Science.gov

Sample records for 10b states analogue

  1. Analysis of T = 1 {sup 10}B States Analogue to {sup 10}Be Cluster States

    SciTech Connect

    Uroic, M.; Miljanic, D.; Blagus, S.; Bogovac, M.; Prepolec, L.; Skukan, N.; Soic, N.; Majer, M.; Milin, M.; Lattuada, M.; Musumarra, A.; Acosta, L.

    2009-08-26

    Current status of the search for T = 1 cluster states in {sup 10}Be, {sup 10}B and {sup 10}C is presented. The best known of the three, {sup 10}Be, has an established rotational band (6.18, 7.54 and 10.15 MeV) with unusually large moment of inertia. Search of their isobaric analogue in {sup 10}B is presented, with emphasis on {sup 3}He+{sup 11}B reaction.

  2. Excited state dynamics of brightly fluorescent second generation epicocconone analogues.

    PubMed

    Chatterjee, Soumit; Karuso, Peter; Boulangé, Agathe; Franck, Xavier; Datta, Anindya

    2015-05-21

    The natural product epicocconone, owing to its unique fluorescence properties, has been developed into a range of products used in biotechnology, especially proteomics. However, its weak green fluorescence in its native state, while advantageous for proteomics applications, is a disadvantage in other applications that require two-color readouts. Here we report the photophysical characterization of two brightly fluorescent analogues of epicocconone. These analogues, with naphthyl or pyridyl groups replacing the heptatriene chain, resulted in bright fluorescence in both the native state and the long Stokes shifted enamine. Time-resolved fluorescence studies and DFT calculations were carried out to understand the excited state processes involved in fluorescence. Results showed the p-chloro group on the pyridyl is responsible for the high fluorescence of the native fluorophore. The application of one of these compounds for staining electrophoresis gels is exemplified. PMID:25902354

  3. OptZyme: Computational Enzyme Redesign Using Transition State Analogues

    PubMed Central

    Grisewood, Matthew J.; Gifford, Nathanael P.; Pantazes, Robert J.; Li, Ye; Cirino, Patrick C.; Janik, Michael J.; Maranas, Costas D.

    2013-01-01

    OptZyme is a new computational procedure for designing improved enzymatic activity (i.e., kcat or kcat/KM) with a novel substrate. The key concept is to use transition state analogue compounds, which are known for many reactions, as proxies for the typically unknown transition state structures. Mutations that minimize the interaction energy of the enzyme with its transition state analogue, rather than with its substrate, are identified that lower the transition state formation energy barrier. Using Escherichia coli β-glucuronidase as a benchmark system, we confirm that KM correlates (R2 = 0.960) with the computed interaction energy between the enzyme and the para-nitrophenyl- β, D-glucuronide substrate, kcat/KM correlates (R2 = 0.864) with the interaction energy of the transition state analogue, 1,5-glucarolactone, and kcat correlates (R2 = 0.854) with a weighted combination of interaction energies with the substrate and transition state analogue. OptZyme is subsequently used to identify mutants with improved KM, kcat, and kcat/KM for a new substrate, para-nitrophenyl- β, D-galactoside. Differences between the three libraries reveal structural differences that underpin improving KM, kcat, or kcat/KM. Mutants predicted to enhance the activity for para-nitrophenyl- β, D-galactoside directly or indirectly create hydrogen bonds with the altered sugar ring conformation or its substituents, namely H162S, L361G, W549R, and N550S. PMID:24116038

  4. Potential transition state analogue inhibitors for the penicillin-binding proteins.

    PubMed

    Pechenov, Aleksandr; Stefanova, Miglena E; Nicholas, Robert A; Peddi, Sridhar; Gutheil, William G

    2003-01-21

    Penicillin-binding proteins (PBPs) are ubiquitous bacterial enzymes involved in cell wall biosynthesis. The development of new PBP inhibitors is a potentially viable strategy for developing new antibacterial agents. Several potential transition state analogue inhibitors for the PBPs were synthesized, including peptide chloromethyl ketones, trifluoromethyl ketones, aldehydes, and boronic acids. These agents were characterized chemically, stereochemically, and as inhibitors of a set of low molecular mass PBPs: Escherichia coli (EC) PBP 5, Neisseria gonorrhoeae (NG) PBP 3, and NG PBP 4. A peptide boronic acid was the most effective PBP inhibitor in the series, with a preference observed for a d-boroAla-based over an l-boroAla-based inhibitor, as expected given that physiological PBP substrates are based on d-Ala at the cleavage site. The lowest K(I) of 370 nM was obtained for NG PBP 3 inhibition by Boc-l-Lys(Cbz)-d-boroAla (10b). Competitive inhibition was observed for this enzyme-inhibitor pair, as expected for an active site-directed inhibitor. For the three PBPs included in this study, an inverse correlation was observed between the values for log K(I) with 10b and the values for log(k(cat)/K(m)) for activity against the analogous substrate, and K(m)/K(I) ratios were 90, 1900, and 9600 for NG PBP 4, EC PBP 5, and NG PBP 3, respectively. These results demonstrate that peptide boronic acids can be effective transition state analogue inhibitors for the PBPs and provide a basis for the use of these agents as probes of PBP structure, function, and mechanism, as well as a possible basis for the development of new PBP-targeted antibacterial agents. PMID:12525187

  5. Martin B-10B

    NASA Technical Reports Server (NTRS)

    1935-01-01

    Martin B-10B: Although the front turret looks like it may have bee too high, the drag of the Martin B-10 bomber was low enough for it to have been faster than any U. S. Fighter when it was first ordered in January 1933. The NACA flew one of these B-10Bs in 1937 at the Langley Memorial Aeronautical Laboratory.

  6. Phosphonate analogues of carboxypeptidase A substrates are potent transition-state analogue inhibitors.

    PubMed

    Hanson, J E; Kaplan, A P; Bartlett, P A

    1989-07-25

    Analogues of tri- and tetrapeptide substrates of carboxypeptidase A in which the scissile peptide linkage is replaced with a phosphonate moiety (-PO2--O-) were synthesized and evaluated as inhibitors of the enzyme. The inhibitors terminated with either L-lactate or L-phenyllactate [designated (O) Ala and (O) Phe, respectively] in the P1' position. Transition-state analogy was shown for a series of 14 tri- and tetrapeptide derivatives containing the structure RCO-AlaP-(O)Ala [RCO-AP(O)A, AP indicates the phosphonic acid analogue of alanine] by the correlation of the Ki values for the inhibitors and the Km/kcat values for the corresponding amide substrates. This correlation supports a transition state for the enzymatic reaction that resembles the tetrahedral intermediate formed upon addition of water to the scissile carbonyl group. The inhibitors containing (O) Phe at the P1' position proved to be the most potent reversible inhibitors of carboxypeptidase A reported to date: the dissociation constants of ZAFP(O)F, ZAAP(O)F, and ZFAP(O)F are 4, 3, and 1 pM, respectively. Because of the high affinity of these inhibitors, their dissociation constants could not be determined by steady-state methods. Instead, the course of the association and dissociation processes was monitored for each inhibitor as its equilibrium with the enzyme was established in both the forward and reverse directions. A phosphonamidate analogue, ZAAPF, in which the peptide linkage is replaced with a -PO2-NH- moiety, was prepared and shown to hydrolyze rapidly at neutral pH (t1/2 = 20 min at pH 7.5). This inhibitor is bound an order of magnitude less tightly than the corresponding phosphonate, ZAAP(O)F, a result that contrasts with the 840-fold higher affinity of phosphonamidates for thermolysin [Bartlett, P. A., & Marlowe, C. K. (1987) Science 235, 569-571], a zinc peptidase with a similar arrangement of active-site catalytic residues. PMID:2790000

  7. A Transition State Analogue for an RNA-Editing Reaction

    PubMed Central

    Haudenschild, Brittany L.; Maydanovych, Olena; Véliz, Eduardo A.; Macbeth, Mark R.; Bass, Brenda L.; Beal, Peter A.

    2007-01-01

    Deamination at C6 of adenosine in RNA catalyzed by the ADAR enzymes generates inosine at the corresponding position. Because inosine is decoded as guanosine during translation, this modification can lead to codon changes in messenger RNA. Hydration of 8-azanebularine across the C6–N1 double bond generates an excellent mimic of the transition state proposed for the hydrolytic deamination reaction catalyzed by ADARs. Here, we report the synthesis of a phosphoramidite of 8-azanebularine and its use in the preparation of RNAs mimicking the secondary structure found at a known editing site in the glutamate receptor B subunit pre-mRNA. The binding properties of analogue-containing RNAs indicate that a tight binding ligand for an ADAR can be generated by incorporation of 8-azanebularine. The observed high-affinity binding is dependent on a functional active site, the presence of one, but not the other, of ADAR2’s two double-stranded RNA-binding motifs (dsRBMs), and the correct placement of the nucleoside analogue into the sequence/structural context of a known editing site. These results advance our understanding of substrate recognition during ADAR-catalyzed RNA editing and are important for structural studies of ADAR· RNA complexes. PMID:15355102

  8. QM/MM Analysis of Transition States and Transition State Analogues in Metalloenzymes.

    PubMed

    Roston, D; Cui, Q

    2016-01-01

    Enzymology is approaching an era where many problems can benefit from computational studies. While ample challenges remain in quantitatively predicting behavior for many enzyme systems, the insights that often come from computations are an important asset for the enzymology community. Here we provide a primer for enzymologists on the types of calculations that are most useful for mechanistic problems in enzymology. In particular, we emphasize the integration of models that range from small active-site motifs to fully solvated enzyme systems for cross-validation and dissection of specific contributions from the enzyme environment. We then use a case study of the enzyme alkaline phosphatase to illustrate specific application of the methods. The case study involves examination of the binding modes of putative transition state analogues (tungstate and vanadate) to the enzyme. The computations predict covalent binding of these ions to the enzymatic nucleophile and that they adopt the trigonal bipyramidal geometry of the expected transition state. By comparing these structures with transition states found through free energy simulations, we assess the degree to which the transition state analogues mimic the true transition states. Technical issues worth treating with care as well as several remaining challenges to quantitative analysis of metalloenzymes are also highlighted during the discussion. PMID:27498640

  9. Anomalous transition in {sup 10}B

    SciTech Connect

    Kurath, D.

    1995-08-01

    The transitions between the J,T = 3,0 ground state of {sup 10}B and the 3,0 state at 4.77 MeV present some puzzling features. The gamma transition between the states is of unknown multipolarity and very weak, with a strength of only 0.1 WU even if it is a pure E2. The shell model with the Cohen-Kurath POT interaction predicts a nearly pure E2 transition but with a transition probability about 4 times too strong. Recent inelastic pion scattering experiments on {sup 10}B excited this state with a strength only one tenth the value predicted by the shell model. It was found that these weak transitions are very sensitive to the wave functions and that orthogonally mixing the states with an intensity of 2% can satisfy both the pion scattering and the {gamma} decay (60% E2, 40% M1).

  10. Transition State Analogues of Purine Nucleoside Phosphorylase: the Work of Vernon L. Schramm

    PubMed Central

    Kresge, Nicole; Simoni, Robert D.; Hill, Robert L.

    2010-01-01

    Transition State Analogue Inhibitors of Purine Nucleoside Phosphorylase from Plasmodium falciparum (Kicska, G. A., Tyler, P. C., Evans, G. B., Furneaux, R. H., Kim, K., and Schramm, V. L. (2002) J. Biol. Chem. 277, 3219–3225) Purine-less Death in Plasmodium falciparum Induced by Immucillin-H, a Transition State Analogue of Purine Nucleoside Phosphorylase (Kicska, G. A., Tyler, P. C., Evans, G. B., Furneaux, R. H., Schramm, V. L., and Kim, K. (2002) J. Biol. Chem. 277, 3226–3231) Achieving the Ultimate Physiological Goal in Transition State Analogue Inhibitors for Purine Nucleoside Phosphorylase (Lewandowicz, A., Tyler, P. C., Evans, G. B., Furneaux, R. H., and Schramm, V. L. (2003) J. Biol. Chem. 278, 31465–31468)

  11. Four Generations of Transition State Analogues for Human Purine Nucleoside Phosphorylase

    SciTech Connect

    Ho, M.; Shi, W; Rinaldo-Mathis, A; Tyler, P; Evans, G; Almo, S; Schramm, V

    2010-01-01

    Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*{sub i} = 58 pM, first-generation) contains an iminoribitol cation with four asymmetric carbons. DADMe-Immucillin-H (K*{sub i} = 9 pM, second-generation), uses a methylene-bridged dihydroxypyrrolidine cation with two asymmetric centers. DATMe-Immucillin-H (K*{sub i} = 9 pM, third-generation) contains an open-chain amino alcohol cation with two asymmetric carbons. SerMe-ImmH (K*{sub i} = 5 pM, fourth-generation) uses achiral dihydroxyaminoalcohol seramide as the ribocation mimic. Crystal structures of PNPs establish features of tight binding to be; (1) ion-pair formation between bound phosphate (or its mimic) and inhibitor cation, (2) leaving-group interactions to N1, O6, and N7 of 9-deazahypoxanthine, (3) interaction between phosphate and inhibitor hydroxyl groups, and (4) His257 interacting with the 5{prime}-hydroxyl group. The first generation analogue is an imperfect fit to the catalytic site with a long ion pair distance between the iminoribitol and bound phosphate and weaker interactions to the leaving group. Increasing the ribocation to leaving-group distance in the second- to fourth-generation analogues provides powerful binding interactions and a facile synthetic route to powerful inhibitors. Despite chemical diversity in the four generations of transition-state analogues, the catalytic site geometry is almost the same for all analogues. Multiple solutions in transition-state analogue design are available to convert the energy of catalytic rate enhancement to binding energy in human PNP.

  12. Nematic order-disorder state transition in a liquid crystal analogue formed by oriented and migrating amoeboid cells

    NASA Astrophysics Data System (ADS)

    Kemkemer, R.; Teichgräber, V.; Schrank-Kaufmann, S.; Kaufmann, D.; Gruler, H.

    2000-10-01

    In cell culture, liquid crystal analogues are formed by elongated, migrating, and interacting amoeboid cells. An apolar nematic liquid crystal analogue is formed by different cell types like human melanocytes (=pigment cells of the skin), human fibroblasts (=connective tissue cells), human osteoblasts (=bone cells), human adipocytes (=fat cells), etc. The nematic analogue is quite well described by i) a stochastic machine equation responsible for cell orientation and ii) a self-organized extracellular guiding signal, E_2, which is proportional to the orientational order parameter as well as to the cell density. The investigations were mainly made with melanocytes. The transition to an isotropic state analogue can be accomplished either by changing the strength of interaction (e.g. variation of the cell density) or by influencing the cellular machinery by an externally applied signal: i) An isotropic gaseous state analogue is observed at low cell density (ρ < 110melanocytes/mm^2) and a nematic liquid crystal state analogue at higher cell density. ii) The nematic state analogue disappears if the bipolar shaped melanocytes are forced to become a star-like shape (induced by colchicine or staurosporine). The analogy between nematic liquid crystal state analogue formed by elongated, migrating and interacting cells and the nematic liquid crystal phase formed by interacting elongated molecules is discussed.

  13. Stationary bound states of massless scalar fields around black holes and black hole analogues

    NASA Astrophysics Data System (ADS)

    Benone, Carolina L.; Crispino, Luís C. B.; Herdeiro, Carlos A. R.; Radu, Eugen

    2015-06-01

    We discuss stationary bound states, a.k.a. clouds, for a massless test scalar field around Kerr black holes (BHs) and spinning acoustic BH analogues. In view of the absence of a mass term, the trapping is achieved via enclosing the BH — scalar field system in a cavity and imposing Dirichlet or Neumann boundary conditions. We discuss the variation of these bounds states with the discrete parameters that label them, as well as their spatial distribution, complementing results in our previous work [C. L. Benone, L. C. B. Crispino, C. Herdeiro and E. Radu, Phys. Rev. D91 (2015) 104038].

  14. Modern Climate Analogues of Late-Quaternary Paleoclimates for the Western United States.

    NASA Astrophysics Data System (ADS)

    Mock, Cary Jeffrey

    This study examined spatial variations of modern and late-Quaternary climates for the western United States. Synoptic climatological analyses of the modern record identified the predominate climatic controls that normally produce the principal modes of spatial climatic variability. They also provided a modern standard to assess past climates. Maps of the month-to-month changes in 500 mb heights, sea-level pressure, temperature, and precipitation illustrated how different climatic controls govern the annual cycle of climatic response. The patterns of precipitation ratios, precipitation bar graphs, and the seasonal precipitation maximum provided additional insight into how different climatic controls influence spatial climatic variations. Synoptic-scale patterns from general circulation model (GCM) simulations or from analyses of climatic indices were used as the basis for finding modern climate analogues for 18 ka and 9 ka. Composite anomaly maps of atmospheric circulation, precipitation, and temperature were compared with effective moisture maps compiled from proxy data to infer how the patterns, which were evident from the proxy data, were generated. The analyses of the modern synoptic climatology indicate that smaller-scale climatic controls must be considered along with larger-scale ones in order to explain patterns of spatial climate heterogeneity. Climatic extremes indicate that changes in the spatial patterns of precipitation seasonality are the exception rather than the rule, reflecting the strong influence of smaller-scale controls. Modern climate analogues for both 18 ka and 9 ka clearly depict the dry Northwest/wet Southwest contrast that is suggested by GCM simulations and paleoclimatic evidence. 18 ka analogues also show the importance of smaller-scale climatic controls in explaining spatial climatic variation in the Northwest and northern Great Plains. 9 ka analogues provide climatological explanations for patterns of spatial heterogeneity over several

  15. Transition state analogues in structures of ricin and saporin ribosome-inactivating proteins

    SciTech Connect

    Ho, Meng-Chiao; Sturm, Matthew B.; Almo, Steven C.; Schramm, Vern L.

    2010-01-12

    Ricin A-chain (RTA) and saporin-L1 (SAP) catalyze adenosine depurination of 28S rRNA to inhibit protein synthesis and cause cell death. We present the crystal structures of RTA and SAP in complex with transition state analogue inhibitors. These tight-binding inhibitors mimic the sarcin-ricin recognition loop of 28S rRNA and the dissociative ribocation transition state established for RTA catalysis. RTA and SAP share unique purine-binding geometry with quadruple {pi}-stacking interactions between adjacent adenine and guanine bases and 2 conserved tyrosines. An arginine at one end of the {pi}-stack provides cationic polarization and enhanced leaving group ability to the susceptible adenine. Common features of these ribosome-inactivating proteins include adenine leaving group activation, a remarkable lack of ribocation stabilization, and conserved glutamates as general bases for activation of the H{sub 2}O nucleophile. Catalytic forces originate primarily from leaving group activation evident in both RTA and SAP in complex with transition state analogues.

  16. The Origin of Bond Selectivity and Excited-State Reactivity in Retinal Analogues.

    PubMed

    Schapiro, Igor

    2016-05-19

    The effect of different conformations and substitutions on the photoisomerization of a retinal protonated Schiff base model is investigated by nonadiabatic molecular dynamics simulations. Three groups of retinal analogues are studied: (i) conformational isomers, (ii) methyl-substituted retinals, and (iii) C11-C12 bond locked retinals. In total 259 trajectories are calculated in the gas phase starting from different initial conditions. The effect on bond selectivity, the directionality of the isomerization, excited-state lifetime, and product distribution is derived from the ensemble of trajectories. Among the group of four isomers (9-, 11-, 13-cis, and all-trans) the 11-cis analogue is the most selective in terms of isomerizing double bond, while the other three produce a mixture of isomers. However, there is no preference for isomerization directionality and the product formation for the 11-cis isomer. In the group of analogues with different methylation patterns, it is found that a methyl group at position C10 can introduce unidirectionality. This methyl group also speeds the photoisomerization. In case of the analogue that is demethylated at the positions C10 and C13, all trajectories isomerize successfully from cis to trans conformation. The three C11-C12 bond locked retinals are found to have very different properties, which depend on the number of methylene units bridging this bond. The five-membered ring imposes a too-large restriction; hence, all trajectories remain on the excited state in the simulation time of 300 fs. The seven-membered ring is more flexible with preference for isomerization of the C9-C10 bond. Interestingly, the eight-membered ring leads to the fastest isomerization time and full directionality of C11-C12 bond isomerization. The trends observed in these simulations can help to understand whether the effects are intrinsic to the chromophore or are induced by the protein environment, by comparing to the trends from experiment. Furthermore

  17. Mapping visual analogue scale health state valuations onto standard gamble and time trade-off values.

    PubMed

    Dolan, P; Sutton, M

    1997-05-01

    Despite becoming increasingly common in evaluations of health care, different methods of quantitatively measuring health status appear to produce different valuations for identical descriptions of health. This paper reports on a study that elicited health state valuations from the general public using three different methods: the visual analogue scale (VAS), the standard gamble (SG) and the time trade-off (TTO). Two variants of the SG and TTO were tested: Props (using specially designed boards and cards); and No Props (using a self-completion booklet). This paper focuses on empirical relationships between health state valuations from the VAS and the (four) other methods. The relationships were estimated using Tobit regression of individual-level data. In contrast to a priori expectations, the mapping functions estimated suggest that differences are more pronounced across variant than across method. Furthermore, relationships with VAS scores are found to depend on the severity of the state: TTO Props valuations are higher than VAS responses for mild states and lower for more severe states; SG Props valuations are broadly similar to VAS scores over a wide range; and No Props responses are consistently higher than VAS valuations, particularly for more severe states. Explanations are proposed for these findings. PMID:9160441

  18. Two-proton decay of the isobaric analogue state of 31Ar

    NASA Astrophysics Data System (ADS)

    Mukha, I.; Axelsson, L.; Äystö, J.; Bergmann, U. C.; Borge, M. J. G.; Fraile, L. M.; Fynbo, H. O. U.; Honkanen, A.; Hornshøj, P.; Jading, Y.; Jonson, B.; Jokinen, A.; Martel, I.; Oinonen, M.; Nilsson, T.; Nyman, G.; Petersen, B.; Riisager, K.; Siiskonen, T.; Smedberg, M. H.; Tengblad, O.; Wenander, F.; Isolde Collaboration

    1998-02-01

    We have studied several two proton branches in the β-decay of 31Ar, the most intensive ones proceeding through the isobaric analogue state (IAS) in 31Cl. The energy and angular correlations of the two protons originating from the IAS have been measured. An indication of non-isotropic emission has been observed in the p+p+ 29P branch. The energy spectra of protons from the IAS 2p-branches seem to be continuous, which is difficult to explain by a sequential emission through a few intermediate levels in 30S. The model of non-sequential or democratic three-particle decay gives the best fit to the present data favoring the IAS spin-parity {5}/{2 +}.

  19. Isospin nonconserving interaction in the T =1 analogue states of the mass-70 region

    NASA Astrophysics Data System (ADS)

    Kaneko, K.; Sun, Y.; Mizusaki, T.; Tazaki, S.

    2014-03-01

    Mirror energy differences (MEDs) and triplet energy differences (TEDs) in the T =1 analogue states are important probes of isospin-symmetry breaking. Inspired by the recent spectroscopic data of 66Se, we investigate these quantities for A =66-78 nuclei with large-scale shell-model calculations. For the first time, we find clear evidence suggesting that the isospin nonconserving (INC) nuclear force has a significant effect for the upper fp shell region. Detailed analysis shows that, in addition to the INC force, the electromagnetic spin-orbit interaction plays an important role for the large, negative MED in A =66 and 70 and the multipole Coulomb term contributes to the negative TED in all the T =1 triplet nuclei. The INC force and its strength needed to reproduce the experimental data are compared with those from the G-matrix calculation using the modern charge-dependent nucleon-nucleon forces.

  20. Measurement of 10B content in thin-film 10B samples.

    PubMed

    Zhang, Guohui; Liu, Jiaming; Xue, Zhihua; Wu, Hao; Liu, Yuxiao; Yuan, Xi; Liu, Xiang

    2011-06-01

    Two thin-film (10)B samples on tantalum backings were made for measurement of cross sections of the (10)B(n,α)(7)Li reaction in the MeV neutron energy region. The number of (10)B atoms in the samples was determined using the relative comparison method by detecting alpha and triton particles from thermal neutron induced nuclear reactions of (10)B(n(th),α)(7)Li and (6)Li(n(th),t)(4)He with a (6)LiF sample as the reference. A twin gridded ionization chamber was used as the detector of charged particles. PMID:21353786

  1. The spin-free analogue of Mukherjee's state-specific multireference coupled cluster theory

    NASA Astrophysics Data System (ADS)

    Datta, Dipayan; Mukherjee, Debashis

    2011-02-01

    In this paper, we develop a rigorously spin-adapted version of Mukherjee's state-specific multireference coupled cluster theory (SS-MRCC, also known as Mk-MRCC) [U. S. Mahapatra, B. Datta, and D. Mukherjee, J. Chem. Phys. 110, 6171 (1999)] for reference spaces comprising open-shell configurations. The principal features of our approach are as follows: (1) The wave operator Ω is written as Ω = ∑μΩμ|ϕμ>cμ, where {ϕμ} is the set of configuration state functions spanning a complete active space. (2) In contrast to the Jeziorski-Monkhorst Ansatz in spin-orbital basis, we write Ωμ as a power series expansion of cluster operators Rμ defined in terms of spin-free unitary generators. (3) The operators Rμ are either closed-shell-like n hole-n particle excitations (denoted as Tμ) or they involve valence (active) destruction operators (denoted as Sμ); these latter type of operators can have active-active scatterings, which can also carry the same active orbital labels (such Sμ's are called to have spectator excitations). (4) To simulate multiple excitations involving powers of cluster operators, we allow the Sμ's carrying the same active orbital labels to contract among themselves. (5) We exclude Sμ's with direct spectator scatterings. (6) Most crucially, the factors associated with contracted composites are chosen as the inverse of the number of ways the Sμ's can be joined among one another leading to the same excitation. The factors introduced in (6) have been called the automorphic factors by us. One principal thrust of this paper is to show that the use of the automorphic factors imparts a remarkable simplicity to the final amplitude equations: the equations consist of terms that are at most quartic in cluster amplitudes, barring only a few. In close analogy to the Mk-MRCC theory, the inherent linear dependence of the cluster amplitudes leading to redundancy is resolved by invoking sufficiency conditions, which are exact spin-free analogues of the

  2. Inhibition and structure of Trichomonas vaginalis purine nucleoside phosphorylase with picomolar transition state analogues.

    PubMed

    Rinaldo-Matthis, Agnes; Wing, Corin; Ghanem, Mahmoud; Deng, Hua; Wu, Peng; Gupta, Arti; Tyler, Peter C; Evans, Gary B; Furneaux, Richard H; Almo, Steven C; Wang, Ching C; Schramm, Vern L

    2007-01-23

    Trichomonas vaginalis is a parasitic protozoan purine auxotroph possessing a unique purine salvage pathway consisting of a bacterial type purine nucleoside phosphorylase (PNP) and a purine nucleoside kinase. Thus, T. vaginalis PNP (TvPNP) functions in the reverse direction relative to the PNPs in other organisms. Immucillin-A (ImmA) and DADMe-Immucillin-A (DADMe-ImmA) are transition state mimics of adenosine with geometric and electrostatic features that resemble early and late transition states of adenosine at the transition state stabilized by TvPNP. ImmA demonstrates slow-onset tight-binding inhibition with TvPNP, to give an equilibrium dissociation constant of 87 pM, an inhibitor release half-time of 17.2 min, and a Km/Kd ratio of 70,100. DADMe-ImmA resembles a late ribooxacarbenium ion transition state for TvPNP to give a dissociation constant of 30 pM, an inhibitor release half-time of 64 min, and a Km/Kd ratio of 203,300. The tight binding of DADMe-ImmA supports a late SN1 transition state. Despite their tight binding to TvPNP, ImmA and DADMe-ImmA are weak inhibitors of human and P. falciparum PNPs. The crystal structures of the TvPNP x ImmA x PO4 and TvPNP x DADMe-ImmA x PO4 ternary complexes differ from previous structures with substrate analogues. The tight binding with DADMe-ImmA is in part due to a 2.7 A ionic interaction between a PO4 oxygen and the N1' cation of the hydroxypyrrolidine and is weaker in the TvPNP x ImmA x PO4 structure at 3.5 A. However, the TvPNP x ImmA x PO4 structure includes hydrogen bonds between the 2'-hydroxyl and the protein that are not present in TvPNP x DADMe-ImmA x PO4. These structures explain why DADMe-ImmA binds tighter than ImmA. Immucillin-H is a 12 nM inhibitor of TvPNP but a 56 pM inhibitor of human PNP. And this difference is explained by isotope-edited difference infrared spectroscopy with [6-18O]ImmH to establish that O6 is the keto tautomer in TvPNP x ImmH x PO4, causing an unfavorable leaving-group interaction

  3. One- and two-step mechanisms of the 9Be( 12C, 11B) 10B reaction at Elab( 12C)=65 MeV and the energy dependence of 11,10B+ 10B interactions

    NASA Astrophysics Data System (ADS)

    Rudchik, A. T.; Momotyuk, O. A.; Budzanowski, A.; Chernievsky, V. K.; Koshchy, E. I.; Mokhnach, A. V.; Ziman, V. A.; Kliczewski, S.; Siudak, R.; Skwirczyńska, I.; Szczurek, A.; Makowska-Rzeszutko, M.; G l̵owacka, L.; Turkiewicz, J.

    2000-09-01

    Angular distributions of the 9Be( 12C, 11B) 10B reaction were measured at the energy of Elab( 12C)=65 MeV for transitions to the ground and 0.72 MeV (1 +), 1.74 MeV (0 +, T=1), 3.59 MeV (2 +) excited states of the 10B nucleus and 2.12 MeV (1/2 -)+2.15 MeV (1 +) excited states of 11B and 10B nuclei, respectively. Data were analyzed within the coupled reaction channel (CRC) model including one- and two-step transfer mechanisms. The elastic and inelastic scattering and p-, d-, (d + n)-, (n + p)-, ( 3He + p)- and ( 3He + d)-transfer mechanisms were included in the coupled channel scheme. It was found that two-step processes are important for all transitions. Data of 10B+ 10B elastic scattering from the literature were included in the analysis of the energy dependence of optical model parameters for 10B+ 10B and 10B+ 11B interactions. A good description of all sets of experimental data was achieved.

  4. Effects of Wnt-10b on proliferation and differentiation of murine melanoma cells

    SciTech Connect

    Misu, Masayasu; Ouji, Yukiteru; Kawai, Norikazu; Nishimura, Fumihiko; Nakamura-Uchiyama, Fukumi; Yoshikawa, Masahide

    2015-08-07

    In spite of the strong expression of Wnt-10b in melanomas, its role in melanoma cells has not been elucidated. In the present study, the biological effects of Wnt-10b on murine B16F10 (B16) melanoma cells were investigated using conditioned medium from Wnt-10b-producing COS cells (Wnt-CM). After 2 days of culture in the presence of Wnt-CM, proliferation of B16 melanoma cells was inhibited, whereas tyrosinase activity was increased. An in vitro wound healing assay demonstrated that migration of melanoma cells to the wound area was inhibited with the addition of Wnt-CM. Furthermore, evaluation of cellular senescence revealed prominent induction of SA-β-gal-positive senescent cells in cultures with Wnt-CM. Finally, the growth of B16 melanoma cell aggregates in collagen 3D-gel cultures was markedly suppressed in the presence of Wnt-CM. These results suggest that Wnt-10b represses tumor cell properties, such as proliferation and migration of B16 melanoma cells, driving them toward a more differentiated state along a melanocyte lineage. - Highlights: • Wnt-10b inhibited proliferation and migration of melanoma cells. • Wnt-10b induced tyrosinase activity and senescence of melanoma cells. • Wnt-10b suppressed growth of cell aggregates in collagen 3D-gel cultures. • Wnt-10b represses tumor cell properties, driving them toward a more differentiated state along a melanocyte lineage.

  5. Novel Convenient Synthesis of (10)B-Enriched Sodium Borohydride.

    PubMed

    Safronov, Alexander V; Jalisatgi, Satish S; Hawthorne, M Frederick

    2016-06-01

    A convenient and efficient synthesis of (10)B-enriched sodium borohydride [Na(10)BH4] from commercially available (10)B-enriched boric acid [(10)B(OH)3] is described. The reaction sequence (10)B(OH)3 → (10)B(On-Bu)3 → (10)BH3·Et3N → Na(10)BH4 afforded the product in 60-80% yield. The reaction was successfully scaled to hundreds of gram per run. PMID:27195803

  6. NASA/ESMD Analogue Mission Plans

    NASA Technical Reports Server (NTRS)

    Hoffman, Stephen J.

    2007-01-01

    A viewgraph presentation exploring Earth and its analogues is shown. The topics include: 1) ESMD Goals for the Use of Earth Analogues; 2) Stakeholders Summary; 3) Issues with Current Analogue Situation; 4) Current state of Analogues; 5) External Implementation Plan (Second Step); 6) Recent Progress in Utilizing Analogues; 7) Website Layout Example-Home Page; 8) Website Layout Example-Analogue Site; 9) Website Layout Example-Analogue Mission; 10) Objectives of ARDIG Analog Initiatives; 11) Future Plans; 12) Example: Cold-Trap Sample Return; 13) Example: Site Characterization Matrix; 14) Integrated Analogue Studies-Prerequisites for Human Exploration; and 15) Rating Scale Definitions.

  7. Analogue mouse pointer control via an online steady state visual evoked potential (SSVEP) brain-computer interface

    NASA Astrophysics Data System (ADS)

    Wilson, John J.; Palaniappan, Ramaswamy

    2011-04-01

    The steady state visual evoked protocol has recently become a popular paradigm in brain-computer interface (BCI) applications. Typically (regardless of function) these applications offer the user a binary selection of targets that perform correspondingly discrete actions. Such discrete control systems are appropriate for applications that are inherently isolated in nature, such as selecting numbers from a keypad to be dialled or letters from an alphabet to be spelled. However motivation exists for users to employ proportional control methods in intrinsically analogue tasks such as the movement of a mouse pointer. This paper introduces an online BCI in which control of a mouse pointer is directly proportional to a user's intent. Performance is measured over a series of pointer movement tasks and compared to the traditional discrete output approach. Analogue control allowed subjects to move the pointer faster to the cued target location compared to discrete output but suffers more undesired movements overall. Best performance is achieved when combining the threshold to movement of traditional discrete techniques with the range of movement offered by proportional control.

  8. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a)...

  9. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a)...

  10. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a)...

  11. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2013 CFR

    2000-04-01

    ... 17 Commodity and Securities Exchanges 3 2000-04-01 2000-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each application for a stay of a trustee's duty...

  12. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2010 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a)...

  13. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2014 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a)...

  14. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2010 CFR

    2005-04-01

    ... 17 Commodity and Securities Exchanges 3 2005-04-01 2005-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a)...

  15. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2010 CFR

    2015-04-01

    ... 17 Commodity and Securities Exchanges 4 2015-04-01 2015-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a)...

  16. Study of the 10B(p,α)7Be Reaction through the Indirect Trojan Horse Method

    NASA Astrophysics Data System (ADS)

    Puglia, S. M. R.; Romano, S.; Del Santo, M. G.; Lamia, L.; Spitaleri, C.; Carlin, N.; Cherubini, S.; Gulino, M.; Kroha, V.; Kubono, S.; La Cognata, M.; Li, C.; Pizzone, R. G.; Qungang, W.; Rapisarda, G. G.; Sergi, M. L.; Somoryai, E.; Souza, F.; Szanto de Toledo, A.; Tudisco, S.; Tumino, A.; Wakabayashi, Y.; Yamaguchi, H.

    2010-03-01

    The 10B(p,α)7Be reaction is the main responsible for 10B destruction in stellar interior. In such environments the process takes places mainly through a resonant state of the compound 11C nucleus. The 10B(p,α)7Be reaction has been studied by means of the Trojan Horse Method using the 2H(10B,α7Be)n three-body reaction. The experiment was performed at the Laboratori Nazionali del Sud in Catania. The 10B(p,α)7Be reaction cross section has been extracted at low neutron momentum.

  17. Two Active Site Divalent Ions in the Crystal Structure of the Hammerhead Ribozyme Bound to a Transition State Analogue.

    PubMed

    Mir, Aamir; Golden, Barbara L

    2016-02-01

    The crystal structure of the hammerhead ribozyme bound to the pentavalent transition state analogue vanadate reveals significant rearrangements relative to the previously determined structures. The active site contracts, bringing G10.1 closer to the cleavage site and repositioning a divalent metal ion such that it could, ultimately, interact directly with the scissile phosphate. This ion could also position a water molecule to serve as a general acid in the cleavage reaction. A second divalent ion is observed coordinated to O6 of G12. This metal ion is well-placed to help tune the pKA of G12. On the basis of this crystal structure as well as a wealth of biochemical studies, we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid. PMID:26551631

  18. Acute and subacute toxicity of 10B-paraboronophenylalanine

    SciTech Connect

    Taniyama, K.; Fujiwara, H.; Kuno, T.; Saito, N.; Shuntoh, H.; Sakaue, M.; Tanaka, C. )

    1989-07-01

    The acute and subacute toxicities of 10B-paraboronophenylalanine (10B-BPA) were investigated in the rat, according to the Good Laboratory Practice Standard for safety studies on drugs in Japan. In the acute toxicity test of 10B-BPA, LD50 values of acidic 10B-BPA for intraperitoneal and subcutaneous injections were 640 mg/kg for male and 710 mg/kg for female rats, and more than 1,000 mg/kg for male and female rats, respectively. The LD50 values of neutral 10B-BPA for intraperitoneal and subcutaneous injections were more than 3,000 mg/kg for male and female rats. The difference in LD50 values between acidic and neutral 10B-BPA may be attributed to the acidity of material. From the subacute toxicity test, in which the rats were injected daily subcutaneously for 28 days, the following toxic effects of 10B-BPA were observed. Increase in ketone level in the urine was induced in all rats treated with 10B-BPA. High dose of 10B-BPA (1,500 mg/kg) induced increase in spleen weight and reticulocyte count, and decrease in hemoglobin count, thereby suggesting that 10B-BPA causes hemolysis. Increases in the leukocyte count and the ratio of neutrophils and lymphocytes were also observed in rats treated with a high dose of 10B-BPA. This may be attributed to local reactions at the injection site. There were no significant differences in the findings between control rats and rats treated with a low dose of 10B-BPA (300 mg/kg). Thus, low doses of neutral 10B-BPA may be available for use as a drug.

  19. Occurrence of eight bisphenol analogues in indoor dust from the United States and several Asian countries: implications for human exposure.

    PubMed

    Liao, Chunyang; Liu, Fang; Guo, Ying; Moon, Hyo-Bang; Nakata, Haruhiko; Wu, Qian; Kannan, Kurunthachalam

    2012-08-21

    Bisphenol A has been reported to be a ubiquitous contaminant in indoor dust, and human exposure to this compound is well documented. Information on the occurrence of and human exposure to other bisphenol analogues is limited. In this study, eight bisphenol analogues, namely 2,2-bis(4-hydroxyphenyl)propane (BPA), 4,4'-(hexafluoroisopropylidene)diphenol (BPAF), 4,4'-(1-phenylethylidene)bisphenol (BPAP), 2,2-bis(4-hydroxyphenyl)butane (BPB), 4,4'-dihydroxydiphenylmethane (BPF), 4,4'-(1,4-phenylenediisopropylidene)bisphenol (BPP), 4,4'- sulfonyldiphenol (BPS), and 4,4'-cyclohexylidenebisphenol (BPZ), were determined in indoor dust samples (n = 156) collected from the United States (U.S.), China, Japan, and Korea. Samples were extracted by solid-liquid extraction, purified by automated solid phase extraction methods, and determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total concentrations of bisphenols (∑BPs; sum of eight bisphenols) in dust were in the range of 0.026-111 μg/g (geometric mean: 2.29 μg/g). BPA, BPS, and BPF were the three major bisphenols, accounting for >98% of the total concentrations. Other bisphenol analogues were rare or not detected, with the exception of BPAF, which was found in 76% of the 41 samples collected in Korea (geometric mean: 0.0039 μg/g). The indoor dust samples from Korea contained the highest concentrations of both individual and total bisphenols. BPA concentrations in dust were compared among three microenvironments (house, office, and laboratory). The estimated median daily intake (EDI) of ∑BPs through dust ingestion in the U.S., China, Japan, and Korea was 12.6, 4.61, 15.8, and 18.6 ng/kg body weight (bw)/day, respectively, for toddlers and 1.72, 0.78, 2.65, and 3.13 ng/kg bw/day, respectively, for adults. This is the first report on the occurrence of bisphenols, other than BPA, in indoor dust. PMID:22784190

  20. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2011 CFR

    1998-04-01

    ... 17 Commodity and Securities Exchanges 3 1998-04-01 1998-04-01 false Content. 260.10b-5 Section 260.10b-5 GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each application for a stay of a trustee's duty to resign under section 310(b) of the...

  1. Formation of substrate and transition-state analogue complexes in crystals of phosphoglucomutase after removing the crystallization salt.

    PubMed

    Ray, W J; Puvathingal, J M; Liu, Y W

    1991-07-16

    Crystals of phosphoglucomutase, grown in 2.1 M ammonium sulfate, "desalted", and suspended in a 30% polyoxyethylene-8000/1 M glycine solution as described in the accompanying paper [Ray, W. J., Jr., Puvathingal, J. M., Bolin, J. T., Minor, W., Liu, Y., & Muchmore, S. W. (1991) Biochemistry 30 (preceding paper in this issue)], were treated with glucose phosphates to form an equilibrium mixture of the catalytically active substrate/product complexes. However, this treatment extensively fractured the crystals, even when very dilute solutions of glucose phosphates were used. But formation of the desired complexes was achieved, without fracturing, by introducing the glucose phosphates at high salt concentration, where they do not bind significantly to the enzyme, and maintaining their presence during subsequent sulfate-removal steps, in order to obtain essentially uniform binding throughout the crystal at all times. Although this procedure produced unfractured crystals of the catalytically active complexes, an adjustment in water activity was required to prevent the crystals from slowly liquefying in the presence of the added glucose phosphates. After this adjustment, the quality of diffraction-grade crystals subjected to this treatment was not significantly altered. An even larger adjustment in water activity was required to stabilize crystals that had been largely converted into a mixture of vanadate-based transition-state analogue complexes [cf. Ray, W. J., Jr., & Puvathingal, J. M. (1990) Biochemistry 29, 2790-2801] by means of an analogous procedure. The rationale for, and the implications of, this adjustment of water activity are discussed. The phenomenon of lattice-based binding cooperativity also is discussed together with a possible role for such cooperativity in the fracturing of protein crystals during formation of ligand complexes and possible ways to circumvent such fracturing based on the annealing of crystals at fractional saturation. An assay for

  2. Population-Based Preference Weights for the EQ-5D Health States Using the Visual Analogue Scale (VAS) in Iran

    PubMed Central

    Goudarzi, Reza; Zeraati, Hojjat; Akbari Sari, Ali; Rashidian, Arash; Mohammad, Kazem

    2016-01-01

    Background Health-related quality of life (HRQoL) is used as a measure to valuate healthcare interventions and guide policy making. The EuroQol EQ-5D is a widely used generic preference-based instrument to measure Health-related quality of life. Objectives The objective of this study was to develop a value set of the EQ-5D health states for an Iranian population. Patients and Methods This study is a cross-sectional study of Iranian populations. Our sample from Iranian populations consists out of 869 participants, who were selected for this study using a stratified probability sampling method. The sample was taken from individuals living in the city of Tehran and was stratified by age and gender from July to November 2013. Respondents valued 13 health states using the visual analogue scale (VAS) of the EQ-5D. Several fixed effects regression models were tested to predict the full set of health states. We selected the final model based on the logical consistency of the estimates, the sign and magnitude of the regression coefficients, goodness of fit, and parsimony. We also compared predicted values with a value set from similar studies in the UK and other countries. Results Our results show that the HRQoL does not vary among socioeconomic groups. Models at the individual level resulted in an additive model with all coefficients being statistically significant, R2 = 0.55, a value of 0.75 for the best health state (11112), and a value of -0.074 for the worst health state (33333). The value set obtained for the study sample remarkably differs from those elicited in developed countries. Conclusions This study is the first estimate for the EQ-5D value set based on the VAS in Iran. Given the importance of locally adapted value set the use of this value set can be recommended for future studies in Iran and In the EMRO regions. PMID:27186384

  3. Measurement of the 4. 8-MeV /sup 9/B state width by the reaction /sup 10/B(/sup 3/He,. cap alpha. )/sup 9/B(. cap alpha. ) /sup 5/Li at E( /sup 3/He) = 2. 3 and 5. 0 MeV

    SciTech Connect

    Arena, N.; Cavallaro, S.; Fazio, G.; Giardina, G.; Italiano, A.; Mezzanares, F.

    1986-10-13

    The analog of the 4.7-MeV state of the /sup 9/Be nucleus has been observed in its mirror /sup 9/B by the reaction /sup 10/B(/sup 3/He, ..cap alpha..)/sup 9/B(..cap alpha..) /sup 5/Li (g.s.) at E( /sup 3/He) = 2.3 and 5.0 MeV. The excitation energy and width of the state have been deduced. The value of 1.5 +- 0.3 MeV found for the width is in line with the value deduced by the reaction /sup 7/Li(/sup 3/He,n) /sup 9/B, but it is larger by a factor of about 4 than the one measured by the proton following the ..beta../sup +/ decay of the /sup 9/C nucleus.

  4. 17 CFR 260.10b-1 - Calculation of percentages.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Calculation of percentages. 260.10b-1 Section 260.10b-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Calculation of percentages. The percentages of voting securities and other securities specified in section...

  5. 18 CFR 35.10b - Electric Quarterly Reports.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Electric Quarterly Reports. 35.10b Section 35.10b Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT FILING OF RATE SCHEDULES AND...

  6. 18 CFR 35.10b - Electric Quarterly Reports.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Electric Quarterly Reports. 35.10b Section 35.10b Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT FILING OF RATE SCHEDULES AND...

  7. 18 CFR 35.10b - Electric Quarterly Reports.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Electric Quarterly Reports. 35.10b Section 35.10b Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT FILING OF RATE SCHEDULES AND...

  8. 18 CFR 35.10b - Electric Quarterly Reports.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Electric Quarterly Reports. 35.10b Section 35.10b Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... energy or transmission services within the Electric Reliability Council of Texas or any entity...

  9. 18 CFR 35.10b - Electric Quarterly Reports.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Electric Quarterly Reports. 35.10b Section 35.10b Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... energy or transmission services within the Electric Reliability Council of Texas or any entity...

  10. Transient resonance Raman spectra of benzophenone and its four isotopic analogues in the lowest excited triplet state

    SciTech Connect

    Tahara, T.; Hamaguchi, H.; Tasumi, M.

    1987-11-05

    Transient resonance Raman spectra of T/sub 1/ benzophenone (T/sub 1/BP) and its four isotopic analogues in carbon tetrachloride solutions were measured. Vibrational assignments of eight T/sub 1/ bands have been made on the basis of the observed isotopic frequency shifts. The assignments clarified the following three points concerning the structure of T/sub 1/ BP in solution. (1) The CO bond order in T/sub 1/ BP is much lower than that in the ground-state benzophenone (S/sub 0/ BP). The CO stretching frequency in T/sub 1/ is found to be 1222 cm/sup -1/, whereas the corresponding value in S/sub 0/ is 1665 cm/sup -1/. The former frequency indicates a single-bond-like character of the CO bonding in the T/sub 1/ state. (2) Vibrational frequencies of several ring modes show marked downshifts in going from S/sub 0/ to T/sub 1/. This suggests the delocalization of the ..pi..* electron into the ring part. (3) The assignment (1302 cm/sup -1/) of the symmetric C-phenyl stretch mode in the T/sub 1/ withdraws S/sub 0/ absorption spectrum is questioned. According to the present assignment, the frequency of this mode (approx. 1100 cm/sup -1/) is slightly lower than that in the ground state (1150 cm/sup -1/). The simple quantum chemical picture of T/sub 1/ BP, which predicted the increase of the C-phenyl bond order with the ..pi..* withdraws n excitation, should therefore be reconsidered.

  11. Study of the 10B(p, αγ) 7Be and 10B (p,p‧ γ)10B reactions for PIGE purposes

    NASA Astrophysics Data System (ADS)

    Lagoyannis, A.; Preketes-Sigalas, K.; Axiotis, M.; Foteinou, V.; Harissopulos, S.; Kokkoris, M.; Misaelides, P.; Paneta, V.; Patronis, N.

    2015-01-01

    Differential cross sections were measured at 8 angles and at proton energies from 2 to 5 MeV for the 10B(p, αγ) 7Be and 10B (p,p‧ γ)10B reactions using two thin targets. The γ-rays emitted at Eγ = 429 and 718 keV respectively, were detected by four HPGe detectors placed on a motorized turntable. The overall systematic uncertainty of the measurements was estimated to be ∼8% while the statistical errors did not exceed 5%. The validity of the obtained cross sections was tested by performing a thick target benchmarking experiment. The results of the present work are compared with existing ones from literature and possible explanations for the observed differences are discussed.

  12. Competitive radiative and reactive relaxation channels in the excited state decay of some thio-analogues of EE-distyrylbenzene.

    PubMed

    Ginocchietti, G; Galiazzo, G; Mazzucato, U; Spalletti, A

    2005-07-01

    The photophysical and photochemical properties of some thio-analogues of symmetrically substituted EE-1,4-distyrylbenzene (linear conjugation) and EE-1,3-distyrylbenzene (crossed conjugation), where thiophene rings replace the side benzene rings or the central benzene ring, have been investigated. The kinetic competition between the radiative and reactive relaxation channels of the lowest excited singlet state has been compared with that found for the corresponding hydrocarbons. The photobehaviour markedly depends on the type of conjugation and on the position (2' or 3') of the ethenic bridge with respect to the sulfur atom. The main effect of the heteroatom is an increase in the photoisomerization yield due to a decrease of the torsional barrier in S(1) and to an increase in the S(1)--> T(1) intersystem crossing, which opens the way to isomerization in the triplet manifold. Conformational equilibria, due to restricted rotation around the quasi-single bonds with the ethenic carbons, have also been investigated by selective photoexcitation for the compounds with side 3'-thienyl groups. PMID:15986063

  13. Inhibition and Structure of Trichomonas vaginalis Purine Nucleoside Phosphorylase with Picomolar Transition State Analogues

    SciTech Connect

    Rinaldo-Matthis,A.; Wing, C.; Ghanem, M.; Deng, H.; Wu, P.; Gupta, A.; Tyler, P.; Evans, G.; Furneaux, R.; et al.

    2007-01-01

    Trichomonas vaginalis is a parasitic protozoan purine auxotroph possessing a unique purine salvage pathway consisting of a bacterial type purine nucleoside phosphorylase (PNP) and a purine nucleoside kinase. Thus, T. vaginalis PNP (TvPNP) functions in the reverse direction relative to the PNPs in other organisms. Immucillin-A (ImmA) and DADMe-Immucillin-A (DADMe-ImmA) are transition stte mimics of adenosine with geometric and electrostatic features that resemble early and late transition states of adenosine at the transition state stabilized by TvPNP. ImmA demonstrates slow-onset tight-binding inhibition with TvPNP, to give an equilibrium dissociation constant of 87 pM, an inhibitor release half-time of 17.2 min, and a K{sub m}/K{sub d} ratio of 70,100. DADMe-ImmA resembles a late ribooxacarbenium ion transition state for TvPNP to give a dissociation constant of 30 pM, an inhibitor release half-time of 64 min, and a K{sub m}/K{sub d} ratio of 203,300. The tight binding of DADMe-ImmA supports a late S{sub N}1 transition state. Despite their tight binding to TvPNP, ImmA and DADMe-ImmA are weak inhibitors of human and P. falciparum PNPs. The crystal structures of the TvPNP-ImmA{center_dot}PO{sub 4} and TvPNP{center_dot}DADMe-ImmA{center_dot}PO{sub 4} ternary complexes differ from previous structures with substrate anologues. The tight binding with DADMe-ImmA is in part due to a 2.7 {angstrom} ionic interaction between a PO{sub 4} oxygen and the N1 cation of the hydroxypyrrolidine and is weaker in the TvPNP{center_dot}ImmA{center_dot}PO{sub 4} structure at 3.5 {angstrom}. However, the TvPNP{center_dot}ImmA{center_dot}PO{sub 4} structure includes hydrogen bonds between the 2'-hydroxyl and the protein that are not present in TvPNP{center_dot}DADMe-ImmA{center_dot}PO{sub 4}. These structures explain why DADMe-ImmA binds tighter than ImmA. Immucillin-H is a 12 nM inhibitor of TvPNP but a 56 pM inhibitor of human PNP. And this difference is explained by isotope

  14. Immune Modulation of the T Cell Response in Asthma through Wnt10b.

    PubMed

    Trischler, Jordis; Shiomi, Takayuki; Turner, Damian L; Sklepkiewicz, Piotr L; Goldklang, Monica P; Tanaka, Kenji F; Xu, Ming; Farber, Donna L; D'Armiento, Jeanine M

    2016-04-01

    Asthma is a chronic inflammatory disease, which is characterized by activation of CD4(+) T helper 2 cells orchestrating an allergic airway response. Whereas the role of Wnt family members in regulating T cell maintenance and maturation is established, their contribution to T cell activation in allergic asthma is not known. We hypothesized that Wnt10b plays a role in the modulation of the allergic airway response and affects T cell activation and polarization. Using an in vivo house dust mite asthma model, Wnt10b-deficient (Wnt10b(-/-)) mice were allergen-sensitized and inflammation, as well as T cell activation, was studied in vivo and in vitro. Wnt10b(-/-) mice exhibited an augmented inflammatory phenotype with an increase in eosinophils in the bronchoalveolar lavage and IL-4 and IL-13 in the lungs when compared with wild-type mice. In vitro studies confirmed an increased T helper type 2 polarization and increased T cell activation of Wnt10b(-/-) cells. Accordingly, the percentage of naive T cells was elevated by the addition of recombinant Wnt10b protein. Finally, Wnt10b(-/-) mice exhibited an increase in the percentage of effector T cells in the lungs after house dust mite sensitization, which indicated a heightened activation state, measured by an increased percentage of CD69(hi)CD11a(hi) cells. These findings suggest that Wnt10b plays an important role in regulating asthmatic airway inflammation through modification of the T cell response and is a prospective target in the disease process. PMID:26436894

  15. 33 CFR 157.10b - Segregated ballast tanks, dedicated clean ballast tanks, and special ballast arrangements for...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Continental Shelf oil. 157.10b Section 157.10b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Continental Shelf oil. (a) Each tank vessel that is engaged in the transfer of crude oil from an offshore oil exploitation or production facility on the Outer Continental Shelf of the United States on or after June...

  16. 33 CFR 157.10b - Segregated ballast tanks, dedicated clean ballast tanks, and special ballast arrangements for...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Continental Shelf oil. 157.10b Section 157.10b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Continental Shelf oil. (a) Each tank vessel that is engaged in the transfer of crude oil from an offshore oil exploitation or production facility on the Outer Continental Shelf of the United States on or after June...

  17. 33 CFR 157.10b - Segregated ballast tanks, dedicated clean ballast tanks, and special ballast arrangements for...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Continental Shelf oil. 157.10b Section 157.10b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Continental Shelf oil. (a) Each tank vessel that is engaged in the transfer of crude oil from an offshore oil exploitation or production facility on the Outer Continental Shelf of the United States on or after June...

  18. 33 CFR 157.10b - Segregated ballast tanks, dedicated clean ballast tanks, and special ballast arrangements for...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Continental Shelf oil. 157.10b Section 157.10b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Continental Shelf oil. (a) Each tank vessel that is engaged in the transfer of crude oil from an offshore oil exploitation or production facility on the Outer Continental Shelf of the United States on or after June...

  19. 33 CFR 157.10b - Segregated ballast tanks, dedicated clean ballast tanks, and special ballast arrangements for...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Continental Shelf oil. 157.10b Section 157.10b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Continental Shelf oil. (a) Each tank vessel that is engaged in the transfer of crude oil from an offshore oil exploitation or production facility on the Outer Continental Shelf of the United States on or after June...

  20. The locus of microRNA-10b

    PubMed Central

    Biagioni, Francesca; Bossel Ben-Moshe, Noa; Fontemaggi, Giulia; Yarden, Yosef; Domany, Eytan; Blandino, Giovanni

    2013-01-01

    Contemporary microRNA research has led to significant advances in our understanding of the process of tumorigenesis. MicroRNAs participate in different events of a cancer cell’s life, through their ability to target hundreds of putative transcripts involved in almost every cellular function, including cell cycle, apoptosis, and differentiation. The relevance of these small molecules is even more evident in light of the emerging linkage between their expression and both prognosis and clinical outcome of many types of human cancers. This identifies microRNAs as potential therapeutic modifiers of cancer phenotypes. From this perspective, we overview here the miR-10b locus and its involvement in cancer, focusing on its role in the establishment (miR-10b*) and spreading (miR-10b) of breast cancer. We conclude that targeting the locus of microRNA 10b holds great potential for cancer treatment. PMID:23839045

  1. Field investigation of dried lakes in western United States as an analogue to desiccation fractures on Mars

    NASA Astrophysics Data System (ADS)

    El-Maarry, M. R.; Watters, W. A.; Yoldi, Z.; Pommerol, A.; Fischer, D.; Eggenberger, U.; Thomas, N.

    2015-12-01

    Potential Desiccation Polygons (PDPs), tens to hundreds of meters in size, have been observed in numerous regions on Mars, particularly in ancient (>3 Gyr old) terrains of inferred paleolacustrine/playa geologic setting, and in association with hydrous minerals such as smectites. Therefore, a better understanding of the conditions in which large desiccation polygons form could yield unique insight into the ancient climate on Mars. Many dried lakebeds/playas in western United States display large (>50 m wide) desiccation polygons, which we consider to be analogues for PDPs on Mars. Therefore, we have carried out fieldwork in seven of these dried lakes in San Bernardino and the Death Valley National Park regions complemented with laboratory and spectral analysis of collected samples. Our study shows that the investigated lacustrine/playa sediments have (a) a soil matrix containing ~40-75% clays and fine silt (by volume) where the clay minerals are dominated by illite/muscovite followed by smectite, (b) carbonaceous mineralogy with variable amounts of chloride and sulfate salts, and significantly, (c) roughly similar spectral signatures in the visible-near-infrared (VIS-NIR) range. We conclude that the development of large desiccation fractures is consistent with water table retreat. In addition, the comparison of the mineralogical to the spectral observations further suggests that remote sensing VIS-NIR spectroscopy has its limitations for detailed characterization of lacustrine/playa deposits. Finally, our results imply that the widespread distribution of PDPs on Mars indicates global or regional climatic transitions from wet conditions to more arid ones making them important candidate sites for future in situ missions.

  2. Effects of State and Decompression Rate on the Decompressive Response of Volatile- and Crystal-Bearing Analogue Magmas.

    NASA Astrophysics Data System (ADS)

    Spina, L.; Cimarelli, C.; Scheu, B.; Dingwell, D. B.

    2014-12-01

    Volcanic eruptive styles are influenced both by the physical properties of the ascending magma as well as the decompression rates involved. Systematic experimental investigations of both state and rate have been performed here on analogue basaltic systems. Controlled decompression experiments were performed in a shock tube system, using a silicon oil basis as the basalt proxy. The samples were saturated with 10 MPa of Ar for 72h, followed by controlled decompression. Four series of experiments were performed: 1) Pure liquids with viscosities ranging from 1 to 1000 Pa s were used to map the liquid response. 2) Micrometric spherical particles were added to the liquid to evaluate the effect of crystal fraction. 3) The role of crystal shape was examined by using particles with different aspect ratios. 4) Finally, the effects of saturation time and of pressure were examined via a series of experiments at 24 h, performed over a range of saturation pressure. The dynamics of foaming and flow of the bubbly fluid during decompression were constrained using image analysis, by measuring the height of the expanding column, as well as analyzing the bubble size distribution. At the onset a delayed nucleation event is observed. When the amount of nucleated bubbles approaches a critical thickness, a foam develops. Finally, the foam reaches equilibrium, and starts oscillating in response to the balance between foam disruption and growth. These observation may have important implications for oscillatory eruptive phenomena observed in active volcanoes (i.e. gas piston activity). Finally, the effect of crystals was investigated. In their presence, heterogeneous nucleation enhances the number of bubble nuclei, even at low crystal fractions. As a consequence, the foam develops earlier, and is able to ascend with major upward speed, in comparison to the pure oil. Experimental decompression of silicon oil has proven to be a unique tool to unravel the hidden dynamics of magma into the

  3. Study of the {sup 10}B(p,alpha){sup 7}Be Reaction through the Indirect Trojan Horse Method

    SciTech Connect

    Puglia, S. M. R.; Romano, S.; Lamia, L.; Spitaleri, C.; Cherubini, S.; Gulino, M.; La Cognata, M.; Pizzone, R. G.; Rapisarda, G. G.; Sergi, M. L.; Tudisco, S.; Del Santo, M. G.; Carlin, N.; Souza, F.; Szanto de Toledo, A.; Kroha, V.; Kubono, S.; Wakabayashi, Y.; Yamaguchi, H.; Li, C.

    2010-03-01

    The {sup 10}B(p,alpha){sup 7}Be reaction is the main responsible for {sup 10}B destruction in stellar interior. In such environments the process takes places mainly through a resonant state of the compound {sup 11}C nucleus. The {sup 10}B(p,alpha){sup 7}Be reaction has been studied by means of the Trojan Horse Method using the {sup 2}H({sup 10}B,alpha{sup 7}Be)n three-body reaction. The experiment was performed at the Laboratori Nazionali del Sud in Catania. The {sup 10}B(p,alpha){sup 7}Be reaction cross section has been extracted at low neutron momentum.

  4. Size-frequency analysis of petroleum accumulations in selected United States plays: potential analogues for frontier areas

    USGS Publications Warehouse

    Attanasi, E.D.; Freeman, P.A.

    2004-01-01

    This report presents the petroleum accumulation size-frequency relationships of selected mature plays assessed in the U.S. Geological Survey?s 1995 National Assessment of Oil and Gas Resources. The plays provide assessors with potential analogue models from which to estimate the numbers of undiscovered accumulations in medium and smaller size categories. Each play selected was required to have at least 50 discovered accumulations. Discovered accumulations plus the mean number of undiscovered accumulations equals the total accumulations assessed at the play level. There were 36 plays that met the criteria for oil accumulations and 25 plays that met the criteria for gas accumulations. Other properties of the plays such as primary trap type, lithology, depth, and hydrocarbon characteristics are also provided to assist the geologist in choosing an appropriate analogue. The text explains how the analogue size-frequency relationships can be used to estimate the number of small and medium size accumulations for frontier-area plays or partially explored plays in high cost areas. Although this document has been written in support of the Alaska North Slope Assessment, the basic size?frequency relationships provided are applicable elsewhere.

  5. Low-Luminosity AGN As Analogues of Galactic Black Holes in the Low/Hard State: Evidence from X-Ray Timing of NGC 4258

    NASA Technical Reports Server (NTRS)

    Markowitz, A.; Uttley, P.

    2005-01-01

    We present a broadband power spectral density function (PSD) measured from extensive RXTE monitoring data of the low-luminosity AGN NGC 4258, which has an accurate, maser-determined black hole mass of (3.9 plus or minus 0.1) x 10(exp 7) solar mass. We constrain the PSD break time scale to be greater than 4.5 d at greater than 90% confidence, which appears to rule out the possibility that NGC 4258 is an analogue of black hole X-ray binaries (BHXRBs) in the high/soft state. In this sense, the PSD of NGC 4258 is different to that of some more-luminous Seyferts, which appear similar to the PSDs of high/soft state X-ray binaries. This result supports previous analogies between LLAGN and X-ray binaries in the low/hard state based on spectral energy distributions, indicating that the AGN/BHXRB analogy is valid across a broad range of accretion rates.

  6. Modeling Ranking, Time Trade-Off and Visual Analogue Scale Values for EQ-5D Health States

    PubMed Central

    Craig, Benjamin M.; Busschbach, Jan J. V.; Salomon, Joshua A.

    2009-01-01

    Background There is rising interest in eliciting health state valuations using rankings. Due to their relative simplicity, ordinal measurement methods may offer an attractive practical alternative to cardinal methods, such as time trade-off (TTO) and visual analog scale (VAS). In this paper, we explore alternative models for estimating cardinal health state values from rank responses in a unique multi-country database. We highlight an estimation challenge pertaining to health states just below perfect health (the ‘non-optimal gap’) and propose an analytic solution to ameliorate this problem. Methods Using rank, a standardized protocol developed by the EuroQol Group, TTO and VAS responses were collected for 43 health states in eight countries: Slovenia, Argentina, Denmark, Japan, Netherlands, Spain, United Kingdom, and United States, yielding a sample of 179,431 state responses from 11,483 subjects. States were described using the EQ-5D system, which allows for three different possible levels on five different dimensions of health. We estimated conditional logit and probit regression models for rank responses. The regressions included 17 health-state attribute variables reflecting specific levels on each dimension and counts of different levels across dimensions. This flexible specification accommodates previously published valuation models, such as models applied in the United Kingdom and United States. In addition to fitting standard conditional logit and probit models, which assume equal variance across health states (homoskedasticity), we examined a heteroskedastic probit model that assumes no variance for the two points anchoring the scale (“optimal health” and “dead”) and relaxes the equal-variance assumption for all other states. Rank-based predictions for the 243 unique states defined by the EQ-5D system were compared to predictions from conventional linear models fitted to TTO and VAS responses. Results By construction, the TTO and VAS models

  7. Reprocessing of 10B-contaminated 10Be AMS targets

    NASA Astrophysics Data System (ADS)

    Simon, K. J.; Pedro, J. B.; Smith, A. M.; Child, D. P.; Fink, D.

    2013-01-01

    10Be accelerator mass spectrometry (AMS) is an increasingly important tool in studies ranging from exposure age dating and palaeo-geomagnetism to the impact of solar variability on the Earth’s climate. High levels of boron in BeO AMS targets can adversely impact the quality of 10Be measurements through interference from the isobar 10B. Numerous methods in chemical sample preparation and AMS measurement have been employed in order to reduce the impact of excessive boron rates. We present details of a method developed to chemically reprocess a set of forty boron-contaminated BeO targets derived from modern Antarctic ice. Previously, the excessive boron levels in these samples, as measured in an argon-filled absorber cell preceding the ionisation detector, had precluded routine AMS measurement. The procedure involved removing the BeO + Nb mixture from the target holders and dissolving the BeO in hot concentrated H2SO4. The solution was then heated with HF to remove the boron as volatile BF3 before re-precipitating as Be(OH)2 and calcining to BeO. This was again mixed with niobium and pressed into fresh target holders. Following reprocessing, the samples gave boron rates reduced by 10-100×, which were sufficiently low and similar to previous successful batches of ice core, snow and associated blank samples, thus allowing a successful 10Be measurement in the absence of any boron correction. Overall recovery of the BeO for this process averaged 40%. Extensive testing of relevant processing equipment and reagents failed to determine the source of the boron. As a precautionary measure, a similar H2SO4 + HF step has been subsequently added to the standard ice processing method.

  8. Flat band analogues and flux driven extended electronic states in a class of geometrically frustrated fractal networks.

    PubMed

    Nandy, Atanu; Pal, Biplab; Chakrabarti, Arunava

    2015-04-01

    We demonstrate, by explicit construction, that a single band tight binding Hamiltonian defined on a class of deterministic fractals of the b = 3N Sierpinski type can give rise to an infinity of dispersionless, flat-band like states which can be worked out analytically using the scale invariance of the underlying lattice. The states are localized over clusters of increasing sizes, displaying the existence of a multitude of localization areas. The onset of localization can, in principle, be 'delayed' in space by an appropriate choice of the energy of the electron. A uniform magnetic field threading the elementary plaquettes of the network is shown to destroy this staggered localization and generate absolutely continuous sub-bands in the energy spectrum of these non-translationally invariant networks. PMID:25751071

  9. 17 CFR 240.10b-16 - Disclosure of credit terms in margin transactions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Disclosure of credit terms in margin transactions. 240.10b-16 Section 240.10b-16 Commodity and Securities Exchanges SECURITIES AND... § 240.10b-16 Disclosure of credit terms in margin transactions. (a) It shall be unlawful for any...

  10. 17 CFR 240.10b-16 - Disclosure of credit terms in margin transactions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Disclosure of credit terms in margin transactions. 240.10b-16 Section 240.10b-16 Commodity and Securities Exchanges SECURITIES AND... § 240.10b-16 Disclosure of credit terms in margin transactions. (a) It shall be unlawful for any...

  11. Growth and Metastases of Human Lung Cancer Are Inhibited in Mouse Xenografts by a Transition State Analogue of 5′-Methylthioadenosine Phosphorylase*

    PubMed Central

    Basu, Indranil; Locker, Joseph; Cassera, Maria B.; Belbin, Thomas J.; Merino, Emilio F.; Dong, Xinyuan; Hemeon, Ivan; Evans, Gary B.; Guha, Chandan; Schramm, Vern L.

    2011-01-01

    The S-adenosylmethionine (AdoMet) salvage enzyme 5′-methylthioadenosine phosphorylase (MTAP) has been implicated as both a cancer target and a tumor suppressor. We tested these hypotheses in mouse xenografts of human lung cancers. AdoMet recycling from 5′-methylthioadenosine (MTA) was blocked by inhibition of MTAP with methylthio-DADMe-Immucillin-A (MTDIA), an orally available, nontoxic, picomolar transition state analogue. Blood, urine, and tumor levels of MTA increased in response to MTDIA treatment. MTDIA treatment inhibited A549 (human non-small cell lung carcinoma) and H358 (human bronchioloalveolar non-small cell lung carcinoma cells) xenograft tumor growth in immunodeficient Rag2−/−γC−/− and NCr-nu mice. Systemic MTA accumulation is implicated as the tumor-suppressive metabolite because MTDIA is effective for in vivo treatment of A549 MTAP−/− and H358 MTAP+/+ tumors. Tumors from treated mice showed increased MTA and decreased polyamines but little alteration in AdoMet, methionine, or adenine levels. Gene expression profiles of A549 tumors from treated and untreated mice revealed only modest alterations with 62 up-regulated and 63 down-regulated mRNAs (≥3-fold). MTDIA antitumor activity in xenografts supports MTAP as a target for lung cancer therapy. PMID:21135097

  12. Rational design of a transition state analogue with picomolar affinity for Pseudomonas aeruginosa PvdQ, a siderophore biosynthetic enzyme.

    PubMed

    Clevenger, Kenneth D; Wu, Rui; Er, Joyce A V; Liu, Dali; Fast, Walter

    2013-10-18

    The Pseudomonas aeruginosa enzyme PvdQ can process different substrates involved in quorum-sensing or in siderophore biosynthesis. Substrate selectivity was evaluated using steady-state kinetic constants for hydrolysis of N-acyl-homoserine lactones (HSLs) and p-nitrophenyl fatty acid esters. PvdQ prefers substrates with alkyl chains between 12 and 14 carbons long that do not bear a 3-oxo substitution and is revealed here to have a relatively high specificity constant for selected N-acyl-HSLs (kcat/KM = 10(5) to 10(6) M(-1) s(-1)). However, endogenous P. aeruginosa N-acyl-HSLs are ≥100-fold disfavored, supporting the conclusion that PvdQ was not primarily evolved to regulate endogenous quorum-sensing. PvdQ plays an essential biosynthetic role for the siderophore pyoverdine, on which P. aeruginosa depends for growth in iron-limited environments. A series of alkylboronate inhibitors was found to be reversible, competitive, and extremely potent (Ki ≥ 190 pM). A 1.8 Å X-ray structure shows that 1-tridecylboronic acid forms a monocovalent bond with the N-terminal β-chain Ser residue in the PvdQ heterodimer, mimicking a reaction transition state. This boronic acid inhibits growth of P. aeruginosa in iron-limited media, reproducing the phenotype of a genetic pvdQ disruption, although co-administration of an efflux pump inhibitor is required to maintain growth inhibition. These findings support the strategy of designing boron-based inhibitors of siderophore biosynthetic enzymes to control P. aeruginosa infections. PMID:23883096

  13. Thermal-induced conformational changes in the product release area drive the enzymatic activity of xylanases 10B: Crystal structure, conformational stability and functional characterization of the xylanase 10B from Thermotoga petrophila RKU-1

    SciTech Connect

    Santos, Camila Ramos; Meza, Andreia Navarro; Hoffmam, Zaira Bruna; Silva, Junio Cota; Alvarez, Thabata Maria; Ruller, Roberto; Giesel, Guilherme Menegon; Verli, Hugo; Squina, Fabio Marcio; Prade, Rolf Alexander; Murakami, Mario Tyago

    2010-12-10

    Research highlights: {yields} The hyperthermostable xylanase 10B from Thermotoga petrophila RKU-1 produces exclusively xylobiose at the optimum temperature. {yields} Circular dichroism spectroscopy suggests a coupling effect of temperature-induced structural changes with its enzymatic behavior. {yields} Crystallographic and molecular dynamics studies indicate that conformational changes in the product release area modulate the enzyme action mode. -- Abstract: Endo-xylanases play a key role in the depolymerization of xylan and recently, they have attracted much attention owing to their potential applications on biofuels and paper industries. In this work, we have investigated the molecular basis for the action mode of xylanases 10B at high temperatures using biochemical, biophysical and crystallographic methods. The crystal structure of xylanase 10B from hyperthermophilic bacterium Thermotoga petrophila RKU-1 (TpXyl10B) has been solved in the native state and in complex with xylobiose. The complex crystal structure showed a classical binding mode shared among other xylanases, which encompasses the -1 and -2 subsites. Interestingly, TpXyl10B displayed a temperature-dependent action mode producing xylobiose and xylotriose at 20 {sup o}C, and exclusively xylobiose at 90 {sup o}C as assessed by capillary zone electrophoresis. Moreover, circular dichroism spectroscopy suggested a coupling effect of temperature-induced structural changes with this particular enzymatic behavior. Molecular dynamics simulations supported the CD analysis suggesting that an open conformational state adopted by the catalytic loop (Trp297-Lys326) provokes significant modifications in the product release area (+1,+2 and +3 subsites), which drives the enzymatic activity to the specific release of xylobiose at high temperatures.

  14. Influence of the Charge State on the Structures and Interactions of Vancomycin Antibiotics with Cell-Wall Analogue Peptides: Experimental and Theoretical Studies

    SciTech Connect

    Yang, Zhibo; Vorpagel, Erich R.; Laskin, Julia

    2009-02-16

    In this study we examined the effect of the charge state on the energetics and dynamics of dissociation of the non-covalent complex between the vancomycin and the cell wall peptide analogue Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala (V-Ac2KDADA). The binding energies between the vancomycin and the peptide were obtained from the RRKM modeling of the time- and energy resolved surface-induced dissociation (SID) experiments. Our results demonstrate that the stability of the complex toward fragmentation increases in the order: [V+Ac2KDADA+H]+2 < [V+Ac2KDADA+H]+ < [V+Ac2KDADA-H]-. Dissociation of the singly protonated and singly deprotonated complex is characterized by very large entropy effects indicating substantial increase in the conformational flexibility of the resulting products. The experimental threshold energies of 1.75 eV and 1.34 eV obtained for the [V+Ac2KDADA-H]- and [V+Ac2KDADA+H]+ , respectively, are in excellent agreement with the results of density functional theory (DFT) calculations. The increased stability of the deprotonated complex observed experimentally is attributed to the presence of three charged sites in the deprotonated complex as compared to only one charged site in the singly protonated complex. The low binding energy of 0.93 eV obtained for the doubly protonated complex suggests that this ion is destabilized by Coulomb repulsion between the singly protonated vancomycin and the singly protonated peptide comprising the complex.

  15. 17 CFR 240.10b5-2 - Duties of trust or confidence in misappropriation insider trading cases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... in misappropriation insider trading cases. 240.10b5-2 Section 240.10b5-2 Commodity and Securities... Devices and Contrivances § 240.10b5-2 Duties of trust or confidence in misappropriation insider trading... of insider trading under Section 10(b) of the Act and Rule 10b-5. The law of insider trading...

  16. Wnt-10b promotes differentiation of skin epithelial cells in vitro

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

    2006-03-31

    To evaluate the role of Wnt-10b in epithelial differentiation, we investigated the effects of Wnt-10b on adult mouse-derived primary skin epithelial cells (MPSEC). Recombinant Wnt-10b protein (rWnt-10b) was prepared using a gene engineering technique and MPSEC were cultured in its presence, which resulted in morphological changes from cuboidal to spindle-shaped and inhibited their proliferation. Further, involvement of the canonical Wnt signal pathway was also observed. MPSEC treated with rWnt-10b showed characteristics of the hair shaft and inner root sheath of the hair follicle, in results of Ayoub Shklar staining and immunocytochemistry. Further, the cells expressed mRNA for differentiated epithelial cells, including keratin 1, keratin 2, loricrin, mHa5, and mHb5, in association with a decreased expression of the basal cell marker keratin 5. These results suggest that Wnt-10b promotes the differentiation of MPSEC.

  17. microRNA-10b Is Overexpressed and Critical for Cell Survival and Proliferation in Medulloblastoma

    PubMed Central

    Pal, Rekha; Greene, Stephanie

    2015-01-01

    This study demonstrates the effects of miRNA-10b on medulloblastoma proliferation through transcriptional induction of the anti-apoptotic protein BCL2. Using a cancer specific miRNA-array, high expression of miRNA-10b in medulloblastoma cell lines compared to a normal cerebellar control was shown, and this was confirmed with real time PCR (RT-PCR). Two medulloblastoma cell lines (DAOY and UW228) were transiently transfected with control miRNA, miRNA-10b inhibitor or miRNA-10b mimic and subjected to RT-PCR, MTT, apoptosis, clonogenic assay and western blot analysis. Transfection of miRNA-10b inhibitor induced a significant down-regulation of miRNA-10b expression, inhibited proliferation, and induced apoptosis, while miRNA-10b mimic exerted an opposite effect. Inhibition of miRNA-10b abrogated the colony-forming capability of medulloblastoma cells, and markedly down-regulated the expression of BCL2. Down-regulation of BCL2 by antisense oligonucleotides or siRNA also significantly down-regulated miRNA-10b, suggesting that BCL2 is a major mediator of the effects of miRNA-10b. ABT-737 and ABT-199, potent inhibitors of BCL2, downregulated the expression of miRNA-10b and increased apoptosis. Analysis of miRNA-10b levels in 13 primary medulloblastoma samples revealed that the 2 patients with the highest levels of miRNA-10b had multiple recurrences (4.5) and died within 8 years of diagnosis, compared with the 11 patients with low levels of miRNA-10b who had a mean of 1.2 recurrences and nearly 40% long-term survival. The data presented here indicate that miRNA-10b may act as an oncomir in medulloblastoma tumorigenesis, and reveal a previously unreported mechanism with Bcl-2 as a mediator of the effects of miRNA-10b upon medulloblastoma cell survival. PMID:26394044

  18. microRNA-10b Is Overexpressed and Critical for Cell Survival and Proliferation in Medulloblastoma.

    PubMed

    Pal, Rekha; Greene, Stephanie

    2015-01-01

    This study demonstrates the effects of miRNA-10b on medulloblastoma proliferation through transcriptional induction of the anti-apoptotic protein BCL2. Using a cancer specific miRNA-array, high expression of miRNA-10b in medulloblastoma cell lines compared to a normal cerebellar control was shown, and this was confirmed with real time PCR (RT-PCR). Two medulloblastoma cell lines (DAOY and UW228) were transiently transfected with control miRNA, miRNA-10b inhibitor or miRNA-10b mimic and subjected to RT-PCR, MTT, apoptosis, clonogenic assay and western blot analysis. Transfection of miRNA-10b inhibitor induced a significant down-regulation of miRNA-10b expression, inhibited proliferation, and induced apoptosis, while miRNA-10b mimic exerted an opposite effect. Inhibition of miRNA-10b abrogated the colony-forming capability of medulloblastoma cells, and markedly down-regulated the expression of BCL2. Down-regulation of BCL2 by antisense oligonucleotides or siRNA also significantly down-regulated miRNA-10b, suggesting that BCL2 is a major mediator of the effects of miRNA-10b. ABT-737 and ABT-199, potent inhibitors of BCL2, downregulated the expression of miRNA-10b and increased apoptosis. Analysis of miRNA-10b levels in 13 primary medulloblastoma samples revealed that the 2 patients with the highest levels of miRNA-10b had multiple recurrences (4.5) and died within 8 years of diagnosis, compared with the 11 patients with low levels of miRNA-10b who had a mean of 1.2 recurrences and nearly 40% long-term survival. The data presented here indicate that miRNA-10b may act as an oncomir in medulloblastoma tumorigenesis, and reveal a previously unreported mechanism with Bcl-2 as a mediator of the effects of miRNA-10b upon medulloblastoma cell survival. PMID:26394044

  19. miR-10b promotes invasion by targeting HOXD10 in colorectal cancer

    PubMed Central

    WANG, YUNFENG; LI, ZHEN; ZHAO, XUHONG; ZUO, XIAOMING; PENG, ZHIHAI

    2016-01-01

    Studies have shown that homeobox D10 (HOXD10) is the target gene of microRNA-10b (miR-10b) and is closely associated with the inhibition of cell migration and invasion. Ras homolog family member C (RhoC) has been reported to promote tumor metastasis in various types of cancer. The effect of miR-10b on colorectal cancer (CRC) metastasis and the associated molecular mechanisms remain elusive. The present study aimed to investigate whether miR-10b could promote invasion by targeting HOXD10 in CRC by exploring the association between miR-10b and HOXD10 expression in CRC patients. The findings revealed that miR-10b levels were elevated in the CRC specimens and significantly correlated with advanced clinical stage and lymph node metastasis. In addition, HOXD10 was a direct target of miR-10b, and the increased expression of RhoC and downregulation of HOXD10 correlated with the increased expression level of miR-10b. HOXD10 protein level was also markedly attenuated in lymph node metastasis-positive tumor tissues compared with lymph node metastasis-free tumor tissues. These findings suggest that miR-10b may stimulate the upregulation of RhoC through targeting HOXD10, thus promoting the invasion and migration in CRC tumor. PMID:27347170

  20. The 10B(n,α0)7Li and 10B(n,αlγ)7Li alpha-particle angular distributions, branching ratios and cross-sections measurements for En < 3 MeV

    NASA Astrophysics Data System (ADS)

    Hambsch, F. J.; Ruskov, I.; Vidali, M.

    2010-01-01

    The 10B(n,α0)7Li and 10B(n,αiγ)7Li angular distributions have been measured at the GELINA time-of-flight spectrometer in the incident neutron energy range from 0.1 keV to 1 MeV by means of a twin Frisch-grid ionization chamber. With this type of detector it is possible to measure the angular distribution of the charged reaction fragments in a close to 2×2π solid angle with ~100% efficiency and a clear separation of both reaction channels: emission to the 7Li ground state (α0) or to its first excited state (α1). A strong angular anisotropy was observed at ~ 520 keV. In order to extend the energy range up to 2.5-3 MeV and to measure, also, the reaction cross sections, a double twin Frisch-grid ionization chamber was constructed. It is loaded with two very thin 94% 10B-enriched samples, mounted back-to-back with 235U samples on the common cathodes. New data acquisition, visualization and analysis software is used in a new set of long-term measurements, which are still going on.

  1. ATR LEU Monothlic and Dispersed with 10B Loading Minimization Design – Neutronics Performance Analysis

    SciTech Connect

    G. S. Chang

    2001-10-01

    The Advanced Test Reactor (ATR), currently operating in the United States, is used for material testing at very high neutron fluxes. Powered with highly enriched uranium (HEU), the ATR has a maximum thermal power rating of 250 MWth. Because of the large test volumes located in high flux areas, the ATR is an ideal candidate for assessing the feasibility of converting HEU driven reactor cores to low-enriched uranium (LEU) cores. The present work investigates the optimized LEU Monolithic and Dispersed fuel with 10B loading minimization design and evaluates the subsequent neutronics operating effects of these optimized fuel designs. The MCNP ATR 1/8th core model was used to optimize the 235U and minimize the 10B loading in the LEU core, such that the differences in K-eff and heat flux profiles between the HEU and LEU cores were minimized. The fuel depletion methodology MCWO was used to calculate K eff versus effective full power days (EFPD) in this paper. The MCWO-calculated results for the optimized LEU Monolithic and Dispersed fuel cases demonstrated adequate excess reactivity such that the K-eff versus EFPD plot is similar to the ATR reference HEU case study. Each HEU fuel element contains 19 fuel plates with a fuel meat thickness of 0.508 mm (20 mil). In this work, the proposed LEU Monolithic (U-10Mo) core conversion case with nominal fuel meat thickness of 0.330 mm (13 mil) and 235U enrichment of 19.7 wt% is used to optimize the radial heat flux profile by varying the fuel meat thickness. The proposed LEU fuel meat varies from 0.203 mm (8.0 mil) to 0.254 mm (10.0 mil) at the inner four fuel plates (1-4) and outer four fuel plates (16-19). In addition, an optimized LEU dispersed (U7Mo) case with all the fuel meat thickness of 0.635 mm (25 mil) was also proposed. Then, for both Monolithic and dispersed cases, a burnable absorber – 10B, was added in the inner and outer plates to reduce the initial excess reactivity, and the higher to average ratio of the inner

  2. Overexpression of tissue microRNA10b may help predict glioma prognosis.

    PubMed

    Zhang, Xinxin; Cheng, Jian; Fu, Ling; Li, Qingshui

    2016-07-01

    We investigated the relationship between microRNA-10b (miR-10b) expression and prognosis in human glioma patients. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to characterize the expression patterns of miR-10b in 128 glioma and 20 normal brain tissues. Clinical information - age, sex, Karnofsky Performance Status (KPS) and World Health Organization (WHO) grade - were also collected. The associations between miR-10b expression and the clinicopathological factors and outcome of glioma patients were statistically analyzed. Expression levels of miR-10b in glioma tissue were significantly higher than in normal brain tissue (P<0.001). High-grade glioma (WHO grade III and IV) had much higher miR-10b expression levels than low-grade tumors (WHO grade I and II). Additionally, the increased miR-10b expression in the glioma tissues was significantly associated with a low KPS (P=0.03). Kaplan-Meier survival curves and Cox regression analyses showed that overexpression of miR-10b (P=0.01) and high grade (P=0.02) were independent factors predicting poor outcome for glioma patients. Furthermore, subgroup analyses showed that the miR-10b expression level was significantly associated with poor overall survival in glioma patients with high grades (P<0.001). Up-regulation of miR-10b may have value in predicting clinical outcome in glioma patients, particularly for those with high pathological grades. PMID:26988656

  3. 10B(n, Z) measurements in the energy range 0.7 to 5.0 MeV

    DOE PAGESBeta

    Massey, T. N.; Ralston, J.; Grimes, S. M.; Haight, R. C.

    2014-09-03

    Four ΔE E telescopes were used at the WNR (n,Z) station to investigate the production of charged particles from 10B. The telescope consisted of a gas proportional detector and a silicon surface barrier detector. The flux was determined using a 238U fission chamber. A clear separation of the ground state alpha group and first excited state a was not achieved due to the target thickness. Proton emission was also observed. Furthermore, the proton branch was up to an order of magnitude larger than predicted in ENDF/B-VII A simple R-matrix analysis has been performed on the available data

  4. Effects of Wnt-10b on hair shaft growth in hair follicle cultures

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Moriya, Kei; Ishizaka, Shigeaki

    2007-08-03

    Wnts are deeply involved in the proliferation and differentiation of skin epithelial cells. We previously reported the differentiation of cultured primary skin epithelial cells toward hair shaft and inner root sheath (IRS) of the hair follicle via {beta}-catenin stabilization caused by Wnt-10b, however, the effects of Wnt-10b on cultured hair follicles have not been reported. In the present study, we examined the effects of Wnt-10b on shaft growth using organ cultures of whisker hair follicles in serum-free conditions. No hair shaft growth was observed in the absence of Wnt-10b, whereas its addition to the culture promoted elongation of the hair shaft, intensive incorporation of BrdU in matrix cells flanking the dermal papilla (DP), and {beta}-catenin stabilization in DP and IRS cells. These results suggest a promoting effect of Wnt-10b on hair shaft growth that is involved with stimulation of the DP via Wnt-10b/{beta}-catenin signalling, proliferation of matrix cells next to the DP, and differentiation of IRS cells by Wnt-10b.

  5. A Point Mutation in the Gene for Asparagine-Linked Glycosylation 10B (Alg10b) Causes Nonsyndromic Hearing Impairment in Mice (Mus musculus)

    PubMed Central

    Probst, Frank J.; Corrigan, Rebecca R.; del Gaudio, Daniela; Salinger, Andrew P.; Lorenzo, Isabel; Gao, Simon S.; Chiu, Ilene; Xia, Anping

    2013-01-01

    The study of mouse hearing impairment mutants has led to the identification of a number of human hearing impairment genes and has greatly furthered our understanding of the physiology of hearing. The novel mouse mutant neurological/sensory 5 (nse5) demonstrates a significantly reduced or absent startle response to sound and is therefore a potential murine model of human hearing impairment. Genetic analysis of 500 intercross progeny localized the mutant locus to a 524 kilobase (kb) interval on mouse chromosome 15. A missense mutation in a highly-conserved amino acid was found in the asparagine-linked glycosylation 10B gene (Alg10b), which is within the critical interval for the nse5 mutation. A 20.4 kb transgene containing a wildtype copy of the Alg10b gene rescued the mutant phenotype in nse5/nse5 homozygous animals, confirming that the mutation in Alg10b is responsible for the nse5/nse5 mutant phenotype. Homozygous nse5/nse5 mutants had abnormal auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and cochlear microphonics (CMs). Endocochlear potentials (EPs), on the other hand, were normal. ABRs and DPOAEs also confirmed the rescue of the mutant nse5/nse5 phenotype by the wildtype Alg10b transgene. These results suggested a defect in the outer hair cells of mutant animals, which was confirmed by histologic analysis. This is the first report of mutation in a gene involved in the asparagine (N)-linked glycosylation pathway causing nonsyndromic hearing impairment, and it suggests that the hearing apparatus, and the outer hair cells in particular, are exquisitely sensitive to perturbations of the N-linked glycosylation pathway. PMID:24303013

  6. a New Method to Measure 10B Uptake in Lung Adenocarcinoma in Hospital Bnct

    NASA Astrophysics Data System (ADS)

    Donegani, E. M.; Basilico, F.; Bolognini, D.; Borasio, P.; Capelli, E.; Cappelletti, P.; Chiari, P.; Frigerio, M.; Gelosa, S.; Giannini, G.; Hasan, S.; Mattera, A.; Mauri, P.; Monti, A. F.; Ostinelli, A.; Prest, M.; Vallazza, E.; Zanini, A.

    2010-04-01

    Boron Neutron Capture Therapy (BNCT) is a radiotherapic technique still under development that could become crucial in the fight against some types of cancer (extended ones, located near vital organs or radio resistant). This binary technique requires the administration to the patient of a boron delivery agent and the irradiation with a thermal neutron beam. The high LET particles produced in the 10B(n,α)7Li reaction are exploited to destroy the tumour cells. This work presents a new system based on neutron autoradiography with a non-depleted self-triggering microstrip silicon detector, using a neutron beam produced by a hospital Linac. The system is fast, real time and allows the detection of 10B contents down to 25 ng. The main results on the study of 10B uptake in biological samples will be described in terms of kinetic curves (10B uptake as a function of time).

  7. A Gallium-Substituted Distibene and an Antimony-Analogue Bicyclo[1.1.0]butane: Synthesis and Solid-State Structures.

    PubMed

    Tuscher, Lars; Ganesamoorthy, Chelladurai; Bläser, Dieter; Wölper, Christoph; Schulz, Stephan

    2015-09-01

    RGa {R=HC[C(Me)N(2,6-iPr2C6H3)]2} reacts with Sb(NMe2)3 with insertion into the Sb-N bond and elimination of RGa(NMe2)2 (2), yielding the Ga-substituted distibene R(Me2N)GaSb=SbGa(NMe2 )R (1). Thermolysis of 1 proceeded with elimination of RGa and 2 and subsequent formation of the bicyclo[1.1.0]butane analogue [R(Me2N)Ga]2Sb4 (3). PMID:26248643

  8. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 8 2012-07-01 2012-07-01 false Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (CONTINUED) Pt. 60, App. A-4 Appendix A-4 to Part 60—Test Methods 6 through 10B Method...

  9. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 8 2014-07-01 2014-07-01 false Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (CONTINUED) Pt. 60, App. A-4 Appendix A-4 to Part 60—Test Methods 6 through 10B Method...

  10. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 7 2010-07-01 2010-07-01 true Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (CONTINUED) Pt. 60, App. A-4 Appendix A-4 to Part 60—Test Methods 6 through 10B Method...

  11. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 7 2011-07-01 2011-07-01 false Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (CONTINUED) Pt. 60, App. A-4 Appendix A-4 to Part 60—Test Methods 6 through 10B Method...

  12. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model

    PubMed Central

    Ma, Li; Reinhardt, Ferenc; Pan, Elizabeth; Soutschek, Jürgen; Bhat, Balkrishen; Marcusson, Eric; Teruya-Feldstein, Julie; Bell, George W.; Weinberg, Robert A.

    2010-01-01

    MicroRNAs (miRNAs) are increasingly implicated in regulating metastasis. Despite progress in silencing miRNAs in normal tissues of rodents and non-human primates, the development of effective approaches for sequence-specific inhibition of miRNAs in fast-growing tumors remains a significant scientific and clinical challenge. Here we show that systemic treatment of tumor-bearing mice with miR-10b antagomirs – a class of chemically modified anti-miRNA oligonucleotides – suppresses breast cancer metastasis. Silencing of miR-10b both in vitro and in vivo with antagomirs significantly decreases miR-10b levels and increases levels of a functionally important miR-10b target, Hoxd10. Administration of miR-10b antagomirs to mice bearing highly metastatic cells does not reduce primary mammary tumor growth but instead markedly suppresses formation of lung metastases. This metastasis-suppressing effect is sequence-specific. The miR-10b antagomir, which is well tolerated by normal animals, appears to be a promising candidate and a starting point for the development of new anti-metastasis agents. PMID:20351690

  13. Wnt-10b secreted from lymphocytes promotes differentiation of skin epithelial cells

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

    2006-04-21

    Wnt-10b was originally isolated from lymphoid tissue and is known to be involved in a wide range of biological actions, while recently it was found to be expressed early in the development of hair follicles. However, few studies have been conducted concerning the role of Wnt-10b with the differentiation of skin epithelial cells. To evaluate its role in epithelial differentiation, we purified Wnt-10b from the supernatant of a concanavalin A-stimulated lymphocyte culture using an affinity column and investigated its effects on the differentiation of adult mouse-derived primary skin epithelial cells (MPSEC). MPSEC cultured with Wnt-10b showed morphological changes from cuboidal to spindle-shaped with inhibited proliferation, and also obtained characteristics of the hair shaft and inner root sheath of the hair follicle, represented by red-colored Ayoub Shklar staining, and reactions to AE-13 and AE-15 as seen with immunocytology. Further, RT-PCR analysis demonstrated the expression of mRNA for keratin 1, keratin 2, loricrin, mHa5, and mHb5, in association with a decreased expression of the basal cell marker keratin 5, in Wnt-10b-treated MPSEC. In addition, involvement of the canonical Wnt signal pathway was demonstrated by a TCF reporter (pTOPFLASH) assay. These results suggest that Wnt-10b promotes the differentiation of MPSEC and may play an important role in hair follicle development by promoting differentiation of epithelial cells.

  14. Canonical Wnts, specifically Wnt-10b, show ability to maintain dermal papilla cells

    SciTech Connect

    Ouji, Yukiteru Nakamura-Uchiyama, Fukumi; Yoshikawa, Masahide

    2013-08-30

    Highlights: •First report on effects of various Wnts on DP cells. •Wnt-10b promoted trichogenesis, while Wnt-3a showed to a limited extent. •Canonical Wnts, specifically Wnt-10b, is important for DP cells maintenance. -- Abstract: Although Wnts are expressed in hair follicles (HFs) and considered to be crucial for maintaining dermal papilla (DP) cells, the functional differences among them remain largely unknown. In the present study, we investigated the effects of Wnts (Wnt-3a, 5a, 10b, 11) on the proliferation of mouse-derived primary DP cells in vitro as well as their trichogenesis-promoting ability using an in vivo skin reconstitution protocol. Wnt-10b promoted cell proliferation and trichogenesis, while Wnt-3a showed those abilities to a limited extent, and Wnt-5a and 11 had no effects. Furthermore, we investigated the effects of these Wnts on cultured DP cells obtained from versican-GFP transgenic mice and found that Wnt-10b had a potent ability to sustain their GFP-positivity. These results suggest that canonical Wnts, specifically Wnt-10b, play important roles in the maintenance of DP cells and trichogenesis.

  15. Structures in 9,10Be and 10B studied with the tensor-optimized shell model

    NASA Astrophysics Data System (ADS)

    Myo, Takayuki; Umeya, Atsushi; Toki, Hiroshi; Ikeda, Kiyomi

    2015-06-01

    We study the structures of ^{9,10}Be and ^{10}B with the tensor-optimized shell model (TOSM) using an effective interaction based on the bare nucleon-nucleon interaction AV8^'. The tensor correlation is treated in TOSM using the full space of 2p2h configurations including high-momentum components. The short-range correlation is treated with the unitary correlation operator method. It is found that the level orders of the low-lying states of ^{9,10}Be and ^{10}B are entirely reproduced. For ^9Be, ground band states are located at relatively higher energies than the experiments, which indicates missing α clustering correlation in these states as seen in the case of ^8Be. In addition, the tensor force gives a larger attraction for T=1/2 states than for T=3/2 ones for ^9Be. The level order of the three nuclei is found to be sensitive to the presence of the tensor force in comparison with the results using the Minnesota effective interaction without the tensor force.

  16. Design and testing of a 10B4C capsule for spectral-tailoring in mixed-spectrum reactors

    NASA Astrophysics Data System (ADS)

    Greenwood, L. R.; Wittman, R.; Metz, L. A.; Finn, E. C.; Friese, J. I.

    2014-04-01

    A boron carbide capsule highly enriched in 10B has been designed and used for spectral-tailoring experiments at the TRIGA reactor at Washington State University. New experiments show that enriching the boron to 96% B-10 results in additional absorption of neutrons in the resonance region thereby producing a neutron spectrum that is much closer to a pure 235U fission spectrum than measured previously with a natural boron carbide capsule. A cadmium outer cover was used to reduce thermal alpha heating. The neutron spectrum calculated with MCNP was found to be in very good agreement with measured activation rates from neutron fluence monitors.

  17. Design and Testing of a 10B4C Capsule for Spectral-Tailoring in Mixed-Spectrum Reactors

    SciTech Connect

    Greenwood, Lawrence R.; Wittman, Richard S.; Metz, Lori A.; Finn, Erin C.; Friese, Judah I.

    2014-04-11

    A boron carbide capsule highly enriched in 10B has been designed and used for spectral-tailoring experiments at the TRIGA reactor at Washington State University. New experiments show that enriching the boron to 96% B-10 results in additional absorption of neutrons in the resonance region thereby producing a neutron spectrum that is much closer to a pure 235U fission spectrum. A cadmium outer cover was used to reduce thermal heating. The neutron spectrum calculated with MCNP was found to be in very good agreement with measured activation rates from neutron fluence monitors.

  18. Rocky super-Earth interiors. Structure and internal dynamics of CoRoT-7b and Kepler-10b

    NASA Astrophysics Data System (ADS)

    Wagner, F. W.; Tosi, N.; Sohl, F.; Rauer, H.; Spohn, T.

    2012-05-01

    Aims: We present interior structure models of the recently discovered exoplanets CoRoT-7b and Kepler-10b addressing their bulk compositions, present thermal states, and internal dynamics. We investigate how mantle convection patterns are influenced by the depth-dependence of thermodynamic parameters (e.g., thermal expansivity and conductivity) caused by the extended pressure and temperature ranges within rocky super-Earths. Methods: To model the interior of rocky exoplanets, we construct a four-layer structural model solving the mass and energy balance equations in conjunction with a generalized Rydberg equation of state providing the radial density distribution within each layer. The present thermal state is calculated according to a modified mixing-length approach for highly viscous fluids. Furthermore, the obtained internal structure is used to carry out two-dimensional convection simulations to visualize the mantle convection pattern within massive exoplanets such as CoRoT-7b and Kepler-10b. Results: Both CoRoT-7b and Kepler-10b most likely have large iron cores and a bulk composition similar to that of Mercury. For a planetary radius of Rp = (1.58 ± 0.10) R⊕, a revised total mass of Mp = (7.42 ± 1.21) M⊕, and the existence of a third planet in the CoRoT-7 planetary system, calculations suggest that an iron core of 64 wt-% and a silicate mantle of 36 wt-% is produced owing to the relatively high average compressed density of ρavg = (10.4 ± 1.8) g cm-3. Kepler-10b's planetary radius and total mass yield an iron core of 59.5 wt-%, which complements the silicate mantle of 40.5 wt-%. An enhanced radiogenic heating rate owing to CoRoT-7b's young age (1.2-2.3 Gyr) raises the radial distribution of temperature by only a few hundred Kelvin, but reduces the viscosity by an order of magnitude. The planform of mantle convection is found to be strongly modified for depth-dependent material properties, with hot plumes rising across the whole mantle and cold slabs

  19. Unstable nuclei in coherent dissociation of relativistic nuclei 7,9Be, 10B and 10,11C

    NASA Astrophysics Data System (ADS)

    Artemenkov, D. A.; Bradnova, V.; Firu, E.; Kornegrutsa, N. K.; Haiduc, M.; Mamatkulov, K. Z.; Kattabekov, R. R.; Neagu, A.; Rukoyatkin, P. A.; Rusakova, V. V.; Sarkisyan, V. R.; Stanoeva, R.; Zaitsev, A. A.; Zarubin, P. I.; Zarubina, I. G.

    2016-06-01

    Contribution of the unstable nuclei 7Be, 8Be and ®B into coherent dissociation events (“white” stars) of relativistic nuclei 7,9Be, 10B and 10,11C is under study on the basis of a nuclear track emulsion exposed to beams of the JINR Nuclotron. Distributions over the opening angle of α-pairs indicate to a simultaneous presence of virtual 8Beg.s. and 8Be2+ states in the ground states of the 9Be and 10C nuclei. The core 9B is manifested in the 10C nucleus with a probability of (30 ± 4)%, Selection of the 10C “white” stars accompanied by 8Beg.s. (9B) leads to the appearance in the excitation energy distribution of 2α2p “quartets” of the distinct peak with a maximum at 4.1 ± 0.3 MeV. 8Beg.s. decays are presented in 21% 2He + 2H and 19% in the 3He of the all 11C “white” stars. 9Bg.s. decays are identified in “white” stars 11C → 2He + 2H constituting 14% of the 11C “white” stars. The 9B nucleus. is manifested in the “white” stars 10B → 2He + 2H with a probability of (9 ± 1)%. For the 10B case yield of 8Beg.s. nuclei with the respect to 9B is about a factor of 3 higher than 9B.

  20. miRNA-10b sponge: An anti-breast cancer study in vitro.

    PubMed

    Liang, Ai-Ling; Zhang, Ting-Ting; Zhou, Ning; Wu, Cui Yun; Lin, Man-Hua; Liu, Yong-Jun

    2016-04-01

    Breast cancer is a malignant tumor with the highest incidence among women. Breast cancer metastasis is the major cause of treatment failure and mortality among such patients. MicroRNAs (miRNAs) are a class of small molecular non-coding regulatory RNAs, which act as oncogenes or tumor suppressors in breast cancer. miRNA-10b has been found to exhibit a high expression level in advanced and metastatic breast cancer, and is closely related to breast cancer metastasis. An miRNA sponge is an mRNA with several repeated sequences of complete or incomplete complementarity to the natural miRNA in its 3' non-translating region. It acts as a sponge adsorbing miRNAs and ensures their separation from their targets and inhibits their function. The present study designed a sponge plasmid against miRNA-10b and transiently transfected it into high and low metastatic human breast cancer cell lines MDA-MB-231 and MCF-7, and analyzed the effects of the miRNA-10b sponge on the growth and proliferation, migration and invasion in these cell lines. qRT-PCR results found that the sponge plasmid effectively inhibited the expression of miRNA-10b, and upregulated the expression of the miRNA‑10b target protein HOXD-10. The results from the CCK-8 assay found that the miRNA-10b sponge inhibited the growth of breast cancer cell lines MDA-MB-231 and MCF-7. Results of the plate cloning experiments indicated that the miRNA-10b sponge suppressed the colony formation of the MDA-MB-231 and MCF-7 cells. The results of wound healing and Transwell assays showed that the miRNA-10b sponge inhibited the migration and invasion of the breast cancer cell lines MDA-MB-231 and MCF-7. Our results demonstrated that the miRNA-10b sponge effectively inhibited the growth and proliferation of breast cancer MDA-MB-231 and MCF-7 cells. In addition, it also restrained the migration and invasion of human highly metastatic breast cancer MDA-MB-231 cells. PMID:26820121

  1. miRNA-10b sponge: An anti-breast cancer study in vitro

    PubMed Central

    LIANG, AI-LING; ZHANG, TING-TING; ZHOU, NING; WU, CUI YUN; LIN, MAN-HUA; LIU, YONG-JUN

    2016-01-01

    Breast cancer is a malignant tumor with the highest incidence among women. Breast cancer metastasis is the major cause of treatment failure and mortality among such patients. MicroRNAs (miRNAs) are a class of small molecular non-coding regulatory RNAs, which act as oncogenes or tumor suppressors in breast cancer. miRNA-10b has been found to exhibit a high expression level in advanced and metastatic breast cancer, and is closely related to breast cancer metastasis. An miRNA sponge is an mRNA with several repeated sequences of complete or incomplete complementarity to the natural miRNA in its 3′ non-translating region. It acts as a sponge adsorbing miRNAs and ensures their separation from their targets and inhibits their function. The present study designed a sponge plasmid against miRNA-10b and transiently transfected it into high and low metastatic human breast cancer cell lines MDA-MB-231 and MCF-7, and analyzed the effects of the miRNA-10b sponge on the growth and proliferation, migration and invasion in these cell lines. qRT-PCR results found that the sponge plasmid effectively inhibited the expression of miRNA-10b, and upregulated the expression of the miRNA-10b target protein HOXD-10. The results from the CCK-8 assay found that the miRNA-10b sponge inhibited the growth of breast cancer cell lines MDA-MB-231 and MCF-7. Results of the plate cloning experiments indicated that the miRNA-10b sponge suppressed the colony formation of the MDA-MB-231 and MCF-7 cells. The results of wound healing and Transwell assays showed that the miRNA-10b sponge inhibited the migration and invasion of the breast cancer cell lines MDA-MB-231 and MCF-7. Our results demonstrated that the miRNA-10b sponge effectively inhibited the growth and proliferation of breast cancer MDA-MB-231 and MCF-7 cells. In addition, it also restrained the migration and invasion of human highly metastatic breast cancer MDA-MB-231 cells. PMID:26820121

  2. AP1- and NF-kappaB-binding sites conserved among mammalian WNT10B orthologs elucidate the TNFalpha-WNT10B signaling loop implicated in carcinogenesis and adipogenesis.

    PubMed

    Katoh, Masuko; Katoh, Masaru

    2007-04-01

    WNT signals are context-dependently transduced to canonical and non-canonical signaling cascades. We cloned and characterized wild-type human WNT10B, while another group cloned aberrant human WNT10B with Gly60Asp amino-acid substitution. Proto-oncogene WNT10B is expressed in gastric cancer, pancreatic cancer, breast cancer, esophageal cancer, and cervical cancer. Because WNT10B blocks adipocyte differentiation, coding SNP of WNT10B gene is associated with familial obesity. In 2001, we reported WNT10B upregulation by TNFalpha. Here, comparative integromics analyses on WNT10B orthologs were performed to elucidate the transcriptional mechanism of WNT10B. Chimpanzee WNT10B and cow Wnt10b genes were identified within NW_001223159.1 and AC150975.2 genome sequences, respectively, by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee WNT10B and cow Wnt10b showed 98.7% and 95.1% total-amino-acid identity with human WNT10B, respectively. N-terminal signal peptide, 24 Cys residues, two Asn-linked glycosylation sites, and Gly60 of human WNT10B were conserved among mammalian WNT10B orthologs. Transcription start site of human WNT10B gene was 106-bp upstream of NM_003394.2 RefSeq 5'-end. Number of GC di-nucleotide repeats just down-stream of WNT10B transcription start site varied among primates and human population. Comparative genomics analyses revealed that double AP1-binding sites in the 5'-flanking promoter region and NF-kappaB-binding site in intron 3 were conserved among human, chimpanzee, cow, mouse, and rat WNT10B orthologs. Because TNFalpha signaling through TNFR1 and TRADD/RIP/TRAF2 complex activates JUN kinase (JNK) and IkappaB kinase (IKK) signaling cascades, conserved AP1- and NF-kappaB-binding sites explain the mechanism of TNFalpha-induced WNT10B upregulation. TNFalpha-WNT10B signaling loop is the negative feedback mechanism of adipogenesis to prevent obesity and metabolic syndrome. On the other hand, TNFalpha-WNT10B signaling loop is

  3. Data for the neutron interactions with /sup 6/Li and /sup 10/B

    SciTech Connect

    Poenitz, W.P.

    1984-01-01

    The /sup 10/B(n,..cap alpha..), /sup 10/B(n,..cap alpha../sub 1/) and, increasingly in more recent measurement, the /sup 6/Li(n,..cap alpha..) cross sections are the major references used in low energy experiments. Many data from modern measurements are available for the neutron interaction with /sup 6/Li, including total, scattering, and absolute and relative (n,..cap alpha..) cross sections. A consensus has been reached with these new /sup 6/Li + n data. In contrast, the data base for the /sup 10/B neutron interaction cross sections is unfortunately poor. This is even the case for the total cross section which is supposed to be the easiest quantity to be measured. The most serious deficiency is the absence of data from absolute measurements of the /sup 10/B(n,..cap alpha..) and /sup 10/B(n,..cap alpha../sub 1/) cross sections in the last 10 to 15 years. The available cross section data which were used for the ENDF/B-VI evaluation will be discussed. 43 references.

  4. An update on 11B,10B fractionation in the fundamental reaction: 10B(OH)3 + 11B(OH)4- = 11B(OH)3 + 10B(OH)4-

    NASA Astrophysics Data System (ADS)

    Klochko, K.; Tossell, J. A.

    2007-12-01

    It has recently been demonstrated experimentally by Byrne, et al. (2006) and Klochko, et al. (2006) that the equilibrium constant for the isotopic exchange reaction: 10B(OH)3 + 11B(OH)4- = 11B(OH)3 + 10B(OH)4- (1) has a value around 1.027 for seawater at 25°C, for total B concentrations from 0.01 to 0.05 molal. These experimental studies involved essentially the accurate determination of the small pKa difference between the 11B and 10B isotopomers of boric acid. This new equilibrium constant value is significantly higher than the traditional value of 1.0194 from Kakihana, et al. (1977). This result has been obscured in recent controversies (Honisch, et al., 2007). The new value agrees well with the ab initio quantum cluster calculated values of Liu and Tossell (2005) and with the ab initio MD harmonic values of Rustad and Bylaska (2007). We will present additional calculations supporting and extending the study of Liu and Tossell (2005) and will discuss the general unsuitability of methods such as Sanchez-Valle, et al. (2005) which employ experimental spectral data. We have also established that polyborate formation in solutions as concentrated as 0.50 molal total B has little effect on the equilibrium constant. A mechanism is also presented for the interaction of B(OH)3 and B(OH)4- with HCO3- species occurring on the calcite surface. References: Byrne, et al. Deep-Sea Research I (2006) 53, 684-688. Honisch, et al. Geochim. Cosmochim. Acta (2007) 71, 1636-1641. Kakihana, et al. Bull. Chem. Soc. Jpn. (1977) 50, 158-163. Klochko, et al. Earth Planet. Sci. Lett. (2006) 248, 276-285. Liu and Tossell Geochim. Cosmochim. Acta (2005) 69, 3995-4006. Rustad and Bylaska J. Am. Chem. Soc. (2007) 129, 2222-2223. Sanchez-Valle, et al. Geochim. Cosmochim. Acta (2005) 69, 4301-4313.

  5. Aspartame and Its Analogues

    NASA Astrophysics Data System (ADS)

    Pavlova, L. A.; Komarova, T. V.; Davidovich, Yurii A.; Rogozhin, S. V.

    1981-04-01

    The results of studies on the biochemistry of the sweet taste are briefly reviewed. The methods of synthesis of "aspartame" — a sweet dipeptide — are considered, its structural analogues are described, and quantitative estimates are made of the degree of sweetness relative to sucrose. Attention is concentrated mainly on problems of the relation between the structure of the substance and its taste in the series of aspartyl derivatives. The bibliography includes 118 references.

  6. Wnt-10b, uniquely among Wnts, promotes epithelial differentiation and shaft growth

    SciTech Connect

    Ouji, Yukiteru Yoshikawa, Masahide; Moriya, Kei; Nishiofuku, Mariko; Matsuda, Ryosuke; Ishizaka, Shigeaki

    2008-03-07

    Although Wnts are expressed in hair follicles throughout life from embryo to adult, and considered to be critical for their development and maturation, their roles remain largely unknown. In the present study, we investigated the effects of Wnts (Wnt-3a, Wnt-5a, Wnt-10b, and Wnt-11) on epithelial cell differentiation using adult mouse-derived primary skin epithelial cell (MPSEC) cultures and hair growth using hair follicle organ cultures. Only Wnt-10b showed evident promotion of epithelial cell differentiation and hair shaft growth, in contrast to Wnt-3a, 5a, and 11. Our results suggest that Wnt-10b is unique and plays an important role in differentiation of epithelial cells in the hair follicle.

  7. Concentrations and profiles of bisphenol A and other bisphenol analogues in foodstuffs from the United States and their implications for human exposure.

    PubMed

    Liao, Chunyang; Kannan, Kurunthachalam

    2013-05-15

    As the concern over the safety of bisphenol A (BPA) continues to grow, this compound is gradually being replaced, in industrial applications, with compounds such as bisphenol F (BPF) and bisphenol S (BPS). Occurrence of bisphenols, including BPA and BPS, has been reported in paper products and in environmental matrices. Information on the occurrence of bisphenols, other than BPA, in foodstuffs, however, is scarce. In this study, several bisphenol analogues, including BPA, BPF, and BPS, were analyzed in foodstuffs (N = 267) collected from Albany, NY, USA, using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Foodstuffs were divided into nine categories of beverages, dairy products, fats and oils, fish and seafood, cereals, meat and meat products, fruits, vegetables, and "others". Bisphenols were found in the majority (75%) of the food samples, and the total concentrations of bisphenols (ΣBPs: sum of eight bisphenols) were in the range of below the limit of quantification (LOQ) to 1130 ng/g fresh weight, with an overall mean value of 4.38 ng/g. The highest overall mean concentration of ΣBPs was found in the "others" category, which included condiments (preserved, ready-to-serve foods). A sample of mustard (dressing) and ginger, placed in the category of vegetables, contained the highest concentrations of 1130 ng/g for bisphenol F (BPF) and 237 ng/g for bisphenol P (BPP). Concentrations of BPs in beverages (mean = 0.341 ng/g) and fruits (0.698 ng/g) were low. The predominant bisphenol analogues found in foodstuffs were BPA and BPF, which accounted for 42 and 17% of the total BP concentrations, respectively. Canned foods contained higher concentrations of individual and total bisphenols in comparison to foods sold in glass, paper, or plastic containers. On the basis of measured concentrations and daily ingestion rates of foods, the daily dietary intakes of bisphenols (calculated from the mean concentration) were estimated to be 243, 142

  8. Fully analogue photonic reservoir computer.

    PubMed

    Duport, François; Smerieri, Anteo; Akrout, Akram; Haelterman, Marc; Massar, Serge

    2016-01-01

    Introduced a decade ago, reservoir computing is an efficient approach for signal processing. State of the art capabilities have already been demonstrated with both computer simulations and physical implementations. If photonic reservoir computing appears to be promising a solution for ultrafast nontrivial computing, all the implementations presented up to now require digital pre or post processing, which prevents them from exploiting their full potential, in particular in terms of processing speed. We address here the possibility to get rid simultaneously of both digital pre and post processing. The standalone fully analogue reservoir computer resulting from our endeavour is compared to previous experiments and only exhibits rather limited degradation of performances. Our experiment constitutes a proof of concept for standalone physical reservoir computers. PMID:26935166

  9. Fully analogue photonic reservoir computer

    PubMed Central

    Duport, François; Smerieri, Anteo; Akrout, Akram; Haelterman, Marc; Massar, Serge

    2016-01-01

    Introduced a decade ago, reservoir computing is an efficient approach for signal processing. State of the art capabilities have already been demonstrated with both computer simulations and physical implementations. If photonic reservoir computing appears to be promising a solution for ultrafast nontrivial computing, all the implementations presented up to now require digital pre or post processing, which prevents them from exploiting their full potential, in particular in terms of processing speed. We address here the possibility to get rid simultaneously of both digital pre and post processing. The standalone fully analogue reservoir computer resulting from our endeavour is compared to previous experiments and only exhibits rather limited degradation of performances. Our experiment constitutes a proof of concept for standalone physical reservoir computers. PMID:26935166

  10. 76 FR 12845 - Airworthiness Directives; APEX Aircraft Model CAP 10 B Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-09

    ... Register on December 30, 2010 (75 FR 82335). That NPRM proposed to correct an unsafe condition for the... Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and (3) Will not have a significant... CAP 10 B Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation...

  11. 8Be and 9B nuclei in dissociation of relativistic 10B and 11C nuclei

    NASA Astrophysics Data System (ADS)

    Artemenkov, D. A.; Bradnova, V.; Firu, E.; Kornegrutsa, N. K.; Haiduc, M.; Mamatkulov, K. Z.; Kattabekov, R. R.; Neagu, A.; Rukoyatkin, P. A.; Rusakova, V. V.; Stanoeva, R.; Zaitsev, A. A.; Zarubin, P. I.; Zarubina, I. G.

    2016-02-01

    Progress in the study of nuclear clustering in the relativistic 10B and 11C nuclei dissociation in nuclear track emulsion is presented. The contribution of the unbound 8Be and 9B nuclei to their structure is determined on the basis of measurements of the emission angles of relativistic He and H fragments.

  12. Use of nude mice in experimental neutron capture therapy with 10B-BPA

    SciTech Connect

    Tamaoki, N.; Ueda, M.; Tamauchi, S.; Yamamoto, K.; Mishima, Y. )

    1989-07-01

    Mouse B16 melanoma allografts in nude mice were successfully treated by thermal neutron irradiation after IP injection of 10B-paraboronophenylalanine hydrochloride. The tumor growth was significantly suppressed for 4 weeks after irradiation, compared with animals given neutron irradiation alone. Tumor-bearing nude mice were shown to be useful for evaluating the treatment for melanoma.

  13. Mutations in WNT10B Are Identified in Individuals with Oligodontia.

    PubMed

    Yu, Ping; Yang, Wenli; Han, Dong; Wang, Xi; Guo, Sen; Li, Jinchen; Li, Fang; Zhang, Xiaoxia; Wong, Sing-Wai; Bai, Baojing; Liu, Yao; Du, Jie; Sun, Zhong Sheng; Shi, Songtao; Feng, Hailan; Cai, Tao

    2016-07-01

    Tooth agenesis is one of the most common developmental anomalies in humans. Oligodontia, a severe form of tooth agenesis, is genetically and phenotypically a heterogeneous condition. Although significant efforts have been made, the genetic etiology of dental agenesis remains largely unknown. In the present study, we performed whole-exome sequencing to identify the causative mutations in Chinese families in whom oligodontia segregates with dominant inheritance. We detected a heterozygous missense mutation (c.632G>A [p.Arg211Gln]) in WNT10B in all affected family members. By Sanger sequencing a cohort of 145 unrelated individuals with non-syndromic oligodontia, we identified three additional mutations (c.569C>G [p.Pro190Arg], c.786G>A [p.Trp262(∗)], and c.851T>G [p.Phe284Cys]). Interestingly, analysis of genotype-phenotype correlations revealed that mutations in WNT10B affect the development of permanent dentition, particularly the lateral incisors. Furthermore, a functional assay demonstrated that each of these mutants could not normally enhance the canonical Wnt signaling in HEPG2 epithelial cells, in which activity of the TOPFlash luciferase reporter was measured. Notably, these mutant WNT10B ligands could not efficiently induce endothelial differentiation of dental pulp stem cells. Our findings provide the identification of autosomal-dominant WNT10B mutations in individuals with oligodontia, which increases the spectrum of congenital tooth agenesis and suggests attenuated Wnt signaling in endothelial differentiation of dental pulp stem cells. PMID:27321946

  14. Preparation and characterization of (10)B boric acid with high purity for nuclear industry.

    PubMed

    Zhang, Weijiang; Liu, Tianyu; Xu, Jiao

    2016-01-01

    Boric acid is often added into coolant as neutron capture agent for pressurized water reactor, whose amount is influenced by its abundance and purity. Therefore, the preparation of enriched (10)B boric acid with high purity is beneficial to nuclear industry. (10)B is also used in developing tumor-specific boronated drugs in boron neutron capture therapy. The boronated drug can be administered to patient intravenously, intratumorally, or deposited at tumor site in surgical excision. Thus, enriched (10)B boric acid is of practical significance in the field of medicine. Self-made boron trifluoride-methanol-complex solution was selected as one of the experimental reagents, and the preparation of (10)B acid was realized by one-step reaction for the complexes with water and calcium chloride. The determination of electrical conductivity in reaction process proves that the optimum reaction time was 16-20 h. Furthermore, the effect of reaction time, ratio of calcium chloride to complex as well as the amount of water on the purity and yield of boric acid was investigated. Finally, the optimum reaction time was 20 h, the optimal solid-liquid ratio (molar ratio) was 3:1, and the amount of water was 1 L of deionized water for each mol of the complex. H2O2 was added in the reaction process to remove Fe(2+). After recrystallization, IR spectra of (10)B boric acid was measured and compared with standard to verify the product of boric acid. The feasibility of the preparation method was determined by the detection of XRD of boric acid. To observe the morphology by polarizing microscope, crystal structure was obtained. The purity of the final product is 99.95 %, and the yield is 96.47 %. The ion concentration of boric acid accords with the national standard of high purity, which was determined by ICP. PMID:27516940

  15. Structural Analogues of Selfotel.

    PubMed

    Dziuganowska, Zofia A; Ślepokura, Katarzyna; Volle, Jean-Noël; Virieux, David; Pirat, Jean-Luc; Kafarski, Paweł

    2016-06-17

    A small library of phosphonopiperidylcarboxylic acids, analogues of NMDA antagonist selfotel (CGS 19755), was synthesized. First, the series of aromatic esters was obtained via a palladium-catalyzed cross-coupling reaction (Hirao coupling) of dialkyl phosphites with bromopyridinecarboxylates, followed by their hydrolysis. Then, hydrogenation of the resulting phosphonopyridylcarboxylic acids over PtO2 yielded the desired phosphonopiperidylcarboxylic acids. NMR studies indicated that the hydrogenation reaction proceeds predominantly by cis addition. Several compounds were obtained as monocrystal structures. Preliminary biological studies performed on cultures of neurons suggest that the obtained compounds possess promising activity toward NMDA receptors. PMID:27187758

  16. The effects of NaCl concentration and pH on the stability of hyperthermophilic protein Ssh10b

    PubMed Central

    Mao, Yong-Jin; Sheng, Xiang-Rong; Pan, Xian-Ming

    2007-01-01

    Background Hyperthermophiles constitute a group of microorganisms with an optimum growth temperature of between 80°C and 100°C. Although the molecular underpinnings of protein thermostabilization have been the focus of many theoretical and experimental efforts, the properties leading to the higher denaturation temperature of hyperthermophilic proteins are still controversial. Among the large number of factors identified as responsible for the thermostability of hyperthermophilic proteins, the electrostatic interactions are thought to be a universally important factor. Results In this study, we report the effects of pH and salt concentration on the urea-induced denaturation of the protein Ssh10b from a hyperthermophile in low ionic strength buffer. In the absence of NaCl, the unfolding ΔG of the protein increased from about 33 kJ/mol at pH 3 to about 78 kJ/mol at pH 10. At all values of pH, the ΔG increased with increasing NaCl concentration, indicating that salt stabilizes the protein significantly. Conclusion These findings suggests that the increased number of charged residues and ion pairs in the protein Ssh10b from hyperthermophiles does not contribute to the stabilization of the folded protein, but may play a role in determining the denatured state ensemble and also in increasing the denaturation temperature. PMID:18096085

  17. Analogue-to-Digital and Digital-to-Analogue Conversion.

    ERIC Educational Resources Information Center

    Gregory, Martin

    1997-01-01

    Discusses circuits for three-bit and four-bit analogue digital converters and digital analogue converters. These circuits feature slow operating speeds that enable the circuitry to be used to demonstrate the mode of operation using oscilloscopes and signal generators. (DDR)

  18. Space analogue studies in Antarctica

    NASA Astrophysics Data System (ADS)

    Lugg, D.; Shepanek, M.

    1999-09-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mltogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  19. Space analogue studies in Antarctica

    NASA Technical Reports Server (NTRS)

    Lugg, D.; Shepanek, M.

    1999-01-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  20. Study of the 10B ( p ,α)7Be reaction through the indirect Trojan Horse method

    NASA Astrophysics Data System (ADS)

    Puglia, S. M. R.; Spitaleri, C.; Lamia, L.; Romano, S.; Burjan, V.; Carlin, N.; Chengbo, L.; Del Santo, M. G.; Kroha, V.; Hons, Z.; Irgaziev, B.; La Cognata, M.; Mrazek, J.; Mukhamedzhanov, A.; Munhoz, M. G.; Pizzone, R. G.; Qungang, W.; Rapisarda, G. G.; Shu-Hua, Z.; Sergi, M. L.; Somoryai, E.; Souza, F.; Szanto de Toledo, A.; Tabacaru, G.; Tumino, A.; Wakabayashi, Y.; Yamaguchi, H.

    2015-02-01

    Boron abundances in stellar atmospheres, as well as berillium and lithium ones, can give useful hints for non-standard transport processes discrimination in stars. They can also be relevant for understanding several astrophysical processes (e.g. primordial nucleosynthesis and spallation reactions in ISM). A comprehensive study of Li Be B abundances can therefore confirm or not the presence of non-standard mixing processes in stellar envelopes. For this reason nuclear processes producing or depleting boron isotope abundance need to be studied at astrophysical energies. The 10B ( p ,α)7Be reaction has been studied by means of the Trojan Horse Method. The Trojan Horse Method was thus applied to the 10B ( d ,α7Be ) n reaction, studied at 24 MeV. The obtained results will be discussed.

  1. Characterization of a 10B-doped liquid scintillator as a capture-gated neutron spectrometer

    NASA Astrophysics Data System (ADS)

    Hunt, S.; Iliadis, C.; Longland, R.

    2016-03-01

    We use a 250 MHz digitizer to characterize the pulse shape discrimination of a BC-523A 10B-doped liquid scintillator with capture-gating capabilities. Our results are compared to recent work claiming pulse shape discrimination between fast and thermal neutron signals. The capture event is identified, and we explain the origin of signals that are often misinterpreted. We use the time-of-flight method to measure the detector energy resolution for fast incident monoenergetic neutrons and the intrinsic neutron detection efficiency. Monte Carlo simulations are performed and we find agreement between measured and simulated results. These steps are important for understanding 10B-doped capture-gated spectroscopy in mixed radiation environments, as efficiencies using capture-gating are rarely reported in the literature.

  2. Association Analysis of WNT10B With Bone Mass and Structure Among Individuals of African Ancestry

    PubMed Central

    Zmuda, Joseph M; Yerges, Laura M; Kammerer, Candace M; Cauley, Jane A; Wang, Xiaojing; Nestlerode, Cara S; Wheeler, Victor W; Patrick, Alan L; Bunker, ClareAnn H; Moffett, Susan P; Ferrell, Robert E

    2009-01-01

    Wnts comprise a family of secreted growth factors that regulate the development and maintenance of many organs. Recently, Wnt10b was shown to stimulate osteoblastogenesis and bone formation in mice. To evaluate further the role of Wnt10b in bone health in humans, we performed bidirectional sequencing of ∼8 kb of the WNT10B gene region in 192 individuals (96 African, 96 white) to identify single nucleotide polymorphisms (SNPs). We identified 19 SNPs with minor allele frequency (MAF) ≥0.01. Ten of these SNPs were not present in the NCBI dbSNP database (build 127), whereas 10 of the 20 SNPs (50%) reported in dbSNP were not verified. We initially genotyped seven tagging SNPs that captured common (MAF ≥ 0.05) variation in the region with r 2 > 0.80 and a potentially functional SNP in exon 5 in 1035 Afro-Caribbean men ≥40 yr of age. Association analysis showed three SNPs in a 3′ region of linkage disequilibrium that were associated with DXA measures of hip BMD. Associations between two of these three SNPs (rs1051886, rs3741627) with hip BMD were replicated in an additional 980 Afro-Caribbean men (p < 0.05), in the combined sample of 2015 men (p ≤ 0.006), and in 416 individuals ≥18 yr of age (mean, 44 yr) belonging to eight extended, multigenerational Afro-Caribbean families with mean family size >50 (3535 relative pairs; p < 0.05). Further analysis showed that rs1051886 and rs3741627 were associated with cortical cross-sectional area, periosteal circumference, and BMC in the radius, such that individuals with the minor alleles had lower biomechanical indices of long-bone bending strength. This analysis implicates the WNT10B locus as a genetic element in the regulation of bone mass and structural geometry. PMID:19016593

  3. 10B multi-grid proportional gas counters for large area thermal neutron detectors

    NASA Astrophysics Data System (ADS)

    Andersen, K.; Bigault, T.; Birch, J.; Buffet, J. C.; Correa, J.; Hall-Wilton, R.; Hultman, L.; Höglund, C.; Guérard, B.; Jensen, J.; Khaplanov, A.; Kirstein, O.; Piscitelli, F.; Van Esch, P.; Vettier, C.

    2013-08-01

    3He was a popular material in neutrons detectors until its availability dropped drastically in 2008. The development of techniques based on alternative convertors is now of high priority for neutron research institutes. Thin films of 10B or 10B4C have been used in gas proportional counters to detect neutrons, but until now, only for small or medium sensitive area. We present here the multi-grid design, introduced at the ILL and developed in collaboration with ESS for LAN (large area neutron) detectors. Typically thirty 10B4C films of 1 μm thickness are used to convert neutrons into ionizing particles which are subsequently detected in a proportional gas counter. The principle and the fabrication of the multi-grid are described and some preliminary results obtained with a prototype of 200 cm×8 cm are reported; a detection efficiency of 48% has been measured at 2.5 Å with a monochromatic neutron beam line, showing the good potential of this new technique.

  4. Heterogeneity of miR-10b expression in circulating tumor cells

    PubMed Central

    Gasch, Christin; Plummer, Prue N.; Jovanovic, Lidija; McInnes, Linda M.; Wescott, David; Saunders, Christobel M.; Schneeweiss, Andreas; Wallwiener, Markus; Nelson, Colleen; Spring, Kevin J.; Riethdorf, Sabine; Thompson, Erik W.; Pantel, Klaus; Mellick, Albert S.

    2015-01-01

    Circulating tumor cells (CTCs) in the blood of cancer patients are recognized as important potential targets for future anticancer therapies. As mediators of metastatic spread, CTCs are also promising to be used as ‘liquid biopsy’ to aid clinical decision-making. Recent work has revealed potentially important genotypic and phenotypic heterogeneity within CTC populations, even within the same patient. MicroRNAs (miRNAs) are key regulators of gene expression and have emerged as potentially important diagnostic markers and targets for anti-cancer therapy. Here, we describe a robust in situ hybridization (ISH) protocol, incorporating the CellSearch® CTC detection system, enabling clinical investigation of important miRNAs, such as miR-10b on a cell by cell basis. We also use this method to demonstrate heterogeneity of such as miR-10b on a cell-by-cell basis. We also use this method to demonstrate heterogeneity of miR-10b in individual CTCs from breast, prostate and colorectal cancer patients. PMID:26522916

  5. Phosphonate analogues of aminoacyl adenylates.

    PubMed Central

    Southgate, C C; Dixon, H B

    1978-01-01

    Phosphonomethyl analogues of glycyl phosphate and valyl phosphate, i.e. NH2-CHR-CO-CH2-PO(OH)2, were synthesized and esterified with adenosine to give analogues of aminoacyl adenylates. The interaction of these adenylate analogues with valyl-tRNA synthetase from Escherichia coli was studied by fluorescence titration. The analogue of valyl phosphate has an affinity for the enzyme comparable with that of valine, but that of valyl adenylate is bound much less tightly than either valyl adenylate or corresponding derivative of valinol. The affinity of the analogue of glycyl adenylate was too low to be measured. We conclude that this enzyme interacts specifically with both the side chain and the anhydride linkage of the adenylate intermediate. PMID:743207

  6. Parthenolide induces apoptosis via TNFRSF10B and PMAIP1 pathways in human lung cancer cells

    PubMed Central

    2014-01-01

    Background Parthenolide (PTL) is a sesquiterpene lactone which can induce apoptosis in cancer cells and eradicate cancer stem cells such as leukemia stem cells, prostate tumor-initiating cells and so on. However, the mechanism remains largely unclear. Methods Lung cancer cells were treated with parthenolide and the cell lysates were prepared to detect the given proteins by Western Blot analysis, and the cell survival was assayed by SRB and MTT assay. Cell cycle was evaluated by DNA flow cytometry analysis. TNFRSF10B, PMAIP1, ATF4 and DDIT3 genes were knocked down by siRNA technique. Apoptosis was evaluated by using Annexin V-FITC/PI staining and flow cytometry analysis. Results Parthenolide (PTL) induces apoptosis and cell cycle arrest in human lung cancer cells. Moreover, PTL treatment in NSCLC cells increases expression of TNFRSF10B/DR5 and PMAIP1/NOXA. Silencing of TNFRSF10B or PMAIP1 or overexpression of CFLAR /c-FLIP (long form) could protect cells from PTL-induced apoptosis. Furthermore, PTL could increase the levels of endoplasmic reticulum stress hallmarks such as ERN1, HSPA5, p-EIF2A, ATF4 and DDIT3. Knockdown of ATF4 and DDIT3 abrogated PTL-induced apoptosis, which suggested that PTL induced apoptosis in NSCLC cells through activation of endoplasmic reticulum stress pathway. More importantly, we found that ATF4, DDIT3, TNFRSF10B and PMAIP1 were up-regulated more intensively, while CFLAR and MCL1 were down-regulated more dramatically by PTL in A549/shCDH1 cells than that in control cells, suggesting that PTL preferred to kill cancer stem cell-like cells by activating more intensive ER stress response in cancer stem cell-like cells. Conclusion We showed that parthenolide not only triggered extrinsic apoptosis by up-regulating TNFRSF10B and down-regulating CFLAR, but also induced intrinsic apoptosis through increasing the expression of PMAIP1 and decreasing the level of MCL1 in NSCLC cells. In addition, parthenolide triggered stronger ER stress response in

  7. Effect of time period after boric acid injection on 10B absorption in different regions of adult male rat's brain.

    PubMed

    Khojasteh, Nasrin Baghban; Pazirandeh, Ali; Jameie, Behnam; Goodarzi, Samereh

    2012-06-01

    Distribution of (10)B in different regions of rat normal brain was studied. Two groups were chosen as control and trial. Trial group received 2 ml of neutral boron compound. 2, 4 and 6 h after the injection brain removed, coronal sections of forebrain, midbrain and hindbrain were sandwiched between two pieces of polycarbonate. Autoradiography plots of (10)B distribution showed significant differences in three regions with the highest (10)B concentration in the forebrain during 4 h after injection. PMID:22476013

  8. New investigations of the 10B(p,{\\alpha }_{0})7Be reaction at bombarding energies between 0.6 and 1 MeV

    NASA Astrophysics Data System (ADS)

    Lombardo, I.; Dell'Aquila, D.; Conte, F.; Francalanza, L.; La Cognata, M.; Lamia, L.; La Torre, R.; Spadaccini, G.; Spitaleri, C.; Vigilante, M.

    2016-08-01

    We measured the 10B(p,{α }0)7Be reaction in the bombarding energy domain of 0.6-1.0 MeV, a region where very few data (with large uncertainties) have been reported in the literature. Despite the experimental difficulties, due to the unfavourable reaction kinematics and the presence of contaminants in the 10B target, we were able to measure excitation functions at both forward and backward angles thanks to the use of the inverse absorber technique. The obtained angular distributions show a continuous shape evolution, testifying to the contributions of several resonant states in the 11C compound nucleus. An R-matrix analysis of some reaction and scattering channels allows us to refine the spectroscopy of 11C excited states.

  9. Characterization of the new NSLS infrared microspectroscopy beamline U10B

    SciTech Connect

    Carr, G.L.

    1999-07-19

    The first of several new infrared beamlines, built on a modified bending magnet port of the NSLS VUV ring, is now operational for mid-infrared microspectroscopy. The port simultaneously delivers 40 mrad by 40 mrad to two separate beamlines and spectrometer endstations designated U10A and U10B. The latter is equipped with a scanning infrared microspectrometer. The combination of this instrument and high brightness synchrotron radiation makes diffraction-limited microspectroscopy practical. This paper describes the beamline's performance and presents quantitative information on the diffraction-limited resolution.

  10. CHARACTERIZATION OF THE NEW NSLS INFARED MICROSPECTROSCOPY BEAMLINE U10B.

    SciTech Connect

    CARR,G.L.

    1999-07-19

    The first of several new infrared beamlines, built on a modified bending magnet port of the NSLS VUV ring, is now operational for mid-infrared microspectroscopy. The port simultaneously delivers 40 mrad by 40 mrad to two separate beamlines and spectrometer endstations designated U10A and U10B. The latter is equipped with a scanning infrared microspectrometer. The combination of this instrument and high brightness synchrotron radiation makes diffraction-limited microspectroscopy practical. This paper describes the beamline's performance and presents quantitative information on the diffraction-limited resolution.

  11. 75 FR 52344 - Sinicway International Logistics Ltd. Possible Violations of Sections 10(A)(1) and 10(B)(2) of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-25

    ... Distribution Publications, Inc., and is published electronically at https://www.dpiusa.com . Sinicway currently..., in violation of 10(b)(2) of the Shipping Act. Now therefore, it is ordered, That pursuant to sections... Sinicway International Logistics Ltd. Possible Violations of Sections 10(A)(1) and 10(B)(2) of the...

  12. Ultracold neutron detectors based on 10B converters used in the qBounce experiments☆

    PubMed Central

    Jenke, Tobias; Cronenberg, Gunther; Filter, Hanno; Geltenbort, Peter; Klein, Martin; Lauer, Thorsten; Mitsch, Kevin; Saul, Heiko; Seiler, Dominik; Stadler, David; Thalhammer, Martin; Abele, Hartmut

    2013-01-01

    Gravity experiments with very slow, so-called ultracold neutrons connect quantum mechanics with tests of Newton's inverse square law at short distances. These experiments face a low count rate and hence need highly optimized detector concepts. In the frame of this paper, we present low-background ultracold neutron counters and track detectors with micron resolution based on a 10B converter. We discuss the optimization of 10B converter layers, detector design and concepts for read-out electronics focusing on high-efficiency and low-background. We describe modifications of the counters that allow one to detect ultracold neutrons selectively on their spin-orientation. This is required for searches of hypothetical forces with spin–mass couplings. The mentioned experiments utilize a beam-monitoring concept which accounts for variations in the neutron flux that are typical for nuclear research facilities. The converter can also be used for detectors, which feature high efficiencies paired with high spatial resolution of 1–2μm. They allow one to resolve the quantum mechanical wave function of an ultracold neutron bound in the gravity potential above a neutron mirror. PMID:25843998

  13. Structure-based Design, Synthesis, Biochemical and Pharmacological Characterization of Novel Salvinorin A Analogues as Active State Probes of the κ-Opioid Receptor

    PubMed Central

    Yan, Feng; Bikbulatov, Ruslan V.; Mocanu, Viorel; Dicheva, Nedyalka; Parker, Carol E.; Wetsel, William C.; Mosier, Philip D.; Westkaemper, Richard B.; Allen, John A.; Zjawiony, Jordan K.; Roth, Bryan L.

    2009-01-01

    Salvinorin A, the most potent naturally occurring hallucinogen, has gained increasing attention since the κ-opioid receptor (KOR) was identified as its principal molecular target by us (Roth et al, PNAS, 2002). Here we report the design, synthesis and biochemical characterization of novel, irreversible, salvinorin A-derived ligands suitable as active state probes of the KOR. Based on prior substituted cysteine accessibility and molecular modeling studies, C3157.38 was chosen as a potential anchoring point for covalent labeling of salvinorin A-derived ligands. Automated docking of a series of potential covalently-bound ligands suggested that either a haloacetate moiety or other similar electrophilic groups could irreversibly bind with C3157.38. 22-thiocyanatosalvinorin A (RB-64) and 22-chlorosalvinorin A (RB-48) were both found to be extraordinarily potent and selective KOR agonists in vitro and in vivo. As predicted based on molecular modeling studies, RB-64 induced wash-resistant inhibition of binding with a strict requirement for a free cysteine in or near the binding pocket. Mass spectrometry (MS) studies utilizing synthetic KOR peptides and RB-64 supported the hypothesis that the anchoring residue was C3157.38 and suggested one biochemical mechanism for covalent binding. These studies provide direct evidence for the presence of a free cysteine in the agonist-bound state of KOR and provide novel insights into the mechanism by which salvinorin A binds to and activates KOR. PMID:19555087

  14. Direct experimental evidence for a metastable state of D/sub 2/F, an analogue of D/sub 3/O

    SciTech Connect

    Raksit, A.B.; Jeon, S.J.; Porter, R.F.

    1986-05-22

    The D/sub 2/F radical has been studied by a combination of neutralized ion beam and charge stripping techniques. Neutrals formed by D/sub 2/SF/sup +//Na charge exchange are observed in metastable and dissociative states. The lifetime of metastable D/sub 2/F is greater than 0.4 ..mu..s. Metastability is not observed for HDF or H/sub 2/F. The dissociative state of D/sub 2/F releases about 1.9 eV of kinetic energy in its fragmentation products (DF + D). The vertical electron affinity of H/sub 2/F/sup +/ is calculated to be 6.6 +- 0.2 eV. The possibility of observing an emission continuum from electronically excited H/sub 2/F formed by H/sub 2/F/sup +//K charge exchange is suggested. Similarities in the mass spectra of D/sub 2/F and the isoelectronic D/sub 3/O radical are indicated.

  15. MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11

    SciTech Connect

    Liu, Xiaoyou; Dong, Changgui; Jiang, Zhengyao; Wu, William K.K.; Chan, Matthew T.V.; Zhang, Jie; Li, Haibin; Qin, Ke; Sun, Xuyong

    2015-04-10

    Kidney transplantation is the major therapeutic option for end-stage kidney diseases. However, acute rejection could cause allograft loss in some of these patients. Emerging evidence supports that microRNA (miRNA) dysregulation is implicated in acute allograft rejection. In this study, we used next-generation sequencing to profile miRNA expression in normal and acutely rejected kidney allografts. Among 75 identified dysregulated miRNAs, miR-10b was the most significantly downregulated miRNAs in rejected allografts. Transfecting miR-10b inhibitor into human renal glomerular endothelial cells recapitulated key features of acute allograft rejection, including endothelial cell apoptosis, release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor α, interferon-γ, and chemokine (C–C motif) ligand 2) and chemotaxis of macrophages whereas transfection of miR-10b mimics had opposite effects. Downregulation of miR-10b directly derepressed the expression of BCL2L11 (an apoptosis inducer) as revealed by luciferase reporter assay. Taken together, miR-10b downregulation mediates many aspects of disease pathogenicity of acute kidney allograft rejection. Restoring miR-10b expression in glomerular endothelial cells could be a novel therapeutic approach to reduce acute renal allograft loss. - Highlights: • miR-10b was the most downregulated microRNAs in acutely rejected renal allografts. • miR-10b downregulation triggered glomerular endothelial cell apoptosis. • miR-10b downregulation induced release of pro-inflammatory cytokines. • miR-10b downregulation derepressed its pro-apoptotic target BCL2L11.

  16. Capillary electrophoresis-electrospray mass spectrometry and HR-ICP-MS for the detection and quantification of 10B-boronophenylalanine (10B-BPA) used in boron neutron capture therapy.

    PubMed

    Pitois, Aurélien; de las Heras, Laura Aldave; Zampolli, Antonella; Menichetti, Luca; Carlos, Ramon; Lazzerini, Guido; Cionini, Luca; Salvatori, Pietro Alberto; Betti, Maria

    2006-02-01

    Boron neutron capture therapy (BNCT) is a bimodal radiotherapeutic treatment based on the irradiation of neoplastic tissues with neutrons after the tissues have selectively accumulated molecules loaded with nuclides with large neutron capture cross-sections (such boron-10). Boron-10 carriers have been tested to a limited extent, and clinical trials have been conducted on sulfhydryl borane (10B-BSH) and boronophenylalanine (10B-BPA). However, precise and accurate measurements of boron-10 concentrations (0.1-100 microg/g) in specimens and samples of limited size (microg scale) are needed in order to be able to biologically characterise new compounds in predictive tissue dosimetry, toxicology and pharmacology studies as well as in clinical investigations. A new approach based on fast separation and detection of 10B-BPA performed by coupling capillary electrophoresis to electrospray mass spectrometry is reported. This method allows the quantitative analysis and characterisation of 10B-BPA in a short time with a high separation efficiency. Detection limits of 3 microM for 10B-BPA and 30 ng/mL for 10B were obtained with CE-ESI-MS. A quantification limit of 10 microM for 10B-BPA (100 ng/mL for 10B) was attained. The total boron-10 concentration was determined by high-resolution inductively coupled mass spectrometry in order to validate the method. Boron-10 isotope measurements were carried out by HR-ICP-MS at medium resolution (R=4000) due to the presence of an isobaric interference at mass 10. Good agreement was obtained between the values from CE-ESI-MS and those from HR-ICP-MS. The method has been successfully used to determine the 10B-BPA in two lines of cultured cells. PMID:16372182

  17. The Effects of Long Duration Bed Rest as a Spaceflight Analogue on Resting State Sensorimotor Network Functional Connectivity and Neurocognitive Performance

    NASA Technical Reports Server (NTRS)

    Cassady, K.; Koppelmans, V.; Yuan, P.; Cooke, K.; De Dios, Y.; Stepanyan, V.; Szecsy, D.; Gadd, N.; Wood, S.; Reuter-Lorenz, P.; Castenada, R. Riascos; Kofman, I.; Bloomberg, J.; Mulavara, A.; Seidler, R.

    2015-01-01

    Long duration spaceflight has been associated with detrimental alterations in human sensorimotor systems and neurocognitive performance. Prolonged exposure to a head-down tilt position during long duration bed rest can resemble several effects of the microgravity environment such as reduced sensory inputs, body unloading and increased cephalic fluid distribution. The question of whether microgravity affects other central nervous system functions such as brain functional connectivity and its relationship with neurocognitive performance is largely unknown, but of potential importance to the health and performance of astronauts both during and post-flight. The aims of the present study are 1) to identify changes in sensorimotor resting state functional connectivity that occur with extended bed rest exposure, and to characterize their recovery time course; 2) to evaluate how these neural changes correlate with neurocognitive performance. Resting-state functional magnetic resonance imaging (rsfMRI) data were collected from 17 male participants. The data were acquired through the NASA bed rest facility, located at the University of Texas Medical Branch (Galveston, TX). Participants remained in bed with their heads tilted down six degrees below their feet for 70 consecutive days. RsfMRI data were obtained at seven time points: 7 and 12 days before bed rest; 7, 50, and 65 days during bed rest; and 7 and 12 days after bed rest. Functional connectivity magnetic resonance imaging (fcMRI) analysis was performed to measure the connectivity of sensorimotor networks in the brain before, during, and post-bed rest. We found a decrease in left putamen connectivity with the pre- and post-central gyri from pre bed rest to the last day in bed rest. In addition, vestibular cortex connectivity with the posterior cingulate cortex decreased from pre to post bed rest. Furthermore, connectivity between cerebellar right superior posterior fissure and other cerebellar regions decreased from

  18. Effect of oxygen pressure during incubation with a (10)B-carrier on (10)B uptake capacity of cultured p53 wild-type and mutated tumor cells: dependency on p53 status of tumor cells and types of (10)B-carriers.

    PubMed

    Masunaga, Shin-ichiro; Tatebe, Hitoshi; Nishimura, Yasumasa; Tano, Keizo; Sanada, Yu; Moriwaki, Takahiro; Sakurai, Yoshinori; Tanaka, Hiroki; Suzuki, Minoru; Kondo, Natsuko; Maruhashi, Akira; Ono, Koji

    2016-01-01

    Purpose To evaluate the effect of oxygen pressure during incubation with a (10)B-carrier on (10)B uptake capacity of cultured p53 wild-type and mutated tumor cells. Materials and methods Cultured human head and neck squamous cell carcinoma cell line transfected with mutant TP53 (SAS/mp53), or with a neo vector as a control (SAS/neo) was incubated with L-para-boronophenylalanine-(10)B (BPA) or sodium mercaptoundecahydrododecaborate-(10)B (BSH) as a (10)B-carrier at the (10)B concentration of 60 ppm for 24 h under aerobic (20.7% of oxygen) or hypoxic (0.28% of oxygen) conditions. Immediately after incubation, cultured tumor cells received reactor thermal neutron beams, and a cell survival assay was performed. (10)B concentration of cultured SAS/neo or SAS/mp53 cells incubated under aerobic or hypoxic conditions was determined with a thermal neutron guide tube. Results Hypoxic incubation significantly decreased (10)B concentration of cultured cells with a clearer tendency observed following BPA than BSH treatment in both SAS/neo and SAS/mp53 cells. Following neutron beam irradiation, SAS/mp53 cells showed significantly higher relative biological effectiveness values than SAS/neo cells because of the significantly lower radiosensitivity of SAS/mp53 to γ-rays than SAS/neo cells. Conclusion Oxygen pressure during incubation with a (10)B-carrier had a critical impact on (10)B uptake of cultured tumor cells. PMID:26887694

  19. Promotion of hair follicle development and trichogenesis by Wnt-10b in cultured embryonic skin and in reconstituted skin

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

    2006-06-30

    We previously showed that Wnt-10b promoted the differentiation of primary skin epithelial cells (MPSEC) toward hair shaft and inner root sheath of the hair follicle (IRS) cells in vitro. In the present study, we found that Wnt-10b promotes the development of hair follicles using a culture of mouse embryonic skin tissue and trichogenesis using a reconstitution experiment with nude mice. Hair follicle development was observed in skin taken from mouse embryos on embryonic day 10.5 following a 2-day culture with recombinant Wnt-10b (rWnt-10b), however, not without rWnt-10b. Brown hair growth was observed at the site of reconstituted skin in Balb/c nude mice where dermal fibroblasts and keratinocytes, derived from C3H/HeN new born mice, were transplanted with Wnt-10b-producing COS cells (Wnt-COS). Without the co-transplantation of Wnt-COS, no hair growth was observed. Our results suggest an important role of Wnt-10b in the initiation of hair follicle development and following trichogenesis.

  20. The edaravone and 3-n-butylphthalide ring-opening derivative 10b effectively attenuates cerebral ischemia injury in rats

    PubMed Central

    Hua, Kai; Sheng, Xiao; Li, Ting-ting; Wang, Lin-na; Zhang, Yi-hua; Huang, Zhang-jian; Ji, Hui

    2015-01-01

    Aim: Compound 10b is a hybrid molecule of edaravone and a ring-opening derivative of 3-n-butylphthalide (NBP). The aim of this study was to examine the effects of compound 10b on brain damage in rats after focal cerebral ischemia. Methods: SD rats were subjected to 2-h-middle cerebral artery occlusion (MCAO). At the onset of reperfusion, the rats were orally treated with NBP (60 mg/kg), edaravone (3 mg/kg), NBP (60 mg/kg)+edaravone (3 mg/kg), or compound 10b (70, 140 mg/kg). The infarct volume, motor behavior deficits, brain water content, histopathological alterations, and activity of GSH, SOD, and MDA were analyzed 24 h after reperfusion. The levels of relevant proteins in the ipsilateral striatum were examined using immunoblotting. Results: Administration of compound 10b (70 or 140 mg/kg) significantly reduced the infarct volume and neurological deficits in MCAO rats. The neuroprotective effects of compound 10b were more pronounced compared to NBP, edaravone or NBP+edaravone. Furthermore, compound 10b significantly upregulated the protein levels of the cytoprotective molecules Bcl-2, HO-1, Nrf2, Trx, P-NF-κB p65, and IκB-α, while decreasing the expression of Bax, caspase 3, caspase 9, Txnip, NF-κB p65, and P-IκB-α. Conclusion: Oral administration of compound 10b effectively attenuates rat cerebral ischemia injury. PMID:26073328

  1. miR-148a is a downstream effector of X-box-binding protein 1 that silences Wnt10b during adipogenesis of 3T3-L1 cells

    PubMed Central

    Cho, Yoon Mi; Kim, Tae-Min; Hun Kim, Dae; Hee Kim, Dong; Jeong, Seong-Whan; Kwon, Oh-Joo

    2016-01-01

    Wnt10b, an endogenous inhibitor of adipogenesis, maintains preadipocytes in an undifferentiated state by suppressing adipogenic transcription factors. We have previously demonstrated that Wnt10b transcription during adipogenesis is negatively regulated by X-box-binding protein 1 (XBP1), an important transcription factor of the unfolded protein response. In this report, we demonstrate that XBP1s can directly induce the transcription of microRNA-148a, which in turn mediates the silencing of Wnt10b mRNA during adipogenic differentiation of 3T3-L1 cells. Stability of Wnt10b mRNA was found to be significantly increased by knockdown of XBP1s. Using computational algorithms, a set of microRNAs was predicted to bind Wnt10b mRNA, of which microRNA-148a was selected as a potential target for XBP1s. Our results revealed that microRNA-148a could bind to the 3′UTR of Wnt10b mRNA. Its ectopic expression significantly suppressed both Wnt10b expression and β-catenin activity. When we altered the expression of XBP1 in 3T3-L1 cells, microRNA-148a levels changed accordingly. A potential XBP1 response element was found in the promoter region of microRNA-148a, and XBP1s directly bound to this response element as shown by point mutation analysis and chromatin immunoprecipitation assay. In addition, a microRNA-148a mimic significantly restored adipogenic potential in XBP1-deficient 3T3-L1 cells. These findings provide the first evidence that XBP1s can regulate Wnt10b by a post-transcriptional mechanism through directly inducing microRNA-148a. PMID:27055562

  2. Over-expression of miR-10b in NPC patients: correlation with LMP1 and Twist1.

    PubMed

    Allaya, Nesrine; Khabir, Abdelmajid; Sallemi-Boudawara, Tahia; Sellami, Noura; Daoud, Jamel; Ghorbel, Abdelmonem; Frikha, Mounir; Gargouri, Ali; Mokdad-Gargouri, Raja; Ayadi, Wajdi

    2015-05-01

    Aberrant expression of miR-10b has been described in many cancers but remains unexplored in nasopharyngeal carcinoma (NPC). Therefore, we aimed to study the miR-10b expression level in 43 NPC biopsies collected from Tunisian patients and three NPC xenografts. Then, we investigated the correlation between miR-10b expression and its upstream regulators LMP1/Twist1 as well as its adjacent gene HoxD4. We showed that miR-10b was significantly up-regulated in NPC biopsies compared to non-tumor nasopharyngeal tissues (fold change 153; p = 0.004) and associated with advanced clinical stage and young age at diagnosis (p = 0.005 and p = 0.011, respectively). In addition, over-expression of miR-10b was positively associated with the transcription factor Twist1 as well as the EBV oncoprotein LMP1 (fold change 6.32; p = 0.014, fold change 6.58; p = 0.01 respectively). Furthermore, higher level of miR-10b was observed in tumors with simultaneous expression of LMP1 and Twist1, compared to those expressing only Twist1 (fold change 2.49; p = 0.033). Meanwhile, the analysis of the link between miR-10b and its neighbor gene HoxD4 did not show any significant correlation (Fisher test p = 0.205; Mann-Whitney test p = 0.676). This study reports the first evidence of miR-10b over-expression in NPC patients. Furthermore, our findings can support hsa-miR-10b gene regulation through LMP1/Twist1 in NPC malignancy. PMID:25597482

  3. Role of miR-10b in breast cancer metastasis

    PubMed Central

    2010-01-01

    Ninety percent of cancer-related mortality is caused by metastasis. Current cancer treatments can control many primary tumors but rarely stop the metastatic spread. Accumulating evidence demonstrates that miRNAs are involved in cancer initiation and progression. Furthermore, several miRNAs have been found to regulate metastasis. In particular, recent studies provide the first functional evidence that overexpression of a specific miRNA, miR-10b, can contribute to the development of metastasis, which can be exploited therapeutically in treating breast cancer metastasis in mice. Further in-depth analysis should provide more precise evaluation of the roles, mechanisms, and therapeutic utility of this miRNA in breast cancer. PMID:21067538

  4. XRD, TDPAC and LAPW study of Hf10B2 under high pressure

    NASA Astrophysics Data System (ADS)

    Halevy, I.; Beck, A.; Yaar, I.; Kahane, S.; Levy, O.; Auster, E.; Ettedgui, U.; Caspi, E. N.; Rivin, O.; Berant, Z.; Hu, J.

    The crystallographic structure and electronic properties of Hf10B2 were studied as a function of pressure by combining X-ray diffraction measurements with full potential linearized augmented plane wave (LAPW) calculations. No phase transition was observed up to a pressure of 30.8 GPa, with a total volume contraction of V/V 0 =0.85 and a bulk modulus value of B 0=232±13 GPa. The calculated V zz value at the hafnium site is linearly increasing as a function of the pressure induced volume reduction, while the V zz value at the boron site stays almost zero. The major contribution to the V zz value at the hafnium site comes from a p-p contribution next to the probe nucleus, with a relatively large d-d contribution of about 25%. This unusual large d-d contribution arises from the hafnium p-d electrons coupling.

  5. XRD, TDPAC and LAPW study of Hf10B2 under high pressure

    NASA Astrophysics Data System (ADS)

    Halevy, I.; Beck, A.; Yaar, I.; Kahane, S.; Levy, O.; Auster, E.; Ettedgui, H.; Caspi, E. N.; Rivin, O.; Berant, Z.; Hu, J.

    2007-06-01

    The crystallographic structure and electronic properties of Hf10B2 were studied as a function of pressure by combining X-ray diffraction measurements with full potential linearized augmented plane wave (LAPW) calculations. No phase transition was observed up to a pressure of 30.8 GPa, with a total volume contraction of V/ V 0 = 0.85 and a bulk modulus value of B 0 = 232 ±13 GPa. The calculated V zz value at the hafnium site is linearly increasing as a function of the pressure induced volume reduction, while the V zz value at the boron site stays almost zero. The major contribution to the V zz value at the hafnium site comes from a p p contribution next to the probe nucleus, with a relatively large d d contribution of about 25%. This unusual large d d contribution arises from the hafnium p d electrons coupling.

  6. Combined TL and 10B-alanine ESR dosimetry for BNCT.

    PubMed

    Bartolotta, A; D'Oca, M C; Lo Giudice, B; Brai, M; Borio, R; Forini, N; Salvadori, P; Manera, S

    2004-01-01

    The dosimetric technique described in this paper is based on electron spin resonance (ESR) detectors using an alanine-boric compound acid enriched with (10)B, and beryllium oxide thermoluminescent (TL) detectors; with this combined dosimetry, it is possible to discriminate the doses due to thermal neutrons and gamma radiation in a mixed field. Irradiations were carried out inside the thermal column of a TRIGA MARK II water-pool-type research nuclear reactor, also used for Boron Neutron Capture therapy (BNCT) applications, with thermal neutron fluence from 10(9) to 10(14) nth cm(-2). The ESR dosemeters using the alanine-boron compound indicated ESR signals about 30-fold stronger than those using only alanine. Moreover, a negligible correction for the gamma contribution, measured with TL detectors, almost insensitive to thermal neutrons, was necessary. Therefore, a simultaneous analysis of our TL and ESR detectors allows discrimination between thermal neutron and gamma doses, as required in BNCT. PMID:15353720

  7. Tidal dissipation in a homogeneous spherical body. II. Three examples: Mercury, Io, and Kepler-10 b

    SciTech Connect

    Makarov, Valeri V.; Efroimsky, Michael E-mail: michael.efroimsky@usno.navy.mil

    2014-11-01

    In Efroimsky and Makarov (Paper I), we derived from the first principles a formula for the tidal heating rate in a homogeneous sphere, compared it with the previously used formulae, and noted the differences. Now we present case studies: Mercury, Kepler-10 b, and a triaxial Io. A sharp frequency dependence of k {sub 2}/Q near spin-orbit resonances yields a sharp dependence of k {sub 2}/Q (and, therefore, of tidal heating) upon the spin rate. Thereby physical libration plays a major role in tidal heating of synchronously rotating planets. The magnitude of libration in the spin rate being defined by the planet's triaxiality, the latter becomes a factor determining the dissipation rate. Other parameters equal, a strongly triaxial synchronized body generates more heat than a similar body of a more symmetrical shape. After an initially triaxial object melts and loses its triaxiality, dissipation becomes less intensive; the body can solidify, with the tidal bulge becoming a new figure with triaxiality lower than the original. We derive approximate expressions for the dissipation rate in a Maxwell planet with the Maxwell time longer than the inverse tidal frequency. The expressions derived pertain to the 1:1 and 3:2 resonances and a nonresonant case; so they are applicable to most close-in super-Earths detected. In these planets, the heating outside synchronism is weakly dependent on the eccentricity and obliquity, provided both these parameters's values are moderate. According to our calculation, Kepler-10 b could hardly survive the intensive tidal heating without being synchronized, circularized, and reshaped through a complete or partial melt-down.

  8. Detection of the secondary eclipse of WASP-10b in the Ks-band

    NASA Astrophysics Data System (ADS)

    Cruz, Patricia; Barrado, David; Lillo-Box, Jorge; Diaz, Marcos; Birkby, Jayne; López-Morales, Mercedes; Hodgkin, Simon; Fortney, Jonathan J.

    2015-02-01

    Context. WASP-10b, a non-inflated hot Jupiter, was discovered around a K-dwarf in a near circular orbit (~0.06). Since its discovery in 2009, different published parameters for this system have led to a discussion about the size, density, and eccentricity of this exoplanet. Aims: In order to test the hypothesis of a circular orbit for WASP-10b, we observed its secondary eclipse in the Ks-band, where the contribution of planetary light is high enough to be detected from the ground. Methods: Observations were performed with the OMEGA2000 instrument at the 3.5 m telescope at Calar Alto (Almería, Spain), in staring mode during 5.4 continuous hours, with the telescope defocused, monitoring the target during the expected secondary eclipse. A relative light curve was generated and corrected from systematic effects, using the principal component analysis (PCA) technique. The final light curve was fitted using a transit model to find the eclipse depth and a possible phase shift. Results: The best model obtained from the Markov chain Monte Carlo analysis resulted in an eclipse depth of ΔF of 0.137%+0.013%-0.019% and a phase offset of Δφ of -0.0028 +0.0005-0.0004. The eclipse phase offset derived from our modeling has systematic errors that were not taken into account and should not be considered as evidence of an eccentric orbit. The offset in phase obtained leads to a value for | ecosω | of 0.0044. The derived eccentricity is too small to be of any significance. Based on observations collected at the Calar Alto Observatory, Almería, Spain.

  9. Ruthenium(0) nanoparticle-catalyzed isotope exchange between 10B and 11B nuclei in decaborane(14).

    PubMed

    Yinghuai, Zhu; Widjaja, Effendi; Sia, Shirley Lo Pei; Zhan, Wang; Carpenter, Keith; Maguire, John A; Hosmane, Narayan S; Hawthorne, M Frederick

    2007-05-23

    Well dispersed ruthenium(0) nanoparticles, stabilized in the ionic liquid agent, trihexyltetradecylphosphonium dodecylbenzenesulfonate, have been successfully prepared via a reduction reaction of the precursor [CpRuCp*RuCp*]PF6 (Cp* = C5Me5). The ruthenium(0) nanoparticles were shown to catalyze the isotope exchange reaction between 10B enriched diborane and natural abundant B10H14 to produce highly 10B enriched (approximately 90%) decaborane(14) products. The ruthenium(0) nanoparticles were characterized by TEM, XRD, and XPS. The 10B enriched decaborane(14) has been analyzed by Raman spectroscopy, NMR, and high-resolution MS. PMID:17472379

  10. Materials analogue of zero-stiffness structures

    NASA Astrophysics Data System (ADS)

    Kumar, Arun; Subramaniam, Anandh

    2011-04-01

    Anglepoise lamps and certain tensegrities are examples of zero-stiffness structures. These structures are in a state of neutral equilibrium with respect to changes in configuration of the system. Using Eshelby's example of an edge dislocation in a thin plate that can bend, we report the discovery of a non-trivial new class of material structures as an analogue to zero-stiffness structures. For extended positions of the edge dislocation in these structures, the dislocation experiences a zero image force. Salient features of these material structures along with the key differences from conventional zero-stiffness structures are pointed out.

  11. Analogue modelling of syntectonic leucosomes in migmatitic schists

    NASA Astrophysics Data System (ADS)

    Druguet, Elena; Carreras, Jordi

    2006-10-01

    Migmatites from the Cap de Creus tectonometamorphic belt display a wide variety of structures, from those formed when the leucosomes were melt-bearing, to those developed during solid-state deformation. The observed field structures have been modelled by means of analogue experiments. The materials used in the models are layered plasticine as a schist analogue, and chocolate as analogue of the crystallizing leucosome. A model for the development of syntectonic migmatites is proposed in which initial melt-bearing patches, preferentially formed within fertile pelitic layers, progressively evolve towards lens-shaped veins. Furthermore, heterogeneous deformation of anisotropic metasediments facilitates formation of extensional sites for further melt accumulation and transport. Melt crystallization implies a rapid increase in effective viscosity of leucosomes producing a reversal in competence contrast with respect to the enclosing schists. During the whole process, deformation localizes around crystallizing veins, giving rise to different and contrasting structures for melt-bearing and for solid-state stages.

  12. Comparison of the Josephson Voltage Standards of the NIMT and the BIPM (part of the ongoing BIPM key comparison BIPM.EM-K10.b)

    NASA Astrophysics Data System (ADS)

    Solve, S.; Chayramy, R.; Stock, M.; Pimsut, S.; Rujirat, N.

    2016-01-01

    A comparison of the Josephson array voltage standards of the Bureau International des Poids et Mesures (BIPM) and the National Institute of Metrology - (Thailand), NIMT, was carried out in November 2015 at the level of 10 V. For this exercise, options A and B of the BIPM.EM-K10.b comparison protocol were applied. Option B required the BIPM to provide a reference voltage for measurement by the NIMT using its Josephson standard with its own measuring device. Option A required the NIMT to provide a reference voltage with its Josephson voltage standard for measurement by the BIPM using an analogue nanovoltmeter and associated measurement loop. In all cases the BIPM array was kept floating from ground. The final results were in good agreement within the combined relative standard uncertainty of 2.6 parts in 1010 for the nominal voltage of 10 V. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  13. 5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells.

    PubMed

    Henry, Sean; Kidner, Ria; Reisenauer, Mary R; Magedov, Igor V; Kiss, Robert; Mathieu, Véronique; Lefranc, Florence; Dasari, Ramesh; Evidente, Antonio; Yu, Xiaojie; Ma, Xiuye; Pertsemlidis, Alexander; Cencic, Regina; Pelletier, Jerry; Cavazos, David A; Brenner, Andrew J; Aksenov, Alexander V; Rogelj, Snezna; Kornienko, Alexander; Frolova, Liliya V

    2016-09-14

    Plants of the Amaryllidaceae family produce a large variety of alkaloids and non-basic secondary metabolites, many of which are investigated for their promising anticancer activities. Of these, crinine-type alkaloids based on the 5,10b-ethanophenanthridine ring system were recently shown to be effective at inhibiting proliferation of cancer cells resistant to various pro-apoptotic stimuli and representing tumors with dismal prognoses refractory to current chemotherapy, such as glioma, melanoma, non-small-cell lung, esophageal, head and neck cancers, among others. Using this discovery as a starting point and taking advantage of a concise biomimetic route to the crinine skeleton, a collection of crinine analogues were synthetically prepared and evaluated against cancer cells. The compounds exhibited single-digit micromolar activities and retained this activity in a variety of drug-resistant cancer cell cultures. This investigation resulted in the discovery of new bicyclic ring systems with significant potential in the development of effective clinical cancer drugs capable of overcoming cancer chemotherapy resistance. PMID:27218860

  14. Phosphonomethyl analogues of hexose phosphates.

    PubMed

    Webster, D; Jondorf, W R; Dixon, H B

    1976-05-01

    The analogue of fructose 1,6-bisphosphate in which the phosphate group, -O-PO3H2, on C-6 is replaced by the phosphonomethyl group, -CH2-PO3H2, was made enzymically from the corresponding analogue of 3-phosphoglycerate. It was a substrate for aldolase, which was used to form it, but not for fructose 1,6-bisphosphatase. It was hydrolysed chemically to yield the corresponding analogue of fructose 6-phosphate [i.e. 6-deoxy-6-(phosphonomethyl)-D-fructose, or, more strictly, 6,7-dideoxy-7-phosphono-D-arabino-2-heptulose]. This proved to be a substrate for the sequential actions of glucose 6-phosphate isomerase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Thus seven out of the nine enzymes of the glycolytic and pentose phosphate pathways so far tested catalyse the reactions of the phosphonomethyl isosteres of their substrates. PMID:7247

  15. The locus of microRNA-10b: a critical target for breast cancer insurgence and dissemination.

    PubMed

    Biagioni, Francesca; Bossel Ben-Moshe, Noa; Fontemaggi, Giulia; Yarden, Yosef; Domany, Eytan; Blandino, Giovanni

    2013-08-01

    Contemporary microRNA research has led to significant advances in our understanding of the process of tumorigenesis. MicroRNAs participate in different events of a cancer cell's life, through their ability to target hundreds of putative transcripts involved in almost every cellular function, including cell cycle, apoptosis, and differentiation. The relevance of these small molecules is even more evident in light of the emerging linkage between their expression and both prognosis and clinical outcome of many types of human cancers. This identifies microRNAs as potential therapeutic modifiers of cancer phenotypes. From this perspective, we overview here the miR-10b locus and its involvement in cancer, focusing on its role in the establishment (miR-10b*) and spreading (miR-10b) of breast cancer. We conclude that targeting the locus of microRNA 10b holds great potential for cancer treatment. PMID:23839045

  16. Capability of NIPAM polymer gel in recording dose from the interaction of (10)B and thermal neutron in BNCT.

    PubMed

    Khajeali, Azim; Reza Farajollahi, Ali; Kasesaz, Yaser; Khodadadi, Roghayeh; Khalili, Assef; Naseri, Alireza

    2015-11-01

    The capability of N-isopropylacrylamide (NIPAM) polymer gel to record the dose resulting from boron neutron capture reaction in BNCT was determined. In this regard, three compositions of the gel with different concentrations of (10)B were prepared and exposed to gamma radiation and thermal neutrons. Unlike irradiation with gamma rays, the boron-loaded gels irradiated by neutron exhibited sensitivity enhancement compared with the gels without (10)B. It was also found that the neutron sensitivity of the gel increased by the increase of concentration of (10)B. It can be concluded that NIPAM gel might be suitable for the measurement of the absorbed dose enhancement due to (10)B and thermal neutron reaction in BNCT. PMID:26356043

  17. The Complete Genome Sequence of Escherichia coli DH10B: Insights into the Biology of a Laboratory Workhorse▿ †

    PubMed Central

    Durfee, Tim; Nelson, Richard; Baldwin, Schuyler; Plunkett, Guy; Burland, Valerie; Mau, Bob; Petrosino, Joseph F.; Qin, Xiang; Muzny, Donna M.; Ayele, Mulu; Gibbs, Richard A.; Csörgő, Bálint; Pósfai, György; Weinstock, George M.; Blattner, Frederick R.

    2008-01-01

    Escherichia coli DH10B was designed for the propagation of large insert DNA library clones. It is used extensively, taking advantage of properties such as high DNA transformation efficiency and maintenance of large plasmids. The strain was constructed by serial genetic recombination steps, but the underlying sequence changes remained unverified. We report the complete genomic sequence of DH10B by using reads accumulated from the bovine sequencing project at Baylor College of Medicine and assembled with DNAStar's SeqMan genome assembler. The DH10B genome is largely colinear with that of the wild-type K-12 strain MG1655, although it is substantially more complex than previously appreciated, allowing DH10B biology to be further explored. The 226 mutated genes in DH10B relative to MG1655 are mostly attributable to the extensive genetic manipulations the strain has undergone. However, we demonstrate that DH10B has a 13.5-fold higher mutation rate than MG1655, resulting from a dramatic increase in insertion sequence (IS) transposition, especially IS150. IS elements appear to have remodeled genome architecture, providing homologous recombination sites for a 113,260-bp tandem duplication and an inversion. DH10B requires leucine for growth on minimal medium due to the deletion of leuLABCD and harbors both the relA1 and spoT1 alleles causing both sensitivity to nutritional downshifts and slightly lower growth rates relative to the wild type. Finally, while the sequence confirms most of the reported alleles, the sequence of deoR is wild type, necessitating reexamination of the assumed basis for the high transformability of DH10B. PMID:18245285

  18. 77 FR 56681 - Order Granting Limited Exemptions From Exchange Act Rule 10b-17 and Rules 101 and 102 of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-13

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Order Granting Limited Exemptions From Exchange Act Rule 10b-17 and Rules 101 and 102 of Regulation M to iShares, Inc. and iShares MSCI Frontier 100 Index Fund Pursuant to Exchange Act Rule 10b-17(b)(2) and Rule 101(d) and 102(e) of...

  19. Boron uptake in tumors, cerebrum and blood from [10B]NA4B24H22S2

    DOEpatents

    Slatkin, Daniel N.; Micca, Peggy L.; Fairchild, Ralph G.

    1988-08-02

    A stable boronated (.sup.10 B-labeled) compound, sodium mercaptoundecahydrododecaborate is infused in the form of the disulfide dimer, [.sup.10 B]Na.sub.4 B.sub.24 H.sub.22 S.sub.2, at a dose of about 200 .mu.g .sup.10 B per gm body weight. The infusion is performed into the blood or peritoneal cavity of the patient slowly over a period of many days, perhaps one week or more, at the rate of roughly 1 .mu.g .sup.10 B per gm body weight per hour. Use of this particular boronated dimer in the manner or similarly to the manner so described permits radiotherapeutically effective amounts of boron to accumulate in tumors to be treated by boron neutron capture radiation therapy and also permits sufficient retention of boron in tumor after the cessation of the slow infusion, so as to allow the blood concentration of .sup.10 B to drop or to be reduced artificially to a radiotherapeutically effective level, less than one-half of the concentration of .sup.10 B in the tumor.

  20. Boron uptake in tumors, cerebrum and blood from [10B]NA4B24H22S2

    DOEpatents

    Slatkin, Daniel N.; Micca, Peggy L.; Fairchild, Ralph G.

    1988-01-01

    A stable boronated (.sup.10 B-labeled) compound, sodium mercaptoundecahydrododecaborate is infused in the form of the disulfide dimer, [.sup.10 B]Na.sub.4 B.sub.24 H.sub.22 S.sub.2, at a dose of about 200 .mu.g .sup.10 B per gm body weight. The infusion is performed into the blood or peritoneal cavity of the patient slowly over a period of many days, perhaps one week or more, at the rate of roughly 1 .mu.g .sup.10 B per gm body weight per hour. Use of this particular boronated dimer in the manner or similarly to the manner so described permits radiotherapeutically effective amounts of boron to accumulate in tumors to be treated by boron neutron capture radiation therapy and also permits sufficient retention of boron in tumor after the cessation of the slow infusion, so as to allow the blood concentration of .sup.10 B to drop or to be reduced artificially to a radiotherapeutically effective level, less than one-half of the concentration of .sup.10 B in the tumor.

  1. XRD, TDPAC and LAPW Study of Hf10B2 Under High Pressure

    SciTech Connect

    Halevy, I.; Beck, A; Yaar, I; Kahane, S; Levy, O; Auster, E; Ettedgui, H; Caspi, E; Rivin, O; et. al.

    2008-01-01

    The crystallographic structure and electronic properties of Hf{sup 10}B{sub 2} were studied as a function of pressure by combining X-ray diffraction measurements with full potential linearized augmented plane wave (LAPW) calculations. No phase transition was observed up to a pressure of 30.8 GPa, with a total volume contraction of V/V{sub 0}=0.85 and a bulk modulus value of B{sub 0}=232 {+-}13 GPa. The calculated V{sub zz} value at the hafnium site is linearly increasing as a function of the pressure induced volume reduction, while the V{sub zz} value at the boron site stays almost zero. The major contribution to the V{sub zz} value at the hafnium site comes from a p-p contribution next to the probe nucleus, with a relatively large d-d contribution of about 25%. This unusual large d-d contribution arises from the hafnium p-d electrons coupling.

  2. Copper ion detection using novel silver nanoclusters stabilized with amido black 10B.

    PubMed

    Ma, Fangfang; Liang, Sheng; Peng, Yibo; Kuang, Yangfang; Zhang, Xing; Chen, Shu; Long, Yunfei; Zeng, Rongjin

    2016-05-01

    Novel fluorescent silver nanoclusters (AgNCs) were synthesized using amido black 10B (AB) as a stabilizing agent and then employed for the detection of copper ions (Cu(2+)). The AB-stabilized AgNCs (AB-AgNCs) were well dispersed in aqueous solution with an average diameter of around 1.3 nm and exhibited illustrious blue fluorescence emission. Moreover, the fluorescence of AB-AgNCs could be quenched efficiently by Cu(2+), which might be a result of the coordination between Cu(2+) and the free recognition group of AB on surfaces of AB-AgNCs, inducing the aggregation of AB-AgNCs. Based on the linear decrease of fluorescence intensity, the Cu(2+) concentration was determined in the range of 0.01-1.1 μmol L(-1) and the limit of detection (LOD) was 4.0 nΜ. In addition, the detection of Cu(2+) could be performed with AB-AgNCs in the presence of other ions, including 13 kinds of conventional metal ions and 11 kinds of anions. Based on the above experiment, the developed AB-AgNC probe was successfully further applied to detect Cu(2+) in three electroplating effluents, which showed high accuracy. Graphical abstract The process of synthesised silver nanoclusters and the application for Cu(2+) detection. PMID:26873219

  3. A new study of 10B(p,α)7Be reaction at low energies

    NASA Astrophysics Data System (ADS)

    Caciolli, A.; Depalo, R.; Broggini, C.; La Cognata, M.; Lamia, L.; Menegazzo, R.; Mou, L.; Puglia, S. M. R.; Rigato, V.; Romano, S.; Rossi Alvarez, C.; Sergi, M. L.; Spitaleri, C.; Tumino, A.

    2016-05-01

    The 10B(p,α)7Be reaction is of great interest since it has many applications in different fields of research such as nuclear astrophysics, nuclear physics, and models of new reactors for clean energy generation. This reaction has been studied at the AN2000 accelerator of the INFN National Laboratories of Legnaro (LNL). The total cross section has been measured in a wide energy range (250-1182 keV) by using the activation method. The decays of the 7Be nuclei produced by the reaction were measured at the low counting facility of LNL by using two fully shielded high-purity germanium detectors. The present dataset shows a large discrepancy with respect to one of the previous data at the same energies and reduces the total uncertainty to the level of 6%. An R-matrix calculation has been performed on the present data using the parameters from previous Trojan Horse measurements for the 10 and 500keV resonances. The present data do not lay on the R-matrix fit in one point suggesting the existence of a 11C level not observed yet. Further nuclear investigations are needed to confirm this hypothesis.

  4. New measurement of the 10B(p,α0)7Be reaction cross section at low energies and the structure of 11C

    NASA Astrophysics Data System (ADS)

    Lombardo, I.; Dell'Aquila, D.; Conte, F.; Francalanza, L.; La Cognata, M.; Lamia, L.; La Torre, R.; Spadaccini, G.; Spitaleri, C.; Vigilante, M.

    2016-05-01

    We report preliminary results of a new measurement of the 10B(p,α0)7Be cross section in the 0.6 - 1.0 MeV bombarding energy domain. In this region very few data have been reported in the literature. Excitation functions at both forward and backward angles have been obtained. Angular distributions testify the contribution due to several excited states in the 11C compound nucleus. The experimental S-factor is about 30% lower than the one reported in the literature and based on activation methods.

  5. Farnesyl Diphosphate Analogues with Aryl Moieties are Efficient Alternate Substrates for Protein Farnesyltransferase

    PubMed Central

    Subramanian, Thangaiah; Pais, June E.; Liu, Suxia; Troutman, Jerry M.; Suzuki, Yuta; Subramanian, Karunai Leela; Fierke, Carol; Andres, Douglas A.; Spielmann, H. Peter

    2012-01-01

    Farnesylation is an important post-translational modification essential for proper localization and function of many proteins. Transfer of the farnesyl group from farnesyl diphosphate (FPP) to proteins is catalyzed by protein farnesyltransferase (FTase). We employed a library of FPP analogues with a range of aryl groups substituting for individual isoprene moieties to examine some of the structural and electronic properties of analogue transfer to peptide catalyzed by FTase. Analysis of steady-state kinetics for modification of peptide substrates revealed that the multiple turnover activity depends on the analogue structure. Analogues where the first isoprene is replaced by a benzyl group and an analogue where each isoprene is replaced by an aryl group are good substrates. In sharp contrast with the steady-state reaction, the single turnover rate constant for dansyl-GCVLS alkylation was found to be the same for all analogues, despite the increased chemical reactivity of the benzyl analogues and the increased steric bulk of other analogues. However, the single turnover rate constant for alkylation does depend on the Ca1a2X peptide sequence. These results suggest that the isoprenoid transition state conformation is preferred over the inactive E•FPP• Ca1a2X ternary complex conformation. Furthermore, these data suggest that the farnesyl binding site in the exit groove may be significantly more selective for the farnesyl diphosphate substrate than the active site binding pocket and therefore might be a useful site for design of novel inhibitors. PMID:22989235

  6. Review of insulin and its analogues in diabetes mellitus.

    PubMed

    Mane, Krishnappa; Chaluvaraju, Kc; Niranjan, Ms; Zaranappa, Tr; Manjuthej, Tr

    2012-03-01

    Diabetes is a metabolic disorder where in human body does not produce or properly uses insulin, a hormone that is required to convert sugar, starches and other food into energy. Diabetes finally leads to more complications and to prevent these complications insulin and its analogues are used. After more than half a century of treating diabetics with animal insulin's, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogues were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid, intermediate and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analogue, lispro, confirmed the hopes by showing that improved glycaemic control can be achieved without an increase in hypoglycaemic events. Two new insulin analogues, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States and several other analogues are being intensively tested. PMID:24826038

  7. Thermal conductivity changes upon neutron transmutation of {sup 10}B doped diamond

    SciTech Connect

    Jagannadham, K.; Verghese, K.; Butler, J. E.

    2014-08-28

    {sup 10}B doped p-type diamond samples were subjected to neutron transmutation reaction using thermal neutron flux of 0.9 × 10{sup 13} cm{sup −2} s{sup −1} and fast neutron flux of 0.09 × 10{sup 13} cm{sup −2} s{sup −1}. Another sample of epilayer grown on type IIa (110) single crystal diamond substrate was subjected to equal thermal and fast neutron flux of 10{sup 14} cm{sup −2} s{sup −1}. The defects in the diamond samples were previously characterized by different methods. In the present work, thermal conductivity of these diamond samples was determined at room temperature by transient thermoreflectance method. The thermal conductivity change in the samples as a function of neutron fluence is explained by the phonon scattering from the point defects and disordered regions. The thermal conductivity of the diamond samples decreased more rapidly initially and less rapidly for larger neutron fluence. In addition, the thermal conductivity in type IIb diamond decreased less rapidly with thermal neutron fluence compared to the decrease in type IIa diamond subjected to fast neutron fluence. It is concluded that the rate of production of defects during transmutation reaction is slower when thermal neutrons are used. The thermal conductivity of epilayer of diamond subjected to high thermal and fast neutron fluence is associated with the covalent carbon network in the composite structure consisting of disordered carbon and sp{sup 2} bonded nanocrystalline regions.

  8. Microanalytical techniques for boron analysis using the 10B(n,alpha)7Li reaction.

    PubMed

    Fairchild, R G; Gabel, D; Laster, B H; Greenberg, D; Kiszenick, W; Micca, P L

    1986-01-01

    In order to predict the efficacy of boronated compounds for neutron capture therapy (NCT), it is mandatory that the boron concentration in tissues be known. Various techniques for measurement of trace amounts of boron (1-100 ppm) are available, including chemical and physical procedures. Experience has shown that, with the polyhedral boranes and carboranes in particular, the usual colorimetric and spark emission spectroscopic methods are not reliable. Although these compounds may be traced with additional radiolabels, direct physical detection of boron by nondestructive methods is clearly preferable. Boron analysis via detection of the prompt-gamma ray from the 10B(n, alpha)7Li reaction has been shown to be a reliable technique. Two prompt-gamma facilities developed at Brookhaven National Laboratory are described. One, at the 60-MW high flux beam reactor, uses sophisticated beam extraction techniques to enhance thermal neutron intensity and reduce fast neutron and gamma contamination. The other was constructed at Brookhaven's 5-MW medical research reactor and uses conventional shielding and electronics to provide an "on-line" boron analysis facility adjacent to beams designed for NCT, thus satisfying one of the requisites for clinical application of this procedure. Technical restrictions attendant upon the synthesis and testing of boronated biomolecules often require the measurement of trace amounts of boron in extremely small (mg) samples. A track-etching technique capable of detecting ng amounts of boron in mg liquid or cell samples is described. Thus it is possible to measure the boron content in small amounts (mg samples) of antibodies, or boron uptake in cells grown in tissue culture. PMID:3951409

  9. Curcumin analogues with high activity for inhibiting human prostate cancer cell growth and androgen receptor activation.

    PubMed

    Zhou, Dai-Ying; Ding, Ning; Du, Zhi-Yun; Cui, Xiao-Xing; Wang, Hong; Wei, Xing-Chuan; Conney, Allan H; Zhang, Kun; Zheng, Xi

    2014-09-01

    The androgen receptor (AR) has a critical role in prostate cancer development and progression. Several curcumin analogues (A10, B10, C10, E10 and F10) with different linker groups were investigated for their effects in human prostate cancer CWR‑22Rv1 and LNCaP cell lines. The ability of these compounds to inhibit testosterone (TT)‑ or dihydrotestosterone (DHT)‑induced AR activity was determined by an AR‑linked luciferase assay and by TT‑ or DHT‑induced expression of prostate specific antigen. Compounds F10 and E10 had stronger inhibitory effects on the growth of cultured CWR‑22Rv1 and LNCaP cell lines, and they also had enhanced stimulatory effects on apoptosis compared with curcumin and other curcumin analogues (A10, B10, C10) in CWR‑22Rv1 cells. E10 and F10 were more potent inhibitors of AR activity than curcumin, A10 and B10. The higher activities of E10 and F10 may be correlated with a heteroatom linker. The results indicate that one of the potential mechanisms for the anticancer effect of the curcumin analogues was inhibition of AR pathways in human prostate cancer cells. PMID:25060817

  10. Peculiarities of changes of some physicomechanical characteristics of monoisotopes {sup 10}B, {sup 11}B and natural {beta}-boron

    SciTech Connect

    Gabunia, D. . E-mail: d_gabunia@hotmail.com; Tsagareishvili, O.; Lezhava, D.; Gabunia, L.; Antadze, M.; Darsavelidze, G.; Tanaka, T.

    2006-09-15

    Real structure and some physicomechanical characteristics of the samples of natural beta-rhombohedral boron B as well as of its {sup 10}B and {sup 11}B monoisotopes have been studied. It was shown that the influence of {sup 10}B and {sup 11}B isotopes on physicomechanical properties of boron had a different character. In particular, the samples enriched with {sup 11}B had high values of microhardness, shear modulus (SM) and elastic limit if compared to those of boron, while the samples enriched with {sup 10}B monoisotopes were characterized with high values of thermal expansion coefficient (TEC) and thermal conductivity; lattice parameters a and c increased by the sequence: {sup 11}B, B, {sup 10}B. It was established that TEC, thermal conductivity, microhardness, SM and shear elastic limit increased in all samples at annealing for 5 h at 1500 deg. C regardless of isotope content. - Graphical abstract: Temperature dependence of the SM in the samples of natural boron B, {sup 10}B and {sup 11}B monoisotopes.

  11. WNT10B/β-catenin signalling induces HMGA2 and proliferation in metastatic triple-negative breast cancer

    PubMed Central

    Wend, Peter; Runke, Stephanie; Wend, Korinna; Anchondo, Brenda; Yesayan, Maria; Jardon, Meghan; Hardie, Natalie; Loddenkemper, Christoph; Ulasov, Ilya; Lesniak, Maciej S; Wolsky, Rebecca; Bentolila, Laurent A; Grant, Stephen G; Elashoff, David; Lehr, Stephan; Latimer, Jean J; Bose, Shikha; Sattar, Husain; Krum, Susan A; Miranda-Carboni, Gustavo A

    2013-01-01

    Wnt/β-catenin signalling has been suggested to be active in basal-like breast cancer. However, in highly aggressive metastatic triple-negative breast cancers (TNBC) the role of β-catenin and the underlying mechanism(s) for the aggressiveness of TNBC remain unknown. We illustrate that WNT10B induces transcriptionally active β-catenin in human TNBC and predicts survival-outcome of patients with both TNBC and basal-like tumours. We provide evidence that transgenic murine Wnt10b-driven tumours are devoid of ERα, PR and HER2 expression and can model human TNBC. Importantly, HMGA2 is specifically expressed during early stages of embryonic mammogenesis and absent when WNT10B expression is lost, suggesting a developmentally conserved mode of action. Mechanistically, ChIP analysis uncovered that WNT10B activates canonical β-catenin signalling leading to up-regulation of HMGA2. Treatment of mouse and human triple-negative tumour cells with two Wnt/β-catenin pathway modulators or siRNA to HMGA2 decreases HMGA2 levels and proliferation. We demonstrate that WNT10B has epistatic activity on HMGA2, which is necessary and sufficient for proliferation of TNBC cells. Furthermore, HMGA2 expression predicts relapse-free-survival and metastasis in TNBC patients. PMID:23307470

  12. The electrical properties of Mars analogue dust

    NASA Astrophysics Data System (ADS)

    Merrison, J.; Jensen, J.; Kinch, K.; Mugford, R.; Nørnberg, P.

    2004-03-01

    Dust is a major environmental factor on the surface and in the atmosphere of Mars. Knowing the electrical charge state of this dust would be of both scientific interest and important for the safety of instruments on the Martian surface. In this study the first measurements have been performed of dust electrification using suspended Mars analogue material. This has been achieved by attracting suspended dust onto electrodes placed inside a Mars simulation wind tunnel. The Mars analogue used was from Salten Skov in Denmark, this contained a high concentration of ferric oxide precipitate. Once suspended, this dust was found to consist of almost equal quantities of negatively (46±6%) and positively (44±15%) charged grains. These grains were estimated to typically carry a net charge of around 10 5e, this is sufficient to dominate the processes of adhesion and cohesion of this suspended dust. Evidence is presented for electrostatic aggregation of the dust while in suspension. Development of a simple instrument for measuring electrical charging of the suspended dust on Mars will be discussed.

  13. Structural insights into the specificity of Xyn10B from Paenibacillus barcinonensis and its improved stability by forced protein evolution.

    PubMed

    Gallardo, Oscar; Pastor, F I Javier; Polaina, Julio; Diaz, Pilar; Łysek, Robert; Vogel, Pierre; Isorna, Pablo; González, Beatriz; Sanz-Aparicio, Julia

    2010-01-22

    Paenibacillus barcinonensis is a soil bacterium bearing a complex set of enzymes for xylan degradation, including several secreted enzymes and Xyn10B, one of the few intracellular xylanases reported to date. The crystal structure of Xyn10B has been determined by x-ray analysis. The enzyme folds into the typical (beta/alpha)(8) barrel of family 10 glycosyl hydrolases (GH10), with additional secondary structure elements within the beta/alpha motifs. One of these loops -L7- located at the beta7 C terminus, was essential for xylanase activity as its partial deletion yielded an inactive enzyme. The loop contains residues His(249)-Glu(250), which shape a pocket opened to solvent in close proximity to the +2 subsite, which has not been described in other GH10 enzymes. This wide cavity at the +2 subsite, where methyl-2,4-pentanediol from the crystallization medium was found, is a noteworthy feature of Xyn10B, as compared with the narrow crevice described for other GH10 xylanases. Docking analysis showed that this open cavity can accommodate glucuronic acid decorations of xylo-oligosaccharides. Co-crystallization experiments with conduramine derivative inhibitors supported the importance of this open cavity at the +2 subsite for Xyn10B activity. Several mutant derivatives of Xyn10B with improved thermal stability were obtained by forced evolution. Among them, mutant xylanases S15L and M93V showed increased half-life, whereas the double mutant S15L/M93V exhibited a further increase in stability, showing a 20-fold higher heat resistance than the wild type xylanase. All the mutations obtained were located on the surface of Xyn10B. Replacement of a Ser by a Leu residue in mutant xylanase S15L can increase hydrophobic packing efficiency and fill a superficial indentation of the protein, giving rise to a more compact structure of the enzyme. PMID:19940147

  14. Analysis of 10B antitumoral compounds by means of flow-injection into ESI-MS/MS.

    PubMed

    Basilico, F; Sauerwein, W; Pozzi, F; Wittig, A; Moss, R; Mauri, P L

    2005-12-01

    Boron neutron capture therapy (BNCT) is a promising binary treatment for cancer. BNCT is based on the ability of the nonradioactive isotope (10)B to capture, with a very high probability, thermal neutrons. This nuclear reaction results in two particles (an alpha and a lithium nucleus). The particles have a high biological effectiveness, which is limited in tissue to approximately the diameter of one cell. If the reaction can be limited to a tumor cell, the physical characteristic opens up the possibility to selectively destroy cancer cells, while sparing the surrounding healthy tissue. Quality control of (10)B-containing compounds and their distribution at present are very important, and different analytical methods have been developed, such as time-of-flight secondary ion mass spectrometry (TOF-SIMS), electron energy loss spectrometry (EELS), prompt gamma analysis and inductively coupled plasma-optical emission spectrometry (ICP-OES). These methods allow the analyses of (10)B, but it is not possible to characterize the specific molecular compounds containing (10)B. For this reason, we propose a fast and quantitative method that permits the determination of closo-undecahydro-1-mercaptododecaborate (BSH) and (10)boron-phenylalanine (BPA) and their eventual metabolites. In particular, (10)B-containing compounds are detected by means of flow-injection electrospray tandem mass spectrometry (FI/ESI-MS/MS). This approach allows the identification of Boron compounds, BSH and BPA, using tandem mass spectrometry, and quantitative analysis is also possible (c.v. +/-4.7%; n = 5; linear range 10-10,000 ng/ml). Furthermore, (10)B-containing compounds were detected in actual biological sample (urine and plasma, diluted 10,000- and 1,000-fold, respectively) injecting a small volume (1 microl) of diluted samples. PMID:16320299

  15. Reduction of TIP30 in esophageal squamous cell carcinoma cells involves promoter methylation and microRNA-10b

    SciTech Connect

    Dong, Wenjie; Shen, Ruizhe; Cheng, Shidan

    2014-10-31

    Highlights: • TIP30 expression is frequently suppressed in ESCC. • TIP30 was hypermethylated in ESCC. • Reduction of TIP30 was significantly correlated with LN metastasis. • miR-10b is a direct regulator of TIP30. - Abstract: TIP30 is a putative tumor suppressor that can promote apoptosis and inhibit angiogenesis. However, the role of TIP30 in esophageal squamous cell carcinoma (ESCC) biology has not been investigated. Immunohistochemistry was used to investigate the expression of TIP30 in 70 ESCC. Hypermethylation of TIP30 was evaluated by the methylation specific PCR (MSP) method in ESCC (tumor and paired adjacent non-tumor tissues). Lost expression of TIP30 was observed in 50 of 70 (71.4%) ESCC. 61.4% (43 of 70) of primary tumors analyzed displayed TIP30 hypermethylation, indicating that this aberrant characteristic is common in ESCC. Moreover, a statistically significant inverse association was found between TIP30 methylation status and expression of the TIP30 protein in tumor tissues (p = 0.001). We also found that microRNA-10b (miR-10b) targets a homologous DNA region in the 3′untranslated region of the TIP30 gene and represses its expression at the transcriptional level. Reporter assay with 3′UTR of TIP30 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-10b, providing strong evidence that miR-10b is a direct regulator of TIP30. These results suggest that TIP30 expression is regulated by promoter methylation and miR-10b in ESCC.

  16. Muscarinic interactions of bisindolylmaleimide analogues.

    PubMed

    Lazareno, S; Popham, A; Birdsall, N J

    1998-11-01

    We have used radioligand binding studies to determine the affinities of seven bisindolylmaleimide analogues, six of which are selective inhibitors of protein kinase C, at human muscarinic M1-M4 receptors. The compounds were most potent at M1 receptors, and Ro-31-8220 was the most potent analogue, with a Kd of 0.6 microM at M1 receptors. The weakest compounds, bisindolylmaleimide IV and bisindolylmaleimide V, had Kd values of 100 microM. If it is necessary to use protein kinase C inhibitors at concentrations of 10 microM or more in studies involving muscarinic receptors then bisindolylmaleimide IV may be the most appropriate inhibitor to use. PMID:9851596

  17. Irradiation data for the MFA-1 and MFA-2 tests during FFTF cycles 10A and 10B

    SciTech Connect

    Nelson, J.V.

    1996-10-30

    This report provides key information on the irradiation environment of the MONJU fuel test MFA-1 and MFA-2 in the Fast Flux Test Facility (FFTF) during operating cycles 10A and 10B.This information includes the fission powers, neutron fluxes, sodium temperatures and sodium flow rates in MFA-1, MFA-2, and adjacent assemblies. It also includes MFA-1 and MFA-2 compositions as a function of exposure during cycles 10A and 10B. The work was performed at the request of Power Reactor and Nuclear Fuels (PNC) of Japan.

  18. Measurements of 10B(p,a)7Be Cross-sections: A Reaction Relevant to Nuclear Fusion Energy Research

    NASA Astrophysics Data System (ADS)

    Fisher, Barbara; Kafkarkou, Adamos; Ahmed, Mohammad; Weller, Henry; Myers, Luke; Sparker, Mark; Zimmerman, William; Mueller, Jon; Sikora, Mark; Mazumdar, Indral

    2012-10-01

    There is growing interest in aneutronic nuclear fusion reactors. One facility proposes to utilize the 11B(p,a)7Be reaction. The Radiative Capture Group at Triangle University Nuclear Laboratory (TUNL) has been engaged in a long-term study of this and related reactions. This poster will present preliminary data and analysis of the 10B(p,a)7Be reaction which is of interest because 10B is a potential reactor contaminant. Differential and total cross-sections will be presented for incident protons of 4.4 and 4.6 MeV. The data is necessary for simulations of an aneutrionic nuclear fusion reactor.

  19. Substrate analogues for isoprenoid enzymes

    SciTech Connect

    Stremler, K.E.

    1987-01-01

    Diphosphonate analogues of geranyl diphosphate, resistant to degradation by phosphatases, were found to be alternate substrates for the reaction with farnesyl diphosphate synthetase isolated from avian liver. The difluoromethane analogue was shown to be the better alternate substrate, in agreement with solvolysis results which indicate that the electronegativity of the difluoromethylene unit more closely approximates that of the normal bridging oxygen. The usefulness of the C/sub 10/ difluoro analogue, for detecting low levels of isoprenoid enzymes in the presence of high levels of phosphatase activity, was demonstrated with a cell-free preparation from lemon peel. A series of C/sub 5/ through C/sub 15/ homoallylic and allylic diphosphonates, as well as two 5'-nucleotide diphosphonates, was prepared in high overall yield using the activation-displacement sequence. Radiolabeled samples of several of the allylic diphosphonates were prepared with tritium located at C1. A series of geraniols, stereospecifically deuterated at C1, was prepared. The enantiomeric purities and absolute configurations were determined by derivatization as the mandelate esters for analysis by /sup 1/H NMR. The stereochemistry of the activation-displacement sequence was examined using C1-deuterated substrates.

  20. Policy issues in space analogues

    NASA Astrophysics Data System (ADS)

    Auger, Robin N.; Facktor, Debra D.

    Space mission planning is increasingly focusing on destinations beyond Earth orbit. Advancements in technology will inevitably be required to enable long-duration human spaceflight missions, and breakthroughs in the policy arena will also be needed to achieve success in such missions. By exploring how policy issues have been addressed in analogous extreme environments, policymakers can develop a framework for addressing these issues as they apply to long-term human spaceflight. Policy issues that need to be addressed include: crew selection, training, organization, and activities, medical testing, illness, injury, and death; communication; legal accountability and liability; mission safety and risk management; and environmental contamination. This paper outlines the approach of a study underway by The George Washington University and ANSER to examine how these policy issues have been addressed in several analogues and how the experiences of these analogues can help formulate policies for long-duration human spaceflight missions. Analogues being studied include Antarctic bases, submarine voyages, undersea stations, Biosphere 2, and the U.S. Skylab and Russian Mir space stations.

  1. Phosphonate analogue substrates for enolase.

    PubMed

    Anderson, V E; Cleland, W W

    1990-11-20

    Phosphonate analogues in which the bridge between C-2 and phosphorus is a CH2 group are slow substrates for yeast enolase. The pH variation of the kinetic parameters for the methylene analogue of 2-phosphoglycerate suggests that the substrate binds as a dianion and that Mg2+ can bind subsequently only if a metal ligand and the catalytic base are unprotonated. Primary deuterium isotope effects of 4-8 on V/KMg, but ones of only 1.15-1.32 on V for dehydration, show that proton removal to give the carbanion intermediate largely limits V/KMg and that a slow step follows which largely limits V (presumably carbanion breakdown). Since there is a D2O solvent isotope effect on V for the reverse reaction of 5, but not an appreciable one on the forward reaction, it appears that the slow rates with phosphonate analogues result from the fact that the carbanion intermediate is more stable than that formed from the normal substrates, and its reaction in both directions limits V. Increased stability as a result of replacement of oxygen by carbon at C-2 of the carbanion is the expected chemical behavior. PMID:2271661

  2. miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours

    PubMed Central

    Biagioni, Francesca; Bossel Ben-Moshe, Noa; Fontemaggi, Giulia; Canu, Valeria; Mori, Federica; Antoniani, Barbara; Di Benedetto, Anna; Santoro, Raffaela; Germoni, Sabrina; De Angelis, Fernanda; Cambria, Anna; Avraham, Roi; Grasso, Giuseppe; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Yarden, Yosef; Domany, Eytan; Blandino, Giovanni

    2012-01-01

    Deregulated proliferation is a hallmark of cancer cells. Here, we show that microRNA-10b* is a master regulator of breast cancer cell proliferation and is downregulated in tumoural samples versus matched peritumoural counterparts. Two canonical CpG islands (5 kb) upstream from the precursor sequence are hypermethylated in the analysed breast cancer tissues. Ectopic delivery of synthetic microRNA-10b* in breast cancer cell lines or into xenograft mouse breast tumours inhibits cell proliferation and impairs tumour growth in vivo, respectively. We identified and validated in vitro and in vivo three novel target mRNAs of miR-10b* (BUB1, PLK1 and CCNA2), which play a remarkable role in cell cycle regulation and whose high expression in breast cancer patients is associated with reduced disease-free survival, relapse-free survival and metastasis-free survival when compared to patients with low expression. This also suggests that restoration of microRNA-10b* expression might have therapeutic promise. PMID:23125021

  3. miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours.

    PubMed

    Biagioni, Francesca; Bossel Ben-Moshe, Noa; Fontemaggi, Giulia; Canu, Valeria; Mori, Federica; Antoniani, Barbara; Di Benedetto, Anna; Santoro, Raffaela; Germoni, Sabrina; De Angelis, Fernanda; Cambria, Anna; Avraham, Roi; Grasso, Giuseppe; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Yarden, Yosef; Domany, Eytan; Blandino, Giovanni

    2012-11-01

    Deregulated proliferation is a hallmark of cancer cells. Here, we show that microRNA-10b* is a master regulator of breast cancer cell proliferation and is downregulated in tumoural samples versus matched peritumoural counterparts. Two canonical CpG islands (5 kb) upstream from the precursor sequence are hypermethylated in the analysed breast cancer tissues. Ectopic delivery of synthetic microRNA-10b* in breast cancer cell lines or into xenograft mouse breast tumours inhibits cell proliferation and impairs tumour growth in vivo, respectively. We identified and validated in vitro and in vivo three novel target mRNAs of miR-10b* (BUB1, PLK1 and CCNA2), which play a remarkable role in cell cycle regulation and whose high expression in breast cancer patients is associated with reduced disease-free survival, relapse-free survival and metastasis-free survival when compared to patients with low expression. This also suggests that restoration of microRNA-10b* expression might have therapeutic promise. PMID:23125021

  4. Associations of TCF12, CTNNAL1 and WNT10B gene polymorphisms with litter size in pigs.

    PubMed

    Tao, Hu; Mei, Shuqi; Sun, Xiaojie; Peng, Xianwen; Zhang, Xuying; Ma, Changping; Wang, Lei; Hua, Lun; Li, Fenge

    2013-08-01

    In previous research, several WNT signaling pathway genes including transcription factor 12 (TCF12), catenin alpha-like protein 1 (CTNNAL1) and wingless-type MMTV integration site family, member 10B (WNT10B) were differentially expressed in PMSG-hCG stimulated preovulatory ovarian follicles of Large White and Chinese Taihu sows. In the present research, these three genes were selected as the candidate genes for litter size traits in pigs. Four mutations (TCF12 c.-201+65 G>A, TCF12 c.-200-300 G>A, CTNNAL1 c.1878 G>C and WNT10B c.*12 C>T) were detected in eleven pig populations, and results indicated CTNNAL1 c.1878 G and WNT10B c.*12 C were the major alleles in all tested pig populations, while TCF12 c.-201+65 A and TCF12 c.-200-300 A were the major alleles in several Chinese native pig breeds. Association analysis of four mutations with litter size in Large White and DIV pigs showed that both the signficant differences of total number born (TNB) and number born alive (NBA) among three genotypes and the significance of additive effects appeared at TCF12 c.-200-300 G>A and CTNNAL1 c.1878 G>C loci, suggesting these two mutations might be reliable markers for pig selection and breeding. PMID:23820070

  5. Inherited deficiency of second component of complement and HLA haplotype A10,B18 associated with inflammatory bowel disease.

    PubMed

    Slade, J D; Luskin, A T; Gewurz, H; Kraft, S C; Kirsner, J B; Zeitz, H J

    1978-06-01

    A patient with inflammatory bowel disease and sacroiliitis had haplotypes A10,B18 and Aw32,b18 at the major histocompatibility locus. Serum total complement and C2 hemolytic complement activities were undetectable; levels of the remaining C1-C9 components were normal. The parents, both siblings, and a child each had half-normal levels of C2 and either the A10,B18 or the Aw32,b18 hla haplotype. In a second unrelated family, an only child and both parents developed inflammatory bowel disease. The father and child had HLA haplotype A10,B18, but, along with the mother, each had normal serum levels of hemolytic C and C2. Homozygous C2 deficiency, often in association with the A10,B18 haplotype, has previously been linked with various autoimmune diseases and with propensity to infection. Our findings suggest that C2 deficiency or this haplotype also may predispose to inflammatory diseases of the intestine. PMID:666136

  6. Uptake of [sup 10]B in gliosarcomas following the injection of gluthathione monoethyl ester and sulfhydryl borane

    SciTech Connect

    Joel, D.D.; Slatkin, D.N.; Coderre, J.A.

    1992-01-01

    The sulfhydryl borane Na[sub 2][sup 10]B[sub 12]H[sub 11]SH (BSH) was developed as a capture agent for BNCT about 20 years ago and is the compound currently used clinically in Japan for BNCT of malignant brain tumors. Tumor [sup 10]B concentrations following the infusion of the oxidized BSH, a disulfide dimer (Na[sub 4][sup 10]B[sub 24]H[sub 22]S[sub 2]), are nearly twice those obtained following administration of equal amounts of boron as BSH. Also, the rate of decrease of tumor [sup 10]B concentration is slower after dimer infusion than after BSH infusion. When BNCT was administered to rats bearing intracerebral gliosarcomas, the animals infused with dimer had a significant longer median survival time. Dimer, on the other hand, induces a moderately severe, but reversible, hepatotoxicity which may complicate its use in humans. Intracellular glutathione plays an important role in defense against radical-mediated tissue injury. Glutathione monoesters have been reported to have a protective effective on cisplatin toxicity and on radical-induced acute pancreatitis. We investigated the possibility of reducing dimer-induced hepatotoxicity by pre-administration of GSH-ME. The results indicate that not only does the pre-administration of GSH-ME markedly reduce dimer-induced hepatotoxicity, but also results in nearly a doubling of tumor boron concentration. Furthermore, GSH-ME markedly increases tumor boron uptake and retention following administration of BSH.

  7. Uptake of {sup 10}B in gliosarcomas following the injection of gluthathione monoethyl ester and sulfhydryl borane

    SciTech Connect

    Joel, D.D.; Slatkin, D.N.; Coderre, J.A.

    1992-12-31

    The sulfhydryl borane Na{sub 2}{sup 10}B{sub 12}H{sub 11}SH (BSH) was developed as a capture agent for BNCT about 20 years ago and is the compound currently used clinically in Japan for BNCT of malignant brain tumors. Tumor {sup 10}B concentrations following the infusion of the oxidized BSH, a disulfide dimer (Na{sub 4}{sup 10}B{sub 24}H{sub 22}S{sub 2}), are nearly twice those obtained following administration of equal amounts of boron as BSH. Also, the rate of decrease of tumor {sup 10}B concentration is slower after dimer infusion than after BSH infusion. When BNCT was administered to rats bearing intracerebral gliosarcomas, the animals infused with dimer had a significant longer median survival time. Dimer, on the other hand, induces a moderately severe, but reversible, hepatotoxicity which may complicate its use in humans. Intracellular glutathione plays an important role in defense against radical-mediated tissue injury. Glutathione monoesters have been reported to have a protective effective on cisplatin toxicity and on radical-induced acute pancreatitis. We investigated the possibility of reducing dimer-induced hepatotoxicity by pre-administration of GSH-ME. The results indicate that not only does the pre-administration of GSH-ME markedly reduce dimer-induced hepatotoxicity, but also results in nearly a doubling of tumor boron concentration. Furthermore, GSH-ME markedly increases tumor boron uptake and retention following administration of BSH.

  8. 78 FR 14376 - Order Granting Limited Exemptions From Exchange Act Rule 10b-17 and Rules 101 and 102 of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-05

    ... COMMISSION Order Granting Limited Exemptions From Exchange Act Rule 10b-17 and Rules 101 and 102 of.... The Fund's investment objective is to seek investment results that correspond generally to the... transactions may raise, including, but not limited to the adequacy of the disclosure concerning, and...

  9. Two-dimensional combinatorial screening enables the bottom-up design of a microRNA-10b inhibitor.

    PubMed

    Velagapudi, Sai Pradeep; Disney, Matthew D

    2014-03-21

    The RNA motifs that bind guanidinylated kanamycin A (G Kan A) and guanidinylated neomycin B (G Neo B) were identified via two-dimensional combinatorial screening (2DCS). The results of these studies enabled the "bottom-up" design of a small molecule inhibitor of oncogenic microRNA-10b. PMID:24503738

  10. Two-dimensional combinatorial screening enables the bottom-up design of a microRNA-10b inhibitor

    PubMed Central

    Velagapudi, Sai Pradeep; Disney, Matthew D.

    2014-01-01

    The RNA motifs that bind guanidinylated kanamycin A (G Kan A) and guanidinylated neomycin B (G Neo B) were identified via two-dimensional combinatorial screening (2DCS). The results of these studies enabled the “bottom-up” design of a small molecule inhibitor of oncogenic microRNA-10b. PMID:24503738

  11. The influence of Leucine-rich amelogenin peptide on MSC fate by inducing Wnt10b expression.

    PubMed

    Wen, Xin; Cawthorn, William P; MacDougald, Ormond A; Stupp, Samuel I; Snead, Malcolm L; Zhou, Yan

    2011-09-01

    Amelogenin is the most abundant protein of the enamel organic matrix and is a structural protein indispensable for enamel formation. One of the amelogenin splicing isoforms, Leucine-rich Amelogenin Peptide (LRAP) induces osteogenesis in various cell types. Previously, we demonstrated that LRAP activates the canonical Wnt signaling pathway to induce osteogenic differentiation of mouse ES cells through the concerted regulation of Wnt agonists and antagonists. There is a reciprocal relationship between osteogenic and adipogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs). Wnt10b-mediated activation of canonical Wnt signaling has been shown to regulate mesenchymal stem cell fate. Using the bipotential bone marrow stromal cell line ST2, we have demonstrated that LRAP activates the canonical Wnt/β-catenin signaling pathway. A specific Wnt inhibitor sFRP-1 abolishes the effect of LRAP on the stimulation of osteogenesis and the inhibition of adipogenesis of ST2 cells. LRAP treatment elevates the Wnt10b expression level whereas Wnt10b knockdown by siRNA abrogates the effect of LRAP. We show here that LRAP promotes osteogenesis of mesenchymal stem cells at the expense of adipogenesis through upregulating Wnt10b expression to activate Wnt signaling. PMID:21663957

  12. 76 FR 18761 - Worldwide Logistics Co., Ltd.; Possible Violations of Sections 10(a)(1) and 10(b)(2) of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... Worldwide Logistics Co., Ltd.; Possible Violations of Sections 10(a)(1) and 10(b)(2) of the Shipping Act of 1984; Order of Investigation and Hearing Worldwide Logistics Co., Ltd. (Worldwide) is a company based.... It is a part of the Worldwide Logistics Group, said to be one of the leading integrated...

  13. 77 FR 76106 - Order Granting Limited Exemptions From Exchange Act Rule 10b-17 and Rules 101 and 102 of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-26

    ... Regulation M to ALPS ETF Trust, ALPS/GS Momentum Builder Growth Markets Equities and U.S. Treasuries Index ETF, ALPS/GS Momentum Builder Multi-Asset Index ETF, and ALPS/GS Momentum Builder Asia ex-Japan Equities and U.S. Treasuries Index ETF Pursuant to Exchange Act Rule 10b-17(b)(2) and Rules 101(d) and...

  14. Alpha particles accompanying the weak decay of {sub {lambda}}{sup 10}Be and {sub {lambda}}{sup 10}B hypernuclei

    SciTech Connect

    Majling, L. Kuzmin, V. A. Tetereva, T. V.

    2006-05-15

    The possibility of a detailed investigation of weak {lambda}N interaction in the {sub {lambda}}{sup 10}Be and {sub {lambda}}{sub /10}B hypernuclei, which stand out owing to their {alpha}{alpha}N{lambda} cluster structure, is discussed. The detection of a few groups of correlated {alpha}{alpha} pairs will furnish information about decays to specific states of product nuclei ({sup 8}Be*, {sup 8}Li, {sup 8}B), thereby paving the way to a phenomenological analysis of the weak decays of p-shell hypernuclei. The ratios of the intensities of individual alpha-particle groups to be measured in experiments at the cyclotron of the Joint Institute for Nuclear Research (JINR, Dubna) will provide a useful criterion for choosing an appropriate model of weak {lambda}N interaction. The current state of hypernuclear physics is briefly reviewed.

  15. Search for the isovector monopole resonance via the 28Si(10Be,10B+ γ)28Al reaction

    NASA Astrophysics Data System (ADS)

    Scott, Michael; e11021 Collaboration Team

    2013-10-01

    The isovector giant monopole resonance (IVGMR) is a fundamental mode of collective oscillation in which the neutron and proton fluids in a nucleus radially expand and contract in an out-of-phase manner. Observation of the IVGMR has been difficult due to the lack of a probe that will excite only its non-spin-flip (ΔS = 0) transitions. The IVGMR's spin-transfer (ΔS = 1) counterpart, the isovector spin giant monopole resonance, is much more strongly excited at bombarding energies higher than 60 MeV/ u. By way of the (10Be,10B+ γ) charge-exchange reaction, the selectivity for the excitation of the IVGMR can be gained. In this probe, the superallowed Fermi transition 10Be(0+,g.s.) -->10B(01+,1.74 MeV, T = 1) allows a nearly pure isolation of the ΔS = 0 component by detecting the 1022 keV gamma rays from the deexcitation of the 10B. We measured the double differential cross sections for the 28Si(10Be,10B+ γ) reaction at 100 MeV/ u using the large acceptance S800 Spectrometer at the National Superconducting Cyclotron Laboratory with the GRETINA array detecting the gamma rays emitted from the 10B ejectile. In this presentation, we will report preliminary reults of the IVGMR in 28Al. GRETINA was funded by the US DOE - Office of Science. Operation of the array at NSCL is supported by NSF under Cooperative Agreement PHY-1102511(NSCL) and DOE under grant DE-AC02-05CH11231(LBNL).

  16. Elastic anomalies and acoustic dissipation associated with spin state transitions in LnCoO3 (Ln=La, Nd, Gd) and Co3O4: analogue behaviour for spin state transitions in minerals

    NASA Astrophysics Data System (ADS)

    Zhang, Z.; Carpenter, M. A.; Koppensteiner, J.; Schranz, W.

    2010-12-01

    Iron ions in lower mantle minerals magnesiowüstitue (Mg,Fe)O, perovskite (Mg,Fe)(Si,Al)O3 and post-perovskite phases undergo electronic spin state transitions from high spin (HS) to low spin (LS) or intermediate spin (IS) at high pressures and high temperatures. These spin state transitions give rise to changes in bulk and shear moduli which have significant implications for the physical and chemical properties of the lower mantle. However, the possibility of increased attenuation does not appear to have been considered yet. Co3+ is isoelectronic with Fe2+ and shows analogous HS/LS behaviour at ambient pressure in a temperature range which is easily accessible for in-situ investigations. We have studied spin state transitions in cobalt perovskites LaCoO3, NdCoO3, GdCoO3 and in Co3O4 using resonant ultrasound spectroscopy (RUS) at high frequencies 0.1-1.5 MHz, and dynamic mechanical analysis (DMA) at low frequencies 0.1-50 Hz, in the temperature range 10-1200 K. The specific objectives were to characterize anomalies in the shear moduli and in acoustic attenuation accompanying changes in the spin state of Co3+. Anomalies in shear moduli have been observed at ~110 K and ~590 K for LaCoO3, ~325 K and ~695 K for NdCoO3, ~720 K for GdCoO3, and ~30 K for Co3O4. For LaCoO3, a spin order parameter qspin is expected to couple with volume strain ea as λeaqspin and with shear strain es as λes2qspin. As a consequence of linear/quadratic coupling with es, the shear modulus is expected to vary linearly with qspin. This appears to be approximately the case for LaCoO3. Changes in spin state do not appear to give rise to acoustic attenuation at either DMA frequencies (~1 Hz) or RUS frequencies (~1 MHz), consistent with the expectation that spin/lattice relaxation is rapid in comparison with the time scale of applied stress in each case. On the other hand, for LaCoO3 there is a peak in dissipation near 590 K at low frequencies, which is attributed to freezing of ferroelastic twin

  17. The silicate and carbon-rich models of CoRoT-7b, Kepler-9d and Kepler-10b

    NASA Astrophysics Data System (ADS)

    Gong, Yan-Xiang; Zhou, Ji-Lin

    2012-06-01

    Possible bulk compositions of the super-Earth exoplanets CoRoT-7b, Kepler-9d, and Kepler-10b are investigated by applying a commonly used silicate model and a non-standard carbon model. Their internal structures are deduced using a suitable equation of state for the materials. The degeneracy problems of their compositions can be partly overcome, based on the fact that all three planets are extremely close to their host stars. By analyzing the numerical results, we conclude: 1) the iron core of CoRoT-7b is not more than 27% of its total mass within 1σ mass-radius error bars, so an Earth-like composition is less likely, but its carbon rich model can be compatible with an Earth-like core/mantle mass fraction; 2) Kepler-10b is more likely to have a Mercury-like composition, with its old age implying that its high iron content may be a result of strong solar wind or giant impact; 3) the transiting-only super-Earth Kepler-9d is also discussed. Combining its possible composition with the formation theory, we can place some constraints on its mass and bulk composition.

  18. Characteristics of BDE dependent on 10B concentration for accelerator-based BNCT using near-threshold 7Li(p,n)7Be direct neutrons.

    PubMed

    Tanaka, K; Kobayashi, T; Bengua, G; Nakagawa, Y; Endo, S; Hoshi, M

    2004-11-01

    The characteristics boron-dose enhancer (BDE) was evaluated as to the dependence on the (10)B concentration for BNCT using near-threshold (7)Li(p,n)(7)Be direct neutrons. The treatable protocol depth (TPD) was utilized as an evaluation index. MCNP-4B calculations were performed for near-threshold (7)Li(p,n)(7)Be at a proton energy of 1.900MeV and for a polyethylene BDE. Consequently, the TPD was increased by increasing T/N ratio, i.e., the ratio of the (10)B concentration in the tumor ((10)B(Tumor)) to that in the normal tissue ((10)B(Normal)), and by increasing (10)B(Tumor) and (10)B(Normal) for constant T/N ratio. It has been found that the BDE becomes unnecessary from the viewpoint of increasing the TPD, when (10)B(Tumor) is over a certain level. PMID:15308161

  19. FUNCTION GENERATOR FOR ANALOGUE COMPUTERS

    DOEpatents

    Skramstad, H.K.; Wright, J.H.; Taback, L.

    1961-12-12

    An improved analogue computer is designed which can be used to determine the final ground position of radioactive fallout particles in an atomic cloud. The computer determines the fallout pattern on the basis of known wind velocity and direction at various altitudes, and intensity of radioactivity in the mushroom cloud as a function of particle size and initial height in the cloud. The output is then displayed on a cathode-ray tube so that the average or total luminance of the tube screen at any point represents the intensity of radioactive fallout at the geographical location represented by that point. (AEC)

  20. Ecstasy analogues found in cacti.

    PubMed

    Bruhn, Jan G; El-Seedi, Hesham R; Stephanson, Nikolai; Beck, Olof; Shulgin, Alexander T

    2008-06-01

    Human interest in psychoactive phenethylamines is known from the use of mescaline-containing cacti and designer drugs such as Ecstasy. From the alkaloid composition of cacti we hypothesized that substances resembling Ecstasy might occur naturally. In this article we show that lophophine, homopiperonylamine and lobivine are new minor constituents of two cactus species, Lophophora williamsii (peyote) and Trichocereus pachanoi (San Pedro). This is the first report of putatively psychoactive phenethylamines besides mescaline in these cacti. A search for further biosynthetic analogues may provide new insights into the structure-activity relationships of mescaline. An intriguing question is whether the new natural compounds can be called "designer drugs." PMID:18720674

  1. Particle Leaking, Cross-Section Ratio 10B(n,{alpha})/238U(n,fission), and Excitation Function of the Reaction 10B(n,{alpha})7Li at MeV Energies

    SciTech Connect

    Giorginis, Georgios; Khryachkov, Vitali

    2005-05-24

    The 10B(n,{alpha})7Li reaction was studied in the energy range between 1.5 MeV and 5.6 MeV at the 7-MV Van de Graaff accelerator of IRMM by using a gridded ionisation chamber, signal digitisation, and an intrinsic 238U neutron monitor. The aim was to obtain accurate data for the IAEA Coordinated Research Project (CRP) on the improvement of standard cross sections for light elements. The effect of particle leaking was discovered and its implications investigated. The determination of the cross section {sigma}({alpha}0+{alpha}1) strongly benefits from it but measurements of angular distributions, individual cross sections {sigma}({alpha}0) and {sigma}({alpha}1), and the branching ratio {alpha}0/{alpha}1 are negatively affected. The correct number of reaction events was obtained by identification of unknown particle signatures in the energy spectra as 10B(n,{alpha})7Li events in the form of quasi 7Li+{alpha} particles created by particle leaking. The cross-section ratio 10B(n,{alpha})7Li/238U(n,fission) was measured and the excitation function of 10B(n,{alpha})7Li determined by simultaneously detecting the charged particles from the boron disintegration in the forward hemisphere and the 238U fission fragments in the backward hemisphere. The IRMM cross sections are compared to experimental data of other groups and to predictions of the ENDF/B-VI.8, JENDL-3.3, and JEF-2.2 evaluations.

  2. q-bosons and the q-analogue quantized field

    NASA Technical Reports Server (NTRS)

    Nelson, Charles A.

    1995-01-01

    The q-analogue coherent states are used to identify physical signatures for the presence of a 1-analogue quantized radiation field in the q-CS classical limits where the absolute value of z is large. In this quantum-optics-like limit, the fractional uncertainties of most physical quantities (momentum, position, amplitude, phase) which characterize the quantum field are O(1). They only vanish as O(1/absolute value of z) when q = 1. However, for the number operator, N, and the N-Hamiltonian for a free q-boson gas, H(sub N) = h(omega)(N + 1/2), the fractional uncertainties do still approach zero. A signature for q-boson counting statistics is that (Delta N)(exp 2)/ (N) approaches 0 as the absolute value of z approaches infinity. Except for its O(1) fractional uncertainty, the q-generalization of the Hermitian phase operator of Pegg and Barnett, phi(sub q), still exhibits normal classical behavior. The standard number-phase uncertainty-relation, Delta(N) Delta phi(sub q) = 1/2, and the approximate commutation relation, (N, phi(sub q)) = i, still hold for the single-mode q-analogue quantized field. So, N and phi(sub q) are almost canonically conjugate operators in the q-CS classical limit. The q-analogue CS's minimize this uncertainty relation for moderate (absolute value of z)(exp 2).

  3. Extreme projection of a proton into the pi-cloud of an aromatic ring: record shielding of an aromatic proton in trans-10b-methyl-10c-(1-naphthyl)-10b,10c-dihydropyrene.

    PubMed

    Ting, Yuhua; Lai, Yee-Hing

    2004-01-28

    A synthetic sequence involving dithiametacyclophane --> metacyclophanediene --> dihydropyrene was employed to prepare trans-10b-methyl-10c-(2-naphthyl)- and trans-10b-methyl-10c-(1-naphthyl)-10b,10c-dihydropyrene 5 and 6, respectively. Both exhibit a strong diamagnetic ring current despite the introduction of an internal bulky substituent within the pi-electron cloud. Their electronic spectra suggest interaction between the two near-perpendicular naphthyl and dihydropyrenyl pi systems, resulting in red shift and band broadening. All naphthyl protons are well resolved in their 1H NMR spectra due to a strong shielding effect of the dihydropyrene ring. The most shielded protons in 5 and 6 are H1' and H2' at delta 2.47 and 1.42, respectively, being 5.25 and 5.95 ppm shifted from those of reference protons. There is evidence for free rotation on the NMR time scale of the 2-naphthyl ring in 5 with a preference for a particular conformer, whereas the 1-naphthyl ring in 6 is conformationally rigid with its H2' projecting deeply into the pi-cloud, thus accounting for the most shielded aromatic proton (H2' in 6) reported to date. PMID:14733567

  4. The Valles natural analogue project

    SciTech Connect

    Stockman, H.; Krumhansl, J.; Ho, C.; McConnell, V.

    1994-12-01

    The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a highlevel waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, X-ray diffraction; and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and {sup 39}Ar/{sup 4O} isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks.

  5. New measurement of the 10B(n,α)7 Li through the Trojan Horse Method

    NASA Astrophysics Data System (ADS)

    Spartá, Roberta

    2016-04-01

    B(n,α) Li reaction cross section has been measured using the Trojan Horse method, with the specific aim to separate the α1 contribution (coming from the first Li excited level) by the αo (related to the Li ground state), using a very thin target. Preliminary results are shown of the three-body B(d,α7 Li)H cross section.

  6. Current european regulatory perspectives on insulin analogues.

    PubMed

    Enzmann, Harald G; Weise, Martina

    2011-01-01

    Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions. PMID:21736748

  7. Study of the {sup 10}B(p,α){sup 7}Be reaction through the indirect Trojan Horse method

    SciTech Connect

    Puglia, S. M. R.; Spitaleri, C.; Lamia, L.; Romano, S.; La Cognata, M.; Pizzone, R. G.; Rapisarda, G. G.; Sergi, M. L.; Burjan, V.; Kroha, V.; Hons, Z.; Mrazek, J.; Carlin, N.; Del Santo, M. G.; Munhoz, M. G.; Souza, F.; Szanto de Toledo, A.; Chengbo, L.; Qungang, W.; Shu-Hua, Z.; and others

    2015-02-24

    Boron abundances in stellar atmospheres, as well as berillium and lithium ones, can give useful hints for non-standard transport processes discrimination in stars. They can also be relevant for understanding several astrophysical processes (e.g. primordial nucleosynthesis and spallation reactions in ISM). A comprehensive study of Li Be B abundances can therefore confirm or not the presence of non-standard mixing processes in stellar envelopes. For this reason nuclear processes producing or depleting boron isotope abundance need to be studied at astrophysical energies. The {sup 10}B(p,α){sup 7}Be reaction has been studied by means of the Trojan Horse Method. The Trojan Horse Method was thus applied to the {sup 10}B(d,α{sup 7}Be)n reaction, studied at 24 MeV. The obtained results will be discussed.

  8. Microstructural evolution of HFIR-irradiated low activation F82H and F82H-{sup 10}B steels

    SciTech Connect

    Wakai, E.; Shiba, K.; Sawai, T.; Hashimoto, N.; Robertson, J.P.; Klueh, R.L.

    1998-03-01

    Microstructures of reduced-activation F82H (8Cr-2W-0.2V-0.04Ta) and the F82H steels doped with {sup 10}B, irradiated at 250 and 300 C to 3 and 57 dpa in the High Flux Isotope Reactor (HFIR), were examined by TEM. In the F82H irradiated at 250 C to 3 dpa, dislocation loops, small unidentified defect clusters with a high number density, and a few MC precipitates were observed in the matrix. The defect microstructure after 300 C irradiation to 57 dpa is dominated by the loops, and the number density of loops was lower than that of the F82H-{sup 10}B steel. Cavities were observed in the F82H-{sup 10}B steels, but the swelling value is insignificant. Small particles of M{sub 6}C formed on the M{sub 23}C{sub 6} carbides that were present in both steels before the irradiation at 300 C to 57 dpa. A low number density of MC precipitate particles formed in the matrix during irradiation at 300 C to 57 dpa.

  9. CO2 Capture with Enzyme Synthetic Analogue

    SciTech Connect

    Cordatos, Harry

    2010-11-08

    Overview of an ongoing, 2 year research project partially funded by APRA-E to create a novel, synthetic analogue of carbonic anhydrase and incorporate it into a membrane for removal of CO2 from flue gas in coal power plants. Mechanism background, preliminary feasibility study results, molecular modeling of analogue-CO2 interaction, and program timeline are provided.

  10. An analogue study of intrusions.

    PubMed

    Laposa, Judith M; Alden, Lynn E

    2006-07-01

    According to cognitive theorists, intrusive trauma memories have their origin in how information during the event is processed. Two studies investigated functional cognitive strategies during medical crises that might protect against intrusions. In Study 1, interviews with health-care professionals were used to identify cognitive strategies judged to be effective in controlling emotions and dealing with medical crises. Study 2 systematically manipulated the use of those strategies in a trauma analogue film paradigm. Experimental participants reported fewer intrusions, and less fear and avoidance of film-related stimuli during the subsequent week than controls. The manipulation did not affect anxiety during the film or memory disorganization. Implications for cognitive theories of intrusion development are discussed. PMID:16125135

  11. Laboratory study of cometary analogues

    NASA Astrophysics Data System (ADS)

    Colangeli, L.; Brucato, J.; Mennella, V.; Palumbo, P.

    In situ exploration (e.g., GIOTTO mission) and astronomical observations (e.g., ISO) of comets have provided fundamental information about the structure, chemistry and physical properties of materials present in such primordial bodies of the Solar System. Moreover, it is known that cosmic materials evolve, depending on the efficiency of active processes (e.g., thermal annealing, UV irradiation, ion bombardment, gassolid interactions) in different space environments. Thus, the properties of cometary constituents must be considered in a wider perspective, including cosmic dust formation around cold stars and evolution in the interstellar medium until the formation of proto-planetary nebulae. In this scenario, laboratory experiments provide important hints to clarify the status of cometary compounds. The laboratory work is aimed at both reproducing material properties and at simulating their evolution based on the most effective mechanisms active in space. Several techniques are used to synthesise "analogues" of cometary compounds with controlled chemical and physical characteristics. The study of optical properties, complemented by other analytical techniques, is applied to investigate the products of synthesis in the experiments. The monitoring of the effects produced by processing methods, similar to those active in space, provides information both on the reactivity of materials and on the efficiency of treatments. Such an approach is able to provide quantitative information on chemical and structural modifications produced on organic and refractory materials. The comparison of laboratory results with data coming from space observations and in situ measurements provides a powerful tool to understand the real nature of comets and to place constraints on formation and evolution pathways. The laboratory experiments on analogues gain even more relevance as a sort of training in the future perspective of analysing cometary samples returned to Earth by space missions (e

  12. Numerical simulation of an experimental analogue of a planetary magnetosphere

    NASA Astrophysics Data System (ADS)

    Liao, Andy Sha; Li, Shule; Hartigan, Patrick; Graham, Peter; Fiksel, Gennady; Frank, Adam; Foster, John; Kuranz, Carolyn

    2015-12-01

    Recent improvements to the Omega Laser Facility's magneto-inertial fusion electrical discharge system (MIFEDS) have made it possible to generate strong enough magnetic fields in the laboratory to begin to address the physics of magnetized astrophysical flows. Here, we adapt the MHD code AstroBEAR to create 2D numerical models of an experimental analogue of a planetary magnetosphere. We track the secular evolution of the magnetosphere analogue and we show that the magnetospheric components such as the magnetopause, magnetosheath, and bow shock, should all be observable in experimental optical band thermal bremsstrahlung emissivity maps, assuming equilibrium charge state distributions of the plasma. When the magnetosphere analogue nears the steady state, the mid-plane altitude of the magnetopause from the wire surface scales as the one-half power of the ratio of the magnetic pressure at the surface of the free wire to the ram pressure of an unobstructed wind; the mid-plane thickness of the magnetosheath is directly related to the radius of the magnetopause. This behavior conforms to Chapman and Ferraro's theory of planetary magnetospheres. Although the radial dependence of the magnetic field strength differs between the case of a current-carrying wire and a typical planetary object, the major morphological features that develop when a supersonic flow passes either system are identical. Hence, this experimental concept is an attractive one for studying the dynamics of planetary magnetospheres in a controlled environment.

  13. Could CoRoT-7b and Kepler-10b be remnants of evaporated gas or ice giants?

    PubMed Central

    Leitzinger, M.; Odert, P.; Kulikov, Yu.N.; Lammer, H.; Wuchterl, G.; Penz, T.; Guarcello, M.G.; Micela, G.; Khodachenko, M.L.; Weingrill, J.; Hanslmeier, A.; Biernat, H.K.; Schneider, J.

    2011-01-01

    We present thermal mass loss calculations over evolutionary time scales for the investigation if the smallest transiting rocky exoplanets CoRoT-7b (∼1.68REarth) and Kepler-10b (∼1.416REarth) could be remnants of an initially more massive hydrogen-rich gas giant or a hot Neptune-class exoplanet. We apply a thermal mass loss formula which yields results that are comparable to hydrodynamic loss models. Our approach considers the effect of the Roche lobe, realistic heating efficiencies and a radius scaling law derived from observations of hot Jupiters. We study the influence of the mean planetary density on the thermal mass loss by placing hypothetical exoplanets with the characteristics of Jupiter, Saturn, Neptune, and Uranus to the orbital location of CoRoT-7b at 0.017 AU and Kepler-10b at 0.01684 AU and assuming that these planets orbit a K- or G-type host star. Our findings indicate that hydrogen-rich gas giants within the mass domain of Saturn or Jupiter cannot thermally lose such an amount of mass that CoRoT-7b and Kepler-10b would result in a rocky residue. Moreover, our calculations show that the present time mass of both rocky exoplanets can be neither a result of evaporation of a hydrogen envelope of a “Hot Neptune” nor a “Hot Uranus”-class object. Depending on the initial density and mass, these planets most likely were always rocky planets which could lose a thin hydrogen envelope, but not cores of thermally evaporated initially much more massive and larger objects. PMID:21969736

  14. Could CoRoT-7b and Kepler-10b be remnants of evaporated gas or ice giants?

    PubMed

    Leitzinger, M; Odert, P; Kulikov, Yu N; Lammer, H; Wuchterl, G; Penz, T; Guarcello, M G; Micela, G; Khodachenko, M L; Weingrill, J; Hanslmeier, A; Biernat, H K; Schneider, J

    2011-10-01

    We present thermal mass loss calculations over evolutionary time scales for the investigation if the smallest transiting rocky exoplanets CoRoT-7b (∼1.68REarth) and Kepler-10b (∼1.416REarth) could be remnants of an initially more massive hydrogen-rich gas giant or a hot Neptune-class exoplanet. We apply a thermal mass loss formula which yields results that are comparable to hydrodynamic loss models. Our approach considers the effect of the Roche lobe, realistic heating efficiencies and a radius scaling law derived from observations of hot Jupiters. We study the influence of the mean planetary density on the thermal mass loss by placing hypothetical exoplanets with the characteristics of Jupiter, Saturn, Neptune, and Uranus to the orbital location of CoRoT-7b at 0.017 AU and Kepler-10b at 0.01684 AU and assuming that these planets orbit a K- or G-type host star. Our findings indicate that hydrogen-rich gas giants within the mass domain of Saturn or Jupiter cannot thermally lose such an amount of mass that CoRoT-7b and Kepler-10b would result in a rocky residue. Moreover, our calculations show that the present time mass of both rocky exoplanets can be neither a result of evaporation of a hydrogen envelope of a "Hot Neptune" nor a "Hot Uranus"-class object. Depending on the initial density and mass, these planets most likely were always rocky planets which could lose a thin hydrogen envelope, but not cores of thermally evaporated initially much more massive and larger objects. PMID:21969736

  15. Plant volatile analogues strengthen attractiveness to insect.

    PubMed

    Sun, Yufeng; Yu, Hao; Zhou, Jing-Jiang; Pickett, John A; Wu, Kongming

    2014-01-01

    Green leaf bug Apolygus lucorum (Meyer-Dür) is one of the major pests in agriculture. Management of A. lucorum was largely achieved by using pesticides. However, the increasing population of A. lucorum since growing Bt cotton widely and the increased awareness of ecoenvironment and agricultural product safety makes their population-control very challenging. Therefore this study was conducted to explore a novel ecological approach, synthetic plant volatile analogues, to manage the pest. Here, plant volatile analogues were first designed and synthesized by combining the bioactive components of β-ionone and benzaldehyde. The stabilities of β-ionone, benzaldehyde and analogue 3 g were tested. The electroantennogram (EAG) responses of A. lucorum adult antennae to the analogues were recorded. And the behavior assay and filed experiment were also conducted. In this study, thirteen analogues were acquired. The analogue 3 g was demonstrated to be more stable than β-ionone and benzaldehyde in the environment. Many of the analogues elicited EAG responses, and the EAG response values to 3 g remained unchanged during seven-day period. 3 g was also demonstrated to be attractive to A. lucorum adults in the laboratory behavior experiment and in the field. Its attractiveness persisted longer than β-ionone and benzaldehyde. This indicated that 3 g can strengthen attractiveness to insect and has potential as an attractant. Our results suggest that synthetic plant volatile analogues can strengthen attractiveness to insect. This is the first published study about synthetic plant volatile analogues that have the potential to be used in pest control. Our results will support a new ecological approach to pest control and it will be helpful to ecoenvironment and agricultural product safety. PMID:24911460

  16. Plant Volatile Analogues Strengthen Attractiveness to Insect

    PubMed Central

    Sun, Yufeng; Yu, Hao; Zhou, Jing-Jiang; Pickett, John A.; Wu, Kongming

    2014-01-01

    Green leaf bug Apolygus lucorum (Meyer-Dür) is one of the major pests in agriculture. Management of A. lucorum was largely achieved by using pesticides. However, the increasing population of A. lucorum since growing Bt cotton widely and the increased awareness of ecoenvironment and agricultural product safety makes their population-control very challenging. Therefore this study was conducted to explore a novel ecological approach, synthetic plant volatile analogues, to manage the pest. Here, plant volatile analogues were first designed and synthesized by combining the bioactive components of β-ionone and benzaldehyde. The stabilities of β-ionone, benzaldehyde and analogue 3 g were tested. The electroantennogram (EAG) responses of A. lucorum adult antennae to the analogues were recorded. And the behavior assay and filed experiment were also conducted. In this study, thirteen analogues were acquired. The analogue 3 g was demonstrated to be more stable than β-ionone and benzaldehyde in the environment. Many of the analogues elicited EAG responses, and the EAG response values to 3 g remained unchanged during seven-day period. 3 g was also demonstrated to be attractive to A. lucorum adults in the laboratory behavior experiment and in the field. Its attractiveness persisted longer than β-ionone and benzaldehyde. This indicated that 3 g can strengthen attractiveness to insect and has potential as an attractant. Our results suggest that synthetic plant volatile analogues can strengthen attractiveness to insect. This is the first published study about synthetic plant volatile analogues that have the potential to be used in pest control. Our results will support a new ecological approach to pest control and it will be helpful to ecoenvironment and agricultural product safety. PMID:24911460

  17. MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration.

    PubMed

    Yu, Xin; Li, Zheng; Shen, Jianxiong; Wu, William K K; Liang, Jinqian; Weng, Xisheng; Qiu, Guixing

    2013-01-01

    Aberrant proliferation of nucleus pulposus cell is implicated in the pathogenesis of intervertebral disc degeneration. Recent findings revealed that microRNAs, a class of small noncoding RNAs, could regulate cell proliferation in many pathological conditions. Here, we showed that miR-10b was dramatically upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues isolated from patients with idiopathic scoliosis. Moreover, miR-10b levels were associated with disc degeneration grade and downregulation of HOXD10. In cultured nucleus pulposus cells, miR-10b overexpression stimulated cell proliferation with concomitant translational inhibition of HOXD10 whereas restored expression of HOXD10 reversed the mitogenic effect of miR-10b. MiR-10b-mediated downregulation of HOXD10 led to increased RhoC expression and Akt phosphorylation. Either knockdown of RhoC or inhibition of Akt abolished the effect of miR-10b on nucleus pulposus cell proliferation. Taken together, aberrant miR-10b upregulation in intervertebral disc degeneration could contribute to abnormal nucleus pulposus cell proliferation through derepressing the RhoC-Akt pathway by targeting HOXD10. Our study also underscores the potential of miR-10b and the RhoC-Akt pathway as novel therapeutic targets in intervertebral disc degeneration. PMID:24376640

  18. MicroRNA-10b Promotes Nucleus Pulposus Cell Proliferation through RhoC-Akt Pathway by Targeting HOXD10 in Intervetebral Disc Degeneration

    PubMed Central

    Shen, Jianxiong; Wu, William K. K.; Liang, Jinqian; Weng, Xisheng; Qiu, Guixing

    2013-01-01

    Aberrant proliferation of nucleus pulposus cell is implicated in the pathogenesis of intervertebral disc degeneration. Recent findings revealed that microRNAs, a class of small noncoding RNAs, could regulate cell proliferation in many pathological conditions. Here, we showed that miR-10b was dramatically upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues isolated from patients with idiopathic scoliosis. Moreover, miR-10b levels were associated with disc degeneration grade and downregulation of HOXD10. In cultured nucleus pulposus cells, miR-10b overexpression stimulated cell proliferation with concomitant translational inhibition of HOXD10 whereas restored expression of HOXD10 reversed the mitogenic effect of miR-10b. MiR-10b-mediated downregulation of HOXD10 led to increased RhoC expression and Akt phosphorylation. Either knockdown of RhoC or inhibition of Akt abolished the effect of miR-10b on nucleus pulposus cell proliferation. Taken together, aberrant miR-10b upregulation in intervertebral disc degeneration could contribute to abnormal nucleus pulposus cell proliferation through derepressing the RhoC-Akt pathway by targeting HOXD10. Our study also underscores the potential of miR-10b and the RhoC-Akt pathway as novel therapeutic targets in intervertebral disc degeneration. PMID:24376640

  19. Sensitivity of groundwater recharge using climatic analogues and HYDRUS-1D

    NASA Astrophysics Data System (ADS)

    Leterme, B.; Mallants, D.; Jacques, D.

    2012-08-01

    The sensitivity of groundwater recharge to different climate conditions was simulated using the approach of climatic analogue stations, i.e. stations presently experiencing climatic conditions corresponding to a possible future climate state. The study was conducted in the context of a safety assessment of a future near-surface disposal facility for low and intermediate level short-lived radioactive waste in Belgium; this includes estimation of groundwater recharge for the next millennia. Groundwater recharge was simulated using the Richards based soil water balance model HYDRUS-1D and meteorological time series from analogue stations. This study used four analogue stations for a warmer subtropical climate with changes of average annual precipitation and potential evapotranspiration from -42% to +5% and from +8% to +82%, respectively, compared to the present-day climate. Resulting water balance calculations yielded a change in groundwater recharge ranging from a decrease of 72% to an increase of 3% for the four different analogue stations. The Gijon analogue station (Northern Spain), considered as the most representative for the near future climate state in the study area, shows an increase of 3% of groundwater recharge for a 5% increase of annual precipitation. Calculations for a colder (tundra) climate showed a change in groundwater recharge ranging from a decrease of 97% to an increase of 32% for four different analogue stations, with an annual precipitation change from -69% to -14% compared to the present-day climate.

  20. New thermal neutron capture therapy for malignant melanoma: melanogenesis-seeking 10B molecule-melanoma cell interaction from in vitro to first clinical trial

    SciTech Connect

    Mishima, Y.; Ichihashi, M.; Hatta, S.; Honda, C.; Yamamura, K.; Nakagawa, T. )

    1989-07-01

    Human melanoma regression by single thermal neutron capture therapy (NCT) using melanoma-seeking 10B compounds has been achieved. Since 1972, the aim of my team has been to synthesize tumor-seeking 10B-compounds possessing selective affinity for specific metabolic activity of the target cancer cells. Once the melanoma takes up these 10B compounds, thermal neutrons, which cause insignificant cell damage, are easily absorbed by nonradioactive 10B, inducing the 10B(n, alpha)7Li reaction and releasing the high LET particles to 14 mu melanoma cell diameter, destroying the tumor without damaging surrounding tissue. Radiobiological and preclinical studies culminated in the first successful human NCT treatment, with no recurrence of the treated melanoma since July, 1987.23 references.

  1. Neutron reflectometry on highly absorbing films and its application to 10B4C-based neutron detectors

    PubMed Central

    Piscitelli, F.; Khaplanov, A.; Devishvili, A.; Schmidt, S.; Höglund, C.; Birch, J.; Dennison, A. J. C.; Gutfreund, P.; Hall-Wilton, R.; Van Esch, P.

    2016-01-01

    Neutron reflectometry is a powerful tool used for studies of surfaces and interfaces. The absorption in the typical studied materials is neglected and this technique is limited only to the reflectivity measurement. For strongly absorbing nuclei, the absorption can be directly measured by using the neutron-induced fluorescence technique which exploits the prompt particle emission of absorbing isotopes. This technique is emerging from soft matter and biology where highly absorbing nuclei, in very small quantities, are used as a label for buried layers. Nowadays, the importance of absorbing layers is rapidly increasing, partially because of their application in neutron detection; a field that has become more active also due to the 3He-shortage. We extend the neutron-induced fluorescence technique to the study of layers of highly absorbing materials, in particular 10B4C. The theory of neutron reflectometry is a commonly studied topic; however, when a strong absorption is present the subtle relationship between the reflection and the absorption of neutrons is not widely known. The theory for a general stack of absorbing layers has been developed and compared to measurements. We also report on the requirements that a 10B4C layer must fulfil in order to be employed as a converter in neutron detection. PMID:26997902

  2. Central nervous system radiation syndrome in mice from preferential 10B(n, alpha)7Li irradiation of brain vasculature.

    PubMed

    Slatkin, D N; Stoner, R D; Rosander, K M; Kalef-Ezra, J A; Laissue, J A

    1988-06-01

    Ionizing radiations were directed at the heads of anesthetized mice in doses that evoked the acute central nervous system (CNS) radiation syndrome. Irradiations were done using either a predominantly thermal neutron field at a nuclear reactor after intraperitoneal injection of 10B-enriched boric acid or 250-kilovolt-peak x-rays with and without previous intraperitoneal injection of equivalent unenriched boric acid. Since 10B concentrations were approximately equal to 3-fold higher in blood than in cerebral parenchyma during the reactor irradiations, more radiation from alpha and 7Li particles was absorbed by brain endothelial cells than by brain parenchymal cells. Comparison of the LD50 dose for CNS radiation lethality from the reactor experiments with the LD50 dose from the x-ray experiments gives results compatible with morphologic evidence that endothelial cell damage is a major determinant of acute lethality from the CNS radiation syndrome. It was also observed that boric acid is a low linear energy transfer radiation-enhancement agent in vivo. PMID:3375251

  3. Secondary Eclipse Observations of the Low-Mass Hot-Jupiter WASP-11b/HAT-P-10b

    NASA Astrophysics Data System (ADS)

    Bowman, M. Oliver; Harrington, J.; Blecic, J.; Foster, A.; Stevenson, K. B.; Cubillos, P.; Collier Cameron, A.; UCF Exoplanets Group

    2013-10-01

    WASP-11b/HAT-P-10b is a hot-Jupiter planet that orbits a K3 dwarf every 3.722 days at a distance of 0.0439 AU. Using the Spitzer Space Telescope in 2009 (Harrington, P.I.) and 2010 (Knutson, P.I), we observed five secondary eclipses of WASP-11b/HAT-P-10b: two in the 3.6-micron channel, two in the 4.5-micron channel, and one in the 8-micron channel. We present eclipse-depth measurements, estimates of infrared brightness temperatures, and the first constraints on the atmospheric pressure and temperature profile and chemical compositions. We also refine its orbit using our own secondary-eclipse measurements in combination with external radial-velocity and transit observations from both professional and amateur observers. Spitzer is operated by the Jet Propulsion Laboratory, California Institute of Technology, under a contract with NASA. This work was supported in part by NASA Planetary Atmospheres grant NNX13AF38G.

  4. Central nervous system radiation syndrome in mice from preferential 10B(n, alpha)7Li irradiation of brain vasculature.

    PubMed Central

    Slatkin, D N; Stoner, R D; Rosander, K M; Kalef-Ezra, J A; Laissue, J A

    1988-01-01

    Ionizing radiations were directed at the heads of anesthetized mice in doses that evoked the acute central nervous system (CNS) radiation syndrome. Irradiations were done using either a predominantly thermal neutron field at a nuclear reactor after intraperitoneal injection of 10B-enriched boric acid or 250-kilovolt-peak x-rays with and without previous intraperitoneal injection of equivalent unenriched boric acid. Since 10B concentrations were approximately equal to 3-fold higher in blood than in cerebral parenchyma during the reactor irradiations, more radiation from alpha and 7Li particles was absorbed by brain endothelial cells than by brain parenchymal cells. Comparison of the LD50 dose for CNS radiation lethality from the reactor experiments with the LD50 dose from the x-ray experiments gives results compatible with morphologic evidence that endothelial cell damage is a major determinant of acute lethality from the CNS radiation syndrome. It was also observed that boric acid is a low linear energy transfer radiation-enhancement agent in vivo. Images PMID:3375251

  5. An analogue conceptual rainfall-runoff model for educational purposes

    NASA Astrophysics Data System (ADS)

    Herrnegger, Mathew; Riedl, Michael; Schulz, Karsten

    2016-04-01

    Conceptual rainfall-runoff models, in which runoff processes are modelled with a series of connected linear and non-linear reservoirs, remain widely applied tools in science and practice. Additionally, the concept is appreciated in teaching due to its somewhat simplicity in explaining and exploring hydrological processes of catchments. However, when a series of reservoirs are used, the model system becomes highly parametrized and complex and the traceability of the model results becomes more difficult to explain to an audience not accustomed to numerical modelling. Since normally the simulations are performed with a not visible digital code, the results are also not easily comprehensible. This contribution therefore presents a liquid analogue model, in which a conceptual rainfall-runoff model is reproduced by a physical model. This consists of different acrylic glass containers representing different storage components within a catchment, e.g. soil water or groundwater storage. The containers are equipped and connected with pipes, in which water movement represents different flow processes, e.g. surface runoff, percolation or base flow. Water from a storage container is pumped to the upper part of the model and represents effective rainfall input. The water then flows by gravity through the different pipes and storages. Valves are used for controlling the flows within the analogue model, comparable to the parameterization procedure in numerical models. Additionally, an inexpensive microcontroller-based board and sensors are used to measure storage water levels, with online visualization of the states as time series data, building a bridge between the analogue and digital world. The ability to physically witness the different flows and water levels in the storages makes the analogue model attractive to the audience. Hands-on experiments can be performed with students, in which different scenarios or catchment types can be simulated, not only with the analogue but

  6. Condensed matter analogues of cosmology

    NASA Astrophysics Data System (ADS)

    Kibble, Tom; Srivastava, Ajit

    2013-10-01

    It is always exciting when developments in one branch of physics turn out to have relevance in a quite different branch. It would be hard to find two branches farther apart in terms of energy scales than early-universe cosmology and low-temperature condensed matter physics. Nevertheless ideas about the formation of topological defects during rapid phase transitions that originated in the context of the very early universe have proved remarkably fruitful when applied to a variety of condensed matter systems. The mathematical frameworks for describing these systems can be very similar. This interconnection has led to a deeper understanding of the phenomena in condensed matter systems utilizing ideas from cosmology. At the same time, one can view these condensed matter analogues as providing, at least in a limited sense, experimental access to the phenomena of the early universe for which no direct probe is possible. As this special issue well illustrates, this remains a dynamic and exciting field. The basic idea is that when a system goes through a rapid symmetry-breaking phase transition from a symmetric phase into one with spontaneously broken symmetry, the order parameter may make different choices in different regions, creating domains that when they meet can trap defects. The scale of those domains, and hence the density of defects, is constrained by the rate at which the system goes through the transition and the speed with which order parameter information propagates. This is what has come to be known as the Kibble-Zurek mechanism. The resultant scaling laws have now been tested in a considerable variety of different systems. The earliest experiments illustrating the analogy between cosmology and condensed matter were in liquid crystals, in particular on the isotropic-to-nematic transition, primarily because it is very easy to induce the phase transition (typically at room temperature) and to image precisely what is going on. This field remains one of the

  7. Antimicrobial activity of resveratrol analogues.

    PubMed

    Chalal, Malik; Klinguer, Agnès; Echairi, Abdelwahad; Meunier, Philippe; Vervandier-Fasseur, Dominique; Adrian, Marielle

    2014-01-01

    Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew). Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold). The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups) and antimicrobial activity. PMID:24918540

  8. Actions of Thyroid Hormone Analogues on Chemokines

    PubMed Central

    Glinsky, Gennadi V.

    2016-01-01

    The extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3′-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 to the integrin. Fractalkine (CX3CL1) is a chemokine relevant to inflammatory processes in the CNS that are microglia-dependent but also important to normal brain development. Expression of the CX3CL1 gene is downregulated by tetrac, suggesting that T4 and T3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to αvβ3 at a site proximal to the thyroid hormone-tetrac receptor and changes the physical state of the integrin. Tetrac also affects expression of the genes for other CNS-relevant chemokines, including CCL20, CCL26, CXCL2, CXCL3, and CXCL10. The chemokine products of these genes are important to vascularity of the brain, particularly of the choroid plexus, to inflammatory processes in the CNS and, in certain cases, to neuroprotection. Thyroid hormones are known to contribute to regulation of each of these CNS functions. We propose that actions of thyroid hormone and hormone analogues on chemokine gene expression contribute to regulation of inflammatory processes in brain and of brain blood vessel formation and maintenance. PMID:27493972

  9. Actions of Thyroid Hormone Analogues on Chemokines.

    PubMed

    Davis, Paul J; Glinsky, Gennadi V; Lin, Hung-Yun; Mousa, Shaker A

    2016-01-01

    The extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3'-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 to the integrin. Fractalkine (CX3CL1) is a chemokine relevant to inflammatory processes in the CNS that are microglia-dependent but also important to normal brain development. Expression of the CX3CL1 gene is downregulated by tetrac, suggesting that T4 and T3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to αvβ3 at a site proximal to the thyroid hormone-tetrac receptor and changes the physical state of the integrin. Tetrac also affects expression of the genes for other CNS-relevant chemokines, including CCL20, CCL26, CXCL2, CXCL3, and CXCL10. The chemokine products of these genes are important to vascularity of the brain, particularly of the choroid plexus, to inflammatory processes in the CNS and, in certain cases, to neuroprotection. Thyroid hormones are known to contribute to regulation of each of these CNS functions. We propose that actions of thyroid hormone and hormone analogues on chemokine gene expression contribute to regulation of inflammatory processes in brain and of brain blood vessel formation and maintenance. PMID:27493972

  10. Heterocyclic chalcone analogues as potential anticancer agents.

    PubMed

    Sharma, Vikas; Kumar, Vipin; Kumar, Pradeep

    2013-03-01

    Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties. PMID:22721390

  11. Synthesis and SAR of vinca alkaloid analogues.

    PubMed

    Voss, Matthew E; Ralph, Jeffery M; Xie, Dejian; Manning, David D; Chen, Xinchao; Frank, Anthony J; Leyhane, Andrew J; Liu, Lei; Stevens, Jason M; Budde, Cheryl; Surman, Matthew D; Friedrich, Thomas; Peace, Denise; Scott, Ian L; Wolf, Mark; Johnson, Randall

    2009-02-15

    Versatile intermediates 12'-iodovinblastine, 12'-iodovincristine and 11'-iodovinorelbine were utilized as substrates for transition metal based chemistry which led to the preparation of novel analogues of the vinca alkaloids. The synthesis of key iodo intermediates, their transformation into final products, and the SAR based upon HeLa and MCF-7 cell toxicity assays is presented. Selected analogues 27 and 36 show promising anticancer activity in the P388 murine leukemia model. PMID:19147348

  12. MicroRNA-10b regulates epithelial-mesenchymal transition by modulating KLF4/Notch1/E-cadherin in cisplatin-resistant nasopharyngeal carcinoma cells

    PubMed Central

    Zhang, Pei; Hong, Haiyu; Sun, Xiaojin; Jiang, Hao; Ma, Shiyin; Zhao, Surong; Zhang, Mengxiao; Wang, Zhiwei; Jiang, Chenchen; Liu, Hao

    2016-01-01

    Epithelial-mesenchymal transition (EMT) is an initiating event in tumor cell invasion and metastasis that contributes to therapeutic resistance to compounds including cisplatin. MicroRNAs (miRNAs) have been associated with EMT as well as resistance to standard therapies. However, the underlying mechanisms by which miRNAs control the development of resistance to cisplatin (DDP), and the accompanying EMT-like properties are required to elucidate. Here we show that microRNA-10b (miR-10b) is up-regulated in HNE1/DDP cells, and inhibition of miR-10b expression reversed the EMT phenotype. However, over-expression of miR-10b was able to promote the acquisition of an EMT phenotype in HNE1 cells. Additionally, we identified that miR-10b expression inversely correlates with KLF4, which then controls expression of Notch1. Knock-down of Notch1 inhibited cell migration, invasion, and reversed EMT in HNE1/DDP cells, which was dependent on miR-10b. In summary, our results reveal that miR-10b regulates EMT by modulating KLF4/Notch1/E-cadherin expression, which promotes invasion and migration of nasal pharyngeal carcinoma cells. PMID:27186392

  13. Planetary habitability: lessons learned from terrestrial analogues

    NASA Astrophysics Data System (ADS)

    Preston, Louisa J.; Dartnell, Lewis R.

    2014-01-01

    Terrestrial analogue studies underpin almost all planetary missions and their use is essential in the exploration of our Solar system and in assessing the habitability of other worlds. Their value relies on the similarity of the analogue to its target, either in terms of their mineralogical or geochemical context, or current physical or chemical environmental conditions. Such analogue sites offer critical ground-truthing for astrobiological studies on the habitability of different environmental parameter sets, the biological mechanisms for survival in extreme environments and the preservation potential and detectability of biosignatures. The 33 analogue sites discussed in this review have been selected on the basis of their congruence to particular extraterrestrial locations. Terrestrial field sites that have been used most often in the literature, as well as some lesser known ones which require greater study, are incorporated to inform on the astrobiological potential of Venus, Mars, Europa, Enceladus and Titan. For example, the possibility of an aerial habitable zone on Venus has been hypothesized based on studies of life at high-altitudes in the terrestrial atmosphere. We also demonstrate why many different terrestrial analogue sites are required to satisfactorily assess the habitability of the changing environmental conditions throughout Martian history, and recommend particular sites for different epochs or potential niches. Finally, habitable zones within the aqueous environments of the icy moons of Europa and Enceladus and potentially in the hydrocarbon lakes of Titan are discussed and suitable analogue sites proposed. It is clear from this review that a number of terrestrial analogue sites can be applied to multiple planetary bodies, thereby increasing their value for astrobiological exploration. For each analogue site considered here, we summarize the pertinent physiochemical environmental features they offer and critically assess the fidelity with which

  14. Wnt6, Wnt10a and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis through a β-catenin-dependent mechanism.

    PubMed

    Cawthorn, William P; Bree, Adam J; Yao, Yao; Du, Baowen; Hemati, Nahid; Martinez-Santibañez, Gabriel; MacDougald, Ormond A

    2012-02-01

    Wnt10b is an established regulator of mesenchymal stem cell (MSC) fate that inhibits adipogenesis and stimulates osteoblastogenesis, thereby impacting bone mass in vivo. However, downstream mechanisms through which Wnt10b exerts these effects are poorly understood. Moreover, whether other endogenous Wnt ligands also modulate MSC fate remains to be fully addressed. In this study, we identify Wnt6 and Wnt10a as additional Wnt family members that, like Wnt10b, are downregulated during development of white adipocytes in vivo and in vitro, suggesting that Wnt6 and/or Wnt10a may also inhibit adipogenesis. To assess the relative activities of Wnt6, Wnt10a and Wnt10b to regulate mesenchymal cell fate, we used gain- and loss-of function approaches in bipotential ST2 cells and in 3T3-L1 preadipocytes. Enforced expression of Wnt10a stabilizes β-catenin, suppresses adipogenesis and stimulates osteoblastogenesis to a similar extent as Wnt10b, whereas stable expression of Wnt6 has a weaker effect on these processes than Wnt10a or Wnt10b. In contrast, knockdown of endogenous Wnt6 is associated with greater preadipocyte differentiation and impaired osteoblastogenesis than knockdown of Wnt10a or Wnt10b, suggesting that, among these Wnt ligands, Wnt6 is the most potent endogenous regulator of MSC fate. Finally, we show that knockdown of β-catenin completely prevents the inhibition of adipogenesis and stimulation of osteoblast differentiation by Wnt6, Wnt10a or Wnt10b. Potential mechanisms whereby Wnts regulate fate of MSCs downstream of β-catenin are also investigated. In conclusion, this study identifies Wnt10a and Wnt6 as additional regulators of MSC fate and demonstrates that mechanisms downstream of β-catenin are required for Wnt6, Wnt10a and Wnt10b to influence differentiation of mesenchymal precursors. PMID:21872687

  15. MicroRNA-10b inhibition reduces E2F1-mediated transcription and miR-15/16 activity in glioblastoma

    PubMed Central

    Teplyuk, Nadiya M.; Uhlmann, Erik J.; Wong, Andus Hon-Kit; Karmali, Priya; Basu, Meenakshi; Gabriely, Galina; Jain, Anant; Wang, Yang; Chiocca, E. Antonio; Stephens, Robert; Marcusson, Eric; Yi, Ming; Krichevsky, Anna M.

    2015-01-01

    MicroRNA-10b (miR-10b) is commonly elevated in glioblastoma (GBM), while not expressed in normal brain tissues. Targeted inhibition of miR-10b has pleiotropic effects on GBM derived cell lines, it reduces GBM growth in animal models, but does not affect normal neurons and astrocytes. This data raises the possibility of developing miR-10b-targeting GBM therapy. However, the mechanisms contributing to miR-10b-mediated glioma cell survival and proliferation are unexplored. We found that inhibition of miR-10b has distinct effects on specific glioma cell lines. In cells expressing high levels of tumor suppressor p21WAF1/Cip1, it represses E2F1-mediated transcription, leading to down-regulation of multiple E2F1 target genes encoding for S-phase specific proteins, epigenetic modulators, and miRNAs (e.g. miR-15/16), and thereby stalling progression through the S-phase of cell cycle. Subsequently, miR-15/16 activities are reduced and many of their direct targets are de-repressed, including ubiquitin ligase FBXW7 that destabilizes Cyclin E. Conversely, GBM cells expressing low p21 level, or after p21 knock-down, exhibit weaker or no E2F1 response to miR-10b inhibition. Comparative analysis of The Cancer Genome Atlas revealed a strong correlation between miR-10b and multiple E2F target genes in GBM and low-grade glioma. Taken together, these findings indicate that miR-10b regulates E2F1-mediated transcription in GBM, in a p21-dependent fashion. PMID:25738367

  16. miR-10b expression in breast cancer stem cells supports self-renewal through negative PTEN regulation and sustained AKT activation.

    PubMed

    Bahena-Ocampo, Ivan; Espinosa, Magali; Ceballos-Cancino, Gisela; Lizarraga, Floria; Campos-Arroyo, Denise; Schwarz, Angela; Maldonado, Vilma; Melendez-Zajgla, Jorge

    2016-05-01

    Cancer stem cells (CSCs) are linked to metastasis. Moreover, a discrete group of miRNAs (metastamiRs) has been shown to promote metastasis. Accordingly, we propose that miRNAs that function as metastatic promoters may influence the CSC phenotype. To study this issue, we compared the expression of 353 miRNAs in CSCs enriched from breast cancer cell lines using qRT-PCR analysis. One of the most altered miRNAs was miR-10b, which is a reported promoter of metastasis and migration. Stable overexpression of miR-10b in MCF-7 cells (miR-10b-OE cells) promoted higher self-renewal and expression of stemness and epithelial-mesenchymal transition (EMT) markers. In agreement with these results, inhibiting miR-10b expression using synthetic antisense RNAs resulted in a decrease in CSCs self-renewal. Bioinformatics analyses identified several potential miR-10b mRNA targets, including phosphatase and tensin homolog (PTEN), a key regulator of the PI3K/AKT pathway involved in metastasis, cell survival, and self-renewal. The targeting of PTEN by miR-10b was confirmed using a luciferase reporter, qRT-PCR, and Western blot analyses. Lower PTEN levels were observed in CSCs, and miR-10b depletion not only increased PTEN mRNA and protein expression but also decreased the activity of AKT, a downstream PTEN target kinase. Correspondingly, PTEN knockdown increased stem cell markers, whereas AKT inhibitors compromised the self-renewal ability of CSCs and breast cancer cell lines overexpressing miR-10b. In conclusion, miR-10b regulates the self-renewal of the breast CSC phenotype by inhibiting PTEN and maintaining AKT pathway activation. PMID:27113763

  17. Evaluating 10B-enriched Boric Acid, Bromide, and Heat as Tracers of Recycled Groundwater Flow near MAR Operations

    NASA Astrophysics Data System (ADS)

    Becker, T.; Clark, J. F.

    2012-12-01

    County, CA, USA) has been in progress since September 6, 2011, following injection of boric acid enriched in boron-10 (10B) and bromide (Br-) tracers. Tracer concentrations are collected at 9 monitoring wells that have pre-experiment estimated travel times between 0.5 to 180 days. Results indicate that 10B-enriched boric acid is an effective deliberate tracer at MAR sites; however, the ion's movement is slightly retarded relative to bromide by the substrate. 10B/Br- travel time ratios range from 1 to 1.4. In addition to the two deliberate geochemical tracers, heat is being evaluated as a possible intrinsic tracer at MAR sites. At the time of the experiment (late summer), reclaimed water was significantly warmer (~20°F) than the native groundwater as it entered the system. Time series are developed from loggers outfitted at each monitoring well, with measurements recorded hourly accurate to one thousandth of a degree. Results are similar to 10B & Br- travel times and validate the potential of heat as an intrinsic tracer.

  18. Novel and efficient 10B lined tubelet detector as a replacement for 3He neutron proportional counters

    NASA Astrophysics Data System (ADS)

    Tsorbatzoglou, Kyriakos; McKeag, Robert D.

    2011-10-01

    This paper presents a novel and robust proportional detector which addresses the well publicized shortage of 3He gas by using a 10B lining applied to a tubelet configuration. The advantage of the tubelet structure is that it yields a detector maintaining the form factor of a conventional 3He tube whilst achieving a sensitivity of up to 75% of a 3 atm 3He device. The design and fabrication of the tubelet detector is presented and discussed with test data comparing the new detector to existing 3He and BF 3 tubes. The application of the tubelet design to security and industrial applications including retro-fitting to existing portals and suitability for high integrity oil and gas installations is addressed.

  19. Nuclear structure with accurate chiral perturbation theory nucleon-nucleon potential: Application to 6Li and 10B

    SciTech Connect

    Navratil, P; Caurier, E

    2003-10-14

    The authors calculate properties of A = 6 system using the accurate charge-dependent nucleon-nucleon (NN) potential at fourth order of chiral perturbation theory. By application of the ab initio no-core shell model (NCSM) and a variational calculation in the harmonic oscillator basis with basis size up to 16 {h_bar}{Omega} they obtain the {sup 6}Li binding energy of 28.5(5) MeV and a converged excitation spectrum. Also, they calculate properties of {sup 10}B using the same NN potential in a basis space of up to 8 {h_bar}{Omega}. The results are consistent with results obtained by standard accurate NN potentials and demonstrate a deficiency of Hamiltonians consisting of only two-body terms. At this order of chiral perturbation theory three-body terms appear. It is expected that inclusion of such terms in the Hamiltonian will improve agreement with experiment.

  20. Morphology and magnetic behavior of cobalt rich amorphous/nanocrystalline (Co-Ni)70Ti10B20 alloyed powders

    NASA Astrophysics Data System (ADS)

    Raanaei, Hossein; Mohammad-Hosseini, Vahid

    2016-09-01

    The effect of milling time on microstructural and magnetic behavior of mechanically alloyed Co49Ni21Ti10B20 is investigated by using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectroscopy, differential scanning calorimetry and vibrating sample magnetometer. It is shown, with increasing milling time, the crystallite size decreases and finally reaches to a low value after 190 h of milling time. The increase in microstrain is also observed during the milling process. The results indicate the coexistence between amorphous and nanocrystalline phases after 190 h of milling time. Moreover, the lowest magnetic coercivity of about 39 Oe at the final milling stage is observed. The results of annealed sample reveal structural ordering of constituent elements.

  1. Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity-A Review.

    PubMed

    Chen, Da; Kannan, Kurunthachalam; Tan, Hongli; Zheng, Zhengui; Feng, Yong-Lai; Wu, Yan; Widelka, Margaret

    2016-06-01

    Numerous studies have investigated the environmental occurrence, human exposure, and toxicity of bisphenol A (BPA). Following stringent regulations on the production and usage of BPA, several bisphenol analogues have been produced as a replacement for BPA in various applications. The present review outlines the current state of knowledge on the occurrence of bisphenol analogues (other than BPA) in the environment, consumer products and foodstuffs, human exposure and biomonitoring, and toxicity. Whereas BPA was still the major bisphenol analogue found in most environmental monitoring studies, BPF and BPS were also frequently detected. Elevated concentrations of BPAF, BPF, and BPS (i.e., similar to or greater than that of BPA) have been reported in the abiotic environment and human urine from some regions. Many analogues exhibit endocrine disrupting effects, cytotoxicity, genotoxicity, reproductive toxicity, dioxin-like effects, and neurotoxicity in laboratory studies. BPAF, BPB, BPF, and BPS have been shown to exhibit estrogenic and/or antiandrogenic activities similar to or even greater than that of BPA. Knowledge gaps and research needs have been identified, which include the elucidation of environmental occurrences, persistence, and fate of bisphenol analogues (other than BPA), sources and pathways for human exposure, effects on reproductive systems and the mammary gland, mechanisms of toxicity from coexposure to multiple analogues, metabolic pathways and products, and the impact of metabolic modification on toxicity. PMID:27143250

  2. Set-up and calibration of a method to measure 10B concentration in biological samples by neutron autoradiography

    NASA Astrophysics Data System (ADS)

    Gadan, M. A.; Bortolussi, S.; Postuma, I.; Ballarini, F.; Bruschi, P.; Protti, N.; Santoro, D.; Stella, S.; Cansolino, L.; Clerici, A.; Ferrari, C.; Zonta, A.; Zonta, C.; Altieri, S.

    2012-03-01

    A selective uptake of boron in the tumor is the base of Boron Neutron Capture Therapy, which can destroy the tumor substantially sparing the normal tissue. In order to deliver a lethal dose to the tumor, keeping the dose absorbed by normal tissues below the tolerance level, it is mandatory to know the 10B concentration present in each kind of tissue at the moment of irradiation. This work presents the calibration procedure adopted for a boron concentration measurement method based on neutron autoradiography, where biological samples are deposited on sensitive films and irradiated in the thermal column of the TRIGA reactor (University of Pavia). The latent tracks produced in the film by the charged particles coming from the neutron capture in 10B are made visible by a proper etching, allowing the measurement of the track density. A calibration procedure with standard samples provides curves of track density as a function of boron concentration, to be used in the measurement of biological samples. In this paper, the bulk etch rate parameter and the calibration curves obtained for both liquid samples and biological tissues with known boron concentration are presented. A bulk etch rate value of (1.64 ± 0.02) μm/h and a linear dependence with etching time were found. The plots representing the track density versus the boron concentration in a range between 5 and 50 μg/g (ppm) are linear, with an angular coefficient of (1.614 ± 0.169)·10-3 tracks/(μm2 ppm) for liquids and (1.598 ± 0.097)·10-2 tracks/(μm2 ppm) for tissues.

  3. Glucagonlike Peptide 2 Analogue Teduglutide

    PubMed Central

    Chaturvedi, Lakshmi S.; Basson, Marc D.

    2015-01-01

    IMPORTANCE Short bowel syndrome occurs when a shortened intestine cannot absorb sufficient nutrients or fluids. Teduglutide is a recombinant analogue of human glucagonlike peptide 2 that reduces dependence on parenteral nutrition in patients with short bowel syndrome by promoting enterocytic proliferation, increasing the absorptive surface area. However, enterocyte function depends not only on the number of cells that are present but also on differentiated features that facilitate nutrient absorption and digestion. OBJECTIVE To test the hypothesis that teduglutide impairs human intestinal epithelial differentiation. DESIGN AND SETTING We investigated the effects of teduglutide in the modulation of proliferation and differentiation in human Caco-2 intestinal epithelial cells at a basic science laboratory. This was an in vitro study using Caco-2 cells, a human-derived intestinal epithelial cell line commonly used to model enterocytic biology. EXPOSURE Cells were exposed to teduglutide or vehicle control. MAINOUTCOMESAND MEASURES We analyzed the cell cycle by bromodeoxyuridine incorporation or propidium iodide staining and flow cytometry and measured cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. We used quantitative reverse transcription–polymerase chain reaction to assay the expression of the enterocytic differentiation markers villin, sucrase-isomaltase, glucose transporter 2 (GLUT2), and dipeptidyl peptidase 4 (DPP-4), as well as that of the putative differentiation signals schlafen 12 (SLFN12) and caudal-related homeobox intestine-specific transcription factor (Cdx2). Villin promoter activity was measured by a luciferase-based assay. RESULTS The MTS assay demonstrated that teduglutide increased cell numbers by a mean (SD) of 10% (2%) over untreated controls at a maximal 500nM (n = 6, P < .05). Teduglutide increased bromodeoxyuridine-positive cells vs untreated controls by a mean (SD

  4. Analogue Aharonov-Bohm effect in neo-Newtonian theory

    NASA Astrophysics Data System (ADS)

    Anacleto, M. A.; Salako, I. G.; Brito, F. A.; Passos, E.

    2015-12-01

    We address the issues of the scattering of massless planar scalar waves by an acoustic black hole in neo-Newtonian hydrodynamics. We then compute the differential cross section through the use of the partial wave approach in the neo-Newtonian theory which is a modification of the usual Newtonian theory that correctly incorporates the effects of pressure. We mainly show that the scattering of planar waves leads to a modified analogue Aharonov-Bohm effect due to a nontrivial response of the parameters defining the equation of state.

  5. Convergent syntheses of LeX analogues

    PubMed Central

    Wang, An; Hendel, Jenifer

    2010-01-01

    Summary The synthesis of three Lex derivatives from one common protected trisaccharide is reported. These analogues will be used respectively for competitive binding experiments, conjugation to carrier proteins and immobilization on gold. An N-acetylglucosamine monosaccharide acceptor was first glycosylated at O-4 with a galactosyl imidate. This coupling was performed at 40 °C under excess of BF3·OEt2 activation and proceeded best if the acceptor carried a 6-chlorohexyl rather than a 6-azidohexyl aglycon. The 6-chlorohexyl disaccharide was then converted to an acceptor and submitted to fucosylation yielding the corresponding protected 6-chlorohexyl Lex trisaccharide. This protected trisaccharide was used as a precursor to the 6-azidohexyl, 6-acetylthiohexyl and 6-benzylthiohexyl trisaccharide analogues which were obtained in excellent yields (70–95%). In turn, we describe the deprotection of these intermediates in one single step using dissolving metal conditions. Under these conditions, the 6-chlorohexyl and 6-azidohexyl intermediates led respectively to the n-hexyl and 6-aminohexyl trisaccharide targets. Unexpectedly, the 6-acetylthiohexyl analogue underwent desulfurization and gave the n-hexyl glycoside product, whereas the 6-benzylthiohexyl analogue gave the desired disulfide trisaccharide dimer. This study constitutes a particularly efficient and convergent preparation of these three Lex analogues. PMID:20485599

  6. 18,18'-Dihexyl[9,9']biphenanthro[9,10-b]triphenylene: construction and consequences of a profoundly hindered aryl-aryl single bond.

    PubMed

    Hilton, Cameron L; Crowfoot, Jeremy M; Rempala, Pawel; King, Benjamin T

    2008-10-01

    The title compound, 1-Hex, was synthesized by the Zr-mediated biphenylation of 4,4'-dihexyloctabromobiphenyl using (Li(THF)4)2 x Zr(biphe)3, where biphe is the 2,2'-biphenyldiyl ligand, in 5% isolated yield. Two independent X-ray diffraction analyses revealed that arene 1-Hex possesses a highly strained and hindered aryl-aryl single bond. This bond causes the phenanthro[9,10-b]triphenylene (PTP) moieties to twist (anthracene subunit dihedral, 69 degrees); the interlocked, helical, homochiral PTP moieties give rise to effective D2 symmetry. The calculated adiabatic homolytic bond dissociation energy of this strained bond is only 67 kcal/mol, but nonetheless the bond exhibits a surprisingly normal length (1.49 A); the reason is elongation only slowly releases strain. Variable temperature NMR revealed two dynamic processes: hexyl rotation (12.0 +/- 0.4 kcal/mol) and inversion of chirality (15.2 +/- 0.6 kcal/mol). DFT calculations provide rate-determining transitions states, whose energies agree with measured values, and provide insight to the mechanism of these processes. Rotation about the central bond is not involved in either observed process. Calculations demonstrate that rotation does not involve a simple torsion of the equilibrium structure, but rather a complex movement with a barrier of 49 kcal/mol from a slipped-parallel, C(2h) intermediate. PMID:18781754

  7. Past and present of analogue modelling, and its future trend

    NASA Astrophysics Data System (ADS)

    Koyi, Hemin

    2015-04-01

    Since Hull (1815) published his article on modelling, analogue modelling has expanded to simulate both a wider range of tectonic regimes and target more challenging set-ups, and has become an integrated part of the fields of tectonics and structural geology. Establishment of new laboratories testifies for the increased attention the technique receives. The ties between modellers and field geoscientists have become stronger with the focus being on understanding the parameters that govern the evolution of a tectonic regime and the processes that dominate it. Since the first sand castle was built with damp sand on a beach, sand has proven to be an appropriate material analogue. Even though granular materials is the most widely used analogue material, new materials are also (re)introduced as rock analogues. Emphasis has been on more precise measurements of the mechanical properties of the materials and on minimizing the preparation effects, which have a great impact on scaling, interpretations and benchmarking. The analytical technique used to quantify model results has also seen a great deal of improvement. In addition to X-ray tomography used to visualise internal structures of models, new techniques (e.g. PIV, high-resolution laser scanning, and interferometry) have enabled monitoring kinematics with a higher precision. Benchmarking exercises have given modelling an additional checking tool by outlining, in addition to the rheology of the modelling materials, the impact of different preparation approaches, the effect of boundary conditions, and the human factor on model results. However, despite the different approaches and deformation rigs, results of models of different tectonic laboratories have shown a great deal of similarities. Even with the introduction of more sophisticated numerical codes and usage of more powerful computers which enable the simulation of more challenging material properties and combinations of those, and 3D model set-up, analogue modelling

  8. High affinity ATP/ADP analogues as new tools for studying CFTR gating.

    PubMed

    Zhou, Zhen; Wang, Xiaohui; Li, Min; Sohma, Yoshiro; Zou, Xiaoqin; Hwang, Tzyh-Chang

    2005-12-01

    Previous studies using non-hydrolysable ATP analogues and hydrolysis-deficient cystic fibrosis transmembrane conductance regulator (CFTR) mutants have indicated that ATP hydrolysis precedes channel closing. Our recent data suggest that ATP binding is also important in modulating the closing rate. This latter hypothesis predicts that ATP analogues with higher binding affinities should stabilize the open state more than ATP. Here we explore the possibility of using N6-modified ATP/ADP analogues as high-affinity ligands for CFTR gating, since these analogues have been shown to be more potent than native ATP/ADP in other ATP-binding proteins. Among the three N6-modified ATP analogues tested, N6-(2-phenylethyl)-ATP (P-ATP) was the most potent, with a K(1/2) of 1.6 +/- 0.4 microm (>50-fold more potent than ATP). The maximal open probability (P(o)) in the presence of P-ATP was approximately 30% higher than that of ATP, indicating that P-ATP also has a higher efficacy than ATP. Single-channel kinetic analysis showed that as [P-ATP] was increased, the opening rate increased, whereas the closing rate decreased. The fact that these two kinetic parameters have different sensitivities to changes of [P-ATP] suggests an involvement of two different ATP-binding sites, a high-affinity site modulating channel closing and a low affinity site controlling channel opening. The effect of P-ATP on the stability of open states was more evident when ATP hydrolysis was abolished, either by mutating the nucleotide-binding domain 2 (NBD2) Walker B glutamate (i.e. E1371) or by using the non-hydrolysable ATP analogue AMP-PNP. Similar strategies to develop nucleotide analogues with a modified adenine ring could be valuable for future studies of CFTR gating. PMID:16223764

  9. High affinity ATP/ADP analogues as new tools for studying CFTR gating

    PubMed Central

    Zhou, Zhen; Wang, Xiaohui; Li, Min; Sohma, Yoshiro; Zou, Xiaoqin; Hwang, Tzyh-Chang

    2005-01-01

    Previous studies using non-hydrolysable ATP analogues and hydrolysis-deficient cystic fibrosis transmembrane conductance regulator (CFTR) mutants have indicated that ATP hydrolysis precedes channel closing. Our recent data suggest that ATP binding is also important in modulating the closing rate. This latter hypothesis predicts that ATP analogues with higher binding affinities should stabilize the open state more than ATP. Here we explore the possibility of using N6-modified ATP/ADP analogues as high-affinity ligands for CFTR gating, since these analogues have been shown to be more potent than native ATP/ADP in other ATP-binding proteins. Among the three N6-modified ATP analogues tested, N6-(2-phenylethyl)-ATP (P-ATP) was the most potent, with a K½ of 1.6 ± 0.4 μm (>50-fold more potent than ATP). The maximal open probability (Po) in the presence of P-ATP was ∼30% higher than that of ATP, indicating that P-ATP also has a higher efficacy than ATP. Single-channel kinetic analysis showed that as [P-ATP] was increased, the opening rate increased, whereas the closing rate decreased. The fact that these two kinetic parameters have different sensitivities to changes of [P-ATP] suggests an involvement of two different ATP-binding sites, a high-affinity site modulating channel closing and a low affinity site controlling channel opening. The effect of P-ATP on the stability of open states was more evident when ATP hydrolysis was abolished, either by mutating the nucleotide-binding domain 2 (NBD2) Walker B glutamate (i.e. E1371) or by using the non-hydrolysable ATP analogue AMP-PNP. Similar strategies to develop nucleotide analogues with a modified adenine ring could be valuable for future studies of CFTR gating. PMID:16223764

  10. Effects of sleep deprivation on behaviors and abnormal hippocampal BDNF/miR-10B expression in rats with chronic stress depression.

    PubMed

    Jiang, Yuxue; Zhu, Jinfu

    2015-01-01

    Being sleep-deprived can relieve the depressed emotions in rats, but the underlying mechanisms remain unknown. In this study, male rats were divided into 3 groups: normal control (NC), chronicunpredictable stress (CUPS) and sleep-deprived (SD). All of the groups were examined using the sucrose consumption test and the open field test. The sucrose consumption test and the open field test were performed for all three groups. The BDNF and miR-10B expressions were examined using real-time PCR and the level of BNDF was discovered by western blotting. In the sucrose consumption test and the open field test, the CUPS rats consumed less sucrose and got fewer score than the NC rats, however the SD rats consumed significantly more sucrose and received higher scores than the CUPS rats. Both the expression of BNDF and the protein levels in the CUPS group was significantly lower than in the NC group. Also, the CUPS group also showed a higher miR-10B expression than the NC group. However, the SD group demonstrated higher BDNF expression and lower miR-10B expression when compared with the CUPS group. Further investigation demonstrated that the BDNF is the direct target gene of miR-10B and BDNF expression, which is negatively correlated with the expression of miR-10B. In the sucrose consumption test, BNDF expression is positively correlated with the sucrose preference rate whereas miR-10B has an opposing correlation. Moreover, the open field test demonstrated that BNDF expression is positively correlated with the scores and the miR-10B expression is negatively correlated. These results indicate that sleep deprivation is closely linked with the downregulation of miR-10B and possibly the upregulation of BDNF in the hippocampus in the CUPS rats. PMID:25755749

  11. Effects of sleep deprivation on behaviors and abnormal hippocampal BDNF/miR-10B expression in rats with chronic stress depression

    PubMed Central

    Jiang, Yuxue; Zhu, Jinfu

    2015-01-01

    Being sleep-deprived can relieve the depressed emotions in rats, but the underlying mechanisms remain unknown. In this study, male rats were divided into 3 groups: normal control (NC), chronicunpredictable stress (CUPS) and sleep-deprived (SD). All of the groups were examined using the sucrose consumption test and the open field test. The sucrose consumption test and the open field test were performed for all three groups. The BDNF and miR-10B expressions were examined using real-time PCR and the level of BNDF was discovered by western blotting. In the sucrose consumption test and the open field test, the CUPS rats consumed less sucrose and got fewer score than the NC rats, however the SD rats consumed significantly more sucrose and received higher scores than the CUPS rats. Both the expression of BNDF and the protein levels in the CUPS group was significantly lower than in the NC group. Also, the CUPS group also showed a higher miR-10B expression than the NC group. However, the SD group demonstrated higher BDNF expression and lower miR-10B expression when compared with the CUPS group. Further investigation demonstrated that the BDNF is the direct target gene of miR-10B and BDNF expression, which is negatively correlated with the expression of miR-10B. In the sucrose consumption test, BNDF expression is positively correlated with the sucrose preference rate whereas miR-10B has an opposing correlation. Moreover, the open field test demonstrated that BNDF expression is positively correlated with the scores and the miR-10B expression is negatively correlated. These results indicate that sleep deprivation is closely linked with the downregulation of miR-10B and possibly the upregulation of BDNF in the hippocampus in the CUPS rats. PMID:25755749

  12. 17 CFR 240.10b5-1 - Trading “on the basis of” material nonpublic information in insider trading cases.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Trading âon the basis ofâ material nonpublic information in insider trading cases. 240.10b5-1 Section 240.10b5-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and...

  13. Selection of Actinide Chemical Analogues for WIPP Tests: Potential Nonradioactive Sorbing and Nonsorbing Tracers for Study of Ion Transport in the Environment

    SciTech Connect

    Dale Spall; Robert Villarreal

    1998-08-01

    Chemical characteristics of the actinides (Th, U, Np, Pu, Am) have been studied relative to nonradioactive chemical elements that have similar characteristics in an attempt to identify a group of actinide chemical analogues that are nonradioactive. In general, the chemistries of the actinides, especially U, Np, Pu, and Am, are very complex and attempts to identify a single chemical analogue for each oxidation state were not successful. However, the rationale for selecting a group of chemical analogues that would mimic the actinides as a group is provided. The categorization of possible chemical analogues (tracers) with similar chemical properties was based on the following criteria. Categorization was studied according.

  14. Hyperthermostable Thermotoga maritima xylanase XYN10B shows high activity at high temperatures in the presence of biomass-dissolving hydrophilic ionic liquids.

    PubMed

    Yu, Tianyi; Anbarasan, Sasikala; Wang, Yawei; Telli, Kübra; Aslan, Aşkın Sevinç; Su, Zhengding; Zhou, Yin; Zhang, Li; Iivonen, Piia; Havukainen, Sami; Mentunen, Tero; Hummel, Michael; Sixta, Herbert; Binay, Baris; Turunen, Ossi; Xiong, Hairong

    2016-07-01

    The gene of Thermotoga maritima GH10 xylanase (TmXYN10B) was synthesised to study the extreme limits of this hyperthermostable enzyme at high temperatures in the presence of biomass-dissolving hydrophilic ionic liquids (ILs). TmXYN10B expressed from Pichia pastoris showed maximal activity at 100 °C and retained 92 % of maximal activity at 105 °C in a 30-min assay. Although the temperature optimum of activity was lowered by 1-ethyl-3-methylimidazolium acetate ([EMIM]OAc), TmXYN10B retained partial activity in 15-35 % hydrophilic ILs, even at 75-90 °C. TmXYN10B retained over 80 % of its activity at 90 °C in 15 % [EMIM]OAc and 15-25 % 1-ethyl-3-methylimidazolium dimethylphosphate ([EMIM]DMP) during 22-h reactions. [EMIM]OAc may rigidify the enzyme and lower V max. However, only minor changes in kinetic parameter K m showed that competitive inhibition by [EMIM]OAc of TmXYN10B is minimal. In conclusion, when extended enzymatic reactions under extreme conditions are required, TmXYN10B shows extraordinary potential. PMID:27240671

  15. Boron uptake in tumors, cerebrum and blood from (/sup 10/B)Na/sub 4/B/sub 24/H/sub 22/S/sub 2/

    DOEpatents

    Slatkin, D.N.; Micca, P.L.; Fairchild, R.G.

    1986-03-11

    A stable boronated (/sup 10/B-labeled) compound, sodium mercaptoundecahydrododecaborate is infused in the form of the disulfide dimer, (/sup 10/B)Na/sub 4/B/sub 24/H/sub 22/S/sub 2/, at a dose of about 200 ..mu..g /sup 10/B per gm body weight. The infusion is preformed into the blood or peritoneal cavity of the patient slowly over a period of many days, perhaps one week or more, at the rate of roughly 1 ..mu..g /sup 10/B per gm body weight per hour. Use of this particular boronated dimer in the manner or similarly to the manner so described permits radiotherapeutically effective amounts of boron to accumulate in tumors to be treated by boron neutron capture radiation therapy and also permits sufficient retention of boron in tumor after the cessation of the slow infusion, so as to allow the blood concentration of /sup 10/B to drop or to be reduced artificially to a radiotherapeutically effective level, less than one-half of the concentration of /sup 10/B in the tumor. 1 tab.

  16. Dolastatin 11 conformations, analogues and pharmacophore.

    PubMed

    Ali, Md Ahad; Bates, Robert B; Crane, Zackary D; Dicus, Christopher W; Gramme, Michelle R; Hamel, Ernest; Marcischak, Jacob; Martinez, David S; McClure, Kelly J; Nakkiew, Pichaya; Pettit, George R; Stessman, Chad C; Sufi, Bilal A; Yarick, Gayle V

    2005-07-01

    Twenty analogues of the natural antitumor agent dolastatin 11, including majusculamide C, were synthesized and tested for cytotoxicity against human cancer cells and stimulation of actin polymerization. Only analogues containing the 30-membered ring were active. Molecular modeling and NMR evidence showed the low-energy conformations. The amide bonds are all trans except for the one between the Tyr and Val units, which is cis. Since an analogue restricted to negative 2-3-4-5 angles stimulated actin polymerization but was inactive in cells, the binding conformation (most likely the lowest-energy conformation in water) has a negative 2-3-4-5 angle, whereas a conformation with a positive 2-3-4-5 angle (most likely the lowest energy conformation in chloroform) goes through cell walls. The highly active R alcohol from borohydride reduction of dolastatin 11 is a candidate for conversion to prodrugs. PMID:15878670

  17. Classical Simulated Annealing Using Quantum Analogues

    NASA Astrophysics Data System (ADS)

    La Cour, Brian R.; Troupe, James E.; Mark, Hans M.

    2016-08-01

    In this paper we consider the use of certain classical analogues to quantum tunneling behavior to improve the performance of simulated annealing on a discrete spin system of the general Ising form. Specifically, we consider the use of multiple simultaneous spin flips at each annealing step as an analogue to quantum spin coherence as well as modifications of the Boltzmann acceptance probability to mimic quantum tunneling. We find that the use of multiple spin flips can indeed be advantageous under certain annealing schedules, but only for long anneal times.

  18. Classical Simulated Annealing Using Quantum Analogues

    NASA Astrophysics Data System (ADS)

    La Cour, Brian R.; Troupe, James E.; Mark, Hans M.

    2016-06-01

    In this paper we consider the use of certain classical analogues to quantum tunneling behavior to improve the performance of simulated annealing on a discrete spin system of the general Ising form. Specifically, we consider the use of multiple simultaneous spin flips at each annealing step as an analogue to quantum spin coherence as well as modifications of the Boltzmann acceptance probability to mimic quantum tunneling. We find that the use of multiple spin flips can indeed be advantageous under certain annealing schedules, but only for long anneal times.

  19. D-luciferin analogues: a multicolor toolbox for bioluminescence imaging.

    PubMed

    Sun, Yuan-Qiang; Liu, Jing; Wang, Pi; Zhang, Jingyu; Guo, Wei

    2012-08-20

    Colorful mixture: Three types of luciferin analogues, that is, alkylaminoluciferins, aminoselenoluciferin, and luciferins with a benzimidazole scaffold, have been reported. These analogues show excellent bioluminescent properties and great potential in bioluminescence imaging. PMID:22807027

  20. Synthesis and Cytoxicity of Sempervirine and Analogues.

    PubMed

    Pan, Xiaohong; Yang, Chunying; Cleveland, John L; Bannister, Thomas D

    2016-03-01

    Sempervirine and analogues were synthesized using a route featuring Sonogashira and Larock Pd-catalyzed reactions. Structure-activity relationships were investigated using three human cancer cell lines. 10-Fluorosempervirine is the most potently cytotoxic member of the family yet described. PMID:26828413

  1. Solanapyrone analogues from a Hawaiian fungicolous fungus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four new solanayrone analogues (solanapyrones J-M; 1-4) have been isolated from an unidentified fungicolous fungus collected in Hawaii. The structures and relative configurations of these compounds were determined by analysis of ID NMR, 2D NMR, and MS data. Solanapyrone J(1) showed antifungal acti...

  2. New cytotoxic analogues of annonaceous acetogenins.

    PubMed

    Rodier, S; Le Huerou, Y; Renoux, B; Doyon, J; Renard, P; Pierré, A; Gesson, J P; Grée, R

    2001-01-01

    A series of new acetogenin analogues incorporating a central catechol moiety instead of the tetrahydrofuran ring(s) have been prepared and tested against L1210 leukemia cells. Although less potent than bullatacinone, which has the same terminal lactone, these compounds display interesting cell cycle effects. PMID:11962508

  3. CO2 Capture with Enzyme Synthetic Analogue

    SciTech Connect

    Cordatos, Harry

    2010-03-01

    Project overview provides background on carbonic anhydrase transport mechanism for CO2 in the human body and proposed approach for ARPA-E project to create a synthetic enzyme analogue and utilize it in a membrane for CO2 capture from flue gas.

  4. Synthesis of lipid II phosphonate analogues.

    PubMed

    Borbás, Anikó; Herczegh, Pál

    2011-09-01

    Simple analogues of lipid II were synthesized from 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-1-thio-β-D-glucopyranose using conjugate addition onto ethylidene bisphosphonate and subsequent Wadsworth-Horner-Emmons reaction with long chain aliphatic aldehydes. PMID:21600568

  5. The arsonomethyl analogue of 3-phosphoglycerate.

    PubMed Central

    Adams, S R; Sparkes, M J; Dixon, H B

    1983-01-01

    4-Arsono-2-hydroxybutanoic acid, the analogue of 3-phosphoglycerate in which -CH2-AsO3H2 replaces -O-PO3H2, was synthesized. It proved to be a substrate for phosphoglycerate kinase. Its Michaelis constant was only slightly higher than that of the natural substrate, but its catalytic constant was about 1300 times smaller. PMID:6615422

  6. Synthesis and antimicrobial activity of squalamine analogue.

    PubMed

    Kim, H S; Choi, B S; Kwon, K C; Lee, S O; Kwak, H J; Lee, C H

    2000-08-01

    Synthesis and antimicrobial activity of squalamine analogue 2 are reported. The synthesis of 2 was accomplished from bisnoralcohol 3. The spermidine moiety was introduced via reductive amination of an appropriately functionalized 3beta-aminosterol with spermidinyl aldehyde 17 utilizing sodium triacetoxyborohydride as the reducing agent. Compound 2 shows weaker antimicrobial activity than squalamine. PMID:11003150

  7. [Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

    PubMed

    Cai, Yunxin; Lu, Dandan; Chen, Zhen; Ding, Yi; Chung, Nga N; Li, Tingyou; Schiller, Peter W

    2016-08-01

    Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment. PMID:27301366

  8. Dipolar Quinoidal Acene Analogues as Stable Isoelectronic Structures of Pentacene and Nonacene.

    PubMed

    Shi, Xueliang; Kueh, Weixiang; Zheng, Bin; Huang, Kuo-Wei; Chi, Chunyan

    2015-11-23

    Quinoidal thia-acene analogues, as the respective isoelectronic structures of pentacene and nonacene, were synthesized and an unusual 1,2-sulfur migration was observed during the Friedel-Crafts alkylation reaction. The analogues display a closed-shell quinoidal structure in the ground state with a distinctive dipolar character. In contrast to their acene isoelectronic structures, both compounds are stable because of the existence of more aromatic sextet rings, a dipolar character, and kinetic blocking. They exhibit unique packing in single crystals resulting from balanced dipole-dipole and [C-H⋅⋅⋅π]/[C-H⋅⋅⋅S] interactions. PMID:26447720

  9. Adsorption of Amido Black 10B from aqueous solutions onto Zr (IV) surface-immobilized cross-linked chitosan/bentonite composite

    NASA Astrophysics Data System (ADS)

    Zhang, Lujie; Hu, Pan; Wang, Jing; Huang, Ruihua

    2016-04-01

    Zr(IV) surface-immobilized cross-linked chitosan/bentonite composite was synthesized by immersing cross-linked chitosan/bentonite composite in zirconium oxychloride solution, and characterized by X-ray diffraction, Fourier transform infrared spectroscopy, Scanning electron microscopy techniques. The adsorption of an anionic dye, Amido Black 10B, from aqueous solution by Zr(IV) loaded cross-linked chitosan/bentonite composite was investigated as a function of loading amount of Zr(IV), adsorbent dosage, pH value of initial dye solution, and ionic strength. The removal of Amido Black 10B increased with an increase in loading amount of Zr(IV) and adsorbent dosage, but decreased with an increase in pH or ionic strength. The adsorption of AB10B onto Zr(IV) loaded cross-linked chitosan/bentonite composite was favored at lower pH values and higher temperatures. The Langmuir isotherm model fitted well with the equilibrium adsorption isotherm data and the maximum monolayer adsorption capacity was 418.4 mg/g at natural pH value and 298 K. The pseudo-second-order kinetic model well described the adsorption process of Amido Black 10B onto Zr(IV) loaded cross-linked chitosan/bentonite composite. The possible mechanisms controlling Amido Black 10B adsorption included hydrogen bonding and electrostatic interactions.

  10. Recent advances in topoisomerase I-targeting agents, camptothecin analogues.

    PubMed

    Kim, Dae-Kee; Lee, Namkyu

    2002-12-01

    The present review concentrates on camptothecin (CPT) analogues, the most extensively studied topoisomerase I (topo I) inhibitors, and provides concise information on the structural features of human topo I enzyme, mechanisms of interaction of CPT with topo I, structure-activity relationship study of CPT analogues including the influence of lactone stability on antitumor activity, and recent updates of valuable CPT analogues. PMID:12370044

  11. Cystic fibrosis transmembrane conductance regulator: the NBF1+R (nucleotide-binding fold 1 and regulatory domain) segment acting alone catalyses a Co2+/Mn2+/Mg2+-ATPase activity markedly inhibited by both Cd2+ and the transition-state analogue orthovanadate.

    PubMed

    Annereau, Jean Philippe; Ko, Young Hee; Pedersen, Peter L

    2003-04-15

    Cystic fibrosis (CF) is caused by mutations in the gene encoding CFTR (cystic fibrosis transmembrane conductance regulator), a regulated anion channel and member of the ATP-binding-cassette transporter (ABC transporter) superfamily. Of CFTR's five domains, the first nucleotide-binding fold (NBF1) has been of greatest interest both because it is the major 'hotspot' for mutations that cause CF, and because it is connected to a unique regulatory domain (R). However, attempts have failed to obtain a catalytically active NBF1+R protein in the absence of a fusion partner. Here, we report that such a protein can be obtained following its overexpression in bacteria. The pure NBF1+R protein exhibits significant ATPase activity [catalytic-centre activity (turnover number) 6.7 min(-1)] and an apparent affinity for ATP ( K (m), 8.7 microM) higher than reported previously for CFTR or segments thereof. As predicted, the ATPase activity is inhibited by mutations in the Walker A motif. It is also inhibited by vanadate, a transition-state analogue. Surprisingly, however, the best divalent metal activator is Co(2+), followed by Mn(2+) and Mg(2+). In contrast, Ca(2+) is ineffective and Cd(2+) is a potent inhibitor. These novel studies, while demonstrating clearly that CFTR's NBF1+R segment can act independently as an active, vanadate-sensitive ATPase, also identify its unique cation activators and a new inhibitor, thus providing insight into the nature of its active site. PMID:12523935

  12. Investigation of the Application of miR10b and miR135b in the Identification of Semen Stains

    PubMed Central

    Xue, Tianyu; Ma, Xiaoyan; Zhang, Jinxiang; Ou, Xueling; Cheng, Jianding; Sun, Hongyu

    2015-01-01

    To evaluate the identification method using the microRNA markers miR10b and miR135b to distinguish semen stains from menstrual blood, peripheral blood, vaginal fluid and so on body fluid stains. The expression levels of miR10b and miR35b in semen stains and menstrual blood and so on were detected utilizing a real-time quantitative PCR technique with a specific fluorescence-labeled TaqMan probe. RNU6b was used as the internal reference gene; the difference in their expression was analyzed, and the specificity, sensitivity, and detection capability of the techniques were evaluated. The expression of miR10b and miR135b in semen stains was significantly higher than that of other body fluid stains, with a mean value of ΔCт from-6 to-7. However, it ranged from-2 to-4 for other body fluid stains. The initial criteria for judging which semen stains can be identified were determined by analyzing the research results. When the threshold value was set to 0.04, the CT value could be detected in the target genes miR10b, miR135b and in the internal reference gene RNU6b, and CT values are<40, ΔCT[10b-U6]<-5.5, and ΔCT[135b-U6]<-6, respectively, and the semen stain could be identified. The expression levels of miR10b and miR135b are higher in semen with strong tissue specificity; thus, they can be used to differentiate semen stains from other body fluid stains in forensic science. PMID:26355456

  13. Inactivation of ca10a and ca10b Genes Leads to Abnormal Embryonic Development and Alters Movement Pattern in Zebrafish

    PubMed Central

    Aspatwar, Ashok; Barker, Harlan R.; Saralahti, Anni K.; Bäuerlein, Carina A.; Ortutay, Csaba; Pan, Peiwen; Kuuslahti, Marianne; Parikka, Mataleena; Rämet, Mika; Parkkila, Seppo

    2015-01-01

    Carbonic anhydrase related proteins (CARPs) X and XI are highly conserved across species and are predominantly expressed in neural tissues. The biological role of these proteins is still an enigma. Ray-finned fish have lost the CA11 gene, but instead possess two co-orthologs of CA10. We analyzed the expression pattern of zebrafish ca10a and ca10b genes during embryonic development and in different adult tissues, and studied 61 CARP X/XI-like sequences to evaluate their phylogenetic relationship. Sequence analysis of zebrafish ca10a and ca10b reveals strongly predicted signal peptides, N-glycosylation sites, and a potential disulfide, all of which are conserved, suggesting that all of CARP X and XI are secretory proteins and potentially dimeric. RT-qPCR showed that zebrafish ca10a and ca10b genes are expressed in the brain and several other tissues throughout the development of zebrafish. Antisense morpholino mediated knockdown of ca10a and ca10b showed developmental delay with a high rate of mortality in larvae. Zebrafish morphants showed curved body, pericardial edema, and abnormalities in the head and eye, and there was increased apoptotic cell death in the brain region. Swim pattern showed abnormal movement in morphant zebrafish larvae compared to the wild type larvae. The developmental phenotypes of the ca10a and ca10b morphants were confirmed by inactivating these genes with the CRISPR/Cas9 system. In conclusion, we introduce a novel zebrafish model to investigate the mechanisms of CARP Xa and CARP Xb functions. Our data indicate that CARP Xa and CARP Xb have important roles in zebrafish development and suppression of ca10a and ca10b expression in zebrafish larvae leads to a movement disorder. PMID:26218428

  14. [Insulin analogues: modifications in the structure, molecular and metabolic consequences].

    PubMed

    de Luis, D A; Romero, E

    2013-01-01

    Recombinant DNA technology has provided insulin analogues for the treatment of diabetes mellitus, with an efficacy and safety that has improved the treatment of this disease. We briefly review the principal characteristics of the insulin analogues currently available. Both rapid-acting (lispro, aspart and glulisine) and long acting (glargine and determir) insulin analogues are included in this review. We describe the pharmacology of each insulin analogue, their differences with the human insulin, the administration, indication, efficacy and safety. In addition we discussed the main controversies of the use of these insulin analogues. In particular, those related with the risk of cancer and retinopathy, and their use in pregnant women. PMID:23517895

  15. Carbon storage at defect sites in mantle mineral analogues

    NASA Astrophysics Data System (ADS)

    Wu, Jun; Buseck, Peter R.

    2013-10-01

    A significant fraction of Earth's carbon resides in the mantle, but the mode of carbon storage presents a long-standing problem. The mantle contains fluids rich in carbon dioxide and methane, carbonate-bearing melts, carbonate minerals, graphite, diamond and carbides, as well as dissolved carbon atoms in metals. However, it is uncertain whether these can sufficiently account for the total amount of carbon thought to be stored in the mantle and the volume of carbon degassed from the mantle at volcanoes. Moreover, such carbon hosts should significantly affect the physical and chemical behaviour of the mantle, including its melting temperature, electrical conductivity and oxidation state. Here we use in situ transmission electron microscopy to measure the storage of carbon within common mantle mineral analogues--nickel-doped lanthanum chromate perovskite and titanium dioxide--in laboratory experiments at high pressure and temperature. We detect elevated carbon concentrations at defect sites in the nanocrystals, maintained at high pressures within annealed carbon nanocages. Specifically, our experiments show that small stacking faults within the mantle analogue materials are effective carbon sinks at mantle conditions, potentially providing an efficient mechanism for carbon storage in the mantle. Furthermore, this carbon can be readily released under lower pressure conditions, and may therefore help to explain carbon release in volcanic eruptions.

  16. Glucocorticoid analogues: potential therapeutic alternatives for treating inflammatory muscle diseases.

    PubMed

    Reeves, Erica K M; Rayavarapu, Sree; Damsker, Jesse M; Nagaraju, Kanneboyina

    2012-03-01

    Glucocorticoids (GCs) have been prescribed to treat a variety of diseases, including inflammatory myopathies and Duchenne muscular dystrophy for over 50 years. However, their prescription remains controversial due to the significant side effects associated with the chronic treatment. It is a common belief that the clinical efficacy of GCs is due to their transrepression of pro-inflammatory genes through inhibition of inflammatory transcription factors (i.e. NF-κB, AP-1) whereas the adverse side effects are attributed to the glucocorticoid receptor (GR)-mediated transcription of target genes (transactivation). The past decade has seen an increased interest in the development of GR modulators that maintain the effective anti-inflammatory properties but lack the GR-dependent transcriptional response as a safe alternative to traditional GCs. Many of these analogues or "dissociative" compounds show potential promise in in vitro studies but fail to reach human clinical trials. In this review, we discuss molecular effects of currently prescribed GCs on skeletal muscle and also discuss the current state of development of GC analogues as alternative therapeutics for inflammatory muscle diseases. PMID:22214335

  17. Structure of Mandelate Racemase with Bound Intermediate Analogues Benzohydroxamate and Cupferron

    SciTech Connect

    Lietzan, Adam D.; Nagar, Mitesh; Pellmann, Elise A.; Bourque, Jennifer R.; Bearne, Stephen L.; Maurice, Martin St.

    2012-05-09

    Mandelate racemase (MR, EC 5.1.2.2) from Pseudomonas putida catalyzes the Mg{sup 2+}-dependent interconversion of the enantiomers of mandelate, stabilizing the altered substrate in the transition state by 26 kcal/mol relative to the substrate in the ground state. To understand the origins of this binding discrimination, we determined the X-ray crystal structures of wild-type MR complexed with two analogues of the putative aci-carboxylate intermediate, benzohydroxamate and Cupferron, to 2.2-{angstrom} resolution. Benzohydroxamate is shown to be a reasonable mimic of the transition state and/or intermediate because its binding affinity for 21 MR variants correlates well with changes in the free energy of transition state stabilization afforded by these variants. Both benzohydroxamate and Cupferron chelate the active site divalent metal ion and are bound in a conformation with the phenyl ring coplanar with the hydroxamate and diazeniumdiolate moieties, respectively. Structural overlays of MR complexed with benzohydroxamate, Cupferron, and the ground state analogue (S)-atrolactate reveal that the para carbon of the substrate phenyl ring moves by 0.8-1.2 {angstrom} between the ground state and intermediate state, consistent with the proposal that the phenyl ring moves during MR catalysis while the polar groups remain relatively fixed. Although the overall protein structure of MR with bound intermediate analogues is very similar to that of MR with bound (S)-atrolactate, the intermediate-Mg{sup 2+} distance becomes shorter, suggesting a tighter complex with the catalytic Mg{sup 2+}. In addition, Tyr 54 moves closer to the phenyl ring of the bound intermediate analogues, contributing to an overall constriction of the active site cavity. However, site-directed mutagenesis experiments revealed that the role of Tyr 54 in MR catalysis is relatively minor, suggesting that alterations in enzyme structure that contribute to discrimination between the altered substrate in the

  18. Design and synthesis of new fluconazole analogues.

    PubMed

    Pore, Vandana S; Agalave, Sandip G; Singh, Pratiksha; Shukla, Praveen K; Kumar, Vikash; Siddiqi, Mohammad I

    2015-06-21

    We have synthesized new fluconazole analogues containing two different 1,2,3-triazole units in the side chain. The synthesis of new amide analogues using a variety of acids is also described. All the compounds showed very good antifungal activity. A hemolysis study of the most active compounds 6e and 13j showed that both compounds did not cause any hemolysis at the dilutions tested. These compounds did not exhibit any toxicity to L929 cells at MIC and lower concentrations. In the docking study, the overall binding mode of 6e and 13j appeared to be reasonable and provided a good insight into the structural basis of inhibition of Candida albicans Cyp51 by these compounds. PMID:25975803

  19. Efficient synthesis of esermethole and its analogues.

    PubMed

    Zhou, Yongyun; Zhao, Yuanhong; Dai, Xiaoyong; Liu, Jianping; Li, Liang; Zhang, Hongbin

    2011-06-01

    In this work, a general and flexible synthetic route towards the synthesis of pyrroloindoline alkaloids was developed. This new strategy features with a palladium mediated sequential arylation-allylation of o-bromoanilides and leads to the construction of oxindoles bearing a full carbon quaternary center. The cheap triphenylphosphine was proved to be a highly effective ligand for this one pot transformation. On the basis of this new method, esermethole and its analogues were synthesized. PMID:21472186

  20. Synthesis of constrained analogues of tryptophan

    PubMed Central

    Negrato, Marco; Abbiati, Giorgio; Dell’Acqua, Monica

    2015-01-01

    Summary A Lewis acid-catalysed diastereoselective [4 + 2] cycloaddition of vinylindoles and methyl 2-acetamidoacrylate, leading to methyl 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate derivatives, is described. Treatment of the obtained cycloadducts under hydrolytic conditions results in the preparation of a small library of compounds bearing the free amino acid function at C-3 and pertaining to the class of constrained tryptophan analogues. PMID:26664620

  1. Synthesis and cytotoxic activity of acetogenin analogues.

    PubMed

    Rodier, S; Le Huérou, Y; Renoux, B; Doyon, J; Renard, P; Pierré, A; Gesson, J P; Grée, R

    2000-06-19

    A set of 16 new simplified analogues of acetogenins has been designed based on: (i) the replacement of the bis THF moiety of these natural products by an ethylene glycol bis ether unit; (ii) the introduction of different lipophilic side chains (alkyl, aryl, dialkylamino, O-cholesteryl); (iii) the presence of the same terminal isolactone. In vitro cytotoxic activity against L1210 leukemia is reported. PMID:10890167

  2. The Brookhaven electron analogue, 1953--1957

    SciTech Connect

    Plotkin, M.

    1991-12-18

    The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary.

  3. Blood Loss Estimation Using Gauze Visual Analogue

    PubMed Central

    Ali Algadiem, Emran; Aleisa, Abdulmohsen Ali; Alsubaie, Huda Ibrahim; Buhlaiqah, Noora Radhi; Algadeeb, Jihad Bagir; Alsneini, Hussain Ali

    2016-01-01

    Background Estimating intraoperative blood loss can be a difficult task, especially when blood is mostly absorbed by gauze. In this study, we have provided an improved method for estimating blood absorbed by gauze. Objectives To develop a guide to estimate blood absorbed by surgical gauze. Materials and Methods A clinical experiment was conducted using aspirated blood and common surgical gauze to create a realistic amount of absorbed blood in the gauze. Different percentages of staining were photographed to create an analogue for the amount of blood absorbed by the gauze. Results A visual analogue scale was created to aid the estimation of blood absorbed by the gauze. The absorptive capacity of different gauze sizes was determined when the gauze was dripping with blood. The amount of reduction in absorption was also determined when the gauze was wetted with normal saline before use. Conclusions The use of a visual analogue may increase the accuracy of blood loss estimation and decrease the consequences related to over or underestimation of blood loss. PMID:27626017

  4. Probing the C-terminal domain of lipid-free apoA-I demonstrates the vital role of the H10B sequence repeat in HDL formation.

    PubMed

    Mei, Xiaohu; Liu, Mingjing; Herscovitz, Haya; Atkinson, David

    2016-08-01

    apoA-I plays important structural and functional roles in reverse cholesterol transport. We have described the molecular structure of the N-terminal domain, Δ(185-243) by X-ray crystallography. To understand the role of the C-terminal domain, constructs with sequential elongation of Δ(185-243), by increments of 11-residue sequence repeats were studied and compared with Δ(185-243) and WT apoA-I. Constructs up to residue 230 showed progressively decreased percent α-helix with similar numbers of helical residues, similar detergent and lipid binding affinity, and exposed hydrophobic surface. These observations suggest that the C-terminal domain is unstructured with the exception of the last 11-residue repeat (H10B). Similar monomer-dimer equilibrium suggests that the H10B region is responsible for nonspecific aggregation. Cholesterol efflux progressively increased with elongation up to ∼60% of full-length apoA-I in the absence of the H10B. In summary, the sequential repeats in the C-terminal domain are probably unstructured with the exception of H10B. This segment appears to be responsible for initiation of lipid binding and aggregation, as well as cholesterol efflux, and thus plays a vital role during HDL formation. Based on these observations and the Δ(185-243) crystal structure, we propose a lipid-free apoA-I structural model in solution and update the mechanism of HDL biogenesis. PMID:27317763

  5. MicroRNA-10b Triggers the Epithelial-Mesenchymal Transition (EMT) of Laryngeal Carcinoma Hep-2 Cells by Directly Targeting the E-cadherin.

    PubMed

    Zhang, Lin; Sun, Jing; Wang, Bin; Ren, Ji-Chen; Su, Wei; Zhang, Tian

    2015-05-01

    Laryngeal carcinoma is the second most common malignancy of the head and neck squamous cell carcinoma. Therefore, there is an urgent need to understand the molecular mechanism of its metastasis. The present study was designed to investigate effects of miR-10b on the invasion and migration of laryngeal Hep-2 cells. We found that miR-10b had limited effects on cell proliferation; however, it can significantly promote the migration and invasion of Hep-2 cells. Further studies revealed that overexpression of miR-10b can induce the epithelial-mesenchymal transition (EMT) of Hep-2 cells by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin (N-Cad) with a concomitant decrease of E-cadherin (E-Cad). However, the messenger RNA (mRNA) and protein level of transcription factors such as Snail, Slug, Twist and ZEB was not changed during this process. Bioinformatic analysis revealed that miR-10b can directly target CDH1 (E-Cad gene) at nucleotides 461 and 481 within the 3'-UTR. This was confirmed by the results that miR-10 downregulated the protein and mRNA levels of E-Cad via a time-dependent manner and luciferase analysis by use of four-nucleotide substitution in the core binding sites. The present study provided a better understanding of laryngeal carcinoma metastasis and the roles of miR-10b during this process. PMID:25875782

  6. Enhancing HOTAIR/MiR-10b Drives Normal Liver Stem Cells Toward a Tendency to Malignant Transformation Through Inducing Epithelial- to-Mesenchymal Transition.

    PubMed

    Ye, Ping; Wang, Tao; Liu, Wei-Hui; Li, Xiu-Chuan; Tang, Li-Jun; Tian, Fu-Zhou

    2015-08-01

    Previously, other groups and our team consistently have demonstrated that the possible origination of liver cancer stem cells (LCSCs) is the malignant transformation from liver normal stem cells (LNSCs). However, this complex and multi-step process is far from clear due to the accumulation of various gene dysregulations. Because non-coding RNAs (ncRNAs) could regulate multiple genes, a family of genes, and even whole chromosomes, this study further investigated the effect of dysregulated short ncRNA microRNA-10b and long ncRNA HOX transcript antisense RNA (HOTAIR) between LNSCs and LCSCs on phenotype reversion. To clarify the role of ncRNA in malignant transformation of LNSCs, we used lentivirus transduction to enhance the miR-10b and HOTAIR expression levels in our previously isolated rat LNSCs. The malignant abilities of proliferation, invasiveness, and tumorigenesis were observed and compared in cells before and after ncRNAs enhancement. After microRNA-10b and HOTAIR were enhanced separately, several cancer stem cell (CSC)-like traits appeared in these LNSCs, including in vitro-enhanced proliferative capacity, expression of putative LCSC markers, progressive invasive ability, and even in vivo aggravation into and taking the place of normal liver tissue. Furthermore, strengthened expression of these ncRNAs partially degraded E-cadherin in LNSCs, which is one of the classic markers in epithelial-to-mesenchymal transition (EMT). HOTAIR or miR-10b enhanced in LNSCs may drive the LNSCs to a tendency toward malignant transformation. This study partially uncovers the mechanism by which miR-10b or HOTAIR promotes malignant transformation of LNSCs through down-regulating E-cadherin and inducing EMT. PMID:25708830

  7. Encoding complexity within supramolecular analogues of frustrated magnets.

    PubMed

    Cairns, Andrew B; Cliffe, Matthew J; Paddison, Joseph A M; Daisenberger, Dominik; Tucker, Matthew G; Coudert, François-Xavier; Goodwin, Andrew L

    2016-05-01

    The solid phases of gold(I) and/or silver(I) cyanides are supramolecular assemblies of inorganic polymer chains in which the key structural degrees of freedom-namely, the relative vertical shifts of neighbouring chains-are mathematically equivalent to the phase angles of rotating planar ('XY') spins. Here, we show how the supramolecular interactions between chains can be tuned to mimic different magnetic interactions. In this way, the structures of gold(I) and/or silver(I) cyanides reflect the phase behaviour of triangular XY magnets. Complex magnetic states predicted for this family of magnets-including collective spin-vortices of relevance to data storage applications-are realized in the structural chemistry of these cyanide polymers. Our results demonstrate how chemically simple inorganic materials can behave as structural analogues of otherwise inaccessible 'toy' spin models and also how the theoretical understanding of those models allows control over collective ('emergent') phenomena in supramolecular systems. PMID:27102677

  8. Hexaethylsubporphyrins: β-alkyl analogues in the subporphyrin family.

    PubMed

    Chandra, Brijesh; Kumar, B Sathish; Mondal, Navendu; Samanta, Anunay; Panda, Pradeepta K

    2015-12-14

    Two new subporphyrins were synthesized for the first time from a β-substituted pyrrole i.e. 3,4-diethylpyrrole via pyridine-tri-N-(3,4-diethylpyrrolyl)borane as building blocks. These β-hexaethylsubporphyrins are true contracted congeners of β-octaethylporphyrin (OEP). While the meso-triphenyl derivative of hexaethylsubporphyrin could be synthesized by following the reported method, the meso-free analogue could only be synthesized by condensation with trioxane, in the presence of catalytic methanesulfonic acid. These contracted macrocycles display interesting absorption, and emission behaviour including substituent dependent S2 fluorescence owing to the presence of flexible electron donating ethyl groups at their β-positions. The optical response and ultrafast S2 state dynamics of these systems suggest that it may be possible to tune the properties of the subporphyrin to develop efficient systems for solar energy capture and conversion processes. PMID:26524153

  9. Inhibition of topoisomerase II α activity and induction of apoptosis in mammalian cells by semi-synthetic andrographolide analogues.

    PubMed

    Nateewattana, Jintapat; Saeeng, Rungnapha; Kasemsook, Sakkasem; Suksen, Kanoknetr; Dutta, Suman; Jariyawat, Surawat; Chairoungdua, Arthit; Suksamrarn, Apichart; Piyachaturawat, Pawinee

    2013-04-01

    Topoisomerase II α enzyme plays a critical role in DNA replication process. It controls the topologic states of DNA during transcription and is essential for cell proliferation. Human DNA topoisomerase II α (hTopo II α) is a promising chemotherapeutic target for anticancer agents against a variety of cancer types. In the present study, andrographolide and its structurally modified analogues were investigated for their inhibitory activities on hTopo II α enzyme. Five out of nine andrographolide analogues potently reduced hTopo II α activity and inhibited cell proliferation in four mammalian cell lines (Hela, CHO, BCA-1 and HepG2 cells). IC50 values for cytotoxicity of analogues 3A.1, 3A.2, 3A.3, 1B and 2C were 4 to 7 μM. Structure-activity relationship studies revealed that both core structure of andrographolide and silicon based molecule of functional group were important for the inhibition of hTopo II α activity whereas position C-19 of analogues was required for anti-proliferation. In addition, the analogue 2C at 10 μM concentration inhibited hTopo II α, and induced apoptosis with nuclear fragmentation and formation of apoptotic bodies in HepG2 cells. The analogue 2C may, therefore, have a therapeutic potential as effective anticancer agent targeting the hTopo II α functions. PMID:22899371

  10. Inhibition of ATP Synthase by Chlorinated Adenosine Analogue

    PubMed Central

    Chen, Lisa S.; Nowak, Billie J.; Ayres, Mary L.; Krett, Nancy L.; Rosen, Steven T.; Zhang, Shuxing; Gandhi, Varsha

    2009-01-01

    8-Chloroadenosine (8-Cl-Ado) is a ribonucleoside analogue that is currently in clinical trial for chronic lymphocytic leukemia. Based on the decline in cellular ATP pool following 8-Cl-Ado treatment, we hypothesized that 8-Cl-ADP and 8-Cl-ATP may interfere with ATP synthase, a key enzyme in ATP production. Mitochondrial ATP synthase is composed of two major parts; FO intermembrane base and F1 domain, containing α and β subunits. Crystal structures of both α and β subunits that bind to the substrate, ADP, are known in tight binding (αdpβdp) and loose binding (αtpβtp) states. Molecular docking demonstrated that 8-Cl-ADP/8-Cl-ATP occupied similar binding modes as ADP/ATP in the tight and loose binding sites of ATP synthase, respectively, suggesting that the chlorinated nucleotide metabolites may be functional substrates and inhibitors of the enzyme. The computational predictions were consistent with our whole cell biochemical results. Oligomycin, an established pharmacological inhibitor of ATP synthase, decreased both ATP and 8-Cl-ATP formation from exogenous substrates, however, did not affect pyrimidine nucleoside analogue triphosphate accumulation. Synthesis of ATP from ADP was inhibited in cells loaded with 8-Cl-ATP. These biochemical studies are in consent with the computational modeling; in the αtpβtp state 8-Cl-ATP occupies similar binding as ANP, a non-hydrolyzable ATP mimic that is a known inhibitor. Similarly, in the substrate binding site (αdpβdp) 8-Cl-ATP occupies a similar position as ATP mimic ADP-BeF3 −. Collectively, our current work suggests that 8-Cl-ADP may serve as a substrate and the 8-Cl-ATP may be an inhibitor of ATP synthase. PMID:19477165

  11. Three Efficient Methods for Preparation of Coelenterazine Analogues.

    PubMed

    Shakhmin, Anton; Hall, Mary P; Walker, Joel R; Machleidt, Thomas; Binkowski, Brock F; Wood, Keith V; Kirkland, Thomas A

    2016-07-18

    The growing popularity of bioluminescent assays has highlighted the need for coelenterazine analogues possessing properties tuned for specific applications. However, the structural diversity of known coelenterazine analogues has been limited by current syntheses. Known routes for the preparation of coelenterazine analogues employ harsh reaction conditions that limit access to many substituents and functional groups. Novel synthetic routes reported here establish simple and robust methods for synthesis and investigation of structurally diverse marine luciferase substrates. Specifically, these new routes allow synthesis of coelenterazine analogues containing various heterocyclic motifs and substituted aromatic groups with diverse electronic substituents at the R(2) position. Interesting analogues described herein were characterized by their physicochemical properties, bioluminescent half-life, light output, polarity and cytotoxicity. Some of the analogues represent leads that can be utilized in the development of improved bioluminescent systems. PMID:27305599

  12. U.S. Nuclear Regulatory Commission natural analogue research program

    SciTech Connect

    Kovach, L.A.; Ott, W.R.

    1995-09-01

    This article describes the natural analogue research program of the U.S. Nuclear Regulatory Commission (US NRC). It contains information on the regulatory context and organizational structure of the high-level radioactive waste research program plan. It also includes information on the conditions and processes constraining selection of natural analogues, describes initiatives of the US NRC, and describes the role of analogues in the licensing process.

  13. CO2 Removal using a Synthetic Analogue of Carbonic Anhydrase

    SciTech Connect

    Cordatos, Harry

    2010-09-14

    Project attempts to develop a synthetic analogue for carbonic anhydrase and incorporate it in a membrane for separation of CO2 from coal power plant flue gas. Conference poster presents result of first 9 months of project progress including concept, basic system architecture and membrane properties target, results of molecular modeling for analogue - CO2 interaction, and next steps of testing analogue resistance to flue gas contaminants.

  14. Conformationally restrained aromatic analogues of fosmidomycin and FR900098.

    PubMed

    Kurz, Thomas; Schlüter, Katrin; Pein, Miriam; Behrendt, Christoph; Bergmann, Bärbel; Walter, Rolf D

    2007-07-01

    The synthesis and in-vitro antimalarial activity of conformationally restrained bis(pivaloyloxymethyl) ester analogues of the natural product fosmidomycin is presented. In contrast to alpha-aryl-substituted analogues, conformationally restrained aromatic analogues exhibit only moderate in-vitro antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. The most active derivative displays an IC(50) value of 47 microM. PMID:17611943

  15. Phonon analogue of topological nodal semimetals

    NASA Astrophysics Data System (ADS)

    Po, Hoi Chun; Bahri, Yasaman; Vishwanath, Ashvin

    2015-03-01

    Recently, Kane and Lubensky proposed a mapping between bosonic phonon problems on isostatic lattices to chiral fermion systems based on factorization of the dynamical matrix [Nat. Phys. 10, 39 (2014)]. The existence of topologically protected zero modes in such mechanical problems is related to their presence in the fermionic system and is dictated by a local index theorem. Here we adopt the proposed mapping to construct a two-dimensional mechanical analogue of a fermionic topological nodal semimetal that hosts a robust bulk node in its linearized phonon spectrum. Such topologically protected soft modes with tunable wavevector may be useful in designing mechanical structures with fault-tolerant properties.

  16. Digitoxin Analogues with Improved Anticytomegalovirus Activity

    PubMed Central

    2014-01-01

    Cardiac glycosides are potent inhibitors of cancer cell growth and possess antiviral activities at nanomolar concentrations. In this study we evaluated the anticytomegalovirus (CMV) activity of digitoxin and several of its analogues. We show that sugar type and sugar length attached to the steroid core structure affects its anticytomegalovirus activity. Structure–activity relationship (SAR) studies identified the l-sugar containing cardiac glycosides as having improved anti-CMV activity and may lead to better understanding of how these compounds inhibit CMV replication. PMID:24900847

  17. Analogue factoring algorithm based on polychromatic interference

    NASA Astrophysics Data System (ADS)

    Tamma, Vincenzo; Garuccio, Augusto; Shih, Yanhua

    2010-08-01

    We present a novel factorization algorithm which can be computed using an analogue computer based on a polychromatic source with a given wavelength bandwidth, a multi-path interferometer and a spectrometer. The core of this algorithm stands on the measurement of the periodicity of a "factoring" function given by an exponential sum at continuous argument by recording a sequence of interferograms associated with suitable units of displacement in the inteferometer. A remarking rescaling property of such interferograms allows, in principle, the prime number decomposition of several large integers. The information about factors is encoded in the location of the inteferogram maxima.

  18. Spectroscopic study of solar twins and analogues

    NASA Astrophysics Data System (ADS)

    Datson, Juliet; Flynn, Chris; Portinari, Laura

    2015-02-01

    Context. Many large stellar surveys have been and are still being carried out, providing huge amounts of data, for which stellar physical parameters will be derived. Solar twins and analogues provide a means to test the calibration of these stellar catalogues because the Sun is the best-studied star and provides precise fundamental parameters. Solar twins should be centred on the solar values. Aims: This spectroscopic study of solar analogues selected from the Geneva-Copenhagen Survey (GCS) at a resolution of 48 000 provides effective temperatures and metallicities for these stars. We test whether our spectroscopic parameters, as well as the previous photometric calibrations, are properly centred on the Sun. In addition, we search for more solar twins in our sample. Methods: The methods used in this work are based on literature methods for solar twin searches and on methods we developed in previous work to distinguish the metallicity-temperature degeneracies in the differential comparison of spectra of solar analogues versus a reference solar reflection spectrum. Results: We derive spectroscopic parameters for 148 solar analogues (about 70 are new entries to the literature) and verify with a-posteriori differential tests that our values are well-centred on the solar values. We use our dataset to assess the two alternative calibrations of the GCS parameters; our methods favour the latest revision. We show that the choice of spectral line list or the choice of asteroid or time of observation does not affect the results. We also identify seven solar twins in our sample, three of which are published here for the first time. Conclusions: Our methods provide an independent means to differentially test the calibration of stellar catalogues around the values of a well-known benchmark star, which makes our work interesting for calibration tests of upcoming Galactic surveys. Based on observations made with ESO Telescopes at the La Silla Observatory under programme ID 077.D

  19. Cross-section measurement for the 10B(n, alpha)7Li reaction at 4.0 and 5.0 MeV.

    PubMed

    Zhang, Guohui; Guo, Li'an; Cao, Rongtai; Zhang, Jiaguo; Chen, Jinxiang

    2008-10-01

    Cross-sections of the (10)B(n, alpha)(7)Li reaction were measured at En=4.0 and 5.0 MeV. A gridded ionization chamber (GIC) was used as charged particle detector. Neutrons were produced through the D(d, n)(3)He reaction with a deuterium gas target. Experiments were performed at the 4.5 MV Van de Graaff accelerator of Peking University. Cross-section data of the (238)U(n, f) reaction were employed as standard. The measured cross-sections of the (10)B(n, alpha)(7)Li reaction at 4.0 and 5.0 MeV are 211+/-17 and 169+/-14 mb, respectively, and they are compared with existing results of measurements and evaluations. PMID:18387305

  20. Charged analogues of Schwarzschild interior solution in terms of pressure

    NASA Astrophysics Data System (ADS)

    Bijalwan, Naveen

    2011-12-01

    Recently, Bijalwan (Astrophys. Space Sci., doi:10.1007/s10509-011-0691-0, 2011a) discussed charged fluid spheres with pressure while Bijalwan and Gupta (Astrophys. Space Sci. 317, 251-260, 2008) suggested using a monotonically decreasing function f to generate all possible physically viable charged analogues of Schwarzschild interior solutions analytically. They discussed some previously known and new solutions for Schwarzschild parameter u( =GM/c^{2a} ) le 0.142, a being radius of star. In this paper we investigate wide range of u by generating a class of solutions that are well behaved and suitable for modeling Neutron star charge matter. We have exploited the range u≤0.142 by considering pressure p= p( ω) and f = ( f0(1 - R2(1 - ω )/a2) +faR2(1 - ω )/a2 ), where ω = 1 -r2/R2 to explore new class of solutions. Hence, class of charged analogues of Schwarzschild interior is found for barotropic equation of state relating the radial pressure to the energy density. The analytical models thus found are well behaved with surface red shift z s ≤0.181, central red shift z c ≤0.282, mass to radius ratio M/ a≤0.149, total charge to total mass ratio e/ M≤0.807 and satisfy Andreasson's (Commun. Math. Phys. 288, 715-730, 2009) stability condition. Red-shift, velocity of sound and p/ c 2 ρ are monotonically decreasing towards the surface while adiabatic index is monotonically increasing. The maximum mass found to be 1.512 M Θ with linear dimension 14.964 km. Class of charged analogues of Schwarzschild interior discussed in this paper doesn't have neutral counter part. These solutions completely describe interior of a stable Neutron star charge matter since at centre the charge distribution is zero, e/ M≤0.807 and a typical neutral Neutron star has mass between 1.35 and about 2.1 solar mass, with a corresponding radius of about 12 km (Kiziltan et al., arXiv:1011.4291 [astro-ph.GA], 2010).

  1. Isoelectronic analogues of PN: Remarkably stable multiply charged cations

    SciTech Connect

    Wong, Ming Wah; Radom, L. )

    1990-01-25

    The structures and stabilities of PN and its 27 isoelectronic analogues, CS, SiO, BCl, AlF, BeAr, MgNe, Sn{sup +}, PO{sup +}, CCl{sup +}, SiF{sup +}, BAr{sup +}, AlNe{sup +}, SO{sup 2+}, NCl{sup 2+}, PF{sup 2+}, CAr{sup 2+}, SiNe{sup 2+}, OCl{sup 3+}, SF{sup 3+}, NAr{sup 3+}, PNe{sup 3+}, FCl{sup 4+}, OAr{sup 4+}, SNe{sup 4+}, FAr{sup 5+}, ClNe{sup 5+}, and ArNe{sup 6+}, have been examined by ab initio molecular orbital theory. The CASSCF/6-311G(MC)(d) level was used to determine the ground-state potential energy curves and spectroscopic constants for the 28 diatomic systems. Equilibrium structures were also obtained with the 6-311G(MC)(d) basis set at the MP3 and ST4CCD levels, and dissociation energies were determined at the MP4/6-311 + G(MC)(2df) and MP4/6-311 + G(MC)(3d2f) levels. For the neutral and monocation analogues of PN, the calculated equilibrium geometries (at MP3/6-311G(MC)(d)) and dissociation energies (at MP4/6-311 + G(MC)(3d2f)) are in very good agreement with available experimental values. All the dication analogues of PN, namely, SO{sup 2+}, NCl{sup 2+}, PF{sup 2+}, CAr{sup 2+}, and SiNe{sup 2+}, are predicted to be experimentally observable species. Of these, the SO{sup 2+}, NCl{sup 2+}, and CAr{sup 2+} dications are calculated to be kinetically stable species, with large barriers associated with the exothermic charge-separation reactions, while the PF{sup 2+} and SiNe{sup 2+} dications are predicted not only to be kinetically stable but also to be thermodynamically stable species.

  2. KELT-10b: The First Transiting Exoplanet from the KELT-South Survey - A Hot Sub-Jupiter Transiting a V=10.7 Early G-Star

    NASA Astrophysics Data System (ADS)

    Kuhn, Rudolf B.; Rodriguez, Joseph E.; Collins, Karen A.; Lund, Michael B.; Siverd, Robert J.; Colón, Knicole D.; Pepper, Joshua; Stassun, Keivan G.; Cargile, Phillip A.; James, David J.; Penev, Kaloyan; Zhou, George; Bayliss, Daniel; Tan, T. G.; Curtis, Ivan A.; Udry, Stephane; Segransan, Damien; Mawet, Dimitri; Dhital, Saurav; Soutter, Jack; Hart, Rhodes; Carter, Brad; Gaudi, B. Scott; Myers, Gordon; Beatty, Thomas G.; Eastman, Jason D.; Reichart, Daniel E.; Haislip, Joshua B.; Kielkopf, John; Bieryla, Allyson; Latham, David W.; Jensen, Eric L. N.; Oberst, Thomas E.; Stevens, Daniel J.

    2016-04-01

    We report the discovery of KELT-10b, the first transiting exoplanet discovered using the KELT-South telescope. KELT-10b is a highly inflated sub-Jupiter mass planet transiting a relatively bright V = 10.7 star (TYC 8378-64-1), with Teff = 5948 ± 74 K, log g = 4.319_{-0.030}^{+0.020} and [Fe/H] = 0.09_{-0.10}^{+0.11}, an inferred mass M★ = 1.112_{-0.061}^{+0.055} M⊙ and radius R★ = 1.209_{-0.035}^{+0.047} R⊙. The planet has a radius Rp = 1.399_{-0.049}^{+0.069} RJ and mass Mp = 0.679_{-0.038}^{+0.039} MJ. The planet has an eccentricity consistent with zero and a semi-major axis a = 0.05250_{-0.00097}^{+0.00086} AU. The best fitting linear ephemeris is T0 = 2457066.72045±0.00027 BJDTDB and P = 4.1662739±0.0000063 days. This planet joins a group of highly inflated transiting exoplanets with a radius larger and a mass less than that of Jupiter. The planet, which boasts deep transits of 1.4%, has a relatively high equilibrium temperature of Teq = 1377_{-23}^{+28} K, assuming zero albedo and perfect heat redistribution. KELT-10b receives an estimated insolation of 0.817_{-0.054}^{+0.068} × 109 erg s-1 cm-2, which places it far above the insolation threshold above which hot Jupiters exhibit increasing amounts of radius inflation. Evolutionary analysis of the host star suggests that KELT-10b may not survive beyond the current subgiant phase, depending on the rate of in-spiral of the planet over the next few Gyr. The planet transits a relatively bright star and exhibits the third largest transit depth of all transiting exoplanets with V < 11 in the southern hemisphere, making it a promising candidate for future atmospheric characterization studies.

  3. Predictive Value of Serum miR-10b, miR-29c, and miR-205 as Promising Biomarkers in Esophageal Squamous Cell Carcinoma Screening

    PubMed Central

    Xu, Hang; Yao, Yuanfei; Meng, Fanyu; Qian, Xu; Jiang, Xiaofeng; Li, Xiaoxi; Gao, Zhuo; Gao, Lu

    2015-01-01

    Abstract Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide. The high mortality of ESCC is mainly due to late diagnosis. Current detection methods have their own weakness, including high costs and invasive procedures. MicroRNA assays are shown to have great potential to be accurate and noninvasive methods for ESCC screening. In this study, we selected 3 microRNAs, miR-10b, miR-29c, and miR-205, to assess their diagnostic value in ESCC screening. Fifty ESCC patients and 50 healthy controls are recruited in our study. Blood samples are collected from the total 100 participants. MicroRNAs were extracted from serum and quantified by qRT-PCR, which their relative expressions were normalized by internal control, U6 snRNA. Statistical analyses were conducted to compare microRNAs level as well as other clinical characteristics between 2 groups. The levels of serum miR-29c and miR-205 were significantly downregulated in ESCC patients compared with healthy volunteers. In contrast, ESCC patients appeared to have a higher level of miR-10b than healthy controls. ROC curve analyses revealed that the AUC value for miR-10b, miR-29c, and miR-205 were 0.85 (95% CI: 0.79–0.93; sensitivity = 76%; specificity = 84%), 0.72 (95% CI: 0.62–0.82; sensitivity = 68%; specificity = 68%), and 0.72 (95% CI: 0.62–0.83; sensitivity = 70%; specificity = 64%), respectively, suggesting that miR-10b, miR-29c, and miR-205 have great potential to be noninvasive screening tools for ESCC detection. PMID:26554762

  4. Purification, crystallization and crystallographic analysis of Clostridium thermocellum endo-1,4-β-d-xylanase 10B in complex with xylohexaose

    SciTech Connect

    Najmudin, Shabir; Pinheiro, Benedita A.; Romão, Maria J.; Prates, José A. M.; Fontes, Carlos M. G. A.

    2008-08-01

    The N-terminal moiety of C. thermocellum endo-1,4-β-d-xylanase 10B, comprising a carbohydrate-binding module (CBM22-1) and a GH10 E337A mutant domain, has been crystallized in complex with xylohexaose. The crystals belong to the trigonal space group P3{sub 2}21, contain a dimer in the asymmetric unit and diffract to beyond 2.0 Å resolution. The cellulosome of Clostridium thermocellum is a highly organized multi-enzyme complex of cellulases and hemicellulases involved in the hydrolysis of plant cell-wall polysaccharides. The bifunctional multi-modular xylanase Xyn10B is one of the hemicellulase components of the C. thermocellum cellulosome. The enzyme contains an internal glycoside hydrolase family 10 catalytic domain (GH10) and a C-terminal family 1 carbohydrate esterase domain (CE1). The N-terminal moiety of Xyn10B (residues 32–551), comprising a carbohydrate-binding module (CBM22-1) and the GH10 E337A mutant, was crystallized in complex with xylohexaose. The crystals belong to the trigonal space group P3{sub 2}21 and contain a dimer in the asymmetric unit. The crystals diffracted to beyond 2.0 Å resolution.

  5. Using the Doppler broadened γ line of the 10B(n,αγ)7Li reaction for thermal neutron detection

    NASA Astrophysics Data System (ADS)

    Ben-Galim, Y.; Wengrowicz, U.; Moreh, R.; Orion, I.; Raveh, A.

    2016-02-01

    When a thermal neutron is absorbed by 10B in the 10B(n,α)7Li reaction, there is a chance of 94% that a 478 keV photon be emitted by an excited 7Li nucleus. This reaction is exothermic with a Q-value of 2.31 MeV and the nuclei are emitted with kinetic energies of E(α)=1.47 MeV and E(7Li*)=0.84 MeV. This implies that the 478 keV γ line is emitted by a moving 7Li nucleus and hence is expected to be Doppler broadened. In the present work we suggest to use this broadening of the γ line as a fingerprint for the detection of thermal neutrons using a high resolution gamma spectrometer. We thus developed a Monte Carlo program using a MATLAB code based on a High Purity Germanium (HPGe) detector coupled with a Boron Carbide (B4C) sheet to calculate the γ line broadening. Our simulation shows that the FWHM width of the resulting γ line is 12.6 keV, in good agreement with our measurement. Hence the broadened γ line emitted by the 10B(n,αγ)7Li reaction and detected by a HPGe detector shows that this method is an effective tool for neutron detection while maintaining good gamma discrimination.

  6. Context-dependent differences in miR-10b breast oncogenesis can be targeted for the prevention and arrest of lymph node metastasis

    PubMed Central

    Yigit, MV; Ghosh, SK; Kumar, M; Petkova, V; Kavishwar, A; Moore, A; Medarova, Z

    2013-01-01

    Metastases, and not the primary tumor from which they originate, are the main reason for mortality from carcinoma. Although the molecular mechanisms behind metastasis are poorly understood, it is clear that epigenetic dysregulation at the level of microRNA expression is a key characteristic of the metastatic process that can be exploited for therapy. Here, we describe an miRNA-targeted therapeutic approach for the prevention and arrest of lymph node metastasis. Therapy relies on the inhibition of the pro-metastatic microRNA-10b. It is delivered to primary and lymph node metastatic tumor cells using an imaging-capable nanodrug that is designed to specifically home to these tissues. Treatment of invasive human breast tumor cells (MDA-MB-231) with the nanodrug in vitro downregulates miR-10b and abolishes the invasion and migration of the tumor cells. After intravenous delivery to mice bearing orthotopic MDA-MB-231-luc-D3H2LN tumors, the nanodrug accumulates in the primary tumor and lymph nodes. When treatment is initiated before metastasis to lymph nodes, metastasis is prevented. Treatment after the formation of lymph node metastases arrests the metastatic process without a concomitant effect on primary tumor growth raising the possibility of a context-dependent variation in miR-10b breast oncogenesis. PMID:22580603

  7. Long-term predictions using natural analogues

    SciTech Connect

    Ewing, R.C.

    1995-09-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  8. Self-Powered Analogue Smart Skin.

    PubMed

    Shi, Mayue; Zhang, Jinxin; Chen, Haotian; Han, Mengdi; Shankaregowda, Smitha A; Su, Zongming; Meng, Bo; Cheng, Xiaoliang; Zhang, Haixia

    2016-04-26

    The progress of smart skin technology presents unprecedented opportunities for artificial intelligence. Resolution enhancement and energy conservation are critical to improve the perception and standby time of robots. Here, we present a self-powered analogue smart skin for detecting contact location and velocity of the object, based on a single-electrode contact electrification effect and planar electrostatic induction. Using an analogue localizing method, the resolution of this two-dimensional smart skin can be achieved at 1.9 mm with only four terminals, which notably decreases the terminal number of smart skins. The sensitivity of this smart skin is remarkable, which can even perceive the perturbation of a honey bee. Meanwhile, benefiting from the triboelectric mechanism, extra power supply is unnecessary for this smart skin. Therefore, it solves the problems of batteries and connecting wires for smart skins. With microstructured poly(dimethylsiloxane) films and silver nanowire electrodes, it can be covered on the skin with transparency, flexibility, and high sensitivity. PMID:27010713

  9. An analogue of Weyl’s law for quantized irreducible generalized flag manifolds

    SciTech Connect

    Matassa, Marco E-mail: mmatassa@math.uio.no

    2015-09-15

    We prove an analogue of Weyl’s law for quantized irreducible generalized flag manifolds. This is formulated in terms of a zeta function which, similarly to the classical setting, satisfies the following two properties: as a functional on the quantized algebra it is proportional to the Haar state and its first singularity coincides with the classical dimension. The relevant formulas are given for the more general case of compact quantum groups.

  10. Spin-orbit laser mode transfer via a classical analogue of quantum teleportation

    NASA Astrophysics Data System (ADS)

    Pinheiro da Silva, B.; Astigarreta Leal, M.; Souza, C. E. R.; Galvão, E. F.; Khoury, A. Z.

    2016-03-01

    We translate the quantum teleportation protocol into a sequence of coherent operations involving three degrees of freedom of a classical laser beam. The protocol, which we demonstrate experimentally, transfers the polarization state of the input beam to the transverse mode of the output beam. The role of quantum entanglement is played by a non-separable mode describing the path and transverse degrees of freedom. Our protocol illustrates the possibility of new optical applications based on this intriguing classical analogue of quantum entanglement.

  11. Functional Analysis: The Use of Analogues in Applied Settings.

    ERIC Educational Resources Information Center

    Stichter, Janine Peck

    2001-01-01

    This article suggests possible applications of experimental analyses using analogues to empirically verify results of functional assessments in classrooms for students with autism and related disabilities. Analogue assessments involve creating conditions in which antecedents and consequences are held constant and specific variables suspected to…

  12. Space Analogue Environments: Are the Populations Comparable?

    NASA Astrophysics Data System (ADS)

    Sandal, G. M.

    Background: Much of our present understanding about psychology in space is based on studies of groups operating in so-called analogue environments where personnel are exposed to many of the same stressors as those experienced by astronauts in space. One possible problem with extrapolating results is that personnel operating in various hazardous and confined environments might differ in characteristics influencing coping, interaction, and performance. The object of this study was to compare the psychological similarity of these populations in order to get a better understanding of whether this extrapolation is justifiable. The samples investigated include polar crossings (N= 22), personnel on Antarctic research stations (N= 183), several military occupations (N= 187), and participants in space simulation studies (N=20). Methods: Personnel in each of these environments were assessed using the Personality Characteristic Inventory (PCI) and Utrecht Coping List (UCL). The PCI is a multidimensional trait assessment battery that measures various aspects of achievement orientation and social competence. The UCL is a questionnaire designed to assess habitual coping strategies when encountering stressful or demanding situations. Results: Only minor differences in use of habitual coping strategies were evident across the different samples. In relation to personality scores, the military subjects and participants in space simulation studies indicated higher competitiveness and negative instrumentality compared to both the personnel on Antarctic research stations and participants in polar expedition. Among the personnel on Antarctic research stations, significant gender differences were found with women scoring lower on competitiveness, negative instrumentality and impatience/irritability. Compared to the other samples, the participants in polar expeditions were found to be more homogeneous in personality and no significant gender differences were evident on the traits that

  13. Development of new mitomycin C and porfiromycin analogues.

    PubMed

    Iyengar, B S; Lin, H J; Cheng, L; Remers, W A; Bradner, W T

    1981-08-01

    New mitomycin C and porfiromycin analogues were prepared by treating mitomycin A and N-methylmitomycin A with a variety of amines, including aziridines, allylamines, propargylamines, chloroalkylamines, hydroxyalkylamines, glycine derivatives, aralkylamines, and heterocyclic amines. All analogues were evaluated against P-388 murine leukemia and selected ones were examined for their leukopenic properties. Certain analogues were found to be superior to mitomycin C in potency, efficacy, and therapeutic ratio in the P-388 assay. The most active substituents at the mitosane 7 position included aziridine, 2-methylaziridine, propargylamine, furfurylamine, methyl glycinate, and 3-aminopyridine. Mitomycin A and the 7-aziridino, 7-(2-methylaziridino), and 3-aminopyridine analogues were less leukopenic than mitomycin C. Certain other analogues, including propargylamino and methyl glycinate, were highly leukopenic. The three compounds tested against B-16 melanoma in mice were significantly more effective than mitomycin C in this assay. Previously established structure--activity relationships were found inadequate to account for all of the new data. PMID:7328599

  14. Synthesis and biological activity of tetralone abscisic acid analogues.

    PubMed

    Nyangulu, James M; Nelson, Ken M; Rose, Patricia A; Gai, Yuanzhu; Loewen, Mary; Lougheed, Brenda; Quail, J Wilson; Cutler, Adrian J; Abrams, Suzanne R

    2006-04-01

    Bicyclic analogues of the plant hormone abscisic acid (ABA) were designed to incorporate the structural elements and functional groups of the parent molecule that are required for biological activity. The resulting tetralone analogues were predicted to have enhanced biological activity in plants, in part because oxidized products would not cyclize to forms corresponding to the inactive catabolite phaseic acid. The tetralone analogues were synthesized in seven steps from 1-tetralone and a range of analogues were accessible through a second route starting with 2-methyl-1-naphthol. Tetralone ABA 8 was found to have greater activity than ABA in two bioassays. The absolute configuration of (+)-8 was established by X-ray crystallography of a RAMP hydrazone derivative. The hydroxymethyl compounds 10 and 11, analogues for studying the roles of 8- and 9-hydroxy ABA 3 and 6, were also synthesized and found to be active. PMID:16557330

  15. Derivatisable Cyanobactin Analogues: A Semisynthetic Approach

    PubMed Central

    Oueis, Emilia; Adamson, Catherine; Mann, Greg; Ludewig, Hannes; Redpath, Philip; Migaud, Marie

    2015-01-01

    Abstract Many natural cyclic peptides have potent and potentially useful biological activities. Their use as therapeutic starting points is often limited by the quantities available, the lack of known biological targets and the practical limits on diversification to fine‐tune their properties. We report the use of enzymes from the cyanobactin family to heterocyclise and macrocyclise chemically synthesised substrates so as to allow larger‐scale syntheses and better control over derivatisation. We have made cyclic peptides containing orthogonal reactive groups, azide or dehydroalanine, that allow chemical diversification, including the use of fluorescent labels that can help in target identification. We show that the enzymes are compatible and efficient with such unnatural substrates. The combination of chemical synthesis and enzymatic transformation could help renew interest in investigating natural cyclic peptides with biological activity, as well as their unnatural analogues, as therapeutics. PMID:26507241

  16. Solution Processed PEDOT Analogues in Electrochemical Supercapacitors.

    PubMed

    Österholm, Anna M; Ponder, James F; Kerszulis, Justin A; Reynolds, John R

    2016-06-01

    We have designed fully soluble ProDOTx-EDOTy copolymers that are electrochemically equivalent to electropolymerized PEDOT without using any surfactants or dispersants. We show that these copolymers can be incorporated as active layers in solution processed thin film supercapacitors to demonstrate capacitance, stability, and voltage similar to the values of those that use electrodeposited PEDOT as the active material with the added advantage of the possibility for large scale, high-throughput processing. These Type I supercapacitors provide exceptional cell voltages (up to 1.6 V), highly symmetrical charge/discharge behavior, promising long-term stability exceeding 50 000 charge/discharge cycles, as well as energy (4-18 Wh/kg) and power densities (0.8-3.3 kW/kg) that are comparable to those of electrochemically synthesized analogues. PMID:27195798

  17. Natural analogues of nuclear waste glass corrosion.

    SciTech Connect

    Abrajano, T.A. Jr.; Ebert, W.L.; Luo, J.S.

    1999-01-06

    This report reviews and summarizes studies performed to characterize the products and processes involved in the corrosion of natural glasses. Studies are also reviewed and evaluated on how well the corrosion of natural glasses in natural environments serves as an analogue for the corrosion of high-level radioactive waste glasses in an engineered geologic disposal system. A wide range of natural and experimental corrosion studies has been performed on three major groups of natural glasses: tektite, obsidian, and basalt. Studies of the corrosion of natural glass attempt to characterize both the nature of alteration products and the reaction kinetics. Information available on natural glass was then compared to corresponding information on the corrosion of nuclear waste glasses, specifically to resolve two key questions: (1) whether one or more natural glasses behave similarly to nuclear waste glasses in laboratory tests, and (2) how these similarities can be used to support projections of the long-term corrosion of nuclear waste glasses. The corrosion behavior of basaltic glasses was most similar to that of nuclear waste glasses, but the corrosion of tektite and obsidian glasses involves certain processes that also occur during the corrosion of nuclear waste glasses. The reactions and processes that control basalt glass dissolution are similar to those that are important in nuclear waste glass dissolution. The key reaction of the overall corrosion mechanism is network hydrolysis, which eventually breaks down the glass network structure that remains after the initial ion-exchange and diffusion processes. This review also highlights some unresolved issues related to the application of an analogue approach to predicting long-term behavior of nuclear waste glass corrosion, such as discrepancies between experimental and field-based estimates of kinetic parameters for basaltic glasses.

  18. Evolving a polymerase for hydrophobic base analogues.

    PubMed

    Loakes, David; Gallego, José; Pinheiro, Vitor B; Kool, Eric T; Holliger, Philipp

    2009-10-21

    Hydrophobic base analogues (HBAs) have shown great promise for the expansion of the chemical and coding potential of nucleic acids but are generally poor polymerase substrates. While extensive synthetic efforts have yielded examples of HBAs with favorable substrate properties, their discovery has remained challenging. Here we describe a complementary strategy for improving HBA substrate properties by directed evolution of a dedicated polymerase using compartmentalized self-replication (CSR) with the archetypal HBA 5-nitroindole (d5NI) and its derivative 5-nitroindole-3-carboxamide (d5NIC) as selection substrates. Starting from a repertoire of chimeric polymerases generated by molecular breeding of DNA polymerase genes from the genus Thermus, we isolated a polymerase (5D4) with a generically enhanced ability to utilize HBAs. The selected polymerase. 5D4 was able to form and extend d5NI and d5NIC (d5NI(C)) self-pairs as well as d5NI(C) heteropairs with all four bases with efficiencies approaching, or exceeding, those of the cognate Watson-Crick pairs, despite significant distortions caused by the intercalation of the d5NI(C) heterocycles into the opposing strand base stack, as shown by nuclear magnetic resonance spectroscopy (NMR). Unlike Taq polymerase, 5D4 was also able to extend HBA pairs such as Pyrene: varphi (abasic site), d5NI: varphi, and isocarbostyril (ICS): 7-azaindole (7AI), allowed bypass of a chemically diverse spectrum of HBAs, and enabled PCR amplification with primers comprising multiple d5NI(C)-substitutions, while maintaining high levels of catalytic activity and fidelity. The selected polymerase 5D4 promises to expand the range of nucleobase analogues amenable to replication and should find numerous applications, including the synthesis and replication of nucleic acid polymers with expanded chemical and functional diversity. PMID:19778048

  19. Resonance IR: a coherent multidimensional analogue of resonance Raman.

    PubMed

    Boyle, Erin S; Neff-Mallon, Nathan A; Handali, Jonathan D; Wright, John C

    2014-05-01

    This work demonstrates the use of triply resonant sum frequency (TRSF) spectroscopy as a "resonance IR" analogue to resonance Raman spectroscopy. TRSF is a four-wave-mixing process where three lasers with independent frequencies interact coherently with a sample to generate an output at their triple summation frequency. The first two lasers are in the infrared and result in two vibrational excitations, while the third laser is visible and induces a two-quantum anti-Stokes resonance Raman transition. The signal intensity grows when the laser frequencies are all in resonance with coupled vibrational and electronic states. The method therefore provides electronic enhancement of IR-active vibrational modes. These modes may be buried beneath solvent in the IR spectrum and also be Raman-inactive and therefore inaccessible by other techniques. The method is presented on the centrosymmetric complex copper phthalocyanine tetrasulfonate. In this study, the two vibrational frequencies were scanned across ring-breathing modes, while the visible frequency was left in resonance with the copper phthalocyanine tetrasulfonate Q band, resulting in a two-dimensional infrared plot that also reveals coupling between vibrational states. TRSF has the potential to be a very useful probe of structurally similar biological motifs such as hemes, as well as synthetic transition-metal complexes. PMID:24707979

  20. Mechanism of cis-prenyltransferase reaction probed by substrate analogues

    SciTech Connect

    Lu, Yen-Pin; Liu, Hon-Ge; Teng, Kuo-Hsun; Liang, Po-Huang

    2010-10-01

    Research highlights: {yields} The extremely slow trans-OPPS reaction using 2-Fluoro-FPP supports the sequential mechanism with the carbocation intermediate. {yields} The similar UPPS reaction rate under single turnover supports the concerted mechanism, without the carbocation intermediate. {yields} The secondary kinetic isotope effect also supports associate transition state for UPPS reaction, without the carbocation intermediate. -- Abstract: Undecaprenyl pyrophosphate synthase (UPPS) is a cis-type prenyltransferases which catalyzes condensation reactions of farnesyl diphosphate (FPP) with eight isopentenyl pyrophosphate (IPP) units to generate C{sub 55} product. In this study, we used two analogues of FPP, 2-fluoro-FPP and [1,1-{sup 2}H{sub 2}]FPP, to probe the reaction mechanism of Escherichia coli UPPS. The reaction rate of 2-fluoro-FPP with IPP under single-turnover condition is similar to that of FPP, consistent with the mechanism without forming a farnesyl carbocation intermediate. Moreover, the deuterium secondary KIE of 0.985 {+-} 0.022 measured for UPPS reaction using [1,1-{sup 2}H{sub 2}]FPP supports the associative transition state. Unlike the sequential mechanism used by trans-prenyltransferases, our data demonstrate E. coli UPPS utilizes the concerted mechanism.

  1. KELT-10b: the first transiting exoplanet from the KELT-South survey - a hot sub-Jupiter transiting a V = 10.7 early G-star

    NASA Astrophysics Data System (ADS)

    Kuhn, Rudolf B.; Rodriguez, Joseph E.; Collins, Karen A.; Lund, Michael B.; Siverd, Robert J.; Colón, Knicole D.; Pepper, Joshua; Stassun, Keivan G.; Cargile, Phillip A.; James, David J.; Penev, Kaloyan; Zhou, George; Bayliss, Daniel; Tan, T. G.; Curtis, Ivan A.; Udry, Stephane; Segransan, Damien; Mawet, Dimitri; Dhital, Saurav; Soutter, Jack; Hart, Rhodes; Carter, Brad; Gaudi, B. Scott; Myers, Gordon; Beatty, Thomas G.; Eastman, Jason D.; Reichart, Daniel E.; Haislip, Joshua B.; Kielkopf, John; Bieryla, Allyson; Latham, David W.; Jensen, Eric L. N.; Oberst, Thomas E.; Stevens, Daniel J.

    2016-07-01

    We report the discovery of KELT-10b, the first transiting exoplanet discovered using the KELT-South telescope. KELT-10b is a highly inflated sub-Jupiter mass planet transiting a relatively bright V = 10.7 star (TYC 8378-64-1), with Teff = 5948 ± 74 K, log g = 4.319_{-0.030}^{+0.020} and [Fe/H] = 0.09_{-0.10}^{+0.11}, an inferred mass M* = 1.112_{-0.061}^{+0.055} M⊙ and radius R* = 1.209_{-0.035}^{+0.047} R⊙. The planet has a radius Rp = 1.399_{-0.049}^{+0.069} RJ and mass Mp = 0.679_{-0.038}^{+0.039} MJ. The planet has an eccentricity consistent with zero and a semimajor axis a = 0.052 50_{-0.000 97}^{+0.000 86} au. The best-fitting linear ephemeris is T0 = 2457 066.720 45 ± 0.000 27 BJDTDB and P = 4.166 2739 ± 0.000 0063 d. This planet joins a group of highly inflated transiting exoplanets with a larger radius and smaller mass than that of Jupiter. The planet, which boasts deep transits of 1.4 per cent, has a relatively high equilibrium temperature of Teq = 1377_{-23}^{+28} K, assuming zero albedo and perfect heat redistribution. KELT-10b receives an estimated insolation of 0.817_{-0.054}^{+0.068} × 109 erg s-1 cm-2, which places it far above the insolation threshold above which hot Jupiters exhibit increasing amounts of radius inflation. Evolutionary analysis of the host star suggests that KELT-10b may not survive beyond the current subgiant phase, depending on the rate of in-spiral of the planet over the next few Gyr. The planet transits a relatively bright star and exhibits the third largest transit depth of all transiting exoplanets with V < 11 in the Southern hemisphere, making it a promising candidate for future atmospheric characterization studies.

  2. Analysis of new high-precision transit light curves of WASP-10 b: starspot occultations, small planetary radius, and high metallicity

    NASA Astrophysics Data System (ADS)

    Maciejewski, G.; Raetz, St.; Nettelmann, N.; Seeliger, M.; Adam, C.; Nowak, G.; Neuhäuser, R.

    2011-11-01

    Context. The WASP-10 planetary system is intriguing because different values of radius have been reported for its transiting exoplanet. The host star exhibits activity in terms of photometric variability, which is caused by the rotational modulation of the spots. Moreover, a periodic modulation has been discovered in transit timing of WASP-10 b, which could be a sign of an additional body perturbing the orbital motion of the transiting planet. Aims: We attempt to refine the physical parameters of the system, in particular the planetary radius, which is crucial for studying the internal structure of the transiting planet. We also determine new mid-transit times to confirm or refute observed anomalies in transit timing. Methods: We acquired high-precision light curves for four transits of WASP-10 b in 2010. Assuming various limb-darkening laws, we generated best-fit models and redetermined parameters of the system. The prayer-bead method and Monte Carlo simulations were used to derive error estimates. Results: Three transit light curves exhibit signatures of the occultations of dark spots by the planet during its passage across the stellar disk. The influence of stellar activity on transit depth is taken into account while determining system parameters. The radius of WASP-10 b is found to be no greater than 1.03+0.07-0.03 Jupiter radii, a value significantly smaller than most previous studies indicate. We calculate interior structure models of the planet, assuming a two-layer structure with one homogeneous envelope atop a rock core. The high value of the WASP-10 b's mean density allows one to consider the planet's internal structure including 270 to 450 Earth masses of heavy elements. Our new mid-transit times confirm that transit timing cannot be explained by a constant period if all literature data points are considered. They are consistent with the ephemeris assuming a periodic variation of transit timing. We show that possible starspot features affecting the

  3. A Sensitive Mass-spectrum Assay to Characterize Engineered Methionine Adenosyltransferases with S-Alkyl Methionine Analogues as Substrates

    PubMed Central

    Wang, Rui; Zheng, Weihong; Luo, Minkui

    2014-01-01

    Methionine adenosyltransferases (MATs) catalyze the formation of S-adenosyl-L-methionine (SAM) inside living cells. Recently, S-alkyl analogues of SAM have been documented as cofactor surrogates to label novel targets of methyltransferases. However, these chemically synthesized SAM analogues are not suitable for cell-based studies because of their poor membrane permeability. This issue was recently addressed under a cellular setting through a chemoenzymatic strategy to process membrane-permeable S-alkyl analogues of methionine (SAAM) into the SAM analogues with engineered MATs. Here we describe a general, sensitive activity assay for engineered MATs by converting the reaction products into S-alkyl-thioadenosines, followed by HPLC/MS/MS quantification. With this assay, 40 human MAT mutants were evaluated against seven SAAM as potential substrates. The structure-activity-relationship revealed that, besides better engaged SAAM binding by the MAT mutants (lower Km value in contrast to native MATs), the gained activity towards the bulky SAAM stems from their ability to maintain the desired linear SN2 transition state (reflected by higher kcat value). Here the I117A mutant of human MATI was identified as the most active variant for biochemical production of SAM analogues from diverse SAAM. PMID:24374249

  4. Characteristics of boron-dose enhancer dependent on dose protocol and 10B concentration for BNCT using near-threshold 7Li(p,n)7Be direct neutrons.

    PubMed

    Tanaka, Kenichi; Kobayashi, Tooru; Bengua, Gerard; Nakagawa, Yoshinobu; Endo, Satoru; Hoshi, Masaharu

    2005-01-01

    The dependence of boron-dose enhancer (BDE) characteristics on dose protocol and 10B concentration was evaluated for BNCT using near-threshold 7Li(p,n)7Be direct neutrons. The treatable protocol depth (TPD) was utilized as an evaluation index. MCNP calculations were performed for near-threshold 7Li(p,n)7Be at a proton energy of 1.900 MeV and for a polyethylene BDE. The effect of dose protocol on BDE characteristics was reflected in terms of the optimum BDE thickness needed for maximum TPD which was found to be independent of the treatable dose but was observed to vary for different combinations of the tolerance doses for heavy charged particles and gamma rays. For the 10B concentration dependence, the TPD was increased by increasing the T/N ratio, i.e., the ratio of the 10B concentration in the tumour (10B(Tumour)) to that in the normal tissue (10B(Normal)), and by increasing 10B(Tumour) and 10B(Normal) at constant T/N ratio. It was found that the use of BDE becomes unnecessary from the viewpoint of increasing the TPD, when 10B(Tumour) is over a certain level which is decided by the conditions of the dose protocol. PMID:15715430

  5. Redox Viscosity of Iron Rich Silicate Melts - Martian Mantle Analogues.

    NASA Astrophysics Data System (ADS)

    Dingwell, D. B.

    2004-12-01

    The dependence of shear viscosity on the oxidation state of ferrosilicate melts has been measured using the concentric cylinder method and a gas mixing furnace. Two different simple Fe-bearing systems have been studied to date: (i) anorthite-diopside eutectic composition (AnDi) with variable amount of Fe (up to 20 wt%) as a basalt analogue and (ii) sodium disilicate (NS2 up to 30 wt % Fe). In addition, the compositional range has been extended to include the more complex SNC meteorite composition, a composition more relevant to Mars. The measurements were performed under air, CO2 and CO2-CO mixture at 1 atm and in a temperature range of 1300 to 1350 \\ºC. The experimental procedure involve a continuous measurement of viscosity during stepwise reduction state. The melt was reduced by flowing CO2 and then successively reducing mixtures of CO2-CO through the alumina muffle tube. Gas flow rates were electronically controlled using Tylan mass flow controllers and oxygen fugacity was directly measured using a sensor and calculated with Nernst equation. The composition and oxidation state of the melt was monitored by obtaining a melt sample after each redox equilibrium step. The melts were sampled by dipping an alumina rod into the sample and drawing out a drop of liquid, which was then plunged into water for quenching. The resulting glasses were analyzed by electron microprobe, and the volumetric potassium dichromate titration were employed to determine FeO. In addition, the redox dependence of viscosity of our samples have been compared with data from literature (Mysen et al. 1985, Dingwell and Virgo, 1988; Dingwell 1989, Dingwell 1991). The viscosity of all melts investigated herein decreases with melt reduction. The viscosity decrease is, in general, a nonlinear function of oxidation state expressed as Fe2+/Fetot and can be fitted using logarithmic equation.

  6. Natural geochemical analogues of the near field of high-level nuclear waste repositories

    SciTech Connect

    Apps, J.A.

    1995-09-01

    United States practice has been to design high-level nuclear waste (HLW) geological repositories with waste densities sufficiently high that repository temperatures surrounding the waste will exceed 100{degrees}C and could reach 250{degrees}C. Basalt and devitrified vitroclastic tuff are among the host rocks considered for waste emplacement. Near-field repository thermal behavior and chemical alteration in such rocks is expected to be similar to that observed in many geothermal systems. Therefore, the predictive modeling required for performance assessment studies of the near field could be validated and calibrated using geothermal systems as natural analogues. Examples are given which demonstrate the need for refinement of the thermodynamic databases used in geochemical modeling of near-field natural analogues and the extent to which present models can predict conditions in geothermal fields.

  7. Functionalized Congener Approach to Muscarinic Antagonists: Analogues of Pirenzepine

    PubMed Central

    Karton, Yishai; Bradbury, Barton J.; Baumgold, Jesse; Paek, Robert; Jacobson, Kenneth A.

    2012-01-01

    The M1-selective muscarinic receptor antagonist pirenzepine (5,11-dihydro-11-[(4-methyl-1-piperazinyl)acetyl]-6H-pyrido[2,3-b] [1,4]benzodiazepin-6-one) was derivatized to explore points of attachment of functionalized side chains for the synthesis of receptor probes and ligands for affinity chromatography. The analogues prepared were evaluated in competitive binding assays versus [3H]-N-methylscopolamine at four muscarinic receptor subtypes (m1AChR-m4AChR) in membranes from rat heart tissue and transfected A9L cells. 9-(Hydroxymethyl)pirenzepine, 8-(methylthio)pirenzepine, and a series of 8-aminosulfonyl derivatives were synthesized. Several 5-substituted analogues of pirenzepine also were prepared. An alternate series of analogues substituted on the 4-position of the piperazine ring was prepared by reaction of 4-desmethylpirenzepine with various electrophiles. An N-chloroethyl analogue of pirenzepine was shown to form a reactive aziridine species in aqueous buffer yet failed to affinity label muscarinic receptors. Within a series of aminoalkyl analogues, the affinity increased as the length of the alkyl chain increased. Shorter chain analogues were generally much less potent than pirenzepine, and longer analogues (7–10 carbons) were roughly as potent as pirenzepine at m1 receptors, but were nonselective. Depending on the methylene chain length, acylation or alkyl substitution of the terminal amine also influenced the affinity at muscarinic receptors. PMID:2066986

  8. Astrophysical Impact of the Updated 9Be(p,α)6Li and 10B(p,α)7Be Reaction Rates As Deduced By THM

    NASA Astrophysics Data System (ADS)

    Lamia, L.; Spitaleri, C.; Tognelli, E.; Degl'Innocenti, S.; Pizzone, R. G.; Prada Moroni, P. G.

    2015-10-01

    The complete understanding of the stellar abundances of lithium, beryllium, and boron represents one of the most interesting open problems in astrophysics. These elements are largely used to probe stellar structure and mixing phenomena in different astrophysical scenarios, such as pre-main-sequence or main-sequence stars. Their different fragility against (p,α) burning reactions allows one to investigate different depths of the stellar interior. Such fusion mechanisms are triggered at temperatures between T ≈ (2-5) × {10}6 K, thus defining a corresponding Gamow energy between ≈ 3-10 keV, where S(E)-factor measurements need to be performed to get reliable reaction rate evaluations. The Trojan Horse Method is a well defined procedure to measure cross sections at Gamow energies overcoming the uncertainties due to low-energy S(E)-factor extrapolation as well as electron screening effects. Taking advantage of the {\\mathtt{THM}} measure of the 9Be(p,α)6Li and 10B(p,α)7Be cross sections, the corresponding reaction rates have been calculated and compared with the evaluations by the NACRE collaboration, widely used in the literature. The impact on surface abundances of the updated 9Be and 10B (p,α) burning rates is discussed for pre-MS stars.

  9. THE ORBITAL PHASES AND SECONDARY TRANSITS OF KEPLER-10b. A PHYSICAL INTERPRETATION BASED ON THE LAVA-OCEAN PLANET MODEL

    SciTech Connect

    Rouan, D.; Deeg, H. J.; Demangeon, O.; Samuel, B.; Cavarroc, C.; Leger, A.; Fegley, B.

    2011-11-10

    The Kepler mission has made an important observation: the first detection of photons from a terrestrial planet by observing its phase curve (Kepler-10b). This opens a new field in exoplanet science: the possibility of obtaining information about the atmosphere and surface of rocky planets, objects of prime interest. In this Letter, we apply the Lava-ocean model to interpret the observed phase curve. The model, a planet without atmosphere and a surface partially made of molten rocks, has been proposed for planets of the class of CoRoT-7b, i.e., rocky planets very close to their star (at a few stellar radii). Kepler-10b is a typical member of this family. It predicts that the light from the planet has an important emission component in addition to the reflected one, even in the Kepler spectral band. Assuming an isotropical reflection of light by the planetary surface (Lambertian-like approximation), we find that a Bond albedo of {approx}50% can account for the observed amplitude of the phase curve, as opposed to a first attempt where an unusually high value was found. We propose a physical process to explain this still large value of the albedo. The overall interpretation can be tested in the future with instruments such as the James Webb Space Telescope or the Exoplanet Characterization Observatory. Our model predicts a spectral dependence that is clearly distinguishable from that of purely reflected light and from that of a planet at a uniform temperature.

  10. 6MAP, a fluorescent adenine analogue, is a probe of base flipping by DNA photolyase.

    PubMed

    Yang, Kongsheng; Matsika, Spiridoula; Stanley, Robert J

    2007-09-01

    Cyclobutylpyrimidine dimers (CPDs) are formed between adjacent pyrimidines in DNA when it absorbs ultraviolet light. CPDs can be directly repaired by DNA photolyase (PL) in the presence of visible light. How PL recognizes and binds its substrate is still not well understood. Fluorescent nucleic acid base analogues are powerful probes of DNA structure. We have used the fluorescent adenine analogue 6MAP, a pteridone, to probe the local double helical structure of the CPD substrate when bound by photolyase. Duplex melting temperatures were obtained by both UV-vis absorption and fluorescence spectroscopies to ascertain the effect of the probe and the CPD on DNA stability. Steady-state fluorescence measurements of 6MAP-containing single-stranded and doubled-stranded oligos with and without protein show that the local region around the CPD is significantly disrupted. 6MAP shows a different quenching pattern compared to 2-aminopurine, another important adenine analogue, although both probes show that the structure of the complementary strand opposing the 5'-side of the CPD lesion is more destacked than that opposing the 3'-side in substrate/protein complexes. We also show that 6MAP/CPD duplexes are substrates for PL. Vertical excitation energies and transition dipole moment directions for 6MAP were calculated using time-dependent density functional theory. Using these results, the Förster resonance energy transfer efficiency between the individual adenine analogues and the oxidized flavin cofactor was calculated to account for the observed intensity pattern. These calculations suggest that energy transfer is highly efficient for the 6MAP probe and less so for the 2Ap probe. However, no experimental evidence for this process was observed in the steady-state emission spectra. PMID:17696385

  11. Solution structures of purine base analogues 9-deazaguanine and 9-deazahypoxanthine.

    PubMed

    Karnawat, Vishakha; Puranik, Mrinalini

    2016-03-01

    Deaza analogues of nucleobases are potential drugs against infectious diseases caused by parasites. A caveat is that apart from binding their target parasite enzymes, they also bind and inhibit enzymes of the host. In order to design derivatives of deaza analogues which specifically bind target enzymes, knowledge of their molecular structure, protonation state, and predominant tautomers at physiological conditions is essential. We have employed resonance Raman spectroscopy at an excitation wavelength of 260 nm, to decipher solution structure of 9-deazaguanine (9DAG) and 9-deazahypoxanthine (9DAH). These are analogues of guanine and hypoxanthine, respectively, and have been exploited to study static complexes of nucleobase binding enzymes. Such enzymes are known to perturb pKa of their ligands, and thus, we also determined solution structures of these analogues at two, acidic and alkaline, pH. Structure of each possible protonation state and tautomer was computed using density functional theoretical calculations. Species at various pHs were identified based on isotopic shifts in experimental wavenumbers and by comparing these shifts with corresponding computed isotopic shifts. Our results show that at physiological pH, N1 of pyrimidine ring in 9DAG and 9DAH bears a proton. At lower pH, N3 is place of protonation, and at higher pH, deprotonation occurs at N1 position. The proton at N7 of purine ring remains intact even at pH 12.5. We have further compared these results with naturally occurring nucleotides. Our results identify key vibrational modes which can report on hydrogen bonding interactions, protonation and deprotonation in purine rings upon binding to the active site of enzymes. PMID:25894214

  12. Are there pre-Quaternary geological analogues for a future greenhouse warming?

    USGS Publications Warehouse

    Haywood, A.M.; Ridgwell, A.; Lunt, D.J.; Hill, D.J.; Pound, M.J.; Dowsett, H.J.; Dolan, A.M.; Francis, J.E.; Williams, M.

    2011-01-01

    Given the inherent uncertainties in predicting how climate and environments will respond to anthropogenic emissions of greenhouse gases, it would be beneficial to society if science could identify geological analogues to the human race's current grand climate experiment. This has been a focus of the geological and palaeoclimate communities over the last 30 years, with many scientific papers claiming that intervals in Earth history can be used as an analogue for future climate change. Using a coupled ocean-atmosphere modelling approach, we test this assertion for the most probable pre-Quaternary candidates of the last 100 million years: the Mid- and Late Cretaceous, the Palaeocene-Eocene Thermal Maximum (PETM), the Early Eocene, as well as warm intervals within the Miocene and Pliocene epochs. These intervals fail as true direct analogues since they either represent equilibrium climate states to a long-term CO2 forcing-whereas anthropogenic emissions of greenhouse gases provide a progressive (transient) forcing on climate-or the sensitivity of the climate system itself to CO2 was different. While no close geological analogue exists, past warm intervals in Earth history provide a unique opportunity to investigate processes that operated during warm (high CO2) climate states. Palaeoclimate and environmental reconstruction/modelling are facilitating the assessment and calculation of the response of global temperatures to increasing CO2 concentrations in the longer term (multiple centuries); this is now referred to as the Earth System Sensitivity, which is critical in identifying CO2 thresholds in the atmosphere that must not be crossed to avoid dangerous levels of climate change in the long term. Palaeoclimatology also provides a unique and independent way to evaluate the qualities of climate and Earth system models used to predict future climate. ?? 2011 The Royal Society.

  13. Are there pre-Quaternary geological analogues for a future greenhouse warming?

    PubMed

    Haywood, Alan M; Ridgwell, Andy; Lunt, Daniel J; Hill, Daniel J; Pound, Matthew J; Dowsett, Harry J; Dolan, Aisling M; Francis, Jane E; Williams, Mark

    2011-03-13

    Given the inherent uncertainties in predicting how climate and environments will respond to anthropogenic emissions of greenhouse gases, it would be beneficial to society if science could identify geological analogues to the human race's current grand climate experiment. This has been a focus of the geological and palaeoclimate communities over the last 30 years, with many scientific papers claiming that intervals in Earth history can be used as an analogue for future climate change. Using a coupled ocean-atmosphere modelling approach, we test this assertion for the most probable pre-Quaternary candidates of the last 100 million years: the Mid- and Late Cretaceous, the Palaeocene-Eocene Thermal Maximum (PETM), the Early Eocene, as well as warm intervals within the Miocene and Pliocene epochs. These intervals fail as true direct analogues since they either represent equilibrium climate states to a long-term CO(2) forcing--whereas anthropogenic emissions of greenhouse gases provide a progressive (transient) forcing on climate--or the sensitivity of the climate system itself to CO(2) was different. While no close geological analogue exists, past warm intervals in Earth history provide a unique opportunity to investigate processes that operated during warm (high CO(2)) climate states. Palaeoclimate and environmental reconstruction/modelling are facilitating the assessment and calculation of the response of global temperatures to increasing CO(2) concentrations in the longer term (multiple centuries); this is now referred to as the Earth System Sensitivity, which is critical in identifying CO(2) thresholds in the atmosphere that must not be crossed to avoid dangerous levels of climate change in the long term. Palaeoclimatology also provides a unique and independent way to evaluate the qualities of climate and Earth system models used to predict future climate. PMID:21282155

  14. The preparation of zaragozic acid A analogues by directed biosynthesis.

    PubMed

    Chen, T S; Petuch, B; MacConnell, J; White, R; Dezeny, G; Arison, B; Bergstrom, J D; Colwell, L; Huang, L; Monaghan, R L

    1994-11-01

    Zaragozic acid A analogues are produced by an unidentified sterile fungus when it is exogenously supplied with 2-thiophenecarboxylic acid, 3-thiophenecarboxylic acid, 2-furoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, or 4-fluorobenzoic acid. The analogues carry 2-thiophenyl, 3-thiophenyl, 2-furyl, o-fluorophenyl, m-fluorophenyl, or p-fluorophenyl group, respectively, at C-6' of the C-1 alkyl side chain replacing the phenyl group of natural zaragozic acid A. All the new analogues of zaragozic acid A possess picomolar inhibitory activity against squalene synthase in vitro. PMID:8002393

  15. Recent developments in naturally derived antimalarials: cryptolepine analogues.

    PubMed

    Wright, Colin W

    2007-06-01

    Increasing resistance of Plasmodium falciparum to commonly used antimalarial drugs has made the need for new agents increasingly urgent. In this paper, the potential of cryptolepine, an alkaloid from the West African shrub Cryptolepis sanguinolenta, as a lead towards new antimalarial agents is discussed. Several cryptolepine analogues have been synthesized that have promising in-vitro and in-vivo antimalarial activity. Studies on the antimalarial modes of action of these analogues indicate that they may have different or additional modes of action to the parent compound. Elucidation of the mode of action may facilitate the development of more potent antimalarial cryptolepine analogues. PMID:17637183

  16. Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues.

    PubMed

    Roselli, Mariagrazia; Carocci, Alessia; Budriesi, Roberta; Micucci, Matteo; Toma, Maddalena; Di Cesare Mannelli, Lorenzo; Lovece, Angelo; Catalano, Alessia; Cavalluzzi, Maria Maddalena; Bruno, Claudio; De Palma, Annalisa; Contino, Marialessandra; Perrone, Maria Grazia; Colabufo, Nicola Antonio; Chiarini, Alberto; Franchini, Carlo; Ghelardini, Carla; Habtemariam, Solomon; Lentini, Giovanni

    2016-10-01

    Four mexiletine analogues have been tested for their antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues and to assess calcium antagonist activity, in comparison with the parent compound mexiletine. All analogues showed from moderate to high antiarrhythmic activity. In particular, three of them (1b,c,e) were more active and potent than the reference drug, while exhibiting only modest or no negative inotropic and chronotropic effects and vasorelaxant activity, thus showing high selectivity of action. All compounds showed no cytotoxicity and 1b,c,d did not impair motor coordination. All in, these new analogues exhibit an interesting cardiovascular profile and deserve further investigation. PMID:27267000

  17. MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology.

    PubMed

    Sáez-Briones, P; Hernández, A

    2013-09-01

    Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine MDMA (3,4-methylenedioxymethamphetamine, XTC, "Ecstasy") is the prototypical representative of a separate class of psychotropic substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of consciousness, usually described as an "open mind state", may have relevant therapeutic applications, both in psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure. Nevertheless, a comprehensive and systematic exploration of the structure-activity relationships associated with entactogenic activity has remained incomplete and controversial, highlighting the possibility that MDMA might represent a pharmacological rarity in the field of psychotropics. As the latter is still an open question, the pharmacological characterization of MDMA analogues remains the logical strategy to attempt the elucidation of the structural requirements needed to elicit typical MDMA-like effects. Intriguingly, almost no experimental evidence supports the existence of actual MDMA analogues that truly resemble the whole pharmacological profile of MDMA, probably due to its complex (and partially not fully understood) mechanism of action that includes a disruption of monoaminergic neurotransmission. The present review presents a brief summary of the pharmacology of MDMA, followed by the evidence accumulated over the years regarding the characterization of classical structurally related MDMA analogues in different models and how this state of the art highlights the need to develop new and better MDMA analogues. PMID:24403876

  18. Antithyroid drugs and their analogues: synthesis, structure, and mechanism of action.

    PubMed

    Manna, Debasish; Roy, Gouriprasanna; Mugesh, Govindasamy

    2013-11-19

    understood. Most investigations have revealed that MMI and PTU irreversibly inhibit TPO. PTU, MTU, and their selenium analogues also inhibit ID-1, most likely by reacting with the selenenyl iodide intermediate. The good ID-1 inhibitory activity of PTU and its analogues can be ascribed to the presence of the -N(H)-C(═O)- functionality that can form hydrogen bonds with nearby amino acid residues in the selenenyl sulfide state. In addition to the TPO and ID-1 inhibition, the selenium analogues are very good antioxidants. In the presence of cellular reducing agents such as GSH, these compounds catalytically reduce hydrogen peroxide. They can also efficiently scavenge peroxynitrite, a potent biological oxidant and nitrating agent. PMID:23883148

  19. Radiolabeled Somatostatin Analogue Therapy Of Gastroenteropancreatic Cancer.

    PubMed

    Bodei, Lisa; Kwekkeboom, Dik J; Kidd, Mark; Modlin, Irvin M; Krenning, Eric P

    2016-05-01

    Peptide receptor radionuclide therapy (PRRT) has been utilized for more than two decades and has been accepted as an effective therapeutic modality in the treatment of inoperable or metastatic gastroenteropancreatic neuroendocrine neoplasms (NENs) or neuroendocrine tumors (NETs). The two most commonly used radiopeptides for PRRT, (90)Y-octreotide and (177)Lu-octreotate, produce disease-control rates of 68%-94%, with progression-free survival rates that compare favorably with chemotherapy, somatostatin analogues, and newer targeted therapies. In addition, biochemical and symptomatic responses are commonly observed. In general, PRRT is well tolerated with only low to moderate toxicity in most individuals. In line with the need to place PRRT in the therapeutic sequence of gastroenteropancreatic NENs, a recently sponsored phase III randomized trial in small intestine NENs treated with (177)Lu-octreotate vs high-dose octreotide long-acting release demonstrated that (177)Lu-octreotate significantly improved progression-free survival. Other strategies that are presently being developed include combinations with targeted therapies or chemotherapy, intra-arterial PRRT, and salvage treatments. Sophisticated molecular tools need to be incorporated into the management strategy to more effectively define therapeutic efficacy and for an early identification of adverse events. The strategy of randomized controlled trials is a key issue to standardize the treatment and establish the position of PRRT in the therapeutic algorithm of NENs. PMID:27067503

  20. Quantum chimera states

    NASA Astrophysics Data System (ADS)

    Viennot, David; Aubourg, Lucile

    2016-02-01

    We study a theoretical model of closed quasi-hermitian chain of spins which exhibits quantum analogues of chimera states, i.e. long life classical states for which a part of an oscillator chain presents an ordered dynamics whereas another part presents a disordered dynamics. For the quantum analogue, the chimera behaviour deals with the entanglement between the spins of the chain. We discuss the entanglement properties, quantum chaos, quantum disorder and semi-classical similarity of our quantum chimera system. The quantum chimera concept is novel and induces new perspectives concerning the entanglement of multipartite systems.

  1. Photophysical properties of pyrrolocytosine, a cytosine fluorescent base analogue.

    PubMed

    Nguyen, Quynh L; Spata, Vincent A; Matsika, Spiridoula

    2016-07-27

    The photophysical behavior of pyrrolocytosine (PC), a fluorescent base analogue of cytosine, has been investigated using theoretical approaches. The similarities between the PC and cytosine structures allow PC to maintain the pseudo-Watson-Crick base-pairing arrangement with guanine. Cytosine, similar to the other natural nucleobases, is practically non-fluorescent, because of ultrafast radiationless decay occurring through conical intersections. PC displays a much higher fluorescence quantum yield than cytosine, making it an effective fluorescent marker to study the structure, function, and dynamics of DNA/RNA complexes. Similar to 2-aminopurine, a constitutional isomer of adenine that base-pairs with thymine, PC's fluorescence is quenched when it is incorporated into a dinucleotide or a trinucleotide. In this work we examine the photophysical properties of isolated PC, microhydrated PC, as well as, complexes where PC is either base-stacked or hydrogen-bonded with guanine. Our results indicate that hydration affects the radiationless decay pathways in PC by destabilizing conical intersections. The calculations of dimers and trimers show that the radiative decay is affected by π stacking, while the presence of charge transfer states between PC and guanine may contribute to radiationless decay. PMID:27251599

  2. Encoding complexity within supramolecular analogues of frustrated magnets

    NASA Astrophysics Data System (ADS)

    Cairns, Andrew B.; Cliffe, Matthew J.; Paddison, Joseph A. M.; Daisenberger, Dominik; Tucker, Matthew G.; Coudert, François-Xavier; Goodwin, Andrew L.

    2016-05-01

    The solid phases of gold(I) and/or silver(I) cyanides are supramolecular assemblies of inorganic polymer chains in which the key structural degrees of freedom—namely, the relative vertical shifts of neighbouring chains—are mathematically equivalent to the phase angles of rotating planar (‘XY’) spins. Here, we show how the supramolecular interactions between chains can be tuned to mimic different magnetic interactions. In this way, the structures of gold(I) and/or silver(I) cyanides reflect the phase behaviour of triangular XY magnets. Complex magnetic states predicted for this family of magnets—including collective spin-vortices of relevance to data storage applications—are realized in the structural chemistry of these cyanide polymers. Our results demonstrate how chemically simple inorganic materials can behave as structural analogues of otherwise inaccessible ‘toy’ spin models and also how the theoretical understanding of those models allows control over collective (‘emergent’) phenomena in supramolecular systems.

  3. Photochemistry of nucleic acid bases and their thio- and aza-analogues in solution.

    PubMed

    Pollum, Marvin; Martínez-Fernández, Lara; Crespo-Hernández, Carlos E

    2015-01-01

    The steady-state and time-resolved photochemistry of the natural nucleic acid bases and their sulfur- and nitrogen-substituted analogues in solution is reviewed. Emphasis is given to the experimental studies performed over the last 3-5 years that showcase topical areas of scientific inquiry and those that require further scrutiny. Significant progress has been made toward mapping the radiative and nonradiative decay pathways of nucleic acid bases. There is a consensus that ultrafast internal conversion to the ground state is the primary relaxation pathway in the nucleic acid bases, whereas the mechanism of this relaxation and the level of participation of the (1)πσ*, (1) nπ*, and (3)ππ* states are still matters of debate. Although impressive research has been performed in recent years, the microscopic mechanism(s) by which the nucleic acid bases dissipate excess vibrational energy to their environment, and the role of the N-glycosidic group in this and in other nonradiative decay pathways, are still poorly understood. The simple replacement of a single atom in a nucleobase with a sulfur or nitrogen atom severely restricts access to the conical intersections responsible for the intrinsic internal conversion pathways to the ground state in the nucleic acid bases. It also enhances access to ultrafast and efficient inter-system crossing pathways that populate the triplet manifold in yields close to unity. Determining the coupled nuclear and electronic pathways responsible for the significantly different photochemistry in these nucleic acid base analogues serves as a convenient platform to examine the current state of knowledge regarding the photodynamic properties of the DNA and RNA bases from both experimental and computational perspectives. Further investigations should also aid in forecasting the prospective use of sulfur- and nitrogen-substituted base analogues in photochemotherapeutic applications. PMID:25238718

  4. Cell-Cycle Analyses Using Thymidine Analogues in Fission Yeast

    PubMed Central

    Anda, Silje; Boye, Erik; Grallert, Beata

    2014-01-01

    Thymidine analogues are powerful tools when studying DNA synthesis including DNA replication, repair and recombination. However, these analogues have been reported to have severe effects on cell-cycle progression and growth, the very processes being investigated in most of these studies. Here, we have analyzed the effects of 5-ethynyl-2′-deoxyuridine (EdU) and 5-Chloro-2′-deoxyuridine (CldU) using fission yeast cells and optimized the labelling procedure. We find that both analogues affect the cell cycle, but that the effects can be mitigated by using the appropriate analogue, short pulses of labelling and low concentrations. In addition, we report sequential labelling of two consecutive S phases using EdU and 5-bromo-2′-deoxyuridine (BrdU). Furthermore, we show that detection of replicative DNA synthesis is much more sensitive than DNA-measurements by flow cytometry. PMID:24551125

  5. Synthesis of a stable and orally bioavailable englerin analogue.

    PubMed

    Fash, David M; Peer, Cody J; Li, Zhenwu; Talisman, Ian J; Hayavi, Sima; Sulzmaier, Florian J; Ramos, Joe W; Sourbier, Carole; Neckers, Leonard; Figg, W Douglas; Beutler, John A; Chain, William J

    2016-06-01

    Synthesis of analogues of englerin A with a reduced propensity for hydrolysis of the glycolate moiety led to a compound which possessed the renal cancer cell selectivity of the parent and was orally bioavailable in mice. PMID:27107948

  6. Efficient total syntheses and biological activities of two teixobactin analogues.

    PubMed

    Parmar, Anish; Iyer, Abhishek; Vincent, Charlotte S; Van Lysebetten, Dorien; Prior, Stephen H; Madder, Annemieke; Taylor, Edward J; Singh, Ishwar

    2016-04-26

    The discovery of the new antibiotic teixobactin has been timely in the race for unearthing novel antibiotics wherein the emergence of drug resistant bacteria poses a serious threat worldwide. Herein, we present the total syntheses and biological activities of two teixobactin analogues. This approach is simple, efficient and has several advantages: it uses commercially available building blocks (except AllocHN-d-Thr-OH), has a single purification step and a good recovery (22%). By using this approach we have synthesised two teixobactin analogues and established that the d-amino acids are critical for the antimicrobial activity of these analogues. With continuing high expectations from teixobactin, this work can be regarded as a stepping stone towards an in depth study of teixobactin, its analogues and the quest for synthesising similar molecules. PMID:26984316

  7. Defining Analytical Strategies for Mars Sample Return with Analogue Missions

    NASA Astrophysics Data System (ADS)

    Osinski, G. R.; Sapers, H. M.; Francis, R.; Pontefract, A.; Tornabene, L. L.; Haltigin, T.

    2016-05-01

    The characterization of biosignatures in MSR samples will require integrated, cross-platform laboratory analyses carefully correlated and calibrated with Rover-based technologies. Analogue missions provide context for implementation and assessment.

  8. Effects of Prostaglandin Analogues on Aqueous Humor Outflow Pathways

    PubMed Central

    Winkler, Nelson S.

    2014-01-01

    Abstract Elevated intraocular pressure (IOP) is the most prevalent risk factor for glaucoma. All treatments, whether surgical or pharmaceutical, are aimed at lowering IOP. Prostaglandin analogues are a first line therapy for glaucoma due to their ability to reduce IOP, once-daily dosing, efficacy, and minimal side-effect profile. Whereas prostaglandin analogues have been known to alter aqueous humor outflow through the unconventional (uveoscleral) pathway, more recent evidence suggests their action also occurs through the conventional (trabecular) pathway. Understanding how prostaglandin analogues successfully lower IOP is important, as this information may lead to the discovery of new molecular targets for future therapeutic intervention. This review explores the current understanding of prostaglandin analogue biology as it pertains to IOP reduction and improved aqueous humor outflow facility. PMID:24359106

  9. Practical enantiospecific syntheses of lysobisphosphatidic acid and its analogues.

    PubMed

    Jiang, Guowei; Xu, Yong; Prestwich, Glenn D

    2006-02-01

    We describe a versatile, efficient, and practical method for the preparation of enantiomerically pure lysobisphosphatidic acid (LBPA), bisether analogues, and phosphorothioate analogues of LBPA from solketal. Phosphorylation of a protected sn-2-O-oleoyl glycerol with 2-cyanoethyl bis(N,N-diisopropylamino)phosphite, followed by oxidation and deprotection, generated the enantiomers of 2,2'-LBPA. The corresponding phosphorothioate analogues were obtained by oxidation with sulfur. The (R,R) and (S,S) enantiomers of both LBPA and phosphorothioate LBPA were synthesized from (S)- and (R)-solketal, respectively. The ether analogue of (S,S)-lysobisphosphatidic acid (LBPA) and its enantiomer were synthesized from the same enantiomer (S)-solketal by simply changing the sequence of deprotection steps. PMID:16438504

  10. From BPA to its analogues: Is it a safe journey?

    PubMed

    Usman, Afia; Ahmad, Masood

    2016-09-01

    Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful? PMID:27262103

  11. Structural analogues of diosgenyl saponins: synthesis and anticancer activity.

    PubMed

    Kaskiw, Matthew J; Tassotto, Mary Lynn; Mok, Mac; Tokar, Stacey L; Pycko, Roxanne; Th'ng, John; Jiang, Zi-Hua

    2009-11-15

    Saponins display various biological activities including anti-tumor activity. Recently intensive research has been focused on developing saponins for tumor therapies. The diosgenyl saponin dioscin is one of the most common steroidal saponins and exhibits potent anticancer activity in several human cancer cells through apoptosis-inducing pathways. In this paper, we describe the synthesis of several diosgenyl saponin analogues containing either a 2-amino-2-deoxy-beta-d-glucopyranosyl residue or an alpha-l-rhamnopyranosyl-(1-->4)-2-amino-2-deoxy-beta-d-glucopyranosyl residue with different acyl substituents on the amino group. The cytotoxic activity of these compounds was evaluated in MCF-7 breast cancer cells and HeLa cervical cancer cells. Structure-activity relationship studies show that the disaccharide saponin analogues are in general less active than their corresponding monosaccharide analogues. The incorporation of an aromatic nitro functionality into these saponin analogues does not exhibit significant effect on their cytotoxic activity. PMID:19819703

  12. Analogue modelling of salt diapirism induced by differential loading

    NASA Astrophysics Data System (ADS)

    Warsitzka, Michael; Kley, Jonas; Kukowski, Nina; Jähne, Fabian

    2010-05-01

    In salt tectonics, two general concepts exist to explain salt diapirism. First, the theory of active piercement by Trusheim (1960) states that salt rises up and pierces its overburden autonomously by buoyancy forces. Second, the theory of reactive piercement by Vendeville and Jackson (1992) considers a tectonic stress field responsible for initiation of salt uplift and has been tested in many analogue experiments. In this study, we investigated the hypothesis in which salt diapir formation is activated by sedimentary processes alone, i.e. without a tectonic trigger. Our models consisted of a viscous silicone layer simulating rock salt overlain by layers of sand that mimic brittle behaviour in natural overburden sediments. The experiments were monitored with a high-resolution strain analysis tool based on digital image correlation (particle image velocimetry, PIV). Deformation in the silicone was initiated by a lateral variation in the thickness or density of the overburden, which established a differential loading on the silicone layer. Subsequent sedimentation in certain time intervals forced the silicone to rise up and break through the initial sand layer by buoyancy forces. The model results support the hypothesis of active piercement of diapirs. Uplift of the silicone and creation of a pillow structure with a significant elevation can be achieved if the overburden does not exceed a critical thickness and if the load gradient in the overburden reaches a minimum value. Then, ongoing sedimentation in adjacent areas increases the lateral load gradient until the buoyancy force in the silicone is high enough to overcome the shear strength of the sand. Synkinematic sedimentation produces some typical strata geometries in the sand layer that can also be observed in nature, e.g. drag folds bordering the diapirs and layer thickening in the peripherical rim synclines. The creation of one diapir and its peripherical sinks induces a lateral migration of the deformation to

  13. Combined use of FLUKA and MCNP-4A for the Monte Carlo simulation of the dosimetry of 10B neutron capture enhancement of fast neutron irradiations.

    PubMed

    Pignol, J P; Cuendet, P; Brassart, N; Fares, G; Colomb, F; M'Bake Diop, C; Sabattier, R; Hachem, A; Prevot, G

    1998-06-01

    Boron neutron capture enhancement (BNCE) of the fast neutron irradiations use thermal neutrons produced in depth of the tissues to generate neutron capture reactions on 10B within tumor cells. The dose enhancement is correlated to the 10B concentration and to thermal neutron flux measured in the depth of the tissues, and in this paper we demonstrate the feasibility of Monte Carlo simulation to study the dosimetry of BNCE. The charged particle FLUKA code has been used to calculate the primary neutron yield from the beryllium target, while MCNP-4A has been used for the transport of these neutrons in the geometry of the Biomedical Cyclotron of Nice. The fast neutron spectrum and dose deposition, the thermal flux and thermal neutron spectrum in depth of a Plexiglas phantom has been calculated. The thermal neutron flux has been compared with experimental results determined with calibrated thermoluminescent dosimeters (TLD-600 and TLD-700, respectively, doped with 6Li or 7Li). The theoretical results were in good agreement with the experimental results: the thermal neutron flux was calculated at 10.3 X 10(6) n/cm2 s1 and measured at 9.42 X 10(6) n/cm2 s1 at 4 cm depth of the phantom and with a 10 cm X 10 cm irradiation field. For fast neutron dose deposition the calculated and experimental curves have the same slope but different shape: only the experimental curve shows a maximum at 2.27 cm depth corresponding to the build-up. The difference is due to the Monte Carlo simulation which does not follow the secondary particles. Finally, a dose enhancement of, respectively, 4.6% and 10.4% are found for 10 cm X 10 cm or 20 cm X 20 cm fields, provided that 100 micrograms/g of 10B is loaded in the tissues. It is anticipated that this calculation method may be used to improve BNCE of fast neutron irradiations through collimation modifications. PMID:9650176

  14. Erbium: YAG laser (2,940 nm) treatment stimulates hair growth through upregulating Wnt 10b and β-catenin expression in C57BL/6 mice

    PubMed Central

    Ke, Jin; Guan, Huiwen; Li, Shan; Xu, Li; Zhang, Li; Yan, Yuehua

    2015-01-01

    Aim: To evaluate the role of 2,940 nm erbium: YAG laser in hair growth in C57BL/6 mice. Methods: Anagen was experimentally induced by depilation. Healthy C57BL/6 mice (n=22) were randomly divided into four groups, with treatment of laser or minoxidil, or with combined laser and minoxidil treatments. The skin color of each mouse was observed each day. The time from telogen (pink skin color) to anagen (black coloration) phase and from anagen (black coloration) to catagen (all hairs grew out of the depilated skin) have been recorded. Hematoxylin and eosin (H&E) assay was done at fifteen days after the first treatment for each group to observe hair follicles and hair cycle score. Western blot analysis was utilized to detect the expression levels of Wnt 10-b and β-catenin. Results: Black pigmentation started significantly earlier both in the laser and combination group than in the control group. Moreover, the time from anagen to catagen in the laser, minoxidil and combination groups were all significantly shorter from the control group. Histopathology with H&E staining showed an obvious increase in the number of hair follicles in the anagen phase caused by the treatment of 2,940 nm erbium: YAG laser and minoxidil. Similarly, the percentage of hair follicles in anagen VI accounted for 19.5%, 37.5%, 41.5% and 44% in control, laser, minoxidil, and combination group, respectively. Western blot analysis showed that both the levels of Wnt 10b and β-catenin were significantly increased by the treatment of 2,940 nm erbium: YAG laser. Conclusion: Our findings showed that 2,940-nm Er: YAG laser could promote hair growth by inducing hair cycle transition from telogen to anagen phases in C57BL/6 mice through up regulating Wnt 10b and β-catenin. These results suggest that 2,940-nm Er: YAG laser may be a potential therapy for hair loss. PMID:26885014

  15. Deletion of angiotensin II type 2 receptor accelerates adipogenesis in murine mesenchymal stem cells via Wnt10b/beta-catenin signaling.

    PubMed

    Matsushita, Kenichi; Wu, Yaojiong; Pratt, Richard E; Dzau, Victor J

    2016-08-01

    Recent evidence suggests that the renin-angiotensin system (RAS) has a vital role in adipocyte biology and the pathophysiology of metabolic syndrome. Obesity is the main culprit of metabolic syndrome; and mesenchymal stem cells (MSCs) have been forwarded as a major source of adipocyte generation. Previously, we reported that MSCs have a local RAS and that pharmacological blockade of angiotensin II type 2 receptor (AT2R) promotes adipogenesis in human MSCs. However, the definitive roles of AT2R and how AT2R functions in adipogenesis remains unknown. To this end, we employed AT2R-null murine MSCs to characterize how AT2R affects the differentiation of MSCs into adipocytes. Murine MSCs were isolated from AT2R-null mice and wild-type littermates, grown to confluency, and then differentiated into adipocytes. Adipogenesis was quantitated by assessing the lipid droplet accumulation. Using the lipophilic fluorescent dye, the AT2R-null cells showed significantly increased total fluorescence (261.6±49.6% vs littermate) on day 7. Oil red O staining followed by extraction of the absorbed dye and measurement of the absorbance on day 14 also exhibited significantly increased lipid droplet accumulation in the AT2R-null cells (202.7±14.1% vs littermate). We also examined the expression of adipogenic marker genes by quantitative RT-PCR. The AT2R-null group exhibited significantly increased expression of PPAR-gamma, fatty acid synthase, and adiponectin (vs littermate). We further examined the role of Wnt10b/beta-catenin signaling, which reportedly has an important inhibitory role in adipogenesis. The AT2R-null group exhibited significantly decreased Wnt10b expression accompanied by decreased beta-catenin (vs littermate). Our results thus revealed that the AT2R inhibits adipogenic differentiation in murine MSCs. Moreover, this inhibitory effect is associated with Wnt10b/beta-catenin signaling. These results provide important insights into the pathophysiology of obesity and obesity

  16. Carbacaprazamycins: Chemically Stable Analogues of the Caprazamycin Nucleoside Antibiotics.

    PubMed

    Ichikawa, Satoshi; Yamaguchi, Mayumi; Hsuan, Lee Shang; Kato, Yuta; Matsuda, Akira

    2015-04-10

    Carbacaprazamycins, which are chemically stable analogues of caprazamycins, were designed and synthesized. These analogues were active against drug-resistant bacterial pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, and their activities were comparable to those of the parent caprazamycins. The effect of treatment with carbacaprazamycin on morphological changes in S. aureus indicated that the mode of action was completely different from those of existing peptidoglycan inhibitors. PMID:27622529

  17. Analogue and digital linear modulation techniques for mobile satellite

    NASA Technical Reports Server (NTRS)

    Whitmarsh, W. J.; Bateman, A.; Mcgeehan, J. P.

    1990-01-01

    The choice of modulation format for a mobile satellite service is complex. The subjective performance is summarized of candidate schemes and voice coder technologies. It is shown that good performance can be achieved with both analogue and digital voice systems, although the analogue system gives superior performance in fading. The results highlight the need for flexibility in the choice of signaling format. Linear transceiver technology capable of using many forms of narrowband modulation is described.

  18. Amphiphilic Tobramycin Analogues as Antibacterial and Antifungal Agents

    PubMed Central

    Shrestha, Sanjib K.; Fosso, Marina Y.; Green, Keith D.

    2015-01-01

    In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C12 and C14 chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter and 1.95 to 7.8 mg/liter, respectively. However, C4, C6, and C8 TOB analogues and TOB itself exhibited little to no antifungal activity. Fifty percent inhibitory concentrations (IC50s) for the most potent TOB analogues (C12 and C14) against A549 and Beas 2B cells were 4- to 64-fold and 32- to 64-fold higher, respectively, than their antifungal MIC values against various fungi. Unlike conventional aminoglycoside antibiotics, TOB analogues with alkyl chain lengths of C12 and C14 appear to inhibit fungi by inducing apoptosis and disrupting the fungal membrane as a novel mechanism of action. Amphiphilic TOB analogues showed broad-spectrum antifungal activities with minimal mammalian cell cytotoxicity. This study provides novel lead compounds for the development of antifungal drugs. PMID:26033722

  19. Analogue gravitational phenomena in Bose-Einstein condensates

    NASA Astrophysics Data System (ADS)

    Finazzi, Stefano

    2012-08-01

    Analogue gravity is based on the simple observation that perturbations propagating in several physical systems can be described by a quantum field theory in a curved spacetime. While phenomena like Hawking radiation are hardly detectable in astrophysical black holes, these effects may be experimentally tested in analogue systems. In this Thesis, focusing on Bose-Einstein condensates, we present our recent results about analogue models of gravity from three main perspectives: as laboratory tests of quantum field theory in curved spacetime, for the techniques that they provide to address various issues in general relativity, and as toy models of quantum gravity. The robustness of Hawking-like particle creation is investigated in flows with a single black hole horizon. Furthermore, we find that condensates with two (white and black) horizons develop a dynamical instability known in general relativity as black hole laser effect. Using techniques borrowed from analogue gravity, we also show that warp drives, which are general relativistic spacetimes allowing faster-than-light travel, are unstable. Finally, the cosmological constant issue is investigated from an analogue gravity perspective and relativistic Bose-Einstein condensates are proposed as new analogue systems with novel interesting properties.

  20. Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides

    PubMed Central

    Satishkumar, Sakilam; Vuram, Prasanna K.; Relangi, Siva Subrahmanyam; Gurram, Venkateshwarlu; Zhou, Hong; Kreitman, Robert J.; Montemayor, Michelle M. Martínez; Yang, Lijia; Kaliyaperumal, Muralidharan; Sharma, Somesh; Pottabathini, Narender; Lakshman, Mahesh K.

    2016-01-01

    Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest on the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL), and chronic lymphocytic leukemia (CLL) cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribo analogue of cladribine possessed activity, but was least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, only cladribine and its ribose analogue were most active. PMID:26556315

  1. Bisphenol A and Its Analogues Activate Human Pregnane X Receptor

    PubMed Central

    Sui, Yipeng; Ai, Ni; Park, Se-Hyung; Rios-Pilier, Jennifer; Perkins, Jordan T.; Welsh, William J.

    2012-01-01

    Background: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA and its analogues are present in environmental and human samples. Many endocrine-disrupting chemicals, including BPA, have been shown to activate the pregnane X receptor (PXR), a nuclear receptor that functions as a master regulator of xenobiotic metabolism. However, the detailed mechanism by which these chemicals activate PXR remains unknown. Objective: We investigated the mechanism by which BPA interacts with and activates PXR and examined selected BPA analogues to determine whether they bind to and activate PXR. Methods: Cell-based reporter assays, in silico ligand–PXR docking studies, and site-directed mutagenesis were combined to study the interaction between BPA and PXR. We also investigated the influence of BPA and its analogues on the regulation of PXR target genes in human LS180 cells. Results: We found that BPA and several of its analogues are potent agonists for human PXR (hPXR) but do not affect mouse PXR activity. We identified key residues within hPXR’s ligand-binding pocket that constitute points of interaction with BPA. We also deduced the structural requirements of BPA analogues that activate hPXR. BPA and its analogues can also induce PXR target gene expression in human LS180 cells. Conclusions: The present study advances our understanding of the mechanism by which BPA interacts with and activates human PXR. Activation of PXR by BPA may explain some of the adverse effects of BPA in humans. PMID:22214767

  2. Understanding Rubredoxin Redox Sites by Density Functional Theory Studies of Analogues

    SciTech Connect

    Luo, Yan; Niu, Shuqiang; Ichiye, Toshiko

    2012-09-06

    Determining the redox energetics of redox site analogues of metalloproteins is essential in unraveling the various contributions to electron transfer properties of these proteins. Since studies of the [4Fe-4S] analogues show that the energies are dependent on the ligand dihedral angles, broken symmetry density functional theory (BS-DFT) with the B3LYP functional and double-ζ basis sets calculations of optimized geometries and electron detachment energies of [1Fe] rubredoxin analogues are compared to crystal structures and gas-phase photoelectron spectroscopy data, respectively, for [Fe(SCH3)4]0/1-/2-, [Fe(S2-o-xyl)2]0/1-/2-, and Na+[Fe(S2-oxyl) 2]1-/2- in different conformations. In particular, the study of Na+[Fe(S2-o-xyl)2]1-/2- is the only direct comparison of calculated and experimental gas phase detachment energies for the 1-/2- couple found in the rubredoxins. These results show that variations in the inner sphere energetics by up to ~0.4 eV can be caused by differences in the ligand dihedral angles in either or both redox states. Moreover, these results indicate that the protein stabilizes the conformation that favors reduction. In addition, the free energies and reorganization energies of oxidation and reduction as well as electrostatic potential charges are calculated, which can be used as estimates in continuum electrostatic calculations of electron transfer properties of [1Fe] proteins.

  3. Hot Fire Ignition Test with Densified Liquid Hydrogen using a RL10B-2 Cryogenic H2/O2 Rocket Engine

    NASA Technical Reports Server (NTRS)

    McNelis, Nancy B.; Haberbusch, Mark S.

    1997-01-01

    Enhancements to propellants provide an opportunity to either increase performance of an existing vehicle, or reduce the size of a new vehicle. In the late 1980's the National AeroSpace Plane (NASP) reopened the technology chapter on densified propellants, in particular hydrogen. Since that point in time the NASA Lewis Research Center (LERC) in Cleveland, Ohio has been leading the way to provide critical research on the production and transfer of densified propellants. On October 4, 1996 NASA LeRC provided another key demonstration towards the advancement of densified propellants as a viable fuel. Successful ignition of an RL10B-2 engine was achieved with near triple point liquid hydrogen.

  4. MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology

    PubMed Central

    Sáez-Briones, P.; Hernández, A.

    2013-01-01

    Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine MDMA (3,4-methylenedioxymethamphetamine, XTC, “Ecstasy”) is the prototypical representative of a separate class of psychotropic substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of consciousness, usually described as an “open mind state”, may have relevant therapeutic applications, both in psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure. Nevertheless, a comprehensive and systematic exploration of the structure-activity relationships associated with entactogenic activity has remained incomplete and controversial, highlighting the possibility that MDMA might represent a pharmacological rarity in the field of psychotropics. As the latter is still an open question, the pharmacological characterization of MDMA analogues remains the logical strategy to attempt the elucidation of the structural requirements needed to elicit typical MDMA-like effects. Intriguingly, almost no experimental evidence supports the existence of actual MDMA analogues that truly resemble the whole pharmacological profile of MDMA, probably due to its complex (and partially not fully understood) mechanism of action that includes a disruption of monoaminergic neurotransmission. The present review presents a brief summary of the pharmacology of MDMA, followed by the evidence accumulated over the years regarding the characterization of classical structurally related MDMA analogues in different models and how this state of the art highlights the need to develop new and better MDMA analogues. PMID:24403876

  5. Genetic association of G-607C Located at wnt10b promoter with bi-sup type among Korean cerebral infarction patients

    PubMed Central

    Ko, Mi Mi; Lee, Myeong Soo; Cha, Min Ho

    2015-01-01

    Obesity is a disease threatening health and is known one of risk factors causing chronic disease. In Traditional Korean Medicine, bi-sup is casus of obesity. Wnt10b has been indicated as a potential regulator of adipogenesis in vivo and in vitro models of obesity. To analyze the distribution of wnt10b polymorphism between bi-sup group and non-bi-sup group in Korean elder subjects with cerebral infarction (CI). The study group was composed of patients with CIwho were admitted to one of the thirteen Korean oriental medical hospitals participating in this study from 2009 to 2010. A total of 670 CI patients, including 416 with bi-sup group and 254 with non-bi-sup group, participated in this study. Genotype of G-607C was conducted by primer extension using TaqManprobe and five percent of subjects were re-genotyped by direct sequencing to confirm the accuracy of the genotyping. The association of the SNP with the bi-sup group versus non-bi-sup group was performed by multiple logistic regression. Frequency of C allele in bi-sup was 45.75% which was significantly lower than 56.69% in non-bi-sup (P=0.0043, OR=0.628 [0.453-0.864]). Subjects with GC or CC type in bi-sup was also 72.36%, that was also small compared with 78.35% in non-bi-sup (P=0.0467, OR=0.675 [0.458-0.994]). These results suggest that G-607C might be used as a diagnostic genetic marker for bi-sup in stroke patients and in the development of personalized medical care. PMID:26885084

  6. Analytical procedure for mapping the distribution of 10B and 99Tc markers in cryo-sections of animal tissue samples by secondary ion mass spectrometry

    NASA Astrophysics Data System (ADS)

    Marchetti, Ilaria; Menichetti, Luca; Kusmic, Claudia; de las Heras, Laura Aldave; Salvadori, Piero; Fuoco, Roger; Belloni, Fabio; L'Abbate, Antonio; Betti, Maria

    2009-09-01

    The development of a complete, standard analytical procedure for a quantitative use of secondary ion mass spectrometry to map the distribution in animal tissues of exogenous isotopes presents difficulties inherently related to sample preparation and preservation, as well as to the specific application being considered. We have tested in two very different cases a procedure based on the cryo-preparation of samples and calibration standards. The applications under investigation were the mapping of 10B in mouse brain tissue, with relevance to the boron neutron capture therapy, and of the perfusion tracer 99Tc in mouse heart tissue, with relevance to the study of microcirculation and cardiovascular pathologies. Scanning electron microscopy and inductively coupled mass spectrometry analysis were used as reference techniques for secondary ion mass spectrometry images and analyte measurements, respectively. Cryo-preparation of tissue sections for ion microscopy proved to be simple and efficient (in terms of structural and chemical integrity) for both brain and heart samples derived from fresh organs. This technique, however, turned out to be reliable only on the brain tissue when applied to the preparation of standards, which required chemical fixation of portions of organs. Brain and heart tissues showed a totally different response to chemical fixation, from both a structural and an analytical point of view. On the one hand, we were able to estimate a relative sensitivity factor for 10B in the cryo-sectioned brain matrix; on the other hand, even without the possibility of an absolute quantification of the 99Tc signal and notwithstanding the presence of an isobaric interference, secondary ion mass spectrometry mapping however proved to be capable to resolve the specific response of the cardiac tissue to the perfusion mechanism.

  7. The solution structure of a superpotent B-chain-shortened single-replacement insulin analogue.

    PubMed Central

    Kurapkat, G.; Siedentop, M.; Gattner, H. G.; Hagelstein, M.; Brandenburg, D.; Grötzinger, J.; Wollmer, A.

    1999-01-01

    This paper reports on an insulin analogue with 12.5-fold receptor affinity, the highest increase observed for a single replacement, and on its solution structure, determined by NMR spectroscopy. The analogue is [D-AlaB26]des-(B27-B30)-tetrapeptide-insulin-B26-amide. C-terminal truncation of the B-chain by four (or five) residues is known not to affect the functional properties of insulin, provided the new carboxylate charge is neutralized. As opposed to the dramatic increase in receptor affinity caused by the substitution of D-Ala for the wild-type residue TyrB26 in the truncated molecule, this very substitution reduces it to only 18% of that of the wild-type hormone when the B-chain is present in full length. The insulin molecule in solution is visualized as an ensemble of conformers interrelated by a dynamic equilibrium. The question is whether the "active" conformation of the hormone, sought after in innumerable structure/function studies, is or is not included in the accessible conformational space, so that it could be adopted also in the absence of the receptor. If there were any chance for the active conformation, or at least a predisposed state to be populated to a detectable extent, this chance should be best in the case of a superpotent analogue. This was the motivation for the determination of the three-dimensional structure of [D-AlaB26]des-(B27-B30)-tetrapeptide-insulin-B26-amide. However, neither the NMR data nor CD spectroscopic comparison of a number of related analogues provided a clue concerning structural features predisposing insulin to high receptor affinity. After the present study it seems more likely than before that insulin will adopt its active conformation only when exposed to the force field of the receptor surface. PMID:10091652

  8. Hydrophobic surfactant proteins and their analogues.

    PubMed

    Walther, Frans J; Waring, Alan J; Sherman, Mark A; Zasadzinski, Joseph A; Gordon, Larry M

    2007-01-01

    Lung surfactant is a complex mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C and SP-D). Its major function in the lung alveolus is to reduce surface tension at the air-water interface in the terminal airways by the formation of a surface-active film enriched in surfactant lipids, hence preventing cellular collapse during respiration. Surfactant therapy using bovine or porcine lung surfactant extracts, which contain only polar lipids and native SP-B and SP-C, has dramatically improved the therapeutic outcomes of preterm infants with respiratory distress syndrome (RDS). One important goal of surfactant researchers is to replace animal-derived therapies with fully synthetic preparations based on SP-B and SP-C, produced by recombinant technology or peptide synthesis, and reconstituted with selected synthetic lipids. Here, we review recent research developments with peptide analogues of SP-B and SP-C, designed using either the known primary sequence and three-dimensional (3D) structure of the native proteins or, alternatively, the known 3D structures of closely homologous proteins. Such SP-B and SP-C mimics offer the possibility of studying the mechanisms of action of the respective native proteins, and may allow the design of optimized surfactant formulations for specific pulmonary diseases (e.g., acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)). These synthetic surfactant preparations may also be a cost-saving therapeutic approach, with better quality control than may be obtained with animal-based treatments. PMID:17575474

  9. Vascular disrupting activity of combretastatin analogues.

    PubMed

    Porcù, Elena; Salvador, Alessia; Primac, Irina; Mitola, Stefania; Ronca, Roberto; Ravelli, Cosetta; Bortolozzi, Roberta; Vedaldi, Daniela; Romagnoli, Romeo; Basso, Giuseppe; Viola, Giampietro

    2016-08-01

    Tubulin binding agents (TBAs) are drugs commonly used in cancer therapy as antimitotics. In the last years it has been described that TBAs, like combretastatin A-4 (CA-4), present also vascular disrupting activity and among its derivatives we identified three analogues endowed with potent microtubule depolymerizing activity, higher than that of the lead compound. In this paper we have investigated the anti-vascular activity of these derivatives. We tested the anti-angiogenic effects in human umbilical endothelial cells (HUVEC) and in vivo in chick chorioallantoic membrane assay (CAM), and in a syngeneic tumor mouse model. The three molecules, compound 1: 1-(3,4,5-trimethoxyphenyl)-5-(4-ethoxyphenyl)-1H-1,2,4-triazole; compound 2: (1-(3,4,5-trimethoxyphenyl)-5-(4-ethoxyphenyl)-1H-tetrazole, compound-3 (4-amino-2-p-tolylaminothiazol-5-yl)-(3,4,5-trimethoxyphenyl)-methanone) showed a moderate effect on the growth of HUVEC cells at concentrations below 200nM. At lower concentrations (5-20nM), in particular compound 2, they induced inhibition of capillary tube formation, inhibition of endothelial cell migration and affected endothelial cell morphology as demonstrated by the alteration of the microfilaments network. Moreover, they also increased permeability of HUVEC cells in a time dependent manner. In addition, compounds 1 and 3, as well as the reference compound CA-4, inhibited VEGF-induced phosphorylation of VE-cadherin and in addition compound 3 prevented the VEGF-induced phosphorylation of FAK. In CAM assay, both compounds 2 and 3 efficiently counteracted the strong angiogenic response induced by bFGF, even at the lowest concentration used (1pmol/egg). Moreover in a syngenic mouse model, compounds 1-3 after a single i.p. injection (30mg/kg), showed a stronger reduction of microvascular density. Altogether our results identified these derivatives as potential new vascular disrupting agents candidates. PMID:27235861

  10. Somatostatin Analogues for Receptor Targeted Photodynamic Therapy

    PubMed Central

    Kaščáková, Slávka; Hofland, Leo J.; De Bruijn, Henriette S.; Ye, Yunpeng; Achilefu, Samuel; van der Wansem, Katy; van der Ploeg-van den Heuvel, Angelique; van Koetsveld, Peter M.; Brugts, Michael P.; van der Lelij, Aart-Jan; Sterenborg, Henricus J. C. M.; ten Hagen, Timo L. M.; Robinson, Dominic J.; van Hagen, Martin P.

    2014-01-01

    Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2+ AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate. PMID:25111655

  11. Habitability & Astrobiology Research in Mars Terrestrial Analogues

    NASA Astrophysics Data System (ADS)

    Foing, Bernard

    2014-05-01

    We performed a series of field research campaigns (ILEWG EuroMoonMars) in the extreme Utah desert relevant to Mars environments, and in order to help in the interpretation of Mars missions measurements from orbit (MEX, MRO) or from the surface (MER, MSL), or Moon geochemistry (SMART-1, LRO). We shall give an update on the sample analysis in the context of habitability and astrobiology. Methods & Results: In the frame of ILEWG EuroMoonMars campaigns (2009 to 2013) we deployed at Mars Desert Research station, near Hanksville Utah, a suite of instruments and techniques [A, 1, 2, 9-11] including sample collection, context imaging from remote to local and microscale, drilling, spectrometers and life sensors. We analyzed how geological and geochemical evolution affected local parameters (mineralogy, organics content, environment variations) and the habitability and signature of organics and biota. Among the important findings are the diversity in the composition of soil samples even when collected in close proximity, the low abundances of detectable PAHs and amino acids and the presence of biota of all three domains of life with significant heterogeneity. An extraordinary variety of putative extremophiles was observed [3,4,9]. A dominant factor seems to be soil porosity and lower clay-sized particle content [6-8]. A protocol was developed for sterile sampling, contamination issues, and the diagnostics of biodiversity via PCR and DGGE analysis in soils and rocks samples [10, 11]. We compare the 2009 campaign results [1-9] to new measurements from 2010-2013 campaigns [10-12] relevant to: comparison between remote sensing and in-situ measurements; the study of minerals; the detection of organics and signs of life. Keywords: field analogue research, astrobiology, habitability, life detection, Earth-Moon-Mars, organics References [A] Foing, Stoker & Ehrenfreund (Editors, 2011) "Astrobiology field Research in Moon/Mars Analogue Environments", Special Issue of International

  12. Incorporation of tryptophan analogues into the lantibiotic nisin.

    PubMed

    Zhou, Liang; Shao, Jinfeng; Li, Qian; van Heel, Auke J; de Vries, Marcel P; Broos, Jaap; Kuipers, Oscar P

    2016-05-01

    Lantibiotics are posttranslationally modified peptides with efficient inhibitory activity against various Gram-positive bacteria. In addition to the original modifications, incorporation of non-canonical amino acids can render new properties and functions to lantibiotics. Nisin is the most studied lantibiotic and contains no tryptophan residues. In this study, a system was constructed to incorporate tryptophan analogues into nisin, which included the modification machinery (NisBTC) and the overexpression of tryptophanyl-tRNA synthetase (TrpRS). Tryptophan and three different tryptophan analogues (5-fluoroTrp (5FW), 5-hydroxyTrp (5HW) and 5-methylTrp (5MeW)) were successfully incorporated at four different positions of nisin (I1W, I4W, M17W and V32W). The incorporation efficiency of tryptophan analogues into mutants I1W, M17W and V32W was over 97 %, while the mutant I4W showed relatively low incorporation efficiency (69-93 %). The variants with 5FW showed relatively higher production yield, while 5MeW-containing variants showed the lowest yield. The dehydration efficiency of serines or threonines was affected by the tryptophan mutants of I4W and V32W. The affinity of the peptides for the cation-ion exchange and reverse phase chromatography columns was significantly reduced when 5HW was incorporated. The antimicrobial activity of IIW and its 5FW analogue both decreased two times compared to that of nisin, while that of its 5HW analogue decreased four times. The 5FW analogue of I4W also showed two times decreased activity than nisin. However, the mutant M17W and its 5HW analogue both showed 32 times reduced activity relative to that of nisin. PMID:26872656

  13. Terrestrial research in Mars analogue environments

    NASA Astrophysics Data System (ADS)

    Osipov, G.

    Fatty acids (FA) content was measured by GC-MS SIM technique in Sulfide ores of present day (Mid-Atlantic Ridge and others) and ancient (Ural Paleocene, Russia) black smokers; Early Proterozoic kerites of Volyn; Siberian, Canadian and Antarctic permafrosts and also in rocks of East-European platform Achaean crystalline basement. Analysis was shown presence those and only those fatty acids which are specific to microorganisms. FA with 12 up 19 of carbon atoms are thought to be a bacterial biomass sign. 3-Hydroxy fatty acids also found in samples and are strong specific markers of gram-negative bacteria. Cultivation yield living bacteria in some cases. The East-European platform Achaean crystalline basement rocks opened by Vorotilov Deep Well (VDW) drilled through Puchezh-Katunski impact structure were studied within depths 2575 - 2805 m. 34 microbial lipid markers were detected by GC-MS and 22 species were identified. Bacteria of g. Bacillus reached 6,8 % in subsurface communities. However, members of gg. Clostridium (37,1 - 33,2 %) and Rhodococcus (27,6 - 33,7 %) were absolute dominants within studied depth interval. Some lipid patterns of kerite samples could be assessed to definite genera or, in special cases, to species of contemporary microorganisms. For instance, 2-hydroxylauric acid is specific to Pseudomonas putida group or Acinetobacter spp., and hydroxymyristic together with hydroxypalmitic are specific to P.cepacea and cyanobacteria. 3-hydroxystearic acid was known as component of Acetobacter diazothrophycus and Gloebacter violaceous cyanobacterium. 10-hydroxystearic acid associated with Nocardia spp., which oxidizes oleic acid in organic substrates. 10-methylhexadecanoic (10Me16) acid together with 10Me14, 10Me15 and 10Me17 analogues are markers of actinomycetes. Significant part of Black Smokers organic matter is probably biogenic. Fatty acid features strongly assigns it to bacterial, microeucariotic and planta cells. Par example 3-hydroxy acids are

  14. Spectral analysis of lunar analogue samples

    NASA Astrophysics Data System (ADS)

    Offringa, Marloes; Foing, Bernard

    2016-04-01

    Analyses of samples derived from terrestrial analogue sites are used to study lunar processes in their geological context (Foing, Stoker, Ehrenfreund, 2011). For this study samples from the volcanic region of the Eifel, Germany collected during field campaigns (Foing et al., 2010), are analyzed with a variety of spectrometers. The aim is to obtain a database of analyzed samples that could be used as a reference for future in situ measurements. Equipment used in the laboratory consists of a Fourier Transform Infrared (FTIR) spectrometer, an X-Ray Fluorescence (XRF) spectrometer, a Raman laser spectrometer, as well as UV-VIS and NIR reflectance spectrometers. The Raman, UV-VIS and NIR are also used in combination with the EXoGeoLab mock-up lander during field campaigns (Foing, Stoker, Ehrenfreund, 2011). Calibration of the UV-VIS and NIR reflectance spectrometers is the main focus of this research in order to obtain the clearest spectra. The calibration of the UV-VIS and NIR reflectance spectrometers requires the use of a good light source as well as suitable optical fibers to create a signal that covers the widest range in wavelengths available. To eliminate noise towards the edges of this range, multiple measurements are averaged and data is processed by dividing the signal by reference spectra. Calibration of the devices by creating a new dark and reference spectra has to take place after every sample measurement. In this way we take into account changes that occur in the signal due to the eating of the devices during the measurements. Moreover, the integration time is adjusted to obtain a clear signal without leading to oversaturation in the reflectance spectrum. The typical integration times for the UV-VIS reflectance spectrometer vary between 1 - 18 s, depending on the amount of daylight during experiments. For the NIR reflectance spectrometer the integration time resulting in the best signals is approximately 150 ms in combination with a broad spectrum light

  15. Iron isotopes in an Archean ocean analogue

    NASA Astrophysics Data System (ADS)

    Busigny, Vincent; Planavsky, Noah J.; Jézéquel, Didier; Crowe, Sean; Louvat, Pascale; Moureau, Julien; Viollier, Eric; Lyons, Timothy W.

    2014-05-01

    Iron isotopes have been extensively used to trace the history of microbial metabolisms and the redox evolution of the oceans. Archean sedimentary rocks display greater variability in iron isotope ratios and more markedly negative values than those deposited in the Proterozoic and Phanerozoic. This increased variability has been linked to changes in either water column iron cycling or the extent of benthic microbial iron reduction through time. We tested these contrasting scenarios through a detailed study of anoxic and ferruginous Lac Pavin (France), which can serve as a modern analogue of the Archean ocean. A depth-profile in the water column of Lac Pavin shows a remarkable increase in dissolved Fe concentration (0.1-1200 μM) and δ56Fe values (-2.14‰ to +0.31‰) across the oxic-anoxic boundary to the lake bottom. The largest Fe isotope variability is found at the redox boundary and is related to partial oxidation of dissolved ferrous iron, leaving the residual Fe enriched in light isotopes. The analysis of four sediment cores collected along a lateral profile (one in the oxic layer, one at the redox boundary, one in the anoxic zone, and one at the bottom of the lake) indicates that bulk sediments, porewaters, and reactive Fe mostly have δ56Fe values near 0.0 ± 0.2‰, similar to detrital iron. In contrast, pyrite δ56Fe values in sub-chemocline cores (60, 65, and 92 m) are highly variable and show significant deviations from the detrital iron isotope composition (δ56Fepyrite between -1.51‰ and +0.09‰; average -0.93‰). Importantly, the pyrite δ56Fe values mirror the δ56Fe of dissolved iron at the redox boundary—where near quantitative sulfate and sulfide drawdown occurs—suggesting limited iron isotope fractionation during iron sulfide formation. This finding has important implications for the Archean environment. Specifically, this work suggests that in a ferruginous system, most of the Fe isotope variability observed in sedimentary pyrites can

  16. Structural insights into the interactions of xpt riboswitch with novel guanine analogues: a molecular dynamics simulation study.

    PubMed

    Jain, Swapan S; Sonavane, Uddhavesh B; Uppuladinne, Mallikarjunachari V N; McLaughlin, Emily C; Wang, Weiqing; Black, Sheneil; Joshi, Rajendra R

    2015-01-01

    Ligand recognition in purine riboswitches is a complex process requiring different levels of conformational changes. Recent efforts in the area of purine riboswitch research have focused on ligand analogue binding studies. In the case of the guanine xanthine phosphoribosyl transferase (xpt) riboswitch, synthetic analogues that resemble guanine have the potential to tightly bind and subsequently influence the genetic expression of xpt mRNA in prokaryotes. We have carried out 25 ns Molecular Dynamics (MD) simulation studies of the aptamer domain of the xpt G-riboswitch in four different states: guanine riboswitch in free form, riboswitch bound with its cognate ligand guanine, and with two guanine analogues SJ1 and SJ2. Our work reveals novel interactions of SJ1 and SJ2 ligands with the binding core residues of the riboswitch. The ligands proposed in this work bind to the riboswitch with greater overall stability and lower root mean square deviations and fluctuations compared to guanine ligand. Reporter gene assay data demonstrate that the ligand analogues, upon binding to the RNA, lower the genetic expression of the guanine riboswitch. Our work has important implications for future ligand design and binding studies in the exciting field of riboswitches. PMID:24404773

  17. Design of potent substrate-analogue inhibitors of canine renin

    NASA Technical Reports Server (NTRS)

    Hui, K. Y.; Siragy, H. M.; Haber, E.

    1992-01-01

    Through a systematic study of structure-activity relationships, we designed potent renin inhibitors for use in dog models. In assays against dog plasma renin at neutral pH, we found that, as in previous studies of rat renin inhibitors, the structure at the P2 position appears to be important for potency. The substitution of Val for His at this position increases potency by one order of magnitude. At the P3 position, potency appears to depend on a hydrophobic side chain that does not necessarily have to be aromatic. Our results also support the approach of optimizing potency in a renin inhibitor by introducing a moiety that promotes aqueous solubility (an amino group) at the C-terminus of the substrate analogue. In the design of potent dog plasma renin inhibitors, the influence of the transition-state residue 4(S)-amino-3(S)-hydroxy-5-cyclohexylpentanoic acid (ACHPA)-commonly used as a substitute for the scissile-bond dipeptide to boost potency-is not obvious, and appears to be sequence dependent. The canine renin inhibitor Ac-paF-Pro-Phe-Val-statine-Leu-Phe-paF-NH2 (compound 15; IC50 of 1.7 nM against dog plasma renin at pH 7.4; statine, 4(S)-amino-3(S)-hydroxy-6-methylheptanoic acid; paF, para-aminophenylalanine) had a potent hypotensive effect when infused intravenously into conscious, sodium-depleted, normotensive dogs. Also, compound 15 concurrently inhibited plasma renin activity and had a profound diuretic effect.

  18. Two-dimensional graphene analogues for biomedical applications.

    PubMed

    Chen, Yu; Tan, Chaoliang; Zhang, Hua; Wang, Lianzhou

    2015-05-01

    The increasing demand of clinical biomedicine and fast development of nanobiotechnology has substantially promoted the generation of a variety of organic/inorganic nanosystems for biomedical applications. Biocompatible two-dimensional (2D) graphene analogues (e.g., nanosheets of transition metal dichalcogenides, transition metal oxides, g-C3N4, Bi2Se3, BN, etc.), which are referred to as 2D-GAs, have emerged as a new unique family of nanomaterials that show unprecedented advantages and superior performances in biomedicine due to their unique compositional, structural and physicochemical features. In this review, we summarize the state-of-the-art progress of this dynamically developed material family with a particular focus on biomedical applications. After the introduction, the second section of the article summarizes a range of synthetic methods for new types of 2D-GAs as well as their surface functionalization. The subsequent section provides a snapshot on the use of these biocompatible 2D-GAs for a broad spectrum of biomedical applications, including therapeutic (photothermal/photodynamic therapy, chemotherapy and synergistic therapy), diagnostic (fluorescent/magnetic resonance/computed tomography/photoacoustic imaging) and theranostic (concurrent diagnostic imaging and therapy) applications, especially on oncology. In addition, we briefly present the biosensing applications of these 2D-GAs for the detection of biomacromolecules and their in vitro/in vivo biosafety evaluations. The last section summarizes some critical unresolved issues, possible challenges/obstacles and also proposes future perspectives related to the rational design and construction of 2D-GAs for biomedical engineering, which are believed to promote their clinical translations for benefiting the personalized medicine and human health. PMID:25519856

  19. Quantum sine-Gordon dynamics on analogue curved spacetime in a weakly imperfect scalar Bose gas

    NASA Astrophysics Data System (ADS)

    Volkoff, T. J.; Fischer, Uwe R.

    2016-07-01

    Using the coherent state functional integral expression of the partition function, we show that the sine-Gordon model on an analogue curved spacetime arises as the effective quantum field theory for phase fluctuations of a weakly imperfect Bose gas on an incompressible background superfluid flow when these fluctuations are restricted to a subspace of the single-particle Hilbert space. We consider bipartitions of the single-particle Hilbert space relevant to experiments on ultracold bosonic atomic or molecular gases, including, e.g., restriction to high- or low-energy sectors of the dynamics and spatial bipartition corresponding to tunnel-coupled planar Bose gases. By assuming full unitary quantum control in the low-energy subspace of a trapped gas, we show that (1) appropriately tuning the particle number statistics of the lowest-energy mode partially decouples the low- and high-energy sectors, allowing any low-energy single-particle wave function to define a background for sine-Gordon dynamics on curved spacetime and (2) macroscopic occupation of a quantum superposition of two states of the lowest two modes produces an analogue curved spacetime depending on two background flows, with respective weights continuously dependent on the corresponding weights of the superposed quantum states.

  20. A microdosimetric study of {sup 10}B(n,{alpha}){sup 7}Li and {sup 157}Gd(n,{gamma}) reactions for neutron capture therapy

    SciTech Connect

    Wang, C.K.C.; Sutton, M.; Evans, T.M.; Laster, B.H.

    1999-01-01

    This paper presents the microdosimetric analysis for the most interesting cell survival experiment recently performed at the Brookhaven National Laboratory (BNL). In this experiment, the cells were first treated with a gadolinium (Gd) labeled tumor-seeking boronated porphyrin (Gd-BOPP) or with BOPP alone, and then irradiated with thermal neutrons. The resulting cell-survival curves indicate that the {sup 157}Gd(n,{gamma}) reactions are very effective in cell killing. The death of a cell treated with Gd-BOPP was attributed to either the {sup 10}B(n,{alpha}){sup 7}Li reactions or the {sup 157}Gd(n,{gamma}) reactions (or both). However, the quantitative relationship between the two types of reaction and the cell-survival fraction was not clear. This paper presents the microdosimetric analysis for the BNL experiment based on the measured experimental parameters, and the results clearly suggest a quantitative relationship between the two types of reaction and the cell survival fraction. The results also suggest new research in gadolinium neutron capture therapy (GdNCT) which may lead to a more practical modality than the boron neutron capture therapy (BNCT) for treating cancers.

  1. A microdosimetric study of {sup 10}B(n,{alpha}){sup 7}Li and {sup 157}Gd(n,{gamma}) reactions for neutron capture therapy

    SciTech Connect

    Wang, C.K.C.; Sutton, M.; Evans, T.M.; Laster, B.H.

    1996-12-31

    This paper presents the microdosimetric analysis for the most interesting cell survival experiment recently performed at the Brookhaven National Laboratory (BNL). In this experiment, the cells were first treated with a gadolinium (Gd) labeled tumor-seeking boronated porphyrin (Gd-BOPP) or with BOPP alone, and then irradiated with thermal neutrons. The resulting cell survival curves indicate that the {sup 157}Gd(n,{gamma}) reactions is very effective in cell killing. The death of a cell treated with GD-BOPP were attributed to either the {sup 10}B(n,{alpha}) {sup 7}Li reactions or the {sup 157}Gd(n,{gamma}) reactions (or both). However, the quantitative relationship between the two types of reaction and the cell survival fraction was not clear. This paper presents the microdosimetric analysis for the BNL experiment based on the measured experimental parameters, and the results clearly suggest a quantitative relationship between the two types of reaction and the cell survival fraction. The results also suggest new research in Gadolinium neutron capture therapy (GDNCT) which may lead to a more practical modality than the boron neutron capture therapy (BNCT) for treating cancers.

  2. Hydrothermal synthesis of Ni 2FeBO 5 in near-supercritical PWR coolant and possible effects of neutron-induced 10B fission in fuel crud

    NASA Astrophysics Data System (ADS)

    Sawicki, Jerzy A.

    2011-08-01

    The hydrothermal synthesis of a nickel-iron oxyborate, Ni 2FeBO 5, known as bonaccordite, was investigated at pressures and temperatures that might occur at the surface of high-power fuel rods in PWR cores and in supercritical water reactors, especially during localized departures from nucleate boiling and dry-outs. The tests were performed using aqueous mixtures of nickel and iron oxides with boric acid or boron oxide, and as a function of lithium hydroxide addition, temperature and time of heating. At subcritical temperatures nickel ferrite NiFe 2O 4 was always the primary reaction product. High yield of Ni 2FeBO 5 synthesis started near critical water temperature and was strongly promoted by additions of LiOH up to Li/Fe and Li/B molar ratios in a range 0.1-1. The synthesis of bonaccordite was also promoted by other alkalis such as NaOH and KOH. The bonaccordite particles were likely formed by dissolution and re-crystallization by means of an intermediate nickel ferrite phase. It is postulated that the formation of Ni 2FeBO 5 in deposits of borated nickel and iron oxides on PWR fuel cladding can be accelerated by lithium produced in thermal neutron capture 10B(n,α) 7Li reactions. The process may also be aided in the reactor core by kinetic energy of α-particles and 7Li ions dissipated in the crud layer.

  3. Lytic Polysaccharide Monooxygenases ScLPMO10B and ScLPMO10C Are Stable in Ionic Liquids As Determined by Molecular Simulations.

    PubMed

    Sprenger, K G; Choudhury, Alaksh; Kaar, Joel L; Pfaendtner, Jim

    2016-04-28

    Lytic polysaccharide monooxygenases (LPMOs) are a newly discovered family of enzymes proposed to work synergistically with cellulases and aid in the decomposition of cellulose for the creation of environmentally friendly fuels and chemicals. To our knowledge, evaluation of the stability of LPMOs in ionic liquid (IL) solvents at relevant biomass processing conditions has not been explored. Herein, molecular dynamics simulations of ScLPMO10B and ScLPMO10C in three ILs at 10 and 20 wt% in water and in pure water have been performed. Enzyme stability was predicted to be high on the basis of structural and dynamic analyses we performed. We used the simulations to identify key areas that deviate from the crystal structures as a starting place for surface charge modifications to increase stability in ILs. Results show that, in general, both enzymes have a high degree of stability across the range of IL solutions tested. For each enzyme, two regions were identified that showed notable deviations from the crystal structure. In addition to providing a basis for future rational design efforts, this work represents a first step toward engineering LPMOs to function efficiently in enzyme cocktails for use in industrial biomass processing applications with ILs. PMID:27052057

  4. KELT-10b and KELT-11b: Two Sub-Jupiter Mass Planets well-Suited for Atmospheric Characterization in the Southern Hemisphere

    NASA Astrophysics Data System (ADS)

    Rodriguez, Joseph E.

    2015-12-01

    The Kilodegree Extremely Little Telescope (KELT) project is a photometric survey in both the northern and southern hemispheres for transiting planets around bright stars (8 < V < 11), and has discovered 15 planets to date. Of these, several possess unique characteristics that make them especially well suited for study of planet atmospheres. Here, I present the first two discoveries from the KELT-South survey. KELT-10b is an inflated transiting sub-Jupiter mass planet (0.68 MJ) around a V=10.7 early G-star. It has the 3rd deepest transit (1.4%) in the southern hemisphere for a star V < 12.5, making it a great target for transmission spectroscopy. KELT-11b is a highly inflated transiting Saturn mass planet (0.22 MJ) orbiting one of the brightest planet-hosting stars in the southern hemisphere. Interestingly, KELT-11b's host star is a clear sub-giant star (log(g) ~ 3.7). I will discuss their impact for atmospheric characterization. For example, the highly inflated nature of the KELT-11b planet provides the ability to study a sub-Jupiter atmosphere at very low planetary gravity, while the sub-giant nature of its host star allows us to study the effects of post main sequence evolution of a host star on a hot Jupiter.

  5. Migrastatin analogues target fascin to block tumour metastasis

    SciTech Connect

    Chen, L.; Jakoncic, J.; Yang, S.; Zhang, J.; Huang, X.Y.

    2010-04-15

    Tumour metastasis is the primary cause of death of cancer patients. Development of new therapeutics preventing tumour metastasis is urgently needed. Migrastatin is a natural product secreted by Streptomyces, and synthesized migrastatin analogues such as macroketone are potent inhibitors of metastatic tumour cell migration, invasion and metastasis. Here we show that these migrastatin analogues target the actin-bundling protein fascin to inhibit its activity. X-ray crystal structural studies reveal that migrastatin analogues bind to one of the actin-binding sites on fascin. Our data demonstrate that actin cytoskeletal proteins such as fascin can be explored as new molecular targets for cancer treatment, in a similar manner to the microtubule protein tubulin.

  6. Membrane-permeable Triphosphate Prodrugs of Nucleoside Analogues.

    PubMed

    Gollnest, Tristan; Dinis de Oliveira, Thiago; Rath, Anna; Hauber, Ilona; Schols, Dominique; Balzarini, Jan; Meier, Chris

    2016-04-18

    The metabolic conversion of nucleoside analogues into their triphosphates often proceeds insufficiently. Rate-limitations can be at the mono-, but also at the di- and triphosphorylation steps. We developed a nucleoside triphosphate (NTP) delivery system (TriPPPro-approach). In this approach, NTPs are masked by two bioreversible units at the γ-phosphate. Using a procedure involving H-phosphonate chemistry, a series of derivatives bearing approved, as well as potentially antivirally active, nucleoside analogues was synthesized. The enzyme-triggered delivery of NTPs was demonstrated by pig liver esterase, in human T-lymphocyte cell extracts and by a polymerase chain reaction using a prodrug of thymidine triphosphate. The TriPPPro-compounds of some HIV-inactive nucleoside analogues showed marked anti-HIV activity. For cellular uptake studies, a fluorescent TriPPPro-compound was prepared that delivered the triphosphorylated metabolite to intact CEM cells. PMID:27008042

  7. The metabolic and mitogenic properties of basal insulin analogues

    PubMed Central

    2013-01-01

    Context Retrospective, observational studies have reported an association between diabetes treatment with insulin and a higher incidence of cancer. Objective Overview the literature for in vitro and in vivo studies of the metabolic and mitogenic properties of basal insulin analogues and assess the implications for clinical use. Methods Relevant studies were identified through PubMed and congress abstract database searches; data on metabolic and mitogenic signalling in relation to insulin treatment of diabetes are included in this review. Results The balance of evidence shows that although some analogues have demonstrated mitogenic potency in some in vitro studies in cancer cell lines, these findings do not translate to the in vivo setting in animals or to the clinical setting in humans. Conclusions The current consensus is that there is no clinical or in vivo evidence to indicate that any commercially available insulin analogue has carcinogenic effects. Large-scale, prospective clinical and observational studies will further establish any potential link. PMID:23373726

  8. Synthesis and cytotoxic activities of semisynthetic zearalenone analogues.

    PubMed

    Tadpetch, Kwanruthai; Kaewmee, Benyapa; Chantakaew, Kittisak; Kantee, Kawalee; Rukachaisirikul, Vatcharin; Phongpaichit, Souwalak

    2016-08-01

    Zearalenone is a β-resorcylic acid macrolide with various biological activities. Herein we report the synthesis and cytotoxic activities of 34 zearalenone analogues against human oral epidermoid carcinoma (KB) and human breast adenocarcinoma (MCF-7) cells as well as noncancerous Vero cells. Some zearalenone analogues showed moderately enhanced cytotoxic activities against the two cancer cell lines. We have discovered the potential lead compounds with diminished or no cytotoxicity to Vero cells. Preliminary structure-activity relationship studies revealed that the double bond at the 1' and 2' positions of zearalenone core was crucial for cytotoxic activities on both cell lines. In addition, for zearalenol analogues, the unprotected hydroxyl group at C-2 and an alkoxy substituent at C-4 played key roles on cytotoxic effects of both cell lines. PMID:27311894

  9. Synthesis and Biological Evaluation of New (-)-Englerin Analogues.

    PubMed

    López-Suárez, Laura; Riesgo, Lorena; Bravo, Fernando; Ransom, Tanya T; Beutler, John A; Echavarren, Antonio M

    2016-05-01

    We report the synthesis and biological evaluation of a series of (-)-englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth-inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC). PMID:27005578

  10. Analogue peptides for the immunotherapy of human acute myeloid leukemia.

    PubMed

    Hofmann, Susanne; Mead, Andrew; Malinovskis, Aleksandrs; Hardwick, Nicola R; Guinn, Barbara-Ann

    2015-11-01

    The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies. PMID:26438084

  11. Nicorandil analogues containing NO-donor furoxans and related furazans.

    PubMed

    Boschi, D; Cena, C; Di Stilo, A; Fruttero, R; Gasco, A

    2000-07-01

    The synthesis and in vitro vasodilating properties of hybrid compounds in which furoxan (1,2,5-oxadiazole 2-oxide) moieties, endowed with different NO-donor properties, were substituted for the nitroxy function of Nicorandil are reported. The corresponding cyanoguanidine analogues are also considered. This approach has led to a series of vasorelaxing compounds devoid of affinity for K(ATP) channels, whose activity is prevalently due to their ability to activate sGC, at the concentrations of the experiments. Related furazan (1,2,5-oxadiazole) derivatives, unable to release nitric oxide were also prepared and studied for control. The amide analogues of Nicorandil display feeble vasorelaxing action not involving the activation of K+ channels, while in the guanidine analogues, this mechanism seems to underlie this action. PMID:10976520

  12. Relative benefits of linear analogue and advanced digital hearing aids.

    PubMed

    Wood, Sally A; Lutman, Mark E

    2004-03-01

    Speech recognition performance and self-reported benefit from linear analogue and advanced (digital) hearing aids were compared in 100 first-time hearing aid users with mild-to-moderate sensorineural hearing loss fitted monaurally with a behind-the-ear (BTE) hearing aid in a single-blind randomized crossover trial. Subjects used each aid for 5 weeks in turn, with aid order balanced across subjects. Three alternative models of digital hearing aid were assigned to subjects according to a balanced design. Aid type was disguised to keep subjects blind within practical limitations. Aided speech recognition performance in noise was measured at speech levels of 65 and 75dB at a speech-to-noise ratio (SNR) of +2dB for closed sets of single words. Self-rated benefit was measured using the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Glasgow Hearing Aid Benefit Profile (GHABP). Quality of life, hearing aid use and user preferences were also assessed. Speech recognition scores with the digital aids were significantly better at 75dB than with the analogue aids Self-reported benefit (APHAB, GHABP) and improvement in quality of life were generally not significantly different between analogue and digital aids, although aversiveness measured with the APHAB was significantly lower with digital aids, and satisfaction measured with the GHABP was greater. The digital aids were preferred significantly more often than the analogue aids, with 61 subjects choosing their digital aid, 26 choosing the analogue aid, and nine being equivocal. Overall, this study shows advantages for advanced digital over simple linear analogue aids in terms of both objective and subjective outcomes, although average differences are not large. PMID:15198378

  13. The Object-analogue approach for probabilistic forecasting

    NASA Astrophysics Data System (ADS)

    Frediani, M. E.; Hopson, T. M.; Anagnostou, E. N.; Hacker, J.

    2015-12-01

    The object-analogue is a new method to estimate forecast uncertainty and to derive probabilistic predictions of gridded forecast fields over larger regions rather than point locations. The method has been developed for improving the forecast of 10-meter wind speed over the northeast US, and it can be extended to other forecast variables, vertical levels, and other regions. The object-analogue approach combines the analog post-processing technique (Hopson 2005; Hamill 2006; Delle Monache 2011) with the Method for Object-based Diagnostic Evaluation (MODE) for forecast verification (Davis et al 2006a, b). Originally, MODE is used to verify mainly precipitation forecasts using features of a forecast region represented by an object. The analog technique is used to reduce the NWP systematic and random errors of a gridded forecast field. In this study we use MODE-derived objects to characterize the wind fields forecasts into attributes such as object area, centroid location, and intensity percentiles, and apply the analogue concept to these objects. The object-analogue method uses a database of objects derived from reforecasts and their respective reanalysis. Given a real-time forecast field, it searches the database and selects the top-ranked objects with the most similar set of attributes using the MODE fuzzy logic algorithm for object matching. The attribute probabilities obtained with the set of selected object-analogues are used to derive a multi-layer probabilistic prediction. The attribute probabilities are combined into three uncertainty layers that address the main concerns of most applications: location, area, and magnitude. The multi-layer uncertainty can be weighted and combined or used independently in such that it provides a more accurate prediction, adjusted according to the application interest. In this study we present preliminary results of the object-analogue method. Using a database with one hundred storms we perform a leave-one-out cross-validation to

  14. Opto-electronic properties of low band gap fused-ring thieno[3,4-b]pyrazine analogues - A theoretical study

    NASA Astrophysics Data System (ADS)

    Saranya, G.; Kolandaivel, P.; Senthilkumar, K.

    2013-10-01

    The structural, optical and ionic properties of thieno[3,4-b]pyrazine (TP) analogues have been studied using quantum chemical methods. The density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods were employed to optimise the ground- and excited-state geometries of TP analogues. Based on the ground- and excited-state geometries, the absorption and emission spectra have been calculated by using TD-DFT method with 6-311G(d,p) basis set. All the calculations were carried out in gas phase and in acetonitrile and chloroform medium. The solvent-phase calculations were performed using the polarisable continuum model (PCM). It has been observed that the effect of medium on the calculated absorption and emission spectra of these analogues is negligible. The calculated absorption and emission spectra are in good agreement with the available experimental results. This theoretical investigation shows that the fused-ring thieno[3,4-b]pyrazine analogues dibenzo[f,h]thieno[3,4-b]quinoxalines and thieno[3‧,4‧:5,6]pyrazino[2,3-f][1,10] phenanthroline have lower band gap than the thieno[3,4-b]pyrazine. Hence, these analogues can be used for the production of low band gap conjugated polymers.

  15. Substrate analogues as probes of the catalytic mechanism of L-mandelate dehydrogenase from Rhodotorula graminis.

    PubMed Central

    Smékal, O; Reid, G A; Chapman, S K

    1994-01-01

    A detailed kinetic analysis of the oxidation of mono-substituted mandelates catalysed by L-(+)-mandelate dehydrogenase (L-MDH) from Rhodotorula graminis has been carried out to elucidate the role of the substrate in the catalytic mechanism. Values of Km and kcat. (25 degrees C, pH 7.5) were determined for mandelate and eight substrate analogues. Values of the activation parameters, delta H++ and delta S++ (determined over the range 5-37 degrees C), for mandelate and all substrate analogues were compensatory resulting in similar low values for free energies of activation delta G++ (approx. 60 kJ.mol-1 at 298.15 K) in all cases. A kinetic-isotope-effect value of 1.1 +/- 0.1 was observed using D,L-[2-2H]mandelate as substrate and was invariant over the temperature range studied. The logarithm of kcat. values for the enzymic oxidation of mandelate and all substrate analogues (except 4-hydroxymandelate) showed good correlation with Taft's dual substituent constant omega (where omega = omega I + 0.64 omega +R) and gave a positive reaction constant value, rho, of 0.36 +/- 0.07. This linear free-energy relationship was verified by analysing the data using isokinetic methods. These findings support the hypothesis that the enzyme-catalysed reaction proceeds via the same transition state for each substrate and indicates that this transition state is relatively nonpolar but has an electron-rich centre at the alpha-carbon position. PMID:8110205

  16. Naturally occurring crystalline phases: analogues for radioactive waste forms

    SciTech Connect

    Haaker, R.F.; Ewing, R.C.

    1981-01-01

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included.

  17. Halogenase Engineering for the Generation of New Natural Product Analogues.

    PubMed

    Brown, Stephanie; O'Connor, Sarah E

    2015-10-12

    Halogenases catalyze the incorporation of halogen atoms into organic molecules. Given the importance that halogenation has on the biological activity of small molecules, these enzymes have been subjected to intense engineering efforts to make them more suitable for biotechnology applications. The ability to biohalogenate complex molecules provides, in principle, the opportunity for rapid generation of a series of analogues with new or improved properties. Here we discuss the potential and limitations of using halogenases as biocatalysts, including recent advances in engineering halogenases to generate halogenated natural product analogues. PMID:26256103

  18. Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

    PubMed Central

    Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

    1992-01-01

    In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines

  19. 12-Amino-andrographolide analogues: synthesis and cytotoxic activity.

    PubMed

    Kasemsuk, Sakkasem; Sirion, Uthaiwan; Suksen, Kanoknetr; Piyachaturawat, Pawinee; Suksamrarn, Apichart; Saeeng, Rungnapha

    2013-12-01

    Andrographolide, a diterpenoid lactone of the plant Andrographis paniculata, has been shown to be cytotoxic against various cancer cells in vitro. In the present study, a series of β-amino-γ-butyrolactone analogues has been synthesized from naturally occurring andrographolide via one pot tandem aza-conjugate addition-elimination reaction. By using economic procedure without any base or catalyst at room temperature, the products obtained were in fair to excellent yields with high stereoselectivity. The cytotoxicity of all new amino analogues were evaluated against six cancer cell lines and revealed their potential for being developed as promising anti-cancer agents. PMID:23709127

  20. Concise synthesis of ether analogues of lysobisphosphatidic acid.

    PubMed

    Jiang, Guowei; Xu, Yong; Falguières, Thomas; Gruenberg, Jean; Prestwich, Glenn D

    2005-09-01

    We describe a versatile, efficient method for the preparation of ether analogues of (S,S)-lysobisphosphatidic acid (LBPA) and its enantiomer from (S)-solketal. Phosphorylation of a protected sn-2-O-octadecenyl glyceryl ether with 2-cyanoethyl bis-N,N-diisopropylamino phosphine and subsequent deprotection generated the bisether LBPA analogues. By simply changing the sequence of deprotection steps, we obtained the (R,R)- and (S,S)-enantiomers of 2,2'-bisether LBPA. An ELISA assay with anti-LBPA monoclonal antibodies showed that the bisether LBPAs were recognized with the same affinity as the natural 2,2'-bisoleolyl LBPA. [reaction: see text] PMID:16119911

  1. Synthesis of Conformationally Locked Versions of Puromycin Analogues

    PubMed Central

    Saneyoshi, Hisao; Michel, Benoît Y.; Choi, Yongseok; Strazewski, Peter; Marquez, Victor E.

    2009-01-01

    Conformationally locked North and South versions of puromycin analogues built on a bicyclo[3.1.0]hexane pseudosugar template were synthesized. The final assembly of the products was accomplished by the Staudinger-Vilarrasa coupling of the corresponding North (2 and 3) and South (6 and 7) 3′-azidopurine carbanucleosides with the Fmoc-protected 1-hydroxybenzotriazole ester of 4-methoxy-L-tyrosine. North azides 2 and 3 were reported earlier. The 3′-azido intermediates 6 and 7 that are necessary for the synthesis of the South puromycin analogues are described herein for the first time. PMID:18991379

  2. Tumor imaging and therapy using radiolabeled somatostatin analogues.

    PubMed

    de Jong, Marion; Breeman, Wout A P; Kwekkeboom, Dik J; Valkema, Roelf; Krenning, Eric P

    2009-07-21

    Molecular imaging plays an essential role in balancing the clinical benefits and risks of radionuclide-based cancer therapy. To effectively treat individual patients, careful assessment of biodistribution, dosimetry, and toxicity is essential. In this Account, we describe advances that combine features of molecular imaging and radionuclide therapy to provide new avenues toward individualized cancer treatment. Selective receptor-targeting radiopeptides have emerged as an important class of radiopharmaceuticals for molecular imaging and therapy of tumors that overexpress peptide receptors on the cell membrane. After such peptides labeled with gamma-emitting radionuclides bind to their receptors, they allow clinicians to visualize receptor-expressing tumors non-invasively. Peptides labeled with beta-particle emitters could also eradicate receptor-expressing tumors. The somatostatin receptors, which are overexpressed in a majority of neuroendocrine tumors, represent the first and best example of targets for radiopeptide-based imaging and radionuclide therapy. The somatostatin analogue (111)In-octreotide permits the localization and staging of neuroendocrine tumors that express the appropriate somatostatin receptors. Newer modified somatostatin analogues, including Tyr(3)-octreotide and Tyr(3)-octreotate, are successfully being used for tumor imaging and radionuclide therapy. Because there are few effective therapies for patients with inoperable or metastasized neuroendocrine tumors, this therapy is a promising novel treatment option for these patients. Peptide receptor imaging and radionuclide therapy can be combined in a single probe, called a "theranostic". To select patients who are likely to benefit from this type of intervention, we first use a peptide analogue labeled with a diagnostic radionuclide to obtain a scan. Selected patients will be treated using the same or a similar peptide analogue labeled with a therapeutic radionuclide. The development of such

  3. Synthesis and Cytotoxicity of Semisynthetic Withalongolide A Analogues

    PubMed Central

    2013-01-01

    The natural product withaferin A exhibits potent antitumor activity and other diverse pharmacological activities. The recently discovered withalongolide A, a C-19 hydroxylated congener of withaferin A, was recently reported to possess cytotoxic activity against head and neck squamous cell carcinomas. Semisynthetic acetylated analogues of withalongolide A were shown to be considerably more cytotoxic than the parent compound. To further explore the structure–activity relationships, 20 new semisynthetic analogues of withalongolide A were synthesized and evaluated for cytotoxic activity against four different cancer cell lines. A number of derivatives were found to be more potent than the parent compound and withaferin A. PMID:24273633

  4. Non-natural acetogenin analogues as potent Trypanosoma brucei inhibitors

    PubMed Central

    Florence, Gordon J.; Fraser, Andrew L.; Gould, Eoin R.; King, Elizabeth F.; Menzies, Stefanie K.; Morris, Joanne C.; Tulloch, Lindsay B.; Smith, Terry K.

    2015-01-01

    A series of novel bis-tetrahydropyran 1,4-triazole analogues based on the acetogenin framework display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness. A divergent synthetic strategy was adopted for the synthesis of the key tetrahydropyran intermediates to enable rapid access to diastereochemical variation either side of the 1,4-triazole core. The resulting diastereomeric analogues displayed varying degrees of trypanocidal activity and selectivity in structure activity relationship studies. PMID:25145275

  5. A model of analogue K-winners-take-all neural circuit.

    PubMed

    Tymoshchuk, Pavlo V

    2013-06-01

    A model of analogue K-winners-take-all (KWTA) neural circuit which can identify the K largest from N unknown wide range inputs, where 1≤Kstate equation with discontinuous right-hand side and output equation. An existence and uniqueness, stability and convergence to the KWTA operation of the model states are analysed. A corresponding functional block diagram of the circuit is presented as N feedforward and one feedback hard-limiting neurons, which is used to determine the dynamic shift of inputs. The model combines such properties as high accuracy and convergence speed, low computational and hardware implementation complexity, and independency on initial states. PMID:23501169

  6. Stream food web response to a salmon carcass analogue addition in two central Idaho, U.S.A. streams

    PubMed Central

    KOHLER, ANDRE E; RUGENSKI, AMANDA; TAKI, DOUG

    2008-01-01

    Pacific salmon and steelhead once contributed large amounts of marine-derived carbon, nitrogen and phosphorus to freshwater ecosystems in the Pacific Northwest of the United States of America (California, Oregon, Washington and Idaho). Declines in historically abundant anadromous salmonid populations represent a significant loss of returning nutrients across a large spatial scale. Recently, a manufactured salmon carcass analogue was developed and tested as a safe and effective method of delivering nutrients to freshwater and linked riparian ecosystems where marine-derived nutrients have been reduced or eliminated. We compared four streams: two reference and two treatment streams using salmon carcass analogue(s) (SCA) as a treatment. Response variables measured included: surface streamwater chemistry; nutrient limitation status; carbon and nitrogen stable isotopes; periphyton chlorophyll a and ash-free dry mass (AFDM); macroinvertebrate density and biomass; and leaf litter decomposition rates. Within each stream, upstream reference and downstream treatment reaches were sampled 1 year before, during, and 1 year after the addition of SCA. Periphyton chlorophyll a and AFDM and macroinvertebrate biomass were significantly higher in stream reaches treated with SCA. Enriched stable isotope (δ15N) signatures were observed in periphyton and macroinvertebrate samples collected from treatment reaches in both treatment streams, indicating trophic transfer from SCA to consumers. Densities of Ephemerellidae, Elmidae and Brachycentridae were significantly higher in treatment reaches. Macroinvertebrate community composition and structure, as measured by taxonomic richness and diversity, did not appear to respond significantly to SCA treatment. Leaf breakdown rates were variable among treatment streams: significantly higher in one stream treatment reach but not the other. Salmon carcass analogue treatments had no detectable effect on measured water chemistry variables. Our results

  7. Nanocrystallization kinetics and glass forming ability of the Fe{sub 65}Nb{sub 10}B{sub 25} metallic alloy

    SciTech Connect

    Torrens-Serra, J.; Rodriguez-Viejo, J.; Clavaguera-Mora, M. T.

    2007-12-01

    The crystallization kinetics of glassy Fe{sub 65}Nb{sub 10}B{sub 25} melt-spun ribbons is studied by differential scanning calorimetry in the mode of continuous heating and isothermal annealing and by x-ray diffraction and transmission electron microscopy. Continuous heat treatments of the ribbons show the presence of multiple exothermic peaks before melting. The low-temperature peak corresponds to the precipitation of nanoscale Fe{sub 23}B{sub 6}-type crystalline metastable phase, and further annealing leads to its transformation into the metastable Fe{sub 3}B phase and subsequent formation of bcc-Fe, Fe{sub 2}B, and FeNbB stable crystalline phases. The nucleation frequency and the growth rate are determined at selected temperatures from the analysis of the microstructures that emerge during the Fe{sub 23}B{sub 6}-type nanocrystallization. The master curve method is used to obtain the apparent activation energy and the Avrami exponent at the nanocrystallization onset. The nanocrystallization kinetics is explained in the framework of the Kolmogorov-Johnson-Mehl-Avrami theory. The rejection of insoluble alloy atoms during primary crystallization, the formation of diffusion layers around the crystals, and the decrease in the nucleation frequency caused by alloy enrichment of the residual disordered matrix is modeled through a soft impingement factor. Estimated values for the interfacial energy that provide a satisfactory agreement between experiments and modeling are derived considering that homogeneous nucleation frequency and interface-controlled grain growth are dominant at the onset of the nanocrystallization. Consequently, the time-temperature-transformation diagram is also drawn and the critical cooling rate estimated for this glass forming alloy.

  8. The isotopic composition of lead in potassium feldspars from some 1.0-b.y. old North American igneous rocks

    USGS Publications Warehouse

    Zartman, R.E.; Wasserburg, G.J.

    1969-01-01

    The isotopic composition of lead and the uranium, thorium and lead concentrations in potassium feldspars are determined for more than 30 1.0-b.y. old North American igneous rocks. Samples representing a broad spectrum in petrographic type and mode of occurrence were chosen; an effort was made to include only rocks having well-documented ages from 950 to 1140 m.y. and showing minimal evidence of subsequent metamorphism. Most samples, including those from extensive terranes of contemporaneous age, have limited lead isotope variations ( Pb206 Pb204 = 16.74-17.38; Pb207 Pb204 = 15.39-15.59; Pb208 Pb204 = 36.38-37.10), which yield model ages close to the radiometric ages. Granite, pegmatite, and rhyolite from within the Grenville province of Canada and age-equivalent rocks of New York, Virginia, Texas, and Colorado and granophyric units associated with the Duluth Gabbro Complex of Minnesota are among the materials yielding this main isotopic spectrum. Several samples were encountered which had isotopic compositions very different from the above group. Lead showing a marked deficiency in radiogenic isotopes was found in two granitic bodies associated with older Labrador Trough rocks from Quebec, in a rapakivi granite from southern Nevada, and in a small granite stock from Mellen, Wisconsin. These occurrences all involve small intrusions of granite which lie near considerably older areas of basement rock. Model ages calculated from the Pb206 Pb204 ratio are older than the age of the intrusions and approach the age of the host basement rock. Several possible interpretations are offered to explain the isotopic behavior encountered in this study. In particular, a "vertically differentiated crust" model is proposed which will account for both the main spectrum and the anomalous lead. The significance of lead isotopic studies in understanding crustal structure in continental regions is discussed. ?? 1969.

  9. Regulation of Cell Proliferation and Migration by miR-203 via GAS41/miR-10b Axis in Human Glioblastoma Cells

    PubMed Central

    Pal, Dhananjaya; Mukhopadhyay, Debasmita; Ramaiah, M. Janaki; Sarma, Pranjal; Bhadra, Utpal; Bhadra, Manika Pal

    2016-01-01

    Glioma amplified sequence 41(GAS41) is a potent transcription factor that play a crucial role in cell proliferation and survival. In glioblastoma, the expression of GAS41 at both transcriptional and post transcriptional level needs to be tightly maintained in response to cellular signals. Micro RNAs (miRNA) are small non coding RNA that act as important regulators for modulating the expression of various target genes. Studies have shown that several miRNAs play role in the post-transcriptional regulation of GAS41. Here we identified GAS41 as a novel target for endogenous miR-203 and demonstrate an inverse correlation of miR-203 expression with GAS41 in glioma cell lines (HNGC2 and U87). Over expression of miR-203 negatively regulates GAS41 expression in U87 and HNGC2 cell lines. Moreover, miR-203 restrained miR-10b action by suppressing GAS41. GAS41 is essential for repressing p53 in tumor suppressor pathway during cell proliferation. Enforced expression of GAS41 produced contradictory effect on miR-203 but was able to enhance p53 tumor suppressor pathway associated protein. It was also found that miR-203 maintains the stability of p53 as knock down of p53 expression using siRNA resulted in down regulation of pri-miR and mature miR-203 expression. Conversely reconstitution of miR-203 expression induced apoptosis and inhibited migratory property of glioma cells. Taken together, we show that miR-203 is a key negative regulator of GAS41 and acts as tumor suppressor microRNA in glioma. PMID:27467502

  10. Geometry, Electronic Structure, and Pseudo Jahn-Teller Effect in Tetrasilacyclobutadiene Analogues

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Wang, Ya; Bersuker, Isaac B.

    2016-03-01

    We revealed the origin of the structural features of a series of tetrasilacyclobutadiene analogues based on a detailed study of their electronic structure and the pseudo Jahn-Teller effect (PJTE). Starting with the D4h symmetry of the Si4R4 system with a square four-membered silicon ring as a reference geometry, and employing ab initio calculations of energy profiles along lower-symmetry nuclear displacements in the ground and several excited states, we show that the ground-state boat-like and chair-like equilibrium configurations are produced by the PJT interaction with appropriate excited sates. For Si4F4 a full two-mode b1g‑b2g adiabatic potential energy surface is calculated showing explicitly the way of transformation from the unstable D4h geometry to the two equilibrium C2h configurations via the D2h saddle point. The PJTE origin of these structural features is confirmed also by estimates of the vibronic coupling parameters. For Si4R4 with large substituents the origin of their structure is revealed by analyzing the PJT interaction between the frontier molecular orbitals. The preferred chair-like structures of Si4R4 analogues with amido substituents, and heavier germanium-containing systems Ge4R4 (potential precursors for semiconducting materials) are predicted.

  11. Geometry, Electronic Structure, and Pseudo Jahn-Teller Effect in Tetrasilacyclobutadiene Analogues.

    PubMed

    Liu, Yang; Wang, Ya; Bersuker, Isaac B

    2016-01-01

    We revealed the origin of the structural features of a series of tetrasilacyclobutadiene analogues based on a detailed study of their electronic structure and the pseudo Jahn-Teller effect (PJTE). Starting with the D4h symmetry of the Si4R4 system with a square four-membered silicon ring as a reference geometry, and employing ab initio calculations of energy profiles along lower-symmetry nuclear displacements in the ground and several excited states, we show that the ground-state boat-like and chair-like equilibrium configurations are produced by the PJT interaction with appropriate excited sates. For Si4F4 a full two-mode b1g-b2g adiabatic potential energy surface is calculated showing explicitly the way of transformation from the unstable D4h geometry to the two equilibrium C2h configurations via the D2h saddle point. The PJTE origin of these structural features is confirmed also by estimates of the vibronic coupling parameters. For Si4R4 with large substituents the origin of their structure is revealed by analyzing the PJT interaction between the frontier molecular orbitals. The preferred chair-like structures of Si4R4 analogues with amido substituents, and heavier germanium-containing systems Ge4R4 (potential precursors for semiconducting materials) are predicted. PMID:26996445

  12. Block of sodium channels by internal mono- and divalent guanidinium analogues. Modulation by sodium ion concentration.

    PubMed Central

    Danko, M; Smith-Maxwell, C; McKinney, L; Begenisich, T

    1986-01-01

    We have investigated the block of squid axon sodium channels by mono- and divalent guanidinium analogues. The action of these compounds on steady state sodium currents was independent of the presence or absence of the normal inactivation process. Block by both mono- and divalent analogues was voltage-dependent, but was a steeper function of potential for divalent molecules. The voltage-dependence could not, in general, be reproduced by a simple model based on Boltzmann's equation. Inhibition of steady state currents by guanidinium ions with 50 mM internal sodium was reasonably well described by a 1:1 drug/channel binding function. Increasing the internal sodium ion concentration increased both the degree and voltage-dependence of current inhibition. This is in sharp contrast to the decrease in inactivation caused by internal sodium. Changes in the external sodium concentration had very little effect on drug block. These results are consistent with a model of the sodium channel as a multi-ion pore. Only a small increase in block can be produced by increased internal sodium in a three-barrier two-site model, but a four-barrier three-site model can reproduce these experimental findings. The implications of these results for physical models of inactivation are discussed. PMID:2420382

  13. Geometry, Electronic Structure, and Pseudo Jahn-Teller Effect in Tetrasilacyclobutadiene Analogues

    PubMed Central

    Liu, Yang; Wang, Ya; Bersuker, Isaac B.

    2016-01-01

    We revealed the origin of the structural features of a series of tetrasilacyclobutadiene analogues based on a detailed study of their electronic structure and the pseudo Jahn-Teller effect (PJTE). Starting with the D4h symmetry of the Si4R4 system with a square four-membered silicon ring as a reference geometry, and employing ab initio calculations of energy profiles along lower-symmetry nuclear displacements in the ground and several excited states, we show that the ground-state boat-like and chair-like equilibrium configurations are produced by the PJT interaction with appropriate excited sates. For Si4F4 a full two-mode b1g−b2g adiabatic potential energy surface is calculated showing explicitly the way of transformation from the unstable D4h geometry to the two equilibrium C2h configurations via the D2h saddle point. The PJTE origin of these structural features is confirmed also by estimates of the vibronic coupling parameters. For Si4R4 with large substituents the origin of their structure is revealed by analyzing the PJT interaction between the frontier molecular orbitals. The preferred chair-like structures of Si4R4 analogues with amido substituents, and heavier germanium-containing systems Ge4R4 (potential precursors for semiconducting materials) are predicted. PMID:26996445

  14. Theoretical Study of the Photophysics of 8-Vinylguanine, an Isomorphic Fluorescent Analogue of Guanine.

    PubMed

    Kochman, Michał A; Pola, Martina; Miller, R J Dwayne

    2016-08-11

    Paving the way for the application of the algebraic-diagrammatic construction scheme of second-order (ADC(2)) to systems based on the guanine chromophore, we demonstrate the this excited-state electronic structure method provides a realistic description of the photochemistry of 9H-guanine, in close agreement with the benchmark provided by the CASPT2 method. We then proceed to apply the ADC(2) method to the photochemistry of 8-vinylguanine (8vG), a minimally modified analogue of guanine which, unlike the naturally occurring nucleobase, displays intense fluorescence, indicative of a much longer-lived excited electronic state. The emissive electronic state of 8vG is identified as an ππ*-type intramolecular charge transfer (ICT) state, in which a charge of roughly -0.2 e is transferred from the guanine moiety onto the vinyl substituent. The main radiationless deactivation pathway competing with fluorescence is predicted to involve the molecule leaving the minimum on the ICT ππ* state, and reaching a region of the S1 adiabatic state where it resembles the La ππ* state of unmodified 9H-guanine. The topology of the La ππ* region of the S1 state favors subsequent internal conversion at a crossing seam with the ground electronic state. The sensitivity of this process to environment polarity may explain the experimentally observed fluorescence quenching of 8vG upon incorporation in single- and double-stranded DNA. PMID:27427772

  15. Facile Synthesis of Natural Alkoxynaphthalene Analogues from Plant Alkoxybenzenes.

    PubMed

    Tsyganov, Dmitry V; Krayushkin, Mikhail M; Konyushkin, Leonid D; Strelenko, Yuri A; Semenova, Marina N; Semenov, Victor V

    2016-04-22

    Analogues of the bioactive natural alkoxynaphthalene pycnanthulignene D were synthesized by an efficient method. The starting plant allylalkoxybenzenes (1) are easily available from the plant essential oils of sassafras, dill, and parsley. The target 1-arylalkoxynaphthalenes (5) exhibited antiproliferative activity in a phenotypic sea urchin embryo assay. PMID:26910798

  16. Thymidine analogues to assess microperfusion in human tumors

    SciTech Connect

    Janssen, Hilde L.; Ljungkvist, Anna S.; Rijken, Paul F.; Sprong, Debbie; Bussink, Jan; Kogel, Albert J. van der; Haustermans, Karin M.; Begg, Adrian C. . E-mail: a.begg@nki.nl

    2005-07-15

    Purpose: To validate the use of the thymidine analogues as local perfusion markers in human tumors (no labeling indicates no perfusion) by comparison with the well-characterized perfusion marker Hoechst 33342. Methods and Materials: Human tumor xenografts from gliomas and head-and-neck cancers were injected with iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) and the fluorescent dye Hoechst 33342. In frozen sections, each blood vessel was scored for the presence of IdUrd/BrdUrd labeling and Hoechst in surrounding cells. The percentage of analogue-negative vessels was compared with the fraction of Hoechst-negative vessels. Collocalization of the two markers was also scored. Results: We found considerable intertumor variation in the fraction of perfused vessels, measured by analogue labeling, both in the human tumor xenografts and in a series of tumor biopsies from head-and-neck cancer patients. There was a significant correlation between the Hoechst-negative and IdUrd/BrdUrd-negative vessels in the xenografts (r 85, p = 0.0004), despite some mismatches on a per-vessel basis. Conclusions: Thymidine analogues can be successfully used to rank tumors according to their fraction of perfused vessels. Whether this fraction correlates with the extent of acute hypoxia needs further confirmation.

  17. Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

    PubMed Central

    Brulikova, Lucie

    2011-01-01

    Summary This review article summarizes the results of a long-term investigation of 5-alkoxymethyluracil analogues and is aimed, in particular, at methods of syntheses. Most of the presented compounds were synthesized in order to evaluate their biological activity, therefore, a brief survey of biological activity, especially antiviral, cytotoxic and antibacterial, is also reported. PMID:21804865

  18. A Macroscopic Analogue of the Nuclear Pairing Potential

    ERIC Educational Resources Information Center

    Dunlap, Richard A.

    2013-01-01

    A macroscopic system involving permanent magnets is used as an analogue to nucleons in a nucleus to illustrate the significance of the pairing interaction. This illustrates that the view of the total nuclear energy based only on the nucleon occupancy of the energy levels can yield erroneous results and it is only when the pairing interaction is…

  19. Charged Analogues of Henning Knutsen Type Solutions in General Relativity

    NASA Astrophysics Data System (ADS)

    Gupta, Y. K.; Kumar, Sachin; Pratibha

    2011-11-01

    In the present article, we have found charged analogues of Henning Knutsen's interior solutions which join smoothly to the Reissner-Nordstrom metric at the pressure free interface. The solutions are singularity free and analyzed numerically with respect to pressure, energy-density and charge-density in details. The solutions so obtained also present the generalization of A.L. Mehra's solutions.

  20. Synthesis of 4” manipulated Lewis X trisaccharide analogues

    PubMed Central

    Moore, Christopher J

    2012-01-01

    Summary Three analogues of the Lex trisaccharide antigen (β-D-Galp(1→4)[α-L-Fucp(1→3)]-D-GlcNAcp) in which the galactosyl residue is modified at O-4 as a methyloxy, deoxychloro or deoxyfluoro, were synthesized. We first report the preparation of the modified 4-OMe, 4-Cl and 4-F trichloroacetimidate galactosyl donors and then report their use in the glycosylation of an N-acetylglucosamine glycosyl acceptor. Thus, we observed that the reactivity of these donors towards the BF3·OEt2-promoted glycosylation at O-4 of the N-acetylglucosamine glycosyl acceptors followed the ranking 4-F > 4-OAc ≈ 4-OMe > 4-Cl. The resulting disaccharides were deprotected at O-3 of the glucosamine residue and fucosylated, giving access to the desired protected Lex analogues. One-step global deprotection (Na/NH3) of the protected 4”-methoxy analogue, and two-step deprotections (removal of a p-methoxybenzyl with DDQ, then Zemplén deacylation) of the 4”-deoxychloro and 4”-deoxyfluoro protected Lex analogues gave the desired compounds in good yields. PMID:23019441

  1. ON A p-ADIC ANALOGUE OF TATE HEIGHT

    NASA Astrophysics Data System (ADS)

    Berzin'sh, A. A.

    1983-04-01

    This paper is devoted to the study of the Tate height of an elliptic curve and its p-adic analogue. The main result is a series of explicit formulas for computing the local archimedean part of the Tate height. These results are used to obtain a new method for constructing the p-adic Tate height. Bibliography: 5 titles.

  2. Trehalose Analogues: Latest Insights in Properties and Biocatalytic Production

    PubMed Central

    Walmagh, Maarten; Zhao, Renfei; Desmet, Tom

    2015-01-01

    Trehalose (α-d-glucopyranosyl α-d-glucopyranoside) is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals), medical, pharmaceutical and cosmetic industries. Trehalose analogues, like lactotrehalose (α-d-glucopyranosyl α-d-galactopyranoside) or galactotrehalose (α-d-galactopyranosyl α-d-galactopyranoside), offer similar benefits as trehalose, but show additional features such as prebiotic or low-calorie sweetener due to their resistance against hydrolysis during digestion. Unfortunately, large-scale chemical production processes for trehalose analogues are not readily available at the moment due to the lack of efficient synthesis methods. Most of the procedures reported in literature suffer from low yields, elevated costs and are far from environmentally friendly. “Greener” alternatives found in the biocatalysis field, including galactosidases, trehalose phosphorylases and TreT-type trehalose synthases are suggested as primary candidates for trehalose analogue production instead. Significant progress has been made in the last decade to turn these into highly efficient biocatalysts and to broaden the variety of useful donor and acceptor sugars. In this review, we aim to provide an overview of the latest insights and future perspectives in trehalose analogue chemistry, applications and production pathways with emphasis on biocatalysis. PMID:26084050

  3. A new analogue of fatty alcohol from Tamarix hampeana L.

    PubMed

    Aykac, Ahmet; Akgül, Yurdanur

    2010-01-01

    New analogues of a long-chain secondary alcohol (1) and laserine (2) were isolated from the flowers of Tamarix hampeana L. The isolated compounds were identified using 1D and 2D NMR, LCMS/APCI, and chemical methods. Laserine was isolated for the first time from T. hampeana L. PMID:20013470

  4. Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues.

    PubMed

    Hager, Anastasia; Wu, Mingxuan; Wang, Huanchen; Brown, Nathaniel W; Shears, Stephen B; Veiga, Nicolás; Fiedler, Dorothea

    2016-08-22

    The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions. PMID:27460418

  5. Synthesis of monophytanyl ether analogues of lysophosphatidic and lysophosphatidyl glycerol.

    PubMed

    Kates, M; Hancock, A J

    1976-10-01

    The chemical synthesis of 3-O-phytanyl-sn-glycero-1-phosphoric acid (monophytanyl ether analogue of lysophosphatidic acid) was effected by condensation of 1-iodo-2-O-benzyl-3-O-phytanyl-sn-glycerol with silver di-p-nitrobenzyl phosphate in anhydrous toluene followed by catalytic hydrogenolysis of the resulting phosphotriester to remove the benzyl and p-nitrobenzyl groups. Synthesis of 3-O-phytanyl-sn-glycero-1-phosphoryl-1'-sn-glycerol (monophytanyl ether analogue of lysophosphatidyl glycerol) was carried out by conversion of the above phosphotriester to the monosilver salt of the suitably blocked lysophosphatidic acid which was condensed with 1-iodo-2-O-t-butyl-3-O-benzyl-sn-glycerol. Removal of the protecting aromatic and t-butyl groups from the resulting blocked triester intermediate gave the desired phytanyl ether analogue of lysophosphatidyl glycerol. Both lyso analogues were isolated as analytically and chromatographically pure potassium salts. Their physical properties and behavior towards acid hydrolysis are described. PMID:991376

  6. New phosphorus analogues of nitrogen classics--no carbon copies.

    PubMed

    Gudat, Dietrich

    2014-05-01

    Getting heavy: The recently prepared phosphorus analogues of two old acquaintances, urea and dinitrogen tetroxide, bear some structural resemblance to their archetypes but are no carbon copies. Their syntheses and chemical properties reveal rather certain peculiarities, which back the doctrine that the electronic properties of the heavier elements in a group differ from those of the lightest congener. PMID:24718995

  7. Synthesis of glycophostones: cyclic phosphonate analogues of biologically relevant sugars

    PubMed

    Hanessian; Rogel

    2000-05-01

    Analogues of L-fucose, N-acetyl-D-glucosamine, N-acetyl-D-mannosamine, and N-acetyl neuraminic acid in which the anomeric carbon atom was replaced by a phosphonyl group (phostones or cyclic phosphonates) were synthesized by stereocontrolled methods relying on the Abramov reaction. PMID:10808439

  8. An Analysis of an Autoclitic Analogue in Pigeons

    ERIC Educational Resources Information Center

    Kuroda, Toshikazu; Lattal, Kennon A.; García-Penagos, Andrés

    2014-01-01

    Using a conditional discrimination procedure, pigeons were exposed to a nonverbal analogue of qualifying autoclitics such as "definitely" and "maybe." It has been suggested that these autoclitics are similar to tacts except that they are under the control of private discriminative stimuli. Instead of the conventional assumption…

  9. Trehalose Analogues: Latest Insights in Properties and Biocatalytic Production.

    PubMed

    Walmagh, Maarten; Zhao, Renfei; Desmet, Tom

    2015-01-01

    Trehalose (α-D-glucopyranosyl α-D-glucopyranoside) is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals), medical, pharmaceutical and cosmetic industries. Trehalose analogues, like lactotrehalose (α-D-glucopyranosyl α-D-galactopyranoside) or galactotrehalose (α-D-galactopyranosyl α-D-galactopyranoside), offer similar benefits as trehalose, but show additional features such as prebiotic or low-calorie sweetener due to their resistance against hydrolysis during digestion. Unfortunately, large-scale chemical production processes for trehalose analogues are not readily available at the moment due to the lack of efficient synthesis methods. Most of the procedures reported in literature suffer from low yields, elevated costs and are far from environmentally friendly. "Greener" alternatives found in the biocatalysis field, including galactosidases, trehalose phosphorylases and TreT-type trehalose synthases are suggested as primary candidates for trehalose analogue production instead. Significant progress has been made in the last decade to turn these into highly efficient biocatalysts and to broaden the variety of useful donor and acceptor sugars. In this review, we aim to provide an overview of the latest insights and future perspectives in trehalose analogue chemistry, applications and production pathways with emphasis on biocatalysis. PMID:26084050

  10. Non-robust numerical simulations of analogue extension experiments

    NASA Astrophysics Data System (ADS)

    Naliboff, John; Buiter, Susanne

    2016-04-01

    Numerical and analogue models of lithospheric deformation provide significant insight into the tectonic processes that lead to specific structural and geophysical observations. As these two types of models contain distinct assumptions and tradeoffs, investigations drawing conclusions from both can reveal robust links between first-order processes and observations. Recent studies have focused on detailed comparisons between numerical and analogue experiments in both compressional and extensional tectonics, sometimes involving multiple lithospheric deformation codes and analogue setups. While such comparisons often show good agreement on first-order deformation styles, results frequently diverge on second-order structures, such as shear zone dip angles or spacing, and in certain cases even on first-order structures. Here, we present finite-element experiments that are designed to directly reproduce analogue "sandbox" extension experiments at the cm-scale. We use material properties and boundary conditions that are directly taken from analogue experiments and use a Drucker-Prager failure model to simulate shear zone formation in sand. We find that our numerical experiments are highly sensitive to numerous numerical parameters. For example, changes to the numerical resolution, velocity convergence parameters and elemental viscosity averaging commonly produce significant changes in first- and second-order structures accommodating deformation. The sensitivity of the numerical simulations to small parameter changes likely reflects a number of factors, including, but not limited to, high angles of internal friction assigned to sand, complex, unknown interactions between the brittle sand (used as an upper crust equivalent) and viscous silicone (lower crust), highly non-linear strain weakening processes and poor constraints on the cohesion of sand. Our numerical-analogue comparison is hampered by (a) an incomplete knowledge of the fine details of sand failure and sand

  11. Metric optimisation for analogue forecasting by simulated annealing

    NASA Astrophysics Data System (ADS)

    Bliefernicht, J.; Bárdossy, A.

    2009-04-01

    It is well known that weather patterns tend to recur from time to time. This property of the atmosphere is used by analogue forecasting techniques. They have a long history in weather forecasting and there are many applications predicting hydrological variables at the local scale for different lead times. The basic idea of the technique is to identify past weather situations which are similar (analogue) to the predicted one and to take the local conditions of the analogues as forecast. But the forecast performance of the analogue method depends on user-defined criteria like the choice of the distance function and the size of the predictor domain. In this study we propose a new methodology of optimising both criteria by minimising the forecast error with simulated annealing. The performance of the methodology is demonstrated for the probability forecast of daily areal precipitation. It is compared with a traditional analogue forecasting algorithm, which is used operational as an element of a hydrological forecasting system. The study is performed for several meso-scale catchments located in the Rhine basin in Germany. The methodology is validated by a jack-knife method in a perfect prognosis framework for a period of 48 years (1958-2005). The predictor variables are derived from the NCEP/NCAR reanalysis data set. The Brier skill score and the economic value are determined to evaluate the forecast skill and value of the technique. In this presentation we will present the concept of the optimisation algorithm and the outcome of the comparison. It will be also demonstrated how a decision maker should apply a probability forecast to maximise the economic benefit from it.

  12. Biological evaluation of a novel sorafenib analogue, t-CUPM.

    PubMed

    Wecksler, Aaron T; Hwang, Sung Hee; Liu, Jun-Yan; Wettersten, Hiromi I; Morisseau, Christophe; Wu, Jian; Weiss, Robert H; Hammock, Bruce D

    2015-01-01

    Sorafenib (Nexavar®) is currently the only FDA-approved small molecule targeted therapy for advanced hepatocellular carcinoma. The use of structural analogues and derivatives of sorafenib has enabled the elucidation of critical targets and mechanism(s) of cell death for human cancer lines. We previously performed a structure-activity relationship study on a series of sorafenib analogues designed to investigate the inhibition overlap between the major targets of sorafenib Raf-1 kinase and VEGFR-2, and an enzyme shown to be a potent off-target of sorafenib, soluble epoxide hydrolase. In the current work, we present the biological data on our lead sorafenib analogue, t-CUPM, demonstrating that this analogue retains cytotoxicity similar to sorafenib in various human cancer cell lines and strongly inhibits growth in the NCI-60 cell line panel. Co-treatment with the pan-caspase inhibitor, Z-VAD-FMK, failed to rescue the cell viability responses of both sorafenib and t-CUPM, and immunofluorescence microscopy shows similar mitochondrial depolarization and apoptosis-inducing factor release for both compounds. These data suggest that both compounds induce a similar mechanism of caspase-independent apoptosis in hepatoma cells. In addition, t-CUPM displays anti-proliferative effects comparable to sorafenib as seen by a halt in G0/G1 in cell cycle progression. The structural difference between sorafenib and t-CUPM significantly reduces inhibitory spectrum of kinases by this analogue, and pharmacokinetic characterization demonstrates a 20-fold better oral bioavailability of t-CUPM than sorafenib in mice. Thus, t-CUPM may have the potential to reduce the adverse events observed from the multikinase inhibitory properties and the large dosing regimens of sorafenib. PMID:25413440

  13. Convolutamydine A and synthetic analogues have antinociceptive properties in mice.

    PubMed

    Figueiredo, Gabriela S M; Zardo, Renata S; Silva, Bárbara V; Violante, Flávio A; Pinto, Angelo C; Fernandes, Patricia D

    2013-01-01

    Convolutamydine A, an oxindole that originated from a marine bryozoan, has several biological effects. In this study, we aimed to investigate the antinociceptive effects of convolutamydine A and two new synthetic analogues. Convolutamydine A and the two analogues were given orally to assess their ability to induce antinociceptive effects. Formalin-induced licking response, acetic acid-induced contortions, and hot plate models were used to characterize the effects of convolutamydine A and its analogues. Convolutamydine A (4,6-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole), compound 1 (3-(2-oxopropyl)-3-hydroxy-2-oxindole), and compound 2 (5-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole) caused peripheral antinociceptive and anti-inflammatory effects in the acetic acid-induced contortions and the formalin-induced licking models. Supraspinal effects were also observed in the hot plate model and were similar to those obtained with morphine. The peripheral effects were not mediated by the cholinergic or opioid systems. The antinociceptive effects of convolutamydine A seem to be mediated by all three systems (cholinergic, opioid, and nitric oxide systems), and the mechanism of action of compounds 1 and 2 involved cholinergic and nitric oxide-mediated mechanisms. Convolutamydine A and its analogues (compounds 1 and 2) showed good antinociceptive ability after systemic administration in acute pain models. The antinociceptive action mediated by cholinergic, opioid, and nitric oxide systems could explain why convolutamydine A, compound 1, and compound 2 retained their antinociceptive effects. The doses used were similar to the doses of morphine and were much lower than that of acetylsalicylic acid, the classical analgesic and anti-inflammatory drug. In conclusion, convolutamydine A and the two analogues demonstrated antinociceptive effects comparable to morphine's effects. PMID:23046852

  14. Analogue Sites for Mars Missions - A report from two workshops

    NASA Astrophysics Data System (ADS)

    Hipkin, V.; Voytek, M. A.; Glamoclija, M.

    2014-12-01

    Fieldwork, at terrestrial sites that are analogous in some way to Mars, has a key role in defining questions addressed by Mars missions. For MSL, the question is whether its landing site was habitable, and for Mars 2020, the question is how do we search for and what are signs of life in ancient habitable environments. Implementing these investigations by means of a rover mission on a distant planetary surface has challenges due to a limited set of tools and period of operations. Using this context of planetary missions is important in shaping how analog research can be used to advance planetary science. Following a successful 2010 AGU fall meeting session entitled "Analogue Sites for Mars Missions", two community workshops were held at The Woodlands, TX March 2011 and the Carnegie Institute of Washington in July 2013. These activities represent an ongoing dialogue with the analogue and mission communities. The AGU session solicited presentations of current analogue research relevant to MSL, at which time the landing site selection process was still considering four final sites. The 2011 Woodlands workshop solicited details on representative science questions and analogue sites by means of an abstract template. The output from The Woodlands workshop was an initial metric to assess the utility of analogue sites against specific science questions, as well as recommendations for future activities. The 2013 Carnegie workshop, followed up on some of the recommendations from 2011. Both on-line interactive dialogue and in person discussions targeted broad topics, including 'the advantages and problems of using a great terrestrial analog for field testing', and 'knowing what we currently do about Mars, what would be the best place on the planet to collect the first suite of samples to be returned to Earth? What would be appropriate analog sites on Earth?'. The results and recommendations from both workshops are summarized to publicize and stimulate this ongoing discussion.

  15. Climatic Forecasting of Net Infiltration at Yucca Montain Using Analogue Meteororological Data

    SciTech Connect

    B. Faybishenko

    2006-09-11

    At Yucca Mountain, Nevada, future changes in climatic conditions will most likely alter net infiltration, or the drainage below the bottom of the evapotranspiration zone within the soil profile or flow across the interface between soil and the densely welded part of the Tiva Canyon Tuff. The objectives of this paper are to: (a) develop a semi-empirical model and forecast average net infiltration rates, using the limited meteorological data from analogue meteorological stations, for interglacial (present day), and future monsoon, glacial transition, and glacial climates over the Yucca Mountain region, and (b) corroborate the computed net-infiltration rates by comparing them with the empirically and numerically determined groundwater recharge and percolation rates through the unsaturated zone from published data. In this paper, the author presents an approach for calculations of net infiltration, aridity, and precipitation-effectiveness indices, using a modified Budyko's water-balance model, with reference-surface potential evapotranspiration determined from the radiation-based Penman (1948) formula. Results of calculations show that net infiltration rates are expected to generally increase from the present-day climate to monsoon climate, to glacial transition climate, and then to the glacial climate. The forecasting results indicate the overlap between the ranges of net infiltration for different climates. For example, the mean glacial net-infiltration rate corresponds to the upper-bound glacial transition net infiltration, and the lower-bound glacial net infiltration corresponds to the glacial transition mean net infiltration. Forecasting of net infiltration for different climate states is subject to numerous uncertainties-associated with selecting climate analogue sites, using relatively short analogue meteorological records, neglecting the effects of vegetation and surface runoff and runon on a local scale, as well as possible anthropogenic climate changes.

  16. Nouveaux analogues étendus du tétrathiafulvalène à espaceur conjugué rigide

    NASA Astrophysics Data System (ADS)

    Brisset, H.; Le Moustarder, S.; Blanchard, P.; Illien, B.; Riou, A.; Roncali, J.

    1998-06-01

    New hybrid tetrathiafulvalene analogues are built by insertion of bridged transdithienylethylene between two 1,4-dithiafulvenyl electron-releasing groups. Whereas the unbridged analogues are directly oxidized to the dication state, the rigidification of the conjugated spacerleads simultaneously to an increase of the -donor ability and a stabilization of the radical cation state. De nouveaux analogues étendus du tétrathiafulvalène ont été synthétisés par insertion du trans-dithiényléthylène rigide entre deux motifs électrodonneurs 1,4-dithiafulvényl. Alors que les composés non pontés sont oxydés directement à l'état de dication, la rigidification de l'espaceur conjugué conduit simultanément à une augmentation du caractère donneur-pi et à la stabilisation de l'état radical-cation.

  17. Analogue of Caldera Dynamics: the Controlled Salt Cavern Collapse

    NASA Astrophysics Data System (ADS)

    Jousset, P. G.; Rohmer, J.

    2012-12-01

    Caldera collapse (or pit-crater) dynamics are inferred from geological observations and laboratory experiments. Here, we present an analogue of caldera collapse at field scale and possible analogy with large scale caldera dynamics. Through an original exploitation technique in sedimentary environment, a salt layer is emptied, leaving a brine-filled cavern, which eventually collapses after overburden falls into the cavern. Such a collapse was monitored in East France by many instruments (including GPS, extensometers, geophones, broadband seismological sensors, tiltmeter, gravity meter, … ), which allowed us to describe mechanisms of the collapse. Micro-seismicity is a good indicator of spatio-temporal evolution of physical properties of rocks prior to catastrophic events like volcanic eruptions or landslides and may be triggered by a number of causes including dynamic characteristics of processes in play or/and external forces. We show evidence of triggered micro-seismicity observed in the vicinity of this underground salt cavern prone to collapse by a remote M~7.2 earthquake, which occurred ~12000 kilometres away. High-dynamic broadband records reveal the strong time-correlation between a dramatic change in the rate of local high-frequency micro-seismicity and the passage of low-frequency seismic waves, including body, Love and Rayleigh surface waves. Pressure was lowered in the cavern by pumping operations of brine out of the cavern. We demonstrate the near critical state of the cavern before the collapse by means of 2D axisymmetric elastic finite-element simulations. Stress oscillations due to the seismic waves may have exceeded the strength required for the rupture of the complex media made of brine and rock triggering micro-earthquakes and leading to damage of the overburden and eventually collapse of the salt cavern. The increment of stress necessary for the failure of a Dolomite layer is of the same order or magnitude as the maximum dynamic stress magnitude

  18. An analogue of a theorem of Kurzweil

    NASA Astrophysics Data System (ADS)

    Simmons, David

    2015-05-01

    A theorem of Kurzweil ('55) on inhomogeneous Diophantine approximation states that if θ is an irrational number, then the following are equivalent: (A) for every decreasing positive function ψ such that \\sumq = 1^∞ \\psi(q) = ∞ , and for almost every s\\in R , there exist infinitely many q\\in N such that ‖qθ - s‖ < ψ(q), and (B) θ is badly approximable. This theorem is not true if one adds to condition (A) the hypothesis that the function q ↦ qψ(q) is decreasing. In this paper we find a condition on the continued fraction expansion of θ which is equivalent to the modified version of condition (A). This expands on a recent paper of Kim (2014 Nonlinearity 27 1985-97).

  19. Inhibition of receptor/G protein coupling by suramin analogues.

    PubMed

    Beindl, W; Mitterauer, T; Hohenegger, M; Ijzerman, A P; Nanoff, C; Freissmuth, M

    1996-08-01

    Suramin analogues act as direct antagonists of heterotrimeric G proteins because they block the rate-limiting step of G protein activation (i.e., the dissociation of GDP prebound to the G protein alpha subunit). We have used the human brain A1 adenosine receptor and the rat striatal D2 dopamine receptor, two prototypical Gi/G(o)-coupled receptors, as a model system to test whether the following analogues suppress the receptor-dependent activation of G proteins: 8-(3-nitrobenzamido)-1,3,5-naphthalenetrisulfonic acid (NF007), 8-(3-(3-nitrobenzamido)-benzamido)-1,3,5-naphthalenetrisulfonic acid (NF018); 8,8'-(carbonylbis(imino-3,1-phenylene))bis-(1,3,5-naphthalenetr isulfonic acid) (NF023); 8,8'-(carbonylbis(imino-3,1-phenylene)carbonylimino-(3,1- phenylene)) bis(1,3,5-naphthalenetrisulfonic acid) (NF037); and suramin. Suramin and its analogues inhibit the formation of the agonist-specific ternary complex (agonist/receptor/G protein). This inhibition is (i) quasicompetitive with respect to agonist binding in that it can be overcome by increasing receptor occupancy but (ii) does not result from an interaction of the analogues with the ligand binding pocket of the receptors because the binding of antagonists or of agonists in the absence of functional receptor/G protein interaction is not affected. In addition to suppressing the spontaneous release of GDP from defined G protein alpha subunits, suramin and its analogues reduce receptor-catalyzed guanine nucleotide exchange. The site, to which suramin analogues bind, overlaps with the docking site for the receptor on the G protein alpha subunit. The structure-activity relationships for inhibition of agonist binding to the A1 adenosine receptor (suramin > NF037 > NF023) and of agonist binding to the inhibition D2 dopamine receptor (suramin = NF037 > NF023 > NF018) differ. Thus, NF037 discriminates between the ternary complexes formed by the agonist-liganded D2 dopamine receptors and those formed by the A1 adenosine

  20. The use of prostaglandins and their analogues for abortion.

    PubMed

    Bygdeman, M

    1984-12-01

    In general, termination of second trimester pregnancy is associated with three to five times higher morbidity and mortality risks than termination during the first trimester. The procedures mainly used are extra- or intra-amniotic administration of solutions such as hypertonic saline, ethacridine lactate, PGF2 alpha and PGE2. In comparison with these procedures, the use of prostaglandin analogues may offer important advantages, the most important one being the possibility of using non-invasive routes of administration. The continuous development of new analogues has now resulted in compounds that are highly effective in stimulating uterine contractility and are associated with a low frequency of side-effects; these compounds are suitable for both vaginal and intramuscular administration and are applicable for termination of pregnancy during both the early and late parts of the second trimester. The most widely used method for termination of first trimester pregnancy is vacuum aspiration. It is a highly effective procedure and the overall complication rate is low. One problem with vacuum aspiration is the mechanical dilatation of the cervical canal which is necessary from at least the 8th week and onwards. Pretreatment with laminaria tents or with prostaglandin analogues eliminates or reduces the need for mechanical dilatation and significantly facilitates the procedure. Pretreatment with prostaglandin analogues also reduces the risk of both operative and postoperative complications. The prostaglandins also offer a possibility as a non-surgical procedure for termination of very early pregnancy. Both vaginal and intramuscular administration of the latest generation of PG analogues have been shown in several studies to be equally as effective as vacuum aspiration if the treatment is restricted to the first three weeks following the first missed menstrual period. Gastrointestinal side-effects are still a problem although of significantly less importance than if natural

  1. Identifying climate analogues for precipitation extremes for Denmark based on RCM simulations from the ENSEMBLES database.

    PubMed

    Arnbjerg-Nielsen, K; Funder, S G; Madsen, H

    2015-01-01

    Climate analogues, also denoted Space-For-Time, may be used to identify regions where the present climatic conditions resemble conditions of a past or future state of another location or region based on robust climate variable statistics in combination with projections of how these statistics change over time. The study focuses on assessing climate analogues for Denmark based on current climate data set (E-OBS) observations as well as the ENSEMBLES database of future climates with the aim of projecting future precipitation extremes. The local present precipitation extremes are assessed by means of intensity-duration-frequency curves for urban drainage design for the relevant locations being France, the Netherlands, Belgium, Germany, the United Kingdom, and Denmark. Based on this approach projected increases of extreme precipitation by 2100 of 9 and 21% are expected for 2 and 10 year return periods, respectively. The results should be interpreted with caution as the best region to represent future conditions for Denmark is the coastal areas of Northern France, for which only little information is available with respect to present precipitation extremes. PMID:25714642

  2. CpG methylation increases the DNA binding of 9-aminoacridine carboxamide Pt analogues.

    PubMed

    Kava, Hieronimus W; Murray, Vincent

    2016-10-01

    This study investigated the effect of CpG methylation on the DNA binding of cisplatin analogues with an attached aminoacridine intercalator. DNA-targeted 9-aminoacridine carboxamide Pt complexes are known to bind at 5'-CpG sequences. Their binding to methylated and non-methylated 5'-CpG sequences was determined and compared with cisplatin. The damage profiles of each platinum compound were quantified via a polymerase stop assay with fluorescently labelled primers and capillary electrophoresis. Methylation at 5'-CpG was shown to significantly increase the binding intensity for the 9-aminoacridine carboxamide compounds, whereas no significant increase was found for cisplatin. 5'-CpG methylation had the largest effect on the 9-ethanolamine-acridine carboxamide Pt complex, followed by the 9-aminoacridine carboxamide Pt complex and the 7-fluoro complex. The methylation state of a cell's genome is important in maintaining normal gene expression, and is often aberrantly altered in cancer cells. An analogue of cisplatin which differentially targets methylated DNA may be able to improve its therapeutic activity, or alter its range of targets and evade the chemoresistance which hampers cisplatin efficacy in clinical use. PMID:27567075

  3. Towards a smart Holter system with high performance analogue front-end and enhanced digital processing.

    PubMed

    Du, Leilei; Yan, Yan; Wu, Wenxian; Mei, Qiujun; Luo, Yu; Li, Yang; Wang, Lei

    2013-01-01

    Multiple-lead dynamic ECG recorders (Holter) play an important role in the earlier detection of various cardiovascular diseases. In this paper, we present the first several steps towards a 12-lead Holter system with high-performance AFE (Analogue Front-End) and enhanced digital processing. The system incorporates an analogue front-end chip (ADS1298 from TI), which has not yet been widely used in most commercial Holter products. A highly-efficient data management module was designated to handle the data exchange between the ADS1298 and the microprocessor (STM32L151 from ST electronics). Furthermore, the system employs a Field Programmable Gate Array (Spartan-3E from Xilinx) module, on which a dedicated real-time 227-step FIR filter was executed to improve the overall filtering performance, since the ADS1298 has no high-pass filtering capability and only allows limited low-pass filtering. The Spartan-3E FPGA is also capable of offering further on-board computational ability for a smarter Holter. The results indicate that all functional blocks work as intended. In the future, we will conduct clinical trials and compare our system with other state-of-the-arts. PMID:24109911

  4. Noncommutative analogue Aharonov-Bohm effect and superresonance

    NASA Astrophysics Data System (ADS)

    Anacleto, M. A.; Brito, F. A.; Passos, E.

    2013-06-01

    We consider the idea of modeling a rotating acoustic black hole by an idealized draining bathtub vortex which is a planar circulating flow phenomenon with a sink at the origin. We find the acoustic metric for this phenomenon from a noncommutative Abelian Higgs model. As such the acoustic metric not only describes a rotating acoustic black hole but also inherits the noncommutative characteristic of the spacetime. We address the issues of superresonance and analogue Aharonov-Bohm (AB) effect in this background. We mainly show that the scattering of planar waves by a draining bathtub vortex leads to a modified AB effect and due to spacetime noncommutativity, the phase shift persists even in the limit where the parameters associated with the circulation and draining vanish. Finally, we also find that the analogue AB effect and superresonance are competing phenomena at a noncommutative spacetime.

  5. Analogue Transformations in Physics and their Application to Acoustics

    PubMed Central

    García-Meca, C.; Carloni, S.; Barceló, C.; Jannes, G.; Sánchez-Dehesa, J.; Martínez, A.

    2013-01-01

    Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation techniques to other branches of physics is often constrained by the structure of the field equations. We develop here a complete transformation method using the idea of analogue spacetimes. The method is general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an “analogue transformation acoustics” formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give explicit designs of a dynamic compressor, a spacetime cloak for acoustic waves and a carpet cloak for a moving aircraft. PMID:23774575

  6. Synthesis and α1-adrenoceptor antagonist activity of tamsulosin analogues.

    PubMed

    Sagratini, Gianni; Angeli, Piero; Buccioni, Michela; Gulini, Ugo; Marucci, Gabriella; Melchiorre, Carlo; Poggesi, Elena; Giardinà, Dario

    2010-12-01

    Tamsulosin (-)-1 is the most utilized α(1)-adrenoceptor antagonist in the benign prostatic hyperplasia therapy owing to its uroselective antagonism and capability in relieving both obstructive and irritative lower urinary tract symptoms. Here we report the synthesis and pharmacological study of the homochiral (-)-1 analogues (-)-2-(-)-5, bearing definite modifications in the 2-substituted phenoxyethylamino group in order to evaluate their influence on the affinity profile for α(1)-adrenoceptor subtypes. The benzyl analogue (-)-3, displaying a preferential antagonist profile for α1A-than α1D-and α1B-adrenoceptors, and a 12-fold higher potency at α1A-adrenoceptors with respect to the α1B subtype, may have improved uroselectivity compared to (-)-1. PMID:20934789

  7. New selenium-75 labeled radiopharmaceuticals: selenonium analogues of dopamine

    SciTech Connect

    Sadek, S.A.; Basmadjian, G.P.; Hsu, P.M.; Rieger, J.A.

    1983-07-01

    Selenium-75 labeled selenonium analogues of dopamine, (2-(3,4-dimethoxyphenyl)ethyl)dimethylselenonium iodide and its dihydroxy analogue, were prepared by reducing (/sup 75/Se)selenious acid with sodium borohydride at pH 6.0 and reacting the NaSeH produced with 1-(3,4-dimethoxyphenyl)-2-(p-toluenesulfonyloxy)ethane. Tissue distribution studies in rats given the /sup 75/Se-labeled selenonium agents intravenously demonstrated high initial heart uptake. Prolonged adrenal retention and high adrenal to blood ratio of compound 4 were observed. The high uptake and adrenal to blood ratio suggest the potential use of compound 4 as a radiopharmaceutical for the adrenal gland.

  8. Novel Azetidine-Containing TZT-1027 Analogues as Antitumor Agents.

    PubMed

    Yan, Qi; Wang, Yujie; Zhang, Wei; Li, Yingxia

    2016-05-01

    A conformational restriction strategy was used to design and synthesize nine TZT-1027 analogues. 3-Aryl-azetidine moiety was used to replace phenylethyl group of TZT-1027 at the C-terminus. These analogues exhibited moderate to excellent antiproliferative activities, and the most potent compound 1a showed IC50 values of 2.2 nM against A549 and 2.1 nM against HCT116 cell lines, respectively. However, 1a could not achieve effective inhibition at all the dose levels in the A549 xenograft model (up to 5 mg/kg, injection, once a day), which is only 16%-35% inhibition at the end of the experiment. PMID:27136567

  9. Alligator rivers analogue project an OECD/NEA international project

    SciTech Connect

    Duerden, P.; Airey, P.; Pescatore, C.

    1994-12-31

    The Koongarra uranium deposit in the Alligator Rivers Region of the Northern Territory of Australia was studied as a natural analogue of the far field behaviour of high level waste repositories following groundwater ingress. A number of mathematical modelling approaches were developed for processes as diverse as groundwater transport, host rock weathering, radionuclide sorption, evolution of the uranium dispersion fan and the distribution of uranium series nuclides between mineral assemblages in weathered host rock. Some of these models are relevant to performance assessment at the level of individual processes and subsystem performance. Through the project, new insights into the application of the natural analogue approach to the assessment of potential waste repository sites were obtained.

  10. Stereocontrolled Synthesis of Key Advanced Intermediates toward Simplified Acetogenin Analogues.

    PubMed

    Le Huérou, Yvan; Doyon, Julien; Grée, René L.

    1999-09-01

    The stereo- and enantiocontrolled synthesis of substituted beta-hydroxy ethers based on glycol and catechol bearing an alkyne group and a series of substituents is reported. These substrates were designed to mimic the bis-THF array of annonaceous acetogenins and to provide an access to simplified and modified analogues. The key steps of the synthesis involve the condensation of the nonracemic mesylate of solketal with ethylene glycol and catechol, followed by an alkylation with a glycidyl derivative. Under appropriate conditions, the reaction is completely stereoselective and allows the synthesis of all the diastereomers. After the epoxide was opened with triethylsilylacetylene, the second epoxide was unmasked and reacted with a series of alkyl, aryl, amine, and alcohol reagents. A series of 28 analogues was prepared having a glycol or a catechol core, a stereodefined configuration of the flanking hydroxyl groups, and an acetylenic appendage suitable for a coupling to a lactone-bearing fragment. PMID:11674687

  11. Synthesis of Methylenecyclopropane Analogues of Antiviral Nucleoside Phosphonates

    PubMed Central

    Yan, Zhaohua; Zhou, Shaoman; Kern, Earl R.; Zemlicka, Jiri

    2006-01-01

    Synthesis of methylenecyclopropane analogues of nucleoside phosphonates 6a, 6b, 7a and 7b is described. Cyclopropyl phosphonate 8 was transformed in four steps to methylenecyclopropane phosphonate 16. The latter intermediate was converted in seven steps to the key Z- and E-methylenecyclopropane alcohols 23 and 24 separated by chromatography. Selenoxide eliminations (15 → 16 and 22 → 23 + 24) were instrumental in the synthesis. The Z- and E-isomers 23 and 24 were transformed to bromides 25a and 25b which were used for alkylation of adenine and 2-amino-6-chloropurine to give intermediates 26a, 26b, 26c and 26d. Acid hydrolysis provided the adenine and guanine analogues 6a, 6b, 7a and 7b. Phosphonates 6b and 7b are potent inhibitors of replication of Epstein-Barr virus (EBV). PMID:16758001

  12. Millimeter and Submillimeter Studies of Interstellar Ice Analogues

    NASA Astrophysics Data System (ADS)

    Mesko, AJ; Wagner, Ian C.; Smith, Houston Hartwell; Milam, Stefanie N.; Widicus Weaver, Susanna L.

    2015-06-01

    The chemistry of interstellar ice analogues has been a topic of great interest to astrochemists over the last 20 years. Currently, the models of interstellar chemistry feature icy-grain reactions as a primary mechanism for the formation of many astrochemical species as well as potentially astrobiologically-relevant complex organic molecules. This talk presents new spectral results collected by a millimeter and submillimeter spectrometer coupled to a vacuum chamber designed to study the sublimation or sputtered products of icy-grain reactions initiated by thermal-processing or photo-processing of interstellar ice analogues. Initial results from thermal desorption and UV photoprocessing experiments of pure water ice and water + methanol ice mixtures will be presented.

  13. Neurological Effects of Bisphenol A and its Analogues

    PubMed Central

    Inadera, Hidekuni

    2015-01-01

    The endocrine disrupting chemical bisphenol A (BPA) is widely used in the production of polycarbonate plastics and epoxy resins. The use of BPA-containing products in daily life makes exposure ubiquitous, and the potential human health risks of this chemical are a major public health concern. Although numerous in vitro and in vivo studies have been published on the effects of BPA on biological systems, there is controversy as to whether ordinary levels of exposure can have adverse effects in humans. However, the increasing incidence of developmental disorders is of concern, and accumulating evidence indicates that BPA has detrimental effects on neurological development. Other bisphenol analogues, used as substitutes for BPA, are also suspected of having a broad range of biological actions. The objective of this review is to summarize our current understanding of the neurobiological effects of BPA and its analogues, and to discuss preventive strategies from a public health perspective. PMID:26664253

  14. Glaucine analogues as inhibitors of mouse splenocyte activity.

    PubMed

    Philipov, S; Ivanovska, N; Nikolova, P

    1998-10-01

    The inhibitory effect of 15 semi-synthetic analogues of glaucine (1) on the lipopolysaccharide (LPS)-induced and the concanavalin A (Con A)-induced proliferation of mouse splenocytes was compared in vitro. Isoboldine (3), bracteoline (4) and dehydroglaucine (9) showed a significantly higher potency to suppress LPS-induced proliferation than 1, while 7-hydroxy-4-methylglaucine (8), 7-formyldehydroglaucine (11), 7-acetyldehydroglaucine (13), 7-benzoyldehydroglaucine (14), oxoglaucine (15) and glaucine-quinol (16) were less inhibitory. Compounds 3, 4, boldine (5), 15 and 16 surpassed significantly the inhibition expressed by 1 on Con A-induced proliferative response. The effect was equal to the inhibition determined for mitomycin C (Mit C) with both mitogens. In contrast to all others analogues, thaliporphine (2) stimulated splenocyte proliferation in both assays. Antibody response against sheep red blood cells (SRBC) was lowered most strongly by cataline (6), 7-methyldehydroglaucine (10) and 16. PMID:9812336

  15. Optical analogue of relativistic Dirac solitons in binary waveguide arrays

    SciTech Connect

    Tran, Truong X.; Longhi, Stefano; Biancalana, Fabio

    2014-01-15

    We study analytically and numerically an optical analogue of Dirac solitons in binary waveguide arrays in the presence of Kerr nonlinearity. Pseudo-relativistic soliton solutions of the coupled-mode equations describing dynamics in the array are analytically derived. We demonstrate that with the found soliton solutions, the coupled mode equations can be converted into the nonlinear relativistic 1D Dirac equation. This paves the way for using binary waveguide arrays as a classical simulator of quantum nonlinear effects arising from the Dirac equation, something that is thought to be impossible to achieve in conventional (i.e. linear) quantum field theory. -- Highlights: •An optical analogue of Dirac solitons in nonlinear binary waveguide arrays is suggested. •Analytical solutions to pseudo-relativistic solitons are presented. •A correspondence of optical coupled-mode equations with the nonlinear relativistic Dirac equation is established.

  16. Analogue transformations in physics and their application to acoustics.

    PubMed

    García-Meca, C; Carloni, S; Barceló, C; Jannes, G; Sánchez-Dehesa, J; Martínez, A

    2013-01-01

    Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation techniques to other branches of physics is often constrained by the structure of the field equations. We develop here a complete transformation method using the idea of analogue spacetimes. The method is general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an "analogue transformation acoustics" formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give explicit designs of a dynamic compressor, a spacetime cloak for acoustic waves and a carpet cloak for a moving aircraft. PMID:23774575

  17. A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

    NASA Astrophysics Data System (ADS)

    Jameson, Bradford A.; McDonnell, James M.; Marini, Joseph C.; Korngold, Robert

    1994-04-01

    EXPERIMENTAL allergic encephalomyelitis (EAE) is an acute inflammatory autoimmune disease of the central nervous system that can be elicited in rodents and is the major animal model for the study of multiple sclerosis (MS)1,2. The pathogenesis of both EAE and MS directly involves the CD4+ helper T-cell subset3-5. Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents6-9, and are currently being used in human clinical trials for MS. We report here that similar therapeutic effects can be achieved in mice using a small (rationally designed) synthetic analogue of the CD4 protein surface. It greatly inhibits both clinical incidence and severity of EAE with a single injection, but does so without depletion of the CD4+ subset and without the inherent immunogenicity of an antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.

  18. On-chip learning with analogue VLSI neural networks.

    PubMed

    Tarassenko, L; Tombs, J; Cairns, G

    1993-12-01

    Results from simulations of weight perturbation as an on-chip learning scheme for analogue VLSI neural networks are presented. The limitations of analogue hardware are modelled as realistically as possible. Thus synaptic weight precision is defined according to the smallest change in the weight setting voltage which gives a measurable change at the output of the corresponding neuron. Tests are carried out on a hard classification problem constructed from mobile robot navigation data. The simulations show that the degradation in classification performance on a 500-pattern test set caused by the introduction of realistic hardware constraints is acceptable: with 8-bit weights, updated probabilistically and with a simplified output error criterion, the error rate increases by no more than 7% when compared with weight perturbation implemented with full 32-bit precision. PMID:8049803

  19. Synthesis and biological activity of polyalthenol and pentacyclindole analogues.

    PubMed

    Marcos, Isidro S; Moro, Rosalina F; Costales, Isabel; Basabe, Pilar; Díez, David; Gil, Ana; Mollinedo, Faustino; Pérez-de la Rosa, Fátima; Pérez-Roth, Eduardo; Padrón, José M

    2014-02-12

    A series of indole sesquiterpenes analogues of polyalthenol and pentacyclindole have been synthesized starting from ent-halimic acid in order to test their biological activity. These analogues include diverse oxidation levels at the sesquiterpenyl moiety and different functionalization on the indole ring. All synthetic derivatives were tested against a representative panel of Gram positive and Gram negative bacterial strains, and the human solid tumour cell lines A549 (non-small cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast) and WiDr (colon). Overall, the compounds presented activity against the cancer cell lines. The resulting lead, displaying a polyalthenol scaffold, showed GI50 values in the range 1.2-5.7 μM against all cell lines tested. PMID:24412720

  20. Novel Azetidine-Containing TZT-1027 Analogues as Antitumor Agents

    PubMed Central

    Yan, Qi; Wang, Yujie; Zhang, Wei; Li, Yingxia

    2016-01-01

    A conformational restriction strategy was used to design and synthesize nine TZT-1027 analogues. 3-Aryl-azetidine moiety was used to replace phenylethyl group of TZT-1027 at the C-terminus. These analogues exhibited moderate to excellent antiproliferative activities, and the most potent compound 1a showed IC50 values of 2.2 nM against A549 and 2.1 nM against HCT116 cell lines, respectively. However, 1a could not achieve effective inhibition at all the dose levels in the A549 xenograft model (up to 5 mg/kg, injection, once a day), which is only 16%–35% inhibition at the end of the experiment. PMID:27136567

  1. Naturally-occurring chemical analogues for repository-derived radionuclides

    SciTech Connect

    Miller, B.

    1996-12-01

    Studies of natural systems are a valuable means of gaining information on the behavior of elements and radionuclides in the geosphere or biosphere that may be used to support performance assessments for radioactive waste repositories. However, these natural system studies face the problem that some of the chemical and isotopic species that occur in radioactive wastes do not occur naturally. Therefore, when attempting to study transport processes for these species other, naturally-occurring species must be examined as {open_quote}chemical analogues{close_quote} for the waste species. Chemical analogues are chosen on the basis of some similarity with the chemical behavior of the waste species in relevant physico-chemical environments. This is a tricky procedure and each system must be considered on a case-by-case basis, although some guidelines can be established and these are given here.

  2. Charge deficient analogues of the natural polyamines.

    PubMed

    Weisell, Janne; Hyvönen, Mervi T; Alhonen, Leena; Vepsäläinen, Jouko; Keinänen, Tuomo A; Khomutov, Alex R

    2014-01-01

    Mitochondrial dysfunction, either inherited or acquired, is associated with several diseases in humans. Depending on the cell type and location, cells are prone to multiple types of insults that may compromise their proper function. Generally, these insults are overcome by defensive mechanisms but sometimes they lead to sustained damage, requiring the action of scavenging and repair machineries to retain the viability of the cells. As a final measure, severely damaged cells are targeted to a controlled cell death pathway in order to not to compromise the well-being of the whole tissue. The polyamines, spermine and spermidine are essential cellular constituents, participating in many vital functions such as proliferation and differentiation, immune response and scavenging of reactive oxygen species. Therefore, dysregulation of polyamine metabolism is often associated with different pathological states. Polyamine acetylating enzyme spermidine/spermine-N(1)-acetyltransferase is induced by inflammation, drugs and by several other environmental insults. Resulting accelerated polyamine acetylation with accompanying polyamine biosynthesis induction i.e. activation of polyamine futile cycle generates excessive amount of hydrogen peroxide, hampers cell energy metabolism and induces mitochondrial dysfunction and biogenesis. Therefore, the drugs inhibiting polyamine metabolism are valuable in protecting mitochondria and cell energy metabolism. Here we review the current literature focusing on the applicability of chargedeficient polyamine analogs as drugs to modulate polyamine metabolism. Alteration of pK(a) of amino group(s) in a respective analog is achieved by fluorine substitution of hydrogen atom, hydroxylamine substitution of methylamine or by reducing the numbers of carbon atoms between amine groups to two instead of three or four. PMID:23701551

  3. Bis(vinylenedithio)tetrathiafulvalene analogues of BEDT-TTF.

    PubMed

    Ertas, Erdal; Demirtas, İlknur; Ozturk, Turan

    2015-01-01

    This review aims to give an overview of the current status of our research on the synthesis of π-electron donor bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF, ET) analogues prepared from 1,8-diketones via a ring forming reaction. The new synthesized π-electron donors have vinyl moieties producing extended π-electron delocalization over the substituent phenyl rings at the peripheries. PMID:25977714

  4. Bis(vinylenedithio)tetrathiafulvalene analogues of BEDT-TTF

    PubMed Central

    Demirtas, İlknur; Ozturk, Turan

    2015-01-01

    Summary This review aims to give an overview of the current status of our research on the synthesis of π-electron donor bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF, ET) analogues prepared from 1,8-diketones via a ring forming reaction. The new synthesized π-electron donors have vinyl moieties producing extended π-electron delocalization over the substituent phenyl rings at the peripheries. PMID:25977714

  5. Synthesis of phosphonate and phostone analogues of ribose-1-phosphates

    PubMed Central

    Nasomjai, Pitak; Slawin, Alexandra M Z

    2009-01-01

    Summary The synthesis of phosphonate analogues of ribose-1-phosphate and 5-fluoro-5-deoxyribose-1-phosphate is described. Preparations of both the α- and β-phosphonate anomers are reported for the ribose and 5-fluoro-5-deoxyribose series and a synthesis of the corresponding cyclic phostones of each α-ribose is also reported. These compounds have been prepared as tools to probe the details of fluorometabolism in S. cattleya. PMID:19777136

  6. Dimerization and DNA recognition rules of mithramycin and its analogues.

    PubMed

    Weidenbach, Stevi; Hou, Caixia; Chen, Jhong-Min; Tsodikov, Oleg V; Rohr, Jürgen

    2016-03-01

    The antineoplastic and antibiotic natural product mithramycin (MTM) is used against cancer-related hypercalcemia and, experimentally, against Ewing sarcoma and lung cancers. MTM exerts its cytotoxic effect by binding DNA as a divalent metal ion (Me(2+))-coordinated dimer and disrupting the function of transcription factors. A precise molecular mechanism of action of MTM, needed to develop MTM analogues selective against desired transcription factors, is lacking. Although it is known that MTM binds G/C-rich DNA, the exact DNA recognition rules that would allow one to map MTM binding sites remain incompletely understood. Towards this goal, we quantitatively investigated dimerization of MTM and several of its analogues, MTM SDK (for Short side chain, DiKeto), MTM SA-Trp (for Short side chain and Acid), MTM SA-Ala, and a biosynthetic precursor premithramycin B (PreMTM B), and measured the binding affinities of these molecules to DNA oligomers of different sequences and structural forms at physiological salt concentrations. We show that MTM and its analogues form stable dimers even in the absence of DNA. All molecules, except for PreMTM B, can bind DNA with the following rank order of affinities (strong to weak): MTM=MTM SDK>MTM SA-Trp>MTM SA-Ala. An X(G/C)(G/C)X motif, where X is any base, is necessary and sufficient for MTM binding to DNA, without a strong dependence on DNA conformation. These recognition rules will aid in mapping MTM sites across different promoters towards development of MTM analogues as useful anticancer agents. PMID:26760230

  7. Inhibition of telomerase by BIBR 1532 and related analogues.

    PubMed

    Barma, D K; Elayadi, Anissa; Falck, J R; Corey, David R

    2003-04-01

    BIBR 1532 has been reported to be a potent, small molecule inhibitor of human telomerase, suggesting it as a lead for the development of anti-telomerase therapy. We confirm the ability of BIBR 1532 to inhibit telomerase and report the discovery of an equally potent analogue. Importantly, IC(50) values in cell extract are considerably higher than those previously reported using assays for purified enzyme, indicating that substantial improvement may be necessary. PMID:12657276

  8. Lysophosphatidylserine analogues differentially activate three LysoPS receptors.

    PubMed

    Uwamizu, Akiharu; Inoue, Asuka; Suzuki, Kensuke; Okudaira, Michiyo; Shuto, Akira; Shinjo, Yuji; Ishiguro, Jun; Makide, Kumiko; Ikubo, Masaya; Nakamura, Sho; Jung, Sejin; Sayama, Misa; Otani, Yuko; Ohwada, Tomohiko; Aoki, Junken

    2015-03-01

    Lysophosphatidylserine (1-oleoyl-2 R-lysophosphatidylserine, LysoPS) has been shown to have lipid mediator-like actions such as stimulation of mast cell degranulation and suppression of T lymphocyte proliferation, although the mechanisms of LysoPS actions have been elusive. Recently, three G protein-coupled receptors (LPS1/GPR34, LPS2/P2Y10 and LPS3/GPR174) were found to react specifically with LysoPS, raising the possibility that LysoPS serves as a lipid mediator that exerts its role through these receptors. Previously, we chemically synthesized a number of LysoPS analogues and evaluated them as agonists for mast-cell degranulation. Here, we used a transforming growth factor-α (TGFα) shedding assay to see if these LysoPS analogues activated the three LysoPS receptors. Modification of the serine moiety significantly reduced the ability of the analogues to activate the three LysoPS receptors, whereas modification of other parts resulted in loss of activity in receptor-specific manner. We found that introduction of methyl group to serine moiety (1-oleoyl-lysophosphatidylallothreonine) and removal of sn-2 hydroxyl group (1-oleoyl-2-deoxy-LysoPS) resulted in reduction of reactivity with LPS1 and LPS3, respectively. Accordingly, we synthesized a LysoPS analogue with the two modifications (1-oleoyl-2-deoxy-lysophosphatidylallothreonine) and found it to be an LPS2-selective agonist. These pharmacological tools will definitely help to identify the biological roles of these LysoPS receptors. PMID:25320102

  9. Evaluation of anti-HIV-1 mutagenic nucleoside analogues.

    PubMed

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-01

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of "lethal mutagenesis" that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. PMID:25398876

  10. Using fuzzy sets for data interpretation in natural analogue studies

    SciTech Connect

    De Lemos, F.L.; Sullivan, T.; Hellmuth, K.H.

    2008-07-01

    Natural analogue studies can play a key role in deep geological radioactive disposal systems safety assessment. These studies can help develop a better understanding of complex natural processes and, therefore, provide valuable means of confidence building in the safety assessment. In evaluation of natural analogues, there are, however, several sources of uncertainties that stem from factors such as complexity; lack of data; and ignorance. Often, analysts have to simplify the mathematical models in order to cope with the various sources of complexity and this ads uncertainty to the model results. The uncertainties reflected in model predictions must be addressed to understand their impact on safety assessment and therefore, the utility of natural analogues. Fuzzy sets can be used to represent the information regarding the natural processes and their mutual connections. With this methodology we are able to quantify and propagate the epistemic uncertainties in both processes and, thereby, assign degrees of truth to the similarities between them. An example calculation with literature data is provided. In conclusion: Fuzzy sets are an effective way of quantifying semi-quantitative information such as natural analogues data. Epistemic uncertainty that stems from complexity and lack of knowledge regarding natural processes are represented by the degrees of membership. It also facilitates the propagation of this uncertainty throughout the performance assessment by the extension principle. This principle allows calculation with fuzzy numbers, where fuzzy input results in fuzzy output. This may be one of the main applications of fuzzy sets theory to radioactive waste disposal facility performance assessment. Through the translation of natural data into fuzzy numbers, the effect of parameters in important processes in one site can be quantified and compared to processes in other sites with different conditions. The approach presented in this paper can be extended to

  11. Endiandric Acid Analogues from the Roots of Beilschmiedia erythrophloia.

    PubMed

    Yang, Ping-Shin; Cheng, Ming-Jen; Peng, Chien-Fang; Chen, Jih-Jung; Chen, Ih-Sheng

    2009-01-01

    Investigation of the roots of Beilschmiedia erythrophloia has led to the isolation of seven new endiandric acid analogues, erythrophloins A-F (1-6) and beilcyclone A (7), together with 11 known compounds. The structures of 1-7 were determined using spectroscopic techniques. Two constituents, erythrophloin C (3) and suberosol B (8), exhibited antitubercular activity against Mycobacterium tuberculosis H37Rv, showing MIC values of 50 and 28.9 microg/mL, respectively. PMID:19072217

  12. Synthesis of thioglycoside-based UDP-sugar analogues.

    PubMed

    Zhu, Xiangming; Stolz, Florian; Schmidt, Richard R

    2004-10-15

    Arbuzov reaction of O-acetyl-protected glycosylthiomethyl chlorides with triethyl phosphite and then phosphonate ethyl ester cleavage with trimethylsilyl bromide afforded glycosylthiomethyl phosphonates 13, 18, 22, and 26. These intermediates could be readily transformed into the O-deprotected phosphonates 7-10 and into title compounds 1-4. Similarly, sulfonomethyl phosphonate moieties containing UDP-sugar analogues 5 and 6 were obtained. PMID:15471496

  13. Contact zones and hydrothermal systems as analogues to repository conditions

    SciTech Connect

    Wollenberg, H.A.; Flexser, S.

    1984-10-01

    Radioactive waste isolation efforts in the US are currently focused on examining basalt, tuff, salt, and crystalline rock as candidate rock types to encompass waste repositories. As analogues to near-field conditions, the distributions of radio- and trace-elements have been examined across contacts between these rocks and dikes and stocks that have intruded them. The intensive study of the Stripa quartz monzonite has also offered the opportunity to observe the distribution of uranium and its daughters in groundwater and its relationship to U associated with fracture-filling and alteration minerals. Investigations of intrusive contact zones to date have included (1) a tertiary stock into Precambrian gneiss, (2) a stock into ash flow tuff, (3) a rhyodacite dike into Columbia River basalt, and (4) a kimberlite dike into salt. With respect to temperature and pressure, these contact zones may be considered "worst-case scenario" analogues. Results indicate that there has been no appreciable migration of radioelements from the more radioactive intrusives into the less radioactive country rocks, either in response to the intrusions or in the fracture-controlled hydrological systems that developed following emplacement. In many cases, the radioelements are locked up in accessory minerals, suggesting that artificial analogues to these would make ideal waste forms. Emphasis should now shift to examination of active hydrothermal systems, studying the distribution of key elements in water, fractures, and alteration minerals under pressure and temperature conditions most similar to those expected in the near-field environment of a repository. 14 refs.

  14. Simulated Milky Way analogues: implications for dark matter direct searches

    NASA Astrophysics Data System (ADS)

    Bozorgnia, Nassim; Calore, Francesca; Schaller, Matthieu; Lovell, Mark; Bertone, Gianfranco; Frenk, Carlos S.; Crain, Robert A.; Navarro, Julio F.; Schaye, Joop; Theuns, Tom

    2016-05-01

    We study the implications of galaxy formation on dark matter direct detection using high resolution hydrodynamic simulations of Milky Way-like galaxies simulated within the EAGLE and APOSTLE projects. We identify Milky Way analogues that satisfy observational constraints on the Milky Way rotation curve and total stellar mass. We then extract the dark matter density and velocity distribution in the Solar neighbourhood for this set of Milky Way analogues, and use them to analyse the results of current direct detection experiments. For most Milky Way analogues, the event rates in direct detection experiments obtained from the best fit Maxwellian distribution (with peak speed of 223–289 km/s) are similar to those obtained directly from the simulations. As a consequence, the allowed regions and exclusion limits set by direct detection experiments in the dark matter mass and spin-independent cross section plane shift by a few GeV compared to the Standard Halo Model, at low dark matter masses. For each dark matter mass, the halo-to-halo variation of the local dark matter density results in an overall shift of the allowed regions and exclusion limits for the cross section. However, the compatibility of the possible hints for a dark matter signal from DAMA and CDMS-Si and null results from LUX and SuperCDMS is not improved.

  15. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    SciTech Connect

    G. Saulnier and W. Statham

    2006-04-16

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. The Pena Blanca Natural Analogue Performance Assessment Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash-flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following analogous characteristics as compared to the Yucca Mountain repository site: (1) Analogous source--UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geology--(i.e. fractured, welded, and altered rhyolitic ash-flow tuffs); (3) Analogous climate--Semiarid to arid; (4) Analogous setting--Volcanic tuffs overlie carbonate rocks; and (5) Analogous geochemistry--Oxidizing conditions Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table.

  16. Noble gas encapsulation: clathrate hydrates and their HF doped analogues.

    PubMed

    Mondal, Sukanta; Chattaraj, Pratim Kumar

    2014-09-01

    The significance of clathrate hydrates lies in their ability to encapsulate a vast range of inert gases. Although the natural abundance of a few noble gases (Kr and Xe) is poor their hydrates are generally abundant. It has already been reported that HF doping enhances the stability of hydrogen hydrates and methane hydrates, which prompted us to perform a model study on helium, neon and argon hydrates with their HF doped analogues. For this purpose 5(12), 5(12)6(8) and their HF doped analogues are taken as the model clathrate hydrates, which are among the building blocks of sI, sII and sH types of clathrate hydrate crystals. We use the dispersion corrected and gradient corrected hybrid density functional theory for the calculation of thermodynamic parameters as well as conceptual density functional theory based reactivity descriptors. The method of the ab initio molecular dynamics (AIMD) simulation is used through atom centered density matrix propagation (ADMP) techniques to envisage the structural behaviour of different noble gas hydrates on a 500 fs timescale. Electron density analysis is carried out to understand the nature of Ng-OH2, Ng-FH and Ng-Ng interactions. The current results noticeably demonstrate that the noble gas (He, Ne, and Ar) encapsulation ability of 5(12), 5(12)6(8) and their HF doped analogues is thermodynamically favourable. PMID:25047071

  17. Natural analogue studies as supplements to biomineralization research

    SciTech Connect

    McNeil, M.B.

    1995-09-01

    Chemical reactions can alter the chemistry and crystal structure of solid objects over archeological or geological times, while preserving external physical shapes. The reactions resulting in these structures offer natural analogues to laboratory experiments in biomineralization and to biologically influenced alteration of nuclear waste packages, and thus, they offer the only available way of validating models that purport waste package behavior over archaeological or geological times. Potential uses of such analogues in the construction and validation of hypothetical mechanisms of microbiological corrosion and biomineralization are reviewed. Evidence from such analogues suggests that biofilms can control materials alteration in ways usually overlooked. The newly hypothesized mechanisms involve control by biofilms of the cation flow near the solid surface and offer plausible mechanisms for the formation of mixed-cation minerals under conditions that would lead to dealloying in abiotic experiments; they also account for the formation of unusual minerals [such as posnjakite, Cu{sub 4}SO{sub 4}(OH){sub 6{center_dot}}H{sub 2}O] and mineral morphologies unusual in corrosion [malachite, Cu{sub 2}CO{sub 3}(OH){sub 2}, rarely forms botryoidally under corrosion conditions and its occasional presence on archaeological objects that appear to have undergone microbiological corrosion may be related to biofilm phenomena].

  18. Stereochemical Assignment of Strigolactone Analogues Confirms Their Selective Biological Activity.

    PubMed

    Artuso, Emma; Ghibaudi, Elena; Lace, Beatrice; Marabello, Domenica; Vinciguerra, Daniele; Lombardi, Chiara; Koltai, Hinanit; Kapulnik, Yoram; Novero, Mara; Occhiato, Ernesto G; Scarpi, Dina; Parisotto, Stefano; Deagostino, Annamaria; Venturello, Paolo; Mayzlish-Gati, Einav; Bier, Ariel; Prandi, Cristina

    2015-11-25

    Strigolactones (SLs) are new plant hormones with various developmental functions. They are also soil signaling chemicals that are required for establishing beneficial mycorrhizal plant/fungus symbiosis. In addition, SLs play an essential role in inducing seed germination in root-parasitic weeds, which are one of the seven most serious biological threats to food security. There are around 20 natural SLs that are produced by plants in very low quantities. Therefore, most of the knowledge on SL signal transduction and associated molecular events is based on the application of synthetic analogues. Stereochemistry plays a crucial role in the structure-activity relationship of SLs, as compounds with an unnatural D-ring configuration may induce biological effects that are unrelated to SLs. We have synthesized a series of strigolactone analogues, whose absolute configuration has been elucidated and related with their biological activity, thus confirming the high specificity of the response. Analogues bearing the R-configured butenolide moiety showed enhanced biological activity, which highlights the importance of this stereochemical motif. PMID:26502774

  19. Design and synthesis of biotin analogues reversibly binding with streptavidin.

    PubMed

    Yamamoto, Tomohiro; Aoki, Kiyoshi; Sugiyama, Akira; Doi, Hirofumi; Kodama, Tatsuhiko; Shimizu, Yohei; Kanai, Motomu

    2015-04-01

    Two new biotin analogues, biotin carbonate 5 and biotin carbamate 6, have been synthesized. These molecules were designed to reversibly bind with streptavidin by replacing the hydrogen-bond donor NH group(s) of biotin's cyclic urea moiety with oxygen. Biotin carbonate 5 was synthesized from L-arabinose (7), which furnishes the desired stereochemistry at the 3,4-cis-dihydroxy groups, in 11% overall yield (over 10 steps). Synthesis of biotin carbamate 6 was accomplished from L-cysteine-derived chiral aldehyde 33 in 11% overall yield (over 7 steps). Surface plasmon resonance analysis of water-soluble biotin carbonate analogue 46 and biotin carbamate analogue 47 revealed that KD values of these compounds for binding to streptavidin were 6.7×10(-6)  M and 1.7×10(-10)  M, respectively. These values were remarkably greater than that of biotin (KD =10(-15)  M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin. PMID:25691069

  20. Do film soundtracks contain nonlinear analogues to influence emotion?

    PubMed

    Blumstein, Daniel T; Davitian, Richard; Kaye, Peter D

    2010-12-23

    A variety of vertebrates produce nonlinear vocalizations when they are under duress. By their very nature, vocalizations containing nonlinearities may sound harsh and are somewhat unpredictable; observations that are consistent with them being particularly evocative to those hearing them. We tested the hypothesis that humans capitalize on this seemingly widespread vertebrate response by creating nonlinear analogues in film soundtracks to evoke particular emotions. We used lists of highly regarded films to generate a set of highly ranked action/adventure, dramatic, horror and war films. We then scored the presence of a variety of nonlinear analogues in these film soundtracks. Dramatic films suppressed noise of all types, contained more abrupt frequency transitions and musical sidebands, and fewer noisy screams than expected. Horror films suppressed abrupt frequency transitions and musical sidebands, but had more non-musical sidebands, and noisy screams than expected. Adventure films had more male screams than expected. Together, our results suggest that film-makers manipulate sounds to create nonlinear analogues in order to manipulate our emotional responses. PMID:20504815

  1. The UVB1 Vitamin D analogue inhibits colorectal carcinoma progression.

    PubMed

    Ferronato, María Julia; Alonso, Eliana Noelia; Gandini, Norberto Ariel; Fermento, María Eugenia; Villegas, María Emilia; Quevedo, Mario Alfredo; Arévalo, Julián; López Romero, Alejandro; Rivadulla, Marcos Lois; Gómez, Generosa; Fall, Yagamare; Facchinetti, María Marta; Curino, Alejandro Carlos

    2016-10-01

    Vitamin D has been shown to display a wide variety of antitumour effects, but their therapeutic use is limited by its severe side effects. We have designed and synthesized a Gemini vitamin D analogue of calcitriol (UVB1) which has shown to display antineoplastic effects on different cancer cell lines without causing hypercalcemia. The aim of this work has been to investigate, by employing in silico, in vitro, and in vivo assays, whether UVB1 inhibits human colorectal carcinoma progression. We demonstrated that UVB1 induces apoptotic cell death and retards cellular migration and invasion of HCT116 colorectal carcinoma cells. Moreover, the analogue reduced the tumour volume in vivo, and modulated the expression of Bax, E-cadherin and nuclear β-catenin in tumour animal tissues without producing toxic effects. In silico analysis showed that UVB1 exhibits greater affinity for the ligand binding domain of vitamin D receptor than calcitriol, and that several characteristics in the three-dimensional conformation of VDR may influence the biological effects. These results demonstrate that the Gemini vitamin D analogue affects the growth of the colorectal cancer and suggest that UVB1 is a potential chemotherapeutic agent for treatment of this disease. PMID:27208626

  2. Somatostatin and analogues in the treatment of cancer. A review.

    PubMed Central

    Evers, B M; Parekh, D; Townsend, C M; Thompson, J C

    1991-01-01

    Somatostatin is a naturally occurring cyclic tetradecapeptide that inhibits release of growth hormone and all gastrointestinal hormones. The beneficial effect of somatostatin in the treatment of certain hypersecretory disorders of hormone excess in well recognized; however its clinical usefulness has been limited in the past by its extremely short plasma half-life. The development of long-acting somatostatin analogues has provided clinically useful agents for treatment of hormone-producing tumors. In addition to well-known inhibiting effects on hormone release and actions, recent studies using experimental tumor models have demonstrated an antiproliferative effect of somatostatin and its analogues on growth of a variety of neoplasms. The exact role of somatostatin analogues in cancer therapy has yet to be established; however studies suggest that these agents could provide a useful and relatively nontoxic adjuvant therapy in the treatment of certain tumors. In this review, the oncologic application of somatostatin and possible mechanism of action are examined and current clinical and experimental studies are summarized. PMID:1671812

  3. Acyclic nucleoside/nucleotide analogues with an imidazole ring skeleton.

    PubMed

    Chen, H M; Hosmane, R S

    2001-08-01

    Syntheses of a few acyclic nucleoside and acyclic nucleoside phosphonate analogues containing an imidazole ring have been reported. These analogues include methyl 1-(2-hydroxyethoxymethyl)imidazole-4, 5-dicarbo-xylate (1), 4,5-dicarbamoyl-1-(2-hydroxyethoxymethyl)imidazole (2), 4,5-dicyano-1-(2-hydroxyethoxymethyl)imidazole (4), Methyl 1-(2-bromoethoxymethyl)imidazole-4,5-dicarboxylate (7), 4,5-dicyano-(2-bromoethoxymethyl)imidazole (8), and Methyl 1-(2-phosphonomethoxyethyl)imidazole (10). Also reported are a few potential prodrugs of the above compounds, including the acetyl derivatives 5 and 6 (of 1 and 4, respectively), and the diethyl phosphonate ester 9 (of 10). In addition, the corresponding benzyl-protected precursors 11 and 12 (of 1 and 4, respectively), along with their common hydrolysis product, 1-(2-benzyloxy-ethoxymethyl)-4,5-imidazoledicarboxylic acid (3), are reported. Another potential prodrug included in the list is 1-(2-acetoxyethyl)-4,5-dicyanoimidazole (15). The compounds were screened for in vitro antiviral activity against a wide variety of herpes and respiratory viruses. The most active compound was the phosphonate analogue 9 which exhibited an anti-measles virus activity with an EC50 of <2.5 microg/mL and an SI value of > 176. PMID:11554548

  4. Synthetic Nanopores: Biological Analogues and Nanofluidic Devices

    NASA Astrophysics Data System (ADS)

    Davenport, Matthew W.

    Nanoscopic pores in biological systems -- cells, for example -- are responsible for regulating the transport of ionic and molecular species between physiologically distinct compartments maintained by thin plasma membranes. These biological pores are proteinaceous structures: long, contorted chains of chemical building blocks called amino acids. Protein pores have evolved to span a staggering range of shapes, sizes and chemical properties, each crucial to a pore's unique functionality. Protein pores have extremely well-defined jobs. For instance, pores called ion channels only transport ions. Within this family, there are pores designated to selectively transport specific ions, such as sodium channels for sodium, chloride channels for chloride and so on. Further subdivisions exist within each type of ion channel, resulting in a pantheon of specialized proteins pores. Specificity and selectivity are bestowed upon a pore through its unique incorporation and arrangement of its amino acids, which in turn have their own unique chemical and physical properties. With hundreds of task-specific pores, deciphering the precise relationship between form and function in these protein channels is a critical, but daunting task. In this thesis, we examine an alternative for probing the fundamental mechanisms responsible for transport on the nanoscale. Solid-state membranes offer well-defined structural surrogates to directly address the science underlying pore functionality. Numerous protein pores rely on electronic interactions, size exclusion principles and hydrophobic effects to fulfill their duties, regardless of their amino acid sequence. Substituting an engineered and well-characterized pore, we strive to achieve and, thus, understand the hallmarks of biological pore function: analyte recognition and selective transport. While we restrict our study to only two readily available membrane materials -- one a polymer and the other a ceramic -- nanofabrication techniques give us

  5. Using stressful films to analyze risk factors for PTSD in analogue experimental studies--which film works best?

    PubMed

    Weidmann, Anke; Conradi, Ania; Groger, Kathrin; Fehm, Lydia; Fydrich, Thomas

    2009-10-01

    To understand mental disorders, analogue paradigms provide an indispensable contribution. In posttraumatic stress disorder (PTSD), the stressful film paradigm is a frequently used analogue approach: Films depicting traumatic events are shown to non-clinical participants in order to elicit stress responses analogue to responses to traumatic events in real life. Previous studies used a large variety of films, which is problematic with regard to the comparability of results. The main goal of this study was to identify a film clip that (a) consistently provokes stress reactions and (b) provokes reactions that are as similar as possible to traumatic stress. We randomly exposed 105 male and female participants to one of four stressful films, differing, e.g., in content and origin. Intrusive memories of the film, reported immediately after the film and during a diary phase of three days, as well as distress, heart rate, and several mood states were measured. A film clip depicting rape elicited the most consistent reactions that were characterized by a higher heart rate, more distress and more intrusive memories, compared to the other three clips. Intrusive memories across all films were especially related to an increase in heart rate and disgust in response to the film. PMID:19347765

  6. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    SciTech Connect

    G.J. Saulnier Jr; W. Statham

    2006-03-10

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 {+-} 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory

  7. Opioid profiles of Cys2-containing enkephalin analogues.

    PubMed

    Pencheva, Nevena; Milanov, Peter; Vezenkov, Lubomir; Pajpanova, Tamara; Naydenova, Emilia

    2004-09-13

    To elucidate the structural features determining delta-opioid receptor properties of enkephalin analogues containing Cys(O2NH2) in position 2, a series of Cys2-containing derivatives were synthesized and tested for their effectiveness in depressing electrically evoked contractions of the mouse vas deferens (predominantly enkephalin-selective delta-opioid receptors) and the guinea-pig ileum (mu- and kappa-opioid receptors). The peptidase resistance of the compounds was also tested. The ratio IC50 in the guinea-pig ileum/IC50 in the mouse vas deferens, indicating selectivity for delta-opioid receptors, was high for Cys(O2NH2)2-containing analogues and especially for [Cys(O2NH2)2, Leu5]enkephalin, which was about seven times more selective than delta-opioid receptor selective ligand cyclic [D-Pen2, D-Pen5]enkephalin (DPDPE). The dissociation constant (KA) and relative efficacy (e(rel)) of the compounds in the mouse-isolated vas deferens were determined using explicit formulae derived by fitting of the data points with two-parametric hyperbolic function. The obtained values for KA and e(rel) suggest that: (i) incorporation of Cys(O2NH2)2 in the molecule of [Leu5]enkephalin highly increases the efficacy and does not change significantly the affinity of the respective analogues to delta-opioid receptors; [Cys(O2NH2)2, Leu5]enkephalin has higher affinity than DPDPE, but is less resistant to enzyme degradation; the effect of this modification on the efficacy is decreased when methionine is in position 5; (ii) D-configuration of Cys(O2NH2)2-containing analogues increases their peptidase resistance, but reduces efficacy and affinity of the peptides towards delta-opioid receptors; (iii) the substitution of Cys(O2NH2) with Hcy(O2NH2) reduces the efficacy, affinity and potency of the respective analogues and maintains their sensitivity to endogenous peptidases; (iv) the substitution of the sulfonamide group with benzyl group in the molecule of Cys in position 2 decreases their

  8. Probing spin density and local structure in the Prussian blue analogues CsCd[Fe/Co(CN)6]·0.5H2O and Cd3[Fe/Co(CN)6]2·15H2O with solid-state MAS NMR spectroscopy.

    PubMed

    Flambard, Alexandrine; Köhler, Frank H; Lescouëzec, Rodrigue; Revel, Bertrand

    2011-10-01

    Magic-angle spinning (MAS) NMR spectroscopy is used to study the local structure and spin delocalisation in Prussian blue analogues (PBAs). We selected two common archetypes of PBAs (A(I)M(II)[M(III)(CN)(6)]·xH(2)O and M(II)(3)[M(III)(CN)(6)](2)·xH(2)O, in which A(I) is an alkali ion, and M(II) and M(III) are transition-metal ions) that exhibit similar cubic frameworks but different microscopic structures. Whereas the first type of PBA contains interstitial alkali ions and does not exhibit any [M(III)(CN)(6)](3-) vacancies, the second type of PBA exhibits [M(III)(CN)(6)](3-) vacancies, but does not contain inserted alkali ions. In this study, we selected Cd(II) as a divalent metal in order to use the (113)Cd nuclei (I=1/2) as a probe of the local structure. Here, we present a complete MAS NMR study on two series of PBAs of the formulas Cd(II)(3)[Fe(III)(x)Co(III)(1-x)(CN)(6)](2)·15H(2)O with x=0 (1), 0.25 (2), 0.5 (3), 0.75 (4) and 1 (5), and CsCd(II)[Fe(III)(x)Co(III)(1-x)(CN)(6)]·0.5H(2)O with x=0 (6), 0.25 (7), 0.5 (8), 0.75 (9) and 1 (10). Interestingly, the presence of Fe(III) magnetic centres in the vicinity of the cadmium sites has a magnifying-glass effect on the NMR spectrum: it induces a striking signal spread such that the resolution is notably improved compared to that achieved for the diamagnetic PBAs. By doping the sample with varying amounts of diamagnetic Co(III) and comparing the NMR spectra of both types of PBAs, we have been able to give a view of the structure which is complementary to that usually obtained from X-ray diffraction studies. In particular, this study has shown that the vacancies are not randomly distributed in the mesoporous PBAs. Moreover the cadmium chemical shift, which is a measure of the hyperfine coupling, allows the estimation of the spin density on the cadmium nucleus, and consequently, the elucidation of the spin delocalisation mechanism in these compounds along with its dependency on structural parameters. PMID

  9. [Theoretical study on fluorescence spectra of four kinds of p-substituted curcumin analogues].

    PubMed

    Jia, Fei-Yun; Su, Yu; Ran, Ming; Zhu, Jiang; Zhang, Bo

    2014-04-01

    Four kinds of p-substituted curcumin analogues were optimized at B3LYP/6-31G (d, p) level. On this basis, the excited states geometry structure was optimized by the CIS method, and finally the fluorescence emission spectra were calculated through the TD-DFT method. The results showed that: the four compounds, a large conjugated system, is preferably coplanar structure. Because of introducing hydroxyl and halogen atom on the benzene ring, the molecular pi-electron conjugation is relatively larger, emission wavelength is relatively longer, and fluorescence spectra show different degrees of red shift. As the electron donating group is hydroxy, the fluorescence phenomenon is more obviously red shifted. PMID:25007617

  10. Preparation and Magnetic Studies of Mn Substituted Analogues of BiFeO3

    NASA Astrophysics Data System (ADS)

    Choudhary, B. L.; Kumar, Sudhish; Krishnamurthy, Anjali; Srivastava, Bipin K.

    2011-11-01

    Manganese substituted samples (for iron) in the multiferroic BiFeO3 have been prepared using solid state ceramic route. It has been possible to prepare a sample with the highest 40% Mn content. Reitveld analysis of the X-ray diffraction patterns shows that the substituted analogues crystallize in rhombohedral symmetry in R-3¯c space group. Effort to prepare 50 atomic% Mn substituted sample did not succeed. Magnetization measurements have been made in the temperature range 20K-300K and in fields upto 8 kOe. Magnetic nature of the 40 atomic% Mn substituted sample is alike that of 30 atomic% Mn substituted one. Mn induces weak ferromagnetism with the average magnetic moment increasing with its concentration.

  11. Using Geothermal Play Types as an Analogue for Estimating Potential Resource Size

    SciTech Connect

    Terry, Rachel; Young, Katherine

    2015-09-02

    Blind geothermal systems are becoming increasingly common as more geothermal fields are developed. Geothermal development is known to have high risk in the early stages of a project development because reservoir characteristics are relatively unknown until wells are drilled. Play types (or occurrence models) categorize potential geothermal fields into groups based on geologic characteristics. To aid in lowering exploration risk, these groups' reservoir characteristics can be used as analogues in new site exploration. The play type schemes used in this paper were Moeck and Beardsmore play types (Moeck et al. 2014) and Brophy occurrence models (Brophy et al. 2011). Operating geothermal fields throughout the world were classified based on their associated play type, and then reservoir characteristics data were catalogued. The distributions of these characteristics were plotted in histograms to develop probability density functions for each individual characteristic. The probability density functions can be used as input analogues in Monte Carlo estimations of resource potential for similar play types in early exploration phases. A spreadsheet model was created to estimate resource potential in undeveloped fields. The user can choose to input their own values for each reservoir characteristic or choose to use the probability distribution functions provided from the selected play type. This paper also addresses the United States Geological Survey's 1978 and 2008 assessment of geothermal resources by comparing their estimated values to reported values from post-site development. Information from the collected data was used in the comparison for thirty developed sites in the United States. No significant trends or suggestions for methodologies could be made by the comparison.

  12. Testing technologies and strategies for exploration in Australian Mars analogues: A review

    NASA Astrophysics Data System (ADS)

    West, Michael D.; D. A. Clarke, Jonathan; Laing, Jennifer H.; Willson, David; Waldie, James M. A.; Murphy, Guy M.; Thomas, Matilda; Mann, Graham A.

    2010-03-01

    Australia is an ideal testing ground in preparation for the robotic and human exploration of Mars. Numerous sites with landforms or processes analogous to those on Mars are present and the deserts of central Australia provide a range of locations for free-ranging Mars analogue mission simulations. The latest developments in testing technologies and strategies for exploration in Australian Mars analogues are reviewed. These include trials of analogue space suits based on mechanical counter pressure technology and the development of an analogue, crewed, pressurized rover for long-range exploration. Field science activities and instrumentation testing relevant to robotic and future crewed missions are discussed. Australian-led human factors research undertaken during expeditions to Mars analogue research stations and expeditions to Antarctica are also reviewed. Education and public outreach activities related to Mars analogue research in Australia are also detailed.

  13. Quantitative comparisons of analogue models of brittle wedge dynamics

    NASA Astrophysics Data System (ADS)

    Schreurs, Guido

    2010-05-01

    Analogue model experiments are widely used to gain insights into the evolution of geological structures. In this study, we present a direct comparison of experimental results of 14 analogue modelling laboratories using prescribed set-ups. A quantitative analysis of the results will document the variability among models and will allow an appraisal of reproducibility and limits of interpretation. This has direct implications for comparisons between structures in analogue models and natural field examples. All laboratories used the same frictional analogue materials (quartz and corundum sand) and prescribed model-building techniques (sieving and levelling). Although each laboratory used its own experimental apparatus, the same type of self-adhesive foil was used to cover the base and all the walls of the experimental apparatus in order to guarantee identical boundary conditions (i.e. identical shear stresses at the base and walls). Three experimental set-ups using only brittle frictional materials were examined. In each of the three set-ups the model was shortened by a vertical wall, which moved with respect to the fixed base and the three remaining sidewalls. The minimum width of the model (dimension parallel to mobile wall) was also prescribed. In the first experimental set-up, a quartz sand wedge with a surface slope of ˜20° was pushed by a mobile wall. All models conformed to the critical taper theory, maintained a stable surface slope and did not show internal deformation. In the next two experimental set-ups, a horizontal sand pack consisting of alternating quartz sand and corundum sand layers was shortened from one side by the mobile wall. In one of the set-ups a thin rigid sheet covered part of the model base and was attached to the mobile wall (i.e. a basal velocity discontinuity distant from the mobile wall). In the other set-up a basal rigid sheet was absent and the basal velocity discontinuity was located at the mobile wall. In both types of experiments

  14. Dynamics of water in prussian blue analogues: Neutron scattering study

    NASA Astrophysics Data System (ADS)

    Sharma, V. K.; Mitra, S.; Thakur, N.; Yusuf, S. M.; Juranyi, Fanni; Mukhopadhyay, R.

    2014-07-01

    Dynamics of crystal water in Prussian blue (PB), Fe(III)4[Fe(II)(CN)6]3.14H2O and its analogue Prussian green (PG), ferriferricynaide, Fe(III)4[Fe(III)(CN)6]4.16H2O have been investigated using Quasielastic Neutron Scattering (QENS) technique. PB and its analogue compounds are important materials for their various interesting multifunctional properties. It is known that crystal water plays a crucial role towards the multifunctional properties of Prussian blue analogue compounds. Three structurally distinguishable water molecules: (i) coordinated water molecules at empty nitrogen sites, (ii) non-coordinated water molecules in the spherical cavities, and (iii) at interstitial sites exist in PB. Here spherical cavities are created due to the vacant sites of Fe(CN)6 units. However, PG does not have any such vacant N or Fe(CN)6 units, and only one kind of water molecules, exists only at interstitial sites. QENS experiments have been carried out on both the compounds in the temperature range of 260-360 K to elucidate the dynamical behavior of different kinds of water molecules. Dynamics is found to be much more pronounced in case of PB, compared to PG. A detailed data analysis showed that localized translational diffusion model could describe the observed data for both PB and PG systems. The average diffusion coefficient is found to be much larger in the PB than PG. The obtained domain of dynamics is found to be consistent with the geometry of the structure of the two systems. Combining the data of the two systems, a quantitative estimate of the dynamics, corresponding to the water molecules at different locations is made.

  15. Dynamics of water in prussian blue analogues: Neutron scattering study

    SciTech Connect

    Sharma, V. K.; Mitra, S.; Thakur, N.; Yusuf, S. M.; Mukhopadhyay, R.; Juranyi, Fanni

    2014-07-21

    Dynamics of crystal water in Prussian blue (PB), Fe(III){sub 4}[Fe(II)(CN){sub 6}]{sub 3}.14H{sub 2}O and its analogue Prussian green (PG), ferriferricynaide, Fe(III){sub 4}[Fe(III)(CN){sub 6}]{sub 4}.16H{sub 2}O have been investigated using Quasielastic Neutron Scattering (QENS) technique. PB and its analogue compounds are important materials for their various interesting multifunctional properties. It is known that crystal water plays a crucial role towards the multifunctional properties of Prussian blue analogue compounds. Three structurally distinguishable water molecules: (i) coordinated water molecules at empty nitrogen sites, (ii) non-coordinated water molecules in the spherical cavities, and (iii) at interstitial sites exist in PB. Here spherical cavities are created due to the vacant sites of Fe(CN){sub 6} units. However, PG does not have any such vacant N or Fe(CN){sub 6} units, and only one kind of water molecules, exists only at interstitial sites. QENS experiments have been carried out on both the compounds in the temperature range of 260–360 K to elucidate the dynamical behavior of different kinds of water molecules. Dynamics is found to be much more pronounced in case of PB, compared to PG. A detailed data analysis showed that localized translational diffusion model could describe the observed data for both PB and PG systems. The average diffusion coefficient is found to be much larger in the PB than PG. The obtained domain of dynamics is found to be consistent with the geometry of the structure of the two systems. Combining the data of the two systems, a quantitative estimate of the dynamics, corresponding to the water molecules at different locations is made.

  16. Radio-protective effect of some new curcumin analogues.

    PubMed

    El-Gazzar, Marwa G; Zaher, Nashwa H; El-Hossary, Ebaa M; Ismail, Amel F M

    2016-09-01

    In the present study, novel symmetrical curcumin analogues (2-7) have been synthesized by substituting the phenolic OH of curcumin with different linkers providing additional keto-enol tautomerism, very essential for radioprotective activity. The structures of the synthesized compounds (2-7) were elucidated by elemental analysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data and were found consistent with the assigned structures. The curative effect of these new compounds, against the oxidative stress due to exposure of rats to the whole body γ-irradiation (7Gy) was investigated. Gamma-irradiated rats exhibited elevations of ALT, AST activities, urea, creatinine, triglycerides, total cholesterol, malondialdehyde (MDA), nitric oxide (NO), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Nuclear Factor-kappa B (NF-κB) levels. Contrariwise, the total protein, albumin, total calcium level, SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Treatment of gamma-irradiated rats with the new curcumin analogues (2-7) showed significant amelioration in the in-vivo antioxidant status, liver and kidney functions, as well as the anti-inflammatory markers (IL-6, TNF-α and NF-κB). Inhibition of NF-κB could be responsible for the improvement of the antioxidant and anti-inflammatory status in gamma-irradiated animals, by down-regulation of IL-1β and TNF-α level. In conclusion, the new curcumin analogues (2-7) exhibited post-protective effect on gamma-irradiation, by NF-κB inhibition. PMID:27505300

  17. Migrastatin Analogues Inhibit Canine Mammary Cancer Cell Migration and Invasion

    PubMed Central

    Majchrzak, Kinga; Lo Re, Daniele; Gajewska, Małgorzata; Bulkowska, Małgorzata; Homa, Agata; Pawłowski, Karol; Motyl, Tomasz; Murphy, Paul V.; Król, Magdalena

    2013-01-01

    Background Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6) on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. Results Our results showed that two of six fully synthetic analogues of migrastatin: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6) disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. Conclusion Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6) were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs. However, further in

  18. Reactions of trimethylphosphine analogues of auranofin with bovine serum albumin

    SciTech Connect

    Isab, A.A.; Shaw, C.F. III; Hoeschele, J.D.; Locke, J.

    1988-10-05

    The reactions of bovine serum albumin (BSA) with (trimethylphosphine)(2,3,4,6-tetra-O-acetyl-1-thio-..beta..-D-glucopyranosato-S)gold(I), Me/sub 3/PAuSAtg, and its chloro analogue, Me/sub 3/PAuCl, were studied to develop insights into the role of the phosphine ligand in the serum chemistry of the related antiarthritic drug auranofin (triethylphosphine)(2,3,4,6-tetra-O-acetyl-1-thio-..beta..-D-glucopyranosato-S)gold(I). /sup 31/P NMR spectroscopy, protein modification, and gel-exclusion chromatography methods were employed. Comparison of the reactions of the methyl derivatives to the previously reported reactions of auranofin and Et/sub 3/PAuCl with BSA demonstrated that similar chemical species are formed but revealed three major differences. Despite these differences, the results for the methyl analogues provide important confirmation for previously developed chemical models of auranofin reactions in serum. Me/sub 3/PO was not observed in reaction mixtures lacking tetraacetylthioglucose (AtgSH); this result affirms the role of AtgSH, displaced by the reaction of Me/sub 3/PAuSAtg at Cys-34, in the generation of the phosphine oxide (an important metabolite in vivo). The weak binding sites on albumin react with Me/sub 3/PAuCl, but not Me/sub 3/PAuSAtg, demonstrating the importance of the strength and reactivity of the anionic ligand-gold bond on the reactions of auranofin analogues. The gold binding capacity of albumin is enhanced after Me/sub 3/PO is formed, consistent with reductive cleavage of albumin disulfide bonds by trimethylphosphine. 24 references, 2 figures, 3 tables.

  19. Thiophene-3-carboxamide analogue of annonaceous acetogenins as antitumor drug lead.

    PubMed

    Kojima, Naoto; Fushimi, Tetsuya; Tatsukawa, Takahiro; Tanaka, Tetsuaki; Okamura, Mutsumi; Akatsuka, Akinobu; Yamori, Takao; Dan, Shingo; Iwasaki, Hiroki; Yamashita, Masayuki

    2014-10-30

    Five novel acetogenin analogues with a furan, thiophene, or thiazole ring were synthesized, and their inhibitory activities toward human cancer cell lines were evaluated. The analogues showed more potent activities than natural acetogenin. One of them, the thiophene-3-carboxamide analogue, strongly inhibited the growth of human lung cancer cell line NCI-H23 in the xenograft mouse assay without critical toxicity. PMID:25226228

  20. Synthesis and proteinase inhibitory properties of diphenyl phosphonate analogues of aspartic and glutamic acids.

    PubMed

    Hamilton, R; Walker, B; Walker, B J

    1998-07-01

    The synthesis of diphenyl phosphonate analogues of aspartic and glutamic acid, and their inhibitory activity against S. aureus V8 protease and granzyme B, is described. The study has revealed difficulties with protecting group compatibility in the synthesis of these analogues. Two analogues, Acetyl. AspP (OPh)2 and Acetyl.GluP (OPh)2 were found to function as irreversible inactivators of V8 proteinase, yet exhibit no activity against granzyme B. PMID:9873408