehicles, an emergency shelter, and a stationary sensor platform in a realistic work flow were coordinated by a Flight Control Team. A dedicated flight planning group, external control centers for rover tele-operations, and a biomedical monitoring team supported the field operations. A 10 min satellite communication delay and other limitations pertinent to human planetary surface activities were introduced. The fields of research for the experiments were geology, human factors, astrobiology, robotics, tele-science, exploration, and operations research. This paper provides an overview of the geological context and environmental conditions of the test site and the mission architecture, in particular the communication infrastructure emulating the signal travel time between Earth and Mars. We report on the operational work flows and the experiments conducted, including a deployable shelter prototype for multiple-day extravehicular activities and contingency situations.

  4. Amino acid analogs for tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Mark M. (Atlanta, GA); Shoup, Timothy (Decatur, GA)


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

  5. Amino acid analogs for tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Mark M. (Atlanta, GA); Shoup, Timothy (Decatur, GA)


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

  6. Amino acid analogs for tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, M.M.; Shoup, T.


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

  7. Somatostatin analog treatment of acromegaly: new aspects. (United States)

    Lamberts, S W; del Pozo, E


    Ten acromegalics received daily doses of 200-300 micrograms of a long-acting somatostatin analog, SMS 201-995 (Sandostatin, SMS), for an average of 64 weeks. Basal mean GH values of 44 +/- (SE) 7.8 ng/ml had fallen into the normal range at the end of the observation period (mean 64 weeks). This effect was accompanied by a substantial drop in somatomedin-C values. Reduction of pituitary tumor size could be documented in 3 of 6 patients. Whereas SMS did not affect high plasma PRL in 4 microprolactinoma patients, lactotrophs turned sensitive to this agent in mixed GH/PRL tumors. In a comparative study between SMS and bromocriptine, the former normalized circulating GH in 10 of 17 acromegalics in an acute trial, whereas bromocriptine was effective in only 5. A combination of both substances was effective in 2 of 3 patients who were insensitive to single drug administration. Cultures of GH-secreting tumor cells showed a statistically significant hormone decrease in the medium when exposed to SMS. However, in some instances, a diminution of the GH contents of the tumor cells was also observed, presumably as the basis for intracellular breakdown and clinical tumor shrinkage.

  8. Natural CO2 Analogs for Carbon Sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Scott H. Stevens; B. Scott Tye


    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.

  9. Amino acid analogs for tumor imaging (United States)

    Goodman, M.M.; Shoup, T.


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

  10. Biosynthesis of sphinganine-analog mycotoxins. (United States)

    Du, L; Zhu, X; Gerber, R; Huffman, J; Lou, L; Jorgenson, J; Yu, F; Zaleta-Rivera, K; Wang, Q


    Sphinganine-analog mycotoxins (SAMT) are polyketide-derived natural products produced by a number of plant pathogenic fungi and are among the most economically important mycotoxins. The toxins are structurally similar to sphinganine, a key intermediate in the biosynthesis of ceramides and sphingolipids, and competitive inhibitors for ceramide synthase. The inhibition of ceramide and sphingolipid biosynthesis is associated with several fatal diseases in domestic animals and esophageal cancer and neural tube defects in humans. SAMT contains a highly reduced, acyclic polyketide carbon backbone, which is assembled by a single module polyketide synthase. The biosynthesis of SAMT involves a unique polyketide chain-releasing mechanism, in which a pyridoxal 5'-phosphate-dependent enzyme catalyzes the termination, offloading and elongation of the polyketide chain. This leads to the introduction of a new carbon-carbon bond and an amino group to the polyketide chain. The mechanism is fundamentally different from the thioesterase/cyclase-catalyzed polyketide chain releasing found in bacterial and other fungal polyketide biosynthesis. Genetic data suggest that the ketosynthase domain of the polyketide synthase and the chain-releasing enzyme are important for controlling the final product structure. In addition, several post-polyketide modifications have to take place before SAMT become mature toxins.

  11. HERE, THERE, AND EVERYWHEREPublic Science Through Analogy (United States)

    Arcand, Kimberly K.


    Here, There, and Everywhere (HTE) is a program that consists of a series of exhibitions, posters, and supporting hands-on activities that utilize analogies in the teaching of science, engineering, and technology to provide multi-generational and family-friendly content in English and Spanish to small community centers, libraries, under-resourced small science centers. The purpose of the program is to connect crosscutting science content (in Earth, atmospheric and planetary sciences and astrophysics) with everyday phenomena. By using different modes of content delivery, from physical exhibits and handouts,to interpretive stations, facilitated activities for educators, and online resources, HTE helps to demonstrate the universality of physical laws and the connection between our everyday world and the universe as a whole to members of the public who may not identify strongly with science. HTE is part of a series of public science projects created and developed by the Education and Public Outreach group at the Chandra X-ray Center. The authors discuss how HTE fits into the lineage of public science outreach that aims to engage the greater public in non-traditional venues for science learning and appreciation, as well as what might be learned about the participants of such projects.

  12. Natural Analog Studies at Pena Blanca, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    A.M. Simmons


    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.

  13. Nonpeptide somatostatin analogs: recent advances in its application and research

    Institute of Scientific and Technical Information of China (English)


    Along with its wide anatomical distribution, somatostatin (SST) acts on multiple targets via a family of 5 receptors to produce a broad spectrum of biological effects. Therefore, a variety of peptide analogs have been produced and are widely used in clinical treatment. However, because of their flaws in the structure of peptide, the clinical efficacy is limited. In this review, we summarize the structure, pharmacological effects and the potential clinical value of non-peptide SST analogs. We focus on the research and development of non-peptide SST analogs since 1998, and discuss the problems and potential prospects for non-peptide SST analogs. We believe that as more non-peptide somatostatin analogs are successfully developed, the extensive clinical application of SSTs will contribute a great deal to medical science.

  14. Learning Plate Tectonics Using a Pre-Analogy Step (United States)

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


    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.

  15. NASA HRP Immunology Discipline - Use of Terrestrial Analogs (United States)

    Crucian, Brian


    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

  16. The Recognition of Glycolate Oxidase Apoprotein with Flavin Analogs in Higher Plants

    Institute of Scientific and Technical Information of China (English)

    Wei-Jun WANG; Jing-Quan HUANG; Chong YANG; Jiu-Jiu HUANG; Ming-Qi LI


    The dependence of glycolate oxidase apoprotein (apoGO) activity on flavin analogs was surveyed in 9 higher plants from 7 families. Activities of all apoGOs depended not only on flavin mononucleotide (FMN) but also on flavin adenine dinucleotide (FAD), but not on riboflavin. The kinetic analysis showed that FMN was the optimum cofactor for apoGO from leaves ofBrassica campestris. In plant kingdom,FMN, FAD and riboflavin are three flavin analogs with very similar structure, and they could coexist and be inter-converted from each other, so the question is how the apoprotein of glycolate oxidase (GO) recognized these flavin analogs. No inhibition effect of riboflavin on the activity ofapoGO with FMN or FAD was found and no obvious quenching of riboflavin or apoGO protein fluorescence was detected with the addition of apoGO or riboflavin, respectively. These results indicated that riboflavin did not bind to apoGO tightly like FMN and FAD. Inorganic phosphate (Pi) did inhibit the activity of GO, and kinetic analysis revealed that this inhibition was caused by the competitive binding to apoGO between Pi and FMN. This competitive binding was further confirmed by the inhibition of Pi to the quenching of FMN and apoGO protein fluorescence with apoGO and FMN, respectively. It was suggested that the 5′-phosphate group of FMN or FAD may play a key role in the recognition and binding of riboflavin analog cofactors with apoGO.

  17. Using analogy role-play activity in an undergraduate biology classroom to show central dogma revision. (United States)

    Takemura, Masaharu; Kurabayashi, Mario


    For the study of biology in an undergraduate classroom, a classroom exercise was developed: an analogy role-play to learn mechanisms of gene transcription and protein translation (central dogma). To develop the central dogma role-play exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress hanger, and amino acids using Lego® blocks (Lego System A/S, Denmark). Students were studying in the course of mathematics, physics, or chemistry, so biology was not among their usual studies. In this exercise, students perform the central dogma role-play and respectively act out nuclear matrix proteins, a transcription factor, an RNA polymerase II, an mRNA transport protein, nuclear pore proteins, a large ribosomal subunit, a small ribosomal subunit, and several amino-acyl tRNA synthetases. Questionnaire results obtained after the activity show that this central dogma role-play analogy holds student interest in the practical molecular biological processes of transcription and translation.

  18. De Analogía a Digitalia

    Directory of Open Access Journals (Sweden)

    Dr. Xaime Fandiño Alonso


    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

  19. Current-mode analog nonlinear function synthesizer structures

    CERN Document Server

    Popa, Cosmin Radu


    This book is dedicated to the analysis and design of analog CMOS nonlinear function synthesizer structures, based on original superior-order approximation functions. A variety of analog function synthesizer structures are discussed, based on accurate approximation functions.  Readers will be enabled to implement numerous circuit functions with applications in analog signal processing, including exponential, Gaussian or hyperbolic functions. Generalizing the methods for obtaining these particular functions, the author analyzes superior-order approximation functions, which represent the core for developing CMOS analog nonlinear function synthesizers.   ·         Describes novel methods for generating a multitude of circuit functions, based on superior-order improved accuracy approximation functions; ·         Presents techniques for analog function synthesizers that can be applied easily to a wide variety of analog signal processing circuits; ·         Enables the design of analog s...

  20. Structure-activity analysis of thiourea analogs as inhibitors of UT-A and UT-B urea transporters. (United States)

    Esteva-Font, Cristina; Phuan, Puay-Wah; Lee, Sujin; Su, Tao; Anderson, Marc O; Verkman, A S


    Small-molecule inhibitors of urea transporter (UT) proteins in kidney have potential application as novel salt-sparing diuretics. The urea analog dimethylthiourea (DMTU) was recently found to inhibit the UT isoforms UT-A1 (expressed in kidney tubule epithelium) and UT-B (expressed in kidney vasa recta endothelium) with IC50 of 2-3 mM, and was shown to have diuretic action when administered to rats. Here, we measured UT-A1 and UT-B inhibition activity of 36 thiourea analogs, with the goal of identifying more potent and isoform-selective inhibitors, and establishing structure-activity relationships. The analog set systematically explored modifications of substituents on the thiourea including alkyl, heterocycles and phenyl rings, with different steric and electronic features. The analogs had a wide range of inhibition activities and selectivities. The most potent inhibitor, 3-nitrophenyl-thiourea, had an IC50 of ~0.2 mM for inhibition of both UT-A1 and UT-B. Some analogs such as 4-nitrophenyl-thiourea were relatively UT-A1 selective (IC50 1.3 vs. 10 mM), and others such as thioisonicotinamide were UT-B selective (IC50>15 vs. 2.8 mM).


    Elsila, J. E.; Bernstein, M. P.; Sanford, S. A.


    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.

  2. Josephson junction analog and quasiparticle-pair current

    DEFF Research Database (Denmark)

    Bak, Christen Kjeldahl; Pedersen, Niels Falsig


    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 curren....... 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...

  3. Braneworld physics from the analog-gravity perspective

    CERN Document Server

    Barcelo, C; Barcelo, Carlos; Campos, Antonio


    We study Randall-Sundrum brane models from the viewpoint of condensed matter/quantum optics. Following the idea of analog gravity we obtain effective metrics in fluid and Bose-Einstein-condensate systems mimicking those in the brane framework. We see that the effect of warp factors in the bulk geometry translates into finite-size of the analog systems. We stress that many open questions in braneworld physics can benefit from the understanding of critical phenomena of surfaces in finite analog systems.

  4. A radial basis function neurocomputer implemented with analog VLSI circuits (United States)

    Watkins, Steven S.; Chau, Paul M.; Tawel, Raoul


    An electronic neurocomputer which implements a radial basis function neural network (RBFNN) is described. The RBFNN is a network that utilizes a radial basis function as the transfer function. The key advantages of RBFNNs over existing neural network architectures include reduced learning time and the ease of VLSI implementation. This neurocomputer is based on an analog/digital hybrid design and has been constructed with both custom analog VLSI circuits and a commercially available digital signal processor. The hybrid architecture is selected because it offers high computational performance while compensating for analog inaccuracies, and it features the ability to model large problems.

  5. Airframe Noise Prediction by Acoustic Analogy: Revisited (United States)

    Farassat, F.; Casper, Jay H.; Tinetti, A.; Dunn, M. H.


    The present work follows a recent survey of airframe noise prediction methodologies. In that survey, Lighthill s acoustic analogy was identified as the most prominent analytical basis for current approaches to airframe noise research. Within this approach, a problem is typically modeled with the Ffowcs Williams and Hawkings (FW-H) equation, for which a geometry-independent solution is obtained by means of the use of the free-space Green function (FSGF). Nonetheless, the aeroacoustic literature would suggest some interest in the use of tailored or exact Green s function (EGF) for aerodynamic noise problems involving solid boundaries, in particular, for trailing edge (TE) noise. A study of possible applications of EGF for prediction of broadband noise from turbulent flow over an airfoil surface and the TE is, therefore, the primary topic of the present work. Typically, the applications of EGF in the literature have been limited to TE noise prediction at low Mach numbers assuming that the normal derivative of the pressure vanishes on the airfoil surface. To extend the application of EGF to higher Mach numbers, the uniqueness of the solution of the wave equation when either the Dirichlet or the Neumann boundary condition (BC) is specified on a deformable surface in motion. The solution of Lighthill s equation with either the Dirichlet or the Neumann BC is given for such a surface using EGFs. These solutions involve both surface and volume integrals just like the solution of FW-H equation using FSGF. Insight drawn from this analysis is evoked to discuss the potential application of EGF to broadband noise prediction. It appears that the use of a EGF offers distinct advantages for predicting TE noise of an airfoil when the normal pressure gradient vanishes on the airfoil surface. It is argued that such an approach may also apply to an airfoil in motion. However, for the prediction of broadband noise not directly associated with a trailing edge, the use of EGF does not

  6. A Simple Hydraulic Analog Model of Oxidative Phosphorylation. (United States)

    Willis, Wayne T; Jackman, Matthew R; Messer, Jeffrey I; Kuzmiak-Glancy, Sarah; Glancy, Brian


    Mitochondrial oxidative phosphorylation is the primary source of cellular energy transduction in mammals. This energy conversion involves dozens of enzymatic reactions, energetic intermediates, and the dynamic interactions among them. With the goal of providing greater insight into the complex thermodynamics and kinetics ("thermokinetics") of mitochondrial energy transduction, a simple hydraulic analog model of oxidative phosphorylation is presented. In the hydraulic model, water tanks represent the forward and back "pressures" exerted by thermodynamic driving forces: the matrix redox potential (ΔGredox), the electrochemical potential for protons across the mitochondrial inner membrane (ΔGH), and the free energy of adenosine 5'-triphosphate (ATP) (ΔGATP). Net water flow proceeds from tanks with higher water pressure to tanks with lower pressure through "enzyme pipes" whose diameters represent the conductances (effective activities) of the proteins that catalyze the energy transfer. These enzyme pipes include the reactions of dehydrogenase enzymes, the electron transport chain (ETC), and the combined action of ATP synthase plus the ATP-adenosine 5'-diphosphate exchanger that spans the inner membrane. In addition, reactive oxygen species production is included in the model as a leak that is driven out of the ETC pipe by high pressure (high ΔGredox) and a proton leak dependent on the ΔGH for both its driving force and the conductance of the leak pathway. Model water pressures and flows are shown to simulate thermodynamic forces and metabolic fluxes that have been experimentally observed in mammalian skeletal muscle in response to acute exercise, chronic endurance training, and reduced substrate availability, as well as account for the thermokinetic behavior of mitochondria from fast- and slow-twitch skeletal muscle and the metabolic capacitance of the creatine kinase reaction.

  7. In vivo conditions to identify Prkci phosphorylation targets using the analog-sensitive kinase method in zebrafish.

    Directory of Open Access Journals (Sweden)

    Elena Cibrián Uhalte

    Full Text Available Protein kinase C iota is required for various cell biological processes including epithelial tissue polarity and organ morphogenesis. To gain mechanistic insight into different roles of this kinase, it is essential to identify specific substrate proteins in their cellular context. The analog-sensitive kinase method provides a powerful tool for the identification of kinase substrates under in vivo conditions. However, it has remained a major challenge to establish screens based on this method in multicellular model organisms. Here, we report the methodology for in vivo conditions using the analog-sensitive kinase method in a genetically-tractable vertebrate model organism, the zebrafish. With this approach, kinase substrates can uniquely be labeled in the developing zebrafish embryo using bulky ATPγS analogs which results in the thiophosphorylation of substrates. The labeling of kinase substrates with a thiophosphoester epitope differs from phosphoesters that are generated by all other kinases and allows for an enrichment of thiophosphopeptides by immunoaffinity purification. This study provides the foundation for using the analog-sensitive kinase method in the context of complex vertebrate development, physiology, or disease.

  8. A Novel cooked extruded lentils analog: physical and chemical properties. (United States)

    Abu-Ghoush, Mahmoud; Alavi, Sajid; Al-Shathri, Abdulaziz


    Developing an extruded lentil analog is our aim. Lentil analog with six formulations were produced using a pilot-scale single (SS) and twin screw (TS) extruders. Texture analysis of lentil analogs prepared for consumption revealed that the products formulated with 60:40 and 70:30 soy: wheat ratios exhibited a significantly higher hardness, adhesiveness and lower springiness as compared to all other treatments. Differential Scanning Calorimeter (DSC) results indicated that all starches in dry blend are completely 100 % gelatinized by extrusion for all treatments at 100 °C. The maximum peak of viscosity for TS was formed after 5.58 min. from the run at 89.9 °C for the best treatment. However, this lentil analog product can provide a high quality lentil which can be used as a substitute for regular lentils.

  9. Reference-Free CMOS Pipeline Analog-to-Digital Converters

    CERN Document Server

    Figueiredo, Michael; Evans, Guiomar


    This book shows that digitally assisted analog-to-digital converters are not the only way to cope with poor analog performance caused by technology scaling. It describes various analog design techniques that enhance the area and power efficiency without employing any type of digital calibration circuitry. These techniques consist of self-biasing for PVT enhancement, inverter-based design for improved speed/power ratio, gain-of-two obtained by voltage sum instead of charge redistribution, and current-mode reference shifting instead of voltage reference shifting. Together, these techniques allow enhancing the area and power efficiency of the main building blocks of a multiplying digital-to-analog converter (MDAC) based stage, namely, the flash quantizer, the amplifier, and the switched capacitor network of the MDAC. Complementing the theoretical analyses of the various techniques, a power efficient operational transconductance amplifier is implemented and experimentally characterized. Furthermore, a medium-low ...

  10. Digitoxin and its analogs as novel cancer therapeutics

    Directory of Open Access Journals (Sweden)

    Elbaz Hosam A


    Full Text Available Abstract A growing body of evidence indicates that digitoxin cardiac glycoside is a promising anticancer agent when used at therapeutic concentrations. Digitoxin has a prolonged half-life and a well-established clinical profile. New scientific avenues have shown that manipulating the chemical structure of the saccharide moiety of digitoxin leads to synthetic analogs with increased cytotoxic activity. However, the anticancer mechanism of digitoxin or synthetic analogs is still subject to study while concerns about digitoxin's cardiotoxicity preclude its clinical application in cancer therapeutics. This review focuses on digitoxin and its analogs, and their cytotoxicity against cancer cells. Moreover, a new perspective on the pharmacological aspects of digitoxin and its analogs is provided to emphasize new research directions for developing potent chemotherapeutic drugs.

  11. Analog and digital signal analysis from basics to applications

    CERN Document Server

    Cohen Tenoudji, Frédéric


    This book provides comprehensive, graduate-level treatment of analog and digital signal analysis suitable for course use and self-guided learning. This expert text guides the reader from the basics of signal theory through a range of application tools for use in acoustic analysis, geophysics, and data compression. Each concept is introduced and explained step by step, and the necessary mathematical formulae are integrated in an accessible and intuitive way. The first part of the book explores how analog systems and signals form the basics of signal analysis. This section covers Fourier series and integral transforms of analog signals, Laplace and Hilbert transforms, the main analog filter classes, and signal modulations. Part II covers digital signals, demonstrating their key advantages. It presents z and Fourier transforms, digital filtering, inverse filters, deconvolution, and parametric modeling for deterministic signals. Wavelet decomposition and reconstruction of non-stationary signals are also discussed...

  12. Analog implementation of pulse-coupled neural networks. (United States)

    Ota, Y; Wilamowski, B M


    This paper presents a compact architecture for analog CMOS hardware implementation of voltage-mode pulse-coupled neural networks (PCNN's). The hardware implementation methods shows inherent fault tolerance specialties and high speed, which is usually more than an order of magnitude over the software counterpart. A computational style described in this article mimics a biological neural network using pulse-stream signaling and analog summation and multiplication. Pulse-stream encoding technique uses pulse streams to carry information and control analog circuitry, while storing further analog information on the time axis. The main feature of the proposed neuron circuit is that the structure is compact, yet exhibiting all the basic properties of natural biological neurons. Functional and structural forms of neural and synaptic functions are presented along with simulation results. Finally, the proposed design is applied to image processing to demonstrate successful restoration of images and their features.

  13. Interaction of algorithm and implementation for analog VLSI stereo vision (United States)

    Hakkarainen, J. M.; Little, James J.; Lee, Hae-Seung; Wyatt, John L., Jr.


    Design of a high-speed stereo vision system in analog VLSI technology is reported. The goal is to determine how the advantages of analog VLSI--small area, high speed, and low power-- can be exploited, and how the effects of its principal disadvantages--limited accuracy, inflexibility, and lack of storage capacity--can be minimized. Three stereo algorithms are considered, and a simulation study is presented to examine details of the interaction between algorithm and analog VLSI implementation. The Marr-Poggio-Drumheller algorithm is shown to be best suited for analog VLSI implementation. A CCD/CMOS stereo system implementation is proposed, capable of operation at 6000 image frame pairs per second for 48 X 48 images, and faster than frame rate operation on 256 X 256 binocular image pairs.

  14. A Uniform Approach to Analogies, Synonyms, Antonyms, and Associations

    CERN Document Server

    Turney, Peter D


    Recognizing analogies, synonyms, antonyms, and associations appear to be four distinct tasks, requiring distinct NLP algorithms. In the past, the four tasks have been treated independently, using a wide variety of algorithms. These four semantic classes, however, are a tiny sample of the full range of semantic phenomena, and we cannot afford to create ad hoc algorithms for each semantic phenomenon; we need to seek a unified approach. We propose to subsume a broad range of phenomena under analogies. To limit the scope of this paper, we restrict our attention to the subsumption of synonyms, antonyms, and associations. We introduce a supervised corpus-based machine learning algorithm for classifying analogous word pairs, and we show that it can solve multiple-choice SAT analogy questions, TOEFL synonym questions, ESL synonym-antonym questions, and similar-associated-both questions from cognitive psychology.

  15. Wideband Analog Data System (WADS), system design document (United States)

    Brose, J. F.


    The Wideband Analog System (WADS) which performs post flight structural dynamic analysis of wideband FM data recorded during orbital flight tests is defined. Screening, reporting, and plotting steady state and transient wave analysis data are provided by WADS.

  16. A gravito-electromagnetic analogy based on tidal tensors

    CERN Document Server

    Costa, L F; Herdeiro, Carlos A. R.


    We propose a new approach to a physical analogy between General Relativity and Electromagnetism, based on comparing tidal tensors of both theories. Using this approach we write a covariant form for the gravitational analogues of the Maxwell equations, from which the regime of validity of the analogy becomes manifest. Two explicit realisations of the analogy are given. The first one matches linearised gravitational tidal tensors to exact electromagnetic tidal tensors in Minkwoski spacetime. The second one matches exact magnetic gravitational tidal tensors for ultra-stationary metrics to exact magnetic tidal tensors of electromagnetism in curved spaces. We then establish a new proof for a class of tensor identities that define invariants of the type $\\vec{E}^2-\\vec{B}^2$ and $\\vec{E}\\cdot\\vec{B}$, and we exhibit the invariants built from tidal tensors in both gravity and electromagnetism. We contrast our approach with the two gravito-electromagnetic analogies commonly found in the literature, which are reviewed...

  17. Energy Harvesting Using an Analog Circuit under Multimodal Vibration

    Directory of Open Access Journals (Sweden)

    Shigeru Shimose


    Full Text Available The efficiency of harvesting energy from a vibrating structure using a piezoelectric transducer and a simple analog circuit is investigated experimentally. This analog circuit was originally invented for a synchronized switch damping on inductor (SSDI technique, which enhances the damping of mechanical vibration. In this study, the circuit is used to implement a synchronized switch harvesting on inductor (SSHI technique. A multiple degree of freedom (MDOF structure is excited by single sinusoidal forces at its resonant frequencies and by random forces. The piezoelectric transducer converts this mechanical energy into electrical energy which is harvested using a standard rectifier bridge circuit with and without our analog circuit. Experimental results show that our analog circuit makes it possible to harvest twice as much energy under both single sinusoidal and random vibration excitations.

  18. Project Birdseye Aerial Photograph Collection: Digital and Analog Materials (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This collection consists of both analog and digital aerial photographs from Arctic areas in and around Baffin Bay, the Labrador Sea, the Arctic Ocean, the Beaufort...

  19. 22nd Workshop on Advances in Analog Circuit Design

    CERN Document Server

    Makinwa, Kofi; Harpe, Pieter


    This book is based on the 18 tutorials presented during the 22nd 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 frequency reference, power management for systems-on-chip, and smart wireless interfaces.  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 frequency reference, power management for systems-on-chip, and smart wireless interfaces.

  20. Unraveling the biochemistry and provenance of pupylation: a prokaryotic analog of ubiquitination

    Directory of Open Access Journals (Sweden)

    Aravind L


    Full Text Available Abstract Recently Mycobacterium tuberculosis was shown to possess a novel protein modification, in which a small protein Pup is conjugated to the epsilon-amino groups of lysines in target proteins. Analogous to ubiquitin modification in eukaryotes, this remarkable modification recruits proteins for degradation via archaeal-type proteasomes found in mycobacteria and allied actinobacteria. While a mycobacterial protein named PafA was found to be required for this conjugation reaction, its biochemical mechanism has not been elucidated. Using sensitive sequence profile comparison methods we establish that the PafA family proteins are related to the γ-glutamyl-cysteine synthetase and glutamine synthetase. Hence, we predict that PafA is the Pup ligase, which catalyzes the ATP-dependent ligation of the terminal γ-carboxylate of glutamate to lysines, similar to the above enzymes. We further discovered that an ortholog of the eukaryotic PAC2 (e.g. cg2106 is often present in the vicinity of the actinobacterial Pup-proteasome gene neighborhoods and is likely to represent the ancestral proteasomal chaperone. Pup-conjugation is sporadically present outside the actinobacteria in certain lineages, such as verrucomicrobia, nitrospirae, deltaproteobacteria and planctomycetes, and in the latter two lineages it might modify membrane proteins. Reviewers This article was reviewed by M. Madan Babu and Andrei Osterman

  1. In vitro and in vivo studies of the effects of halogenated histidine analogs on Plasmodium falciparum.


    Panton, L J; Rossan, R N; Escajadillo, A; Matsumoto, Y; Lee, A.T.; Labroo, V M; Kirk, K L; Cohen, L. A.; Aikawa, M.; Howard, R J


    The effects of four halogenated analogs of histidine on in vitro growth of Plasmodium falciparum malaria parasites were monitored by measurement of the incorporation of 3H-labeled amino acids into parasite proteins and by light and electron microscopy. The uptake of [3H]isoleucine was reduced to 50% of the control value by addition of 70 microM 2-fluoro-L-histidine (2-F-HIS) or 420 microM 2-iodo-L-histidine (2-I-HIS). [3H]histidine uptake into acid-insoluble material was affected equally by t...


    Directory of Open Access Journals (Sweden)

    Santi Noviasari


    Full Text Available ABSTRACTThe objective of this research was to produce rice analogue as functional food with low glycemic index. The rice was made from white corn and sorghum with additional soybean flour. The physicochemical properties of rice analogue being analysed were resistant starch content, total phenolic content, dietary fiber, color (L*, +a, +b values and whiteness (oHue. Rice analogue was potentially used as functional food indicated by high level of resistant starch 2.59%-3.31%, total phenolic content 0.18-0.25 mg GAE/g sample and dietary fiber 5.35%-6.14%. Rice analogue from white corn with and without soybean flour was further tested for glycemic index. Rice analogue from white corn has 69 GI value, while rice analogue from white corn with 10% soybean flour addition has 50 GI value.Keywords: functional food, glycemic index, rice analogueABSTRAKTujuan penelitian ini adalah untuk mendapatkan beras analog yang berpotensi sebagai pangan fungsional dan bernilai indeks glikemik rendah. Beras analog dibuat dari bahan baku jagung putih dan sorgum dengan penambahan tepung kedelai. Sifat fisiko kimia beras analog yang dianalisis adalah pati resisten, total fenol, serat pangan, warna (nilai L*, +a, +b dan derajat putih (oHue. Beras analog berpotensi sebagai pangan fungsional, yang ditunjukkan dengan tingginya kadar pati resisten yaitu sebanyak 2,59%-3,31%, total fenol sekitar 0,18-0,25 mg GAE/g sampel dan serat pangan antara 5,35%-6,14%. Beras analog berbahan baku jagung putih dengan dan tanpa penambahan kedelai dipilih untuk uji indeks glikemik. Beras analog dari jagung putih memiliki nilai IG 69 sedangkan beras analog dari jagung putih dengan penambahan tepung kedelai 10% memiliki nilai IG 50.Kata kunci: beras analog, indeks glikemik, pangan fungsional



    Hernandez, J. I. Gonzalez; Israelian, G.; Santos,N.C.; Sousa, S.; Delgado-Mena, E.; Neves, V.; Udry, S.


    We present a fully differential chemical abundance analysis using very high-resolution (R >~ 85,000) and very high signal-to-noise (S/N~800 on average) HARPS and UVES spectra of 7 solar twins and 95 solar analogs, 24 are planet hosts and 71 are stars without detected planets. The whole sample of solar analogs provide very accurate Galactic chemical evolution trends in the metalliciy range -0.3

  4. Chemical and physical effects in the bulk of cometary analogs (United States)

    Roessler, K.; Benit, Jean; Sauer, M.


    KOSI comet simulation experiments were designed as a macroscopic tester for the studies of physicochemical problems inherent to comet bodies. The analog samples consist of H2O and CO2 ice, organic admixtures, mineral dust, and carbon. Two of the fundamental changes the analogs undergo when submitted to 'insolation' by artificial sunlight, i.e., the diffusion of frozen gases and subsequent crust formation and the natural isotopic fractionation, are reported.

  5. Microwave assisted synthesis of 6-Substituted aminopurine analogs in water


    Qu, Guirong; Han,Suhui; Zhang,Zhiguang; Geng,Mingwei; Xue, Feng


    Microwave assisted amination of 6-chloropurine derivatives with various amines in water resulted in a "green chemistry" protocol for the preparation of 6-substituted aminopurine analogs in very good yields. Using a simply modified microwave oven with the refluxing apparatus, the amination of the 6-chloro in the purine structure occurred smoothly. 19 known and 16 unknown 6-substituted aminopurine analogs were prepared through nucleophilic aromatic substitution with simple filtration or column ...

  6. Error Models of the Analog to Digital Converters


    Michaeli Linus; Šaliga Ján


    Error models of the Analog to Digital Converters describe metrological properties of the signal conversion from analog to digital domain in a concise form using few dominant error parameters. Knowledge of the error models allows the end user to provide fast testing in the crucial points of the full input signal range and to use identified error models for post correction in the digital domain. The imperfections of the internal ADC structure determine the error characteristics represented by t...

  7. Analog readout modules for the ZEUS microvertex detector

    CERN Document Server

    Fusayasu, T


    Analog readout modules have been developed for a silicon microvertex detector of the electron-proton collision experiment ZEUS. Analog signals kept in the front end are read out and digitized by ADCs and processed afterwards to reduce the data volume while keeping the signal information. We have developed prototype modules with 10-bit 10 MHz ADCs and digital processors built in Field Programmable Gate Arrays. Their performance was investigated.

  8. Analog Filter Design Rules for Multilevel Polybinary Signaling Generation

    DEFF Research Database (Denmark)

    Vegas Olmos, Juan José; Cavallero, Francisco javier Vaquero; Tafur Monroy, Idelfonso


    Polybinary signaling has gained attention lately due to its generation simplicity and reduced spectral usage. This paper presents a study on the requirements for analog filters for the generation of multilevel polybinary signals with three to nine levels.......Polybinary signaling has gained attention lately due to its generation simplicity and reduced spectral usage. This paper presents a study on the requirements for analog filters for the generation of multilevel polybinary signals with three to nine levels....

  9. Fluorinated Analogs of Malachite Green: Synthesis and Toxicity

    Directory of Open Access Journals (Sweden)

    Bahram Parvin


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

  10. Structure- and isoform-specific glucuronidation of six curcumin analogs. (United States)

    Lu, Danyi; Liu, Hui; Ye, Wencai; Wang, Ying; Wu, Baojian


    1. In the present study, we aimed to characterize the glucuronidation of six curcumin analogs (i.e. RAO-3, RAO-8, RAO-9, RAO-18, RAO-19, and RAO-23) derived from galangal using human liver microsomes (HLM) and twelve expressed UGT enzymes. 2. Formation of glucuronide was confirmed using high-resolution mass spectrometry. Single glucuronide metabolite was generated from each of six curcumin analogs. The fragmentation patterns were analyzed and were found to differ significantly between alcoholic and phenolic glucuronides. 3. All six curcumin analogs except one (RAO-23) underwent significant glucuronidation in HLM and expressed UGT enzymes. In general, the methoxy group (close to the phenolic hydroxyl group) enhanced the glucuronidation liability of the curcumin analogs. 4. UGT1A9 and UGT2B7 were primarily responsible for the glucuronidation of two alcoholic analogs (RAO-3 and RAO-18). By contrast, UGT1A9 and four UGT2Bs (UGT2B4, 2B7, 2B15 and 2B17) played important roles in conjugating three phenolic analogs (RAO-8, RAO-9, and RAO-19). Interestingly, the conjugated double bonds system (in the aliphatic chain) was crucial to the substrate selectivity of gastrointestinal UGTs (i.e. UGT1A7, 1A8 and 1A10). 5. In conclusion, glucuronidation of six curcumin analogs from galangal were structure- and isoform-specific. The knowledge should be useful in identifying a curcumin analog with improved metabolic property.

  11. Direct (under) Sampling vs. Analog Downconversion for BPM Electroncs

    CERN Document Server

    Wendt, M


    Digital signal processing by means of undersampling the analog signal has become a popular method for acquiring beam position monitor signals. This presentation discusses the technique and its principle limitations, presents today’s technical limits (e.g. in terms of performance of available ADCs), and provides an outlook for the future. It will also try to compare the technique with more tradition analog downmixing and signal processing methods

  12. Cartographic distortions make dielectric spacetime analog models imperfect mimickers (United States)

    Fathi, Mohsen; Thompson, Robert T.


    It is commonly assumed that if the optical metric of a dielectric medium is identical to the metric of a vacuum space-time then light propagation through the dielectric mimics light propagation in the vacuum. However, just as the curved surface of the Earth cannot be mapped into a flat plane without distortion of some surface features, so too is it impossible to project the behavior of light from the vacuum into a dielectric analog residing in Minkowski space-time without introducing distortions. We study the covariance properties of dielectric analog space-times and the kinematics of a congruence of light in the analog, and show how certain features can be faithfully emulated in the analog depending on the choice of projection, but that not all features can be simultaneously emulated without distortion. These findings indicate conceptual weaknesses in the idea of using analog space-times as a basis for transformation optics, and we show that a certain formulation of transformation optics closely related to analog space-times resolves these issues.

  13. Glycolaldehyde in Perseus young solar analogs (United States)

    De Simone, M.; Codella, C.; Testi, L.; Belloche, A.; Maury, A. J.; Anderl, S.; André, Ph.; Maret, S.; Podio, L.


    Context. The earliest evolutionary stages of low-mass protostars are characterised by the so-called hot-corino stage, when the newly born star heats the surrounding material and enrich the gas chemically. Studying this evolutionary phase of solar protostars may help understand the evolution of prebiotic complex molecules in the development of planetary systems. Aims: In this paper we focus on the occurrence of glycolaldehyde (HCOCH2OH) in young solar analogs by performing the first homogeneous and unbiased study of this molecule in the Class 0 protostars of the nearby Perseus star forming region. Methods: We obtained sub-arcsec angular resolution maps at 1.3 mm and 1.4 mm of glycolaldehyde emission lines using the IRAM Plateau de Bure (PdB) interferometer in the framework of the CALYPSO IRAM large program. Results: Glycolaldehyde has been detected towards 3 Class 0 and 1 Class I protostars out of the 13 continuum sources targeted in Perseus: NGC 1333-IRAS2A1, NGC 1333-IRAS4A2, NGC 1333-IRAS4B1, and SVS13-A. The NGC 1333 star forming region looks particularly glycolaldehyde rich, with a rate of occurrence up to 60%. The glycolaldehyde spatial distribution overlaps with the continuum one, tracing the inner 100 au around the protostar. A large number of lines (up to 18), with upper-level energies Eu from 37 K up to 375 K has been detected. We derived column densities ≥1015 cm-2 and rotational temperatures Trot between 115 K and 236 K, imaging for the first time hot-corinos around NGC 1333-IRAS4B1 and SVS13-A. Conclusions: In multiple systems glycolaldehyde emission is detected only in one component. The case of the SVS13-A+B and IRAS4-A1+A2 systems support that the detection of glycolaldehyde (at least in the present Perseus sample) indicates older protostars (i.e. SVS13-A and IRAS4-A2), evolved enough to develop the hot-corino region (i.e. 100 K in the inner 100 au). However, only two systems do not allow us to firmly conclude whether the primary factor leading to

  14. Understanding Young Exoplanet Analogs with WISE (United States)

    Rice, Emily

    We propose to tackle outstanding questions about the fundamental properties of young brown dwarfs, which are atmospheric analogs to massive gas giant exoplanets, using public archive data from the Wide-field Infrared Survey Explorer (WISE) combined with our extensive dataset of optical and near-infrared observations, including spectra, proper motions, and parallaxes. Using WISE data we will construct color-color diagrams, color- magnitude diagrams, and spectral energy distributions for our sample of candidate young brown dwarfs. We will fully characterize the spectral properties of the candidates and evaluate their membership in nearby young moving groups in order to obtain independent age estimates. The practical outcomes of this project will allow the research community to use observed colors and spectra to reliably constrain the properties - including effective temperature, gravity, and dust/cloud properties - of both brown dwarfs and gas giant exoplanets. We will also search for new young brown dwarfs in the WISE archive using colors and proper motions. The expanded sample of young brown dwarfs will be used to create a self-contained feedback loop to identify and address the shortcomings of cool atmosphere models and low-mass evolutionary tracks, both of which are already being used to infer the properties of massive exoplanets. Disentangling the effects of physical parameters on the observed properties of young brown dwarfs is directly relevant to studies of exoplanets. Direct observations of exoplanets are currently very limited, and young brown dwarfs are the laboratories in which we can solve existing problems before the onslaught of new observations from instruments capable of directly imaging exoplanets, including the Gemini Planet Imager, Project 1640 at the Palomar Observatory, SPHERE on the VLT, and the James Webb Space Telescope. This project addresses the goal of the NASA Science Mission Directorate to discover how the universe works; in particular

  15. Analog Modeling of Continental Lithosphere Subduction (United States)

    Willingshofer, E.; Sokoutis, D.; Luth, S.; Beekman, F.; Cloetingh, S.


    Lithospheric-scale analog modeling sheds light on the consequences of decoupling within the continental lithosphere and along plate interfaces during continental collision. The model results provide valuable information in terms of strain localization, deformation of the subducting slab and the evolution and architecture of the overlying mountain belt and its topography. A weak layer has been implemented in three-layer models to simulate decoupling along the plate interface and at different levels of the lithosphere (brittle-ductile transition, entire lower crust, crust-mantle boundary). Additionally, varying the strength of the mantle lithosphere of both the upper as well as the lower plate regulated the degree of plate coupling. Plate boundaries were orthogonal to the convergence direction. All models emphasize that strong decoupling at the plate interface is a pre-requisite for the subduction of continental lithosphere. In addition, deformation of the subducting slab was found to be sensitive to the strength contrast between the subduction zone and the mantle lithosphere of the downgoing as well as the upper plate. As such, a low strength contrast between the plate interface and the lower plate leads to deformation of the subducting slab by thickening and the development of a shallow slab. Conversely, when the strength contrast is high, deep slabs evolve which undergo relatively less deformation. Furthermore, the level of decoupling in the downgoing plate governs how much continental crust is subducted together with the mantle lithosphere. Shallow decoupling, at the brittle-ductile transition, results in subduction of the lower crust whereas small amounts of lower crust are subducted when decoupling occurs at the level of the Moho. Weak plate coupling and a weak lower crust of the lower plate steer the evolution of mountain belts such that deformation propagates outward, in the direction of the incoming plate, by successive imbrication of upper crustal thrust

  16. The three and a half layers of dynamics : analog, digital, semi-digital, analog

    CERN Document Server

    Singh, T P


    Quantum theory is extremely successful in explaining most physical phenomena, and is not contradicted by any experiment. Yet, the theory has many puzzling features : the occurrence of probabilities, the unclear distinction between the microscopic and the macroscopic, the unexplained absence of superpositions in positions of macroscopic objects, the dependence of the theory on an external classical time, and the experimentally verified but peculiar `influence' outside the light-cone in EPR experiments. These puzzles point towards a conflict between quantum theory and our present understanding of spacetime structure, and suggest the existence of a deeper theory. In this essay we make the case that in the underlying theory the matter and spacetime degrees of freedom are non-commuting matrices, and yet the dynamics is analog. A digital quantum-theory like dynamics for matter as well as spacetime emerges in the statistical thermodynamic approximation to this deeper theory. When most of the matter clumps into macro...

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

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


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

  18. Enhancement of Peripheral Nerve Regrowth by the Purine Nucleoside Analog and Cell Cycle Inhibitor, Roscovitine (United States)

    Law, Vincent; Dong, Sophie; Rosales, Jesusa L.; Jeong, Myung-Yung; Zochodne, Douglas; Lee, Ki-Young


    Peripheral nerve regeneration is a slow process that can be associated with limited outcomes and thus a search for novel and effective therapy for peripheral nerve injury and disease is crucial. Here, we found that roscovitine, a synthetic purine nucleoside analog, enhances neurite outgrowth in neuronal-like PC12 cells. Furthermore, ex vivo analysis of pre-injured adult rat dorsal root ganglion (DRG) neurons showed that roscovitine enhances neurite regrowth in these cells. Likewise, in vivo transected sciatic nerves in rats locally perfused with roscovitine had augmented repopulation of new myelinated axons beyond the transection zone. By mass spectrometry, we found that roscovitine interacts with tubulin and actin. It interacts directly with tubulin and causes a dose-dependent induction of tubulin polymerization as well as enhances Guanosine-5′-triphosphate (GTP)-dependent tubulin polymerization. Conversely, roscovitine interacts indirectly with actin and counteracts the inhibitory effect of cyclin-dependent kinases 5 (Cdk5) on Actin-Related Proteins 2/3 (Arp2/3)-dependent actin polymerization, and thus, causes actin polymerization. Moreover, in the presence of neurotrophic factors such as nerve growth factor (NGF), roscovitine-enhanced neurite outgrowth is mediated by increased activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways. Since microtubule and F-actin dynamics are critical for axonal regrowth, the ability of roscovitine to activate the ERK1/2 and p38 MAPK pathways and support polymerization of tubulin and actin indicate a major role for this purine nucleoside analog in the promotion of axonal regeneration. Together, our findings demonstrate a therapeutic potential for the purine nucleoside analog, roscovitine, in peripheral nerve injury.

  19. Design and evaluation of novel interferon lambda analogs with enhanced antiviral activity and improved drug attributes

    Directory of Open Access Journals (Sweden)

    Yu D


    Full Text Available Debin Yu,1 Mingzhi Zhao,2 Liwei Dong,1 Lu Zhao,1 Mingwei Zou,3 Hetong Sun,4 Mengying Zhang,4 Hongyu Liu,4 Zhihua Zou1 1National Engineering Laboratory for AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, 2State Key Laboratory of Proteomics, National Engineering Research Center for Protein Drugs, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 3Department of Psychology, College of Liberal Arts and Social Sciences, University of Houston, Houston, TX, USA; 4Prosit Sole Biotechnology, Co., Ltd., Beijing, People’s Republic of China Abstract: Type III interferons (IFNs (also called IFN-λ: IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4 are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type I IFNs is weak, and unlike type I IFNs that are associated with severe and diverse side effects, type III IFNs cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointestinal viral infection. However, the antiviral potency of natural type III IFNs is weak compared to type I and, although IFN-λ3 possesses the highest bioactivity among the type III IFNs, IFN-λ1, instead of IFN-λ3, is being developed as a therapeutic drug due to the difficulty to express IFN-λ3 in the prokaryotic expression system. Here, to develop optimal IFN-λ molecules with improved drug attributes, we designed a series of IFN-λ analogs by replacing critical amino acids of IFN-λ1 with the IFN-λ3 counterparts, and vice versa. Four of the designed analogs were successfully expressed in Escherichia coli with high yield and were easily purified from inclusion bodies. Interestingly, all four analogs showed potent activity in inducing the

  20. Construction and characterization of an azurin analog for the purple copper site in cytochrome c oxidase. (United States)

    Hay, M; Richards, J H; Lu, Y


    A protein analog of a purple copper center has been constructed from a recombinant blue copper protein (Pseudomonas aeruginosa azurin) by replacing the loop containing the three ligands to the blue copper center with the corresponding loop of the CuA center in cytochrome c oxidase (COX) from Paracoccus denitrificans. The electronic absorption in the UV and visible region (UV-vis) and electron paramagnetic resonance (EPR) spectra of this analog are remarkably similar to those of the native CuA center in COX from Paracoccus denitrificans. The above spectra can be obtained upon addition of a mixture of Cu2+ and Cu+. Addition of Cu2+ only results in a UV-vis spectrum consisting of absorptions from both a purple copper center and a blue copper center. This spectrum can be converted to the spectrum of a pure purple copper by a prolonged incubation in the air, or by addition of excess ascorbate. The azurin mutant reported here is an example of an engineered purple copper center with the A480/A530 ratio greater than 1 and with no detectable hyperfines, similar to those of the CuA sites in COX of bovine heart and of Paracoccus denitrificans.

  1. PGE1 analog alprostadil induces VEGF and eNOS expression in endothelial cells. (United States)

    Haider, Dominik G; Bucek, Robert A; Giurgea, Aura G; Maurer, Gerald; Glogar, Helmut; Minar, Erich; Wolzt, Michael; Mehrabi, Mohammad R; Baghestanian, Mehrdad


    Endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor 1-alpha (HIF-1alpha) are important regulators of endothelial function, which plays a role in the pathophysiology of heart failure (HF). PGE1 analog treatment in patients with HF elicits beneficial hemodynamic effects, but the precise mechanisms have not been investigated. We have investigated the effects of the PGE1 analog alprostadil on eNOS, VEGF, and HIF-1alpha expression in human umbilical vein endothelial cells (HUVEC) using RT-PCR and immunoblotting under normoxic and hypoxic conditions. In addition, we studied protein expression by immunohistochemical staining in explanted hearts from patients with end-stage HF, treated or untreated with systemic alprostadil. Alprostadil causes an upregulation of eNOS and VEGF protein and mRNA expression in HUVEC and decreases HIF-1alpha. Hypoxia potently increased eNOS, VEGF, and HIF-1alpha synthesis. The alprostadil-induced upregulation of eNOS and VEGF was prevented by inhibition of MAPKs with PD-98056 or U-0126. Consistently, the expression of eNOS and VEGF was increased, and HIF-1alpha was reduced in failing hearts treated with alprostadil. The potent effects of alprostadil on endothelial VEGF and eNOS synthesis may be useful for patients with HF where endothelial dysfunction is involved in the disease process.

  2. An Optimized Analogy-Based Project Effort Estimation

    Directory of Open Access Journals (Sweden)

    Mohammad Azzeh


    Full Text Available despite the predictive performance of Analogy-Based Estimation (ABE in generating better effort estimates, there is no consensus on: (1 how to predetermine the appropriate number of analogies, (2 which adjustment technique produces better estimates. Yet, there is no prior works attempted to optimize both number of analogies and feature distance weights for each test project. Perhaps rather than using fixed number, it is better to optimize this value for each project individually and then adjust the retrieved analogies by optimizing and approximating complex relationships between features and reflects that approximation on the final estimate. The Artificial Bees Algorithm is utilized to find, for each test project, the appropriate number of closest projects and features distance weights that is used to adjust those analogies’ efforts. The proposed technique has been applied and validated to 8 publically datasets from PROMISE repository. Results obtained show that: (1 the predictive performance of ABE has noticeably been improved, (2 the number of analogies was remarkably variable for each test project. While there are many techniques to adjust ABE, Using optimization algorithm provides two solutions in one technique and appeared useful for datasets with complex structure.

  3. Bioisosteric phentolamine analogs as potent alpha-adrenergic antagonists. (United States)

    Hong, Seoung-Soo; Bavadekar, Supriya A; Lee, Sang-Il; Patil, Popat N; Lalchandani, S G; Feller, Dennis R; Miller, Duane D


    The synthesis and biological evaluation of a new series of bioisosteric phentolamine analogs are described. Replacement of the carbon next to the imidazoline ring of phentolamine with a nitrogen atom provides compounds (2, 3) that are about 1.6 times and 4.1 times more potent functionally than phentolamine on rat alpha1-adrenergic receptors, respectively. In receptor binding assays, the affinities of phentolamine and its bioisosteric analogs were determined on the human embryonic kidney (HEK) and Chinese Hamster ovary (CHO) cell lines expressing the human alpha1- and alpha2-AR subtypes, respectively. Analogs 2 and 3, both, displayed higher binding affinities at the alpha2- versus the alpha1-ARs, affinities being the least at the alpha1B-AR. Binding affinities of the methoxy ether analog 2 were greater than those of the phenolic analog 3 at all six alpha-AR subtypes. One of the nitrogen atoms in the imidazoline ring of phentolamine was replaced with an oxygen atom to give compounds 4 and 5, resulting in a 2-substituted oxazoline ring. The low functional antagonist activity on rat aorta, and binding potencies of these two compounds on human alpha1A- and alpha2A-AR subtypes indicate that a basic functional group is important for optimum binding to the alpha1- and alpha2A-adrenergic receptors.

  4. Long-duration bed rest as an analog to microgravity. (United States)

    Hargens, Alan R; Vico, Laurence


    Long-duration bed rest is widely employed to simulate the effects of microgravity on various physiological systems, especially for studies of bone, muscle, and the cardiovascular system. This microgravity analog is also extensively used to develop and test countermeasures to microgravity-altered adaptations to Earth gravity. Initial investigations of bone loss used horizontal bed rest with the view that this model represented the closest approximation to inactivity and minimization of hydrostatic effects, but all Earth-based analogs must contend with the constant force of gravity by adjustment of the G vector. Later concerns about the lack of similarity between headward fluid shifts in space and those with horizontal bed rest encouraged the use of 6 degree head-down tilt (HDT) bed rest as pioneered by Russian investigators. Headward fluid shifts in space may redistribute bone from the legs to the head. At present, HDT bed rest with normal volunteers is the most common analog for microgravity simulation and to test countermeasures for bone loss, muscle and cardiac atrophy, orthostatic intolerance, and reduced muscle strength/exercise capacity. Also, current physiologic countermeasures are focused on long-duration missions such as Mars, so in this review we emphasize HDT bed rest studies with durations of 30 days and longer. However, recent results suggest that the HDT bed rest analog is less representative as an analog for other important physiological problems of long-duration space flight such as fluid shifts, spinal dysfunction and radiation hazards.

  5. Antimicrobial and cell-penetrating properties of penetratin analogs

    DEFF Research Database (Denmark)

    Bahnsen, Jesper Søborg; Franzyk, Henrik; Sandberg-Schaal, Anne;


    Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) show great potential as drug delivery vectors and new antibiotic drug entities, respectively. The current study deals with the properties of a variety of peptide analogs derived from the well-known CPP penetratin as well as octaar......Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) show great potential as drug delivery vectors and new antibiotic drug entities, respectively. The current study deals with the properties of a variety of peptide analogs derived from the well-known CPP penetratin as well...... as octaarginine and different Tat sequences. The effects of peptide length, guanidinium content, and sequence of non-cationic residues were assessed in mammalian and bacterial cells. The arginine (Arg) content in the penetratin analogs was found to influence eukaryotic cell uptake efficiency, antimicrobial...... activity towards both Gram-positive and Gram-negative bacteria as well as eukaryotic cell viability. All examined analogs retained the ability to cross eukaryotic membranes giving rise to a distribution within the vacuolar apparatus. Interestingly, a series of shuffled analogs of penetratin...

  6. New insights into the synergism of nucleoside analogs with radiotherapy. (United States)

    Lee, Michael W; Parker, William B; Xu, Bo


    Nucleoside analogs have been frequently used in combination with radiotherapy in the clinical setting, as it has long been understood that inhibition of DNA repair pathways is an important means by which many nucleoside analogs synergize. Recent advances in our understanding of the structure and function of deoxycytidine kinase (dCK), a critical enzyme required for the anti-tumor activity for many nucleoside analogs, have clarified the mechanistic role this kinase plays in chemo- and radio-sensitization. A heretofore unrecognized role of dCK in the DNA damage response and cell cycle machinery has helped explain the synergistic effect of these agents with radiotherapy. Since most currently employed nucleoside analogs are primarily activated by dCK, these findings lend fresh impetus to efforts focused on profiling and modulating dCK expression and activity in tumors. In this review we will briefly review the pharmacology and biochemistry of the major nucleoside analogs in clinical use that are activated by dCK. This will be followed by discussions of recent advances in our understanding of dCK activation via post-translational modifications in response to radiation and current strategies aimed at enhancing this activity in cancer cells.

  7. VUV spectroscopy of carbon dust analogs: contribution to interstellar extinction (United States)

    Gavilan, L.; Alata, I.; Le, K. C.; Pino, T.; Giuliani, A.; Dartois, E.


    Context. A full spectral characterization of carbonaceous dust analogs is necessary to understand their potential as carriers of observed astronomical spectral signatures such as the ubiquitous UV bump at 217.5 nm and the far-ultraviolet (FUV) rise common to interstellar extinction curves. Aims: Our goal is to study the spectral properties of carbonaceous dust analogs from the FUV to the mid-infrared (MIR) domain. We seek in particular to understand the spectra of these materials in the FUV range, for which laboratory studies are scarce. Methods: We produced analogs to carbonaceous interstellar dust encountered in various phases of the interstellar medium: amorphous hydrogenated carbons (a-C:H), for carbonaceous dust observed in the diffuse interstellar medium, and soot particles, for the polyaromatic component. Analogs to a-C:H dust were produced using a radio-frequency plasma reactor at low pressures, and soot nanoparticles films were produced in an ethylene (C2H4) flame. We measured transmission spectra of these thin films (thickness Kronig inversion. We used these constants for comparison to existing interstellar extinction curves. Conclusions: We extend the spectral measurements of these types of carbonaceous analogs into the VUV and link the spectral features in this range to the 3.4 μm band. We suggest that these two materials might contribute to different classes of interstellar extinction curves.

  8. Novel trypanocidal analogs of 5'-(methylthio)-adenosine. (United States)

    Sufrin, Janice R; Spiess, Arthur J; Marasco, Canio J; Rattendi, Donna; Bacchi, Cyrus J


    The purine nucleoside 5'-deoxy-5'-(hydroxyethylthio)-adenosine (HETA) is an analog of the polyamine pathway metabolite 5'-deoxy-5'-(methylthio)-adenosine (MTA). HETA is a lead structure for the ongoing development of selectively targeted trypanocidal agents. Thirteen novel HETA analogs were synthesized and examined for their in vitro trypanocidal activities against bloodstream forms of Trypanosoma brucei brucei LAB 110 EATRO and at least one drug-resistant Trypanosoma brucei rhodesiense clinical isolate. New compounds were also assessed in a cell-free assay for their activities as substrates of trypanosome MTA phosphorylase. The most potent analog in this group was 5'-deoxy-5'-(hydroxyethylthio)-tubercidin, whose in vitro cytotoxicity (50% inhibitory concentration [IC50], 10 nM) is 45 times greater than that of HETA (IC50, 450 nM) against pentamidine-resistant clinical isolate KETRI 269. Structure-activity analyses indicate that the enzymatic cleavage of HETA analogs by trypanosome MTA phosphorylase is not an absolute requirement for trypanocidal activity. This suggests that additional biochemical mechanisms are associated with the trypanocidal effects of HETA and its analogs.

  9. MicroProteins

    DEFF Research Database (Denmark)

    Eguen, Teinai Ebimienere; Straub, Daniel; Graeff, Moritz;


    MicroProteins (miPs) are short, usually single-domain proteins that, in analogy to miRNAs, heterodimerize with their targets and exert a dominant-negative effect. Recent bioinformatic attempts to identify miPs have resulted in a list of potential miPs, many of which lack the defining...... characteristics of a miP. In this opinion article, we clearly state the characteristics of a miP as evidenced by known proteins that fit the definition; we explain why modulatory proteins misrepresented as miPs do not qualify as true miPs. We also discuss the evolutionary history of miPs, and how the miP concept...

  10. Using Analogies in Teaching Physics: A Study on Latvian Teachers' Views and Experience (United States)

    Jonane, Lolita


    The role of analogies as tools for teaching difficult science concepts has been widely discussed in science education. The application of analogies in the context of sustainable education involves richer potential. The purposeful use of appropriate analogies can facilitate analogical thinking and transfer skills, as well as develop abilities which…

  11. Effects of Multimedia and Schema Induced Analogical Reasoning on Science Learning (United States)

    Zheng, R. Z.; Yang, W.; Garcia, D.; McCadden, E. P.


    The present study investigates the effects of multimedia and schema induced analogical reasoning on science learning. It involves 89 fourth grade elementary students in the north-east of the United States. Participants are randomly assigned into four conditions: (a) multimedia with analogy; (b) multimedia without analogy; (c) analogy without…

  12. The Discourse on Printed and Electronic Books: Analogies, Oppositions, and Perspectives (United States)

    Velagic, Zoran


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

  13. Comparison of analog and digital transceiver systems for MR imaging. (United States)

    Hashimoto, Seitaro; Kose, Katsumi; Haishi, Tomoyuki


    We critically evaluated analog and digital transceivers for magnetic resonance (MR) imaging systems under identical experimental conditions to identify and compare their advantages and disadvantages. MR imaging experiments were performed using a 4.74-tesla vertical-bore superconducting magnet and a high sensitivity gradient coil probe. We acquired 3-dimensional spin echo images of a kumquat with and without using a gain-stepping scan technique to extend the dynamic range of the receiver systems. The acquired MR images clearly demonstrated nearly identical image quality for both transceiver systems, but DC and ghosting artifacts were obtained for the analog transceiver system. We therefore concluded that digital transceivers have several advantages over the analog transceivers.

  14. Hydraulic Analogy for Isentropic Flow Through a Nozzle

    Directory of Open Access Journals (Sweden)

    J. S. Rao


    Full Text Available Modelling aspects of isentropic compressible gas flow using hydraulic analogy are discussed. Subsonic and supersonic flows through a typical nozzle are simulated as free surface incompressible water flow in an equivalent 2-D model on a water table. The results are first compared for the well known classical analogy in order to estimate experimental errors. Correction factors for pressure and temperature, to account for non-ideal compressible gas flow are presented and the results obtained on the water table are modified and compared with gas dynamic solution. Within the experimental errors, it is shown that the hydraulic analogy can be used as an effective tool for the study of two dimensional isentropic flows of gases.

  15. Practice Utilization of Algorithms for Analog Filter Group Delay Optimization

    Directory of Open Access Journals (Sweden)

    K. Hajek


    Full Text Available This contribution deals with an application of three different algorithms which optimize a group delay of analog filters. One of them is a part of the professional circuit simulator Micro Cap 7 and the others two original algorithms are developed in the MATLAB environment. An all-pass network is used to optimize the group delay of an arbitrary analog filter. Introduced algorithms look for an optimal order and optimal coefficients of an all-pass network transfer function. Theoretical foundations are introduced and all algorithms are tested using the optimization of testing analog filter. The optimization is always run three times because the second, third and fourth-order all-pass network is used. An equalization of the original group delay is a main objective of these optimizations. All outputs of all algorithms are critically evaluated and also described.

  16. Analog Circuit Design Optimization Based on Evolutionary Algorithms

    Directory of Open Access Journals (Sweden)

    Mansour Barari


    Full Text Available This paper investigates an evolutionary-based designing system for automated sizing of analog integrated circuits (ICs. Two evolutionary algorithms, genetic algorithm and PSO (Parswal particle swarm optimization algorithm, are proposed to design analog ICs with practical user-defined specifications. On the basis of the combination of HSPICE and MATLAB, the system links circuit performances, evaluated through specific electrical simulation, to the optimization system in the MATLAB environment, for the selected topology. The system has been tested by typical and hard-to-design cases, such as complex analog blocks with stringent design requirements. The results show that the design specifications are closely met. Comparisons with available methods like genetic algorithms show that the proposed algorithm offers important advantages in terms of optimization quality and robustness. Moreover, the algorithm is shown to be efficient.

  17. Integrating Problem Solvers from Analogous Markets in New Product Ideation

    DEFF Research Database (Denmark)

    Franke, Nikolaus; Poetz, Marion; Schreier, Martin


    Who provides better inputs to new product ideation tasks, problem solvers with expertise in the area for which new products are to be developed or problem solvers from “analogous” markets that are distant but share an analogous problem or need? Conventional wisdom appears to suggest that target...... that including problem solvers from analogous markets versus the target market accounts for almost two-thirds of the well-known effect of involving lead users instead of average problem solvers. This effect is further amplified when the analogous distance between the markets increases, i.e., when searching...... market expertise is indispensable, which is why most managers searching for new ideas tend to stay within their own market context even when they do search outside their firms' boundaries. However, in a unique symmetric experiment that isolates the effect of market origin, we find evidence...

  18. The synthesis of spermine analogs of the shark aminosterol squalamine. (United States)

    Shu, Youheng; Jones, Stephen R; Kinney, William A; Selinsky, Barry S


    Aminosterols isolated from the dogfish shark Squalus acanthias are promising therapeutic agents in the treatment of infection and cancer. One of these, MSI-1436, has been shown to possess antimicrobial activity slightly better than squalamine. In this study, a series of analogs of MSI-1436 have been synthesized from stigmasterol. The 7 alpha-hydroxy substituent of MSI-1436 was either omitted or the stereochemistry modified to the 7 beta position. Also, analogs of MSI-1436 with 24-sulfate, 24-amino, and 24-hydroxy substituents were synthesized in order to assess the importance of the side chain functional group on antimicrobial activity. All of the analogs possess significant antimicrobial activity, suggesting that substitution at C7 and C24 of the aminosterols plays a minor role in their antimicrobial potency.

  19. Application of Op-amp Fixators in Analog Circuits

    Directory of Open Access Journals (Sweden)

    R. Rohith Krishnan


    Full Text Available Nullor elements have applications not only in analog behaviour modeling but also in analog circuit design and analysis. Fixator- orator pair, the emerging tool in analog design is a combination of a nullor and sources. A method for the realization of fixator- orator pair is discussed in this paper. Application of fixator-norator pair into a circuit makes it possible to perform the AC and DC designs in a linear like way. Fixator fixes a critical biasing spec at the design, whereas the pairing norator finds the value of power conducting components or DC sources that meets the design. A scaling amplifier design, an active load design and a CMOS differential amplifier design are provided as examples to demonstrate the procedure and the methodology.

  20. Ethnographic analogy, the comparative method, and archaeological special pleading. (United States)

    Currie, Adrian


    Ethnographic analogy, the use of comparative data from anthropology to inform reconstructions of past human societies, has a troubled history. Archaeologists often express concern about, or outright reject, the practice--and sometimes do so in problematically general terms. This is odd, as (or so I argue) the use of comparative data in archaeology is the same pattern of reasoning as the 'comparative method' in biology, which is a well-developed and robust set of inferences which play a central role in discovering the biological past. In pointing out this continuity, I argue that there is no 'special pleading' on the part of archaeologists in this regard: biologists must overcome analogous epistemic difficulties in their use of comparative data. I then go on to emphasize the local, empirically tractable ways in which particular ethnographic analogies may be licensed.

  1. A hybrid digital-analog long pulse integrator (United States)

    Strait, E. J.; Broesch, J. D.; Snider, R. T.; Walker, M. L.


    A digital-analog integrator has been developed for use with inductive magnetic sensors in long-pulse tokamaks. Continuous compensation of input offsets is accomplished by alternating analog-to-digital convertor samples from the sensor and a dummy load, while a RC network provides passive integration between samples. Typically a sampling rate of 10 kHz is used. In operational tests on the DIII-D tokamak, digital and analog integration of tokamak data show good agreement. The output drift error during a 1200 s integration interval corresponds to a few percent of the anticipated signal for poloidal field probes in International Thermonuclear Experimental Reactor, and bench tests suggest that the error can be reduced further.

  2. Diagnosis Method for Analog Circuit Hard fault and Soft Fault

    Directory of Open Access Journals (Sweden)

    Baoru Han


    Full Text Available Because the traditional BP neural network slow convergence speed, easily falling in local minimum and the learning process will appear oscillation phenomena. This paper introduces a tolerance analog circuit hard fault and soft fault diagnosis method based on adaptive learning rate and the additional momentum algorithm BP neural network. Firstly, tolerance analog circuit is simulated by OrCAD / Pspice circuit simulation software, accurately extracts fault waveform data by matlab program automatically. Secondly, using the adaptive learning rate and momentum BP algorithm to train neural network, and then applies it to analog circuit hard fault and soft fault diagnosis. With shorter training time, high precision and global convergence effectively reduces the misjudgment, missing, it can improve the accuracy of fault diagnosis and fast.  

  3. Analogical thinking in ecology: looking beyond disciplinary boundaries. (United States)

    Colyvan, Mark; Ginzburg, Lev R


    We consider several ways in which a good understanding of modern techniques and principles in physics can elucidate ecology, and we focus on analogical reasoning between these two branches of science. Analogical reasoning requires an understanding of both sciences and an appreciation of the similarities and points of contact between the two. In the current ecological literature on the relationship between ecology and physics, there has been some misunderstanding about the nature of modern physics and its methods. Physics is seen as being much cleaner and tidier than ecology. When compared to this idealized, fictional version of physics, ecology looks very different, and the prospect of ecology and physics learning from one another is questionable. We argue that physics, once properly understood, is more like ecology than ecologists have thus far appreciated. Physicists and ecologists can and do learn from each other, and, in this paper, we outline how analogical reasoning can facilitate such exchanges.

  4. Synthesis and biological activity of Wuweizisu C and analogs. (United States)

    Chang, J B; Wang, Q; Li, Y F


    Lignans are widely distributed in nature. The earliest recorded medicinal use of lignans dated back to over 1000 years ago. Lignan-rich plant products were also active ingredients in Chinese and Japanese folk medicines for the treatment of various diseases. The dried root and stem of this plant are listed in the Chinese pharmacopoeia for the treatment of rheumatoid arthritis, gastric, duodenal ulcers and many other diseases. This review highlights synthetic strategies for the Wuweizisu C analogs and the important pharmacological activities as well as therapeutic findings related to the treatment of HBV and other diseases. Notably a significant and ongoing project on Wuweizisu C and its analogs has led to the discovery and development of two potent derivatives alpha-DDB and BICYCLOL which are currently in clinical trials against HBV, especially in lowering elevated SGPT levels. Further design, synthesis, and evaluation of Wuweizisu C analogs are discussed.

  5. Synthetic analogs of anoplin show improved antimicrobial activities

    DEFF Research Database (Denmark)

    Munk, Jens; Uggerhøj, Lars Erik; Poulsen, Tanja Juul;


    We present the antimicrobial and hemolytic activities of the decapeptide anoplin and 19 analogs thereof tested against methicillin-resistant Staphylococcus aureus ATCC 33591 (MRSA), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), vancomycin-resistant Enterococcus faecium (ATCC...... 700221) (VRE), and Candida albicans (ATCC 200955). The anoplin analogs contain substitutions in amino acid positions 2, 3, 5, 6, 8, 9, and 10. We use these peptides to study the effect of altering the charge and hydrophobicity of anoplin on activity against red blood cells and microorganisms. We find...... that increasing the charge and/or hydrophobicity improves antimicrobial activity and increases hemolytic activity. For each strain tested, we identify at least six anoplin analogs with an improved therapeutic index compared with anoplin, the only exception being Enterococcus faecium, against which only few...

  6. Discovery of a Jupiter/Saturn Analog with Gravitational Microlensing

    Energy Technology Data Exchange (ETDEWEB)

    Gaudi, B; Bennett, D; Udalski, A; Gould, A; Christie, G; Maoz, D; Dong, S; McCormick, J; Szymanski, M; Tristram, P; Nikolaev, S; Paczynski, B; Kubiak, M; Pietrzynski, G; Soszynski, I; Szewczyk, O; Ulaczyk, K; Wyrzykowski, L; DePoy, D; Han, C; Kaspi, S; Lee, C; Mallia, F; Natusch, T; Pogge, R; Park, B; Abe, F; Bond, I; Botzler, C; Fukui, A; Hearnshaw, J; Itow, Y; Kamiya, K; Korpela, A; Kilmartin, P; Lin, W; Masuda, K; Matsubara, Y; Motomura, M; Muraki, Y; Nakamura, S; Okumura, T; Ohnishi, K; Rattenbury, N; Sako, T; Saito, T; Sato, S; Skuljan, L; Sullivan, D; Sumi, T; Sweatman, W; Yock, P; Albrow, M; Beaulieu, J; Burgdorf, M; Cook, K; Coutures, C; Dominik, M; Dieters, S; Fouque, P; Greenhill, J; Horne, K; Steele, I; Tsapras, Y; Chaboyer, B; Crocker, A; Frank, S; Macintosh, B


    Searches for extrasolar planets have uncovered an astonishing diversity of planetary systems, yet the frequency of solar system analogs remains unknown. The gravitational microlensing planet search method is potentially sensitive to multiple-planet systems containing analogs of all the solar system planets except Mercury. We report the first detection of a multiple-planet system with microlensing. We identify two planets with masses of {approx} 0.71 and {approx} 0.27 times the mass of Jupiter and orbital separations of {approx} 2.3 and {approx} 4.6 astronomical units orbiting a primary of mass {approx} 0.50 solar masses. This system resembles a scaled version of our solar system in that the mass ratio, separation ratio, and equilibrium temperatures of the planets are similar to those of Jupiter and Saturn. These planets could not have been detected with other techniques; their discovery from only 6 confirmed microlensing planet detections suggests that solar system analogs may be common.

  7. Glutamine analogs promote cytoophidium assembly in human and Drosophila cells

    Institute of Scientific and Technical Information of China (English)

    Kangni Chen; Jing Zhang; (O)mür Yilmaz Tastan; Zillah Anne Deussen; Mayte Yu-Yin Siswick; Ji-Long Liu


    CTP synthase is compartmentalized within a subcellular structure,termed the cytoophidium,in a range of organisms including bacteria,yeast,fruit fly and rat.Here we show that CTP synthase is also compartmentalized into cytoophidia in human cells.Surprisingly,the occurrence of cyloophidia in human cells increases upon treatment with a glutamine analog 6-diazo-5-oxo-L-norleucine (DON),an inhibitor of glutaminedependent enzymes including CTP synthase.Experiments in flies confirmned that DON globally promotes cytoophidium assembly.Clonal analysis via CTP synthase RNA interference in somatic cells indicates that CTP synthase expression level is critical for the formation of cytoophidia.Moreover,DON facilitates cytoophidium assembly even when CTP synthase level is low.A second glutamine analog azaserine also promotes cytoophidum formation.Our data demonstrate that glutamine analogs serve as useful tools in the study of cytoophidia.

  8. Therapeutic outlook of pyrazole analogs: A mini review. (United States)

    Ganguly, Swastika; Sony Jacob, K


    Pyrazole is one of the excellent structural motifs in medicinal chemistry. Various physiological and therapeutic possibilities have been exploited by incorporating different pharmacophoric groups in the pyrazole moiety. This has opened a new arena of pyrazole analogs that can be developed into medicinal agents such as anti-inflammatory, analgesic, antipyretic, antiviral, antibacterial, anticancer, anticonvulsant, hypoglycemic, carbonic anhydrase inhibitors, mono amino oxidase (MAO) inhibitors, etc. Though, pyrazole analogs have proven their clinical efficacy as different pharmacological agents, a few of them have been withdrawn from the market due to their side effects. Thus, research on potential new drug candidates bearing the pyrazole moiety with lesser side effects has fairly increased over the last few years. This review explores diverse pharmacological activities exhibited by pyrazole analogs reported recently, which may be of great help for researchers in the area of drug discovery to understand the current scenario of pyrazole based compounds and to design and develop newer drug candidates with improved efficacy.

  9. Adrenocorticotropic hormone analog use for podocytopathies

    Directory of Open Access Journals (Sweden)

    Filippone EJ


    Full Text Available Edward J Filippone,1 Shirley J Dopson,2 Denise M Rivers,3 Rebeca D Monk,4 Suneel M Udani,5 Golriz Jafari,6 Solomon C Huang,6 Arafat Melhem,7 Bassim Assioun,7 Paul G Schmitz7 1Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, 2Division of Medicine, Washington Health System, Southwestern Nephrology, Inc, Washington, PA, 3Department of Medicine, University Nephrology, University of Tennessee, Knoxville, TN, 4Department of Medicine, Division of Nephrology, University of Rochester Medical Center, Rochester, NY, 5Department of Medicine, Section of Nephrology, University of Chicago, Chicago, IL, 6Division of Nephrology and Hypertension, Olive View–University of California, Los Angeles Medical Center, Sylmar, CA, 7Department of Internal Medicine, Division of Nephrology, Saint Louis University, St Louis, MO, USABackground: Adrenocorticotropic hormone is being increasingly studied for treatment of various glomerulopathies, most notably membranous nephropathy. Less data are available regarding its use in idiopathic nephrotic syndrome (INS secondary to minimal change disease (MCD or focal segmental glomerulosclerosis (FSGS. We report here our experience with H.P. Acthar® Gel (repository corticotropin injection as first-line or subsequent therapy in patients with INS.Methods: Data were taken from three patients with MCD and ten patients with FSGS from around the US, who were treated with Acthar Gel as initial or subsequent therapy. Treatment was solely at the discretion of the primary nephrologist without a specific protocol. A complete response (CR was defined as final urine protein-to-creatinine ratio <500 mg/g and a partial response (PR as 50% decrease without rise of serum creatinine. Side effects and tolerability were noted.Results: All three patients with MCD received Acthar Gel as second-line or later immunosuppressive (IS therapy and all responded (one CR and two PRs. Two of

  10. Analog Group Delay Equalizers Design Based on Evolutionary Algorithm

    Directory of Open Access Journals (Sweden)

    M. Laipert


    Full Text Available This paper deals with a design method of the analog all-pass filter designated for equalization of the group delay frequency response of the analog filter. This method is based on usage of evolutionary algorithm, the Differential Evolution algorithm in particular. We are able to design such equalizers to be obtained equal-ripple group delay frequency response in the pass-band of the low-pass filter. The procedure works automatically without an input estimation. The method is presented on solving practical examples.

  11. Developing a 300C Analog Tool for EGS

    Energy Technology Data Exchange (ETDEWEB)

    Normann, Randy


    This paper covers the development of a 300°C geothermal well monitoring tool for supporting future EGS (enhanced geothermal systems) power production. This is the first of 3 tools planed. This is an analog tool designed for monitoring well pressure and temperature. There is discussion on 3 different circuit topologies and the development of the supporting surface electronics and software. There is information on testing electronic circuits and component. One of the major components is the cable used to connect the analog tool to the surface.

  12. Cognitive constraints on ordering operations: the case of geometric analogies. (United States)

    Novick, L R; Tversky, B


    Many tasks (e.g., solving algebraic equations and running errands) require the execution of several component processes in an unconstrained order. The research reported here uses the geometric analogy task as a paradigm case for studying the ordering of component processes in this type of task. In solving geometric analogies by applying mental transformations such as rotate, change size, and add a part, the order of performing the transformations is unconstrained and does not in principle affect solution accuracy. Nevertheless, solvers may bring cognitive constraints with them to the analogy task that influence the ordering of the transformations. First, we demonstrate that solvers have a preferred order for performing mental transformations during analogy solution. We then investigate three classes of explanations for the preferred order, one based on general information processing considerations, another based on task-specific considerations, and a third based on individual differences in analogy ability. In the first and third experiments, college students solved geometric analogies requiring two or three transformations and indicated the order in which they performed the transformations. There was close agreement on nearly the same order for both types of analogies. In the second experiment, subjects were directed to perform pairs of transformations in the preferred or unpreferred order. Both speed and accuracy were greater for the preferred orders, thus validating subjects' reported orders. Ability differences were observed for only the more difficult three-transformation problems: High- and middle-ability subjects agreed on an overall performance order, but the highs were more consistent in their use of this order. Low-ability subjects did not consistently order the transformations for these difficult problems. The general information processing factor examined was working-memory load. A number of task factors have been shown to affect working-memory load

  13. Volatiles and refratories in solar analogs: no terrestial planet connection


    Hernandez, J. I. Gonzalez; Israelian, G.; Santos,N.C.; Sousa, S.; Delgado-Mena, E.; Neves, V.; Udry, S.


    We have analysed very high-quality HARPS and UVES spectra of 95 solar analogs, 24 hosting planets and 71 without detected planets, to search for any possible signature of terrestial planets in the chemical abundances of volatile and refractory elements with respect to the solar abundances. We demonstrate that stars with and without planets in this sample show similar mean abundance ratios, in particular, a sub-sample of 14 planet-host and 14 "single" solar analogs in the metallicity range 0.14

  14. Low-power Analog VLSI Implementation of Wavelet Transform

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jiang-hong


    For applications requiring low-power, low-voltage and real-time, a novel analog VLSI implementation of continuous Marr wavelet transform based on CMOS log-domain integrator is proposed.Mart wavelet is approximated by a parameterized class of function and with Levenbery-Marquardt nonlinear least square method,the optimum parameters of this function are obtained.The circuits of implementating Mart wavelet transform are composed of analog filter whose impulse response is the required wavelet.The filter design is based on IFLF structure with CMOS log-domain integrators as the main building blocks.SPICE simulations indicate an excellent approximations of ideal wavelet.

  15. Analog versus digital: extrapolating from electronics to neurobiology. (United States)

    Sarpeshkar, R


    We review the pros and cons of analog and digital computation. We propose that computation that is most efficient in its use of resources is neither analog computation nor digital computation but, rather, a mixture of the two forms. For maximum efficiency, the information and information-processing resources of the hybrid form must be distributed over many wires, with an optimal signal-to-noise ratio per wire. Our results suggest that it is likely that the brain computes in a hybrid fashion and that an underappreciated and important reason for the efficiency of the human brain, which consumes only 12 W, is the hybrid and distributed nature of its architecture.

  16. Teamwork in high-risk environments analogous to space (United States)

    Kanki, Barbara G.


    Mountaineering expeditions combine a number of factors which make them potentially good analogs to the planetary exploration facet of long-duration space missions. A study of mountain climbing teams was conducted in order to evaluate the usefulness of the environment as a space analog and to specifically identify the factors and issues surrounding teamwork and 'successful' team performance in two mountaineering environments. This paper focuses on social/organizational factors, including team size and structure, leadership styles and authority structure which were found in the sample of 22 climb teams (122 individuals). The second major issue discussed is the construction of a valid performance measure in this high-risk environment.

  17. Synthesis and Antifeeding Activity of Acetylene-Containing Tonghaosu Analogs

    Institute of Scientific and Technical Information of China (English)

    CHEN,Li; HU,Tai-Shan; XU,Han-Hong; YIN,Biao-Lin; XIAO,Chun; WU,Yu-Lin


    @@ During our continuous efforts towards the search for environmental benign insect antifeedant, we established a concise method for the synthesis of Tonghaosu, a naturally occurring antifeedant.[1] Herein, we report the synthesis and antifeeding activity of 22 new tonghaosu analogs, which contain varied B ring as well as one or two acetylene functionalities. Preliminary bioassay indicates that two acetylene groups containing tonghaosu analogs have better antifeedant activity against large white butterfly (Pieris brassicae L.) than those with one acetylene group. More interestingly,Z-isomers are much more active than their corresponding E-isomers.

  18. Silicon analog components device design, process integration, characterization, and reliability

    CERN Document Server

    El-Kareh, Badih


    This book covers modern analog components, their characteristics, and interactions with process parameters. It serves as a comprehensive guide, addressing both the theoretical and practical aspects of modern silicon devices and the relationship between their electrical properties and processing conditions. Based on the authors’ extensive experience in the development of analog devices, this book is intended for engineers and scientists in semiconductor research, development and manufacturing. The problems at the end of each chapter and the numerous charts, figures and tables also make it appropriate for use as a text in graduate and advanced undergraduate courses in electrical engineering and materials science.

  19. On automatic synthesis of analog/digital circuits

    Energy Technology Data Exchange (ETDEWEB)

    Beiu, V.


    The paper builds on a recent explicit numerical algorithm for Kolmogorov`s superpositions, and will show that in order to synthesize minimum size (i.e., size-optimal) circuits for implementing any Boolean function, the nonlinear activation function of the gates has to be the identity function. Because classical and--or implementations, as well as threshold gate implementations require exponential size, it follows that size-optimal solutions for implementing arbitrary Boolean functions can be obtained using analog (or mixed analog/digital) circuits. Conclusions and several comments are ending the paper.

  20. Dual chain synthetic heparin-binding growth factor analogs (United States)

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua


    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  1. Dual chain synthetic heparin-binding growth factor analogs

    Energy Technology Data Exchange (ETDEWEB)

    Zamora, Paul O. (Gaithersburg, MD); Pena, Louis A. (Poquott, NY); Lin, Xinhua (Plainview, NY)


    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  2. Real time image processing with an analog vision chip system. (United States)

    Kameda, S; Honda, A; Yagi, T


    A linear analog network model is proposed to characterize the function of the outer retinal circuit in terms of the standard regularization theory. Inspired by the function and the architecture of the model, a vision chip has been designed using analog CMOS Very Large Scale Integrated circuit technology. In the chip, sample/hold amplifier circuits are incorporated to compensate for statistic transistor mismatches. Accordingly, extremely low noise outputs were obtained from the chip. Using the chip and a zero-crossing detector, edges of given images were effectively extracted in indoor illumination.

  3. Foucault's Pendulum, Analog for an Electron Spin State (United States)

    Linck, Rebecca


    The classical Lagrangian that describes the coupled oscillations of Foucault's pendulum presents an interesting analog to an electron's spin state in an external magnetic field. With a simple modification, this classical Lagrangian yields equations of motion that directly map onto the Schrodinger-Pauli Equation. This analog goes well beyond the geometric phase, reproducing a broad range of behavior from Zeeman-like frequency splitting to precession of the spin state. By demonstrating that unmeasured spin states can be fully described in classical terms, this research opens the door to using the tools of classical physics to examine an inherently quantum phenomenon.

  4. High-speed analog-to-digital conversion

    CERN Document Server

    Demler, Michael J


    This book covers the theory and applications of high-speed analog-to-digital conversion. An analog-to-digital converter takes real-world inputs (such as visual images, temperature readings, and rates of speed) and transforms them into digital form for processing by computer. This book discusses the design and uses of such circuits, with particular emphasis on improving the speed of the conversion process and the accuracy of its output--how well the output is a corresponding digital representation of the output*b1input signal. As computers become increasingly interfaced to the outside world, ""

  5. The Resilience of Analog Tools in Creative Work Practices

    DEFF Research Database (Denmark)

    Borum, Nanna; Petersson, Eva; Frimodt-Møller, Søren


    This paper discusses the use of digital and analog tools, respectively, in a creative industry. The research was done within the EU-funded research project IdeaGarden, which explores digital platforms for creative collaboration. The findings in a case study of LEGO® Future Lab, one of LEGO Group......’s largest innovation departments, show a preference for analog tools over digital in the creative process. This points towards a general need for tangible tools in the creative work process, a need that has consequences for the development of new digital tools for creative collaboration....

  6. Radiation tests on commercial instrumentation amplifiers, analog switches & DAC's

    CERN Document Server

    Agapito, J A; Cardeira, F M; Casas, C; Fernandes, A; Franco, F J; Gomes, P; Gonçalves, I C; Cachero, A H; Lozano-Bahilo, J; Marques, J G; Paz, A; Prata, M J; Ramalho, A J G; Rodríguez-Ruiz, M A; Santos, J P; Vieira, A


    A study of several commercial instrumentation amplifiers (INA110, INA111, INA114, INA116, INA118 & INA121) under neutron and vestigial gamma radiation was done. Some parameters (Gain, input offset voltage, input bias currents) were measured on-line and bandwidth, and slew rate were determined before and after radiation. The results of the testing of some voltage references REF102 and ADR290GR and the DG412 analog switch are shown. Finally, different digital-to-analog converters were tested under radiation. (6 refs).

  7. Automatic Synthesis of CMOS Algorithmic Analog To-Digital Converter. (United States)

    Jusuf, Gani

    The steady decrease in technological feature size is allowing increasing levels of integration in analog/digital interface functions. These functions consist of analog as well as digital circuits. While the turn around time for an all digital IC chip is very short due to the maturity of digital IC computer-aided design (CAD) tools over the last ten years, most analog circuits have to be designed manually due to the lack of analog IC CAD tools. As a result, analog circuit design becomes the bottleneck in the design of mixed signal processing chips. One common analog function in a mixed signal processing chip is an analog-to-digital conversion (ADC) function. This function recurs frequently but with varying performance requirements. The objective of this research is to study the design methodology of a compilation program capable of synthesizing ADC's with a broad range of sampling rates and resolution, and silicon area and performance comparable with the manual approach. The automatic compilation of the ADC function is a difficult problem mainly because ADC techniques span such a wide spectrum of performance, with radically different implementations being optimum for different ranges of conversion range, resolution, and power dissipation. We will show that a proper choice of the ADC architectures and the incorporation of many analog circuit design techniques will simplify the synthesis procedure tremendously. Moreover, in order to speed up the device sizing, hierarchical optimization procedure and behavioral simulation are implemented into the ADC module generation steps. As a result of this study, a new improved algorithmic ADC without the need of high precision comparators has been developed. This type of ADC lends itself to automatic generation due to its modularity, simplicity, small area consumption, moderate speed, low power dissipation, and single parameter trim capability that can be added at high resolution. Furthermore, a performance-driven CMOS ADC module


    Directory of Open Access Journals (Sweden)



    Full Text Available Nowadays, editing technology has entered the digital age. Technology will demonstrate the evidence of processing analog to digital data has become simpler since editing technology has been integrated in the society in all aspects. Understanding the technique of processing analog to digital data is important in producing a video. To utilize this technology, the introduction of equipments is fundamental to understand the features. The next phase is the capturing process that supports the preparation in editing process from scene to scene; therefore, it will become a watchable video.

  9. Design, modeling, expression, and chemoselective PEGylation of a new nanosize cysteine analog of erythropoietin

    Directory of Open Access Journals (Sweden)

    Ahangari Cohan R


    Full Text Available Reza Ahangari Cohan1, Armin Madadkar-Sobhani2,3, Hossein Khanahmad1, Farzin Roohvand4, Mohammad Reza Aghasadeghi4, Mohammad Hossein Hedayati5, Zahra Barghi5, Mehdi Shafiee Ardestani4, Davoud Nouri Inanlou1, Dariush Norouzian11Research and Development Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran; 2Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; 3Department of Life Sciences, Barcelona Supercomputing Center, Barcelona, Spain; 4Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Iran; 5Quality Control Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, IranBackground: Recombinant human erythropoietin (rhEPO is considered to be one of the most pivotal pharmaceutical drugs in the market because of its clinical application in the treatment of anemia-associated disorders worldwide. However, like other therapeutic proteins, it does not have suitable pharmacokinetic properties for it to be administrated at least two to three times per week. Chemoselective cysteine PEGylation, employing molecular dynamics and graphics in in silico studies, can be considered to overcome such a problem.Methods: A special kind of EPO analog was elicited based on a literature review, homology modeling, molecular dynamic simulation, and factors affecting the PEGylation reaction. Then, cDNA of the selected analog was generated by site-directed mutagenesis and subsequently cloned into the expression vector. The construct was transfected to Chinese hamster ovary/dhfr- cells, and highly expressed clones were selected via methotrexate amplification. Ion-immobilized affinity and size exclusion (SE chromatography techniques were used to purify the expressed analog. Thereafter, chemoselective PEGylation was performed and a nanosize PEGylated EPO was obtained through dialysis. The in vitro biologic assay and in vivo pharmacokinetic parameters were

  10. Immunoreactivity score using an anti-sst2A receptor monoclonal antibody strongly predicts the biochemical response to adjuvant treatment with somatostatin analogs in acromegaly

    NARCIS (Netherlands)

    F. Gatto (Federico); R.A. Feelders (Richard); R. van der Pas (Rob); J.M. Kros (Johan); M. Waaijers (Marlijn); D. Sprij-Mooij (Diana); S.J.C.M.M. Neggers (Bas); A. van der Lelij (Allegonda); F. Minuto (Francesco); S.W.J. Lamberts (Steven); W.W. de Herder (Wouter); D. Ferone (Diego); L.J. Hofland (Leo)


    textabstractContext: Somatostatin receptor subtype 2 (sst2A) protein expression has been demonstrated to positively correlate with somatostatin analog treatment outcome in GH-secreting adenomas. Recently, a new rabbit monoclonal anti-sst2A antibody (clone UMB-1) has been validated as a reliable meth

  11. Los pasiegos. La analogía salvaje y lo salvaje de la analogía

    Directory of Open Access Journals (Sweden)



    -entendiendo salvaje como un pensamiento humano prístino-: por un lado en sus relaciones con el racionalismo (¿emerge la analogía desde el racionalismo?, ¿qué relación guarda con éste?, ¿su nacimiento es resultado de una función «natural»? y por otro sobre la naturaleza social de lo salvaje a partir de las bases sociales que lo producen. Es decir, se rastrea lo que de salvaje tiene la analogía, si la analogía es o no una función ahistórica y asocial del intelecto humano. No se examina todo el complejo analógico de los pasiegos, únicamente aquél que establece relaciones homólogas entre las vacas y el entorno.


    Energy Technology Data Exchange (ETDEWEB)

    Kane, Stephen R. [Department of Physics and Astronomy, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132 (United States); Kopparapu, Ravi Kumar [Department of Geosciences, Penn State University, 443 Deike Building, University Park, PA 16802 (United States); Domagal-Goldman, Shawn D., E-mail: [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States)


    The field of exoplanetary science has seen a dramatic improvement in sensitivity to terrestrial planets over recent years. Such discoveries have been a key feature of results from the Kepler mission which utilizes the transit method to determine the size of the planet. These discoveries have resulted in a corresponding interest in the topic of the Habitable Zone and the search for potential Earth analogs. Within the solar system, there is a clear dichotomy between Venus and Earth in terms of atmospheric evolution, likely the result of the large difference (approximately a factor of two) in incident flux from the Sun. Since Venus is 95% of the Earth's radius in size, it is impossible to distinguish between these two planets based only on size. In this Letter we discuss planetary insolation in the context of atmospheric erosion and runaway greenhouse limits for planets similar to Venus. We define a ''Venus Zone'' in which the planet is more likely to be a Venus analog rather than an Earth analog. We identify 43 potential Venus analogs with an occurrence rate (η{sub ♀}) of 0.32{sub −0.07}{sup +0.05} and 0.45{sub −0.09}{sup +0.06} for M dwarfs and GK dwarfs, respectively.

  13. Metaphors & Analogies: Power Tools for Teaching Any Subject (United States)

    Wormeli, Rick


    Metaphors and analogies are more than figurative language suitable only for English classes and standardized test questions. They are "power tools" that can electrify learning in every subject and at all grade levels. Metaphors show students how to make connections between the concrete and the abstract, prior knowledge and unfamiliar concepts, and…

  14. Digitally assisted analog beamforming for millimeter-wave communication

    NARCIS (Netherlands)

    Kokkeler, A.B.J.; Smit, G.J.M.


    The paper addresses the research question on how digital beamsteering algorithms can be combined with analog beamforming in the context of millimeter-wave communication for next generation (5G) cellular systems. Key is the use of coarse quantisation of the individual antenna signals next to the anal

  15. Analogy and Intersubjectivity: Political Oratory, Scholarly Argument and Scientific Reports. (United States)

    Gross, Alan G.


    Focuses on the different ways political oratory, scholarly argument, and scientific reports use analogy. Specifically, analyzes intersubjective agreement in Franklin D. Roosevelt's First Inaugural address, the scholarly argument between Sir Karl Popper and Thomas S. Kuhn, and the scientific reports of various mathematicians and scientists. (PD)

  16. Assessing the Impact of Bridging Analogies in Mechanics (United States)

    Yilmaz, Serkan; Eryilmaz, Ali; Geban, Omer


    The effects of bridging analogies teaching strategy and gender on Turkish high school students' misconceptions in mechanics were investigated. After a pilot study with 67 students in a nearby high school, the researchers' administered the revised Mechanics Misconception Test to 119 high school students as a pretest. Students in the experimental…

  17. Linking Gestures: Cross-Cultural Variation during Instructional Analogies (United States)

    Richland, Lindsey Engle


    Deictic linking gestures, hand and arm motions that physically embody links being communicated between two or more objects in the shared communicative environment, are explored in a cross-cultural sample of mathematics instruction. Linking gestures are specifically examined here when they occur in the context of communicative analogies designed to…

  18. VUV spectroscopy of carbon dust analogs: contribution to interstellar extinction

    CERN Document Server

    Gavilan, L; Le, K C; Pino, T; Giuliani, A; Dartois, E


    A full spectral characterization of carbonaceous dust analogs is necessary to understand their potential as carriers of observed astronomical spectral signatures such as the ubiquitous UV bump at 217.5 nm and the far-ultraviolet (FUV) rise common to interstellar extinction curves. Our goal is to study the spectral properties of carbonaceous dust analogs from the FUV to the mid-infrared (MIR) domain. We seek in particular to understand the spectra of these materials in the FUV range, for which laboratory studies are scarce. We produced analogs to carbonaceous interstellar dust encountered in various phases of the interstellar medium: amorphous hydrogenated carbons (a-C:H), for carbonaceous dust observed in the diffuse interstellar medium, and soot particles, for the polyaromatic component. Analogs to a-C:H dust were produced using a radio-frequency plasma reactor at low pressures, and soot nanoparticles films were produced in an ethylene (C$_2$H$_4$) flame. We measured transmission spectra of these thin films ...

  19. Analog Video Authentication and Seal Verification Equipment Development

    Energy Technology Data Exchange (ETDEWEB)

    Gregory Lancaster


    Under contract to the US Department of Energy in support of arms control treaty verification activities, the Savannah River National Laboratory in conjunction with the Pacific Northwest National Laboratory, the Idaho National Laboratory and Milagro Consulting, LLC developed equipment for use within a chain of custody regime. This paper discussed two specific devices, the Authentication Through the Lens (ATL) analog video authentication system and a photographic multi-seal reader. Both of these devices have been demonstrated in a field trial, and the experience gained throughout will also be discussed. Typically, cryptographic methods are used to prove the authenticity of digital images and video used in arms control chain of custody applications. However, in some applications analog cameras are used. Since cryptographic authentication methods will not work on analog video streams, a simple method of authenticating analog video was developed and tested. A photographic multi-seal reader was developed to image different types of visual unique identifiers for use in chain of custody and authentication activities. This seal reader is unique in its ability to image various types of seals including the Cobra Seal, Reflective Particle Tags, and adhesive seals. Flicker comparison is used to compare before and after images collected with the seal reader in order to detect tampering and verify the integrity of the seal.

  20. A Total Dose Characterization of Five Commercial Analog Multiplexers. (United States)


    Laboratory, Kirtland Air Force Base, New Mexico , under Job Order 88091145. First Lieutenant Mark R. Ackermann (NTCT) was the Laboratory Project Officer-in...b) the channel resistance R for an n-channel MOS rET. * 25 AFWL-TR-84-07 Vino +5 OTL Figure 8. A CMOS analog transfer gate. VT,, 0 DOSE Figure 9

  1. [General systems theory, analog models and essential arterial hypertension]. (United States)

    Indovina, I; Bonelli, M


    The application of the General System Theory to the fields of biology and particularly of medicine is fraught with many difficulties deriving from the mathematical complexities of application. The authors suggest that these difficulties can be overcome by applying analogical models, thus opening new prospects for the resolution of the manifold problems involved in connection with the study of arterial hypertension.

  2. Descartes highlands: Possible analogs around the Orientale Basin, part D (United States)

    Carroll, A. H.


    Two possible analogs, although not entirely satisfactory, offer reasonable alternatives to the volcanic interpretation of the Descartes highlands. Reconsideration of this complex terrain, prompted by the preliminary results of the Apollo 16 mission, will lead to the revision of some theories on lunar volcanism and also to a better understanding of the landforms caused by the formation of multi-ring basins.

  3. Synthesis of tetracycline analogs and their bone affinities

    Institute of Scientific and Technical Information of China (English)

    Wen Cai Huang; Hu Zheng; Ling Ling Weng


    Tetracycline analogs were designed and synthesized and their bone affinities were tested on hydroxyapatite. The results showedthat the carbonyl-amide-enol structure in A ring and phenol-ketone structure in BCD ring may be responsible for tetracycline's highbone affinity and either A ring or BCD ring has a planar conformation is essential.

  4. Anticipatory Functions, Digital-Analog Forms and Biosemiotics

    DEFF Research Database (Denmark)

    Arnellos, Argyris; Bruni, Luis Emilio; El-Hani, Charbel Niño;


    our overall approach. We adopt a Peircean approach to Biosemiotics, and a dynamical approach to Digital-Analog relations and to the interplay between different levels of functionality in autonomous systems, taking an integrative approach. We then apply the underlying biosemiotic logic to a particular...

  5. Noscapine and its Analogs as Chemotherapeutic Agent: Current updates. (United States)

    Tomar, Vartika; Kukreti, Shrikant; Prakash, Satya; Madan, Jitender; Chandra, Ramesh


    Recently, noscapine was reported as anticancer drug. Unlike, colchicine and podophyllotoxin, noscapine did not depolymerize microtubules even at stoichiometric concentrations but rather only mitigated their dynamics. Other microtubule-interacting chemotherapeutics, although quite effective, have therapy-limiting toxicities including immunosuppression and peripheral neuropathies. Recurrent cancers often become resistant. Noscapine however remains effective in some such instances, e.g., taxane-resistant ovarian cancer. Noscapine and analogs also do not show signs of neurotoxicity or immunosuppression. In addition, 9-bromo noscapine, Red-9-Br-Nos and other analogs were characterized for their structure and further studied in detail. On the other hand, noscapine was shown to be neuroprotective in mouse model of neurodegenerative disease and in stroke patients. Like low doses of colchicine, noscapine and its analog 9-Br-Noscapine also show anti-inflammatory activities. There are indications of a preventive use of noscapine in ischemiareperfusion injury and fibrosis. The entire biosynthetic pathway of noscapine is encoded as gene cluster within 401 kilo bases of genomic DNA, opening up opportunities for the large-scale biotechnological production of noscapine for medicinal needs. Thus, noscapine and its derivatives (noscapinoids) might be cost-effective and safe components for cancer chemotherapy. Owing to its low toxicity, it also might be useful for preventive use in high-risk situations. This brief review is an update of current research activity and patents on noscapine and its analogs.

  6. Using an analogy in the introduction of a portfolio

    NARCIS (Netherlands)

    van Tartwijk, Jan; van Rijswijk, Martine; Tuithof, Hanneke; Driessen, Erik W.


    Students in many teacher education programmes experience confusion about portfolios. This study investigated whether using an analogy in the introduction of a portfolio helps teacher education students understand both the purpose of a portfolio and how to compile it. It was also investigated whether

  7. Using an Analogy in the Introduction of a Portfolio (United States)

    van Tartwijk, Jan; van Rijswijk, Martine; Tuithof, Hanneke; Driessen, Erik W.


    Students in many teacher education programmes experience confusion about portfolios. This study investigated whether using an analogy in the introduction of a portfolio helps teacher education students understand both the purpose of a portfolio and how to compile it. It was also investigated whether these students' understanding correlates with…

  8. Analogy between gambling and measurement-based work extraction (United States)

    Vinkler, Dror A.; Permuter, Haim H.; Merhav, Neri


    In information theory, one area of interest is gambling, where mutual information characterizes the maximal gain in wealth growth rate due to knowledge of side information; the betting strategy that achieves this maximum is named the Kelly strategy. In the field of physics, it was recently shown that mutual information can characterize the maximal amount of work that can be extracted from a single heat bath using measurement-based control protocols, i.e. using ‘information engines’. However, to the best of our knowledge, no relation between gambling and information engines has been presented before. In this paper, we briefly review the two concepts and then demonstrate an analogy between gambling, where bits are converted into wealth, and information engines, where bits representing measurements are converted into energy. From this analogy follows an extension of gambling to the continuous-valued case, which is shown to be useful for investments in currency exchange rates or in the stock market using options. Moreover, the analogy enables us to use well-known methods and results from one field to solve problems in the other. We present three such cases: maximum work extraction when the probability distributions governing the system and measurements are unknown, work extraction when some energy is lost in each cycle, e.g. due to friction, and an analysis of systems with memory. In all three cases, the analogy enables us to use known results in order to obtain new ones.

  9. Shake for Sigma, Pray for Pi: Classroom Orbital Overlap Analogies (United States)

    Dicks, Andrew P.


    An introductory organic classroom demonstration is discussed where analogies are made between common societal hand contact and covalent bond formation. A handshake signifies creation of a [sigma] bond ("head-on" orbital overlap), whereas the action of praying illustrates "sideways" overlap and generation of a [pi] bond. The nature of orbital and…

  10. Design, synthesis and antibacterial activity of novel 1-oxacephem analogs

    Institute of Scientific and Technical Information of China (English)

    Yi He; Jian Bo Wu; Fan Lei; Pei Chen; Li Hai; Yong Wu


    A series of 1-oxacephem analogs were synthesized and their antibacterial properties against five strains of Gram-positive and Gram-negative bacteria were evaluated in vitro while ceftazidine was selected as control.Some of the tested compounds,compound 12c in particular,showed more active against three selected strains than the standard.

  11. New analogies between extreme QCD and cold atoms

    Energy Technology Data Exchange (ETDEWEB)

    Nishida, Yusuke [Los Alamos National Laboratory


    We discuss two new analogies between extreme QCD and cold atoms. One is the analogue of 'hard probes' in cold atoms. The other is the analogue of 'quark-hadron continuity' in cold atoms.

  12. Difference in brain activations during appreciating paintings and photographic analogs. (United States)

    Mizokami, Yoshinori; Terao, Takeshi; Hatano, Koji; Hoaki, Nobuhiko; Kohno, Kentaro; Araki, Yasuo; Kodama, Kensuke; Makino, Mayu; Izumi, Toshihiko; Shimomura, Tsuyoshi; Fujiki, Minoru; Kochiyama, Takanori


    Several studies have investigated neural correlates of aesthetic appreciation for paintings but to date the findings have been heterogeneous. This heterogeneity may be attributed to previous studies' measurement of aesthetic appreciation of not only the beauty of paintings but also the beauty of motifs of the paintings. In order to better elucidate the beauty of paintings, it seems necessary to compare aesthetic appreciation of paintings and photographic analogs which included corresponding real images. We prepared for famous painters' pictures and their photographic analogs which were set up to resemble each painting in order to investigate the hypothesis that there exist specific neural correlates associated with the aesthetic appreciation for paintings. Forty-four subjects participated in functional magnetic resonance study which required comparisons of aesthetic appreciation of paintings of still life and landscape versus photographic analogs including corresponding real images of still life and landscape. Bilateral cuneus and the left lingual gyrus were activated in the comparison of aesthetic appreciation of paintings versus photographic analogs. In conclusion, the present findings suggest a possibility of the existence of specific neural correlates associated with the aesthetic appreciation for paintings and that bilateral cuneus and the left lingual gyrus may be involved.

  13. Synthesis, bioanalysis and pharmacology of nucleoside and nucleotide analogs

    NARCIS (Netherlands)

    Jansen, R.S.


    Nucleoside analogs are an important class of drugs in anticancer and antiviral therapy. The compounds are, however, only active after intracellular conversion to their mono-, di- and triphosphate nucleotide form. In this thesis the development of sensitive liquid chromatography coupled to tandem mas

  14. Analog/RF Circuit Design Techniques for Nanometerscale IC Technologies

    NARCIS (Netherlands)

    Nauta, Bram; Annema, Anne-Johan


    CMOS evolution introduces several problems in analog design. Gate-leakage mismatch exceeds conventional matching tolerances requiring active cancellation techniques or alternative architectures. One strategy to deal with the use of lower supply voltages is to operate critical parts at higher supply

  15. Analog Circuits in Ultra-Deep-Submicron CMOS

    NARCIS (Netherlands)

    Annema, Anne-Johan; Nauta, Bram; Langevelde, van Ronald; Tuinhout, Hans


    Modern and future ultra-deep-submicron (UDSM) technologies introduce several new problems in analog design. Nonlinear output conductance in combination with reduced voltage gain pose limits in linearity of (feedback) circuits. Gate-leakage mismatch exceeds conventional matching tolerances. Increasin

  16. Design and Analog VLSI Implementation of Artificial Neural Network

    Directory of Open Access Journals (Sweden)

    Prof. Bapuray.D.Yammenavar


    Full Text Available Nature has evolved highly advanced systems capable of performing complex computations, adoption and learning using analog computations. Furthermore nature has evolved techniques to deal with imprecise analog computations by using redundancy and massive connectivity. In this paper we are making use of Artificial Neural Network to demonstrate the way in which the biological system processes in analog domain. We are using 180nm CMOS VLSI technology for implementing circuits which performs arithmetic operations and for implementing Neural Network. The arithmetic circuits presented here are based on MOS transistors operating in subthreshold region. The basic blocks of artificial neuron are multiplier, adder and neuron activation function. The functionality of designed neural network is verified for analog operations like signal amplification and frequency multiplication. The network designed can be adopted for digital operations like AND, OR and NOT. The network realizes its functionality for the trained targets which is verified using simulation results. The schematic, Layout design and verification of proposed Neural Network is carried out using Cadence Virtuoso tool.

  17. Content Emphasis, Practice, and Cognitive Style in Analogical Problem Solving. (United States)

    Hsu, Chia-Ling; Wedman, John F.


    This study investigated the effect of content emphasis, learning practice, and field dependence/independence on college students' analogous problem-solving skills. Under certain conditions, field-independent subjects performed significantly better than field-dependent subjects. Subjects given a principle-based content emphasis performed…

  18. Inherently analog quantity representations in olive baboons (Papio anubis

    Directory of Open Access Journals (Sweden)

    Allison M Barnard


    Full Text Available Strong evidence indicates that non-human primates possess a numerical representation system, but the inherent nature of that system is still debated. Two cognitive mechanisms have been proposed to account for non-human primate numerical performance: (1 a discrete object-file system limited to quantities <4, and (2 an analog system which represents quantities comparatively but is limited by the ratio between two quantities. To test the underlying nature of non-human primate quantification, we asked eight experiment -naive olive baboons (Papio anubis to discriminate between number pairs containing small (<4, large (>4, or span (small vs. large numbers of food items presented simultaneously or sequentially. The prediction from the object-file hypothesis is that baboons will only accurately choose the larger quantity in small pairs, but not large or span pairs. Conversely, the analog system predicts that baboons will be successful with all numbers, and that success will be dependent on numerical ratio. We found that baboons successfully discriminated all pair types at above chance levels. In addition, performance significantly correlated with the ratio between the numerical values. Although performance was better for simultaneous trials than sequential trials, evidence favoring analog numerical representation emerged from both conditions, and was present even in the first exposure to number pairs. Together, these data favor the interpretation that a single, coherent analog representation system underlies spontaneous quantitative abilities in primates.

  19. Design, synthesis and antimicrobial evaluation of novel carbendazim dithioate analogs

    DEFF Research Database (Denmark)

    Zahran, Magdy A H; Osman, Amany M A; Wahed, Rania A.;


    -spectroscopy. All the synthesized carbendazim analogs were screened for their in vitro antimicrobial activity against different Gram-positive (Staphylococcus aureus and Micrococcus luteus), Gram-negative (Escherichia coli and Klebsiella pneumonia) bacteria, fungi (Fusarium solani and Fusarium oxysporu) and in vivo...

  20. Synthesis and biological activity of nifuroxazide and analogs. (United States)

    Tavares, L C; Penna, T C; Amaral, A T


    Nifuroxazide and thirteen analogs were synthesized from substituted benzoic acids and minimal inhibitory concentrations were determined using the serial dilution tests, in three sequential steps. Nifuroxazide and chloramphenicol were used as reference standards. The tests were performed in TSB against the standard bacterial strain of Staphylococcus aureus ATCC 25923.