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Sample records for reversibly bound analogues

  1. Butterfly velocity bound and reverse isoperimetric inequality

    NASA Astrophysics Data System (ADS)

    Feng, Xing-Hui; Lü, H.

    2017-03-01

    We study the butterfly effect of the AdS planar black holes in the framework of Einstein's general relativity. We find that the butterfly velocities can be expressed by a universal formula vB2=T S /(2 VthP ). In doing so, we come upon a near-horizon geometrical formula for the thermodynamical volume Vth . We verify the volume formula by examining a variety of AdS black holes. We also show that the volume formula implies that the conjectured reverse isoperimetric inequality follows straightforwardly from the null-energy condition, for static AdS black holes. The inequality is thus related to an upper bound of the butterfly velocities.

  2. Structural basis for activation of alpha-boranophosphate nucleotide analogues targeting drug-resistant reverse transcriptase.

    PubMed

    Meyer, P; Schneider, B; Sarfati, S; Deville-Bonne, D; Guerreiro, C; Boretto, J; Janin, J; Véron, M; Canard, B

    2000-07-17

    AIDS chemotherapy is limited by inadequate intracellular concentrations of the active triphosphate form of nucleoside analogues, leading to incomplete inhibition of viral replication and the appearance of drug-resistant virus. Drug activation by nucleoside diphosphate kinase and inhibition of HIV-1 reverse transcriptase were studied comparatively. We synthesized analogues with a borano (BH(3)(-)) group on the alpha-phosphate, and found that they are substrates for both enzymes. X-ray structures of complexes with nucleotide diphosphate kinase provided a structural basis for their activation. The complex with d4T triphosphate displayed an intramolecular CH.O bond contributing to catalysis, and the R(p) diastereoisomer of thymidine alpha-boranotriphosphate bound like a normal substrate. Using alpha-(R(p))-boranophosphate derivatives of the clinically relevant compounds AZT and d4T, the presence of the alpha-borano group improved both phosphorylation by nucleotide diphosphate kinase and inhibition of reverse transcription. Moreover, repair of blocked DNA chains by pyrophosphorolysis was reduced significantly in variant reverse transcriptases bearing substitutions found in drug-resistant viruses. Thus, the alpha-borano modification of analogues targeting reverse transcriptase may be of generic value in fighting viral drug resistance.

  3. Structural basis for activation of α-boranophosphate nucleotide analogues targeting drug-resistant reverse transcriptase

    PubMed Central

    Meyer, Philippe; Schneider, Benoît; Sarfati, Simon; Deville-Bonne, Dominique; Guerreiro, Catherine; Boretto, Joëlle; Janin, Joël; Véron, Michel; Canard, Bruno

    2000-01-01

    AIDS chemotherapy is limited by inadequate intracellular concentrations of the active triphosphate form of nucleoside analogues, leading to incomplete inhibition of viral replication and the appearance of drug-resistant virus. Drug activation by nucleoside diphosphate kinase and inhibition of HIV-1 reverse transcriptase were studied comparatively. We synthesized analogues with a borano (BH3–) group on the α-phosphate, and found that they are substrates for both enzymes. X-ray structures of complexes with nucleotide diphosphate kinase provided a structural basis for their activation. The complex with d4T triphosphate displayed an intramolecular CH…O bond contributing to catalysis, and the Rp diastereoisomer of thymidine α-boranotriphosphate bound like a normal substrate. Using α-(Rp)-boranophosphate derivatives of the clinically relevant compounds AZT and d4T, the presence of the α-borano group improved both phosphorylation by nucleotide diphosphate kinase and inhibition of reverse transcription. Moreover, repair of blocked DNA chains by pyrophosphorolysis was reduced significantly in variant reverse transcriptases bearing substitutions found in drug-resistant viruses. Thus, the α-borano modification of analogues targeting reverse transcriptase may be of generic value in fighting viral drug resistance. PMID:10899107

  4. 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.

  5. L-Enantiomers of Transition State Analogue Inhibitors Bound to Human Purine Nucleoside Phosphorylase

    SciTech Connect

    Rinaldo-Matthis,A.; Murkin, A.; Ramagopal, U.; Clinch, K.; Mee, S.; Evans, G.; Tyler, P.; Furneaux, R.; Almo, S.; Schramm, v.

    2008-01-01

    Human purine nucleoside phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP.

  6. The Analogue of the Aharonov-Bohm Effect for Bound States for Neutral Particles

    NASA Astrophysics Data System (ADS)

    Bakke, Knut; Furtado, C.

    We study the analogue of the Aharonov-Bohm effect for bound states for a neutral particle with a permanent magnetic dipole moment interacting with an external field. We consider a neutral particle confined to moving between two coaxial cylinders and show the dependence of the energy levels on the Aharonov-Casher quantum flux. Moreover, we show that the same flux dependence of the bound states can be found when the neutral particle is confined to a one-dimensional quantum ring and a quantum dot, and we also calculate the persistent currents in each case.

  7. Structures of mithramycin analogues bound to DNA and implications for targeting transcription factor FLI1

    PubMed Central

    Hou, Caixia; Weidenbach, Stevi; Cano, Kristin E.; Wang, Zhonghua; Mitra, Prithiba; Ivanov, Dmitri N.; Rohr, Jürgen; Tsodikov, Oleg V.

    2016-01-01

    Transcription factors have been considered undruggable, but this paradigm has been recently challenged. DNA binding natural product mithramycin (MTM) is a potent antagonist of oncogenic transcription factor EWS–FLI1. Structural details of MTM recognition of DNA, including the FLI1 binding sequence GGA(A/T), are needed to understand how MTM interferes with EWS–FLI1. We report a crystal structure of an MTM analogue MTM SA–Trp bound to a DNA oligomer containing a site GGCC, and two structures of a novel analogue MTM SA–Phe in complex with DNA. MTM SA–Phe is bound to sites AGGG and GGGT on one DNA, and to AGGG and GGGA(T) (a FLI1 binding site) on the other, revealing how MTM recognizes different DNA sequences. Unexpectedly, at sub-micromolar concentrations MTMs stabilize FLI1–DNA complex on GGAA repeats, which are critical for the oncogenic function of EWS–FLI1. We also directly demonstrate by nuclear magnetic resonance formation of a ternary FLI1–DNA–MTM complex on a single GGAA FLI1/MTM binding site. These biochemical and structural data and a new FLI1–DNA structure suggest that MTM binds the minor groove and perturbs FLI1 bound nearby in the major groove. This ternary complex model may lead to development of novel MTM analogues that selectively target EWS–FLI1 or other oncogenic transcription factors, as anti-cancer therapeutics. PMID:27587584

  8. Reverse signaling through membrane-bound interleukin-15.

    PubMed

    Budagian, Vadim; Bulanova, Elena; Orinska, Zane; Pohl, Thomas; Borden, Ernest C; Silverman, Robert; Bulfone-Paus, Silvia

    2004-10-01

    The results from this study implicate membrane-anchored interleukin (IL)-15 constitutively expressed on the cell surface of PC-3 human prostate carcinoma cells and interferon-gamma-activated human monocytes in reverse signaling upon stimulation with soluble IL-15 receptor-alpha or anti-IL-15 antibodies, mediating the outside-to-inside signal transduction that involves the activation of members of the MAPK family (ERK and p38) and focal adhesion kinase. The presence of membrane-bound IL-15 was not dependent on the expression of the trimeric IL-15 receptor complex by these cells and resisted treatment with acidic buffer or trypsin. Reverse signaling through membrane-bound IL-15 considerably increased the production of several pro-inflammatory cytokines by monocytes, such as IL-6, IL-8, and tumor necrosis factor-alpha, thereby indicating the relevance of this process to the complex immunomodulatory function of these cells. Furthermore, stimulation of transmembrane IL-15 also enhanced the transcription of IL-6 and IL-8 in the PC-3 cell line and promoted migration of PC-3 cells as well as LNCaP human prostate carcinoma cells stably expressing IL-15 on the cell surface. Thus, IL-15 can exist as a biologically active transmembrane molecule that possesses dual ligand-receptor qualities with a potential to induce bidirectional signaling. This fact highlights a new level of complexity in the biology of IL-15 and offers novel important insights into our understanding of the cellular responses modulated by this pleiotropic cytokine.

  9. Specificity of neomycin analogues bound to the packaging region of human immunodeficiency virus type 1 RNA.

    PubMed

    McPike, Mark P; Goodisman, Jerry; Dabrowiak, James C

    2004-04-15

    -neo must be directed away from the binding pocket when these analogues are bivalently bound to RNA. This study showed how variations in the structure of aminoglycosides lead to different binding specificity to part of the packaging region of HIV-1. Such knowledge will be important in design of drugs to target this region.

  10. Transferred nuclear Overhauser effect analyses of membrane-bound enkephalin analogues by sup 1 H nuclear magnetic resonance: Correlation between activities and membrane-bound conformations

    SciTech Connect

    Milon, Alain; Miyazawa, Tatsuo; Higashijima, Tsutomu )

    1990-01-09

    Leu-enkephalin, (D-Ala{sup 2})Leu-enkephalin, and (D-Ala{sup 2})Leu-enkephalinamide (agonists) and (L-Ala{sup 2})Leu-enkephalin (inactive analogue) bind to lipid bilayer consisting of phosphatidylcholine and phosphatidylserine. The conformations that these compounds assume, once bound to perdeuterated phospholipid bilayer, have been shown to be unique, as shown by the transferred nuclear Overhauser effect (TRNOE) of {sup 1}H NMR spectroscopy. In addition, their location in the bilayer was analyzed by TRNOE in the presence of spin-labeled phospholipids. These analyses showed a clear relationship between the activity and the peptide-membrane interaction. The three active peptides, when bound to membranes, adopt the same conformation, characterized by a type II{prime} {beta}-turn around Gly{sup 3}-Phe and a {gamma}-turn around Gly{sup 2} (or D-Ala{sup 2}). The inactive analogue, (L-Ala{sup 2})Leu-enkephalin, displayed a completely different TRNOE pattern corresponding to a different conformation in the membrane-bound state. The tyrosine residue of the active compounds is not inserted into the interior of membrane, but it is inserted into the bilayer for the L-Ala{sup 2} analogue. According to these results, (L-Ala{sup 2})Leu-enkephalin may be explained to be inactive because the mode of binding to the membranes is different from that of active compounds.

  11. OSI-930 analogues as novel reversal agents for ABCG2-mediated multidrug resistance.

    PubMed

    Kuang, Ye-Hong; Patel, Jay P; Sodani, Kamlesh; Wu, Chung-Pu; Liao, Li-Qiu; Patel, Atish; Tiwari, Amit K; Dai, Chun-Ling; Chen, Xiang; Fu, Li-Wu; Ambudkar, Suresh V; Korlipara, Vijaya L; Chen, Zhe-Sheng

    2012-09-15

    OSI-930, a dual c-Kit and KDR tyrosine kinase inhibitor, is reported to have undergone a Phase I dose escalation study in patients with advanced solid tumors. A series of fifteen pyridyl and phenyl analogues of OSI-930 were designed and synthesized. Extensive screening of these compounds led to the discovery that nitropyridyl and ortho-nitrophenyl analogues, VKJP1 and VKJP3, were effective in reversing ABC subfamily G member 2 (ABCG2) transporter-mediated multidrug resistance (MDR). VKJP1 and VKJP3 significantly sensitized ABCG2-expressing cells to established substrates of ABCG2 including mitoxantrone, SN-38, and doxorubicin in a concentration-dependent manner, but not to the non-ABCG2 substrate cisplatin. However, they were unable to reverse ABCB1- or ABCC1-mediated MDR indicating their selectivity for ABCG2. Western blotting analysis was performed to evaluate ABCG2 expression and it was found that neither VKJP1 nor VKJP3 significantly altered ABCG2 protein expression for up to 72 h. [(3)H]-mitoxantrone accumulation study demonstrated that VKJP1 and VKJP3 increased the intracellular accumulation of [(3)H]-mitoxantrone, a substrate of ABCG2. VKJP1 and VKJP3 also remarkably inhibited the transport of [(3)H]-methotrexate by ABCG2 membrane vesicles. Importantly, both VKJP1 and VKJP3 were efficacious in stimulating the activity of ATPase of ABCG2 and inhibited the photoaffinity labeling of this transporter by its substrate [(125)I]-iodoarylazidoprazosin. The results suggested that VKJP1 and VKJP3, specifically inhibit the function of ABCG2 through direct interaction with its substrate binding site(s). Thus VKJP1 and VKJP3 represent a new class of drugs for reducing MDR in ABCG2 over-expressing tumors.

  12. Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue

    DOE PAGES

    Mir, Aamir; Golden, Barbara L.

    2015-11-09

    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. Finally, on the basis of this crystalmore » structure as well as a wealth of biochemical studies, in this paper we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid.« less

  13. Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue

    SciTech Connect

    Mir, Aamir; Golden, Barbara L.

    2015-11-09

    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. Finally, on the basis of this crystal structure as well as a wealth of biochemical studies, in this paper we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid.

  14. Semi-synthetic ocotillol analogues as selective ABCB1-mediated drug resistance reversal agents

    PubMed Central

    Zhang, Guan-Nan; Wang, Yi-Jun; Kathawala, Rishil J.; Si, Rui; Patel, Bhargav A.; Xu, Jinyi; Chen, Zhe-Sheng

    2015-01-01

    Overexpression of ATP-Binding Cassette transporters leads to multidrug resistance in cancer cells and results in the failure of chemotherapy. In this in-vitro study, we investigated whether or not (20S, 24R/S)-epoxy-12β, 25-dihydroxy-dommarane-3β-amine (ORA and OSA), a pair of semi-synthetic ocotillol analogue epimers, could inhibit the ABCB1 transporter. ORA (1 μM and 3 μM) significantly reversed the resistance to paclitaxel and vincristine in ABCB1-overexpressing SW620/Ad300 and HEK/ABCB1 cells, whereas OSA had no significant effects. In addition, ORA (3 μM) significantly increased the intracellular accumulation of [3H]-paclitaxel by suppressing the efflux function of ABCB1. Meanwhile, both ORA (3 μM) and OSA (3 μM) did not significantly alter the expression level or the subcellular location of ABCB1 protein. Moreover, the ABCB1 ATPase study suggested that ORA had a stronger stimulatory effect on the ATPase activity than OSA. ORA also exhibited a higher docking score as compared with OSA inside transmembrane domain of ABCB1. Overall, we concluded that ORA reverse ABCB1-mediated MDR by competitively inhibiting the ABCB1 drug efflux function. PMID:26296969

  15. Reversal-bounded multipushdown machines. [Turing acceptors for context free languages

    NASA Technical Reports Server (NTRS)

    Baker, B. S.; Book, R. V.

    1974-01-01

    Several representations of the recursively enumerable (r.e.) sets are presented. The first states that every r.e. set is the homomorphic image of the intersection of two linear context-free languages. The second states that every r.e. set is accepted by an on-line Turing acceptor with two pushdown stores such that in every computation, each pushdown store can make at most one reversal (that is, one change from 'pushing' to 'popping'). It is shown that this automata theoretic representation cannot be strengthened by restricting the acceptors to be deterministic multitape, nondeterministic one-tape, or nondeterministic multicounter acceptors. This provides evidence that reversal bounds are not a natural measure of computational complexity for multitape Turing acceptors.

  16. Treatment-limiting toxicities associated withnucleoside analogue reverse transcriptase inhibitor therapy: A prospective, observational study**

    PubMed Central

    Palacios, Rosario; Santos, Jesús; Camino, Xavier; Arazo, Piedad; Torres Perea, Rafael; Echevarrfa, Santiago; Ribera, Esteban; Sánchez de la Rosa, Rainel; Moreno Guillen, Santiago

    2005-01-01

    Background: The Recover Study is an ongoing, prospective study designed 10 to assess toxicity associated with the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) (stavudine, zidovudine, lamivudine, didanosine, abacavir) in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) in routine clinical practice. This project is being conducted at 120 HIV units at teaching hospitals across Spain. Objective: The aim of this study was to identify the most common treatment-limiting 10 moderate to severe clinical and laboratory adverse effects (AEs), and the individual NRTIs involved in the development of these effects, in HIV-1-infected patients receiving HAART who discontinued use of an NRTI in the Recover Study. Methods: Patients eligible for participation in the Recover Study are aged10 ≥18 years; have virologically documented HIV-1 infection; have sustained viral suppression (viral load <200 cells/mL or stable, heavily experienced [ie, have received ≥3 antiretroviral regimens] patients with viral load <5000 cells/mL) for ≥6 months; are receiving HAART; are undergoing active follow-up; and have developed 2:1 NRTI-associated AE that, in the opinion of a study investigator and under the conditions of routine clinical practice, justified discontinuation of treatment with the offending drug (principal AE/offending NRTI). The present study included patients recruited for the Recover Study between September 2002 and May 2003. Results: A total of 1391 patients were enrolled (966 men, 425 women; mean 1 age, 42 years [range, 18–67 years]). Five hundred six patients (36.4%) had been diagnosed with AIDS. The mean duration of treatment with the offending NRTI was 74 months (range, 6–156 months). Seven hundred nine patients (51.0%) were receiving fourth-line (or more) therapy. Eight hundred twenty-one patients (59.0%) were receiving nonnucleoside analogues, and 552 patients (39.7%), protease inhibitors, as components of their HAART

  17. Reversal of methylcholanthrene-induced changes in mouse prostates in vitro by retinoic acid and its analogues.

    PubMed Central

    Lasnitzki, I.

    1976-01-01

    The influence of vitamin A-related compounds on hyperplasia and metaplasia induced by methylcholanthrene was studied in mouse prostate glands in organ culture. Methylcholanthrene was found to cause extensive hyperplasia and squamous metaplasia of the prostatic epithelium which persisted after withdrawal of the carcinogen. The retinoids included retinoic acid and 6 of its structural analogues synthesized in an attempt to enhance the anticarcinogenic action and reduce the toxicity of the parent compound. These where the cyclopentenyl analogus 7699, A2-retinoic acid, 13-cis-alpha-retinoic acid and 3 aromatic analogues. Administration of the compounds following the carcinogen reduced the extent and incidence of hyperplasia significantly and with the exception of one compound reversed the squamous metaplasia. Two of the aromatic analogues, one with a terminal ethylamide group (1430), and the other with a terminal ethylester group (9369), proved to be the most potent inhibitors, followed by compound 7699 and (9369), proved to be the most potent inhibitors, followed by compound 7699 and retinoic acid. A2-retinoic acid and 13-cis-alpha-retinoic acid showed the lowest activity. The inhibition of hyperplasia appeared to be mediated via a reduction of DNA synthesis. It seemed unrelated to either the biological growth-promoting activity of the compounds or their surface-active properties. It is tentatively suggested that vitamin A and its analogues may act as hormones. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:987794

  18. Reversible inhibition of central precocious puberty with a long acting GnRH analogue.

    PubMed Central

    Ward, P S; Ward, I; McNinch, A W; Savage, D C

    1985-01-01

    A 7 year old girl with precocious puberty was treated with buserelin, a long acting analogue of gonadotrophin releasing hormone. Spontaneous and stimulated gonadotrophin secretion became prepubertal but returned to pubertal values when buserelin was withdrawn, suggesting that normal sexual maturation should follow cessation of treatment. PMID:3931565

  19. Snapshot of the equilibrium dynamics of a drug bound to HIV-1 reverse transcriptase

    NASA Astrophysics Data System (ADS)

    Kuroda, Daniel G.; Bauman, Joseph D.; Challa, J. Reddy; Patel, Disha; Troxler, Thomas; Das, Kalyan; Arnold, Eddy; Hochstrasser, Robin M.

    2013-03-01

    The anti-AIDS drug rilpivirine undergoes conformational changes to bind HIV-1 reverse transcriptase (RT), which is an essential enzyme for the replication of HIV. These changes allow it to retain potency against mutations that otherwise would render the enzyme resistant. Here we report that water molecules play an essential role in this binding process. Femtosecond experiments and theory expose the molecular level dynamics of rilpivirine bound to HIV-1 RT. Two nitrile substituents, one on each arm of the drug, are used as vibrational probes of the structural dynamics within the binding pocket. Two-dimensional vibrational echo spectroscopy reveals that one nitrile group is unexpectedly hydrogen-bonded to a mobile water molecule, not identified in previous X-ray structures. Ultrafast nitrile-water dynamics are confirmed by simulations. A higher (1.51 Å) resolution X-ray structure also reveals a water-drug interaction network. Maintenance of a crucial anchoring hydrogen bond may help retain the potency of rilpivirine against pocket mutations despite the structural variations they cause.

  20. Reversible and efficient inhibition of UDP-galactopyranose mutase by electrophilic, constrained and unsaturated UDP-galactitol analogues.

    PubMed

    Ansiaux, Christophe; N'Go, Inès; Vincent, Stéphane P

    2012-11-12

    A series of UDP-galactitols were designed as analogues of high-energy intermediates of the UDP-galactopyranose mutase (UGM) catalyzed furanose/pyranose interconversion, an essential step of Mycobacterium tuberculosis cell wall biosynthesis. The final compounds structurally share the UDP and the galactitol substructures that were connected by four distinct electrophilic connections (epoxide, lactone and Michael acceptors). All molecules were synthesized from a common perbenzylated acyclic galactose precursor that was derivatized by alkenylation, alkynylation and cyclopropanation. The inhibition study against UGM could clearly show that slight changes in the relative orientation of the UDP and the galactitol moieties resulted in dramatic variations of binding properties. Compared to known inhibitors, the epoxide derivative displayed a very tight, reversible, inhibition profile. Moreover, a time-dependent inactivation study showed that none of these electrophilic structures could react with UGM, or its FAD cofactor, the catalytic nucleophile of this still intriguing reaction.

  1. Efficiency Statistics and Bounds for Systems with Broken Time-Reversal Symmetry.

    PubMed

    Jiang, Jian-Hua; Agarwalla, Bijay Kumar; Segal, Dvira

    2015-07-24

    Universal properties of the statistics of stochastic efficiency for mesoscopic time-reversal symmetry broken energy transducers are revealed in the Gaussian approximation. We also discuss how the second law of thermodynamics restricts the statistics of stochastic efficiency. The tight-coupling limit becomes unfavorable, characterized by an infinitely broad distribution of efficiency at all times, when time-reversal symmetry breaking leads to an asymmetric Onsager response matrix. The underlying physics is demonstrated through the quantum Hall effect and further elaborated in a triple-quantum-dot three-terminal thermoelectric engine.

  2. A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants

    PubMed Central

    2012-01-01

    Background The recently approved anti-AIDS drug rilpivirine (TMC278, Edurant) is a nonnucleoside inhibitor (NNRTI) that binds to reverse transcriptase (RT) and allosterically blocks the chemical step of DNA synthesis. In contrast to earlier NNRTIs, rilpivirine retains potency against well-characterized, clinically relevant RT mutants. Many structural analogues of rilpivirine are described in the patent literature, but detailed analyses of their antiviral activities have not been published. This work addresses the ability of several of these analogues to inhibit the replication of wild-type (WT) and drug-resistant HIV-1. Results We used a combination of structure activity relationships and X-ray crystallography to examine NNRTIs that are structurally related to rilpivirine to determine their ability to inhibit WT RT and several clinically relevant RT mutants. Several analogues showed broad activity with only modest losses of potency when challenged with drug-resistant viruses. Structural analyses (crystallography or modeling) of several analogues whose potencies were reduced by RT mutations provide insight into why these compounds were less effective. Conclusions Subtle variations between compounds can lead to profound differences in their activities and resistance profiles. Compounds with larger substitutions replacing the pyrimidine and benzonitrile groups of rilpivirine, which reorient pocket residues, tend to lose more activity against the mutants we tested. These results provide a deeper understanding of how rilpivirine and related compounds interact with the NNRTI binding pocket and should facilitate development of novel inhibitors. PMID:23217210

  3. Reversal of arsenic-induced hepatic apoptosis with combined administration of DMSA and its analogues in guinea pigs: role of glutathione and linked enzymes.

    PubMed

    Mishra, Deepshikha; Mehta, Ashish; Flora, Swaran J S

    2008-02-01

    Arsenicosis, due to contaminated drinking water in the Indo-Bangladesh region, is a serious health hazard in terms of morbidity and mortality. Reactive oxygen species (ROS) generated due to arsenic toxicity have been attributed as one of the initial signals that impart cellular toxicity, which is controlled by the internal antioxidant glutathione (GSH). In the present study, we investigated (i) the role of GSH and its linked enzymes, glutathione peroxidase and glutathione reductase, in reversing chronic arsenic toxicity using a thiol chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), or one of its analogues individually or in combination; (ii) if alterations in the carbon side chain of DMSA increased efficacy; and (iii) whether the combination therapy enhance arsenic removal from hepatic tissue and prevent hepatic apoptosis. Results indicated that chronic arsenic exposure led to a ROS-mediated, mitochondrial-driven, caspase-dependent apoptosis in hepatic cells with a significant increase in glutathione disulfide (GSSG) levels and decreased glutathione reductase levels. Monotherapy with DMSA and its analogues did show minimal recovery postchelation. However, the combination of DMSA with long carbon chain analogues like monoisoamyl DMSA (MiADMSA) or monocyclohexyl DMSA (MchDMSA) showed a better efficacy in terms of reducing the arsenic burden as well as reversing altered biochemical variables indicative of oxidative stress and apoptosis. We also observed that GSH and its linked enzymes, especially glutathione reductase, play a vital role in scavenging ROS, maintaining GSH pools, and providing clinical recoveries. On the basis of the above observations, we recommend that combinational therapy of DMSA and its long carbon chain analogues MiADMSA or MchDMSA would be more effective in arsenic toxicity.

  4. Structure of HIV-1 Reverse Transcriptase with the Inhibitor β-thujaplicinol Bound at the RNase H Active Site

    PubMed Central

    Himmel, Daniel M.; Maegley, Karen A.; Pauly, Tom A.; Bauman, Joseph D.; Das, Kalyan; Dharia, Chhaya; Clark, Arthur D.; Ryan, Kevin; Hickey, Michael J.; Love, Robert A.; Hughes, Stephen H.; Bergqvist, Simon; Arnold, Eddy

    2012-01-01

    Summary Novel inhibitors are needed to counteract the rapid emergence of drug-resistant HIV variants. HIV-1 reverse transcriptase (RT) has both DNA polymerase and RNase H (RNH) enzymatic activities, but approved drugs that inhibit RT target the polymerase. Inhibitors that act against new targets, like RNH, would be effective against all of the current drug-resistant variants. Here, we present 2.80 Å and 2.04 Å resolution crystal structures of an RNH inhibitor, β-thujaplicinol, bound at the RNH active site of both HIV-1 RT and an isolated RNH domain. β-thujaplicinol chelates two divalent metal ions at the RNH active site. We provide biochemical evidence that β-thujaplicinol is a slow-binding RNH inhibitor with non-competitive kinetics and suggest that it forms a tropylium ion that interacts favorably with RT and the RNA:DNA substrate. PMID:20004166

  5. Majorana bound states in two-channel time-reversal-symmetric nanowire systems.

    PubMed

    Gaidamauskas, Erikas; Paaske, Jens; Flensberg, Karsten

    2014-03-28

    We consider time-reversal-symmetric two-channel semiconducting quantum wires proximity coupled to a conventional s-wave superconductor. We analyze the requirements for a nontrivial topological phase and find that the necessary conditions are (1) the determinant of the pairing matrix in channel space must be negative, (2) inversion symmetry must be broken, and (3) the two channels must have different spin-orbit couplings. The first condition can be implemented in semiconducting nanowire systems where interactions suppress intra-channel pairing, while the inversion symmetry can be broken by tuning the chemical potentials of the channels. For the case of collinear spin-orbit directions, we find a general expression for the topological invariant by block diagonalization into two blocks with chiral symmetry only. By projection to the low-energy sector, we solve for the zero modes explicitly and study the details of the gap closing, which in the general case happens at finite momenta.

  6. Reversed-phase high-performance liquid chromatography of non-transferrin-bound iron and some hydroxypyridone and hydroxypyrone chelators.

    PubMed

    el-Jammal, A; Templeton, D M

    1994-08-05

    The pursuit of orally available Fe(III) chelating agents has resulted in several clinical trials of 1,2-dimethyl-3-hydroxypyrid-4-one (CP20). Chromatography of this and related Fe chelators on silica-based columns has proven difficult due to unwanted interactions with the stationary phase, including with contaminating Fe bound to silanol groups. By addition of Fe3+ (50 microM ferric ammonium citrate) to an acidified aqueous mobile phase, we have successfully separated a series of hydroxypyridones-including CP20-and the related pyrones maltol and ethylmaltol by HPLC on microBondapak C18. Complexation occurs with these agents even at low pH, and they elute in an order consistent with the partition coefficients of their Fe(III) complexes. By the reverse strategy of adding ethylmaltol to the mobile phase, chelatable Fe was chromatographed and the peak response at 500 nm was linear down to a detection limit below 0.5 microM. This method was applied to pooled serum and to serum spiked with Fe after filtration at 10 kDa cut-off. The direct determination of non-transferrin-bound Fe at micromolar concentrations in serum is possible with this approach.

  7. Rhenium analogues of promising renal imaging agents with a [99mTc(CO)3]+ core bound to cysteine-derived dipeptides, including lanthionine.

    PubMed

    He, Haiyang; Lipowska, Malgorzata; Xu, Xiaolong; Taylor, Andrew T; Marzilli, Luigi G

    2007-04-16

    The coordination chemistry of lanthionine (LANH2) and cystathionine (CSTH2) dipeptides, which respectively consist of two cysteines and one cysteine and one homocysteine linked by a thioether bridge, is almost unstudied. Recently for fac-[99mTc(CO)3(LAN)]- isomers, the first small 99mTc(CO)3 agents evaluated in humans were found to give excellent renal images and to have a high specificity for renal excretion. Herein we report the synthesis and characterization of Re complexes useful for interpreting the nature of tracer 99mTc radiopharmaceuticals. Treatment of [Re(CO)3(H2O)3]OTf with commercially available LANH2 (a mixture of meso (d,l) and chiral (dd,ll) isomers) gave three HPLC peaks, 1A, 1B, and 1C, but treatment with CSTH2 (l,l isomer) gave one major product, Re(CO)3(CSTH) (2). Crystalline Re(CO)3(LANH) products were best obtained with synthetic LANH2, richer in meso or chiral isomers. X-ray crystallography showed that these dipeptides coordinate as tridentate N2S-bound ligands with two dangling carboxyls. The LANH ligand is meso in 1A and 1C and chiral in 1B. While 1A (kinetically favored) is stable at ambient temperature for days, it converted into 1C (thermodynamically favored) at 100 degrees C; after 6 h, equilibrium was reached at a 1A:1C ratio of 1:2 at pH 8. The structures provide a rationale for this behavior and for the fact that 1A and 1C have simple NMR spectra. This simplicity results from fluxional interchange between an enantiomer with both chelate rings having the same delta pucker and an enantiomer with both chelate rings having the same lambda pucker. Agents with the [99mTc(CO)3]+ core and N2S ligands show promise of becoming an important class of 99mTc radiopharmaceuticals. The chemistry of Re analogues with these ligands, such as the LAN2- complexes reported here, provides a useful background for designing new small agents and also tagged large agents because two uncoordinated carboxyl groups are available for conjugation with biological

  8. Reversals.

    ERIC Educational Resources Information Center

    National Center on Educational Media and Materials for the Handicapped, Columbus, OH.

    Selected from the National Instructional Materials Information System (NIMIS)--a computer based on-line interactive retrieval system on special education materials--the bibliography covers nine materials for remediating reversals in handicapped students at the early childhood and elementary levels. Entries are presented in order of NIMIS accession…

  9. Mutation V111I in HIV-2 Reverse Transcriptase Increases the Fitness of the Nucleoside Analogue-Resistant K65R and Q151M Viruses

    PubMed Central

    Deuzing, Ilona P.; Charpentier, Charlotte; Wright, David W.; Matheron, Sophie; Paton, Jack; Frentz, Dineke; van de Vijver, David A.; Coveney, Peter V.; Descamps, Diane; Boucher, Charles A. B.

    2014-01-01

    ABSTRACT Infection with HIV-2 can ultimately lead to AIDS, although disease progression is much slower than with HIV-1. HIV-2 patients are mostly treated with a combination of nucleoside reverse transcriptase (RT) inhibitors (NRTIs) and protease inhibitors designed for HIV-1. Many studies have described the development of HIV-1 resistance to NRTIs and identified mutations in the polymerase domain of RT. Recent studies have shown that mutations in the connection and RNase H domains of HIV-1 RT may also contribute to resistance. However, only limited information exists regarding the resistance of HIV-2 to NRTIs. In this study, therefore, we analyzed the polymerase, connection, and RNase H domains of RT in HIV-2 patients failing NRTI-containing therapies. Besides the key resistance mutations K65R, Q151M, and M184V, we identified a novel mutation, V111I, in the polymerase domain. This mutation was significantly associated with mutations K65R and Q151M. Sequencing of the connection and RNase H domains of the HIV-2 patients did not reveal any of the mutations that were reported to contribute to NRTI resistance in HIV-1. We show that V111I does not strongly affect drug susceptibility but increases the replication capacity of the K65R and Q151M viruses. Biochemical assays demonstrate that V111I restores the polymerization defects of the K65R and Q151M viruses but negatively affects the fidelity of the HIV-2 RT enzyme. Molecular dynamics simulations were performed to analyze the structural changes mediated by V111I. This showed that V111I changed the flexibility of the 110-to-115 loop region, which may affect deoxynucleoside triphosphate (dNTP) binding and polymerase activity. IMPORTANCE Mutation V111I in the HIV-2 reverse transcriptase enzyme was identified in patients failing therapies containing nucleoside analogues. We show that the V111I change does not strongly affect the sensitivity of HIV-2 to nucleoside analogues but increases the fitness of viruses with drug

  10. Reversibly Bound Chloride in the Atrial Natriuretic Peptide Receptor Hormone Binding Domain: Possible Allosteric Regulation and a Conserved Structural Motif for the Chloride-binding Site

    SciTech Connect

    Ogawa, H.; Qiu, Y; Philo, J; Arakawa, T; Ogata, C; Misono, K

    2010-01-01

    The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(-)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. A new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(-) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(-) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis.

  11. Monocyte surface-bound IL-15 can function as an activating receptor and participate in reverse signaling.

    PubMed

    Neely, Graham G; Epelman, Slava; Ma, Ling Ling; Colarusso, Pina; Howlett, Christopher J; Amankwah, Ernest K; McIntyre, Amanda C; Robbins, Stephen M; Mody, Christopher H

    2004-04-01

    IL-15 is a short chain, four-alpha helix cytokine that shares some biological function with IL-2. One striking difference between IL-2 and IL-15 is the ability of monocytes to express IL-15 on their cell surface after activation. In the current study we have investigated the ability of human monocyte cell surface IL-15 to participate in reverse signaling. Cross-linking anti-IL-15 Abs were used as a surrogate ligand for surface IL-15 engagement. Ligation of cell surface-expressed IL-15 induced monocyte adhesion that required the activity of small m.w. GTPases. Reverse signals through surface IL-15 activated the Rho-GTPase Rac3. In addition, engagement of cell surface IL-15 was found to activate a number of signaling pathways, including both extracellular signal-regulated kinase 1/2 and p38, and resulted in the secretion of IL-8. IL-8 production required mitogen-activated protein kinase activity. Thus, the current study has established that cell surface IL-15 is more than just a ligand; it can function as a receptor and participate in reverse signaling that results in cellular adhesion and production of inflammatory cytokines.

  12. CORCEMA refinement of the bound ligand conformation within the protein binding pocket in reversibly forming weak complexes using STD-NMR intensities

    NASA Astrophysics Data System (ADS)

    Jayalakshmi, V.; Rama Krishna, N.

    2004-05-01

    We describe an intensity-restrained optimization procedure for refining approximate structures of ligands within the protein binding pockets using STD-NMR intensity data on reversibly forming weak complexes. In this approach, the global minimum for the bound-ligand conformation is obtained by a hybrid structure refinement method involving CORCEMA calculation of intensities and simulated annealing optimization of torsion angles of the bound ligand using STD-NMR intensities as experimental constraints and the NOE R-factor as the pseudo-energy function to be minimized. This method is illustrated using simulated STD data sets for typical carbohydrate and peptide ligands. Our procedure also allows for the optimization of side chain torsion angles of protein residues within the binding pocket. This procedure is useful in refining and improving initial models based on crystallography or computer docking or other algorithms to generate models for the bound ligand (e.g., a lead compound) within the protein binding pocket compatible with solution STD-NMR data. This method may facilitate structure-based drug design efforts.

  13. Combined administration of oxalic acid, succimer and its analogue for the reversal of gallium arsenide-induced oxidative stress in rats.

    PubMed

    Flora, Swaran J S; Kannan, Gurusamy M; Pant, Bhagwat P; Jaiswal, Devendra K

    2002-06-01

    Gallium arsenide (GaAs), a group III-VA intermetallic semiconductor, possesses superior electronic and optical properties and has a wide application in the electronics industry. Exposure to GaAs in the semiconductor industry is a potential occupational hazard because cleaning and slicing GaAs ingots to yield the desired wafer could generate GaAs particles. The ability of GaAs to induce oxidative stress has not yet been reported. The present study reports the role of oxidative stress in GaAs-induced haematological and liver disorders and its possible reversal overturn by administration of meso-2,3-dimercaptosuccinic acid (DMSA) and one of its analogue, monoisoamyl DMSA (MiADMSA), either individually or in combination with oxalic acid. While DMSA and MiADMSA are potential arsenic chelators, oxalic acid is reported to be an effective gallium chelator. Male rats were exposed to 10 mg/kg GaAs orally, 5 days a week for 8 weeks. GaAs exposure was then stopped and rats were given a 0.5 mmol/kg dose of succimers (DMSA or MiADMSA), oxalic acid or a combination of the two, intraperitoneally once daily for 5 consecutive days. We found a significant fall in blood delta-aminolevulinic acid dehydratase (ALAD) activity and blood glutathione (GSH) level, and an increased urinary excretion of delta-aminolevulinic acid (ALA) and an increased malondialdehyde (MDA) level in erythrocytes of rats exposed to GaAs. Hepatic GSH levels decreased, whereas there was an increase in GSSG and MDA levels. The results suggest a role of oxidative stress in GaAs-induced haematological and hepatic damage. Administration of DMSA and MiADMSA produced effective recovery in most of the above variables. However, a greater effectiveness of the chelation treatment (i.e. removal of both gallium and arsenic from body organs) could be achieved by combined administration of succimer (DMSA) with oxalic acid since, after MiADMSA administration, a marked loss of essential metals (copper and zinc) is of concern.

  14. Pentamethylcyclopentadienyl-rhodium and iridium complexes containing (N^N and N^O) bound chloroquine analogue ligands: synthesis, characterization and antimalarial properties.

    PubMed

    Ekengard, Erik; Kumar, Kamlesh; Fogeron, Thibault; de Kock, Carmen; Smith, Peter J; Haukka, Matti; Monari, Magda; Nordlander, Ebbe

    2016-03-07

    The synthesis and characterization of twenty new pentamethylcyclopentadienyl-rhodium and iridium complexes containing N^N and N^O-chelating chloroquine analogue ligands are described. The in vitro antimalarial activity of the new ligands as well as the complexes was evaluated against the chloroquine sensitive (CQS) NF54 and the chloroquine resistant (CQR) Dd2 strains of Plasmodium falciparum. The antimalarial activity was found to be good to moderate; although all complexes are less active than artesunate, some of the ligands and complexes showed better activity than chloroquine (CQ). In particular, rhodium complexes were found to be considerably more active than iridium complexes against the CQS NF54 strain. Salicylaldimine Schiff base ligands having electron-withdrawing groups (F, Cl, Br, I and NO2) in para position of the salicyl moiety and their rhodium complexes showed good antiplasmodial activity against both the CQS-NF54 and the CQR-Dd2 strains. The crystal structures of (η(5)-pentamethylcyclopentadienyl){N(1)-(7-chloroquinolin-4-yl)-N(2)-(pyridin-2-ylmethyl)ethane-1,2-diamine)} chlororhodium(III) chloride and (η(5)-pentamethylcyclopentadienyl){(4-chloro-2-(((2-((7-chloroquinolin-4-yl)amino)ethyl)imino)methyl)phenolate)}chlororhodium(III) chloride are reported. The crystallization of the amino-pyridyl complex (η(5)-pentamethylcyclopentadienyl){(N(1)-(7-chloroquinolin-4-yl)-N(2)-(pyridin-2-ylmethyl)ethane-1,2-diamine)}chloroiridium(III) chloride in acetone resulted in the formation of the imino-pyridyl derivative (η(5)-pentamethylcyclopentadienyl){(N1-(7-chloroquinolin-4-yl)-N2-(pyridin-2-ylmethylene)ethane-1,2-diamine)}chloroiridium(III) chloride, the crystal structure of which is also reported.

  15. HIV-1 Reverse Transcriptase Structure with RNase H Inhibitor dihydroxy benzoyl naphthyl Hydrazone Bound at a Novel Site

    SciTech Connect

    Himmel,D.; Sarafianos, S.; Dharmasena, S.; Hossain, M.; McCoy-Simandle, K.; Ilina, T.; Clark, A.; Knight, J.; Julias, J.; et al.

    2007-01-01

    The rapid emergence of drug-resistant variants of human immunodeficiency virus, type 1 (HIV-1), has limited the efficacy of anti-acquired immune deficiency syndrome (AIDS) treatments, and new lead compounds that target novel binding sites are needed. We have determined the 3.15 {angstrom} resolution crystal structure of HIV-1 reverse transcriptase (RT) complexed with dihydroxy benzoyl naphthyl hydrazone (DHBNH), an HIV-1 RT RNase H (RNH) inhibitor (RNHI). DHBNH is effective against a variety of drug-resistant HIV-1 RT mutants. While DHBNH has little effect on most aspects of RT-catalyzed DNA synthesis, at relatively high concentrations it does inhibit the initiation of RNA-primed DNA synthesis. Although primarily an RNHI, DHBNH binds >50 {angstrom} away from the RNH active site, at a novel site near both the polymerase active site and the non-nucleoside RT inhibitor (NNRTI) binding pocket. When DHBNH binds, both Tyr181 and Tyr188 remain in the conformations seen in unliganded HIV-1 RT. DHBNH interacts with conserved residues (Asp186, Trp229) and has substantial interactions with the backbones of several less well-conserved residues. On the basis of this structure, we designed substituted DHBNH derivatives that interact with the NNRTI-binding pocket. These compounds inhibit both the polymerase and RNH activities of RT.

  16. Structure of HIV-1 reverse transcriptase bound to a novel 38-mer hairpin template-primer DNA aptamer.

    PubMed

    Miller, Matthew T; Tuske, Steve; Das, Kalyan; DeStefano, Jeffrey J; Arnold, Eddy

    2016-01-01

    The development of a modified DNA aptamer that binds HIV-1 reverse transcriptase (RT) with ultra-high affinity has enabled the X-ray structure determination of an HIV-1 RT-DNA complex to 2.3 Å resolution without the need for an antibody Fab fragment or RT-DNA cross-linking. The 38-mer hairpin-DNA aptamer has a 15 base-pair duplex, a three-deoxythymidine hairpin loop, and a five-nucleotide 5'-overhang. The aptamer binds RT in a template-primer configuration with the 3'-end positioned at the polymerase active site and has 2'-O-methyl modifications at the second and fourth duplex template nucleotides that interact with the p66 fingers and palm subdomains. This structure represents the highest resolution RT-nucleic acid structure to date. The RT-aptamer complex is catalytically active and can serve as a platform for studying fundamental RT mechanisms and for development of anti-HIV inhibitors through fragment screening and other approaches. Additionally, the structure allows for a detailed look at a unique aptamer design and provides the molecular basis for its remarkably high affinity for RT.

  17. Relation between the catalytic efficiency of the synthetic analogues of catechol oxidase with their electrochemical property in the free state and substrate-bound state.

    PubMed

    Chakraborty, Prateeti; Adhikary, Jaydeep; Ghosh, Bipinbihari; Sanyal, Ria; Chattopadhyay, Shyamal Kumar; Bauzá, Antonio; Frontera, Antonio; Zangrando, Ennio; Das, Debasis

    2014-08-18

    A library of 15 dicopper complexes as synthetic analogues of catechol oxidase has been synthesized with the aim to determine the relationship between the electrochemical behavior of the dicopper(II) species in the absence as well as in the presence of 3,5-di-tert-butylcatechol (3,5-DTBC) as model substrate and the catalytic activity, kcat, in DMSO medium. The complexes have been characterized by routine physicochemical techniques as well as by X-ray single-crystal structure analysis in some cases. Fifteen "end-off" compartmental ligands have been designed as 1 + 2 Schiff-base condensation product of 2,6-diformyl-4-R-phenol (R = Me, (t)Bu, and Cl) and five different amines, N-(2-aminoethyl)piperazine, N-(2-aminoethyl)pyrrolidine, N-(2-aminoethyl)morpholine, N-(3-aminopropyl)morpholine, and N-(2-aminoethyl)piperidine. Interestingly, in case of the combination of 2,6-diformyl-4-methylphenol and N-(2-aminoethyl)morpholine/N-(3-aminopropyl)morpholine/N-(2-aminoethyl)piperidine 1 + 1 condensation becomes the reality and the ligands are denoted as L2(1-3). On reaction of copper(II) nitrate with L2(1-3) in situ complexes 3, 12, and 13 are formed having general formula Cu2(L2(1-3))2(NO3)2. The remaining 12 ligands obtained as 1 + 2 condensation products are denoted as L1(1-12), which produce complexes having general formula Cu2(L1(1-12))(NO3)2. Catecholase activity of all 15 complexes has been investigated in DMSO medium using 3,5-DTBC as model substrate. Treatment on the basis of Michaelis-Menten model has been applied for kinetic study, and thereby turnover number, kcat, values have been evaluated. Cyclic voltametric (CV) and differential pulse voltametric (DPV) studies of the complexes in the presence as well as in the absence of 3,5-DTBC have been thoroughly investigated in DMSO medium. From those studies it is evident that oxidation of 3,5-DTBC catalyzed by dicopper(II) complexes proceed via two steps: first, semibenzoquinone followed by benzoquinone with concomitant

  18. Analogue Gravity.

    PubMed

    Barceló, Carlos; Liberati, Stefano; Visser, Matt

    2011-01-01

    Analogue gravity is a research programme which investigates analogues of general relativistic gravitational fields within other physical systems, typically but not exclusively condensed matter systems, with the aim of gaining new insights into their corresponding problems. Analogue models of (and for) gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing) and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity).

  19. Fractional diffusion on bounded domains

    DOE PAGES

    Defterli, Ozlem; D'Elia, Marta; Du, Qiang; ...

    2015-03-13

    We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.

  20. Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors.

    PubMed

    Puig-de-la-Bellacasa, Raimon; Giménez, Laura; Pettersson, Sofia; Pascual, Rosalia; Gonzalo, Encarna; Esté, José A; Clotet, Bonaventura; Borrell, José I; Teixidó, Jordi

    2012-08-01

    New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 2{1,2,3,1} and 2{1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC(50)=0.015 μg/mL; 0.046 μM, SI >1667) and (EC(50)=0.025 μg/mL; 0.086 μM, SI >1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC(50)=1.01 μg/mL; 3.27 μM, SI >25).

  1. 2D, 3D-QSAR and docking studies of 1,2,3-thiadiazole thioacetanilides analogues as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

    PubMed Central

    2012-01-01

    Background The discovery of clinically relevant inhibitors of HIV-RT for antiviral therapy has proven to be a challenging task. To identify novel and potent HIV-RT inhibitors, the quantitative structure–activity relationship (QSAR) approach became very useful and largely widespread technique forligand-based drug design. Methods We perform the two- and three-dimensional (2D and 3D) QSAR studies of a series of 1,2,3-thiadiazole thioacetanilides analogues to elucidate the structural properties required for HIV-RT inhibitory activity. Results The 2D-QSAR studies were performed using multiple linear regression method, giving r2 = 0.97 and q2 = 0.94. The 3D-QSAR studies were performed using the stepwise variable selection k-nearest neighbor molecular field analysis approach; a leave-one-out cross-validated correlation coefficient q2 = 0.89 and a non-cross-validated correlation coefficient r2 = 0.97 were obtained. Docking analysis suggests that the new series have comparable binding affinity with the standard compounds. Conclusions This approach showed that hydrophobic and electrostatic effects dominantly determine binding affinities which will further useful for development of new NNRTIs. PMID:22691718

  2. Forward and reverse (retro) iron(III) or gallium(III) desferrioxamine E and ring-expanded analogues prepared using metal-templated synthesis from endo-hydroxamic acid monomers.

    PubMed

    Lifa, Tulip; Tieu, William; Hocking, Rosalie K; Codd, Rachel

    2015-04-06

    A metal-templated synthesis (MTS) approach was used to preorganize the forward endo-hydroxamic acid monomer 4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoic acid (for-PBH) about iron(III) in a 1:3 metal/ligand ratio to furnish the iron(III) siderophore for-[Fe(DFOE)] (ferrioxamine E) following peptide coupling. Substitution of for-PBH with the reverse (retro) hydroxamic acid analogue 3-(6-amino-N-hydroxyhexanamido)propanoic acid (ret-PBH) furnished ret-[Fe(DFOE)] (ret-ferrioxamine E). As isomers, for-[Fe(DFOE)] and ret-[Fe(DFOE)] gave identical mass spectrometry signals ([M + H(+)](+), m/zcalc 654.3, m/zobs 654.3), yet for-[Fe(DFOE)] eluted in a more polar window (tR = 23.44 min) than ret-[Fe(DFOE)] (tR = 28.13 min) on a C18 reverse-phase high-performance liquid chromatography (RP-HPLC) column. for-[Ga(DFOE)] (tR = 22.99 min) and ret-[Ga(DFOE)] (tR = 28.11 min) were prepared using gallium(III) as the metal-ion template and showed the same trend for the retention time. Ring-expanded analogues of for-[Fe(DFOE)] and ret-[Fe(DFOE)] were prepared from endo-hydroxamic acid monomers with one additional methylene unit in the amine-containing region, 4-[(6-aminohexyl)(hydroxy)amino]-4-oxobutanoic acid (for-HBH) or 3-(7-amino-N-hydroxyheptanamido)propanoic acid (ret-HBH), to give the corresponding tris(homoferrioxamine E) macrocycles, for-[Fe(HHDFOE)] or ret-[Fe(HHDFOE)] ([M + H(+)](+), m/zcalc 696.3, m/zobs 696.4). The MTS reaction using a constitutional isomer of for-HBH that transposed the methylene unit to the carboxylic acid containing region, 5-[(5-aminopentyl)(hydroxy)amino]-5-oxopentanoic acid (for-PPH), gave the macrocycle for-[Fe(HPDFOE)] in a yield significantly less than that for for-[Fe(HHDFOE)], with the gallium(III) analogue for-[Ga(HPDFOE)] unable to be detected. The work demonstrates the utility and limits of MTS for the assembly of macrocyclic siderophores from endo-hydroxamic acid monomers. Indirect measures (RP-HPLC order of elution, c log P values

  3. Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy

    PubMed Central

    2012-01-01

    Background Thymidine analogue resistance mutations (TAMs) selected under treatment with nucleoside analogues generate two distinct genotypic profiles in the HIV-1 reverse transcriptase (RT): (i) TAM1: M41L, L210W and T215Y, and (ii) TAM2: D67N, K70R and K219E/Q, and sometimes T215F. Secondary mutations, including thumb subdomain polymorphisms (e.g. R284K) have been identified in association with TAMs. We have identified mutational clusters associated with virological failure during salvage therapy with tenofovir/emtricitabine-based regimens. In this context, we have studied the role of R284K as a secondary mutation associated with mutations of the TAM1 complex. Results The cross-sectional study carried out with >200 HIV-1 genotypes showed that virological failure to tenofovir/emtricitabine was strongly associated with the presence of M184V (P < 10-10) and TAMs (P < 10-3), while K65R was relatively uncommon in previously-treated patients failing antiretroviral therapy. Clusters of mutations were identified, and among them, the TAM1 complex showed the highest correlation coefficients. Covariation of TAM1 mutations and V118I, V179I, M184V and R284K was observed. Virological studies showed that the combination of R284K with TAM1 mutations confers a fitness advantage in the presence of zidovudine or tenofovir. Studies with recombinant HIV-1 RTs showed that when associated with TAM1 mutations, R284K had a minimal impact on zidovudine or tenofovir inhibition, and in their ability to excise the inhibitors from blocked DNA primers. However, the mutant RT M41L/L210W/T215Y/R284K showed an increased catalytic rate for nucleotide incorporation and a higher RNase H activity in comparison with WT and mutant M41L/L210W/T215Y RTs. These effects were consistent with its enhanced chain-terminated primer rescue on DNA/DNA template-primers, but not on RNA/DNA complexes, and can explain the higher fitness of HIV-1 having TAM1/R284K mutations. Conclusions Our study shows the association

  4. Causality and Tsirelson's bounds

    SciTech Connect

    Buhrman, H.; Massar, S.

    2005-11-15

    We study the properties of no-signaling correlations that cannot be reproduced by local measurements on entangled quantum states. We say that such correlations violate Tsirelson bounds. We show that if these correlations are obtained by some reversible unitary quantum evolution U, then U cannot be written in the product form U{sub A}xU{sub B}. This implies that U can be used for signaling and for entanglement generation. This result is completely general and in fact can be viewed as a characterization of Tsirelson bounds. We then show how this result can be used as a tool to study Tsirelson bounds and we illustrate this by rederiving the Tsirelson bound of 2{radical}(2) for the Clauser-Horn-Shimony-Holt inequality, and by deriving a new Tsirelson bound for qutrits.

  5. Bound Rationality and Organizational Learning.

    DTIC Science & Technology

    1989-09-23

    8217 . 90 0 8 0.. O 4 BOUNDED RATIONALITY AND ORGANIZATIONAL LEARNING Technical Report AlP - 107 Herbert A. Simon Department of Psychology Carnegie Mellon...ACCESSION No N/A N/A N/A N/A 1 1 TITLE (include Security Classificarnon) Bounded rationality and organizational learning 12 PERSONAL AUTHOR(S) HretA io 13a...organizations organizational psychology organizational learning bounded rationality cognitive psychology 𔄃 ABSTRACT (Continue on reverse if necessary

  6. Structural requirements for human inducible nitric oxide synthase substrates and substrate analogue inhibitors.

    PubMed

    Grant, S K; Green, B G; Stiffey-Wilusz, J; Durette, P L; Shah, S K; Kozarich, J W

    1998-03-24

    Inducible nitric oxide synthase (iNOS; EC 1.14.13.39) catalyzes the NADPH-dependent oxidation of one of the free guanidino nitrogens of L-Arg to form nitric oxide and L-citrulline. Analogues of L-Arg and the inhibitor, L-N6-(1-iminoethyl)lysine, were used to define structural elements required for the binding and catalysis of compounds. L-Arg analogues with sequentially shorter methylene spacing between the guanidino group and the amino acid portion of the molecule were not iNOS substrates but were reversible inhibitors. L-Arg analogues such as agmatine with a hydroxyl substitution at the 2-amino position were substrates. Desaminoarginine was not a substrate but a reversible inhibitor. Desaminoarginine, agmatine, and argininic acid bound to the enzyme to give type I difference spectra similar to that of L-Arg. The amidino compounds L-N6-(1-iminoethyl)lysine, L-N5-(1-iminoethyl)ornithine, and N5-(1-iminoethyl)cadaverdine, but not N6-(1-iminoethyl)-6-aminocaproic acid, were NADPH-dependent, irreversible inactivators of iNOS. For both the L-Arg and L-N6-(1-iminoethyl)lysine analogues, the 2-amino group appeared to play an important role in catalytic events leading to either substrate turnover or mechanism-based inactivation. Inactivation of iNOS by L-N6-(1-iminoethyl)lysine was NADPH- and dioxygen-dependent, but low incorporation of radiolabel with DL--4, 5-3H]-N6-(1-iminoethyl)lysine indicates that the mechanism of enzyme inactivation is not covalent modification of the protein.

  7. Quantum reverse hypercontractivity

    SciTech Connect

    Cubitt, Toby; Kastoryano, Michael; Montanaro, Ashley; Temme, Kristan

    2015-10-15

    We develop reverse versions of hypercontractive inequalities for quantum channels. By generalizing classical techniques, we prove a reverse hypercontractive inequality for tensor products of qubit depolarizing channels. We apply this to obtain a rapid mixing result for depolarizing noise applied to large subspaces and to prove bounds on a quantum generalization of non-interactive correlation distillation.

  8. Upward Bound

    ERIC Educational Resources Information Center

    Journal of Aerospace Education, 1976

    1976-01-01

    Describes an Upward Bound program at Embry-Riddle Aeronautical University designed to assist disadvantaged high school juniors and seniors in overcoming academic deficiencies in order to enter and succeed in college. The Saturday program centered on various aspects of aviation, including career opportunities. (MLH)

  9. Outward Bound.

    ERIC Educational Resources Information Center

    Outward Bound, Inc., Andover, MA.

    The Outward Bound concept was developed in Germany and Great Britain with the saving of human life as the ultimate goal. Courses are designed to help students discover their true physical and mental limits through development of skills including emergency medical aid, firefighting, search and rescue, mountaineering, and sailing. Five Outward Bound…

  10. Survey of Analogue Spacetimes

    NASA Astrophysics Data System (ADS)

    Visser, Matt

    Analogue spacetimes (and more boldly, analogue models both of and for gravity), have attracted significant and increasing attention over the last decade and a half. Perhaps the most straightforward physical example, which serves as a template for most of the others, is Bill Unruh's model for a dumb hole,(mute black hole, acoustic black hole), wherein sound is dragged along by a moving fluid—and can even be trapped behind an acoustic horizon. This and related analogue models for curved spacetimes are useful in many ways: analogue spacetimes provide general relativists with extremely concrete physical models to help focus their thinking, and conversely the techniques of curved spacetime can sometimes help improve our understanding of condensed matter and/or optical systems by providing an unexpected and countervailing viewpoint. In this chapter, I shall provide a few simple examples of analogue spacetimes as general background for the rest of the contributions.

  11. Electrostatic evaluation of isosteric analogues

    NASA Astrophysics Data System (ADS)

    Sayle, Roger; Nicholls, Anthony

    2006-04-01

    A method is presented for enumerating a large number of isosteric analogues of a ligand from a known protein-ligand complex structure and then rapidly calculating an estimate of their binding energies. This approach takes full advantage of the observed crystal structure, by reusing the atomic co-ordinates determined experimentally for one ligand, to approximate those of similar compounds that have approximately the same shape. By assuming that compounds with similar shapes adopt similar binding poses, and that entropic and protein flexibility effects are approximately constant across such an isosteric series ("the frozen ligand approximation"), it is possible to order their binding affinities relatively accurately. Additionally, the constraint that the atomic coordinates are invariant allows for a dramatic simplification in the Poisson-Boltzmann method used to calculation the electrostatic component of the binding energy. This algorithmic improvement allows for the calculation of tens of thousands of binding energies per second for drug-like molecules, enabling this technique to be used in screening large virtual libraries of isosteric analogues. Most significantly, this procedure is shown to be able to reproduce SAR effects of subtle medicinal chemistry substitutions. Finally, this paper reports the results of the proposed methodology on␣seven model systems; dihydrofolate reductase, Lck␣kinase, ribosome inactivating protein, l-arabinose binding protein, neuraminidase, HIV-1 reverse transcriptase and COX-2.

  12. Fluoride-mediated capture of a noncovalent bound state of a reversible covalent enzyme inhibitor: X-ray crystallographic analysis of an exceptionally potent α-ketoheterocycle inhibitor of fatty acid amide hydrolase.

    PubMed

    Mileni, Mauro; Garfunkle, Joie; Ezzili, Cyrine; Cravatt, Benjamin F; Stevens, Raymond C; Boger, Dale L

    2011-03-23

    Two cocrystal X-ray structures of the exceptionally potent α-ketoheterocycle inhibitor 1 (K(i) = 290 pM) bound to a humanized variant of rat fatty acid amide hydrolase (FAAH) are disclosed, representing noncovalently and covalently bound states of the same inhibitor with the enzyme. Key to securing the structure of the noncovalently bound state of the inhibitor was the inclusion of fluoride ion in the crystallization conditions that is proposed to bind the oxyanion hole precluding inhibitor covalent adduct formation with stabilization of the tetrahedral hemiketal. This permitted the opportunity to detect important noncovalent interactions stabilizing the binding of the inhibitor within the FAAH active site independent of the covalent reaction. Remarkably, noncovalently bound 1 in the presence of fluoride appears to capture the active site in the same "in action" state with the three catalytic residues Ser241-Ser217-Lys142 occupying essentially identical positions observed in the covalently bound structure of 1, suggesting that this technique of introducing fluoride may have important applications in structural studies beyond inhibiting substrate or inhibitor oxyanion hole binding. Key insights to emerge from the studies include the observations that noncovalently bound 1 binds in its ketone (not gem diol) form, that the terminal phenyl group in the acyl side chain of the inhibitor serves as the key anchoring interaction overriding the intricate polar interactions in the cytosolic port, and that the role of the central activating heterocycle is dominated by its intrinsic electron-withdrawing properties. These two structures are also briefly compared with five X-ray structures of α-ketoheterocycle-based inhibitors bound to FAAH recently disclosed.

  13. Fluoride-Mediated Capture of a Noncovalent Bound State of a Reversible Covalent Enzyme Inhibitor: X-ray Crystallographic Analysis of an Exceptionally Potent α-Ketoheterocycle Inhibitor of Fatty Acid Amide Hydrolase

    PubMed Central

    Mileni, Mauro; Garfunkle, Joie; Ezzili, Cyrine; Cravatt, Benjamin F.; Stevens, Raymond C.; Boger, Dale L.

    2011-01-01

    Two cocrystal X-ray structures of the exceptionally potent α-ketoheterocycle inhibitor 1 (Ki = 290 pM) bound to a humanized variant of rat fatty acid amide hydrolase (FAAH) are disclosed, representing noncovalently and covalently bound states of the same inhibitor with the enzyme. Key to securing the structure of the noncovalently bound state of the inhibitor was the inclusion of fluoride ion in the crystallization conditions that is proposed to bind the oxyanion hole precluding inhibitor covalent adduct formation with stabilization of the tetrahedral hemiketal. This permitted the opportunity to detect important noncovalent interactions stabilizing the binding of the inhibitor within the FAAH active site independent of the covalent reaction. Remarkably, noncovalently bound 1 in the presence of fluoride appears to capture the active site in the same “in action” state with the three catalytic residues Ser241–Ser217–Lys142 occupying essentially identical positions observed in the covalently bound structure of 1, suggesting that this technique of introducing fluoride may have important applications in structural studies beyond inhibiting substrate or inhibitor oxyanion hole binding. Key insights to emerge from the studies include the observations that noncovalently bound 1 binds in its ketone (not gem diol) form, that the terminal phenyl group in the acyl side chain of the inhibitor serves as the key anchoring interaction overriding the intricate polar interactions in the cytosolic port, and that the role of the central activating heterocycle is dominated by its intrinsic electron-withdrawing properties. These two structures are also briefly compared with five X-ray structures of α-ketoheterocycle-based inhibitors bound to FAAH recently disclosed. PMID:21355555

  14. Coulomb Bound States of Strongly Interacting Photons

    NASA Astrophysics Data System (ADS)

    Maghrebi, M. F.; Gullans, M. J.; Bienias, P.; Choi, S.; Martin, I.; Firstenberg, O.; Lukin, M. D.; Büchler, H. P.; Gorshkov, A. V.

    2015-09-01

    We show that two photons coupled to Rydberg states via electromagnetically induced transparency can interact via an effective Coulomb potential. This interaction gives rise to a continuum of two-body bound states. Within the continuum, metastable bound states are distinguished in analogy with quasibound states tunneling through a potential barrier. We find multiple branches of metastable bound states whose energy spectrum is governed by the Coulomb potential, thus obtaining a photonic analogue of the hydrogen atom. Under certain conditions, the wave function resembles that of a diatomic molecule in which the two polaritons are separated by a finite "bond length." These states propagate with a negative group velocity in the medium, allowing for a simple preparation and detection scheme, before they slowly decay to pairs of bound Rydberg atoms.

  15. Carbocyclic nucleoside analogues: classification, target enzymes, mechanisms of action and synthesis

    NASA Astrophysics Data System (ADS)

    Matyugina, E. S.; Khandazhinskaya, A. P.; Kochetkov, Sergei N.

    2012-08-01

    Key biological targets (S-adenosyl-L-homocysteine hydrolase, telomerase, human immunodeficiency virus reverse transcriptase, herpes virus DNA polymerase and hepatitis B virus DNA polymerase) and the mechanisms of action of carbocyclic nucleoside analogues are considered. Structural types of analogues are discussed. Methods of synthesis for the most promising compounds and the spectrum of their biological activities are described. The bibliography includes 126 references.

  16. Prevalence of transmitted nucleoside analogue-resistant HIV-1 strains and pre-existing mutations in pol reverse transcriptase and protease region: outcome after treatment in recently infected individuals.

    PubMed

    Balotta, C; Berlusconi, A; Pan, A; Violin, M; Riva, C; Colombo, M C; Gori, A; Papagno, L; Corvasce, S; Mazzucchelli, R; Facchi, G; Velleca, R; Saporetti, G; Galli, M; Rusconi, S; Moroni, M

    2000-03-01

    We retrospectively studied 38 Italian recently HIV-1-infected subjects who seroconverted from 1994 to 1997 to investigate: (i) the prevalence of nucleoside reverse transcriptase inhibitors (NRTI)-related mutations at primary infection; (ii) the proportion of naturally occurring mutations in reverse transcriptase (RT) and protease regions of patients naive for non-nucleoside RT inhibitors (NNRTIs) and protease inhibitors (PIs); (iii) the drug-susceptibility to NRTIs and PIs in subjects with NRTI- and/or PI-related mutations; and (iv) the outcome of seroconverters treated with various NRTIs or NRTI/PI regimens. Baseline HIV-1 plasma viraemia and absolute CD4 count at baseline could not be used to distinguish patients with NRTI- and/or PI-related pre-existing mutations from those with wild-type virus (P = 0.693 and P = 0.542, respectively). The frequency of zidovudine-related mutations was 21% in the study period. The response to treatment was not significantly different in subjects with or without genotypic zidovudine-related mutations at primary infection (P = 0.744 for HIV-1 RNA and P = 0.102 for CD4 cells). Some natural variation (2.6%) was present within regions 98-108 and 179-190 of RT involved in NNRTI resistance. The high natural polymorphism in the protease region present in our patients was similar to that reported by others. In our study some PI-associated substitutions, thought to be compensatory in protease enzymatic function, could confer intermediate to high PI-resistance. As discrepancies between genotypic and phenotypic results may exist in recent seroconverters, our data suggest that the role of transmitted NRTI- and PI-resistant variants remain to be fully elucidated in vivo.

  17. 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.

  18. Quantum analogue computing.

    PubMed

    Kendon, Vivien M; Nemoto, Kae; Munro, William J

    2010-08-13

    We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

  19. Effects of inorganic phosphate analogues on stiffness and unloaded shortening of skinned muscle fibres from rabbit.

    PubMed Central

    Chase, P B; Martyn, D A; Kushmerick, M J; Gordon, A M

    1993-01-01

    1. We examined the effects of aluminofluoride (AlFx) and orthovanadate (Vi), tightly binding analogues of orthophosphate (Pi), on the mechanical properties of glycerinated fibres from rabbit psoas muscle. Maximum Ca(2+)-activated force, stiffness, and unloaded shortening velocity (Vus) were measured under conditions of steady-state inhibition (up to 1 mM of inhibitor) and during the recovery from inhibition. 2. Stiffness was measured using either step or sinusoidal (1 kHz) changes in fibre length. Sarcomere length was monitored continuously by helium-neon laser diffraction during maximum Ca2+ activation. Stiffness was determined from the changes in sarcomere length and the corresponding changes in force. Vus was measured using the slack test method. 3. AlF chi and Vi each reversibly inhibited force, stiffness and Vus. Actively cycling cross-bridges were required for reversal of these inhibitory effects. Recovery from inhibition by AlF chi was 3- to 4-fold slower than that following removal of V1. 4. At various degrees of inhibition, AlF chi and Vi both inhibited steady-state isometric force more than either Vus or stiffness. For both AlF chi and Vi, the relatively greater inhibition of force over stiffness persisted during recovery from steady-state inhibition. We interpret these results to indicate that the cross-bridges with AlF chi or Vi bound are analogous to those which occur early in the cross-bridge cycle. PMID:8487194

  20. 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)

  1. Mammary Analogue Secretory Carcinoma.

    PubMed

    Stevens, Todd M; Parekh, Vishwas

    2016-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined.

  2. Fluorescent analogues of methotrexate: characterization and interaction with dihydrofolate reductase.

    PubMed

    Kumar, A A; Kempton, R J; Anstead, G M; Freisheim, J H

    1983-01-18

    The dansylated derivatives of lysine and ornithine analogues of methotrexate exhibit fluorescence properties characteristic of the dansyl moiety with an excitation at 328 nm and an emission maximum at 580 nm in aqueous media. As in the case of dansyl amino acids, the fluorescence emission is dependent upon the polarity of the medium. In solvents of low dielectric constant there is an enhancement of the dansyl fluorescence intensity as well as a shift to shorter wavelengths. The dansylated analogues show a reduction in the quantum yields as compared to N epsilon-dansyl-L-lysine and 5-(N,N-dimethylamino)-1-naphthalenesulfonic acid. The absorption spectra of the two dansyl analogues are similar to the spectra of the parent basic amino acid precursors but with reduced molar extinction values. The two fluorescent analogues of methotrexate were found to be potent inhibitors of purified dihydrofolate reductases from Lactobacillus casei and from chicken liver. The binding of these fluorescent analogues to either dihydrofolate reductase resulted in 10-15-nm blue shift of the ligand emission maxima and a 2-5-fold enhancement of the emission. These fluorescent properties of the bound ligands indicate a possible interaction of the dansyl moiety with a region on the enzyme molecule which is more hydrophobic relative to the surrounding solvent.

  3. 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.

  4. Bound states and the Bekenstein bound

    SciTech Connect

    Bousso, Raphael

    2003-10-16

    We explore the validity of the generalized Bekenstein bound, S<= pi M a. We define the entropy S as the logarithm of the number of states which have energy eigenvalue below M and are localized to a flat space region of width alpha. If boundary conditions that localize field modes are imposed by fiat, then the bound encounters well-known difficulties with negative Casimir energy and large species number, as well as novel problems arising only in the generalized form. In realistic systems, however, finite-size effects contribute additional energy. We study two different models for estimating such contributions. Our analysis suggests that the bound is both valid and nontrivial if interactions are properly included, so that the entropy S counts the bound states of interacting fields.

  5. 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.

  6. Reversible sideroblastic anemia associated with the tetracycline analogue COL-3.

    PubMed

    Rudek, M A; Horne, M; Figg, W D; Dahut, W; Dyer, V; Pluda, J M; Reed, E

    2001-05-01

    Eight of 35 patients with cancer receiving COL-3, a tetracycline derivative with antiangiogenic properties, developed anemia while on treatment. All of these patients were enrolled on an approved Phase I clinical trial at the National Cancer Institute. Three of these patients had bone marrow examinations that revealed ringed sideroblasts. This paper describes these cases. Am. J. Hematol. 67:51-53, 2001. Published 2001 Wiley-Liss, Inc.

  7. Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers.

    PubMed

    Liu, Yun; Lehn, Jean-Marie; Hirsch, Anna K H

    2017-02-21

    Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition, molecular

  8. Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers

    PubMed Central

    2017-01-01

    Conspectus Constitutional dynamic chemistry (CDC) features the use of reversible linkages at both molecular and supramolecular levels, including reversible covalent bonds (dynamic covalent chemistry, DCC) and noncovalent interactions (dynamic noncovalent chemistry, DNCC). Due to its inherent reversibility and stimuli-responsiveness, CDC has been widely utilized as a powerful tool for the screening of bioactive compounds, the exploitation of receptors or substrates driven by molecular recognition, and the fabrication of constitutionally dynamic materials. Implementation of CDC in biopolymer science leads to the generation of constitutionally dynamic analogues of biopolymers, biodynamers, at the molecular level (molecular biodynamers) through DCC or at the supramolecular level (supramolecular biodynamers) via DNCC. Therefore, biodynamers are prepared by reversible covalent polymerization or noncovalent polyassociation of biorelevant monomers. In particular, molecular biodynamers, biodynamers of the covalent type whose monomeric units are connected by reversible covalent bonds, are generated by reversible polymerization of bio-based monomers and can be seen as a combination of biopolymers with DCC. Owing to the reversible covalent bonds used in DCC, molecular biodynamers can undergo continuous and spontaneous constitutional modifications via incorporation/decorporation and exchange of biorelevant monomers in response to internal or external stimuli. As a result, they behave as adaptive materials with novel properties, such as self-healing, stimuli-responsiveness, and tunable mechanical and optical character. More specifically, molecular biodynamers combine the biorelevant characters (e.g., biocompatibility, biodegradability, biofunctionality) of bioactive monomers with the dynamic features of reversible covalent bonds (e.g., changeable, tunable, controllable, self-healing, and stimuli-responsive capacities), to realize synergistic properties in one system. In addition

  9. Use of surface plasmon resonance in the binding study of vitamin D, metabolites and analogues with vitamin D binding protein.

    PubMed

    Canoa, Pilar; Rivadulla, Marcos L; Popplewell, Jonathan; van Oosten, René; Gómez, Generosa; Fall, Yagamare

    2017-04-01

    Vitamin D3 and its metabolites are lipophilic molecules with low aqueous solubility and must be transported bound to plasma carrier proteins, primarily to vitamin D binding protein (DBP). The biological functions of vitamin D3 metabolites are intimately dependent on the protein, hence the importance of determining their affinity for DBP. In this study, we developed a novel procedure for measuring the kinetic and equilibrium constants of human-DBP with vitamin D3 and three metabolites: 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 25-hydroxyvitamin D3 (25OHD3) and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] by surface plasmon resonance (SPR). At the same time, five different analogues, synthetized in our laboratory, were evaluated in order to compare the affinity values with the metabolites. Real-time SPR measurements showed that 25OHD3 and 24,25(OH)2D3 had higher affinity (0.3 μM) than 1,25(OH)2D3 (5 μM), with the higher affinity of 25OHD3 and 24,25(OH)2D3 due to dissociation constants 1 order of magnitude slower. In the case of the analogues, the affinity values were lower, with 1-hydroxy-25-nitro-vitamin D3 (NO2-446), structurally closer to 1,25(OH)2D3, showing the highest value with a K D of 50 μM. (24R)-1,25-dihydroxyvitamin-24-buthyl-28-norvitamin D2 (Bu-471) and (24R)-1,25-dihydroxyvitamin-24-phenyl-28-norvitamin D2 (Ph-491), structurally similar, had affinities of 180 and 170 μM, respectively. (22R,23E)-1-hydroxy-22-ethenyl-25-methoxy-23-dehydrovitamin D3 (MeO-455) and 1-hydroxy-20(R)-[5(S)-(2,2-dimethyltetrahydropyran-5-yl)]-22,23-dinor vitamin D3 (Oxan-429) had affinities of 310 and 100 μM, respectively. The binding of the metabolites and analogues was reversible allowing the rapid capture of data for replicates. The kinetic and equilibrium data for both the metabolites and the analogues fitted to the Langmuir model describing a 1:1 interaction. Graphical Abstract Label-free, real time binding study between vitamin D binding protein immmobilized on the

  10. Physical Uncertainty Bounds (PUB)

    SciTech Connect

    Vaughan, Diane Elizabeth; Preston, Dean L.

    2015-03-19

    This paper introduces and motivates the need for a new methodology for determining upper bounds on the uncertainties in simulations of engineered systems due to limited fidelity in the composite continuum-level physics models needed to simulate the systems. We show that traditional uncertainty quantification methods provide, at best, a lower bound on this uncertainty. We propose to obtain bounds on the simulation uncertainties by first determining bounds on the physical quantities or processes relevant to system performance. By bounding these physics processes, as opposed to carrying out statistical analyses of the parameter sets of specific physics models or simply switching out the available physics models, one can obtain upper bounds on the uncertainties in simulated quantities of interest.

  11. 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

  12. Mammalian folylpoly-. gamma. -glutamate synthetase. 3. Specificity for folate analogues

    SciTech Connect

    George, S.; Cichowicz, D.J.; Shane, B.

    1987-01-27

    A variety of folate analogues were synthesized to explore the specificity of the folate binding site of hog liver folypolyglutamate synthetase and the requirements for catalysis. Modifications of the internal and terminal glutamate moieties of folate cause large drops in on rates and/or affinity for the protein. The only exceptions are glutamine, homocysteate, and ornithine analogues, indicating a less stringent specificity around the delta-carbon of glutamate. It is proposed that initial folate binding to the enzyme involves low-affinity interactions at a pterin and a glutamate site and that the first glutamate bound is the internal residue adjacent to the benzoyl group. Processive movement of the polyglutamate chain through the glutamate site and a possible conformational change in the protein when the terminal residue is bound would result in tight binding and would position the ..gamma..-carboxyl of the terminal glutamate in the correct position for catalysis. The 4-amino substitution of folate increases the on rate for monoglutamate derivatives but severely impairs catalysis with diglutamate derivatives. Pteroylornithine derivatives are the first potent and specific inhibitors of folylpolyglutamate synthetase to be identified and may act as analogues of reaction intermediates. Other folate derivatives with tetrahedral chemistry replacing the peptide bond, such as pteroyl-..gamma..-glutamyl-(psi,CH/sub 2/-NH)-glutamate, retain affinity for the protein but are considerably less effective inhibitors than the ornithine derivatives. Enzyme activity was assayed using (/sup 14/C)glutamate.

  13. Interaction of tRNA with antitumor polyamine analogues.

    PubMed

    N'soukpoé-Kossi, C N; Ahmed Ouameur, A; Thomas, T; Thomas, T J; Tajmir-Riahi, H A

    2009-08-01

    We studied the interaction between tRNA and three polyamine analogues (1,11-diamino-4,8-diazaundecane.4HCl (333), 3,7,11,15-tetrazaheptadecane.4HCl (BE-333), and 3,7,11,15,19-pentazahenicosane.5HCl (BE-3333)) using FTIR, UV-visible, and CD spectroscopic methods. Spectroscopic evidence showed that polyamine analogues bound tRNA via guanine N7, adenine, uracil O2, and the backbone phosphate (PO2-) groups, while the most reactive sites for biogenic polyamines were guanine N7/O6, adenine N7, uracil O2, and sugar 2'-OH groups as well as the backbone phosphate group. The binding constants of polyamine analogue-tRNA recognition were lower than those of the biogenic polyamine-tRNA complexes, with K333 = 2.8 (+/-0.5) x 10(4), K(BE-333) = 3.7 (+/-0.7) x 10(4), K(BE-3333) = 4.0 (+/-0.9) x 10(4), K(spm) = 8.7 (+/-0.9) x 10(5), K(spd) = 6.1 (+/-0.7) x 10(5), and K(put) = 1.0 (+/-0.3) x 10(5) mol/L. tRNA remained in the A-family conformation; however, it aggregated at high polyamine analogue concentrations.

  14. 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

  15. Bounding Species Distribution Models

    NASA Technical Reports Server (NTRS)

    Stohlgren, Thomas J.; Jarnevich, Cahterine S.; Morisette, Jeffrey T.; Esaias, Wayne E.

    2011-01-01

    Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5): 642-647, 2011].

  16. Bounding species distribution models

    USGS Publications Warehouse

    Stohlgren, T.J.; Jarnevich, C.S.; Esaias, W.E.; Morisette, J.T.

    2011-01-01

    Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used. ?? 2011 Current Zoology.

  17. Reversible Sterilization

    ERIC Educational Resources Information Center

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  18. Reversible Cardiomyopathies

    PubMed Central

    Patel, Harsh; Madanieh, Raef; Kosmas, Constantine E; Vatti, Satya K; Vittorio, Timothy J

    2015-01-01

    Cardiomyopathies (CMs) have many etiological factors that can result in severe structural and functional dysregulation. Fortunately, there are several potentially reversible CMs that are known to improve when the root etiological factor is addressed. In this article, we discuss several of these reversible CMs, including tachycardia-induced, peripartum, inflammatory, hyperthyroidism, Takotsubo, and chronic illness–induced CMs. Our discussion also includes a review on their respective pathophysiology, as well as possible management solutions. PMID:26052233

  19. Antimycobacterial evaluation of pyrazinoic acid reversible derivatives.

    PubMed

    Dolezal, Martin; Kesetovic, Diana; Zitko, Jan

    2011-01-01

    Design, results of in vitro antimycobacterial evaluation, and study of structure-activity relationships of various pyrazinecarboxylic acid reversible derivatives are presented. This review deals with some pyrazinamide analogues/prodrugs derived from Nphenylpyrazine- 2-carboxamides (1), arylaminopyrazine-2,5-dicarbonitriles (2), aryl/alkylsulphanylpyrazines (3,4), and aroylpyrazines (5) effecting >50% inhibition in the primary antimycobacterial screen. The promising pyrazine candidates for further antimycobacterial evaluation were discovered. Results give good view onto structure-activity relationships of these analogues and promise even better activity of new compounds prepared after some structure optimization experiments.

  20. Virial Expansion Bounds

    NASA Astrophysics Data System (ADS)

    Tate, Stephen James

    2013-10-01

    In the 1960s, the technique of using cluster expansion bounds in order to achieve bounds on the virial expansion was developed by Lebowitz and Penrose (J. Math. Phys. 5:841, 1964) and Ruelle (Statistical Mechanics: Rigorous Results. Benjamin, Elmsford, 1969). This technique is generalised to more recent cluster expansion bounds by Poghosyan and Ueltschi (J. Math. Phys. 50:053509, 2009), which are related to the work of Procacci (J. Stat. Phys. 129:171, 2007) and the tree-graph identity, detailed by Brydges (Phénomènes Critiques, Systèmes Aléatoires, Théories de Jauge. Les Houches 1984, pp. 129-183, 1986). The bounds achieved by Lebowitz and Penrose can also be sharpened by doing the actual optimisation and achieving expressions in terms of the Lambert W-function. The different bound from the cluster expansion shows some improvements for bounds on the convergence of the virial expansion in the case of positive potentials, which are allowed to have a hard core.

  1. Reversible Computing

    DTIC Science & Technology

    1980-02-01

    will have been introduced. 9. Reversible celular autemata We shall assume the reader to have some familiarity with the concept of cel- lular...10003 Mr. Kin B. Thcmpson 1 copy Technical Director Information Systems Divisia.i Naval Research Laboratory (OP-91T) Technical Information Division

  2. REVERSE OSMOSIS,

    DTIC Science & Technology

    acetate membranes. Mechanisms of the process and porous cellulose acetate membrane technology are briefly reviewed. Based on a general capillary...The reverse osmosis process is discussed with particular reference to systems involving aqueous solutions and Loeb-Sourirajan-type porous cellulose

  3. Iodination and stability of somatostatin analogues: comparison of iodination techniques. A practical overview.

    PubMed

    de Blois, Erik; Chan, Ho Sze; Breeman, Wouter A P

    2012-01-01

    For iodination ((125/127)I) of tyrosine-containing peptides, chloramin-T, Pre-Coated Iodo-Gen(®) tubes and Iodo-Beads(®) (Pierce) are commonly used for in vitro radioligand investigations and there have been reliant vendors hereof for decades. However, commercial availability of these radio-iodinated peptides is decreasing. For continuation of our research in this field we investigated and optimized (radio-)iodination of somatostatin analogues. In literature, radioiodination using here described somatostatin analogues and iodination techniques are described separately. Here we present an overview, including High Performance Liquid Chromatography (HPLC) separation and characterisation by mass spectrometry, to obtain mono- and di-iodinated analogues. Reaction kinetics of (125/127)I iodinated somatostatin analogues were investigated as function of reaction time and concentration of reactants, including somatostatin analogues, iodine and oxidizing agent. To our knowledge, for the here described somatostatin analogues, no (127)I iodination and optimization are described. (Radio-)iodinated somatostatin analogues could be preserved with a >90% radiochemical purity for 1 month after reversed phase HPLC-purification.

  4. Validation of EMP bounds

    SciTech Connect

    Warne, L.K.; Merewether, K.O.; Chen, K.C.; Jorgenson, R.E.; Morris, M.E.; Solberg, J.E.; Lewis, J.G.; Derr, W.

    1996-07-01

    Test data on canonical weapon-like fixtures are used to validate previously developed analytical bounding results. The test fixtures were constructed to simulate (but be slightly worse than) weapon ports of entry but have known geometries (and electrical points of contact). The exterior of the test fixtures exhibited exterior resonant enhancement of the incident fields at the ports of entry with magnitudes equal to those of weapon geometries. The interior consisted of loaded transmission lines adjusted to maximize received energy or voltage but incorporating practical weapon geometrical constraints. New analytical results are also presented for bounding the energies associated with multiple bolt joints and for bounding the exterior resonant enhancement of the exciting fields.

  5. Neuronal Analogues of Conditioning Paradigms

    DTIC Science & Technology

    1984-04-24

    Although the mechanisms of interneuronal communication have been well established, the changes underlying most forms of learning have thus far eluded...stimulating electrodes on one of the connectives was adjusted so as to produce a small excitatory postsynaptic potential ( EPSP ) in the impaled cell...two stimuli would constitute a neuronal analogue of conditioning by producing an increased EPSP in response to the test stimulus alone. If so, then

  6. 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.

  7. Vasectomy reversal.

    PubMed

    Belker, A M

    1987-02-01

    A vasovasostomy may be performed on an outpatient basis with local anesthesia, but also may be performed on an outpatient basis with epidural or general anesthesia. Local anesthesia is preferred by most of my patients, the majority of whom choose this technique. With proper preoperative and intraoperative sedation, patients sleep lightly through most of the procedure. Because of the length of time often required for bilateral microsurgical vasoepididymostomy, epidural or general anesthesia and overnight hospitalization are usually necessary. Factors influencing the preoperative choice for vasovasostomy or vasoepididymostomy in patients undergoing vasectomy reversal are considered. The preoperative planned choice of vasovasostomy or vasoepididymostomy for patients having vasectomy reversal described herein does not have the support of all urologists who regularly perform these procedures. My present approach has evolved as the data reported in Tables 1 and 2 have become available, but it may change as new information is evaluated. However, it offers a logical method for planning choices of anesthesia and inpatient or outpatient status for patients undergoing vasectomy reversal procedures.

  8. Computing Graphical Confidence Bounds

    NASA Technical Reports Server (NTRS)

    Mezzacappa, M. A.

    1983-01-01

    Approximation for graphical confidence bounds is simple enough to run on programmable calculator. Approximation is used in lieu of numerical tables not always available, and exact calculations, which often require rather sizable computer resources. Approximation verified for collection of up to 50 data points. Method used to analyze tile-strength data on Space Shuttle thermal-protection system.

  9. Petawatt laser absorption bounded

    PubMed Central

    Levy, Matthew C.; Wilks, Scott C.; Tabak, Max; Libby, Stephen B.; Baring, Matthew G.

    2014-01-01

    The interaction of petawatt (1015 W) lasers with solid matter forms the basis for advanced scientific applications such as table-top particle accelerators, ultrafast imaging systems and laser fusion. Key metrics for these applications relate to absorption, yet conditions in this regime are so nonlinear that it is often impossible to know the fraction of absorbed light f, and even the range of f is unknown. Here using a relativistic Rankine-Hugoniot-like analysis, we show for the first time that f exhibits a theoretical maximum and minimum. These bounds constrain nonlinear absorption mechanisms across the petawatt regime, forbidding high absorption values at low laser power and low absorption values at high laser power. For applications needing to circumvent the absorption bounds, these results will accelerate a shift from solid targets, towards structured and multilayer targets, and lead the development of new materials. PMID:24938656

  10. Reverse preferential spread in complex networks

    NASA Astrophysics Data System (ADS)

    Toyoizumi, Hiroshi; Tani, Seiichi; Miyoshi, Naoto; Okamoto, Yoshio

    2012-08-01

    Large-degree nodes may have a larger influence on the network, but they can be bottlenecks for spreading information since spreading attempts tend to concentrate on these nodes and become redundant. We discuss that the reverse preferential spread (distributing information inversely proportional to the degree of the receiving node) has an advantage over other spread mechanisms. In large uncorrelated networks, we show that the mean number of nodes that receive information under the reverse preferential spread is an upper bound among any other weight-based spread mechanisms, and this upper bound is indeed a logistic growth independent of the degree distribution.

  11. 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."

  12. 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)

  13. Template polymerization of nucleotide analogues

    NASA Technical Reports Server (NTRS)

    Orgel, L. E.

    1991-01-01

    Recent work on the template-directed reactions of the natural D-nucleotides has made it clear that l-nucleotides and nucleotide-like derivatives of other sugars would strongly inhibit the formation of long oligonucleotides. Consequently, attention is focusing on molecules simpler than nucleotides that might have acted as monomers of an information transfer system. We have begun a general exploration of the template directed reactions of diverse peptide analogues. I will present work by Dr. Taifeng Wu on oxidative oligomerization of phosphorothioates and of Dr. Mary Tohidi on the cyclic polymerization of nucleoside and related cyclic pyrophosphates.

  14. Choline Analogues in Malaria Chemotherapy

    PubMed Central

    Peyrottes, Suzanne; Caldarelli, Sergio; Wein, Sharon; Périgaud, Christian; Pellet, Alain; Vial, Henri

    2012-01-01

    Emerging resistance against well-established anti-malaria drugs warrants the introduction of new therapeutic agents with original mechanisms of action. Inhibition of membrane-based phospholipid biosynthesis, which is crucial for the parasite, has thus been proposed as a novel and promising therapeutic strategy. This review compiles literature concerning the design and study of choline analogues and related cation derivatives as potential anti-malarials. It covers advances achieved over the last two decades and describes: the concept validation, the design and selection of a clinical candidate (Albitiazolium), back-up derivatives while also providing insight into the development of prodrug approaches. PMID:22607139

  15. SELECTIVE INHIBITION BY TRYPTOPHAN ANALOGUES OF MURINE TOXIN SYNTHESIS IN PASTEURELLA PESTIS

    PubMed Central

    Montie, Thomas C.; Ajl, Samuel J.

    1964-01-01

    Montie, Thomas C. (Albert Einstein Medical Center, Philadelphia, Pa.), and Samuel J. Ajl. Selective inhibition by tryptophan analogues of murine toxin synthesis in Pasteurella pestis. J. Bacteriol. 88:1467–1475. 1964.—Washed-cell suspensions of Pasteurella pestis, avirulent strain “Tjiwidej,” exhibited a preferential inhibition of toxin synthesis relative to total protein formation, when grown in the presence of various tryptophan analogues. Growth was partially inhibited in the presence of methyl analogues. High concentrations of 5-fluorotryptophan induced slight growth-inhibitory effects. However, toxin production was more sensitive to these levels of the analogue. Growth inhibition appeared not to relate to toxin inhibition. Inhibition of toxin synthesis by analogues was reversed by l-tryptophan and indole. Shikimic acid but not anthranilic acid antagonized the action of 4-methyltryptophan on selective toxin synthesis. The formation of tryptophanless protein accounted for continued protein synthesis in tryptophan-depleted cells. Protein resolved by acrylamide gel electrophoresis from crude cell extracts exhibited two toxic protein bands. The synthesis of one toxin-protein band, the less-mobile of the two, appeared to be associated with the membrane fraction of the cell, and was selectively blocked in cells grown in the presence of tryptophan analogues. Cellular tryptophan levels may determine the quantity and quality of proteins made. Images PMID:14234807

  16. Evaluation of Anti-HIV-1 Mutagenic Nucleoside Analogues*

    PubMed Central

    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

  17. Inhibition of experimental ascending urinary tract infection by an epithelial cell-surface receptor analogue

    NASA Astrophysics Data System (ADS)

    Edén, C. Svanborg; Freter, R.; Hagberg, L.; Hull, R.; Hull, S.; Leffler, H.; Schoolnik, G.

    1982-08-01

    It has been shown that the establishment of urinary tract infection by Escherichia coli is dependent on attachment of the bacteria to epithelial cells1-4. The attachment involves specific epithelial cell receptors, which have been characterized as glycolipids5-10. Reversible binding to cell-surface mannosides may also be important4,11-13. This suggests an approach to the treatment of infections-that of blocking bacterial attachment with cell membrane receptor analogues. Using E. coli mutants lacking one or other of the two binding specificities (glycolipid and mannose), we show here that glycolipid analogues can block in vitro adhesion and in vivo urinary tract infection.

  18. 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.

  19. Heteroatom-Containing Porphyrin Analogues.

    PubMed

    Chatterjee, Tamal; Shetti, Vijayendra S; Sharma, Ritambhara; Ravikanth, Mangalampalli

    2017-02-22

    The heteroatom-containing porphyrin analogues or core-modified porphyrins that resulted from the replacement of one or two pyrrole rings with other five-membered heterocycles such as furan, thiophene, selenophene, tellurophene, indene, phosphole, and silole are highly promising macrocycles and exhibit quite different physicochemical properties compared to regular azaporphyrins. The properties of heteroporphyrins depend on the nature and number of different heterocycle(s) present in place of pyrrole ring(s). The heteroporphyrins provide unique and unprecedented coordination environments for metals. Unlike regular porphyrins, the monoheteroporphyrins are known to stabilize metals in unusual oxidation states such as Cu and Ni in +1 oxidation states. The diheteroporphyrins, which are neutral macrocycles without ionizable protons, also showed interesting coordination chemistry. Thus, significant progress has been made in last few decades on core-modified porphyrins in terms of their synthesis, their use in building multiporphyrin arrays for light-harvesting applications, their use as ligands to form interesting metal complexes, and also their use for several other studies. The synthetic methods available in the literature allow one to prepare mono- and diheteroporphyrins and their functionalized derivatives, which were used extensively to prepare several covalent and noncovalent heteroporphyrin-based multiporphyrin arrays. The methods are also developed to synthesize different hetero analogues of porphyrin derivatives such as heterocorroles, heterochlorins, heterocarbaporphyrinoids, heteroatom-substituted confused porphyrins, and so on. This Review summarizes the key developments that have occurred in heteroporphyrin chemistry over the last four decades.

  20. Universal bounds on current fluctuations

    NASA Astrophysics Data System (ADS)

    Pietzonka, Patrick; Barato, Andre C.; Seifert, Udo

    2016-05-01

    For current fluctuations in nonequilibrium steady states of Markovian processes, we derive four different universal bounds valid beyond the Gaussian regime. Different variants of these bounds apply to either the entropy change or any individual current, e.g., the rate of substrate consumption in a chemical reaction or the electron current in an electronic device. The bounds vary with respect to their degree of universality and tightness. A universal parabolic bound on the generating function of an arbitrary current depends solely on the average entropy production. A second, stronger bound requires knowledge both of the thermodynamic forces that drive the system and of the topology of the network of states. These two bounds are conjectures based on extensive numerics. An exponential bound that depends only on the average entropy production and the average number of transitions per time is rigorously proved. This bound has no obvious relation to the parabolic bound but it is typically tighter further away from equilibrium. An asymptotic bound that depends on the specific transition rates and becomes tight for large fluctuations is also derived. This bound allows for the prediction of the asymptotic growth of the generating function. Even though our results are restricted to networks with a finite number of states, we show that the parabolic bound is also valid for three paradigmatic examples of driven diffusive systems for which the generating function can be calculated using the additivity principle. Our bounds provide a general class of constraints for nonequilibrium systems.

  1. Bounds on the speedup in quantum signaling

    NASA Astrophysics Data System (ADS)

    Arrighi, Pablo; Nesme, Vincent; Werner, Reinhard F.

    2017-01-01

    Given a classical, reversible dynamics over a line of discrete systems, we can define a quantum evolution, which acts on basis states like the classical one but is linearly extended to allow for quantum superpositions. It is a curious fact that in the quantum regime, the speed of propagation of information can sometimes be much greater than in the classical regime. Here we provide optimal bounds on this quantum speedup. In particular we show that over a run of many steps, the quantum propagation neighborhood can only increase by a constant fringe, so that there is no asymptotic increase in speed.

  2. 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.

  3. Blog life: Entropy Bound

    NASA Astrophysics Data System (ADS)

    Steinberg, Peter

    2008-06-01

    Who is the blog written by? Peter Steinberg is a nuclear physicist at the Brookhaven National Laboratory in New York, US. He is acting project manager of the PHOBOS experiment, which used Brookhaven's Relativistic Heavy Ion Collider (RHIC) to search for unusual events produced during collisions between gold nuclei. He is also involved with the PHENIX experiment, which seeks to discover a new state of matter known as the quark-gluon plasma. In addition to his own blog Entropy Bound, Steinberg is currently blogging on a website that was set up last year to publicize the involvement of US scientists with the Large Hadron Collider (LHC) at CERN.

  4. Multifunctions of bounded variation

    NASA Astrophysics Data System (ADS)

    Vinter, R. B.

    2016-02-01

    Consider control systems described by a differential equation with a control term or, more generally, by a differential inclusion with velocity set F (t , x). Certain properties of state trajectories can be derived when it is assumed that F (t , x) is merely measurable w.r.t. the time variable t. But sometimes a refined analysis requires the imposition of stronger hypotheses regarding the time dependence. Stronger forms of necessary conditions for minimizing state trajectories can be derived, for example, when F (t , x) is Lipschitz continuous w.r.t. time. It has recently become apparent that significant addition properties of state trajectories can still be derived, when the Lipschitz continuity hypothesis is replaced by the weaker requirement that F (t , x) has bounded variation w.r.t. time. This paper introduces a new concept of multifunctions F (t , x) that have bounded variation w.r.t. time near a given state trajectory, of special relevance to control. We provide an application to sensitivity analysis.

  5. 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.

  6. Macrolactam analogues of macrolide natural products.

    PubMed

    Hügel, Helmut M; Smith, Andrew T; Rizzacasa, Mark A

    2016-12-07

    The chemical modification of macrolide natural products into aza- or lactam analogues is a strategy employed to improve their metabolic stability and biological activity. The methods for the synthesis of several lactam analogues of macrolide natural products are highlighted and aspects of their biological properties presented.

  7. Dicentrine Analogue-Induced G2/M Arrest and Apoptosis through Inhibition of Topoisomerase II Activity in Human Cancer Cells.

    PubMed

    Lin, Huei-Fang; Huang, Huey-Lan; Liao, Jyh-Fei; Shen, Chien-Chang; Huang, Ray-Ling

    2015-07-01

    Lindera megaphylla has been traditionally used as an antineoplastic and wound healing remedy. We previously demonstrated the antitumor effects of D-dicentrine, a natural aporphine alkaloid from the root of L. megaphylla. To generate analogues, series of phenanthrene alkaloids from D-dicentrine were synthesized by degradation with ethyl chloroformate in pyridine, base hydrolysis, and N-alkylation. In this study, we demonstrated that one of the synthesized D-dicentrine analogues (here after designated as analogue 1) exhibited more potent cytotoxic effects than D-dicentrine in colon adenocarcinoma, hepatoma, leukemia, and epidermoid carcinoma cells. We performed cell cycle and apoptotic analysis by flow cytometry, an apoptotic DNA detection ELISA assay, and topoisomerase II activity by the kinetoplast DNA concatenation assay for studying their cytotoxic mechanisms. We found that both D-dicentrine and analogue 1 induced apoptosis and G2/M arrest in HL-60 leukemia cells. The percentage of apoptotic cells induced by analogue 1 was 4.5-fold higher than that induced by D-dicentrine as evident from measuring the amount of histone-bound DNA fragments. Moreover, we found that analogue 1 was 28-fold more potent than D-dicentrine for inhibition of topoisomerase II activity by the kinetoplast DNA concatenation assay. Our findings indicate that D-dicentrine analogue 1 is very promising as a potential antitumor agent for future study.

  8. The future of somatostatin analogue therapy.

    PubMed

    Stewart, P M; James, R A

    1999-10-01

    Since its discovery almost 30 years ago, the mode of action and therapeutic applications of somatostatin have been defined. In particular the cloning and characterization of somatostatin receptor subtypes has facilitated the development of high affinity analogues. In the context of pituitary disease, long-acting somatostatin analogues (octreotide, lanreotide) have been used to treat a variety of pituitary tumours but are most efficacious for the treatment of GH and TSH-secreting adenomas. In patients with acromegaly, depot preparations of these analogues are administered intramuscularly every 10-28 days and provide consistent suppression of GH levels to < 5 mU/l in approximately 50-65% of all cases. Even more specific somatostatin receptor analogues are under development. Finally, radiolabelled somatostatin analogue scintigraphy and, in larger doses, therapy, are now established tools in the evaluation and treatment of neuroendocrine tumours.

  9. Continuous analogues of matrix factorizations

    PubMed Central

    Townsend, Alex; Trefethen, Lloyd N.

    2015-01-01

    Analogues of singular value decomposition (SVD), QR, LU and Cholesky factorizations are presented for problems in which the usual discrete matrix is replaced by a ‘quasimatrix’, continuous in one dimension, or a ‘cmatrix’, continuous in both dimensions. Two challenges arise: the generalization of the notions of triangular structure and row and column pivoting to continuous variables (required in all cases except the SVD, and far from obvious), and the convergence of the infinite series that define the cmatrix factorizations. Our generalizations of triangularity and pivoting are based on a new notion of a ‘triangular quasimatrix’. Concerning convergence of the series, we prove theorems asserting convergence provided the functions involved are sufficiently smooth. PMID:25568618

  10. Fully analogue photonic reservoir computer.

    PubMed

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

    2016-03-03

    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.

  11. 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

  12. Culture-bound syndromes.

    PubMed

    Levine, R E; Gaw, A C

    1995-09-01

    Since its inception, scholars have struggled with the concept of CBSs. This struggle is reflected in the continuing use of a term that is confusing and inaccurate. Most authors would agree that the term "culture-bound syndrome" was intended to describe forms of otherwise common mental illness that are rendered unusual because of the pathoplastic influence of culture. It was intended not only to describe specific syndromes, but also meanings of illness and non-Western notions of disease causation. The term has become an anachronism, for the word, "syndrome," implies specific disease entities, not illnesses of attribution of idioms of distress. Furthermore, the word "bound" implies that the entities described are restricted to a single culture. Close examination reveals that many of the so-called "culture-bound" syndromes are found in multiple cultures that have in common only that they are "non-Western." It may be unreasonable to expect one term to describe these different concepts. The most accurate of the designations offered might be "folk diagnostic categories." Perhaps the most difficult question remaining is "How can we understand (and classify) these phenomena in such a way that highlights their uniqueness but does not dismiss them as too rare and exotic to warrant attention?" The first step is to recognize that the CBSs are a heterogeneous group of conditions. We must next acknowledge that the concepts represented may be difficult for the average Western clinician to recognize but, in their respective cultures, are neither rare nor unusual. With 80% of our increasingly shrinking world coming from "non-Western" cultures, a familiarity with non-Western notions of disease causation is particularly important for modern clinicians. Many authors have recommended that those CBSs that are "true" syndromes be classified together with their Western counterparts. In order to do this, the folk labels need to be put aside and the fundamental components of each disorder

  13. The effect of purine and pyrimidine analogues and virazole on adenovirus replication.

    PubMed

    Scheffler, P; Haghchenas, D; Wigand, R

    1975-04-01

    The multiplication of adenovirus 19 in HeLa cells was inhibited by various purine and pyrimidine analogues and by virazole. The formation of infectious virus and of capsid proteins (haemagglutin, group-specific complement-fixing antigen) was inhibited to the same degree, while the viral cytopathic effect (CPE) was not inhibited. The reversibility of the inhibition after removal of the substances was more complete for purine than for pyrimidine analogues. The inhibition was counteracted by simulataneous addition of the corresponding nucleosides. Adenosine was more effected than guanosine against purine analogues; both were partially effective against virazole, but none of them against arabinofuranosyladenine. The time-dependence of inhibition, the ensuing eclipse period after removal of the inhibitors, and the successive application of two inhibitors led to the conclusion that most of them affect the viral multiplication mainly by inhibition of DNA synthesis. Azacytidine inhibits the synthesis of structural proteins as well.

  14. 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

  15. Side-on bound diazene and hydrazine complexes of ruthenium.

    PubMed

    Field, Leslie D; Li, Hsiu L; Dalgarno, Scott J

    2010-07-05

    The reaction of cis-[RuCl(2)(PP)(2)] (PP = depe, dmpe) with hydrazine afforded end-on bound ruthenium(II) hydrazine complexes. Treatment of the hydrazine complexes with strong base afforded the side-on bound ruthenium(0) diazene complexes cis-[Ru(eta(2)-NH=NH)(PP)(2)]. Treatment of cis-[Ru(eta(2)-NH=NH)(depe)(2)] with weak acid under chloride-free conditions afforded the side-on bound hydrazine complex cis-[Ru(eta(2)-N(2)H(4))(depe)(2)](2+). These are the first reported side-on bound diazene and hydrazine complexes of ruthenium, and they have been characterized by NMR spectroscopy ((1)H, (31)P, (15)N) and by X-ray crystallography. The interconversion between the ruthenium diazene and the ruthenium hydrazine by acid-base treatment was reversible.

  16. Work extraction from quantum systems with bounded fluctuations in work

    NASA Astrophysics Data System (ADS)

    Richens, Jonathan G.; Masanes, Lluis

    2016-11-01

    In the standard framework of thermodynamics, work is a random variable whose average is bounded by the change in free energy of the system. This average work is calculated without regard for the size of its fluctuations. Here we show that for some processes, such as reversible cooling, the fluctuations in work diverge. Realistic thermal machines may be unable to cope with arbitrarily large fluctuations. Hence, it is important to understand how thermodynamic efficiency rates are modified by bounding fluctuations. We quantify the work content and work of formation of arbitrary finite dimensional quantum states when the fluctuations in work are bounded by a given amount c. By varying c we interpolate between the standard and minimum free energies. We derive fundamental trade-offs between the magnitude of work and its fluctuations. As one application of these results, we derive the corrected Carnot efficiency of a qubit heat engine with bounded fluctuations.

  17. Work extraction from quantum systems with bounded fluctuations in work

    PubMed Central

    Richens, Jonathan G.; Masanes, Lluis

    2016-01-01

    In the standard framework of thermodynamics, work is a random variable whose average is bounded by the change in free energy of the system. This average work is calculated without regard for the size of its fluctuations. Here we show that for some processes, such as reversible cooling, the fluctuations in work diverge. Realistic thermal machines may be unable to cope with arbitrarily large fluctuations. Hence, it is important to understand how thermodynamic efficiency rates are modified by bounding fluctuations. We quantify the work content and work of formation of arbitrary finite dimensional quantum states when the fluctuations in work are bounded by a given amount c. By varying c we interpolate between the standard and minimum free energies. We derive fundamental trade-offs between the magnitude of work and its fluctuations. As one application of these results, we derive the corrected Carnot efficiency of a qubit heat engine with bounded fluctuations. PMID:27886177

  18. Work extraction from quantum systems with bounded fluctuations in work.

    PubMed

    Richens, Jonathan G; Masanes, Lluis

    2016-11-25

    In the standard framework of thermodynamics, work is a random variable whose average is bounded by the change in free energy of the system. This average work is calculated without regard for the size of its fluctuations. Here we show that for some processes, such as reversible cooling, the fluctuations in work diverge. Realistic thermal machines may be unable to cope with arbitrarily large fluctuations. Hence, it is important to understand how thermodynamic efficiency rates are modified by bounding fluctuations. We quantify the work content and work of formation of arbitrary finite dimensional quantum states when the fluctuations in work are bounded by a given amount c. By varying c we interpolate between the standard and minimum free energies. We derive fundamental trade-offs between the magnitude of work and its fluctuations. As one application of these results, we derive the corrected Carnot efficiency of a qubit heat engine with bounded fluctuations.

  19. Inhibition of serine and proline racemases by substrate-product analogues.

    PubMed

    Harty, Matthew; Nagar, Mitesh; Atkinson, Logan; Legay, Christina M; Derksen, Darren J; Bearne, Stephen L

    2014-01-01

    d-Amino acids can play important roles as specific biosynthetic building blocks required by organisms or act as regulatory molecules. Consequently, amino acid racemases that catalyze the formation of d-amino acids are potential therapeutic targets. Serine racemase catalyzes the reversible formation of d-serine (a modulator of neurotransmission) from l-serine, while proline racemase (an essential enzymatic and mitogenic protein in trypanosomes) catalyzes the reversible conversion of l-proline to d-proline. We show the substrate-product analogue α-(hydroxymethyl)serine is a modest, linear mixed-type inhibitor of serine racemase from Schizosaccharomyces pombe (Ki=167±21mM, Ki'=661±81mM, cf. Km=19±2mM). The bicyclic substrate-product analogue of proline, 7-azabicyclo[2.2.1]heptan-7-ium-1-carboxylate is a weak inhibitor of proline racemase from Clostridium sticklandii, giving only 29% inhibition at 142.5mM. However, the more flexible bicyclic substrate-product analogue tetrahydro-1H-pyrrolizine-7a(5H)-carboxylate is a noncompetitive inhibitor of proline racemase from C. sticklandii (Ki=111±15mM, cf. Km=5.7±0.5mM). These results suggest that substrate-product analogue inhibitors of racemases may only be effective when the active site is capacious and/or plastic, or when the inhibitor is sufficiently flexible.

  20. Reversibility conditions for quantum channels and their applications

    SciTech Connect

    Shirokov, M E

    2013-08-31

    Conditions for a quantum channel (noncommutative Markov operator) to be reversible with respect to complete families of quantum states with bounded rank are obtained. A description of all quantum channels reversible with respect to a given (orthogonal or nonorthogonal) complete family of pure states is given. Some applications in quantum information theory are considered. Bibliography: 20 titles.

  1. Specific, reversible binding of [18F]benperidol to baboon D2 receptors: PET evaluation of an improved 18F-labeled ligand.

    PubMed

    Moerlein, S M; Perlmutter, J S; Welch, M J

    1995-08-01

    [18F]Benperidol ([18F]BP), a positron-emitting analogue of the dopaminergic D2 antagonist benperidol, was evaluated as a radiopharmaceutical for use with positron emission tomography (PET). PET imaging of baboons after i.v. injection of [18F]BP indicated that the radiofluorinated ligand rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and that selective disposition was retained for over 2 h. Pretreatment of an animal with unlabeled receptor-specific antagonists prior to injection of [18F]BP confirmed that the radioligand bound specifically to central D2 receptors in vivo, and not to S2 or D1 receptors. [18F]BP bound to D2 receptors in a reversible manner; unlabeled eticlopride displaced D2 receptor-bound [18F]BP in vivo. The radioligand was metabolized in the periphery to polar metabolites which are not expected to cross the blood-brain barrier. [18F]BP has advantages over other tracers as a radiopharmaceutical for PET study of central D2 receptor activity, and can be applied for noninvasive evaluation of the interaction of unlabeled drugs with central D2 receptor sites.

  2. Brief Report: An Experimental Analogue of Consultee "Resistance" Effects on the Consultant's Therapeutic Behavior--A Preliminary Investigation

    ERIC Educational Resources Information Center

    Cautilli, Joseph; Riley-Tillman, T. Chris

    2006-01-01

    This study presents an experimental analogue of resistance in the consultation process. Using an ABAB reversal design, the experimenter measured the ecological effects of teacher resistant behaviors on consultant therapeutic behavior. The study defined therapeutic behaviors as teaching, confronting and problem identification, analysis, and…

  3. 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.

  4. 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

  5. Space analogue studies in Antarctica.

    PubMed

    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.

  6. 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.

  7. Northwest Outward Bound Instructor's Manual.

    ERIC Educational Resources Information Center

    Northwest Outward Bound School, Portland, OR.

    Instructor responsibilities, procedures for completing activities safely, and instructional methods and techniques are outlined to assist instructors in the Northwest Outward Bound School (Portland, Oregon) as they strive for teaching excellence. Information is organized into six chapters addressing: history and philosophy of Outward Bound; course…

  8. Bounds for Asian basket options

    NASA Astrophysics Data System (ADS)

    Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

    2008-09-01

    In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

  9. Binding affinities of amino acid analogues at the charged aqueous titania interface: implications for titania-binding peptides.

    PubMed

    Sultan, Anas M; Hughes, Zak E; Walsh, Tiffany R

    2014-11-11

    Despite the extensive utilization of biomolecule-titania interfaces, biomolecular recognition and interactions at the aqueous titania interface remain far from being fully understood. Here, atomistic molecular dynamics simulations, in partnership with metadynamics, are used to calculate the free energy of adsorption of different amino acid side chain analogues at the negatively-charged aqueous rutile TiO2 (110) interface, under conditions corresponding with neutral pH. Our calculations predict that charged amino acid analogues have a relatively high affinity to the titania surface, with the arginine analogue predicted to be the strongest binder. Interactions between uncharged amino acid analogues and titania are found to be repulsive or weak at best. All of the residues that bound to the negatively-charged interface show a relatively stronger adsorption compared with the charge-neutral interface, including the negatively-charged analogue. Of the analogues that are found to bind to the titania surface, the rank ordering of the binding affinities is predicted to be "arginine" > "lysine" ≈ aspartic acid > "serine". This is the same ordering as was found previously for the charge-neutral aqueous titania interface. Our results show very good agreement with available experimental data and can provide a baseline for the interpretation of peptide-TiO2 adsorption data.

  10. Metabolism of organically bound tritium

    SciTech Connect

    Travis, C.C.

    1984-01-01

    The classic methodology for estimating dose to man from environmental tritium ignores the fact that organically bound tritium in foodstuffs may be directly assimilated in the bound compartment of tissues without previous oxidation. We propose a four-compartment model consisting of a free body water compartment, two organic compartments, and a small, rapidly metabolizing compartment. The utility of this model lies in the ability to input organically bound tritium in foodstuffs directly into the organic compartments of the model. We found that organically bound tritium in foodstuffs can increase cumulative total body dose by a factor of 1.7 to 4.5 times the free body water dose alone, depending on the bound-to-loose ratio of tritium in the diet. Model predictions are compared with empirical measurements of tritium in human urine and tissue samples, and appear to be in close agreement. 10 references, 4 figures, 3 tables.

  11. Loratadine analogues as MAGL inhibitors.

    PubMed

    Patel, Jayendra Z; Ahenkorah, Stephen; Vaara, Miia; Staszewski, Marek; Adams, Yahaya; Laitinen, Tuomo; Navia-Paldanius, Dina; Parkkari, Teija; Savinainen, Juha R; Walczyński, Krzysztof; Laitinen, Jarmo T; Nevalainen, Tapio J

    2015-04-01

    Compound 12a (JZP-361) acted as a potent and reversible inhibitor of human recombinant MAGL (hMAGL, IC50=46 nM), and was found to have almost 150-fold higher selectivity over human recombinant fatty acid amide hydrolase (hFAAH, IC50=7.24 μM) and 35-fold higher selectivity over human α/β-hydrolase-6 (hABHD6, IC50=1.79 μM). Additionally, compound 12a retained H1 antagonistic affinity (pA2=6.81) but did not show cannabinoid receptor activity, when tested at concentrations ⩽ 10 μM. Hence, compound 12a represents a novel dual-acting pharmacological tool possessing both MAGL-inhibitory and antihistaminergic activities.

  12. Synthesis, Biological Activity, and Crystal Structure of Potent Nonnucleoside Inhibitors of HIV-1 Reverse Transcriptase That Retain Activity against Mutant Forms of the Enzyme†

    PubMed Central

    Morningstar, Marshall L.; Roth, Thomas; Farnsworth, David W.; Smith, Marilyn Kroeger; Watson, Karen; Buckheit, Robert W.; Das, Kalyan; Zhang, Wanyi; Arnold, Eddy; Julias, John G.; Hughes, Stephen H.; Michejda, Christopher J.

    2010-01-01

    In an ongoing effort to develop novel and potent nonnucleoside HIV-1 reverse transcriptase (RT) inhibitors that are effective against the wild type (WT) virus and clinically observed mutants, 1,2-bis-substituted benzimidazoles were synthesized and tested. Optimization of the N1 and C2 positions of benzimidazole led to the development of 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-methylbenzimidazole (1) (IC50 = 0.2 μM, EC50 = 0.44 μM, and TC50 ≥ 100 against WT). This paper describes how substitution on the benzimidazole ring profoundly affects activity. Substituents at the benzimidazole C4 dramatically enhanced potency, while at C5 or C6 substituents were generally detrimental or neutral to activity, respectively. A 7-methyl analogue did not inhibit HIV-1 RT. Determination of the crystal structure of 1 bound to RT provided the basis for accurate modeling of additional analogues, which were synthesized and tested. Several derivatives were nanomolar inhibitors of wild-type virus and were effective against clinically relevant HIV-1 mutants. PMID:17663538

  13. On the mechanical analogue of DNA.

    PubMed

    Yakushevich, Ludmila

    2017-03-01

    The creation of mechanical analogues of biological systems is known as a useful instrument that helps to understand better the dynamical mechanisms of the functioning of living organisms. Mechanical analogues of biomolecules are usually constructed for imitation of their internal mobility, which is one of the most important properties of the molecules. Among the different types of internal motions, angular oscillations of nitrous bases are of special interest because they make a substantial contribution to the base pairs opening that in turn is an important element of the process of the DNA-protein recognition. In this paper, we investigate the possibility to construct a mechanical analogue for imitation of angular oscillations of nitrous bases in inhomogeneous DNA. It is shown that the analogue has the form of a mechanical chain of non-identical pendulums that oscillate in the gravitational field of the Earth and coupled by identical springs. The masses and lengths of pendulums, as well as the distances between neighboring pendulums and the rigidity of springs are calculated. To illustrate the approach, we present the result of construction of the mechanical analogue of the fragment of the sequence of bacteriophage T7D.

  14. Analogue Downscaling of Seasonal Rainfall Forecasts

    NASA Astrophysics Data System (ADS)

    Charles, A. N.; Timbal, B.; Hendon, H.

    2010-12-01

    We have taken an existing statistical downscaling model (SDM), based on meteorological analogues that was developed for downscaling climate change projections (Timbal et al 2009), and applied it in the seasonal forecasting context to produce downscaled rainfall hindcasts from a coupled model seasonal forecast system (POAMA). Downscaling of POAMA forecasts is required to provide seasonal climate information at local scales of interest. Analogue downscaling is a simple technique to generate rainfall forecasts appropriate to the local scale by conditioning on the large scale predicted GCM circulation and the local topography and climate. Analogue methods are flexible and have been shown to produce good results when downscaling 20th century South Eastern Australian rainfall output from climate models. A set of re-forecasts for three month rainfall at 170 observing stations in the South Murray Darling region of Australia were generated using predictors from the POAMA re-forecasts as input for the analogue SDM. The predictors were optimised over a number of different GCMS in previous climate change downscaling studies. Downscaling with the analogue SDM results in predicted rainfall with realistic variance while maintaining the modest predictive skill of the dynamical model. Evaluation of the consistency between the large scale mean of downscaled and direct GCM output precipitation is encouraging.

  15. Release of soil bound (nonextractable) residues by various physiological groups of microorganisms

    SciTech Connect

    Khan, S.U.; Ivarson, K.C.

    1982-01-01

    Soil bound /sup 14/C-labeled residues were released by four different physiological groups of microorganisms from an organic soil treated with /sup 14/C-ring-labeled prometryn (2-(methylthio)-4,6-bis(isopropylamino)-s-triazine). The extent to which the different microbial populations released bound /sup 14/C residues (25-30% of the total bound /sup 14/C) from the gamma-irradiated soil after 28 days incubation did not differ considerably. Analysis of the extractable material from the incubated soil showed the presence of small amounts of the parent compound, and its hydroxy and mono-N-dealkylated analogues. Low level of /sup 14/CO2 (1.5-3.0% of the total bound /sup 14/C) was evolved from the microbial systems indicating ring cleavage of the released material as being a very minor reaction.

  16. Release of soil bound (nonextractable) residues by various physiological groups of microorganisms.

    PubMed

    Khan, S U; Ivarson, K C

    1982-01-01

    Soil bound 14C-labeled residues were released by four different physiological groups of microorganisms from an organic soil treated with 14C-ring-labeled prometryn [2-(methylthio)-4,6-bis(isopropylamino)-s-triazine]. The extent to which the different microbial populations released bound 14C residues (25-30% of the total bound 14C) from the gamma-irradiated soil after 28 days incubation did not differ considerably. Analysis of the extractable material from the incubated soil showed the presence of small amounts of the parent compound, and its hydroxy and mono-N-dealkylated analogues. Low level of 14CO2 (1.5-3.0% of the total bound 14C) was evolved from the microbial systems indicating ring cleavage of the released material as being a very minor reaction.

  17. Bounds on the information rate of quantum-secret-sharing schemes

    SciTech Connect

    Sarvepalli, Pradeep

    2011-04-15

    An important metric of the performance of a quantum-secret-sharing scheme is its information rate. Beyond the fact that the information rate is upper-bounded by one, very little is known in terms of bounds on the information rate of quantum-secret-sharing schemes. Furthermore, not every scheme can be realized with rate one. In this paper we derive upper bounds for the information rates of quantum-secret-sharing schemes. We show that there exist quantum access structures on n players for which the information rate cannot be better than O((log{sub 2}n)/n). These results are the quantum analogues of the bounds for classical-secret-sharing schemes proved by Csirmaz.

  18. Efficiency of Rectification: Reversible vs. Irreversible Regimes

    NASA Astrophysics Data System (ADS)

    Sokolov, I. M.

    2002-11-01

    Both man-made locomotive devices and molecular motors use gears to transform a reciprocating motion into a directed one. One of the most common gears is a rectifier, a mechanically irreversible appliance. The maximal energetic efficiency of an isothermic gear is bounded by unity, as a consequence of the Second Law. However, approaching this ideal efficiency does not imply approaching reversibility. We discuss what properties of a rectifier mostly influence the transduction efficiency and show that an appliance which locks under backward force is just the one which can approach the ideal efficiency either in the reversible or in the irreversible regime.

  19. Novel configuration of a myosin II transient intermediate analogue revealed by quick-freeze deep-etch replica electron microscopy.

    PubMed

    Kimori, Yoshitaka; Baba, Norio; Katayama, Eisaku

    2013-02-15

    In the present paper, we described our attempt to characterize the rough three-dimensional features of the structural analogue of the key intermediate of myosin's cross-bridge cycle. Using quick-freeze deep-etch replica electron microscopy, we observed that actin-attached myosin during in vitro sliding was bent superficially as postulated by the conventional hypothesis, but in the opposite direction of the putative pre-power-stroke configuration, as for ADP·Vi (inorganic vanadate)-bound myosin. We searched for the conformational species with a similar appearance and found that SH1-SH2 (thiols 1 and 2)-cross-linked myosin is a good candidate. To characterize such small asymmetric structures, we employed a new pattern-recognition procedure that accommodates the metal-replicated samples. In this method, the best-matched views of the target microscopic images were selected from a comprehensive set of images simulated from known atomic co-ordinates of relevant proteins. Together with effective morphological filtering, we could define the conformational species and the view angles of the catalytic domain and the lever arm cropped from averaged images of disulfide-cross-linked myosin. Whereas the catalytic domain of the new conformer closely resembled the pPDM (N,N'-p-phenylenedimaleimide)-treated, but SH2 Lys705-cross-linked, structure (PDB code 1L2O), a minor product of the same cross-linking reaction, the lever arm projected differently. Using separately determined view angles of the catalytic domain and the lever arm, we built a model of disulfide-cross-linked myosin. Further combination with the 'displacement-mapping' procedure enabled us to reconstruct the global three-dimensional envelope of the unusual structure whose lever arm orientation is compatible with our reports on the actin-sliding cross-bridge structure. Assuming this conformer as the structural analogue of the transient intermediate during actin sliding, the power stroke of the lever arm might

  20. Distribution and characteristics of bound residues of prometryn in an organic soil

    SciTech Connect

    Khan, S.U.

    1982-01-01

    Uniformly /sup 14/C-ring-labeled prometryn (2-(methylthio)-4,6-bis(isopropylamino)-s-triazine) was incubated with an organic soil under laboratory conditions for 1 year. After exhaustive solvent extraction, the soil containing bound (nonextractable) /sup 14/C-labeled residues was fractionated into humic substances by alkali extraction followed by acid precipitation. A considerable proportion of /sup 14/C-labeled residues in humin and humic acid was comprised of the parent herbicide and its mono-N-dealkylated metabolite. However, the soluble fulvic acid fraction contained an appreciable amount of the 2-hydroxy analogue of prometryn. Thermoanalytical methods were used to obtain information on the nature and location of /sup 14/C-labeled bound residues in soil and humic materials. Exhaustive methylation of humin and humic acid released some of the bound /sup 14/C-labeled residues from these fractions. Bound /sup 14/C-labeled residues in aqueous suspensions of humin or humic acid were stable to UV light. However, UV irradiation of the soil suspension resulted in the release of some of the bound /sup 14/C-labeled residues which were subsequently decomposed to hydroxy analogues.

  1. Bound states in string nets

    NASA Astrophysics Data System (ADS)

    Schulz, Marc Daniel; Dusuel, Sébastien; Vidal, Julien

    2016-11-01

    We discuss the emergence of bound states in the low-energy spectrum of the string-net Hamiltonian in the presence of a string tension. In the ladder geometry, we show that a single bound state arises either for a finite tension or in the zero-tension limit depending on the theory considered. In the latter case, we perturbatively compute the binding energy as a function of the total quantum dimension. We also address this issue in the honeycomb lattice where the number of bound states in the topological phase depends on the total quantum dimension. Finally, the internal structure of these bound states is analyzed in the zero-tension limit.

  2. A new approach to the synthesis of the 5'-deoxy-5'-methylphosphonate linked thymidine oligonucleotide analogues.

    PubMed Central

    Szabó, T; Kers, A; Stawinski, J

    1995-01-01

    A new synthetic method for the preparation of the 5'-deoxy-5'-methylphosphonate linked thymidine oligonucleotides (5'-methylenephosphonate analogues) was developed. The method is based on the use of a phosphonate protecting group, 4-methoxy-1-oxido-2-picolyl, enabling intramolecular nucleophilic catalysis which together with the condensing agent, 2,4,6-triisopropylbenzenesulfonyl chloride, secures fast and efficient formation of the 5'-methylenephosphonate internucleosidic bonds. The produced protected oligomers were treated with thiophenol and triethylamine to remove the phosphonate protecting groups, cleaved from the solid support using concentrated aqueous ammonia, and purified by HPLC. Several thymidine oligonucleotide analogues with the chain length of up to 20 nucleotidic units, in which all internal 5'-oxygen atoms have been replaced by methylene groups directly bound to phosphorus, were synthesised using this methodology. PMID:7731801

  3. Synthesis and κ-Opioid Receptor Activity of Furan-Substituted Salvinorin A Analogues

    PubMed Central

    2015-01-01

    The neoclerodane diterpene salvinorin A, found in the leaves of Salvia divinorum, is a potent κ-opioid receptor agonist, making it an attractive scaffold for development into a treatment for substance abuse. Although several successful semisynthetic studies have been performed to elucidate structure–activity relationships, the lack of analogues with substitutions to the furan ring of salvinorin A has prevented a thorough understanding of its role in binding to the κ-opioid receptor. Herein we report the synthesis of several salvinorin A derivatives with modified furan rings. Evaluation of these compounds in a functional assay indicated that sterically less demanding substitutions are preferred, suggesting the furan ring is bound in a congested portion of the binding pocket. The most potent of the analogues successfully reduced drug-seeking behavior in an animal model of drug-relapse without producing the sedation observed with other κ-opioid agonists. PMID:25426797

  4. Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues.

    PubMed

    Riley, Andrew P; Groer, Chad E; Young, David; Ewald, Amy W; Kivell, Bronwyn M; Prisinzano, Thomas E

    2014-12-26

    The neoclerodane diterpene salvinorin A, found in the leaves of Salvia divinorum, is a potent κ-opioid receptor agonist, making it an attractive scaffold for development into a treatment for substance abuse. Although several successful semisynthetic studies have been performed to elucidate structure-activity relationships, the lack of analogues with substitutions to the furan ring of salvinorin A has prevented a thorough understanding of its role in binding to the κ-opioid receptor. Herein we report the synthesis of several salvinorin A derivatives with modified furan rings. Evaluation of these compounds in a functional assay indicated that sterically less demanding substitutions are preferred, suggesting the furan ring is bound in a congested portion of the binding pocket. The most potent of the analogues successfully reduced drug-seeking behavior in an animal model of drug-relapse without producing the sedation observed with other κ-opioid agonists.

  5. GABAA Receptor Modulation by Etomidate Analogues

    PubMed Central

    Pejo, Ervin; Santer, Peter; Wang, Lei; Dershwitz, Philip; Husain, S. Shaukat; Raines, Douglas E.

    2015-01-01

    Background Etomidate is a highly potent anesthetic agent that is believed to produce hypnosis by enhancing γ-aminobutyric acid type A (GABAA) receptor function. We characterized the GABAA receptor and hypnotic potencies of etomidate analogues. We then used computational techniques to build statistical and graphical models that relate the potencies of these etomidate analogues to their structures in order to identify the specific molecular determinants of potency. Methods GABAA receptor potencies were defined with voltage-clamp electrophysiology using α1β3γ2 receptors harboring a channel mutation (α1(L264T)) that enhances anesthetic sensitivity (n = 36 – 60 measurements per concentration-response curve). The hypnotic potencies of etomidate analogues were defined using a loss of righting reflexes assay in Sprague Dawley rats (n = 9 – 21 measurements per dose-response curve). Three-dimensional quantitative structure-activity relationships were determined in silico using comparative molecular field analysis. Results The GABAA receptor and hypnotic potencies of etomidate and the etomidate analogues ranged by 91-fold and 53-fold, respectively. These potency measurements were significantly correlated (r2 = 0.72), but neither measurement correlated with drug hydrophobicity (r2 = 0.019 and 0.005, respectively). Statistically significant and predictive comparative molecular field analysis models were generated and a pharmacophore model was built that revealed both the structural elements in etomidate analogues associated with high potency and the interactions that these elements make with the etomidate binding site. Conclusion There are multiple specific structural elements in etomidate and etomidate analogues that mediate GABAA receptor modulation. Modifying any one element can alter receptor potency by an order of magnitude or more. PMID:26691905

  6. Biological Evaluation of Double Point Modified Analogues of 1,25-Dihydroxyvitamin D₂ as Potential Anti-Leukemic Agents.

    PubMed

    Corcoran, Aoife; Nadkarni, Sharmin; Yasuda, Kaori; Sakaki, Toshiyuki; Brown, Geoffrey; Kutner, Andrzej; Marcinkowska, Ewa

    2016-02-01

    Structurally similar double-point modified analogues of 1,25-dihydroxyvitamin D₂ (1,25D₂) were screened in vitro for their pro-differentiating activity against the promyeloid cell line HL60. Their affinities towards human full length vitamin D receptor (VDR) and metabolic stability against human vitamin D 24-hydroxylase (CYP24A1) were also tested. The analogues (PRI-1730, PRI-1731, PRI-1732, PRI-1733 and PRI-1734) contained 5,6-trans modification of the A-ring and of the triene system, additional hydroxyl or unsaturation at C-22 in the side chain and reversed absolute configuration (24-epi) at C-24 of 1,25D₂. As presented in this paper, introduction of selected structural modifications simultaneously in two distinct parts of the vitamin D molecule resulted in a divergent group of analogues. Analogues showed lower VDR affinity in comparison to that of the parent hormones, 1,25D₂ and 1,25D₃, and they caused effective HL60 cell differentiation only at high concentrations of 100 nM and above. Unexpectedly, introducing of a 5,6-trans modification combined with C-22 hydroxyl and 24-epi configuration switched off entirely the cell differentiation activity of the analogue (PRI-1734). However, this analogue remained a moderate substrate for CYP24A1, as it was metabolized at 22%, compared to 35% for 1,25D₂. Other analogues from this series were either less (12% for PRI-1731 and PRI-1733) or more (52% for PRI-1732) resistant to the enzymatic deactivation. Although the inactive analogue PRI-1734 failed to show VDR antagonism, when tested in HL60 cells, its structure might be a good starting point for our design of a vitamin D antagonist.

  7. Biological Evaluation of Double Point Modified Analogues of 1,25-Dihydroxyvitamin D2 as Potential Anti-Leukemic Agents

    PubMed Central

    Corcoran, Aoife; Nadkarni, Sharmin; Yasuda, Kaori; Sakaki, Toshiyuki; Brown, Geoffrey; Kutner, Andrzej; Marcinkowska, Ewa

    2016-01-01

    Structurally similar double-point modified analogues of 1,25-dihydroxyvitamin D2 (1,25D2) were screened in vitro for their pro-differentiating activity against the promyeloid cell line HL60. Their affinities towards human full length vitamin D receptor (VDR) and metabolic stability against human vitamin D 24-hydroxylase (CYP24A1) were also tested. The analogues (PRI-1730, PRI-1731, PRI-1732, PRI-1733 and PRI-1734) contained 5,6-trans modification of the A-ring and of the triene system, additional hydroxyl or unsaturation at C-22 in the side chain and reversed absolute configuration (24-epi) at C-24 of 1,25D2. As presented in this paper, introduction of selected structural modifications simultaneously in two distinct parts of the vitamin D molecule resulted in a divergent group of analogues. Analogues showed lower VDR affinity in comparison to that of the parent hormones, 1,25D2 and 1,25D3, and they caused effective HL60 cell differentiation only at high concentrations of 100 nM and above. Unexpectedly, introducing of a 5,6-trans modification combined with C-22 hydroxyl and 24-epi configuration switched off entirely the cell differentiation activity of the analogue (PRI-1734). However, this analogue remained a moderate substrate for CYP24A1, as it was metabolized at 22%, compared to 35% for 1,25D2. Other analogues from this series were either less (12% for PRI-1731 and PRI-1733) or more (52% for PRI-1732) resistant to the enzymatic deactivation. Although the inactive analogue PRI-1734 failed to show VDR antagonism, when tested in HL60 cells, its structure might be a good starting point for our design of a vitamin D antagonist. PMID:26840307

  8. Reversible Thermoset Adhesives

    NASA Technical Reports Server (NTRS)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  9. 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.

  10. Insulin analogues: action profiles beyond glycaemic control.

    PubMed

    Eckardt, Kristin; Eckel, Jürgen

    2008-02-01

    A variety of studies have documented significant improvements in the treatment of type 1 and 2 diabetes after the introduction of artificial insulins. This review gives an overview of insulin analogues which are currently approved for therapeutical use. Clinical data regarding the efficiency to control blood glucose level as well as improving HbA1c level in comparison to conventional insulin preparations in type 1 and 2 diabetic patients are summarized. Furthermore, special features of insulin analogues regarding their signalling properties are discussed with focus on the proliferative effects of insulin glargine as well as some recent data of insulin detemir.

  11. SAMHD1 enhances nucleoside-analogue efficacy against HIV-1 in myeloid cells

    PubMed Central

    Ordonez, Paula; Kunzelmann, Simone; Groom, Harriet C. T.; Yap, Melvyn W.; Weising, Simon; Meier, Chris; Bishop, Kate N.; Taylor, Ian A.; Stoye, Jonathan P.

    2017-01-01

    SAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level that cannot support productive reverse transcription. We now show that, in addition to this direct effect on virus replication, manipulating cellular SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotide analogue reverse transcription inhibitors presumably as a result of modulating dNTP pools that compete for recruitment by viral polymerases. Further, a variety of other nucleotide-based analogues, not normally considered antiretrovirals, such as the anti-herpes drugs Aciclovir and Ganciclovir and the anti-cancer drug Clofarabine are now revealed as potent anti-HIV-1 agents, under conditions of low dNTPs. This in turn suggests novel uses for nucleotide analogues to inhibit HIV-1 in differentiated cells low in dNTPs. PMID:28220857

  12. Matrix algorithms for solving (in)homogeneous bound state equations.

    PubMed

    Blank, M; Krassnigg, A

    2011-07-01

    In the functional approach to quantum chromodynamics, the properties of hadronic bound states are accessible via covariant integral equations, e.g. the Bethe-Salpeter equation for mesons. In particular, one has to deal with linear, homogeneous integral equations which, in sophisticated model setups, use numerical representations of the solutions of other integral equations as part of their input. Analogously, inhomogeneous equations can be constructed to obtain off-shell information in addition to bound-state masses and other properties obtained from the covariant analogue to a wave function of the bound state. These can be solved very efficiently using well-known matrix algorithms for eigenvalues (in the homogeneous case) and the solution of linear systems (in the inhomogeneous case). We demonstrate this by solving the homogeneous and inhomogeneous Bethe-Salpeter equations and find, e.g. that for the calculation of the mass spectrum it is as efficient or even advantageous to use the inhomogeneous equation as compared to the homogeneous. This is valuable insight, in particular for the study of baryons in a three-quark setup and more involved systems.

  13. Matrix algorithms for solving (in)homogeneous bound state equations

    PubMed Central

    Blank, M.; Krassnigg, A.

    2011-01-01

    In the functional approach to quantum chromodynamics, the properties of hadronic bound states are accessible via covariant integral equations, e.g. the Bethe–Salpeter equation for mesons. In particular, one has to deal with linear, homogeneous integral equations which, in sophisticated model setups, use numerical representations of the solutions of other integral equations as part of their input. Analogously, inhomogeneous equations can be constructed to obtain off-shell information in addition to bound-state masses and other properties obtained from the covariant analogue to a wave function of the bound state. These can be solved very efficiently using well-known matrix algorithms for eigenvalues (in the homogeneous case) and the solution of linear systems (in the inhomogeneous case). We demonstrate this by solving the homogeneous and inhomogeneous Bethe–Salpeter equations and find, e.g. that for the calculation of the mass spectrum it is as efficient or even advantageous to use the inhomogeneous equation as compared to the homogeneous. This is valuable insight, in particular for the study of baryons in a three-quark setup and more involved systems. PMID:21760640

  14. Species-dependent binding of new synthesized bicalutamide analogues to albumin by optical biosensor analysis.

    PubMed

    Fortugno, Cecilia; van der Gronde, Toon; Varchi, Greta; Guerrini, Andrea; Bertucci, Carlo

    2015-01-01

    The binding of some novel bicalutamide analogues to human serum albumin (HSA) and rat serum albumin (RSA) was investigated by surface plasmon resonance (SPR) based optical biosensor technique. The serum protein binding of the bicalutamide analogues was determined and compared to that of the parent compound. Furthermore, HSA and RSA were used as target plasma proteins, in order to highlight possible differences among species when performing pharmacokinetic studies. HSA and RSA were covalently immobilized on carboxymethyl dextran matrixes, using an amine coupling procedure. The anchoring method was validated by determining the dissociation constant (KD) of a standard analyte to confirm that the binding properties of the proteins were maintained. The ranking of the bicalutamide analogues for their HSA and RSA bound fractions was used to compare the behaviour of the two albumins. Most of the bicalutamide analogues showed higher binding levels with respect to the lead compound, (R)-bicalutamide. Further, meaningful differences in the binding level to the two serum proteins were obtained. The dissociation constants (KD) of the interaction between the lead compound, (R)-bicalutamide, and the two proteins were calculated. As a result, the KD obtained with HSA was one order of magnitude higher than that obtained with RSA. The observed differences in the HSA and RSA bonding of the bicalutamide analogues increase the knowledge on the possible low reliability in extrapolating the distribution data obtained on animals to humans. This work demonstrates that SPR based optical biosensor technique is well suited for the medium-high throughput screening of compounds' ligand binding to serum albumins.

  15. Fluorescent Risedronate Analogues Reveal Bisphosphonate Uptake by Bone Marrow Monocytes and Localization Around Osteocytes In Vivo

    PubMed Central

    Roelofs, Anke J; Coxon, Fraser P; Ebetino, Frank H; Lundy, Mark W; Henneman, Zachary J; Nancollas, George H; Sun, Shuting; Blazewska, Katarzyna M; Bala, Joy Lynn F; Kashemirov, Boris A; Khalid, Aysha B; McKenna, Charles E; Rogers, Michael J

    2010-01-01

    Bisphosphonates are effective antiresorptive agents owing to their bone-targeting property and ability to inhibit osteoclasts. It remains unclear, however, whether any non-osteoclast cells are directly affected by these drugs in vivo. Two fluorescent risedronate analogues, carboxyfluorescein-labeled risedronate (FAM-RIS) and Alexa Fluor 647–labeled risedronate (AF647-RIS), were used to address this question. Twenty-four hours after injection into 3-month-old mice, fluorescent risedronate analogues were bound to bone surfaces. More detailed analysis revealed labeling of vascular channel walls within cortical bone. Furthermore, fluorescent risedronate analogues were present in osteocytic lacunae in close proximity to vascular channels and localized to the lacunae of newly embedded osteocytes close to the bone surface. Following injection into newborn rabbits, intracellular uptake of fluorescently labeled risedronate was detected in osteoclasts, and the active analogue FAM-RIS caused accumulation of unprenylated Rap1A in these cells. In addition, CD14high bone marrow monocytes showed relatively high levels of uptake of fluorescently labeled risedronate, which correlated with selective accumulation of unprenylated Rap1A in CD14+ cells, as well as osteoclasts, following treatment with risedronate in vivo. Similar results were obtained when either rabbit or human bone marrow cells were treated with fluorescent risedronate analogues in vitro. These findings suggest that the capacity of different cell types to endocytose bisphosphonate is a major determinant for the degree of cellular drug uptake in vitro as well as in vivo. In conclusion, this study shows that in addition to bone-resorbing osteoclasts, bisphosphonates may exert direct effects on bone marrow monocytes in vivo. © 2010 American Society for Bone and Mineral Research PMID:20422624

  16. Vasectomy and its reversal.

    PubMed

    Belker, A M

    1985-12-01

    Techniques, results, complications, and medicolegal aspects of vasectomy are discussed in this article. Emphasis is placed on techniques that prevent spontaneous recanalization of the ends of the vas deferens after vasectomy. Factors that affect the reversibility of vasectomy are discussed. New microsurgical techniques of vasectomy reversal are described, and results of these new techniques are compared with results of nonmicrosurgical techniques of vasectomy reversal. Indications for bypass vasoepididymostomy during vasectomy reversal procedures, as well as techniques for performing vasoepididymostomy, are discussed.

  17. Dumb holes: analogues for black holes.

    PubMed

    Unruh, W G

    2008-08-28

    The use of sonic analogues to black and white holes, called dumb or deaf holes, to understand the particle production by black holes is reviewed. The results suggest that the black hole particle production is a low-frequency and low-wavenumber process.

  18. 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.

  19. 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...

  20. Reverse Correlation in Neurophysiology

    ERIC Educational Resources Information Center

    Ringach, Dario; Shapley, Robert

    2004-01-01

    This article presents a review of reverse correlation in neurophysiology. We discuss the basis of reverse correlation in linear transducers and in spiking neurons. The application of reverse correlation to measure the receptive fields of visual neurons using white noise and m-sequences, and classical findings about spatial and color processing in…

  1. Chicoric acid analogues as HIV-1 integrase inhibitors.

    PubMed

    Lin, Z; Neamati, N; Zhao, H; Kiryu, Y; Turpin, J A; Aberham, C; Strebel, K; Kohn, K; Witvrouw, M; Pannecouque, C; Debyser, Z; De Clercq, E; Rice, W G; Pommier, Y; Burke, T R

    1999-04-22

    The present study was undertaken to examine structural features of L-chicoric acid (3) which are important for potency against purified HIV-1 integrase and for reported cytoprotective effects in cell-based systems. Through a progressive series of analogues, it was shown that enantiomeric D-chicoric acid (4) retains inhibitory potency against purified integrase equal to its L-counterpart and further that removal of either one or both carboxylic functionalities results in essentially no loss of inhibitory potency. Additionally, while two caffeoyl moieties are required, attachment of caffeoyl groups to the central linking structure can be achieved via amide or mixed amide/ester linkages. More remarkable is the finding that blockage of the catechol functionality through conversion to tetraacetate esters results in almost no loss of potency, contingent on the presence of at least one carboxyl group on the central linker. Taken as a whole, the work has resulted in the identification of new integrase inhibitors which may be regarded as bis-caffeoyl derivatives of glycidic acid and amino acids such as serine and beta-aminoalanine. The present study also examined the reported ability of chicoric acid to exert cytoprotective effects in HIV-infected cells. It was demonstrated in target and cell-based assays that the chicoric acids do not significantly inhibit other targets associated with HIV-1 replication, including reverse transcription, protease function, NCp7 zinc finger function, or replication of virus from latently infected cells. In CEM cells, for both the parent chicoric acid and selected analogues, antiviral activity was observable under specific assay conditions and with high dependence on the multiplicity of viral infection. However, against HIV-1- and HIV-2-infected MT-4 cells, the chicoric acids and their tetraacetylated esters exhibited antiviral activity (50% effective concentration (EC50) ranging from 1.7 to 20 microM and 50% inhibitory concentration (IC50

  2. [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.

  3. Aluminofluorides and beryllofluorides as inhibitors of sulphatases. Analogues of hydrogen sulphate?

    PubMed Central

    Roy, A B

    1991-01-01

    The inhibition of fluoride of sulphatase A from ox liver and of the sulphatases of Helix pomatia and Aspergillus oryzae is decreased by EDTA and increased by Al3+ or Be2+, implicating aluminofluorides and beryllofluorides in the reaction. The inhibition, which is reversible, takes several minutes to develop fully and, at least for the sulphatase of H. pomatia, is of a non-linear mixed competitive-non-competitive type. It is suggested that the aluminofluorides and beryllofluorides are acting as analogues of HSO4-. If so, then this behaviour must be considered, as well as their role as analogues of phosphate, in interpreting the effects of these compounds in intact cells. PMID:1953634

  4. Maximum common subgraph: some upper bound and lower bound results

    PubMed Central

    Huang, Xiuzhen; Lai, Jing; Jennings, Steven F

    2006-01-01

    Background Structure matching plays an important part in understanding the functional role of biological structures. Bioinformatics assists in this effort by reformulating this process into a problem of finding a maximum common subgraph between graphical representations of these structures. Among the many different variants of the maximum common subgraph problem, the maximum common induced subgraph of two graphs is of special interest. Results Based on current research in the area of parameterized computation, we derive a new lower bound for the exact algorithms of the maximum common induced subgraph of two graphs which is the best currently known. Then we investigate the upper bound and design techniques for approaching this problem, specifically, reducing it to one of finding a maximum clique in the product graph of the two given graphs. Considering the upper bound result, the derived lower bound result is asymptotically tight. Conclusion Parameterized computation is a viable approach with great potential for investigating many applications within bioinformatics, such as the maximum common subgraph problem studied in this paper. With an improved hardness result and the proposed approaches in this paper, future research can be focused on further exploration of efficient approaches for different variants of this problem within the constraints imposed by real applications. PMID:17217524

  5. Quantum Operation Time Reversal

    SciTech Connect

    Crooks, Gavin E.

    2008-03-25

    The dynamics of an open quantum system can be described by a quantum operation: A linear, complete positive map of operators. Here, I exhibit a compact expression for the time reversal of a quantum operation, which is closely analogous to the time reversal of a classical Markov transition matrix. Since open quantum dynamics are stochastic, and not, in general, deterministic, the time reversal is not, in general, an inversion of the dynamics. Rather, the system relaxes toward equilibrium in both the forward and reverse time directions. The probability of a quantum trajectory and the conjugate, time reversed trajectory are related by the heat exchanged with the environment.

  6. Uncertainty bounds using sector theory

    NASA Technical Reports Server (NTRS)

    Waszak, Martin R.; Schmidt, David K.

    1989-01-01

    An approach based on sector-stability theory can furnish a description of the uncertainty associated with the frequency response of a model, given sector-bounds on the individual parameters of the model. The application of the sector-based approach to the formulation of useful uncertainty descriptions for linear, time-invariant multivariable systems is presently explored, and the approach is applied to two generic forms of parameter uncertainty in order to investigate its advantages and limitations. The results obtained show that sector-uncertainty bounds can be used to evaluate the impact of parameter uncertainties on the frequency response of the design model.

  7. Tryptophan analogues. 1. Synthesis and antihypertensive activity of positional isomers.

    PubMed

    Safdy, M E; Kurchacova, E; Schut, R N; Vidrio, H; Hong, E

    1982-06-01

    A series of tryptophan analogues having the carboxyl function at the beta-position was synthesized and tested for antihypertensive activity. The 5-methoxy analogue 46 exhibited antihypertensive activity in the rat via the oral route and was much more potent than the normal tryptophan analogue. The methyl ester was found to be a critical structural feature for activity.

  8. Entropic uncertainty and measurement reversibility

    NASA Astrophysics Data System (ADS)

    Berta, Mario; Wehner, Stephanie; Wilde, Mark M.

    2015-11-01

    The entropic uncertainty relation with quantum side information (EUR-QSI) from [Berta et al., Nat. Phys. 6, 659 (2010)] is a unifying principle relating two distinctive features of quantum mechanics: quantum uncertainty due to measurement incompatibility, and entanglement. In these relations, quantum uncertainty takes the form of preparation uncertainty where one of two incompatible measurements is applied. In particular, the "uncertainty witness" lower bound in the EUR-QSI is not a function of a post-measurement state. An insightful proof of the EUR-QSI from [Coles et al., Phys. Rev. Lett. 108, 210405 (2012)] makes use of a fundamental mathematical consequence of the postulates of quantum mechanics known as the non-increase of quantum relative entropy under quantum channels. Here, we exploit this perspective to establish a tightening of the EUR-QSI which adds a new state-dependent term in the lower bound, related to how well one can reverse the action of a quantum measurement. As such, this new term is a direct function of the post-measurement state and can be thought of as quantifying how much disturbance a given measurement causes. Our result thus quantitatively unifies this feature of quantum mechanics with the others mentioned above. We have experimentally tested our theoretical predictions on the IBM Quantum Experience and find reasonable agreement between our predictions and experimental outcomes.

  9. Entropic uncertainty and measurement reversibility

    NASA Astrophysics Data System (ADS)

    Berta, Mario; Wehner, Stephanie; Wilde, Mark M.

    2016-07-01

    The entropic uncertainty relation with quantum side information (EUR-QSI) from (Berta et al 2010 Nat. Phys. 6 659) is a unifying principle relating two distinctive features of quantum mechanics: quantum uncertainty due to measurement incompatibility, and entanglement. In these relations, quantum uncertainty takes the form of preparation uncertainty where one of two incompatible measurements is applied. In particular, the ‘uncertainty witness’ lower bound in the EUR-QSI is not a function of a post-measurement state. An insightful proof of the EUR-QSI from (Coles et al 2012 Phys. Rev. Lett. 108 210405) makes use of a fundamental mathematical consequence of the postulates of quantum mechanics known as the non-increase of quantum relative entropy under quantum channels. Here, we exploit this perspective to establish a tightening of the EUR-QSI which adds a new state-dependent term in the lower bound, related to how well one can reverse the action of a quantum measurement. As such, this new term is a direct function of the post-measurement state and can be thought of as quantifying how much disturbance a given measurement causes. Our result thus quantitatively unifies this feature of quantum mechanics with the others mentioned above. We have experimentally tested our theoretical predictions on the IBM quantum experience and find reasonable agreement between our predictions and experimental outcomes.

  10. Loosely-Bound Diatomic Molecules.

    ERIC Educational Resources Information Center

    Balfour, W. J.

    1979-01-01

    Discusses concept of covalent bonding as related to homonuclear diatomic molecules. Article draws attention to the existence of bound rare gas and alkaline earth diatomic molecules. Summarizes their molecular parameters and offers spectroscopic data. Strength and variation with distance of interatomic attractive forces is given. (Author/SA)

  11. Variational Bounds for Creeping Composites

    NASA Astrophysics Data System (ADS)

    Procházka, Petr

    2010-05-01

    In the paper time dependent variational bounds are derived based on Extended Hashin-Shtrikman variational principles. Direct calculation leads to explicit formulas to be presented in the text. For various mechanical properties easy coding in Excel, say, can be used and verification of accuracy for numerical procedures is available using the derived formulas.

  12. Pieter Paul Rubens, "Prometheus Bound."

    ERIC Educational Resources Information Center

    Shoemaker, Marla K.

    1986-01-01

    Provides a full-color reproduction of Pieter Paul Rubens' painting, "Prometheus Bound," and a lesson plan for using it with students in grades 10 through 12. The goal of the lesson is to introduce students to the techniques of design and execution used by Rubens. (JDH)

  13. Teacher Education in Outward Bound.

    ERIC Educational Resources Information Center

    Robinson, Richard A.

    A series of Outward Bound programs and experiences was planned for El Paso County, Colorado, school teachers to increase their awareness of their personal characteristics, especially those that might enhance learning on the part of their students. Part of the planning for the program involved a survey of county high school teachers, counselors,…

  14. Wronskian Method for Bound States

    ERIC Educational Resources Information Center

    Fernandez, Francisco M.

    2011-01-01

    We propose a simple and straightforward method based on Wronskians for the calculation of bound-state energies and wavefunctions of one-dimensional quantum-mechanical problems. We explicitly discuss the asymptotic behaviour of the wavefunction and show that the allowed energies make the divergent part vanish. As illustrative examples we consider…

  15. Boundedness of solutions for reversible system via Moser's twist theorem

    NASA Astrophysics Data System (ADS)

    Piao, Daxiong; Li, Wenling

    2008-05-01

    In this paper we consider the problem of the boundedness of all solutions for the reversible system It is shown that all the solutions are bounded provided that the ai(t) (0[less-than-or-equals, slant]i[less-than-or-equals, slant][(n-1)/2]) are of bounded variation in [0,1] and the derivatives of bj(t) and ai(t) are Lipschitzian. It is also shown that there exist ai's being discontinuous everywhere such that all solutions of the equation are bounded. This implies that the continuity of ai's is not necessary for the boundedness of solutions of the equation.

  16. Titania bound sodium titanate ion exchanger

    DOEpatents

    DeFilippi, Irene C. G.; Yates, Stephen Frederic; Shen, Jian-Kun; Gaita, Romulus; Sedath, Robert Henry; Seminara, Gary Joseph; Straszewski, Michael Peter; Anderson, David Joseph

    1999-03-23

    This invention is method for preparing a titania bound ion exchange composition comprising admixing crystalline sodium titanate and a hydrolyzable titanium compound and, thereafter drying the titania bound crystalline sodium titanate and subjecting the dried titania bound ion exchange composition to optional compaction and calcination steps to improve the physical strength of the titania bound composition.

  17. The eyeglass reversal.

    PubMed

    Oh, Songjoo

    2011-07-01

    Some figures, such as the Necker cube, are spontaneously reversible between alternative percepts. Before learning those skilled reversals, how do people achieve reversals for the very first time? It has been known that, in the case of a first reversal, people can be expected to see the reversal when given specific information about how the figures are ambiguous. This point was confirmed by using drawing versions of reversible figures. To demonstrate how intention plays a role in the initial reversal of a real object, a pair of regular eyeglasses, reversible in perspective, were presented to naïve observers in monocular vision. When the eyeglasses were viewed inwardly and the observers were given information that the eyeglasses could be ambiguous, they were able to easily see the reversal. When the eyeglasses were viewed outwardly, observers saw it only after they had been informed of exactly what the two alternative percepts were.Interestingly, many observers often mistakenly saw the inwardly viewed eyeglasses as placed outwardly from the beginning of the observation, while they saw the outwardly viewed eyeglasses correctly. Taking these results together, for the first reversal of a real object, the specificity of intention varies with the ambiguity of the object.

  18. Transversely bounded DFB lasers. [bounded distributed-feedback lasers

    NASA Technical Reports Server (NTRS)

    Elachi, C.; Evans, G.; Yeh, C.

    1975-01-01

    Bounded distributed-feedback (DFB) lasers are studied in detail. Threshold gain and field distribution for a number of configurations are derived and analyzed. More specifically, the thin-film guide, fiber, diffusion guide, and hollow channel with inhomogeneous-cladding DFB lasers are considered. Optimum points exist and must be used in DFB laser design. Different-modes feedback and the effects of the transverse boundaries are included. A number of applications are also discussed.

  19. Optimization of propafenone analogues as antimalarial leads.

    PubMed

    Lowes, David J; Guiguemde, W Armand; Connelly, Michele C; Zhu, Fangyi; Sigal, Martina S; Clark, Julie A; Lemoff, Andrew S; Derisi, Joseph L; Wilson, Emily B; Guy, R Kiplin

    2011-11-10

    Propafenone, a class Ic antiarrythmic drug, inhibits growth of cultured Plasmodium falciparum. While the drug's potency is significant, further development of propafenone as an antimalarial would require divorcing the antimalarial and cardiac activities as well as improving the pharmacokinetic profile of the drug. A small array of propafenone analogues was designed and synthesized to address the cardiac ion channel and PK liabilities. Testing of this array revealed potent inhibitors of the 3D7 (drug sensitive) and K1 (drug resistant) strains of P. falciparum that possessed significantly reduced ion channel effects and improved metabolic stability. Propafenone analogues are unusual among antimalarial leads in that they are more potent against the multidrug resistant K1 strain of P. falciparum compared to the 3D7 strain.

  20. Enzymatic synthesis of lipid II and analogues.

    PubMed

    Huang, Lin-Ya; Huang, Shih-Hsien; Chang, Ya-Chih; Cheng, Wei-Chieh; Cheng, Ting-Jen R; Wong, Chi-Huey

    2014-07-28

    The emergence of antibiotic resistance has prompted active research in the development of antibiotics with new modes of action. Among all essential bacterial proteins, transglycosylase polymerizes lipid II into peptidoglycan and is one of the most favorable targets because of its vital role in peptidoglycan synthesis. Described in this study is a practical enzymatic method for the synthesis of lipid II, coupled with cofactor regeneration, to give the product in a 50-70% yield. This development depends on two key steps: the overexpression of MraY for the synthesis of lipid I and the use of undecaprenol kinase for the preparation of polyprenol phosphates. This method was further applied to the synthesis of lipid II analogues. It was found that MraY and undecaprenol kinase can accept a wide range of lipids containing various lengths and configurations. The activity of lipid II analogues for bacterial transglycolase was also evaluated.

  1. Perspective: reverse evolution.

    PubMed

    Teotónio, H; Rose, M R

    2001-04-01

    For some time, the reversibility of evolution was primarily discussed in terms of comparative patterns. Only recently has this problem been studied using experimental evolution over shorter evolutionary time frames. This has raised questions of definition, experimental procedure, and the hypotheses being tested. Experimental evolution has provided evidence for multiple population genetic mechanisms in reverse evolution, including pleiotropy and mutation accumulation. It has also pointed to genetic factors that might prevent reverse evolution, such as a lack of genetic variability, epistasis, and differential genotype-by-environment interactions. The main focus of this perspective is on laboratory studies and their relevance to the genetics of reverse evolution. We discuss reverse evolution experiments with Drosophila, bacterial, and viral populations. Field studies of the reverse evolution of melanism in the peppered moth are also reviewed.

  2. Reversible logic for supercomputing.

    SciTech Connect

    DeBenedictis, Erik P.

    2005-05-01

    This paper is about making reversible logic a reality for supercomputing. Reversible logic offers a way to exceed certain basic limits on the performance of computers, yet a powerful case will have to be made to justify its substantial development expense. This paper explores the limits of current, irreversible logic for supercomputers, thus forming a threshold above which reversible logic is the only solution. Problems above this threshold are discussed, with the science and mitigation of global warming being discussed in detail. To further develop the idea of using reversible logic in supercomputing, a design for a 1 Zettaflops supercomputer as required for addressing global climate warming is presented. However, to create such a design requires deviations from the mainstream of both the software for climate simulation and research directions of reversible logic. These deviations provide direction on how to make reversible logic practical.

  3. Polyamine analogues targeting epigenetic gene regulation.

    PubMed

    Huang, Yi; Marton, Laurence J; Woster, Patrick M; Casero, Robert A

    2009-11-04

    Over the past three decades the metabolism and functions of the polyamines have been actively pursued as targets for antineoplastic therapy. Interactions between cationic polyamines and negatively charged nucleic acids play a pivotal role in DNA stabilization and RNA processing that may affect gene expression, translation and protein activity. Our growing understanding of the unique roles that the polyamines play in chromatin regulation, and the discovery of novel proteins homologous with specific regulatory enzymes in polyamine metabolism, have led to our interest in exploring chromatin remodelling enzymes as potential therapeutic targets for specific polyamine analogues. One of our initial efforts focused on utilizing the strong affinity that the polyamines have for chromatin to create a backbone structure, which could be combined with active-site-directed inhibitor moieties of HDACs (histone deacetylases). Specific PAHAs (polyaminohydroxamic acids) and PABAs (polyaminobenzamides) polyamine analogues have demonstrated potent inhibition of the HDACs, re-expression of p21 and significant inhibition of tumour growth. A second means of targeting the chromatin-remodelling enzymes with polyamine analogues was facilitated by the recent identification of flavin-dependent LSD1 (lysine-specific demethylase 1). The existence of this enzyme demonstrated that histone lysine methylation is a dynamic process similar to other histone post-translational modifications. LSD1 specifically catalyses demethylation of mono- and di-methyl Lys4 of histone 3, key positive chromatin marks associated with transcriptional activation. Structural and catalytic similarities between LSD1 and polyamine oxidases facilitated the identification of biguanide, bisguanidine and oligoamine polyamine analogues that are potent inhibitors of LSD1. Cellular inhibition of LSD1 by these unique compounds led to the re-activation of multiple epigenetically silenced genes important in tumorigenesis. The use of

  4. Benchmarking analogue models of brittle thrust wedges

    NASA Astrophysics Data System (ADS)

    Schreurs, Guido; Buiter, Susanne J. H.; Boutelier, Jennifer; Burberry, Caroline; Callot, Jean-Paul; Cavozzi, Cristian; Cerca, Mariano; Chen, Jian-Hong; Cristallini, Ernesto; Cruden, Alexander R.; Cruz, Leonardo; Daniel, Jean-Marc; Da Poian, Gabriela; Garcia, Victor H.; Gomes, Caroline J. S.; Grall, Céline; Guillot, Yannick; Guzmán, Cecilia; Hidayah, Triyani Nur; Hilley, George; Klinkmüller, Matthias; Koyi, Hemin A.; Lu, Chia-Yu; Maillot, Bertrand; Meriaux, Catherine; Nilfouroushan, Faramarz; Pan, Chang-Chih; Pillot, Daniel; Portillo, Rodrigo; Rosenau, Matthias; Schellart, Wouter P.; Schlische, Roy W.; Take, Andy; Vendeville, Bruno; Vergnaud, Marine; Vettori, Matteo; Wang, Shih-Hsien; Withjack, Martha O.; Yagupsky, Daniel; Yamada, Yasuhiro

    2016-11-01

    We performed a quantitative comparison of brittle thrust wedge experiments to evaluate the variability among analogue models and to appraise the reproducibility and limits of model interpretation. Fifteen analogue modeling laboratories participated in this benchmark initiative. Each laboratory received a shipment of the same type of quartz and corundum sand and all laboratories adhered to a stringent model building protocol and used the same type of foil to cover base and sidewalls of the sandbox. Sieve structure, sifting height, filling rate, and details on off-scraping of excess sand followed prescribed procedures. Our analogue benchmark shows that even for simple plane-strain experiments with prescribed stringent model construction techniques, quantitative model results show variability, most notably for surface slope, thrust spacing and number of forward and backthrusts. One of the sources of the variability in model results is related to slight variations in how sand is deposited in the sandbox. Small changes in sifting height, sifting rate, and scraping will result in slightly heterogeneous material bulk densities, which will affect the mechanical properties of the sand, and will result in lateral and vertical differences in peak and boundary friction angles, as well as cohesion values once the model is constructed. Initial variations in basal friction are inferred to play the most important role in causing model variability. Our comparison shows that the human factor plays a decisive role, and even when one modeler repeats the same experiment, quantitative model results still show variability. Our observations highlight the limits of up-scaling quantitative analogue model results to nature or for making comparisons with numerical models. The frictional behavior of sand is highly sensitive to small variations in material state or experimental set-up, and hence, it will remain difficult to scale quantitative results such as number of thrusts, thrust spacing

  5. Antitumoral cyclic peptide analogues of chlamydocin.

    PubMed

    Bernardi, E; Fauchere, J L; Atassi, G; Viallefont, P; Lazaro, R

    1993-01-01

    A series of cyclic tetrapeptides bearing the bioactive alkylating group on an epsilon-amino-lysyl function have been examined for their antitumoral activity on L1210 and P388 murine leukemia cell lines. One analogue belonging to the chlamydocin family and bearing a beta-chloroethylnitrosourea group was found to be potent at inhibiting L1210 cell proliferation and had a higher therapeutic index than the reference compound bis-beta-chloroethylnitrosourea (BCNU) on the in vivo P388-induced leukemia model.

  6. 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

  7. 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.

  8. Reversible cortical blindness: posterior reversible encephalopathy syndrome.

    PubMed

    Bandyopadhyay, Sabyasachi; Mondal, Kanchan Kumar; Das, Somnath; Gupta, Anindya; Biswas, Jaya; Bhattacharyya, Subir Kumar; Biswas, Gautam

    2010-11-01

    Cortical blindness is defined as visual failure with preserved pupillary reflexes in structurally intact eyes due to bilateral lesions affecting occipital cortex. Bilateral oedema and infarction of the posterior and middle cerebral arterial territory, trauma, glioma and meningioma of the occipital cortex are the main causes of cortical blindness. Posterior reversible encephalopathy syndrome (PRES) refers to the reversible subtype of cortical blindness and is usually associated with hypertension, diabetes, immunosuppression, puerperium with or without eclampsia. Here, 3 cases of PRES with complete or partial visual recovery following treatment in 6-month follow-up are reported.

  9. Thymidine analogues for tracking DNA synthesis.

    PubMed

    Cavanagh, Brenton L; Walker, Tom; Norazit, Anwar; Meedeniya, Adrian C B

    2011-09-15

    Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation. Tritiated thymidine, targeted using autoradiography was technically demanding and superseded by 5-bromo-2-deoxyuridine (BrdU) and related halogenated analogues, detected using antibodies. Their detection required the denaturation of DNA, often constraining the outcome of investigations. Despite these limitations BrdU alone has been used to target newly synthesised DNA in over 20,000 reviewed biomedical studies. A recent breakthrough in "tagging DNA synthesis" is the thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU). The alkyne group in EdU is readily detected using a fluorescent azide probe and copper catalysis using 'Huisgen's reaction' (1,3-dipolar cycloaddition or 'click chemistry'). This rapid, two-step biolabelling approach allows the tagging and imaging of DNA within cells whilst preserving the structural and molecular integrity of the cells. The bio-orthogonal detection of EdU allows its application in more experimental assays than previously possible with other "unnatural bases". These include physiological, anatomical and molecular biological experimentation in multiple fields including, stem cell research, cancer biology, and parasitology. The full potential of EdU and related molecules in biomedical research remains to be explored.

  10. 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

  11. Secure Key from Bound Entanglement

    NASA Astrophysics Data System (ADS)

    Horodecki, Karol; Horodecki, Michał; Horodecki, Paweł; Oppenheim, Jonathan

    2005-04-01

    We characterize the set of shared quantum states which contain a cryptographically private key. This allows us to recast the theory of privacy as a paradigm closely related to that used in entanglement manipulation. It is shown that one can distill an arbitrarily secure key from bound entangled states. There are also states that have less distillable private keys than the entanglement cost of the state. In general, the amount of distillable key is bounded from above by the relative entropy of entanglement. Relationships between distillability and distinguishability are found for a class of states which have Bell states correlated to separable hiding states. We also describe a technique for finding states exhibiting irreversibility in entanglement distillation.

  12. Lower Bounds on Paraclique Density.

    PubMed

    Hagan, Ronald D; Langston, Michael A; Wang, Kai

    2016-05-11

    The scientific literature teems with clique-centric clustering strategies. In this paper we analyze one such method, the paraclique algorithm. Paraclique has found practical utility in a variety of application domains, and has been successfully employed to reduce the effects of noise. Nevertheless, its formal analysis and worst-case guarantees have remained elusive. We address this issue by deriving a series of lower bounds on paraclique densities.

  13. 78 FR 18326 - Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math Science... Upward Bound Math Science Annual Performance Report. OMB Control Number: 1840-NEW. Type of Review: New... under the regular Upward Bound (UB) and Upward Bound Math and Science (UBMS) Programs. The Department...

  14. Information bounds for Gaussian copulas

    PubMed Central

    Hoff, Peter D.; Niu, Xiaoyue; Wellner, Jon A.

    2013-01-01

    Often of primary interest in the analysis of multivariate data are the copula parameters describing the dependence among the variables, rather than the univariate marginal distributions. Since the ranks of a multivariate dataset are invariant to changes in the univariate marginal distributions, rank-based estimators are natural candidates for semiparametric copula estimation. Asymptotic information bounds for such estimators can be obtained from an asymptotic analysis of the rank likelihood, i.e. the probability of the multivariate ranks. In this article, we obtain limiting normal distributions of the rank likelihood for Gaussian copula models. Our results cover models with structured correlation matrices, such as exchangeable or circular correlation models, as well as unstructured correlation matrices. For all Gaussian copula models, the limiting distribution of the rank likelihood ratio is shown to be equal to that of a parametric likelihood ratio for an appropriately chosen multivariate normal model. This implies that the semiparametric information bounds for rank-based estimators are the same as the information bounds for estimators based on the full data, and that the multivariate normal distributions are least favorable. PMID:25313292

  15. Hydrogen adsorption in thin films of Prussian blue analogue

    SciTech Connect

    Yang, Dali; Ding, Vivian; Luo, Junhua; Currier, Robert P; Obrey, Steve; Zhao, Yusheng

    2008-01-01

    Quartz crystal microbalance with dissipation (QCM-D) measurement was used to investigate the kinetics of the molecular hydrogen adsorption into thin films of prussian blue analogues - Cu{sub 3}[Co(CN){sub 6}]{sub 2} at ambient conditions. Although the equilibrium adsorption seems to be independent of the thickness, the adsorption rate substantially decreases with the thickness of the films. In addition, the reversibility of H{sub 2} adsorption into the Cu{sub 3}[Co(CN){sub 6}]{sub 2} films was investigated. The results indicate that the Cu{sub 3}[Co(CN){sub 6}]{sub 2} maily interacts with H{sub 2} molecules physically. The highest H{sub 2} uptake by the Cu{sub 3}[Co(CN){sub 6}]{sub 2} films is obtained when the gas phase is stagnant inside the testing cell. However, the unusual high H{sub 2} uptake obtained from the QCM-D measurement makes us question how reliable this analytic methodology is.

  16. Muscarinic receptor subtype selectivity of novel heterocyclic QNB analogues

    SciTech Connect

    Baumgold, J.; Cohen, V.I.; Paek, R.; Reba, R.C. )

    1991-01-01

    In an effort at synthesizing centrally-active subtype-selective antimuscarinic agents, the authors derivatized QNB (quinuclidinyl benzilate), a potent muscarinic antagonist, by replacing one of the phenyl groups with less lipophilic heterocyclic moieties. The displacement of ({sup 3}H)-N-methyl scopolamine binding by these novel compounds to membranes from cells expressing ml - m4 receptor subtypes was determined. Most of the novel 4-bromo-QNB analogues were potent and slightly selective for ml receptors. The 2-thienyl derivative was the most potent, exhibiting a 2-fold greater potency than BrQNB at ml receptors, and a 4-fold greater potency than BrQNB at ml receptors, and a 4-fold greater potency at m2 receptors. This compound was also considerably less lipophilic than BrQNB as determined from its retention time on C18 reverse phase HPLC. This compound may therefore be useful both for pharmacological studies and as a candidate for a radioiodinated SPECT imaging agent for ml muscarinic receptors in human brain.

  17. 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.

  18. Quantum secret sharing schemes and reversibility of quantum operations

    SciTech Connect

    Ogawa, Tomohiro; Sasaki, Akira; Iwamoto, Mitsugu; Yamamoto, Hirosuke

    2005-09-15

    Quantum secret sharing schemes encrypting a quantum state into a multipartite entangled state are treated. The lower bound on the dimension of each share given by Gottesman [Phys. Rev. A 61, 042311 (2000)] is revisited based on a relation between the reversibility of quantum operations and the Holevo information. We also propose a threshold ramp quantum secret sharing scheme and evaluate its coding efficiency.

  19. Behavior of a fluorescent analogue of calmodulin in living 3T3 cells

    PubMed Central

    1985-01-01

    interacts with intracellular components with a range of affinities. The mobility of LRB-CM in the cytoplasm was sensitive to treatment of the cells with trifluoperazine, which suggests that at least some of the intracellular binding sites are specific for calmodulin in the calcium-bound form. FRAP of LRB-CM in the nuclei of living 3T3 cells indicated that the analogue was highly mobile within the nucleus but entered the nucleus from the cytoplasm much more slowly than fluorescein isothiocyanate-dextran of comparable molecular size and much more slowly than predicted from its mobility in cytoplasm. PMID:4044638

  20. Reversibility and energy dissipation in adiabatic superconductor logic.

    PubMed

    Takeuchi, Naoki; Yamanashi, Yuki; Yoshikawa, Nobuyuki

    2017-12-01

    Reversible computing is considered to be a key technology to achieve an extremely high energy efficiency in future computers. In this study, we investigated the relationship between reversibility and energy dissipation in adiabatic superconductor logic. We analyzed the evolution of phase differences of Josephson junctions in the reversible quantum-flux-parametron (RQFP) gate and confirmed that the phase differences can change time reversibly, which indicates that the RQFP gate is physically, as well as logically, reversible. We calculated energy dissipation required for the RQFP gate to perform a logic operation and numerically demonstrated that the energy dissipation can fall below the thermal limit, or the Landauer bound, by lowering operation frequencies. We also investigated the 1-bit-erasure gate as a logically irreversible gate and the quasi-RQFP gate as a physically irreversible gate. We calculated the energy dissipation of these irreversible gates and showed that the energy dissipation of these gate is dominated by non-adiabatic state changes, which are induced by unwanted interactions between gates due to logical or physical irreversibility. Our results show that, in reversible computing using adiabatic superconductor logic, logical and physical reversibility are required to achieve energy dissipation smaller than the Landauer bound without non-adiabatic processes caused by gate interactions.

  1. Aniline mustard analogues of the DNA-intercalating agent amsacrine: DNA interaction and biological activity.

    PubMed

    Fan, J Y; Valu, K K; Woodgate, P D; Baguley, B C; Denny, W A

    1997-04-01

    Two series of analogues of the clinical antileukemic drug and DNA-intercalating ligand amsacrine have been prepared, containing aniline mustard sidechains of varying reactivity, linked either at the 4-position of the intercalating acridine chromophore (type A) or at the 1'-position of the 9-anilino group (type B). DNase I footprinting assays showed that compounds of type B had stronger reversible binding to DNA than did compounds of type A. Compounds of each type showed similar patterns of alkylation-induced cleavage of DNA, and alkylate at the N7 of guanines in runs of guanines (similar to the pattern for untargeted mustards) as well as some adenines. Both classes of compounds crosslinked DNA, although those bearing relatively inactive mustards did so only at high drug/base pair ratios. However, while the patterns of DNA alkylation were broadly similar, the compounds were considerably more cytotoxic than analogous untargeted mustards. Comparison of their cytotoxicities in wild-type and DNA repair-deficient lines indicated this toxicity was due to DNA crosslinks (except for the least reactive SO2-linked mustards). The 4-linked analogues showed slightly higher in vivo antileukemic activity than the corresponding 1'-linked analogues.

  2. The carbonate analogues of 5'-halogenated resiniferatoxin as TRPV1 ligands.

    PubMed

    Lim, Kwang Su; Lee, Hobin; Kim, Sung Eun; Ha, Tae-Hwan; Ann, Jihyae; Son, Karam; Choi, Sun; Sun, Wei; Pearce, Larry V; DeAndrea-Lazarus, Ian A; Blumberg, Peter M; Lee, Jeewoo

    2013-10-01

    A series of carbonate analogues of 5'-halogenated RTX have been investigated in order to examine the effect of the carbonate group as a linker and the role of halogens in the reversal of activity from agonism to antagonism for rat and human TRPV1 heterologously expressed in Chinese hamster ovary cells. The carbonate analogues showed similar activities to the corresponding RTX derivatives in rat TRPV1 but lower potency in human TRPV1. 5-Halogenation converted the agonists to partial agonists or full antagonists and the extent of antagonism reflected the order of I>Br>Cl>F, with a somewhat greater extent of antagonism for the derivatives of the 4-amino RTX surrogates compared to the corresponding derivatives of RTX itself. The carbonate analogues of I-RTX (60) and 5-bromo-4-amino-RTX (66) were potent and full antagonists with Ki(ant)=2.23 and 2.46 nM, respectively, for rat TRPV1, which were ca. 5-fold more potent than I-RTX (2) under our conditions. The conformational analysis of the I-RTX-carbonate (60) indicated that its bent conformation was similar to that of I-RTX, consistent with compound 60 and I-RTX showing comparable potent antagonism.

  3. Lower bounds for randomized Exclusive Write PRAMs

    SciTech Connect

    MacKenzie, P.D.

    1995-05-02

    In this paper we study the question: How useful is randomization in speeding up Exclusive Write PRAM computations? Our results give further evidence that randomization is of limited use in these types of computations. First we examine a compaction problem on both the CREW and EREW PRAM models, and we present randomized lower bounds which match the best deterministic lower bounds known. (For the CREW PRAM model, the lower bound is asymptotically optimal.) These are the first non-trivial randomized lower bounds known for the compaction problem on these models. We show that our lower bounds also apply to the problem of approximate compaction. Next we examine the problem of computing boolean functions on the CREW PRAM model, and we present a randomized lower bound, which improves on the previous best randomized lower bound for many boolean functions, including the OR function. (The previous lower bounds for these functions were asymptotically optimal, but we improve the constant multiplicative factor.) We also give an alternate proof for the randomized lower bound on PARITY, which was already optimal to within a constant additive factor. Lastly, we give a randomized lower bound for integer merging on an EREW PRAM which matches the best deterministic lower bound known. In all our proofs, we use the Random Adversary method, which has previously only been used for proving lower bounds on models with Concurrent Write capabilities. Thus this paper also serves to illustrate the power and generality of this method for proving parallel randomized lower bounds.

  4. Bound Anionic States of Aadenine

    SciTech Connect

    Haranczyk, Maciej; Gutowski, Maciej S.; Li, Xiang; Bowen, Kit H.

    2007-03-20

    The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. Anionic states of nucleic acid bases are involved in DNA damage by low-energy electrons and in charge transfer through DNA. Previous gas phase studies of free, unsolvated nucleic acid base parent anions probed only dipole-bound states, which are not present in condensed phase environments, but did not observe valence anionic states, which for purine bases are thought to be adiabatically unbound. Contrary to this expectation,wehave demonstrated that some thus far ignored tautomers of adenine, which result from enamine-imine transformations, support valence anionic states with electron vertical detachment energies as large as 2.2 eV, and at least one of these anionic tautomers is adiabatically bound. Moreover, we predict that the new anionic tautomers should also dominate in solutions and should be characterized by larger values of electron vertical detachment energy than the canonical valence anion. All of the newfound anionic tautomers might be formed in the course of dissociative electron attachment followed by a hydrogen atom attachment to a carbon atom, and they might affect the structure and properties of DNA and RNA exposed to low-energy electrons. The new valence states observed here, unlike the dipole-bound state, could exist in condensed phases and might be relevant to radiobiological damage. The discovery of these valence anionic states of adenine was facilitated by the development of (i) an experimental method for preparing parent anions of nucleic acid bases for photoelectron experiments, and (ii) a combinatorial/quantum chemical approach for identification of the most stable tautomers of organic molecules.

  5. Bound Anionic States of Adenine

    SciTech Connect

    Haranczyk, Maciej; Gutowski, Maciej S.; Li, Xiang; Bowen, Kit H.

    2007-03-20

    The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. Anionic states of nucleic acid bases are involved in DNA damage by low-energy electrons and in charge transfer through DNA. Previous gas phase studies of free, unsolvated nucleic acid base parent anions probed only dipole-bound states, which are not present in condensed phase environments, but did not observe valence anionic states, which for purine bases are thought to be adiabatically unbound. Contrary to this expectation, we have demonstrated that some thus far ignored tautomers of adenine, which result from enamine-imine transformations, support valence anionic states with electron vertical detachment energies as large as 2.2 eV, and at least one of these anionic tautomers is adiabatically bound. Moreover, we predict that the new anionic tautomers should also dominate in solutions and should be characterized by larger values of electron vertical detachment energy than the canonical valence anion. All of the newfound anionic tautomers might be formed in the course of dissociative electron attachment followed by a hydrogen atom attachment to a carbon atom, and they might affect the structure and properties of DNA and RNA exposed to low-energy electrons. The new valence states observed here, unlike the dipole-bound state, could exist in condensed phases and might be relevant to radiobiological damage. The discovery of these valence anionic states of adenine was facilitated by the development of (i) an experimental method for preparing parent anions of nucleic acid bases for photoelectron experiments, and (it) a combinatorial/quantum chemical approach for identification of the most stable tautomers of organic molecules.

  6. Polyamine analogues bind human serum albumin.

    PubMed

    Beauchemin, R; N'soukpoé-Kossi, C N; Thomas, T J; Thomas, T; Carpentier, R; Tajmir-Riahi, H A

    2007-10-01

    Polyamine analogues show antitumor activity in experimental models, and their ability to alter activity of cytotoxic chemotherapeutic agents in breast cancer is well documented. Association of polyamines with nucleic acids and protein is included in their mechanism of action. The aim of this study was to examine the interaction of human serum albumin (HSA) with several polyamine analogues, such as 1,11-diamino-4,8-diazaundecane (333), 3,7,11,15-tetrazaheptadecane.4HCl (BE-333), and 3,7,11,15,19-pentazahenicosane.5HCl (BE-3333), in aqueous solution at physiological conditions using a constant protein concentration and various polyamine contents (microM to mM). FTIR, UV-visible, and CD spectroscopic methods were used to determine the polyamine binding mode and the effects of polyamine complexation on protein stability and secondary structure. Structural analysis showed that polyamines bind nonspecifically (H-bonding) via polypeptide polar groups with binding constants of K333 = 9.30 x 10(3) M(-1), KBE-333 = 5.63 x 10(2) M(-1), and KBE-3333 = 3.66 x 10(2) M(-1). The protein secondary structure showed major alterations with a reduction of alpha-helix from 55% (free protein) to 43-50% and an increase of beta-sheet from 17% (free protein) to 29-36% in the 333, BE-333, and BE-3333 complexes, indicating partial protein unfolding upon polyamine interaction. HSA structure was less perturbed by polyamine analogues compared to those of the biogenic polyamines.

  7. Error bounds in cascading regressions

    USGS Publications Warehouse

    Karlinger, M.R.; Troutman, B.M.

    1985-01-01

    Cascading regressions is a technique for predicting a value of a dependent variable when no paired measurements exist to perform a standard regression analysis. Biases in coefficients of a cascaded-regression line as well as error variance of points about the line are functions of the correlation coefficient between dependent and independent variables. Although this correlation cannot be computed because of the lack of paired data, bounds can be placed on errors through the required properties of the correlation coefficient. The potential meansquared error of a cascaded-regression prediction can be large, as illustrated through an example using geomorphologic data. ?? 1985 Plenum Publishing Corporation.

  8. New synthetic approaches towards analogues of bedaquiline.

    PubMed

    Priebbenow, Daniel L; Barbaro, Lisa; Baell, Jonathan B

    2016-10-12

    Multi-drug resistant tuberculosis (MDR-TB) is of growing global concern and threatens to undermine increasing efforts to control the worldwide spread of tuberculosis (TB). Bedaquiline has recently emerged as a new drug developed to specifically treat MDR-TB. Despite being highly effective as a result of its unique mode of action, bedaquiline has been associated with significant toxicities and as such, safety concerns are limiting its clinical use. In order to access pharmaceutical agents that exhibit an improved safety profile for the treatment of MDR-TB, new synthetic pathways to facilitate the preparation of bedaquiline and analogues thereof have been discovered.

  9. The Lehmer Matrix and Its Recursive Analogue

    DTIC Science & Technology

    2010-01-01

    for failing to comply with a collection of information if it does not display a currently valid OMB control number . 1. REPORT DATE 2010 2. REPORT...TYPE 3. DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE The Lehmer matrix and its recursive analogue 5a. CONTRACT NUMBER 5b...GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND

  10. 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.

  11. 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.

  12. Bounds on multipartite concurrence and tangle

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Li, Ming; Li, Hongfang; Fei, Shao-Ming; Li-Jost, Xianqing

    2016-10-01

    We present an analytical lower bound of multipartite concurrence based on the generalized Bloch representations of density matrices. It is shown that the lower bound can be used as an effective entanglement witness of genuine multipartite entanglement. Tight lower and upper bounds for multipartite tangles are also derived. Since the lower bounds depend on just part of the correlation tensors, the result is experimentally feasible.

  13. Finite Element Output Bounds for Hyperbolic Problems

    SciTech Connect

    Machiels, L.

    2000-03-27

    We propose a Neumann-subproblem a posteriori finite element error bound technique for linear stationary scalar advection problems. The method is similar in many respects to the previous output bound technique developed for elliptic problems. In the new approach, however, the primal residual is enhanced with a streamline diffusion term. We first formulate the bound algorithm, with particular emphasis on the proof of the bounding properties; then, we provide numerical results for an illustrative example.

  14. The Acquisition of Bound and Free Anaphora.

    ERIC Educational Resources Information Center

    Koster, Jan; Koster, Charlotte

    Most linguists assume that bound anaphors such as "himself" are connected with their antecedents in a different way from free anaphors such as "him." Bound anaphora resolution is deterministic, based on Principle A of Chomsky's binding theory. Free anaphors, pronominals, cannot be bound in the domain of reflexives (principle…

  15. Some Educational Implications & Contributions of Outward Bound.

    ERIC Educational Resources Information Center

    Australian Outward Bound School, Sydney.

    The development of Outward Bound, from the early beginnings in Britain through expansion in over 30 locations throughout the world, is outlined, and Outward Bound educational aspects are analyzed in terms of the Australian Outward Bound School. The concepts of experiential education, lifelong education, and the broader Australian educational scene…

  16. Consistent Tolerance Bounds for Statistical Distributions

    NASA Technical Reports Server (NTRS)

    Mezzacappa, M. A.

    1983-01-01

    Assumption that sample comes from population with particular distribution is made with confidence C if data lie between certain bounds. These "confidence bounds" depend on C and assumption about distribution of sampling errors around regression line. Graphical test criteria using tolerance bounds are applied in industry where statistical analysis influences product development and use. Applied to evaluate equipment life.

  17. Synthesis of a cyanopeptide-analogue with trypsin activating properties.

    PubMed

    Radau, G; Rauh, D

    2000-04-17

    An efficient synthesis of a peptidic analogue of cyanobacterial metabolites with proposed serine protease inhibitory activity has been developed. Surprisingly, one trypsin activating compound was obtained.

  18. An algebra of reversible computation.

    PubMed

    Wang, Yong

    2016-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules: basic reversible processes algebra, algebra of reversible communicating processes, recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

  19. Asymmetric dark matter bound state

    NASA Astrophysics Data System (ADS)

    Bi, Xiao-Jun; Kang, Zhaofeng; Ko, P.; Li, Jinmian; Li, Tianjun

    2017-02-01

    We propose an interesting framework for asymmetric scalar dark matter (ADM), which has novel collider phenomenology in terms of an unstable ADM bound state (ADMonium) produced via Higgs portals. ADMonium is a natural consequence of the basic features of ADM: the (complex scalar) ADM is charged under a dark local U (1 )d symmetry which is broken at a low scale and provides a light gauge boson X . The dark gauge coupling is strong and then ADM can annihilate away into X -pair effectively. Therefore, the ADM can form a bound state due to its large self-interaction via X mediation. To explore the collider signature of ADMonium, we propose that ADM has a two-Higgs doublet portal. The ADMonium can have a sizable mixing with the heavier Higgs boson, which admits a large cross section of ADMonium production associated with b b ¯. The resulting signature at the LHC depends on the decays of X . In this paper we consider a case of particular interest: p p →b b ¯ +ADMonium followed by ADMonium→2 X →2 e+e- where the electrons are identified as (un)converted photons. It may provide a competitive explanation to heavy di-photon resonance searches at the LHC.

  20. Quantum correlations beyond Tsirelson's bound

    NASA Astrophysics Data System (ADS)

    Berry, Dominic; Ringbauer, Martin; Fedrizzi, Alessandro; White, Andrew

    2014-03-01

    Violations of Bell inequalities show that there are correlations that cannot explained by any classical theory. Further violation, beyond Tsirelson's bound, shows that there are correlations that are not explained by quantum mechanics. Such super-quantum correlations would enable violation of information causality, where communication of one bit provides more than one bit of information [Nature 461, 1101 (2009)]. An unavoidable feature of all realistic Bell inequality experiments is loss. If one postselects on successful measurements, unentangled states can violate Bell inequalities. On the other hand, loss can be used to enhance the violation of Bell inequalities for entangled states. This can improve the ability to distinguish between entangled and unentangled states, despite loss. Here we report an optical experiment providing maximal violation of the CHSH-Bell inequality with entangled states. Due to loss and postselection, Tsirelson's bound is also violated. This enables us to more easily distinguish between entangled and unentangled states. In addition, it provides violation of information causality for the postselected data.

  1. Endurance bounds of aerial systems

    NASA Astrophysics Data System (ADS)

    Harrington, Aaron M.; Kroninger, Christopher M.

    2014-06-01

    Within the past few years micro aerial vehicles (MAVs) have received much more attention and are starting to proliferate into military as well as civilian roles. However, one of the major drawbacks for this technology currently, has been their poor endurance, usually below 10 minutes. This is a direct result of the inefficiencies inherent in their design. Often times, designers do not consider the various components in the vehicle design and match their performance to the desired mission for the vehicle. These vehicles lack a prescribed set of design guidelines or empirically derived design equations which often limits their design to selection of commercial off-the-shelf components without proper consideration of their affect on vehicle performance. In the current study, the design space for different vehicle configurations has been examined including insect flapping, avian flapping, rotary wing, and fixed wing, and their performance bounds are established. The propulsion system typical of a rotary wing vehicle is analyzed to establish current baselines for efficiency of vehicles at this scale. The power draw from communications is analyzed to determine its impact on vehicle performance. Finally, a representative fixed wing MAV is examined and the effects of adaptive structures as a means for increasing vehicle endurance and range are examined. This paper seeks to establish the performance bounds for micro air vehicles and establish a path forward for future designs so that efficiency may be maximized.

  2. 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.

  3. 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.

  4. Mechanism of muscarinic receptor-induced K+ channel activation as revealed by hydrolysis-resistant GTP analogues

    PubMed Central

    1988-01-01

    The role of a guanine nucleotide-binding protein (Gk) in the coupling between muscarinic receptor activation and opening of an inwardly rectifying K+ channel [IK(M)] was examined in cardiac atrial myocytes, using hydrolysis-resistant GTP analogues. In the absence of muscarinic agonist, GTP analogues produced a membrane current characteristic of IK(M). The initial rate of appearance of this receptor-independent IK(M) was measured for the various analogues in order to explore the kinetic properties of IK(M) activation. We found that IK(M) activation is controlled solely by the intracellular analogue/GTP ratio and not by the absolute concentrations of the nucleotides. Analogues competed with GTP for binding to Gk with the following relative affinities: GTP gamma S greater than GTP greater than GppNHp greater than GppCH2p. At sufficiently high intracellular concentrations, however, all GTP analogues produced the same rate of IK(M) activation. This analogue- independent limiting rate is likely to correspond to the rate of GDP release from inactive, GDP-bound Gk. Muscarinic receptor stimulation by nanomolar concentrations of acetylcholine (ACh), which do not elicit IK(M) under control conditions, catalyzed IK(M) activation in the presence of GTP analogues. The rate of Gk activation by ACh (kACh) was found to be described by the simple relationship kACh = 8.4 X 10(8) min- 1 M-1.[ACh] + 0.44 min-1, the first term of which presumably reflects the agonist-catalyzed rate of GDP release from the Gk.GDP complex, while the second term corresponds to the basal rate of receptor- independent GDP release. Combined with the estimated K0.5 of the IK(M)- [ACh] dose-effect relationship, 160 nM, this result also allowed us to estimate the rate of Gk.GTP hydrolysis, kcat, to be near 135 min-1. These results provide, for the first time, a quantitative description of the salient features of G-protein function in vivo. PMID:2455765

  5. Creating multiphoton-polarization bound entangled states

    SciTech Connect

    Wei, Tzu-Chieh; Lavoie, Jonathan; Kaltenbaek, Rainer

    2011-03-15

    Bound entangled states are the exotic objects in the entangled world. They require entanglement to create them, but once they are formed, it is not possible to locally distill any free entanglement from them. It is only until recently that a few bound entangled states were realized in the laboratory. Motivated by these experiments, we propose schemes for creating various classes of bound entangled states with photon polarization. These include Acin-Bruss-Lewenstein-Sanpara states, Duer's states, Lee-Lee-Kim bound entangled states, and an unextendible-product-basis bound entangled state.

  6. On thermodynamic and microscopic reversibility

    SciTech Connect

    Crooks, Gavin E.

    2011-07-12

    The word 'reversible' has two (apparently) distinct applications in statistical thermodynamics. A thermodynamically reversible process indicates an experimental protocol for which the entropy change is zero, whereas the principle of microscopic reversibility asserts that the probability of any trajectory of a system through phase space equals that of the time reversed trajectory. However, these two terms are actually synonymous: a thermodynamically reversible process is microscopically reversible, and vice versa.

  7. 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

  8. Environment-responsive fluorescent nucleoside analogue probe for studying oligonucleotide dynamics in a model cell-like compartment.

    PubMed

    Pawar, Maroti G; Srivatsan, Seergazhi G

    2013-11-21

    The majority of fluorescent nucleoside analogue probes that have been used in the in vitro study of nucleic acids are not suitable for cell-based biophysical assays because they exhibit excitation maxima in the UV region and low quantum yields within oligonucleotides. Therefore, we propose that the photophysical characterization of oligonucleotides labeled with a fluorescent nucleoside analogue in reverse micelles (RM), which are good biological membrane models and UV-transparent, could provide an alternative approach to studying the properties of nucleic acids in a cell-like confined environment. In this context, we describe the photophysical properties of an environment-sensitive fluorescent uridine analogue (1), based on the 5-(benzo[b]thiophen-2-yl)pyrimidine core, in micelles and RM. The emissive nucleoside, which is polarity- and viscosity-sensitive, reports the environment of the surfactant assemblies via changes in its fluorescence properties. The nucleoside analogue, incorporated into an RNA oligonucleotide and hybridized to its complementary DNA and RNA oligonucleotides, exhibits a significantly higher fluorescence intensity, lifetime, and anisotropy in RM than in aqueous buffer, which is consistent with the environment of RM. Collectively, our results demonstrate that nucleoside 1 could be utilized as a fluorescent label to study the function of nucleic acids in a model cellular milieu.

  9. Bound states in the continuum

    NASA Astrophysics Data System (ADS)

    Hsu, Chia Wei; Zhen, Bo; Stone, A. Douglas; Joannopoulos, John D.; Soljačić, Marin

    2016-09-01

    Bound states in the continuum (BICs) are waves that remain localized even though they coexist with a continuous spectrum of radiating waves that can carry energy away. Their very existence defies conventional wisdom. Although BICs were first proposed in quantum mechanics, they are a general wave phenomenon and have since been identified in electromagnetic waves, acoustic waves in air, water waves and elastic waves in solids. These states have been studied in a wide range of material systems, such as piezoelectric materials, dielectric photonic crystals, optical waveguides and fibres, quantum dots, graphene and topological insulators. In this Review, we describe recent developments in this field with an emphasis on the physical mechanisms that lead to BICs across seemingly very different materials and types of waves. We also discuss experimental realizations, existing applications and directions for future work.

  10. Arenavirus reverse genetics for vaccine development.

    PubMed

    Ortiz-Riaño, Emilio; Cheng, Benson Yee Hin; Carlos de la Torre, Juan; Martínez-Sobrido, Luis

    2013-06-01

    Arenaviruses are important human pathogens with no Food and Drug Administration (FDA)-licensed vaccines available and current antiviral therapy being limited to an off-label use of the nucleoside analogue ribavirin of limited prophylactic efficacy. The development of reverse genetics systems represented a major breakthrough in arenavirus research. However, rescue of recombinant arenaviruses using current reverse genetics systems has been restricted to rodent cells. In this study, we describe the rescue of recombinant arenaviruses from human 293T cells and Vero cells, an FDA-approved line for vaccine development. We also describe the generation of novel vectors that mediate synthesis of both negative-sense genome RNA and positive-sense mRNA species of lymphocytic choriomeningitis virus (LCMV) directed by the human RNA polymerases I and II, respectively, within the same plasmid. This approach reduces by half the number of vectors required for arenavirus rescue, which could facilitate virus rescue in cell lines approved for human vaccine production but that cannot be transfected at high efficiencies. We have shown the feasibility of this approach by rescuing both the Old World prototypic arenavirus LCMV and the live-attenuated vaccine Candid#1 strain of the New World arenavirus Junín. Moreover, we show the feasibility of using these novel strategies for efficient rescue of recombinant tri-segmented both LCMV and Candid#1.

  11. Reverse transcriptase incorporation of 1,5-anhydrohexitol nucleotides

    PubMed Central

    Vastmans, Karen; Froeyen, Matheus; Kerremans, Luc; Pochet, Sylvie; Herdewijn, Piet

    2001-01-01

    Several reverse transcriptases were studied for their ability to accept anhydrohexitol triphosphates, having a conformationally restricted six-membered ring, as substrate for template-directed synthesis of HNA. It was found that AMV, M-MLV, M-MLV (H–), RAV2 and HIV-1 reverse transcriptases were able to recognise the anhydrohexitol triphosphate as substrate and to efficiently catalyse the incorporation of one non-natural anhydrohexitol nucleotide opposite a natural complementary nucleotide. However, only the dimeric enzymes, the RAV2 and HIV-1 reverse transcriptases, seemed to be able to further extend the primer with another anhydrohexitol building block. Subsequently, several HIV-1 mutants (4×AZT, 4×AZT/L100I, L74V, M184V and K65A) were likewise analysed, resulting in selection of K65A and, in particular, M184V as the most succesful mutant HIV-1 reverse transcriptases capable of elongating a DNA primer with several 1,5-anhydrohexitol adenines in an efficient way. Results of kinetic experiments in the presence of this enzyme revealed that incorporation of one anhydrohexitol nucleotide of adenine or thymine gave an increased (for 1,5-anhydrohexitol-ATP) and a slightly decreased (for 1,5-anhydrohexitol-TTP) Km value in comparison to that of their natural counterparts. However, no more than four analogues could be inserted under the experimental conditions required for selective incorporation. Investigation of incorporation of the altritol anhydrohexitol nucleotide of adenine in the presence of M184V and Vent (exo–) DNA polymerase proved that an adjacent hydroxyl group on C3 of 1,5-anhydrohexitol-ATP has a detrimental effect on the substrate activity of the six-ring analogue. These results could be rationalised based on the X-ray structure of HIV-1 reverse transcriptase. PMID:11470872

  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. A nonlinear dynamic analogue model of substorms

    NASA Astrophysics Data System (ADS)

    Klimas, A. J.; Baker, D. N.; Roberts, D. A.; Fairfield, D. H.; Büchner, J.

    Linear prediction filter studies have shown that the magnetospheric response to energy transfer from the solar wind contains both directly driven and unloading components. These studies have also shown that the magnetospheric response is significantly nonlinear and, thus, the linear prediction filtering technique and other correlative techniques which assume a linear magnetospheric response cannot give a complete deacription of that response. Here, the solar wind-magnetosphere interaction is discussed within the framework of deterministic nonlinear dynamics. An earlier dripping faucet mechanical analogue to the magnetosphere is first reviewed and then the plasma physical counterpart to the mechanical model is constructed. A Faraday loop in the magnetotail is considered and the relationship of electric potentials on the loop to changes in the magnetic flux threading the loop is developed. This approach leads to a model of geomagnetic activity which is similar to the earlier mechanical model but described in terms of the geometry and plasma contents of the magnetotail. This Faraday loop response model contains analogues to both the directly driven and the storage-release magnetospheric responses and it includes, in a fundamental way, the inherent nonlinearity of the solar wind-magnetosphere system. It can be chancterized as a nonlinear, damped harmonic oscillator that is driven by the loading-unloading substorm cycle. The model is able to explain many of the features of the linear prediction filter results. In particular, at low geomagnetic activity levels the model exbibits the "regular dripping" response which provides an explanation for the unloading component at 1 hour lag in the linear prediction filters. Further, the model suggests that the disappearance of the unloading component in the linear prediction filters at high geomagnetic activity levels is due to a chaotic transition beyond which the loading-unloading mechanism becomes aperiodic. The model predicts

  14. Using tolerance bounds in scientific investigations

    SciTech Connect

    Wendelberger, J.R.

    1996-07-01

    Assessment of the variability in population values plays an important role in the analysis of scientific data. Analysis of scientific data often involves developing a bound on a proportion of a population. Sometimes simple probability bounds are obtained using formulas involving known mean and variance parameters and replacing the parameters by sample estimates. The resulting bounds are only approximate and fail to account for the variability in the estimated parameters. Tolerance bounds provide bounds on population proportions which account for the variation resulting from the estimated mean and variance parameters. A beta content, gamma confidence tolerance interval is constructed so that a proportion beta of the population lies within the region bounded by the interval with confidence gamma. An application involving corrosion measurements is used to illustrate the use of tolerance bounds for different situations. Extensions of standard tolerance intervals are applied to generate regression tolerance bounds, tolerance bounds for more general models of measurements collected over time, and tolerance intervals for varying precision data. Tolerance bounds also provide useful information for designing the collection of future data.

  15. Tren-based analogues of bacillibactin: structure and stability.

    PubMed

    Dertz, Emily A; Xu, Jide; Raymond, Kenneth N

    2006-07-10

    Synthetic analogues were designed to highlight the effect of the glycine moiety of bacillibactin on the overall stability of the ferric complex as compared to synthetic analogues of enterobactin. Insertion of a variety of amino acids to catecholamide analogues based on a Tren (tris(2-aminoethyl)amine) backbone increased the overall acidity of the ligands, causing an enhancement of the stability of the resulting ferric complex as compared to TRENCAM. Solution thermodynamic behavior of these siderophores and their synthetic analogues was investigated through potentiometric and spectrophotometric titrations. X-ray crystallography, circular dichroism, and molecular modeling were used to determine the chirality and geometry of the ferric complexes of bacillibactin and its analogues. In contrast to the Tren scaffold, addition of a glycine to the catechol chelating arms causes an inversion of the trilactone backbone, resulting in opposite chiralities of the two siderophores and a destabilization of the ferric complex of bacillibactin compared to ferric enterobactin.

  16. Analogue Divider by Averaging a Triangular Wave

    NASA Astrophysics Data System (ADS)

    Selvam, Krishnagiri Chinnathambi

    2017-03-01

    A new analogue divider circuit by averaging a triangular wave using operational amplifiers is explained in this paper. The triangle wave averaging analog divider using operational amplifiers is explained here. The reference triangular waveform is shifted from zero voltage level up towards positive power supply voltage level. Its positive portion is obtained by a positive rectifier and its average value is obtained by a low pass filter. The same triangular waveform is shifted from zero voltage level to down towards negative power supply voltage level. Its negative portion is obtained by a negative rectifier and its average value is obtained by another low pass filter. Both the averaged voltages are combined in a summing amplifier and the summed voltage is given to an op-amp as negative input. This op-amp is configured to work in a negative closed environment. The op-amp output is the divider output.

  17. Naturalness in an emergent analogue spacetime.

    PubMed

    Liberati, Stefano; Visser, Matt; Weinfurtner, Silke

    2006-04-21

    Effective field theories (EFTs) have been widely used as a framework in order to place constraints on the Planck suppressed Lorentz violations predicted by various models of quantum gravity. There are, however, technical problems in the EFT framework when it comes to ensuring that small Lorentz violations remain small--this is the essence of the "naturalness" problem. Herein we present an "emergent" spacetime model, based on the "analogue gravity" program, by investigating a specific condensed-matter system. Specifically, we consider the class of two-component BECs subject to laser-induced transitions between the components, and we show that this model is an example for Lorentz invariance violation due to ultraviolet physics. Furthermore, our model explicitly avoids the naturalness problem, and makes specific suggestions regarding how to construct a physically reasonable quantum gravity phenomenology.

  18. 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

  19. A simple analogue of lung mechanics.

    PubMed

    Sherman, T F

    1993-12-01

    A model of the chest and lungs can be easily constructed from a bottle of water, a balloon, a syringe, a rubber stopper, glass and rubber tubing, and clamps. The model is a more exact analogue of the body than the classic apparatus of Hering in two respects: 1) the pleurae and intrapleural fluid are represented by water rather than air, and 2) the subatmospheric "intrapleural" pressure is created by the elasticity of the "lung" (balloon) rather than by a vacuum pump. With this model, students can readily see how the lung is inflated and deflated by movements of the "diaphragm and chest" (syringe plunger) and how intrapleural pressures change as this is accomplished.

  20. Terrestrial Analogues for Lunar Impact Melt Flows

    NASA Technical Reports Server (NTRS)

    Neish, C. D.; Hamilton, C. W.; Hughes, S. S.; Nawotniak, S. Kobs; Garry, W. B.; Skok, J. R.; Elphic, R. C.; Schaefer, E.; Carter, L. M.; Bandfield, J. L.; Osinski, G. R.; Lim, D.; Heldmann, J. L.

    2016-01-01

    Lunar impact melt deposits have unique physical properties. They have among the highest observed radar returns at S-Band (12.6 cm wavelength), implying that they are rough at the decimeter scale. However, they are also observed in high-resolution optical imagery to be quite smooth at the meter scale. These characteristics distinguish them from well-studied terrestrial analogues, such as Hawaiian pahoehoe and ?a ?a lava flows. The morphology of impact melt deposits can be related to their emplacement conditions, so understanding the origin of these unique surface properties will help to inform us as to the circumstances under which they were formed. In this work, we seek to find a terrestrial analogue for well-preserved lunar impact melt flows by examining fresh lava flows on Earth. We compare the radar return and high-resolution topographic variations of impact melt flows to terrestrial lava flows with a range of surface textures. The lava flows examined in this work range from smooth Hawaiian pahoehoe to transitional basaltic flows at Craters of the Moon (COTM) National Monument and Preserve in Idaho to rubbly and spiny pahoehoe-like flows at the recent eruption at Holuhraun in Iceland. The physical properties of lunar impact melt flows appear to differ from those of all the terrestrial lava flows studied in this work. This may be due to (a) differences in post-emplacement modification processes or (b) fundamental differences in the surface texture of the melt flows due to the melts' unique emplacement and/or cooling environment. Information about the surface properties of lunar impact melt deposits will be critical for future landed missions that wish to sample these materials.

  1. 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.

  2. Terrestrial analogues for lunar impact melt flows

    NASA Astrophysics Data System (ADS)

    Neish, C. D.; Hamilton, C. W.; Hughes, S. S.; Nawotniak, S. Kobs; Garry, W. B.; Skok, J. R.; Elphic, R. C.; Schaefer, E.; Carter, L. M.; Bandfield, J. L.; Osinski, G. R.; Lim, D.; Heldmann, J. L.

    2017-01-01

    Lunar impact melt deposits have unique physical properties. They have among the highest observed radar returns at S-Band (12.6 cm wavelength), implying that they are rough at the decimeter scale. However, they are also observed in high-resolution optical imagery to be quite smooth at the meter scale. These characteristics distinguish them from well-studied terrestrial analogues, such as Hawaiian pāhoehoe and ´a´ā lava flows. The morphology of impact melt deposits can be related to their emplacement conditions, so understanding the origin of these unique surface properties will help to inform us as to the circumstances under which they were formed. In this work, we seek to find a terrestrial analogue for well-preserved lunar impact melt flows by examining fresh lava flows on Earth. We compare the radar return and high-resolution topographic variations of impact melt flows to terrestrial lava flows with a range of surface textures. The lava flows examined in this work range from smooth Hawaiian pāhoehoe to transitional basaltic flows at Craters of the Moon (COTM) National Monument and Preserve in Idaho to rubbly and spiny pāhoehoe-like flows at the recent eruption at Holuhraun in Iceland. The physical properties of lunar impact melt flows appear to differ from those of all the terrestrial lava flows studied in this work. This may be due to (a) differences in post-emplacement modification processes or (b) fundamental differences in the surface texture of the melt flows due to the melts' unique emplacement and/or cooling environment. Information about the surface properties of lunar impact melt deposits will be critical for future landed missions that wish to sample these materials.

  3. Current european regulatory perspectives on insulin analogues

    PubMed Central

    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

  4. Simple bounds on fluctuations and uncertainty relations for first-passage times of counting observables

    NASA Astrophysics Data System (ADS)

    Garrahan, Juan P.

    2017-03-01

    Recent large deviation results have provided general lower bounds for the fluctuations of time-integrated currents in the steady state of stochastic systems. A corollary are so-called thermodynamic uncertainty relations connecting precision of estimation to average dissipation. Here we consider this problem but for counting observables, i.e., trajectory observables which, in contrast to currents, are non-negative and nondecreasing in time (and possibly symmetric under time reversal). In the steady state, their fluctuations to all orders are bound from below by a Conway-Maxwell-Poisson distribution dependent only on the averages of the observable and of the dynamical activity. We show how to obtain the corresponding bounds for first-passage times (times when a certain value of the counting variable is first reached) and their uncertainty relations. Just like entropy production does for currents, dynamical activity controls the bounds on fluctuations of counting observables.

  5. The structure of locally bounded finite-dimensional representations of connected locally compact groups

    SciTech Connect

    Shtern, A. I.

    2014-04-30

    An analogue of a Lie theorem is obtained for (not necessarily continuous) finite-dimensional representations of soluble finite-dimensional locally compact groups with connected quotient group by the centre. As a corollary, the following automatic continuity proposition is obtained for locally bounded finite-dimensional representations of connected locally compact groups: if G is a connected locally compact group, N is a compact normal subgroup of G such that the quotient group G/N is a Lie group, N{sub 0} is the connected identity component in N, H is the family of elements of G commuting with every element of N{sub 0}, and π is a (not necessarily continuous) locally bounded finite-dimensional representation of G, then π is continuous on the commutator subgroup of H (in the intrinsic topology of the smallest analytic subgroup of G containing this commutator subgroup). Bibliography: 23 titles. (paper)

  6. Reversibility of liver fibrosis.

    PubMed

    Sun, Mengxi; Kisseleva, Tatiana

    2015-09-01

    Liver fibrosis is a serious health problem worldwide, which can be induced by a wide spectrum of chronic liver injuries. However, until today, there is no effective therapy available for liver fibrosis except the removal of underlying etiology or liver transplantation. Recent studies indicate that liver fibrosis is reversible when the causative agent(s) is removed. Understanding of mechanisms of liver fibrosis regression will lead to the identification of new therapeutic targets for liver fibrosis. This review summarizes recent research progress on mechanisms of reversibility of liver fibrosis. While most of the research has been focused on HSCs/myofibroblasts and inflammatory pathways, the crosstalk between different organs, various cell types and multiple signaling pathways should not be overlooked. Future studies that lead to fully understanding of the crosstalk between different cell types and the molecular mechanism underlying the reversibility of liver fibrosis will definitely give rise to new therapeutic strategies to treat liver fibrosis.

  7. Dynamics of magnetization reversal

    NASA Astrophysics Data System (ADS)

    Safonov, Vladimir L.

    2000-03-01

    Advanced magnetic recording systems are designed for extremely high areal densities and data rate. These two aspects require both magnetization reversal at very short times (< 1 ns) and long term ( ~ 5-10 years) stability against thermal fluctuations. There are two basic physics problems associated with these requirements. The first is a characterization of thermal-dynamic reversal over very wide time range. The second is an understanding of the physics of the relaxation mechanisms. Both these subjects will be reviewed in this talk. Thermal dynamic reversal requires solution of the Landau-Lifshitz equation with fluctuations. We have solved this problem in terms of the ``random walk" dynamics of a nonlinear oscillator [1,2]. The expressions for the switching field versus pulse time are analytic and show good agreement with measurements on CrO_2. Our studies of fundamental relaxation mechanisms have involved a two step approach. First the results of computer simulations of magnetization reversal without phenomenological damping will be discussed. In this case coherent rotation of the magnetization excites spin waves during which an excess of Zeeman energy is transformed to anisotropy and exchange energies. However, for fine grains whose size is sufficiently small so that the grain magnetization is virtually uniform, non-linear spin waves cannot assist reversal [3]. A new analytic model of reversal that couples coherent rotation to impurity ions by an anisotropic exchange mechanism will be discussed. These impurity ions are assumed to relax at a very high rate to the lattice. [1] V.L.Safonov, JMMM 195, 523 (1999); J.Appl.Phys. 85, 4370 (1999). [2] V.L.Safonov, H.N.Bertram, MMM'99, CU-09. [3] V.L.Safonov, H.N.Bertram, J.Appl.Phys. 85, 5072 (1999); MMM'99, CD-11.

  8. Bound anionic states of adenine

    SciTech Connect

    Haranczyk, Maciej; Gutowski, Maciej S; Li, Xiang; Bowen, Kit H

    2007-03-20

    Anionic states of nucleic acid bases are involved in DNA damage by low-energy electrons and in charge transfer through DNA. Previous gas phase studies of free, unsolvated nucleic acid base parent anions probed only dipole-bound states, which are not present in condensed phase environments, but did not observe valence anionic states, which for purine bases, are thought to be adiabatically unbound. Contrary to this expectation, we have demonstrated that some thus far ignored tautomers of adenine, which result from enamine-imine transformations, support valence anionic states with electron vertical detachment energies as large as 2.2 eV, and at least one of these anionic tautomers is adiabatically bound. Moreover, we predict that the new anionic tautomers should also dominate in solutions and should be characterized by larger values of electron vertical detachment energy than the canonical valence anion. All of the new-found anionic tautomers might be formed in the course of dissociative electron attachment followed by a hydrogen atom attachment to a carbon atom, and they might affect the structure and properties of DNA and RNA exposed to low-energy electrons. The discovery of these valence anionic states of adenine was facilitated by the development of: (i) a new experimental method for preparing parent anions of nucleic acid bases for photoelectron experiments, and (ii) a new combinatorial/ quantum chemical approach for identification of the most stable tautomers of organic molecules. The computational portion of this work was supported by the: (i) Polish State Committee for Scientific Research (KBN) Grants: DS/8000-4-0140-7 (M.G.) and N204 127 31/2963 (M.H.), (ii) European Social Funds (EFS) ZPORR/2.22/II/2.6/ARP/U/2/05 (M.H.), and (iii) US DOE Office of Biological and Environmental Research, Low Dose Radiation Research Program (M.G.). M.H. holds the Foundation for Polish Science (FNP) award for young scientists. The calculations were performed at the Academic

  9. Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties.

    PubMed

    Segal, Meirav; Fischer, Bilha

    2012-02-28

    Uridine cannot be utilized as fluorescent probe due to its extremely low quantum yield. For improving the uracil fluorescence characteristics we extended the natural chromophore at the C5 position by coupling substituted aromatic rings directly or via an alkenyl or alkynyl linker to create fluorophores. Extension of the uracil base was achieved by treating 5-I-uridine with the appropriate boronic acid under the Suzuki coupling conditions. Analogues containing an alkynyl linker were obtained from 5-I-uridine and the suitable boronic acid in a Sonogashira coupling reaction. The uracil fluorescent analogues proposed here were designed to satisfy the following requirements: a minimal chemical modification at a position not involved in base-pairing, resulting in relatively long absorption and emission wavelengths and high quantum yield. 5-((4-Methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6b, was found to be a promising fluorescent probe. Probe 6b exhibits a quantum yield that is 3000-fold larger than that of the natural chromophore (Φ 0.12), maximum emission (478 nm) which is 170 nm red shifted as compared to uridine, and a Stokes shift of 143 nm. In addition, since probe 6b adopts the anti conformation and S sugar puckering favored by B-DNA, it makes a promising nucleoside analogue to be incorporated in an oligonucleotide probe for detection of genetic material.

  10. The feasibility program with security constraints and network rearrangement costs - Application to mixed /analogue and digital/ transmission networks

    NASA Astrophysics Data System (ADS)

    Serreault, J.-Y.; Minoux, M.

    1980-02-01

    This paper presents a second version of the 'feasibility program' (SECURAD) developed by the CNET. This program enables the routing at minimal costs of several thousand of requirements (expressed in circuits or groups of circuits) on very large mixed (analogue and digital) transmission networks, while respecting given capacities and taking into account security constraints and network-rearrangement costs. Consideration is given to a procedure for determining lower bounds for the cost of the optimal solution by solving a dual problem, and thus checking the quality of the approximate solutions obtained.

  11. Fluoride-Cleavable, Fluorescently Labelled Reversible Terminators: Synthesis and Use in Primer Extension

    PubMed Central

    Knapp, Diana C; Serva, Saulius; D'Onofrio, Jennifer; Keller, Angelika; Lubys, Arvydas; Kurg, Ants; Remm, Maido; Engels, Joachim W

    2011-01-01

    Fluorescent 2′-deoxynucleotides containing a protecting group at the 3′-O-position are reversible terminators that enable array-based DNA sequencing-by-synthesis (SBS) approaches. Herein, we describe the synthesis and full characterisation of four reversible terminators bearing a 3′-blocking moiety and a linker-dye system that is removable under the same fluoride-based treatment. Each nucleotide analogue has a different fluorophore attached to the base through a fluoride-cleavable linker and a 2-cyanoethyl moiety as the 3′-blocking group, which can be removed by using a fluoride treatment as well. Furthermore, we identified a DNA polymerase, namely, RevertAid M-MuLV reverse transcriptase, which can incorporate the four modified reversible terminators. The synthesised nucleotides and the optimised DNA polymerase were used on CodeLink slides spotted with hairpin oligonucleotides to demonstrate their potential in a cyclic reversible terminating approach. PMID:21294195

  12. Sequential Polarity-Reversing Circuit

    NASA Technical Reports Server (NTRS)

    Labaw, Clayton C.

    1994-01-01

    Proposed circuit reverses polarity of electric power supplied to bidirectional dc motor, reversible electro-mechanical actuator, or other device operating in direction depending on polarity. Circuit reverses polarity each time power turned on, without need for additional polarity-reversing or direction signals and circuitry to process them.

  13. Andreev bound states in topological superconductors (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Tanaka, Yukio; Lu, Bo; Yada, Keiji; Sato, Masatoshi

    2016-10-01

    Andreev bound states in topological superconductors Yukio Tanaka1, Lu Bo1,, K. Yada1, A. Yamakage1, M. Sato2 1Department of Applied Physics, Nagoya University 2Yukawa Institute, Kyoto University e-mail: ytanaka@nuap.nagoya-u.ac.jp It is known that Andreev bound state is an important ingredient to identify unconventional superconductors [1]. Up to now, there have been several types of Andreev bound states stemming from their topological origins [2-3]. It can be classified into i)dispersionless flat band type realized in cuprate, ii)linear dispersion type realized in chiral superconductor like Sr2RuO4, iii)helical dispersion type realized in non-centrosymmetric superconductor and iv)cone type in the surface state on B-phase of superfluid 3He [3]. It has been noted that certain surfaces of Weyl semimetals have bound states forming open Fermi arcs, which are never seen in typical metallic states. We show that the Fermi arcs enable them to support an even more exotic surface state with crossed flat bands in the superconducting state. We clarify the topological origin of the crossed dispersionless flat bands and the relevant symmetry that stabilizes the cross point. Our symmetry analysis are applicable to known candidate materials of time-reversal breaking Weyl semimetals[4]. [1]S. Kashiwaya and Y. Tanaka, Rep. Prog. Phys. 63 1641 (2000). [2]Y. Tanaka, M. Sato, and N. Nagaosa, J. Phys. Soc. Jpn. 81 011013 (2012). [3] M. Sato, et al., Phys. Rev. Lett. 103 (2009) 020401. [4] B. Lu, K. Yada, M. Sato, and Y. Tanaka, Phys. Rev. Lett. 114 09

  14. Si:P as a laboratory analogue for hydrogen on high magnetic field white dwarf stars.

    PubMed

    Murdin, B N; Li, Juerong; Pang, M L Y; Bowyer, E T; Litvinenko, K L; Clowes, S K; Engelkamp, H; Pidgeon, C R; Galbraith, I; Abrosimov, N V; Riemann, H; Pavlov, S G; Hübers, H-W; Murdin, P G

    2013-01-01

    Laboratory spectroscopy of atomic hydrogen in a magnetic flux density of 10(5) T (1 gigagauss), the maximum observed on high-field magnetic white dwarfs, is impossible because practically available fields are about a thousand times less. In this regime, the cyclotron and binding energies become equal. Here we demonstrate Lyman series spectra for phosphorus impurities in silicon up to the equivalent field, which is scaled to 32.8 T by the effective mass and dielectric constant. The spectra reproduce the high-field theory for free hydrogen, with quadratic Zeeman splitting and strong mixing of spherical harmonics. They show the way for experiments on He and H(2) analogues, and for investigation of He(2), a bound molecule predicted under extreme field conditions.

  15. Solid-phase synthesis of lidocaine and procainamide analogues using backbone amide linker (BAL) anchoring.

    PubMed

    Shannon, Simon K; Peacock, Mandy J; Kates, Steven A; Barany, George

    2003-01-01

    New solid-phase strategies have been developed for the synthesis of lidocaine (1) and procainamide (2) analogues, using backbone amide linker (BAL) anchoring. Both sets were prepared starting from a common resin-bound intermediate, followed by four general steps: (i) attachment of a primary aliphatic or aromatic amine to the solid support via reductive amination (as monitored by a novel test involving reaction of 2,4-dinitrophenylhydrazine with residual aldehyde groups); (ii) acylation of the resultant secondary amine; (iii) displacement of halide with an amine; and (iv) trifluoroacetic acid-mediated release from the support. A manual parallel strategy was followed to provide 60 novel compounds, of which two dozen have not been previously described. In most cases, initial crude purities were >80%, and overall isolated yields were in the 40-88% range.

  16. Role of low density lipoprotein-bound cholesterol esters in acute lymphoblastic leukemia cells

    SciTech Connect

    Cutts, J.L.; Madden, E.A.; Melnykovych, G.

    1986-05-01

    The glucocorticoid sensitive CEM-C7 T-cell line was derived from human acute lymphoblastic leukemia cells by Norman and Thompson. Madden et al. have demonstrated that this growth inhibitory effect is due in part to a glucocorticoid-mediated inhibition of cholesterol synthesis and can be partially reversed by cholesterol dispersions. To further delineate the role of cholesterol in this growth inhibition, they have examined the ability of low density lipoprotein (LDL)-bound (/sup 3/H)cholesterol linoleate to reverse the growth inhibitory effect of 1 ..mu..M dexamethasone (Dex) on the CEM-C7 cells. LDL-bound cholesterol linoleate was unable to reverse the Dex-mediated growth inhibition, although incorporation of (/sup 14/C) acetate into free cholesterol was inhibited by 29%, following the Brown and Goldstein model. The presence of Dex further inhibited acetate incorporation into free cholesterol in the LDL-treated cells. Under all conditions, more than 99% of the acetate incorporated into cholesterol was present as free cholesterol, while over 87% of the LDL-bound cholesterol linoleate taken up remained in the ester compartment. These results indicate that CEM-C7 cells are unable to utilize LDL-bound cholesterol esters as a source of free cholesterol and rely on endogenous synthesis for their free cholesterol requirements.

  17. Reversible Chemochromic Hydrogen Detectors

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Florida Solar Energy Center (FSEC), affiliated with the University of Central Florida, has invented a reversible pigment that changes from light beige to blue when exposed to hydrogen and back to light beige when exposed to atmospheric oxygen. In laboratory and environmental studies, the FSEC pigment in its tape form failed to change color adequately when exposed to hydrogen after one day of exposure at Kennedy Space Center's Beach Corrosion Test Facility. The reversible hydrogen-detecting tape also lost its ability to change color after being placed in an environmental chamber at 45 C for one day. The first attempts at extruding the reversible pigment into various polymers were unsuccessful because of the pigment's poor thermal stability. The goal of this project was to formulate a pigment with improved thermal and environmental stability for extrusion into a variety of appropriate polymer matrices. The formulation of the reversible hydrogen-detecting pigment was modified by removing one reagent and chemically modifying the hydrogen sensitive ingredient. This was intended to improve the hydrophobicity of the pigment and alter the thermal degradation mechanism.

  18. Time reversal communication system

    DOEpatents

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  19. Tubal Ligation Reversal

    MedlinePlus

    ... depending on a woman's age and other factors. Success rates may be as high as 80 percent or ... details of the procedure Discuss the likelihood of success and your ability to get pregnant after the procedure Discuss other options for pregnancy, such as IVF A tubal ligation reversal can be done as ...

  20. Language Reversion Revisited.

    ERIC Educational Resources Information Center

    De Bot, Kees; Clyne, Michael

    1989-01-01

    A longitudinal study on language maintenance and loss among Dutch-English bilinguals in Australia revealed little loss in both languages over the years. This leads to the hypothesis of a "critical threshold" that must be reached to retain the second language. First language reversion appears commonly among immigrants who did not reach this…

  1. Conformational studies of immunodominant myelin basic protein 1-11 analogues using NMR and molecular modeling

    NASA Astrophysics Data System (ADS)

    Laimou, Despina; Lazoura, Eliada; Troganis, Anastassios N.; Matsoukas, Minos-Timotheos; Deraos, Spyros N.; Katsara, Maria; Matsoukas, John; Apostolopoulos, Vasso; Tselios, Theodore V.

    2011-11-01

    Τwo dimensional nuclear magnetic resonance studies complimented by molecular dynamics simulations were conducted to investigate the conformation of the immunodominant epitope of acetylated myelin basic protein residues 1-11 (Ac-MBP1-11) and its altered peptide ligands, mutated at position 4 to an alanine (Ac-MBP1-11[4A]) or a tyrosine residue (Ac-MBP1-11[4Y]). Conformational analysis of the three analogues indicated that they adopt an extended conformation in DMSO solution as no long distance NOE connectivities were observed and seem to have a similar conformation when bound to the active site of the major histocompatibility complex (MHC II). The interaction of each peptide with MHC class II I-Au was further investigated in order to explore the molecular mechanism of experimental autoimmune encephalomyelitis induction/inhibition in mice. The present findings indicate that the Gln3 residue, which serves as a T-cell receptor (TCR) contact site in the TCR/peptide/I-Au complex, has a different orientation in the mutated analogues especially in the Ac-MBP1-11[4A] peptide. In particular the side chain of Gln3 is not solvent exposed as for the native Ac-MBP1-11 and it is not available for interaction with the TCR.

  2. Genuine modern analogues of Precambrian stromatolites from caldera lakes of Niuafo'ou Island, Tonga.

    PubMed

    Kazmierczak, Józef; Kempe, Stephan

    2006-03-01

    Calcareous or dolomitic, often secondarily silicified, laminated microbial structures known as stromatolites are important keys to reconstruct the chemical and biotic evolution of the early ocean. Most authors assume that cyanobacteria-associated microbialitic structures described from Shark Bay, Western Australia, and Exuma Sound, Bahamas, represent modern marine analogues for Precambrian stromatolites. Although they resemble the Precambrian forms macroscopically, their microstructure and mineralogical composition differ from those characterizing their purported ancient counterparts. Most Precambrian stromatolites are composed of presumably in situ precipitated carbonates, while their assumed modern marine analogues are predominantly products of accretion of grains trapped and bound by microbial, predominantly cyanobacterial, benthic mats and biofilms and only occasionally by their physicochemical activity. It has therefore been suggested that the carbonate chemistry of early Precambrian seawater differed significantly from modern seawater, and that some present-day quasi-marine or non-marine environments supporting growth of calcareous microbialites reflect the hydrochemical conditions controlling the calcification potential of Precambrian microbes better than modern seawater. Here we report the discovery of a non-marine environment sustaining growth of calcareous cyanobacterial microbialites showing macroscopic and microscopic features resembling closely those described from many Precambrian stromatolites.

  3. High resolution structure of an M23 peptidase with a substrate analogue

    PubMed Central

    Grabowska, Maja; Jagielska, Elzbieta; Czapinska, Honorata; Bochtler, Matthias; Sabala, Izabela

    2015-01-01

    LytM is a Staphylococcus aureus autolysin and a homologue of the S. simulans lysostaphin. Both enzymes are members of M23 metallopeptidase family (MEROPS) comprising primarily bacterial peptidoglycan hydrolases. LytM occurs naturally in a latent form, but can be activated by cleavage of an inhibitory N-terminal proregion. Here, we present a 1.45 Å crystal structure of LytM catalytic domain with a transition state analogue, tetraglycine phosphinate, bound in the active site. In the electron density, the active site of the peptidase, the phosphinate and the “diglycine” fragment on the P1′ side of the transition state analogue are very well defined. The density is much poorer or even absent for the P1 side of the ligand. The structure is consistent with the involvement of His260 and/or His291 in the activation of the water nucleophile and suggests a possible catalytic role for Tyr204, which we confirmed by mutagenesis. Possible mechanisms of catalysis and the structural basis of substrate specificity are discussed based on the structure analysis. PMID:26437833

  4. Conformational studies of immunodominant myelin basic protein 1-11 analogues using NMR and molecular modeling.

    PubMed

    Laimou, Despina; Lazoura, Eliada; Troganis, Anastassios N; Matsoukas, Minos-Timotheos; Deraos, Spyros N; Katsara, Maria; Matsoukas, John; Apostolopoulos, Vasso; Tselios, Theodore V

    2011-11-01

    Τwo dimensional nuclear magnetic resonance studies complimented by molecular dynamics simulations were conducted to investigate the conformation of the immunodominant epitope of acetylated myelin basic protein residues 1-11 (Ac-MBP(1-11)) and its altered peptide ligands, mutated at position 4 to an alanine (Ac-MBP(1-11)[4A]) or a tyrosine residue (Ac-MBP(1-11)[4Y]). Conformational analysis of the three analogues indicated that they adopt an extended conformation in DMSO solution as no long distance NOE connectivities were observed and seem to have a similar conformation when bound to the active site of the major histocompatibility complex (MHC II). The interaction of each peptide with MHC class II I-A(u) was further investigated in order to explore the molecular mechanism of experimental autoimmune encephalomyelitis induction/inhibition in mice. The present findings indicate that the Gln(3) residue, which serves as a T-cell receptor (TCR) contact site in the TCR/peptide/I-A(u) complex, has a different orientation in the mutated analogues especially in the Ac-MBP(1-11)[4A] peptide. In particular the side chain of Gln(3) is not solvent exposed as for the native Ac-MBP(1-11) and it is not available for interaction with the TCR.

  5. Design of multi-epitope, analogue-based cancer vaccines.

    PubMed

    Fikes, John D; Sette, Alessandro

    2003-09-01

    The current objective of our cancer programme is to develop an effective vaccine based on rationally designed T cell epitope analogues, for use in the adjuvant setting for non-small cell lung cancer (NSCLC) and colon cancer. Analogue epitopes, enhanced for either human leukocyte antigen (HLA) binding or T cell receptor (TCR) signalling, have been shown to be more effective at breaking immunological tolerance than cognate wild-type epitopes. Although encouraging early-phase clinical data has been obtained by others using a limited number of HLA-A2-restricted epitope analogues, the clinical benefits and immune correlates for vaccines comprised of multiple epitope analogues restricted by multiple HLA supertypes remains to be investigated. Clinical studies are currently being conducted on EP-2101, a prototype vaccine that delivers multiple HLA-A2-restricted analogue epitopes. In parallel, fixed anchor and heteroclitic analogues restricted by three other commonly expressed HLA supertypes are being identified. These analogues will be incorporated into future vaccines including optimised minigenes (epigenes) and tested in preclinical and clinical studies addressing various different cancer indications.

  6. 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

  7. Reverse inequalities in {mu}-deformed Segal-Bargmann analysis

    SciTech Connect

    Angulo Aguila, Carlos; Sontz, Stephen Bruce

    2006-04-15

    We prove reverse hypercontractivity inequalities as well as reverse log-Sobolev inequalities in the context of a space of holomorphic functions, which is called the {mu}-deformed Segal-Bargmann space and arises in the works of Wigner, Rosenblum, and Marron. To achieve this we define {mu}-deformations of energy and entropy. Our principle results generalize earlier works of Carlen and Sontz. We also show that the semigroup of this theory is L{sup p} bounded, and we conjecture that it is L{sup p} contractive and, even more strongly, that it is hypercontractive.

  8. A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

    PubMed Central

    Verlee, Arno; Heugebaert, Thomas; van der Meer, Tom; Kerchev, Pavel I; Van Breusegem, Frank

    2017-01-01

    For the synthesis of m-sulfamoylbenzamide analogues, small molecules which are known for their bioactivity, a chemoselective procedure has been developed starting from m-(chlorosulfonyl)benzoyl chloride. Although a chemoselective process in batch was already reported, a continuous-flow process reveals an increased selectivity at higher temperatures and without catalysts. In total, 15 analogues were synthesized, using similar conditions, with yields ranging between 65 and 99%. This is the first automated and chemoselective synthesis of m-sulfamoylbenzamide analogues. PMID:28326139

  9. Mars on Earth: soil analogues for future Mars missions

    NASA Astrophysics Data System (ADS)

    Marlow, Jeffrey J.; Martins, Zita; Sephton, Mark A.

    2008-04-01

    Preparations for missions to Mars are a major concern for scientists. Predicting how equipment and experiments will perform on the planet is difficult because tests are restricted to Earth. Mars soil analogues are being used to solve this problem. These terrestrial materials are chemically and physically similar to martian soils and, because they contain unusual minerals and trace amounts of organic matter, are scientifically interesting in their own right. However, no current analogue is appropriate for all necessary tests. Here we describe Mars soil analogues, identify limitations and suggest the need for new Mars simulants.

  10. 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

    2016-10-04

    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.

  11. Extending the structure-activity relationship study of marine natural ningalin B analogues as P-glycoprotein inhibitors.

    PubMed

    Yang, Chao; Wong, Iris L K; Peng, Kai; Liu, Zhen; Wang, Peng; Jiang, Tingfu; Jiang, Tao; Chow, Larry M C; Wan, Sheng Biao

    2017-01-05

    In the present study, a total of 25 novel ningalin B analogues were synthesized and evaluated for their P-gp modulating activity in a P-gp overexpressed breast cancer cell line LCC6MDR. Preliminary structure-activity study shows that A ring and its two methoxy groups are important pharmacophores for P-gp inhibiting activity. Among all derivatives, 23 is the most potent P-gp modulator with EC50 of 120-165 nM in reversing paclitaxel, DOX, vinblastine and vincristine resistance. It is relatively safe to use with selective index at least greater than 606 compared to verapamil. Mechanistic study demonstrates that compound 23 reverses P-gp mediated drug resistance by inhibiting transport activity of P-gp, thereby restoring intracellular drug accumulation. In summary, our study demonstrates that ningalin B analogue 23 is a non-cytotoxic and effective P-gp chemosensitizer that can be used in the future for reversing P-gp mediated clinical cancer drug resistance.

  12. A lower bound for the QRQW PRAM

    SciTech Connect

    MacKenzie, P.D.

    1995-05-02

    The queue-read, queue-write (QRQW) parallel random access machine (PRAM) model is a shared memory model which allows concurrent reading and writing with a time cost proportional to the contention. This is designed to model currently available parallel machines more accurately than either the CRCW PRAM or EREW PRAM models. Many algorithmic results have been developed for the QRQW PRAM. However, the only lower bound results have been fairly simple reductions from lower bounds for other models, such as the EREW PRAM or the ``few-write`` CREW PRAM. Here we present a lower bound specific to the QRQW PRAM. This lower bound is on the problem of Linear Approximate Compaction (LAC), whose input consists of at most m marked items in an array of size n, and whose output consists of the rn marked items in an array of size 0(m). There is an O({radical}log n), expected time randomized algorithm for LAC on the QRQW PRAM. We prove a lower bound of {Omega}(log log log n) expected time for any randomized algorithm for LAC. This bound applies regardless of the number of processors and memory cells of the QRQW PRAM. The previous best lower bound was {Omega}(log* n) time, taken from the known lower bound for LAC on the CRCW PRAM.

  13. Outward Bound: An Innovative Patient Education Program.

    ERIC Educational Resources Information Center

    Stich, Thomas F.; Gaylor, Michael S.

    A 1975 Dartmouth Outward Bound Mental Health Project, begun with a pilot project for disturbed adolescents, has evolved into an ongoing treatment option in three separate clinical settings for psychiatric patients and recovering alcoholics. Outward Bound consists of a series of prescribed physical and social tasks where the presence of stress,…

  14. Generalized upper bound for inelastic diffraction

    NASA Astrophysics Data System (ADS)

    Troshin, S. M.; Tyurin, N. E.

    2017-01-01

    For inelastic diffraction, we obtain an upper bound valid for the whole range of the elastic scattering amplitude variation allowed by unitarity. We discuss the energy dependence of the inelastic diffractive cross-section on the base of this bound and recent Large Hadron Collider (LHC) data.

  15. THE HOPF BIFURCATION WITH BOUNDED NOISE

    PubMed Central

    Botts, Ryan T.; Homburg, Ale Jan; Young, Todd R.

    2012-01-01

    We study Hopf-Andronov bifurcations in a class of random differential equations (RDEs) with bounded noise. We observe that when an ordinary differential equation that undergoes a Hopf bifurcation is subjected to bounded noise then the bifurcation that occurs involves a discontinuous change in the Minimal Forward Invariant set. PMID:24748762

  16. Outward Bound: an Experience in Human Development

    ERIC Educational Resources Information Center

    Danenburg, William; Gaggi, Silvio

    1974-01-01

    Two authors describe how their participation in an outward bound program has helped them develop a greater degree of general self confidence, greater ease in dealing with complex and frustrating problems, and a greater appreciation of man's place in the natural environment. They also describe Outward Bound courses that have been especially…

  17. Rigorous bounds for optimal dynamical decoupling

    SciTech Connect

    Uhrig, Goetz S.; Lidar, Daniel A.

    2010-07-15

    We present rigorous performance bounds for the optimal dynamical decoupling pulse sequence protecting a quantum bit (qubit) against pure dephasing. Our bounds apply under the assumption of instantaneous pulses and of bounded perturbing environment and qubit-environment Hamiltonians such as those realized by baths of nuclear spins in quantum dots. We show that if the total sequence time is fixed the optimal sequence can be used to make the distance between the protected and unperturbed qubit states arbitrarily small in the number of applied pulses. If, on the other hand, the minimum pulse interval is fixed and the total sequence time is allowed to scale with the number of pulses, then longer sequences need not always be advantageous. The rigorous bound may serve as a testbed for approximate treatments of optimal decoupling in bounded models of decoherence.

  18. Mammary analogue secretory carcinoma mimicking salivary adenoma.

    PubMed

    Williams, Lindsay; Chiosea, Simion I

    2013-12-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor characterized by ETV6 translocation. It appears that prior studies have identified MASC by reviewing salivary gland carcinomas, such as acinic cell carcinoma and adenocarcinoma, not otherwise specified. To address the possibility of MASC mimicking benign salivary neoplasms we reviewed 12 salivary gland (cyst)adenomas diagnosed prior to the discovery of MASC. One encapsulated (cyst)adenoma of the parotid gland demonstrated features of MASC. The diagnosis was confirmed by fluorescence in situ hybridization with an ETV6 break-apart probe. An unusual complex pattern of ETV6 rearrangement with duplication of the telomeric/distal ETV6 probe was identified. This case illustrates that MASC may mimic salivary (cyst)adenomas. To more accurately assess true clinical and morphologic spectrum of MASC, future studies may have to include review of salivary (cyst)adenomas. The differential diagnosis of MASC may have to be expanded to include cases resembling salivary (cyst)adenomas.

  19. Fluorescent polyene ceramide analogues as membrane probes.

    PubMed

    Nieves, Ingrid; Artetxe, Ibai; Abad, José Luis; Alonso, Alicia; Busto, Jon V; Fajarí, Lluís; Montes, L Ruth; Sot, Jesús; Delgado, Antonio; Goñi, Félix M

    2015-03-03

    Three ceramide analogues have been synthesized, with sphingosine-like chains containing five conjugated double bonds. Pentaene I has an N-palmitoyl acyl chain, while the other two pentaenes contain also a doxyl radical, respectively, at C5 (Penta5dox) and at C16 (Penta16dox) positions of the N-acyl chain. Pentaene I maximum excitation and emission wavelengths in a phospholipid bilayer are 353 and 478 nm, respectively. Pentaene I does not segregate from the other lipids in the way natural ceramide does, but rather mixes with them in a selective way according to the lipid phases involved. Fluorescence confocal microscopy studies show that when lipid domains in different physical states coexist, Pentaene I emission is higher in gel than in fluid domains, and in liquid-ordered than in liquid-disordered areas. Electron paramagnetic resonance of the pentaene doxyl probes confirms that these molecules are sensitive to the physical state of the bilayer. Calorimetric and fluorescence quenching experiments suggest that the lipids under study orient themselves in lipid bilayers with their polar moieties located at the lipid-water interface. The doxyl radical in the N-acyl chain quenches the fluorescence of the pentaene group when in close proximity. Because of this property, Penta16dox can detect gel-fluid transitions in phospholipids. The availability of probes for lipids in the gel phase is important in view of novel evidence for the existence of gel microdomains in cell membranes.

  20. 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

  1. Bound-free Spectra for Diatomic Molecules

    NASA Technical Reports Server (NTRS)

    Schwenke, David W.

    2012-01-01

    It is now recognized that prediction of radiative heating of entering space craft requires explicit treatment of the radiation field from the infrared (IR) to the vacuum ultra violet (VUV). While at low temperatures and longer wavelengths, molecular radiation is well described by bound-bound transitions, in the short wavelength, high temperature regime, bound-free transitions can play an important role. In this work we describe first principles calculations we have carried out for bound-bound and bound-free transitions in N2, O2, C2, CO, CN, NO, and N2+. Compared to bound ]bound transitions, bound-free transitions have several particularities that make them different to deal with. These include more complicated line shapes and a dependence of emission intensity on both bound state diatomic and atomic concentrations. These will be discussed in detail below. The general procedure we used was the same for all species. The first step is to generate potential energy curves, transition moments, and coupling matrix elements by carrying out ab initio electronic structure calculations. These calculations are expensive, and thus approximations need to be made in order to make the calculations tractable. The only practical method we have to carry out these calculations is the internally contracted multi-reference configuration interaction (icMRCI) method as implemented in the program suite Molpro. This is a widely used method for these kinds of calculations, and is capable of generating very accurate results. With this method, we must first of choose which electrons to correlate, the one-electron basis to use, and then how to generate the molecular orbitals.

  2. Locating Bound Structures in the Accelerating Universe

    NASA Astrophysics Data System (ADS)

    Pearson, David; Batuski, D. J.

    2013-01-01

    Given the overwhelming evidence of the universe’s accelerating expansion, the question of what structures are gravitationally bound becomes one of utmost interest. Dunner et al. 2006 (D06) and Busha et al. 2003 (B03) set out to answer this question analytically, and they arrived at fairly different answers owing to the differences in their assumptions of velocities at the present epoch. Applying their criteria to different superclusters, it’s possible to make predictions about what structures may be bound. We apply the criteria of D06 and B03 to the Aquarius, Microscopium, Corona Borealis, and Shapley superclusters to make predictions about what structures might be bound and compare with the results of simple N-body simulations to determine which method is a better predictor and to determine the likelihood that parts or all of the superclusters listed above are bound. We find that D06 tend to predict more structure to be bound than B03, and the results of the N-body simulations usually lie somewhere in between the two sets of predictions. Observational evidence, and simulation data suggests that pairs of clusters in Aquarius and Microscopium are gravitationally bound, and that Shapley contains a large complex of clusters that are bound, along with some additional bound pairs. The likelihood that any of the clusters in Corona Borealis are bound to one another is very small, contrary to the claims of Small et al. 1998, who claimed that the entire supercluster is likely gravitationally bound. Busha M. T., Adams F. C., Wechsler R. H., Evrard A. E., 2003, ApJ, 596, 713 Dunner R., Araya P. A., Meza A., Reisenegger A., 2006, MNRAS, 306, 803 Small T. A., Ma C., Sargent W. L. W., Hamilton D., 1998, ApJ, 492, 45

  3. Gridded electron reversal ionizer

    NASA Technical Reports Server (NTRS)

    Chutjian, Ara (Inventor)

    1993-01-01

    A gridded electron reversal ionizer forms a three dimensional cloud of zero or near-zero energy electrons in a cavity within a filament structure surrounding a central electrode having holes through which the sample gas, at reduced pressure, enters an elongated reversal volume. The resultant negative ion stream is applied to a mass analyzer. The reduced electron and ion space-charge limitations of this configuration enhances detection sensitivity for material to be detected by electron attachment, such as narcotic and explosive vapors. Positive ions may be generated by generating electrons having a higher energy, sufficient to ionize the target gas and pulsing the grid negative to stop the electron flow and pulsing the extraction aperture positive to draw out the positive ions.

  4. Design, Synthesis, and Biological Evaluation of Novel Pyridine-Bridged Analogues of Combretastatin-A4 as Anticancer Agents

    PubMed Central

    2015-01-01

    A series of novel pyridine-bridged analogues of combretastatin-A4 (CA-4) were designed and synthesized. As expected, the 4-atom linker configuration retained little cytotoxicities in the compounds 2e, 3e, 3g, and 4i. Activities of the analogues with 3-atom linker varied widely depending on the phenyl ring substitutions, and the 3-atom linker containing nitrogen represents the more favorable linker structure. Among them, three analogues (4h, 4s, and 4t) potently inhibited cell survival and growth, arrested cell cycle, and blocked angiogenesis and vasculature formation in vivo in ways comparable to CA-4. The superposition of 4h and 4s in the colchicine-binding pocket of tubulin shows the binding posture of CA-4, 4h, and 4s are similar, as confirmed by the competitive binding assay where the ability of the ligands to replace tubulin-bound colchicine was measured. The binding data are consistent with the observed biological activities in antiproliferation and suppression of angiogenesis but are not predictive of their antitubulin polymerization activities. PMID:24669888

  5. Paired Magmatic-Metallogenic Belts in Myanmar - an Andean Analogue?

    NASA Astrophysics Data System (ADS)

    Gardiner, Nicholas; Robb, Laurence; Searle, Michael; Morley, Christopher

    2015-04-01

    Myanmar (Burma) is richly endowed in precious and base metals, having one of the most diverse collections of natural resources in SE Asia. Its geological history is dominated by the staged closing of Tethys and the suturing of Gondwana-derived continental fragments onto the South China craton during the Mesozoic-Cenozoic. The country is located at a crucial geologic juncture where the main convergent Tethyan collision zone swings south around the Namche Barwa Eastern Himalayan syntaxis. However, despite recent work, the geological and geodynamic history of Myanmar remains enigmatic. Plate margin processes, magmatism, metasomatism and the genesis of mineral deposits are intricately linked, and there has long been recognized a relationship between the distribution of certain mineral deposit types, and the tectonic settings which favour their genesis. A better knowledge of the regional tectonic evolution of a potential exploration jurisdiction is therefore crucial to understanding its minerals prospectivity. This strong association between tectonics and mineralization can equally be applied in reverse. By mapping out the spatial, and temporal, distribution of presumed co-genetic mineral deposits, coupled with an understanding of their collective metallogenetic origin, a better appreciation of the tectonic evolution of a terrane may be elucidated. Identification and categorization of metallotects within a geodynamically-evolving terrane thus provides a complimentary tool to other methodologies (e.g. geochemical, geochronological, structural, geophysical, stratigraphical), for determining the tectonic history and inferred geodynamic setting of that terrane through time. Myanmar is one such study area where this approach can be undertaken. Here are found two near-parallel magmatic belts, which together contain a significant proportion of that country's mineral wealth of tin, tungsten, copper, gold and silver. Although only a few 100 km's apart, these belts exhibit a

  6. URCHIN: Reverse ray tracer

    NASA Astrophysics Data System (ADS)

    Altay, Gabriel; Theuns, Tom

    2014-12-01

    URCHIN is a Smoothed Particle Hydrodynamics (SPH) reverse ray tracer (i.e. from particles to sources). It calculates the amount of shielding from a uniform background that each particle experiences. Preservation of the adaptive density field resolution present in many gas dynamics codes and uniform sampling of gas resolution elements with rays are two of the benefits of URCHIN; it also offers preservation of Galilean invariance, high spectral resolution, and preservation of the standard uniform UV background in optically thin gas.

  7. Reversing Glass Wettability

    NASA Technical Reports Server (NTRS)

    Frazier, D. O.; Smith, J. E., Jr.; Kaukler, W. F.

    1985-01-01

    Treatment reverses wettability of glassware: Liquids that normally wet glass no longer do, and those that do not wet glass are made to do so. Useful in research on container effects in nucleation and growth of secondary phase from solution. Treatment consists of spreading 3 percent (by weight) solution of silicone oil in hexane isomers over glass, drying in air, and curing at 300 degrees C in vacuum for one hour.

  8. Time reversal interactive objects

    NASA Astrophysics Data System (ADS)

    Ing, Ros Ki; Quieffin, Nicolas; Catheline, Stefan; Fink, Mathias

    2001-05-01

    Time reversal has shown to be a fruitful concept in nondestructive testing in underwater acoustic or in ultrasonic imaging. In this paper this technique is adapted in the audible range to transform every day objects into tactile sensitive interfaces. A quick historical background is presented in the ultrasonic field and specially in chaotic cavity. In all time reversal experiments, it is demonstrated that a wave field spatially and temporally recorded is able to back propagate to its source. In other words, the field contains all the information on the location of the source. In the interactive experiments, it is shown that touching an object like a window, a table or a world globe generates an acoustic field easily detectable with one or two acoustic sensors. Using the concept of time reversal, the source location is deduced in real time. Then, touching objects at specific locations (virtual switches) is used to activate devices. Such devices are for example lights, stereo volume, or computer software. From a technical point of view, all these interactive experiments just use some computation easily performed with a standard personnel computer.

  9. Sulphur Spring: Busy Intersection and Possible Martian Analogue

    NASA Technical Reports Server (NTRS)

    Nankivell, A.; Andre, N.; Thomas-Keprta, K.; Allen, C.; McKay, D.

    2000-01-01

    Life in extreme environments exhibiting conditions similar to early Earth and Mars, such as Sulphur Spring, may harbor microbiota serving as both relics from the past as well as present day Martian analogues.

  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?

  11. Cell-cycle analyses using thymidine analogues in fission yeast.

    PubMed

    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.

  12. Weather and event generators based on analogues of atmospheric circulation

    NASA Astrophysics Data System (ADS)

    Yiou, Pascal

    2015-04-01

    Analogues of atmospheric circulation have had numerous applications on weather prediction, climate reconstructions and detection/attribution analyses. A stochastic weather generator based on circulation analogues was recently proposed by Yiou (2014) to simulate sequences of European temperatures. One of the features of this weather generator is that it preserves the spatial and temporal structures of the climate variables to be simulated. This method is flexible enough to be combined efficiently with a storm detection algorithm in order to generate large catalogues of high impact extra-tropical storms that hit Europe. I will present the gist of the method of circulation analogues and some performances. Two promising applications for weather generators based on this method (ensemble climate prediction and extra-tropical storms) will be tested. References Yiou, P.: AnaWEGE: a weather generator based on analogues of atmospheric circulation, Geosci. Model Dev., 7, 531-543, doi:10.5194/gmd-7-531-2014, 2014.

  13. Effect of glutamate analogues on brain tumor cell lines.

    PubMed

    Campbell, G L; Bartel, R; Freidman, H S; Bigner, D D

    1985-10-01

    Glutamate analogues have been used in many different experimental approaches in neurobiology. A small number of these analogues have been classified as gliotoxic. We have examined the effect of seven glutamate analogues (five gliotoxic and two neurotoxic) on the growth and viability of four human glioma cell lines, one human medulloblastoma cell line, and one human sarcoma cell line. Aminoadipic acid and homocysteic acid predominantly affected the growth of two glioma cell lines in the presence of 4 mM glutamine. Phosphonobutyric acid predominantly affected the other two glioma cell lines and the medulloblastoma cell line in the presence of 4 mM glutamine. In medium containing no glutamine, all three analogues had marked effects on all the cell lines except the sarcoma cell line. These effects were dose dependent. We postulate that these results can in part be explained on the basis of metabolic compartmentalization.

  14. A Non-Verbal Analogue to the Verbal Transformation Effect

    ERIC Educational Resources Information Center

    Lass, Norman J.; And Others

    1973-01-01

    Investigates the effectiveness of non-speech auditory stimuli in eliciting transformations analogous to those reported for speech stimuli to determine if a non-verbal analogue to the verbal transformation effect exists. (DD)

  15. A Fluorescent Adenosine Analogue as a Substrate for an A-to-I RNA Editing Enzyme.

    PubMed

    Mizrahi, Rena A; Shin, Dongwon; Sinkeldam, Renatus W; Phelps, Kelly J; Fin, Andrea; Tantillo, Dean J; Tor, Yitzhak; Beal, Peter A

    2015-07-20

    Adenosine to inosine RNA editing catalyzed by ADAR enzymes is common in humans, and altered editing is associated with disease. Experiments using substrate RNAs with adenosine analogues at editing sites are useful for defining features of the ADAR reaction mechanism. The reactivity of ADAR2 was evaluated with RNA containing the emissive adenosine analogue thieno[3,4-d]-6-aminopyrimidine ((th)A). This nucleoside was incorporated into a mimic of the glutamate receptor B (GluR B) mRNA R/G editing site. We found that (th)A is recognized by AMV reverse transcriptase as A, and is deaminated rapidly by human ADAR2 to give (th)I. Importantly, ADAR reaction progress can be monitored by following the deamination-induced change in fluorescence of the (th)A-modified RNA. The observed high (th)A reactivity adds to our understanding of the structural features that are necessary for an efficient hADAR2 reaction. Furthermore, the new fluorescent assay is expected to accelerate mechanistic studies of ADARs.

  16. Structural Basis for Recognition of Guanosine by a Synthetic Tricyclic Cytosine Analogue: Guanidinium G-Clamp

    SciTech Connect

    Wilds, C.J.; Maier, M.A.; Manoharan, M.; Egli, M.

    2010-03-08

    An oligonucleotide analogue containing a novel heterocyclic analogue, the guanidinium G-clamp, was designed to allow formation of five H-bonds to guanosine. The guanidinium group was introduced postsynthetically by treatment of the deprotected oligonucleotide containing a free amino group with a solution of 1H-pyrazole-1-carboxamidine and purified by a combination of size-exclusion chromatography and reversed-phase HPLC. A single incorporation of this modification into an oligodeoxynucleotide sequence was found to increase duplex stability by 13{sup o} and 16{sup o} per modification to RNA and DNA, respectively. Crystals of a self-complementary decamer sequence containing this modification were grown and diffracted to 1-{angstrom} resolution. The structure was solved by molecular replacement and revealed that the modification forms additional H-bonds to O(6) and N(7) of guanosine through the amino and imino N-atoms, respectively. The origins of enhanced duplex stability are also attributed to increased stacking interactions mediated by the phenoxazine moiety of the G-clamp and formation of H-bond networks between the positively charged guanidinium group, H{sub 2}O molecules, and negatively charged O-atoms from phosphates on the adjacent strand.

  17. Structure-activity relationship of tryptamine analogues on the heart of Venus mercenaria.

    PubMed

    GREENBERG, M J

    1960-09-01

    A number of tryptamine analogues and other exciter agents have been tested on the heart of Venus mercenaria. The method of estimation of potency, especially for irreversibly acting compounds, is discussed. Specificity of action with respect to the site of action of 5-hydroxytryptamine is defined experimentally. The specific activity of tyramine and phenethylamine and the non-specific excitatory action of indole and skatole indicate that the indole ring is neither necessary nor sufficient for 5-hydroxytryptamine-like activity. Tryptamine analogues differ in mode of action as well as potency. Congeners without a 5-hydroxyl group tend to act more slowly and irreversibly as well as less strongly than 5-hydroxytryptamine. Methyl substitution also increases the time of action and difficulty of reversal. However, the potency of such compounds may be increased or decreased depending upon the position of substitution and the presence of the 5-hydroxyl group. The relations between structure and potency and mode of action are discussed. Suggestions are made concerning the effective conformation of the 5-hydroxytryptamine molecule and the nature of its receptor.

  18. Orally active fumagillin analogues: transformations of a reactive warhead in the gastric environment.

    PubMed

    Arico-Muendel, Christopher C; Blanchette, Heather; Benjamin, Dennis R; Caiazzo, Teresa M; Centrella, Paolo A; DeLorey, Jennifer; Doyle, Elisabeth G; Johnson, Steven R; Labenski, Matthew T; Morgan, Barry A; O'Donovan, Gary; Sarjeant, Amy A; Skinner, Steven; Thompson, Charles D; Griffin, Sarah T; Westlin, William; White, Kerry F

    2013-04-11

    Semisynthetic analogues of fumagillin, 1, inhibit methionine aminopeptidase-2 (MetAP2) and have entered the clinic for the treatment of cancer. An optimized fumagillin analogue, 3 (PPI-2458), was found to be orally active, despite containing a spiroepoxide function that formed a covalent linkage to the target protein. In aqueous acid, 3 underwent ring-opening addition of water and HCl, leading to four products, 4-7, which were characterized in detail. The chlorohydrin, but not the diol, products inhibited MetAP2 under weakly basic conditions, suggesting reversion to epoxide as a step in the mechanism. In agreement, chlorohydrin 6 was shown to revert rapidly to 3 in rat plasma. In an ex vivo assay, rats treated with purified acid degradants demonstrated inhibition of MetAP2 that correlated with the biochemical activity of the compounds. Taken together, the results indicate that degradation of the parent compound was compensated by the formation of active equivalents leading to a pharmacologically useful level of MetAP2 inhibition.

  19. Effects of prostaglandins and thromboxane analogues on bullock and dog iris sphincter preparations.

    PubMed

    Dong, Y J; Jones, R L

    1982-05-01

    1 The bullock iris sphincter was contracted by low concentrations of prostaglandin E2 (PGE2), 16, 16-dimethyl PGE2 and 17,18,19,20-tetranor-16-p-chlorophenoxy PGE2. Other compounds with thromboxane-like actions, for example 11,9-epoxymethano PGH2, were also potent spasmogens, ZK 36374, a stable carbacyclin, was a partial agonist on the PGE-sensitive system of this tissue. 2 The thromboxane antagonist, EP 045, had little effect on the action of PGE2 and 16,16-dimethyl PGE2 on the bullock iris. 3 The dog iris sphincter was sensitive to PGF2 alpha but not to PGE2 and 11,9-epoxymethano PGH2. 4 16,16-dimethyl PGE2 had very low activity on the dog iris in contrast to its high activity on the bullock iris. The reverse was found with the 17,18,19,20-tetranor-16-m-trifluoromethylphenoxy analogue of PGF2 alpha (ICI 81008). This indicates a considerable selectivity of action of the two analogues. 5 The results are discussed in relation to the existing knowledge of prostanoid receptors.

  20. Effects of prostaglandins and thromboxane analogues on bullock and dog iris sphincter preparations.

    PubMed Central

    Dong, Y. J.; Jones, R. L.

    1982-01-01

    1 The bullock iris sphincter was contracted by low concentrations of prostaglandin E2 (PGE2), 16, 16-dimethyl PGE2 and 17,18,19,20-tetranor-16-p-chlorophenoxy PGE2. Other compounds with thromboxane-like actions, for example 11,9-epoxymethano PGH2, were also potent spasmogens, ZK 36374, a stable carbacyclin, was a partial agonist on the PGE-sensitive system of this tissue. 2 The thromboxane antagonist, EP 045, had little effect on the action of PGE2 and 16,16-dimethyl PGE2 on the bullock iris. 3 The dog iris sphincter was sensitive to PGF2 alpha but not to PGE2 and 11,9-epoxymethano PGH2. 4 16,16-dimethyl PGE2 had very low activity on the dog iris in contrast to its high activity on the bullock iris. The reverse was found with the 17,18,19,20-tetranor-16-m-trifluoromethylphenoxy analogue of PGF2 alpha (ICI 81008). This indicates a considerable selectivity of action of the two analogues. 5 The results are discussed in relation to the existing knowledge of prostanoid receptors. PMID:6177369

  1. 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

  2. Adjuvant properties of a simplified C32 monomycolyl glycerol analogue.

    PubMed

    Bhowruth, Veemal; Minnikin, David E; Agger, Else Marie; Andersen, Peter; Bramwell, Vincent W; Perrie, Yvonne; Besra, Gurdyal S

    2009-04-01

    A simplified C(32) monomycolyl glycerol (MMG) analogue demonstrated enhanced immunostimulatory activity in a dioctadecyl ammonium bromide (DDA)/Ag85B-ESAT-6 formulation. Elevated levels of IFN-gamma and IL-6 were produced in spleen cells from mice immunised with a C(32) MMG analogue comparable activity to the potent Th1 adjuvant, trehalose 6,6'-di-behenate (TDB).

  3. Semisynthesis of salviandulin E analogues and their antitrypanosomal activity.

    PubMed

    Aoyagi, Yutaka; Fujiwara, Koji; Yamazaki, Akira; Sugawara, Naoko; Yano, Reiko; Fukaya, Haruhiko; Hitotsuyanagi, Yukio; Takeya, Koichi; Ishiyama, Aki; Iwatsuki, Masato; Otoguro, Kazuhiko; Yamada, Haruki; Ōmura, Satoshi

    2014-01-15

    A series of analogues of salviandulin E, a rearranged neoclerodane diterpene originally isolated from Salvia leucantha (Lamiaceae), were prepared and their in vitro activity against Trypanosoma brucei brucei was evaluated with currently used therapeutic drugs as positive controls. One of the 19 compounds prepared and assayed in the present study, butanoyl 3,4-dihydrosalviandulin E analogue was found to be a possible candidate for an antitrypanosomal drug with fairly strong antitrypanosomal activity and lower cytotoxicity.

  4. Catalytic antioxidants: regenerable tellurium analogues of vitamin E.

    PubMed

    Singh, Vijay P; Poon, Jia-fei; Engman, Lars

    2013-12-20

    In an effort to improve the chain-breaking capacity of the natural antioxidants, an octyltelluro group was introduced next to the phenolic moiety in β- and δ-tocopherol. The new vitamin E analogues quenched peroxyl radicals more efficiently than α-tocopherol and were readily regenerable by aqueous N-acetylcysteine in a simple membrane model composed of a stirring chlorobenzene/water two-phase system. The novel tocopherol analogues could also mimic the action of the glutathione peroxidase enzymes.

  5. 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.

  6. Furoxan analogues of the histamine H3-receptor antagonist imoproxifan and related furazan derivatives.

    PubMed

    Tosco, Paolo; Bertinaria, Massimo; Di Stilo, Antonella; Cena, Clara; Sorba, Giovanni; Fruttero, Roberta; Gasco, Alberto

    2005-08-01

    Synthesis and pharmacological characterisation of a series of compounds in which the oxime substructure present in imoproxifan was constrained in the pentatomic NO-donor furoxan ring, as well as their structurally related furazan analogues devoid of NO-donating properties, are described. The whole series of products displayed reversible histamine H3-antagonistic activity on guinea-pig ileum. 4-(4-(3-(1H-Imidazol-4-yl)propoxy)phenyl)furoxan-3-carbonitrile 16 was also able to induce partial relaxation when added to the bath after electrical contraction of the guinea-pig ileum during the study of its H3-antagonistic properties. This phenomenon seems to be dependent on NO-mediated sGC activation. The lipophilic-hydrophilic balance of all the products was investigated.

  7. Cytopathological features of mammary analogue secretory carcinoma--review of literature.

    PubMed

    Takeda, Maiko; Kasai, Takahiko; Morita, Kohei; Takeuchi, Mao; Nishikawa, Takeshi; Yamashita, Akinori; Mikami, Shinji; Hosoi, Hiroshi; Ohbayashi, Chiho

    2015-02-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that morphologically resembles mammary secretory carcinoma and carries the identical ETV6-NTRK3 fusion gene. We report a surgical resected case of MASC in the parotid gland of a 41-year-old man. The cytological smears of a preoperative fine-needle aspiration showed many sheets and crowded clusters of monotonous epithelioid cells with mild atypia, suggestive of monomorphic tumor. Histologically, the tumor was composed of cuboidal cells with follicular, tubular, and solid structures, reminiscent of acinic cell carcinoma of follicular variant, which had been previously classified. This case had ETV6-NTRK3 fusion gene transcript confirmed by fluorescence in situ hybridization and reverse transcription polymerase chain reaction. In the cytological and histopathological diagnosis of monomorphic tumor of salivary gland, MASC needs to be taken into consideration as a differential diagnosis. Further immunohistochemical and gene analyses are needed in diagnosis of MASC.

  8. Radiolabelling, quality control and radiochemical purity assessment of the Octreotide analogue 68Ga DOTA NOC.

    PubMed

    Di Pierro, D; Rizzello, A; Cicoria, G; Lodi, F; Marengo, M; Pancaldi, D; Trespidi, S; Boschi, S

    2008-08-01

    Somatostatin receptors 1-5 are over expressed in neuroendocrine tumours (NETs). 68Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-Octreotide (DOTA NOC), a recent synthesized somatostatin analogue, shows high affinity for those receptors. Herein, modifications of a commercial module for the labelling of DOTA NOC with 68Ga, as well as the assessment of time course of the radiochemical purity variation are described. The evaluation of radiochemical stability was done by two different chromatographic methods: reversed-phase radio HPLC and fast TLC analysis. Labelled compound has been found radiochemically stable within 3h from the end of labelling (EOL) and radiochemical purity was always higher than 99%. After 73 labelling sessions the system showed great reproducibility and high radiochemical yield.

  9. Photophysical and nonlinear optical studies of tetraakynyl zincphthalocyanine and its "clicked" analogue

    NASA Astrophysics Data System (ADS)

    Bankole, Owolabi M.; Nyokong, Tebello

    2015-06-01

    We report here for the first time on the photophysical and nonlinear optical behavior of tetra-substituted alkynyl zinc phthalocyanine and its "clicked" analogue (4 and 5). The compounds exhibited high triplet quantum yields in dimethylsulphoxide (DMSO). Nonlinear optical (NLO) properties were also evaluated for the two compounds at 532 nm and 10 ns in DMSO. We observed two-photon absorption (2PA) and strong reverse saturable absorption (RSA) as the dominant mechanisms at nanosecond laser excitation. The presence of electron acceptor groups fused with triazole linkers in the peripheral positions of 4 provide excellent coexistent features, such as enhanced triplet quantum yields and lifetimes compared to 5. Large third-order susceptibility (2.09 × 10-11 and 3.53 × 10-9 esu) and hyperpolarizability (1.09 × 10-30 and 9.13 × 10-29 esu) were estimated for complexs 4 and 5, respectively.

  10. Operations of Majorana Bound States in Charge-qubit Arrays

    NASA Astrophysics Data System (ADS)

    Mao, Ting; Wang, Zidan

    2014-03-01

    The experimental pursuit of Majorana bound state (MBS) in one-dimensional (1D) solid state systems has been brought into the limelight since the proposal of Kitaev's toy lattice model. Here we use the inductively coupled charge-qubit array to realize a tunable Kitaev model. With the advantages of the superconducting-qubit circuit, we can manipulate the parameters of Kitaev model and change the symmetry class to which the model Hamiltonian belongs from the class D to the class BDI. We also discuss a simple class DIII model constructed by coupling two copies of the class D charge-qubit array. Using the time reversal symmetry and a residual U(1) spin rotation symmetry of the model, we explore the possibility of implementing universal single topological qubit operations.

  11. SPAM: A Simple Approach for Profiling Bound Water Molecules.

    PubMed

    Cui, Guanglei; Swails, Jason M; Manas, Eric S

    2013-12-10

    A method that identifies the hydration shell structure of proteins and estimates the relative free energies of water molecules within that hydration shell is described. The method, which we call "SPAM" (maps spelled in reverse), utilizes explicit solvent molecular dynamics (MD) simulations to capture discrete hydration sites at the water-protein interface and computes a local free energy measure from the distribution of interaction energies between water and the environment at a specific site. SPAM is able to provide a qualitative estimate of the thermodynamic profile of bound water molecules that correlates nicely with well-studied structure-activity relationships and observed binding "hot spots". This is demonstrated in retrospective analyses of HIV1 protease and hen egg white lysozyme, where the effects of water displacement and solvent binding have been studied extensively. The simplicity and effectiveness of SPAM allow for prospective application during the drug discovery process.

  12. The relevance of analogue studies for understanding obsessions and compulsions.

    PubMed

    Abramowitz, Jonathan S; Fabricant, Laura E; Taylor, Steven; Deacon, Brett J; McKay, Dean; Storch, Eric A

    2014-04-01

    Analogue samples are often used to study obsessive-compulsive (OC) symptoms and related phenomena. This approach is based on the hypothesis that results derived from such samples are relevant to understanding OC symptoms in individuals with a diagnosis of obsessive-compulsive disorder (OCD). Two decades ago, Gibbs (1996) reviewed the available literature and found initial support for this hypothesis. Since then there have been many important advances addressing this issue. The purpose of the present review was to synthesize various lines of research examining the assumptions of using analogue samples to draw inferences about people with OCD. We reviewed research on the prevalence of OC symptoms in non-clinical populations, the dimensional (vs. categorical) nature of these symptoms, phenomenology, etiology, and studies on developmental and maintenance factors in clinical and analogue samples. We also considered the relevance of analogue samples in OCD treatment research. The available evidence suggests research with analogue samples is highly relevant for understanding OC symptoms. Guidelines for the appropriate use of analogue designs and samples are suggested.

  13. 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

  14. 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.

  15. Cladribine Analogues via O⁶-(Benzotriazolyl) Derivatives of Guanine Nucleosides.

    PubMed

    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

    2015-10-09

    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 in 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 ribose analogue of cladribine showed activity, but was the 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, cladribine and its ribose analogue were most active.

  16. Reverse lectin ELISA for detecting fucosylated forms of α1-acid glycoprotein associated with hepatocellular carcinoma

    PubMed Central

    Stål, Per; Zenlander, Robin; Edenvik, Pia; Alexandersson, Catharina; Haglund, Mats; Rydén, Ingvar; Påhlsson, Peter

    2017-01-01

    Altered fucosylation of glycoproteins is associated with development of hepatocellular carcinoma (HCC). Lectins have been commonly used to assay changes in fucosylation of plasma glycoproteins. In the present study a recombinantly engineered form of the fucose binding lectin Aleuria aurantia (AAL) consisting of a single binding site for fucose (S2), was used to construct a reverse lectin ELISA method. Microtiter plates coated with the S2 lectin were used to capture glycoproteins from plasma samples followed by antibody detection of S2-bound fucosylated α1-acid glycoprotein (S2-bound AGP). The method was used to compare the level of S2-bound AGP in serum samples from a small cohort of patients with hepatitis, cirrhosis or HCC. Using the reverse S2 lectin ELISA it was shown that the levels of S2-bound AGP was significantly higher in HCC patients compared to non-cancer patients and that there was also a significant elevation of S2-bound AGP in HCC patients compared to cirrhosis patients. There was no correlation between the level of S2-bound AGP and total AGP concentration. The performance of S2-bound AGP in differentiating HCC from cirrhosis samples or hepatitis samples were compared to other markers. A combination of S2-bound AGP, α-fetoprotein and AGP concentration showed performances giving area under receiver operating curves of 0.87 and 0.95 respectively. PMID:28296934

  17. Match-bounded String Rewriting Systems

    NASA Technical Reports Server (NTRS)

    Geser, Alfons; Hofbauer, Dieter; Waldmann, Johannes

    2003-01-01

    We introduce a new class of automated proof methods for the termination of rewriting systems on strings. The basis of all these methods is to show that rewriting preserves regular languages. To this end, letters are annotated with natural numbers, called match heights. If the minimal height of all positions in a redex is h+1 then every position in the reduct will get height h+1. In a match-bounded system, match heights are globally bounded. Using recent results on deleting systems, we prove that rewriting by a match-bounded system preserves regular languages. Hence it is decidable whether a given rewriting system has a given match bound. We also provide a sufficient criterion for the abence of a match-bound. The problem of existence of a match-bound is still open. Match-boundedness for all strings can be used as an automated criterion for termination, for match-bounded systems are terminating. This criterion can be strengthened by requiring match-boundedness only for a restricted set of strings, for instance the set of right hand sides of forward closures.

  18. Bounds on dark matter in solar orbit

    SciTech Connect

    Anderson, J.D.; Lau, E.L.; Taylor, A.H.; Dicus, D.A.; Teplitz, D.C.; Texas Univ., Austin; Maryland Univ., College Park )

    1989-07-01

    The possibility is considered that a spherical distribution of dark matter (DM), matter not visible with current instruments, is trapped in the sun's gravitational field. Bounds are placed from the motion of Uranus and Neptune, on the amount of DM that could be so trapped within the radius of those planets' orbits, as follows: from the Voyager 2, Uranus-flyby data new, more accurate ephemeris values are generated. Trapped DM mass is bounded by noting that such a distribution would increase the effective mass of the sun as seen by the outer planets and by using the new ephemeris values to bound such an increase. 34 refs.

  19. Lightweight Distance Bounding Protocol against Relay Attacks

    NASA Astrophysics Data System (ADS)

    Kim, Jin Seok; Cho, Kookrae; Yum, Dae Hyun; Hong, Sung Je; Lee, Pil Joong

    Traditional authentication protocols are based on cryptographic techniques to achieve identity verification. Distance bounding protocols are an enhanced type of authentication protocol built upon both signal traversal time measurement and cryptographic techniques to accomplish distance verification as well as identity verification. A distance bounding protocol is usually designed to defend against the relay attack and the distance fraud attack. As there are applications to which the distance fraud attack is not a serious threat, we propose a streamlined distance bounding protocol that focuses on the relay attack. The proposed protocol is more efficient than previous protocols and has a low false acceptance rate under the relay attack.

  20. Pattern Search Algorithms for Bound Constrained Minimization

    NASA Technical Reports Server (NTRS)

    Lewis, Robert Michael; Torczon, Virginia

    1996-01-01

    We present a convergence theory for pattern search methods for solving bound constrained nonlinear programs. The analysis relies on the abstract structure of pattern search methods and an understanding of how the pattern interacts with the bound constraints. This analysis makes it possible to develop pattern search methods for bound constrained problems while only slightly restricting the flexibility present in pattern search methods for unconstrained problems. We prove global convergence despite the fact that pattern search methods do not have explicit information concerning the gradient and its projection onto the feasible region and consequently are unable to enforce explicitly a notion of sufficient feasible decrease.

  1. Sound Velocity Bound and Neutron Stars

    SciTech Connect

    Bedaque, Paulo; Steiner, Andrew W.

    2015-01-21

    A conjecture that the velocity of sound in any medium is smaller than the velocity of light in vacuum divided by sqrt(3). Simple arguments support this bound in nonrelativistic and/or weakly coupled theories. Moreover, the bound has been demonstrated in several classes of strongly coupled theories with gravity duals and is saturated only in conformal theories. Here, we point out that the existence of neutron stars with masses around two solar masses combined with the knowledge of the equation of state of hadronic matter at low densities is in strong tension with this bound.

  2. 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

  3. Properties of phosphatidylcholine in the presence of its monofluorinated analogue.

    PubMed

    Smith, Eric A; van Gorkum, Christiaan M; Dea, Phoebe K

    2010-03-01

    In aqueous solution, the monofluorinated phospholipid 1-palmitoyl-2-[16-fluoropalmitoyl]sn-glycero-3-phosphocholine (F-DPPC) interdigitates without the use of inducing agents. To understand the thermal and physical properties of this unique lipid, F-DPPC was combined with the non-fluorinated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-diarachidoyl-sn-glycero-3-phosphocholine (DAPC). Differential scanning calorimetry (DSC) was used to determine the miscibility and thermotropic phase behavior of these binary lipid mixtures. In addition, the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) and a DPH-labeled analogue of DPPC, 2-(3-(diphenylhexatrienyl) propanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine (beta-DPH HPC, aka DPH-PC or DPHpPC), were used to detect interdigitation. In F-DPPC, the fluorescence intensity of both probes decreased a similar amount and to a degree that is consistent with an interdigitated system. We also determined that there are two separate effects of increasing the ratio of F-DPPC in the DPPC/F-DPPC system. With low amounts of F-DPPC, there is little evidence that the system is heavily interdigitated. Instead, we hypothesize that the introduction of F-DPPC provides nucleation sites that alter the kinetics, reversibility, and temperature of the main transition (T(m)). At higher mol% of F-DPPC, we propose that interdigitated F-DPPC-rich domains form to create a phase-segregated system. While DPPC/F-DPPC was highly miscible, the DAPC/F-DPPC system was significantly less miscible. Additionally, we observed that DAPC/F-DPPC samples have reduced solubility in water, which affected the acquisition of fluorescence data. However, our DSC results indicate the existence of DAPC-rich and F-DPPC-rich components. Furthermore, this data support that the mixing was disruptive to lipid packing and that the presence of DAPC hinders the interdigitation of F-DPPC.

  4. New nucleotide analogues with enhanced signal properties.

    PubMed

    Cherkasov, Dmitry; Biet, Thorsten; Bäuml, Englbert; Traut, Walther; Lohoff, Michael

    2010-01-01

    We describe synthesis and testing of a novel type of dye-modified nucleotides which we call macromolecular nucleotides (m-Nucs). Macromolecular nucleotides comprise a nucleotide moiety, a macromolecular linear linker, and a large macromolecular ligand carrying multiple fluorescent dyes. With incorporation of the nucleotide moiety into the growing nucleic acid strand during enzymatic synthesis, the macromolecular ligand together with the coupled dyes is bound to the nucleic acid. By the use of this new class of modified nucleotides, signals from multiple dye molecules can be obtained after a single enzymatic incorporation event. The modified nucleotides are considered especially useful in the fields of nanobiotechnology, where signal stability and intensity is a limiting factor.

  5. Effects of Pseudomonas species on the release of bound sup 14 C residues from soil treated with ( sup 14 C)atrazine

    SciTech Connect

    Khan, S.U.; Behki, R.M. )

    1990-11-01

    The release of bound (nonextractable) {sup 14}C residues from soil previously treated with ({sup 14}C)atrazine was investigated by incubation of the solvent-extracted soil with two species of Pseudomonas capable of metabolizing atrazine. The two species, 192 and 194, released bound {sup 14}C residues from the soil. Addition of glucose, known to increase microbiological activities, to the incubated soil appeared to enhance the release of soil-bound {sup 14}C residues, in particular in the presence of Pseudomonas species 192. The {sup 14}C bound residues in soil, mainly present as the parent compound and its hydroxy and monodealkylated analogues, were released into the incubation mixture and were subsequently metabolized by the two species involving dechlorination and dealkylation.

  6. Reversible Thermal Stiffening in Polymer Nanocomposites.

    PubMed

    Senses, Erkan; Isherwood, Andrew; Akcora, Pinar

    2015-07-15

    Miscible polymer blends with different glass transition temperatures (Tg) are known to create confined interphases between glassy and mobile chains. Here, we show that nanoparticles adsorbed with a high-Tg polymer, poly(methyl methacrylate), and dispersed in a low-Tg matrix polymer, poly(ethylene oxide), exhibit a liquid-to-solid transition at temperatures above Tg's of both polymers. The mechanical adaptivity of nanocomposites to temperature underlies the existence of dynamically asymmetric bound layers on nanoparticles and more importantly reveals their impact on macroscopic mechanical response of composites. The unusual reversible stiffening behavior sets these materials apart from conventional polymer composites that soften upon heating. The presented stiffening mechanism in polymer nanocomposites can be used in applications for flexible electronics or mechanically induced actuators responding to environmental changes like temperature or magnetic fields.

  7. Reversible brazing process

    DOEpatents

    Pierce, Jim D.; Stephens, John J.; Walker, Charles A.

    1999-01-01

    A method of reversibly brazing surfaces together. An interface is affixed to each surface. The interfaces can be affixed by processes such as mechanical joining, welding, or brazing. The two interfaces are then brazed together using a brazing process that does not defeat the surface to interface joint. Interfaces of materials such as Ni-200 can be affixed to metallic surfaces by welding or by brazing with a first braze alloy. The Ni-200 interfaces can then be brazed together using a second braze alloy. The second braze alloy can be chosen so that it minimally alters the properties of the interfaces to allow multiple braze, heat and disassemble, rebraze cycles.

  8. Reversal bending fatigue testing

    DOEpatents

    Wang, Jy-An John; Wang, Hong; Tan, Ting

    2014-10-21

    Embodiments for apparatuses for testing reversal bending fatigue in an elongated beam are disclosed. Embodiments are configured to be coupled to first and second end portions of the beam and to apply a bending moment to the beam and create a pure bending condition in an intermediate portion of the beam. Embodiments are further configured to cyclically alternate the direction of the bending moment applied to the beam such that the intermediate portion of the beam cyclically bends in opposite directions in a pure bending condition.

  9. Selective effects of purine and pyrimidine analogues and of respiratory inhibitors on perithecial development and branching in sordaria.

    PubMed

    Lindenmayer, A; Schoen, H F

    1967-08-01

    The initiation of perithecia in the homothallic ascomycete Sordaria fimicola was completely suppressed, without seriously inhibiting vegetative growth, by growing the fungus on an agar medium containing one of the following additions: 1) 1 mum 5-fluorouracil, 2) 10 to 100 mum 6-azauracil, 8-azaguanine or 8-azaadenine, 3) 50 to 500 mum cyanide or azide, 4) 5% (w/v) casein hydrolysate. In contrast to the selective activity of the analogues of 3 RNA bases, whose inhibition could be reversed by the appropriate normal bases only, none of the analogues of thymine were active, neither were the thio-derivatives of RNA bases. Other inhibitors of RNA and protein synthesis, like actinomycin D, puromycin and cycloheximide, were also without selective activity, although the last of these inhibited perithecial maturation at 0.1 mum concentration but not initiation. Amino acid analogues were inactive, as were the metabolic inhibitors thiourea, 2,4-dinitrophenol and fluoride. The compounds which inhibited the formation of perithecia also lowered the branching frequency of leading hyphae, but not their linear growth rates. Consequently, the branch densities were diminished in their presence. Hypotheses to account for these findings are discussed in terms of inhibition of growth in general, of the synthesis of some specific messenger RNAs, and of RNA-mediated transport across membranes, the last of which seeming the most fruitful for further work.

  10. A neural network for bounded linear programming

    SciTech Connect

    Culioli, J.C.; Protopopescu, V.; Britton, C.; Ericson, N. )

    1989-01-01

    The purpose of this paper is to describe a neural network implementation of an algorithm recently designed at ORNL to solve the Transportation and the Assignment Problems, and, more generally, any explicitly bounded linear program. 9 refs.

  11. Family of nonlocal bound entangled states

    NASA Astrophysics Data System (ADS)

    Yu, Sixia; Oh, C. H.

    2017-03-01

    Bound entanglement, being entangled yet not distillable, is essential to our understanding of the relations between nonlocality and entanglement besides its applications in certain quantum information tasks. Recently, bound entangled states that violate a Bell inequality have been constructed for a two-qutrit system, disproving a conjecture by Peres that bound entanglement is local. Here we construct this kind of nonlocal bound entangled state for all finite dimensions larger than two, making possible their experimental demonstration in most general systems. We propose a Bell inequality, based on a Hardy-type argument for nonlocality, and a steering inequality to identify their nonlocality. We also provide a family of entanglement witnesses to detect their entanglement beyond the Bell inequality and the steering inequality.

  12. Bound states in the Higgs model

    NASA Astrophysics Data System (ADS)

    di Leo, Leo; Darewych, Jurij W.

    1994-02-01

    We derive relativistic wave equations for the bound states of two Higgs bosons within the Higgs sector of the minimal standard model. The variational method and the Hamiltonian formalism of QFT are used to obtain the equations using a simple ||hh>+||hhh> Fock-space ansatz. We present approximate solutions of these equations for a range of Higgs boson masses, and explore the parameter space which corresponds to the existence of two-Higgs-boson bound states.

  13. Hamiltonian anomalies of bound states in QED

    SciTech Connect

    Shilin, V. I.; Pervushin, V. N.

    2013-10-15

    The Bound State in QED is described in systematic way by means of nonlocal irreducible representations of the nonhomogeneous Poincare group and Dirac's method of quantization. As an example of application of this method we calculate triangle diagram Para-Positronium {yields} {gamma}{gamma}. We show that the Hamiltonian approach to Bound State in QED leads to anomaly-type contribution to creation of pair of parapositronium by two photon.

  14. Performance bound for real OTEC heat engines

    SciTech Connect

    Wu, C.

    1987-01-01

    Maximum power and efficiency at the maximum power of an irreversible OTEC heat engine are treated. When time is explicitly considered in the energy exchanges between the heat engine and its surroundings, it is found that there is a bound on the efficiency of the real OTEC heat engine at the maximum power condition. This bound can guide the evaluation of existing OTEC systems or influence design of future OTEC heat engines.

  15. Elastic scattering with weakly bound projectiles

    SciTech Connect

    Figueira, J. M.; Abriola, D.; Arazi, A.; Capurro, O. A.; Marti, G. V.; Martinez Heinmann, D.; Pacheco, A. J.; Testoni, J. E.; Barbara, E. de; Fernandez Niello, J. O.; Padron, I.; Gomes, P. R. S.; Lubian, J.

    2007-02-12

    Possible effects of the break-up channel on the elastic scattering threshold anomaly has been investigated. We used the weakly bound 6,7Li nuclei, which is known to undergo break-up, as projectiles in order to study the elastic scattering on a 27Al target. In this contribution we present preliminary results of these experiments, which were analyzed in terms of the Optical Model and compared with other elastic scattering data using weakly bound nuclei as projectile.

  16. Reverse engineering molecular hypergraphs.

    PubMed

    Rahman, Ahsanur; Poirel, Christopher L; Badger, David J; Estep, Craig; Murali, T M

    2013-01-01

    Analysis of molecular interaction networks is pervasive in systems biology. This research relies almost entirely on graphs for modeling interactions. However, edges in graphs cannot represent multiway interactions among molecules, which occur very often within cells. Hypergraphs may be better representations for networks having such interactions, since hyperedges can naturally represent relationships among multiple molecules. Here, we propose using hypergraphs to capture the uncertainty inherent in reverse engineering gene-gene networks. Some subsets of nodes may induce highly varying subgraphs across an ensemble of networks inferred by a reverse engineering algorithm. We provide a novel formulation of hyperedges to capture this uncertainty in network topology. We propose a clustering-based approach to discover hyperedges. We show that our approach can recover hyperedges planted in synthetic data sets with high precision and recall, even for moderate amount of noise. We apply our techniques to a data set of pathways inferred from genetic interaction data in S. cerevisiae related to the unfolded protein response. Our approach discovers several hyperedges that capture the uncertain connectivity of genes in relevant protein complexes, suggesting that further experiments may be required to precisely discern their interaction patterns. We also show that these complexes are not discovered by an algorithm that computes frequent and dense subgraphs.

  17. Reversal of sterilisation.

    PubMed

    Cartwright, A

    1977-09-03

    It is difficult to know what conclusions one can reach in a study of 103 women who asked for reversal of sterilization (Mr. R.M.L. Winston, July 30, p. 305) when there are no data about the numbers and characteristics of the women who were sterilized and have not asked for reversal. And Mr. Winston's conclusion that it "seems unwise to sterilise women under 30 particularly immediately after pregnancy or if their marriage is in jeopardy" is therefore difficult to justify and has a disconcertingly paternalistic ring. It also implies that the stability or otherwise of a marriage should be a prime concern of obstetricians when women request sterilization. But what distrubed me most about Mr. Winston's article was his statement that "most women in this survey had been told that termination would not be undertaken without sterilisation." I wonder if this form of ultimatum, which Mr. Winston condemns, is likely to increase now that this operation is performed under a fee-for-service system?

  18. 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

  19. Synthesis and Evaluation of Eight- and Four-membered Iminosugar Analogues as Inhibitors of Testicular Ceramide-specific Glucosyltransferase, Testicular β-Glucosidase 2, and other Glycosidases

    PubMed Central

    Lee, Jae Chul; Francis, Subhashree; Dutta, Dinah; Gupta, Vijayalaxmi; Yang, Yan; Zhu, Jin-Yi; Tash, Joseph S.; Schönbrunn, Ernst

    2012-01-01

    Eight- and four-membered analogues of N-butyldeoxynojirimycin (NB-DNJ), a reversible male contraceptive in mice, were prepared and tested. A chiral pool approach was used for the synthesis of the target compounds. Key steps for the synthesis of the eight-membered analogues involve: ringclosing metathesis and Sharpless asymmetric dihydroxylation, and for the four-membered analogues: Sharpless epoxidation, epoxide ring opening (azide), and Mitsunobu reaction to form the four-membered ring. (3S,4R,5S,6R,7R)-1-Nonylazocane-3,4,5,6,7-pentaol (6), was moderately active against rat-derived ceramide-specific glucosyltransferase and four of the other eight-membered analogues were weakly active against rat-derived β-glucosidase 2. Among the four-membered analogues, ((2R,3s,4S)-3-hydroxy-1-nonylazetidine-2,4-diyl)dimethanol (25), displayed selective inhibitory activity against mouse-derived ceramide-specific glucosyltransferase and was about half as potent as NB-DNJ against the rat-derived enzyme. ((2S,4S)-3-Hydroxy-1-nonyl-azetidine-2,4-diyl)dimethanol (27) was found to be a selective inhibitor of β-glucosidase 2, with potency similar to NB-DNJ. Additional glycosidase assays were performed to identify potential other therapeutic applications. The eight-membered iminosugars exhibited specificity for almond-derived β-glucosidase and the 1-nonylazetidine 25 inhibited α-glucosidase (Saccharomyces cerevisiae) with an IC50 of 600 nM and β-glucosidase (almond) with an IC50 of 20 µM. Only N-nonyl derivatives were active, emphasizing the importance of a long lipophilic side chain for inhibitory activity of the analogues studied. PMID:22432895

  20. Review of Insulin and its Analogues in Diabetes Mellitus

    PubMed Central

    Mane, Krishnappa; Chaluvaraju, KC; Niranjan, MS; Zaranappa, TR; Manjuthej, TR

    2012-01-01

    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

  1. Theoretical study on absorption and emission spectra of adenine analogues.

    PubMed

    Liu, Hongxia; Song, Qixia; Yang, Yan; Li, Yan; Wang, Haijun

    2014-04-01

    Fluorescent nucleoside analogues have attracted much attention in studying the structure and dynamics of nucleic acids in recent years. In the present work, we use theoretical calculations to investigate the structural and optical properties of four adenine analogues (termed as A1, A2, A3, and A4), and also consider the effects of aqueous solution and base pairing. The results show that the fluorescent adenine analogues can pair with thymine to form stable H-bonded WC base pairs. The excited geometries of both adenine analogues and WC base pairs are similar to the ground geometries. The absorption and emission maxima of adenine analogues are greatly red shifted compared with nature adenine, the oscillator strengths of A1 and A2 are stronger than A3 and A4 in both absorption and emission spectra. The calculated low-energy peaks in the absorption spectra are in good agreement with the experimental data. In general, the aqueous solution and base pairing can slightly red-shift both the absorption and emission maxima, and can increase the oscillator strengths of absorption spectra, but significantly decrease the oscillator strengths of A3 in emission spectra.

  2. Bioluminescent properties of obelin and aequorin with novel coelenterazine analogues.

    PubMed

    Gealageas, Ronan; Malikova, Natalia P; Picaud, Sandrine; Borgdorff, Aren J; Burakova, Ludmila P; Brûlet, Philippe; Vysotski, Eugene S; Dodd, Robert H

    2014-04-01

    The main analytical use of Ca(2+)-regulated photoproteins from luminous coelenterates is for real-time non-invasive visualization of intracellular calcium concentration ([Ca(2+)]i) dynamics in cells and whole organisms. A limitation of this approach for in vivo deep tissue imaging is the fact that blue light emitted by the photoprotein is highly absorbed by tissue. Seven novel coelenterazine analogues were synthesized and their effects on the bioluminescent properties of recombinant obelin from Obelia longissima and aequorin from Aequorea victoria were evaluated. Only analogues having electron-donating groups (m-OCH3 and m-OH) on the C6 phenol moiety or an extended resonance system at the C8 position (1-naphthyl and α-styryl analogues) showed a significant red shift of light emission. Of these, only the α-styryl analogue displayed a sufficiently high light intensity to allow eventual tissue penetration. The possible suitability of this compound for in vivo assays was corroborated by studies with aequorin which allowed the monitoring of [Ca(2+)]i dynamics in cultured CHO cells and in hippocampal brain slices. Thus, the α-styryl coelenterazine analogue might be potentially useful for non-invasive, in vivo bioluminescence imaging in deep tissues of small animals.

  3. An autonomous and reversible Maxwell's demon

    NASA Astrophysics Data System (ADS)

    Barato, A. C.; Seifert, U.

    2013-03-01

    Building on a model introduced by Mandal and Jarzynski (Proc. Natl. Acad. Sci. U.S.A., 109 (2012) 11641), we present a simple version of an autonomous reversible Maxwell's demon. By changing the entropy of a tape consisting of a sequence of bits passing through the demon, the demon can lift a mass using the coupling to a heat bath. Our model becomes reversible by allowing the tape to move in both directions. In this thermodynamically consistent model, total entropy production consists of three terms one of which recovers the irreversible limit studied by MJ. Our demon allows an interpretation in terms of an enzyme transporting and transforming molecules between compartments. Moreover, both genuine equilibrium and a linear response regime with corresponding Onsager coefficients are well defined. Efficiency and efficiency at maximum power are calculated. In linear response, the latter is shown to be bounded by 1/2, if the demon operates as a machine and by 1/3, if it is operated as an eraser.

  4. The physiological role of reversible methionine oxidation.

    PubMed

    Drazic, Adrian; Winter, Jeannette

    2014-08-01

    Sulfur-containing amino acids such as cysteine and methionine are particularly vulnerable to oxidation. Oxidation of cysteine and methionine in their free amino acid form renders them unavailable for metabolic processes while their oxidation in the protein-bound state is a common post-translational modification in all organisms and usually alters the function of the protein. In the majority of cases, oxidation causes inactivation of proteins. Yet, an increasing number of examples have been described where reversible cysteine oxidation is part of a sophisticated mechanism to control protein function based on the redox state of the protein. While for methionine the dogma is still that its oxidation inhibits protein function, reversible methionine oxidation is now being recognized as a powerful means of triggering protein activity. This mode of regulation involves oxidation of methionine to methionine sulfoxide leading to activated protein function, and inactivation is accomplished by reduction of methionine sulfoxide back to methionine catalyzed by methionine sulfoxide reductases. Given the similarity to thiol-based redox-regulation of protein function, methionine oxidation is now established as a novel mode of redox-regulation of protein function. This article is part of a Special Issue entitled: Thiol-Based Redox Processes.

  5. Error bounds from extra precise iterative refinement

    SciTech Connect

    Demmel, James; Hida, Yozo; Kahan, William; Li, Xiaoye S.; Mukherjee, Soni; Riedy, E. Jason

    2005-02-07

    We present the design and testing of an algorithm for iterative refinement of the solution of linear equations, where the residual is computed with extra precision. This algorithm was originally proposed in the 1960s [6, 22] as a means to compute very accurate solutions to all but the most ill-conditioned linear systems of equations. However two obstacles have until now prevented its adoption in standard subroutine libraries like LAPACK: (1) There was no standard way to access the higher precision arithmetic needed to compute residuals, and (2) it was unclear how to compute a reliable error bound for the computed solution. The completion of the new BLAS Technical Forum Standard [5] has recently removed the first obstacle. To overcome the second obstacle, we show how a single application of iterative refinement can be used to compute an error bound in any norm at small cost, and use this to compute both an error bound in the usual infinity norm, and a componentwise relative error bound. We report extensive test results on over 6.2 million matrices of dimension 5, 10, 100, and 1000. As long as a normwise (resp. componentwise) condition number computed by the algorithm is less than 1/max{l_brace}10,{radical}n{r_brace} {var_epsilon}{sub w}, the computed normwise (resp. componentwise) error bound is at most 2 max{l_brace}10,{radical}n{r_brace} {center_dot} {var_epsilon}{sub w}, and indeed bounds the true error. Here, n is the matrix dimension and w is single precision roundoff error. For worse conditioned problems, we get similarly small correct error bounds in over 89.4% of cases.

  6. Reverse photoacoustic standoff spectroscopy

    DOEpatents

    Van Neste, Charles W.; Senesac, Lawrence R.; Thundat, Thomas G.

    2011-04-12

    A system and method are disclosed for generating a reversed photoacoustic spectrum at a greater distance. A source may emit a beam to a target and a detector measures signals generated as a result of the beam being emitted on the target. By emitting a chopped/pulsed light beam to the target, it may be possible to determine the target's optical absorbance by monitoring the intensity of light collected at the detector at different wavelengths. As the wavelength of light is changed, the target may absorb or reject each optical frequency. Rejection may increase the intensity at the sensing element and absorption may decrease the intensity. Accordingly, an identifying spectrum of the target may be made with the intensity variation of the detector as a function of illuminating wavelength.

  7. Biochemical Reversal of Aging

    NASA Astrophysics Data System (ADS)

    Ely, John T. A.

    2006-03-01

    We cite our progress on biochemical reversal of aging. However, it may be circa 2 years before we have necessary substances at low cost. Meanwhile, without them, a number of measures can be adopted providing marked improvement for the problems of aging in modern societies. For example, enzymes are needed to excrete toxins that accelerate aging; Hg is the ultimate toxin that disables all enzymes (including those needed to excrete Hg itself). Low Hg level in the urine, due to loss of excretory ability, causes the diagnosis of Hg toxicity to almost always be missed. Hg sources must be removed from the body! Another example is excess sugar; hyperglycemia decreases intracellular ascorbic acid (AA) by competitively inhibiting the insulin- mediated active transport of AA into cells. Thus, immunity is impaired by low leucocyte AA. AA is needed for new proteins in aging tissues. Humans must supplement AA; their need same as in AA-synthesizing mammals.

  8. Reverse slapper detonator

    DOEpatents

    Weingart, Richard C.

    1990-01-01

    A reverse slapper detonator (70), and methodology related thereto, are provided. The detonator (70) is adapted to be driven by a pulse of electric power from an external source (80). A conductor (20) is disposed along the top (14), side (18), and bottom (16) surfaces of a sheetlike insulator (12). Part of the conductor (20) comprises a bridge (28), and an aperture (30) is positioned within the conductor (20), with the bridge (28) and the aperture (30) located on opposite sides of the insulator (12). A barrel (40) and related explosive charge (50) are positioned adjacent to and in alignment with the aperture (30), and the bridge (28) is buttressed with a backing layer (60). When the electric power pulse vaporizes the bridge (28), a portion of the insulator (12) is propelled through the aperture (30) and barrel (40), and against the explosive charge (50), thereby detonating it.

  9. Reversible fluctuation rectifier

    NASA Astrophysics Data System (ADS)

    Sokolov, I. M.

    1999-10-01

    The analysis of a Feynman's ratchet system [J. M. R. Parrondo and P. Español, Am. J. Phys. 64, 1125 (1996)] and of its electrical counterpart, a diode engine [I. M. Sokolov, Europhys. Lett. 44, 278 (1998)] has shown that ``fluctuation rectifiers'' consisting of a nonlinear element (ratchet, diode) and a linear element (vane, resistor) kept at different temperatures always show efficiency smaller than the Carnot value, thus indicating the irreversible mode of operation. We show that this irreversibility is not intrinsic for a system in simultaneous contact with two heat baths at different temperatures and that a fluctuation rectifier can work reversibly. This is illustrated by a model with two diodes switched in opposite directions, where the Carnot efficiency is achieved when backward resistivity of the diodes tends to infinity.

  10. Reversed-polarity regions

    NASA Technical Reports Server (NTRS)

    Tang, F.

    1982-01-01

    It is found by a statistical study of 58 reversed-polarity regions (RPRs) covering the 11-year period 1969-1979 that RPRs (1) have a lifespan comparable to normal active regions, (2) do not show a tendency to rotate toward a more normal alignment, and (3) have stable configurations that do not suggest stress due to their anomalous magnetic alignment. As in normal regions, RPR magnetic complexity is found to be the primary factor in flare productivity. Weak-field RPRs produce no flares, and regions with complex spots produce more flares than regions with non-complex spots by a factor of five. The main difference between RPRs and normal regions lies in complex spot frequency, with less that 17% of normal active regions having such spots and fewer than 1.8% having long-lived complex ones, while 41% of RPRs have complex spots and 24% have long-lived complex spots.

  11. Reverse shoulder arthroplasty.

    PubMed

    Smithers, Christopher J; Young, Allan A; Walch, Gilles

    2011-12-01

    The reverse shoulder arthroplasty emerged as a potential solution for those patients who could not be managed effectively with a conventional total shoulder arthroplasty. Grammont revolutionized the design by medializing and distalizing the center of rotation and utilizing a large convex glenoid surface and concave humeral component with a neck-shaft angle of 155°. This design has been highly successful in cuff deficient shoulders, and indications continue to broaden. Many mid-term studies have improved upon the early encouraging results. Long-term studies are starting to emerge, demonstrating good survivorship, but progressive functional and radiographic deterioration continue to be concerning. Careful patient selection and attention to appropriate technique are required to reduce the current high rate of complications. New prosthesis designs are continuing to develop to address some of these limitations.

  12. Reverse Osmosis Optimization

    SciTech Connect

    McMordie Stoughton, Kate; Duan, Xiaoli; Wendel, Emily M.

    2013-08-26

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). ¬The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.¬

  13. Reverse Osmosis Optimization

    SciTech Connect

    2013-08-01

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.

  14. Multiple stimulus reversible hydrogels

    DOEpatents

    Gutowska, Anna; Krzyminski, Karol J.

    2003-12-09

    A polymeric solution capable of gelling upon exposure to a critical minimum value of a plurality of environmental stimuli is disclosed. The polymeric solution may be an aqueous solution utilized in vivo and capable of having the gelation reversed if at least one of the stimuli fall below, or outside the range of, the critical minimum value. The aqueous polymeric solution can be used either in industrial or pharmaceutical environments. In the medical environment, the aqueous polymeric solution is provided with either a chemical or radioisotopic therapeutic agent for delivery to a specific body part. The primary advantage of the process is that exposure to one environmental stimuli alone will not cause gelation, thereby enabling the therapeutic agent to be conducted through the body for relatively long distances without gelation occurring.

  15. Multiple stimulus reversible hydrogels

    DOEpatents

    Gutowska, Anna; Krzyminski, Karol J.

    2006-04-25

    A polymeric solution capable of gelling upon exposure to a critical minimum value of a plurality of environmental stimuli is disclosed. The polymeric solution may be an aqueous solution utilized in vivo and capable of having the gelation reversed if at least one of the stimuli fall below, or outside the range of, the critical minimum value. The aqueous polymeric solution can be used either in industrial or pharmaceutical environments. In the medical environment, the aqueous polymeric solution is provided with either a chemical or radioisotopic therapeutic agent for delivery to a specific body part. The primary advantage of the process is that exposure to one environmental stimuli alone will not cause gelation, thereby enabling the therapeutic agent to be conducted through the body for relatively long distances without gelation occurring.

  16. Upper bounds on superpartner masses from upper bounds on the Higgs boson mass.

    PubMed

    Cabrera, M E; Casas, J A; Delgado, A

    2012-01-13

    The LHC is putting bounds on the Higgs boson mass. In this Letter we use those bounds to constrain the minimal supersymmetric standard model (MSSM) parameter space using the fact that, in supersymmetry, the Higgs mass is a function of the masses of sparticles, and therefore an upper bound on the Higgs mass translates into an upper bound for the masses for superpartners. We show that, although current bounds do not constrain the MSSM parameter space from above, once the Higgs mass bound improves big regions of this parameter space will be excluded, putting upper bounds on supersymmetry (SUSY) masses. On the other hand, for the case of split-SUSY we show that, for moderate or large tanβ, the present bounds on the Higgs mass imply that the common mass for scalars cannot be greater than 10(11)  GeV. We show how these bounds will evolve as LHC continues to improve the limits on the Higgs mass.

  17. New rubrolide analogues as inhibitors of photosynthesis light reactions.

    PubMed

    Varejão, Jodieh O S; Barbosa, Luiz C A; Ramos, Gabriela Álvarez; Varejão, Eduardo V V; King-Díaz, Beatriz; Lotina-Hennsen, Blas

    2015-04-01

    Natural products called rubrolides have been investigated as a model for the development of new herbicides that act on the photosynthesis apparatus. This study comprises a comprehensive analysis of the photosynthesis inhibitory ability of 27 new structurally diverse rubrolide analogues. In general, the results revealed that the compounds exhibited efficient inhibition of the photosynthetic process, but in some cases low water solubility may be a limiting factor. To elucidate their mode of action, the effects of the compounds on PSII and PSI, as well as their partial reaction on chloroplasts and the chlorophyll a fluorescence transients were measured. Our results showed that some of the most active rubrolide analogues act as a Hill reaction inhibitors at the QB level by interacting with the D1 protein at the reducing side of PSII. All of the active analogues follow Tice's rule of 5, which indicates that these compounds present physicochemical properties suitable for herbicides.

  18. 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.

  19. Synthesis and antioxidant activity of a procyanidin B3 analogue.

    PubMed

    Mizuno, Mirei; Nakanishi, Ikuo; Matsubayashi, Satoko; Imai, Kohei; Arai, Takuya; Matsumoto, Ken-Ichiro; Fukuhara, Kiyoshi

    2017-02-15

    Proanthocyanidin, an oligomer of catechin, is a natural antioxidant and a potent inhibitor of lectin-like oxidized LDL receptor-1, which is involved in the pathogenesis of arteriosclerosis. We synthesized proanthocyanidin analogue 1, in which the geometry of one catechin molecule in procyanidin B3, a dimer of (+)-catechin, is constrained to be planar. The antioxidant activities of the compounds were evaluated in terms of their capacities to scavenge galvinoxyl radicals, and results demonstrate that while procyanidin was 3.8 times more potent than (+)-catechin, the radical scavenging activity of proanthocyanidin analogue 1 was further increased to 1.9 times that of procyanidin B3. This newly designed proanthocyanidin analogue 1 may be a promising lead compound for the treatment of arteriosclerosis and related cerebrovascular diseases.

  20. Design of novel CSA analogues as potential safeners and fungicides.

    PubMed

    Zheng, Yang; Liu, Bin; Gou, Zhaopin; Li, Yao; Zhang, Xiao; Wang, Yanqing; Yu, Shujing; Li, Yonghong; Sun, Dequn

    2015-02-15

    Study of safeners has been seldom reported in literature. In this work, a series of novel acylsulfamoylbenzamide analogues was designed and synthesized with newly developed safener cyprosulfamide (CSA) as the leading compound. The activity assay against the herbicide thiencarbazone-methyl (TCM) on maize revealed that fifteen compounds showed better protective effect than CSA on the fresh weight of aerial parts, twelve compounds exhibited better activity on the dry weight of aerial parts. Remarkably, two compounds (6Ih, 7II) had protective effect on the four aspects of TCM treated maize. Further antifungal assay showed their excellent activity against Physollospora piricola. The structure-activity relationships of CSA analogues as safeners and fungicides were discussed and it might be valuable for further molecular modification of new CSA analogues.

  1. Conception, synthesis, and biological evaluation of original discodermolide analogues.

    PubMed

    de Lemos, Elsa; Agouridas, Evangelos; Sorin, Geoffroy; Guerreiro, Antonio; Commerçon, Alain; Pancrazi, Ange; Betzer, Jean-François; Lannou, Marie-Isabelle; Ardisson, Janick

    2011-08-29

    Due to its intriguing biological activity profile and potential chemotherapeutic application discodermolide (DDM) proved to be an attractive target. Therefore, notable efforts have been carried out directed toward its total synthesis and toward the production and evaluation of synthetic analogues. Recently, we achieved the total synthesis of DDM. At the present, guided by the knowledge gained during our DDM total synthesis and by the requirement of keeping the bioactive "U" shape conformation, we report the convergent preparation of five original analogues. Three types of changes were realized through modification of the terminal (Z)-diene moiety, of the methyl group at the C14-position, and the lactone region. All analogues were active in the nanomolar range and two of them turned out to be equipotent to DDM.

  2. Migrastatin analogues target fascin to block tumour metastasis.

    PubMed

    Chen, Lin; Yang, Shengyu; Jakoncic, Jean; Zhang, J Jillian; Huang, Xin-Yun

    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.

  3. Thermalization Time Bounds for Pauli Stabilizer Hamiltonians

    NASA Astrophysics Data System (ADS)

    Temme, Kristan

    2017-03-01

    We prove a general lower bound to the spectral gap of the Davies generator for Hamiltonians that can be written as the sum of commuting Pauli operators. These Hamiltonians, defined on the Hilbert space of N-qubits, serve as one of the most frequently considered candidates for a self-correcting quantum memory. A spectral gap bound on the Davies generator establishes an upper limit on the life time of such a quantum memory and can be used to estimate the time until the system relaxes to thermal equilibrium when brought into contact with a thermal heat bath. The bound can be shown to behave as {λ ≥ O(N^{-1} exp(-2β overline{ɛ}))}, where {overline{ɛ}} is a generalization of the well known energy barrier for logical operators. Particularly in the low temperature regime we expect this bound to provide the correct asymptotic scaling of the gap with the system size up to a factor of N -1. Furthermore, we discuss conditions and provide scenarios where this factor can be removed and a constant lower bound can be proven.

  4. Largazole Analogues Embodying Radical Changes in the Depsipeptide Ring: Development of a More Selective and Highly Potent Analogue.

    PubMed

    Almaliti, Jehad; Al-Hamashi, Ayad A; Negmeldin, Ahmed T; Hanigan, Christin L; Perera, Lalith; Pflum, Mary Kay H; Casero, Robert A; Tillekeratne, L M Viranga

    2016-12-08

    A number of analogues of the marine-derived histone deacetylase inhibitor largazole incorporating major structural changes in the depsipeptide ring were synthesized. Replacing the thiazole-thiazoline fragment of largazole with a bipyridine group gave analogue 7 with potent cell growth inhibitory activity and an activity profile similar to that of largazole, suggesting that conformational change accompanying switching hybridization from sp(3) to sp(2) at C-7 is well tolerated. Analogue 7 was more class I selective compared to largazole, with at least 464-fold selectivity for class I HDAC proteins over class II HDAC6 compared to a 22-fold selectivity observed with largazole. To our knowledge 7 represents the first example of a potent and highly cytotoxic largazole analogue not containing a thiazoline ring. The elimination of a chiral center derived from the unnatural amino acid R-α-methylcysteine makes the molecule more amenable to chemical synthesis, and coupled with its increased class I selectivity, 7 could serve as a new lead compound for developing selective largazole analogues.

  5. Synthesis of daidzin analogues as potential agents for alcohol abuse.

    PubMed

    Gao, Guang-Yao; Li, Dian-Jun; Keung, Wing Ming

    2003-09-01

    Daidzin, the active principle of an herbal remedy for 'alcohol addiction', has been shown to reduce alcohol consumption in all laboratory animals tested to date. Correlation studies using structural analogues of daidzin suggests that it acts by raising the monoamine oxidase (MAO)/mitochondrial aldehyde dehydrogenase (ALDH-2) activity ratio (J. Med. Chem. 2000, 43, 4169). Structure-activity relationship (SAR) studies on the 7-O-substituted analogues of daidzin have revealed structural features important for ALDH-2 and MAO inhibition (J. Med. Chem. 2001, 44, 3320). We here evaluated effects of substitutions at 2, 5, 6, 8, 3' and 4' positions of daidzin on its potencies for ALDH-2 and MAO inhibition. Results show that analogues with 4'-substituents that are small, polar and with hydrogen bonding capacities are most potent ALDH-2 inhibitors, whereas those that are non-polar and with electron withdrawing capacities are potent MAO inhibitors. Analogues with a 5-OH group are less potent ALDH-2 inhibitors but are more potent MAO inhibitors. All the 2-, 6-, 8- and 3'-substituted analogues tested so far do not inhibit ALDH-2 and/or have decreased potencies for MAO inhibition. This, together with the results obtained from previous studies, suggests that a potent antidipsotropic analogue would be a 4',7-disubstituted isoflavone. The 4'-substituent should be small, polar, and with hydrogen bonding capacities such as, -OH and -NH(2); whereas the 7-substituent should be a straight-chain alkyl with a terminal polar function such as -(CH(2))(n)-OH with 2< or =n < or =6, -(CH(2))(n)-COOH with 5< or =n < or =10, or -(CH(2))(n)-NH(2) with n > or =4.

  6. 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

  7. Phase behavior of carbamyloxyphosphatidylcholine, a sphingolipid analogue.

    PubMed

    Curatolo, W; Bali, A; Gupta, C M

    1985-12-01

    The phase behavior of two series of phosphatidylcholines (PC) possessing carbamyloxy-linked fatty acids has been studied by differential scanning calorimetry. These non-natural phosphatidylcholines are of interest because they possess the capability of forming interlipid hydrogen bonds via the carbamyloxy function and as such can serve as a model for sphingolipids, the phase behavior of which is thought to be dominated by interlipid hydrogen bonding. Furthermore, carbamyloxyphosphatidylcholines form unusually stable liposomes, and thus have potential in drug delivery. Carbamyloxyphosphatidylcholines of the type di-(CnH2n+1NHCOO)-PC, where n = 13, 15, or 17, exhibit metastable polymorphism. Cooling from the liquid crystalline state results in formation of a metastable low-temperature polymorph I, which must transform into a stable low-temperature polymorph II before the liquid crystalline state can be reached again. Carbamyloxyphosphatidylcholines of the type 1-C16:0-2-(CnH2n+1NHCOO)-PC exhibit similar metastable polymorphism. This metastability is similar to that exhibited by certain cerebrosides and sphingomyelins and indicates that the sphingosine backbone is not a prerequisite for this type of metastability. Furthermore, the carbamyloxy group is reversed in orientation compared with the amide of sphingolipids (-NHCO- versus -CONH-), suggesting that the intermolecular hydrogen bonding potential, rather than some highly specific steric or conformational constraint, is responsible for the observed metastability of sphingolipids.

  8. Magnetic reversals and mass extinctions

    NASA Technical Reports Server (NTRS)

    Raup, D. M.

    1985-01-01

    The results of a study of reversals of the earth's magnetic field over the past 165 Myr are presented. A stationary periodicity of 30 Myr emerges which predicts pulses of increased reversal activity centered at 10, 40, 70, . . . Myr before the present. The correlation between the reversal intensity and biological extinctions is examined, and a nontrivial discrepancy is found between the magnetic and extinction periodicity.

  9. Inhibition of Mycobacterium tuberculosis dihydrodipicolinate synthase by alpha-ketopimelic acid and its other structural analogues

    PubMed Central

    Shrivastava, Priyanka; Navratna, Vikas; Silla, Yumnam; Dewangan, Rikeshwer P.; Pramanik, Atreyi; Chaudhary, Sarika; Rayasam, GeethaVani; Kumar, Anuradha; Gopal, Balasubramanian; Ramachandran, Srinivasan

    2016-01-01

    The Mycobacterium tuberculosis dihydrodipicolinate synthase (Mtb-dapA) is an essential gene. Mtb-DapA catalyzes the aldol condensation between pyruvate and L-aspartate-beta-semialdehyde (ASA) to yield dihydrodipicolinate. In this work we tested the inhibitory effects of structural analogues of pyruvate on recombinant Mtb-DapA (Mtb-rDapA) using a coupled assay with recombinant dihydrodipicolinate reductase (Mtb-rDapB). Alpha-ketopimelic acid (α-KPA) showed maximum inhibition of 88% and IC50 of 21 μM in the presence of pyruvate (500 μM) and ASA (400 μM). Competition experiments with pyruvate and ASA revealed competition of α-KPA with pyruvate. Liquid chromatography-mass spectrometry (LC-MS) data with multiple reaction monitoring (MRM) showed that the relative abundance peak of final product, 2,3,4,5-tetrahydrodipicolinate, was decreased by 50%. Thermal shift assays showed 1 °C Tm shift of Mtb-rDapA upon binding α-KPA. The 2.4 Å crystal structure of Mtb-rDapA-α-KPA complex showed the interaction of critical residues at the active site with α-KPA. Molecular dynamics simulations over 500 ns of pyruvate docked to Mtb-DapA and of α-KPA-bound Mtb-rDapA revealed formation of hydrogen bonds with pyruvate throughout in contrast to α-KPA. Molecular descriptors analysis showed that ligands with polar surface area of 91.7 Å2 are likely inhibitors. In summary, α-hydroxypimelic acid and other analogues could be explored further as inhibitors of Mtb-DapA. PMID:27501775

  10. On slow light as a black hole analogue

    NASA Astrophysics Data System (ADS)

    Unruh, W. G.; Schützhold, R.

    2003-07-01

    Although slow light (electromagnetically induced transparency) would seem an ideal medium in which to institute a “dumb hole” (black hole analogue), it suffers from a number of problems. We show that the high phase velocity in the slow light regime ensures that the system cannot be used as an analogue displaying Hawking radiation. Even though an appropriately designed slow-light setup may simulate classical features of black holes—such as horizon, mode mixing, “Bogoliubov” coefficients, etc.—it does not reproduce the related quantum effects.

  11. 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.

  12. 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

  13. Retro-1 Analogues Differentially Affect Oligonucleotide Delivery and Toxin Trafficking.

    PubMed

    Yang, Bing; Ming, Xin; Abdelkafi, Hajer; Pons, Valerie; Michau, Aurelien; Gillet, Daniel; Cintrat, Jean-Christophe; Barbier, Julien; Juliano, Rudy

    2016-11-21

    Retro-1 is a small molecule that displays two important biological activities: First, it blocks the actions of certain toxins by altering their intracellular trafficking. Second, it enhances the activity of oligonucleotides by releasing them from entrapment in endosomes. This raises the question of whether the two actions involve the same cellular target. Herein we report the effects of several Retro-1 analogues on both toxins and oligonucleotides. We found analogues that affect toxins but not oligonucleotides and vice-versa, while Retro-1 is the only compound that affects both. This indicates that the molecular target(s) involved in the two processes are distinct.

  14. Synthesis and evaluation of heterocyclic analogues of bromoxynil.

    PubMed

    Cutulle, Matthew A; Armel, Gregory R; Brosnan, James T; Best, Michael D; Kopsell, Dean A; Bruce, Barry D; Bostic, Heidi E; Layton, Donovan S

    2014-01-15

    One attractive strategy to discover more active and/or crop-selective herbicides is to make structural changes to currently registered compounds. This strategy is especially appealing for those compounds with limited herbicide resistance and whose chemistry is accompanied with transgenic tools to enable herbicide tolerance in crop plants. Bromoxynil is a photosystem II (PSII) inhibitor registered for control of broadleaf weeds in several agronomic and specialty crops. Recently at the University of Tennessee-Knoxville several analogues of bromoxynil were synthesized including a previously synthesized pyridine (2,6-dibromo-5-hydroxypyridine-2-carbonitrile sodium salt), a novel pyrimidine (4,6-dibromo-5-hydroxypyrimidine-2-carbonitrile sodium salt), and a novel pyridine N-oxide (2,6-dibromo-1-oxidopyridin-1-ium-4-carbonitrile). These new analogues of bromoxynil were also evaluated for their herbicidal activity on soybean (Glycine max), cotton (Gossypium hirsutum), redroot pigweed (Amaranthus retroflexus), velvetleaf (Abutilon theophrasti), large crabgrass (Digitaria sanguinalis), and pitted morningglory ( Ipomoea lacunose ) when applied at 0.28 kg ha(-1). A second study was conducted on a glyphosate-resistant weed (Amaranthus palmeri) with the compounds being applied at 0.56 kg ha(-1). Although all compounds were believed to inhibit PSII by binding in the quinone binding pocket of D1, the pyridine and pyridine-N-oxide analogues were clearly more potent than bromoxynil on Amaranthus retroflexus. However, application of the pyrimidine herbicide resulted in the least injury to all species tested. These variations in efficacy were investigated using molecular docking simulations, which indicate that the pyridine analogue may form a stronger hydrogen bond in the pocket of the D1 protein than the original bromoxynil. A pyridine analogue was able to control the glyphosate-resistant Amaranthus palmeri with >80% efficacy. The pyridine analogues of bromoxynil showed potential

  15. Relationship between antimold activity and molecular structure of cinnamaldehyde analogues.

    PubMed

    Zhang, Yuanyuan; Li, Shujun; Kong, Xianchao

    2013-03-01

    A quantitative structure-activity relationship (QSAR) modeling of the antimold activity of cinnamaldehyde analogues against of Aspergillus niger and Paecilomyces variotii was presented. The molecular descriptors of cinnamaldehyde analogues were calculated by the CODESSA program, and these descriptors were selected by best multi-linear regression method (BMLR). Satisfactory multilinear regression models of Aspergillus niger and Paecilomyces variotii were obtained with R(2)=0.9099 and 0.9444, respectively. The models were also satisfactorily validated using internal validation and leave one out validation. The QSAR models provide the guidance for further synthetic work.

  16. Synthesis and antihistamine evaluations of novel loratadine analogues.

    PubMed

    Wang, Yue; Wang, Juan; Lin, Yan; Si-Ma, Li-Feng; Wang, Dong-hua; Chen, Li-Gong; Liu, Deng-Ke

    2011-08-01

    A series of loratadine analogues containing hydroxyl group and chiral center were synthesized. The effect of the synthesized compounds on the histamine-induced contractions of guinea-pig ileum muscles was studied. In addition, the in vivo asthma-relieving effect of the analogues in the histamine induced asthmatic reaction in guinea-pigs was determined. Most of the compounds exhibited definite H(1) antihistamine activity. The S-enantiomers, compounds 2, 4 and 8, are more potent than the R-enantiomers, compounds 1, 3 and 7. Compound 6 was the most active one among the eight synthesized compounds.

  17. Fluorescent diethylcarbamazine analogues: sites of accumulation in Brugia malayi.

    PubMed

    Junnila, Amy; Bohle, D Scott; Prichard, Roger; Perepichka, Inna; Spina, Carla

    2007-01-01

    New fluorescein and rhodamine B-labeled antifilarial drug DEC analogues for use in drug localization studies with confocal microscopy have been prepared by a high-yield three-step synthesis. The resulting beta-amine-substituted DEC analogue has a single ethyl substituent which is beta-aminated to accommodate the fluorophore of either fluorescein isothiocyananate or rhodamine B. Confocal microscopy is used to show that the drug accumulates in the adult filarial worms in the pharynx, esophagus, and near the nerve ring of all adults, as well as in the uteri and vulva and the testes of the females and males.

  18. Total Synthesis and Evaluation of Vinblastine Analogues Containing Systematic Deep-Seated Modifications in the Vindoline Subunit Ring System: Core Redesign

    PubMed Central

    Schleicher, Kristin D.; Sasaki, Yoshikazu; Tam, Annie; Kato, Daisuke; Duncan, Katharine K.; Boger, Dale L.

    2013-01-01

    The total synthesis of a systematic series of vinblastine analogues that contain deep-seated structural modifications to the core ring system of the lower vindoline subunit is described. Complementary to the vindoline 6,5 DE ring system, compounds with 5,5, 6,6 and the reversed 5,6 membered DE ring systems were prepared. Both the natural cis and unnatural trans 6,6-membered ring systems proved accessible, with the latter representing a surprisingly effective class for analogue design. Following Fe(III)-promoted coupling with catharanthine and in situ oxidation to provide the corresponding vinblastine analogues, their evaluation provided unanticipated insights into how the structure of the vindoline subunit contributes to activity. Two potent analogues (81 and 44) possessing two different unprecedented modifications to the vindoline subunit core architecture were discovered that matched the potency of the comparison natural products and both lack the 6,7-double bond whose removal in vinblastine leads to a 100-fold drop in activity. PMID:23252481

  19. Two-dimensional chromatography based on on-line HPLC-DPPH bioactivity-guided assay for the preparative isolation of analogue antioxidant compound from Arenaria kansuensis.

    PubMed

    Cui, Yulei; Shen, Na; Yuan, Xiang; Dang, Jun; Shao, Yun; Mei, Lijuan; Tao, Yanduo; Wang, Qilan; Liu, Zenggen

    2017-03-01

    Traditional Tibetan medicine is important for discovery of drug precursors. However, information about the chemical composition of traditional Tibetan medicine is very limited due to the lack of appropriate chromatographic purification methods. In the present work, A. kansuensis was taken as an example and a novel two-dimensional reversed-phase/hydrophilic interaction liquid chromatography(HILIC) method based on on-line HPLC-DPPH bioactivity-guided assay was developed for the purification of analogue antioxidant compounds with high purity from the extract of A. kansuensis. Based on the separation results of many different chromatographic stationary phases, the first-dimensional (1D) preparation was carried on a RP-C18HCE prep column, and 2 antioxidant fractions were obtained from the 800mg crude sample with a recovery of 56.7%. A HILIC-XAmide prep column was selected for the second-dimensional (2D) preparation. Finally, a novel antioxidant β-carboline Alkaloids (Glusodichotomine AK) and 4 known compounds (Tricin, Homoeriodictyol, Luteolin, Glucodichotomine B) were purified from A. kansuensis. The purity of the compounds isolated from the crude extract was >98%, which indicated that the method built in this work was efficient to manufacture single analogue antioxidant compounds of high purity from the extract of A. kansuensis. Additionally, this method showed great potential in the preparation of analogue structure antioxidant compounds and can serve as a good example for the purification of analogue structure antioxidant carboline alkaloids and flavonoids from other plant materials.

  20. Convex Lower Bounds for Free Energy Minimization

    NASA Astrophysics Data System (ADS)

    Moussa, Jonathan

    We construct lower bounds on free energy with convex relaxations from the nonlinear minimization over probabilities to linear programs over expectation values. Finite-temperature expectation values are further resolved into distributions over energy. A superset of valid expectation values is delineated by an incomplete set of linear constraints. Free energy bounds can be improved systematically by adding constraints, which also increases their computational cost. We compute several free energy bounds of increasing accuracy for the triangular-lattice Ising model to assess the utility of this method. This work was supported by the Laboratory Directed Research and Development program at Sandia National Laboratories. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL85000.

  1. Bounds on Neutrino Non-Standard Interactions

    SciTech Connect

    Fernandez-Martinez, Enrique

    2010-03-30

    We review the present model independent bounds on neutrino non-standard interactions both at neutrino production and detection and in its interactions with matter. For matter non-standard interactions the direct bounds are rather weak. However, matter non-standard interactions are related by gauge invariance to the production and detection ones as well as to flavour changing processes involving charged leptons. Taking into account these relations much stronger bounds of at least O(10{sup -2}) can be derived unless significant fine tunings are implemented. Testing non-standard interactions at this level at future neutrino oscillation facilities is challenging but still feasible at very ambitious proposals such as the Neutrino Factory.

  2. Bounded link prediction in very large networks

    NASA Astrophysics Data System (ADS)

    Cui, Wei; Pu, Cunlai; Xu, Zhongqi; Cai, Shimin; Yang, Jian; Michaelson, Andrew

    2016-09-01

    Evaluating link prediction methods is a hard task in very large complex networks due to the prohibitive computational cost. However, if we consider the lower bound of node pairs' similarity scores, this task can be greatly optimized. In this paper, we study CN index in the bounded link prediction framework, which is applicable to enormous heterogeneous networks. Specifically, we propose a fast algorithm based on the parallel computing scheme to obtain all node pairs with CN values larger than the lower bound. Furthermore, we propose a general measurement, called self-predictability, to quantify the performance of similarity indices in link prediction, which can also indicate the link predictability of networks with respect to given similarity indices.

  3. Narrow deeply bound K- atomic states

    NASA Astrophysics Data System (ADS)

    Friedman, E.; Gal, A.

    1999-07-01

    Using optical potentials fitted to a comprehensive set of strong interaction level shifts and widths in K- atoms, we predict that the K- atomic levels which are inaccessible in the atomic cascade process are generally narrow, spanning a range of widths about 50-1500 keV over the entire periodic table. The mechanism for this narrowing is different from the mechanism for narrowing of pionic atom levels. Examples of such `deeply bound' K- atomic states are given, showing that in many cases these states should be reasonably well resolved. Several reactions which could be used to form these `deeply bound' states are mentioned. Narrow deeply bound states are expected also in overlinep atoms.

  4. η-nuclear bound states revisited

    NASA Astrophysics Data System (ADS)

    Friedman, E.; Gal, A.; Mareš, J.

    2013-10-01

    The strong energy dependence of the s-wave ηN scattering amplitude at and below threshold, as evident in coupled-channels K-matrix fits and chiral models that incorporate the S11N* (1535) resonance, is included self-consistently in η-nuclear bound-state calculations. This approach, applied recently in calculations of kaonic atoms and Kbar-nuclear bound states, is found to impose stronger constraints than ever on the onset of η-nuclear binding, with a minimum value of ReaηN ≈ 0.9 fm required to accommodate an η-4He bound state. Binding energies and widths of η-nuclear states are calculated within several underlying ηN models for nuclei across the periodic table, including Mg25η for which some evidence was proposed in a recent COSY experiment.

  5. Bounds on tensor wave and twisted inflation

    SciTech Connect

    Panda, Sudhakar; Sami, M.; Ward, John

    2010-11-15

    We study the bounds on tensor wave in a class of twisted inflation models, where D(4+2k)-branes are wrapped on cycles in the compact manifold and wrap the Kaluza-Klein direction in the corresponding effective field theory. While the lower bound is found to be analogous to that in type IIB models of brane inflation, the upper bound turns out to be significantly different. This is argued for a range of values for the parameter g{sub s}M satisfying the self-consistency relation and the WMAP data. Further, we observe that the wrapped D8-brane appears to be the most attractive from a cosmological perspective.

  6. Malabsorption of protein bound vitamin B12.

    PubMed Central

    Dawson, D W; Sawers, A H; Sharma, R K

    1984-01-01

    Patients with subnormal serum vitamin B12 concentrations were tested for absorption of protein bound vitamin B12 and compared with controls. Absorption of the protein bound vitamin appeared to decrease with increasing age in healthy subjects. Differences between the result of this test and the result of the Schilling test in patients who had undergone gastric surgery were confirmed; such differences were also seen in some patients who had iron deficiency anaemia, an excessive alcohol intake, or folate deficiency. Defective absorption was also found in six patients with an adequate dietary intake of vitamin B12, normal Schilling test results, low serum vitamin concentrations, and tissue changes responding to treatment with vitamin B12. Malabsorption of the vitamin from protein bound sources, which is not detected by the Schilling test, may produce vitamin B12 deficiency of clinical importance. PMID:6421428

  7. Mass dependence of quantum energy inequality bounds

    SciTech Connect

    Eveson, Simon P.; Fewster, Christopher J.

    2007-09-15

    In a recent paper [C. J. Fewster and M. J. Pfenning, J. Math. Phys. 47, 082303 (2006)], quantum energy inequalities were used to place simple geometrical bounds on the energy densities of quantum fields in Minkowskian space-time regions. Here, we refine this analysis for massive fields, obtaining more stringent bounds which decay exponentially in the mass. At the technical level, this involves the determination of the asymptotic behavior of the lowest eigenvalue of a family of polyharmonic differential equations, a result which may be of independent interest. We compare our resulting bounds with the known energy density of the ground state on a cylinder space-time. In addition, we generalize some of our technical results to general L{sup p} spaces and draw comparisons with a similar result in the literature.

  8. Bound water in Kevlar 49 fibers

    SciTech Connect

    Garza, R.G.; Pruneda, C.O.; Morgan, R.J.

    1981-04-01

    From elemental analyses, thermogravimetric-mass spectroscopy studies and re-evaluation of previous water diffusion studies in Kevlar 49 fibers it is concluded that these fibers can contain two types of sorbed moisture. The fibers can absorb up to approx. 6 wt % loosely bound water with an activation energy for outgassing by desorption of 6 kcal/mole. This loosely bound water is a direct result of the presence of Na/sub 2/SO/sub 4/ impurities and the perturbations they induce on the packing of the rod-like poly (p-phenylene terephthalamide) macromolecules. Kevlar 49 fibers also inherently contain up to 30 wt % additional water which is tightly bound within the crystal lattice. This water exhibits an activation energy for outgassing by diffusion of approx. 40 kcal/mole and is only evolved from the fiber in significant quantities at t > 350/sup 0/C over a period of hours.

  9. Influence of the degree of unsaturation of the acyl side chain upon the interaction of analogues of 1-arachidonoylglycerol with monoacylglycerol lipase and fatty acid amide hydrolase.

    PubMed

    Vandevoorde, Séverine; Saha, Bijali; Mahadevan, Anu; Razdan, Raj K; Pertwee, Roger G; Martin, Billy R; Fowler, Christopher J

    2005-11-11

    Little is known as to the structural requirements of the acyl side chain for interaction of acylglycerols with monoacylglycerol lipase (MAGL), the enzyme chiefly responsible for the metabolism of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain. In the present study, a series of twelve analogues of 1-AG (the more stable regioisomer of 2-AG) were investigated with respect to their ability to inhibit the metabolism of 2-oleoylglycerol by cytosolic and membrane-bound MAGL. In addition, the ability of the compounds to inhibit the hydrolysis of anandamide by fatty acid amide hydrolase (FAAH) was investigated. For cytosolic MAGL, compounds with 20 carbon atoms in the acyl chain and 2-5 unsaturated bonds inhibited the hydrolysis of 2-oleoylglycerol with similar potencies (IC50 values in the range 5.1-8.2 microM), whereas the two compounds with a single unsaturated bond were less potent (IC50 values 19 and 21 microM). The fully saturated analogue 1-monoarachidin did not inhibit the enzyme, whereas the lower side chain analogues 1-monopalmitin and 1-monomyristin inhibited the enzyme with IC50 values of 12 and 32 microM, respectively. The 22-carbon chain analogue of 1-AG was also potent (IC50 value 4.5 microM). Introduction of an alpha-methyl group for the C20:4, C20:3, and C22:4 compounds did not affect potency in a consistent manner. For the FAAH and the membrane-bound MAGL, there was no obvious relationship between the degree of unsaturation of the acyl side chain and the ability to inhibit the enzymes. It is concluded that increasing the number of unsaturated bonds on the acyl side chain of 1-AG from 1 to 5 has little effect on the affinity of acylglycerols for cytosolic MAGL.

  10. 49 CFR 230.89 - Reverse gear.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Reverse gear. 230.89 Section 230.89 Transportation... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants... quadrant. Proper counterbalance shall be provided for the valve gear. (b) Air-operated power reverse...

  11. 49 CFR 230.89 - Reverse gear.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Reverse gear. 230.89 Section 230.89 Transportation... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants... quadrant. Proper counterbalance shall be provided for the valve gear. (b) Air-operated power reverse...

  12. 49 CFR 230.89 - Reverse gear.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Reverse gear. 230.89 Section 230.89 Transportation... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants... quadrant. Proper counterbalance shall be provided for the valve gear. (b) Air-operated power reverse...

  13. 49 CFR 230.89 - Reverse gear.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Reverse gear. 230.89 Section 230.89 Transportation... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants... quadrant. Proper counterbalance shall be provided for the valve gear. (b) Air-operated power reverse...

  14. 49 CFR 230.89 - Reverse gear.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Reverse gear. 230.89 Section 230.89 Transportation... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants... quadrant. Proper counterbalance shall be provided for the valve gear. (b) Air-operated power reverse...

  15. OUTWARD BOUND IN THE MAINSTREAM OF AMERICAN EDUCATION, A SYNOPSIS OF SIX OUTWARD BOUND MAINSTREAM PROJECTS.

    ERIC Educational Resources Information Center

    Outward Bound, Inc., Andover, MA.

    A SYNOPSIS IS OFFERED OF SIX DIFFERENT OUTWARD-BOUND PROGRAMS, EACH OF WHICH IS AN ADAPTATION OF THE BASIC OUTWARD-BOUND PHILOSOPHY OF HAVING YOUNG PEOPLE RECOGNIZE FOR THEMSELVES THEIR PHYSICAL, EMOTIONAL, AND SPIRITUAL CAPABILITIES SO THAT THEY WILL DEVELOP A STRONG SENSE OF SELF-RELIANCE AND INNER STRENGTH. THE ADAMS COUNTY, COLORADO,…

  16. Bound states in the Higgs model

    SciTech Connect

    Di Leo, L.; Darewych, J.W. )

    1994-02-01

    We derive relativistic wave equations for the bound states of two Higgs bosons within the Higgs sector of the minimal standard model. The variational method and the Hamiltonian formalism of QFT are used to obtain the equations using a simple [vert bar][ital hh][r angle]+[vert bar][ital hhh][r angle] Fock-space ansatz. We present approximate solutions of these equations for a range of Higgs boson masses, and explore the parameter space which corresponds to the existence of two-Higgs-boson bound states.

  17. The Lovasz bound and some generalizations

    NASA Technical Reports Server (NTRS)

    Mceliece, R. J.; Rodemich, E. R.; Rumsey, H. C., Jr.

    1978-01-01

    The zero error capacity of a discrete memoryless channel is defined as the largest rate at which information can be transmitted over the channel with zero error probability. One channel with five inputs and outputs whose zero capacity remained unsolved until very recently is considered. An extremely powerful and general technique phased in terms of graph theory, for studying combinatorial packing problems is presented. In particular, Delsarte's linear programming bound for cliques in association schemes appears as a special case of the Lovasz bound.

  18. Quantum Kolmogorov complexity and bounded quantum memory

    SciTech Connect

    Miyadera, Takayuki

    2011-04-15

    The effect of bounded quantum memory in a primitive information protocol has been examined using the quantum Kolmogorov complexity as a measure of information. We employed a toy two-party protocol in which Bob, by using a bounded quantum memory and an unbounded classical memory, estimates a message that was encoded in qubits by Alice in one of the bases X or Z. Our theorem gave a nontrivial effect of the memory boundedness. In addition, a generalization of the uncertainty principle in the presence of quantum memory has been obtained.

  19. Majorana fermions and exotic surface Andreev bound states in topological superconductors: application to Cu(x)Bi2Se3.

    PubMed

    Hsieh, Timothy H; Fu, Liang

    2012-03-09

    The recently discovered superconductor Cu(x)Bi2Se3 is a candidate for three-dimensional time-reversal-invariant topological superconductors, which are predicted to have robust surface Andreev bound states hosting massless Majorana fermions. In this work, we analytically and numerically find the linearly dispersing Majorana fermions at k=0, which smoothly evolve into a new branch of gapless surface Andreev bound states near the Fermi momentum. The latter is a new type of Andreev bound states resulting from both the nontrivial band structure and the odd-parity pairing symmetry. The tunneling spectra of these surface Andreev bound states agree well with a recent point-contact spectroscopy experiment [S. Sasaki et al., Phys. Rev. Lett. 107, 217001 (2011)] and yield additional predictions for low temperature tunneling and photoemission experiments.

  20. Time Reversal Violation

    SciTech Connect

    Quinn, H; /SLAC

    2009-01-27

    This talk briefly reviews three types of time-asymmetry in physics, which I classify as universal, macroscopic and microscopic. Most of the talk is focused on the latter, namely the violation of T-reversal invariance in particle physics theories. In sum tests of microscopic T-invariance, or observations of its violation, are limited by the fact that, while we can measure many processes, only in very few cases can we construct a matched pair of process and inverse process and observe it with sufficient sensitivity to make a test. In both the cases discussed here we can achieve an observable T violation making use of flavor tagging, and in the second case also using the quantum properties of an antisymmetric coherent state of two B mesons to construct a CP-tag. Both these tagging properties depend only on very general properties of the flavor and/or CP quantum numbers and so provide model independent tests for T-invariance violations. The microscopic laws of physics are very close to T-symmetric. There are small effects that give CP- and T-violating processes in three-generation-probing weak decays. Where a T-violating observable can be constructed we see the relationships between T-violation and CP-violation expected in a CPT conserving theory. These microscopic effects are unrelated to the 'arrow of time' that is defined by increasing entropy, or in the time direction defined by the expansion of our Universe.

  1. Posterior Reversible Encephalopathy Syndrome

    PubMed Central

    Algahtani, Abdulhadi; Aldarmahi, Ahmad; Hmoud, Mohammed; Marzuk, Yousef; Shirah, Bader

    2016-01-01

    Objectives: Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome characterized by headache, altered mental status, seizures, or loss of vision. In this study, we report the largest series of PRES coming from Saudi Arabia and explore the etiology, clinical presentation, and outcome. We also report new imaging findings associated with this condition. Methods: We performed a retrospective study of all cases of PRES admitted to King Abdulaziz Medical City, Jeddah, Saudi Arabia, between the years 2005 and 2015. A neurologist reviewed all charts and analyzed the clinical presentations, etiological factors, and outcomes, and a neuroradiologist reviewed the imaging studies. Only patients with clinical and imaging features consistent with PRES were included in the study. Results: We collected 31 patients who had clinical and radiological features consistent with PRES. Females were more affected than males (18 females and 13 males), and patients’ age ranged from 6 to 95 years, with a mean of 38.3 years. Patients were treated by removing the precipitating causes and treating the underlying conditions. Resolution of neurologic signs occurred within 2 to 3 weeks in all patients. Conclusion: In our opinion, PRES itself is usually a benign condition with complete recovery if the condition is recognized early and managed appropriately. Although clinical signs are nonspecific, the constellation of symptoms including headache, visual problems, seizures, and altered level of consciousness should suggest the possibility of PRES, especially in high-risk group. Abnormalities on magnetic resonance imaging are often characteristic and may be the first clue to the diagnosis. PMID:28042366

  2. Reversible micromachining locator

    DOEpatents

    Salzer, Leander J.; Foreman, Larry R.

    1999-01-01

    This invention provides a device which includes a locator, a kinematic mount positioned on a conventional tooling machine, a part carrier disposed on the locator and a retainer ring. The locator has disposed therein a plurality of steel balls, placed in an equidistant position circumferentially around the locator. The kinematic mount includes a plurality of magnets which are in registry with the steel balls on the locator. In operation, a blank part to be machined is placed between a surface of a locator and the retainer ring (fitting within the part carrier). When the locator (with a blank part to be machined) is coupled to the kinematic mount, the part is thus exposed for the desired machining process. Because the locator is removably attachable to the kinematic mount, it can easily be removed from the mount, reversed, and reinserted onto the mount for additional machining. Further, the locator can likewise be removed from the mount and placed onto another tooling machine having a properly aligned kinematic mount. Because of the unique design and use of magnetic forces of the present invention, positioning errors of less than 0.25 micrometer for each machining process can be achieved.

  3. Reversible micromachining locator

    DOEpatents

    Salzer, L.J.; Foreman, L.R.

    1999-08-31

    This invention provides a device which includes a locator, a kinematic mount positioned on a conventional tooling machine, a part carrier disposed on the locator and a retainer ring. The locator has disposed therein a plurality of steel balls, placed in an equidistant position circumferentially around the locator. The kinematic mount includes a plurality of magnets which are in registry with the steel balls on the locator. In operation, a blank part to be machined is placed between a surface of a locator and the retainer ring (fitting within the part carrier). When the locator (with a blank part to be machined) is coupled to the kinematic mount, the part is thus exposed for the desired machining process. Because the locator is removably attachable to the kinematic mount, it can easily be removed from the mount, reversed, and reinserted onto the mount for additional machining. Further, the locator can likewise be removed from the mount and placed onto another tooling machine having a properly aligned kinematic mount. Because of the unique design and use of magnetic forces of the present invention, positioning errors of less than 0.25 micrometer for each machining process can be achieved. 7 figs.

  4. Reversibility in nucleocytoplasmic transport

    PubMed Central

    Kopito, Ronen Benjamine; Elbaum, Michael

    2007-01-01

    Nucleocytoplasmic exchange of proteins and RNAs is mediated by receptors that usher their cargo through the nuclear pores. Peptide localization signals on each cargo determine the receptors with which it will interact. Those interactions are normally regulated by the small GTPase Ran. Hydrolysis of GTP provides the chemical energy required to create a bona fide thermodynamic pump that selectively and directionally accumulates its substrates across the nuclear envelope. A common perception is that cargo delivery is irreversible, e.g., a protein imported to the nucleus does not return to the cytoplasm except perhaps via a specific export receptor. Quantitative measurements using cell-free nuclei reconstituted in Xenopus egg extract show that nuclear accumulation follows first-order kinetics and reaches steady state at a level that follows a Michaelis–Menten function of the cytoplasmic cargo concentration. This saturation suggests that receptor-mediated translocation across the nuclear pore occurs bidirectionally. The reversibility of accumulation was demonstrated directly by exchange of the cytosolic medium and by fluorescence recovery after photobleaching. Based on our results, we offer a simple biophysical model that predicts the observed behavior. A far-reaching consequence is that the nuclear localization signal dictates the fate of a protein population rather than that of the individual molecules that bear it, which remain free to shuttle back and forth. This implies an open communication between the nucleus and cytoplasm and a ubiquitous mechanism for signaling in both directions. PMID:17646647

  5. A dynamics-free lower bound on the mass of our Galaxy

    NASA Astrophysics Data System (ADS)

    Zaritsky, Dennis; Courtois, Helene

    2017-03-01

    We use a sample of Milky Way (MW) analogues for which we have stellar and disc gas mass measurements, published measurements of halo gas masses of the MW and of similar galaxies, and the well-established value of the cosmological baryon fraction to place a lower bound on the mass of the Galaxy of 7.7 × 1011 M⊙ and estimate that the mass is likely to be ≥1.2 × 1012 M⊙. Although most dynamical analyses yield measurements consistent with these results, several recent studies have advocated for a total mass well below 1012 M⊙. We reject such low-mass estimates because they imply a Galactic baryon matter fraction significantly above the universal value. Convergence between dynamical mass estimates and those based on the baryonic mass is an important milestone in our understanding of galaxies.

  6. B-Ring-Aryl Substituted Luotonin A Analogues with a New Binding Mode to the Topoisomerase 1-DNA Complex Show Enhanced Cytotoxic Activity

    PubMed Central

    González-Ruiz, Víctor; Pascua, Irene; Fernández-Marcelo, Tamara; Ribelles, Pascual; Bianchini, Giulia; Sridharan, Vellaisamy; Iniesta, Pilar; Ramos, M. Teresa; Olives, Ana I.; Martín, M. Antonia; Menéndez, J. Carlos

    2014-01-01

    Topoisomerase 1 inhibition is an important strategy in targeted cancer chemotherapy. The drugs currently in use acting on this enzyme belong to the family of the camptothecins, and suffer severe limitations because of their low stability, which is associated with the hydrolysis of the δ-lactone moiety in their E ring. Luotonin A is a natural camptothecin analogue that lacks this functional group and therefore shows a much-improved stability, but at the cost of a lower activity. Therefore, the development of luotonin A analogues with an increased potency is important for progress in this area. In the present paper, a small library of luotonin A analogues modified at their A and B rings was generated by cerium(IV) ammonium nitrate-catalyzed Friedländer reactions. All analogues showed an activity similar or higher than the natural luotonin A in terms of topoisomerase 1 inhibition and some compounds had an activity comparable to that of camptothecin. Furthermore, most compounds showed a better activity than luotonin A in cell cytotoxicity assays. In order to rationalize these results, the first docking studies of luotonin-topoisomerase 1-DNA ternary complexes were undertaken. Most compounds bound in a manner similar to luotonin A and to standard topoisomerase poisons such as topotecan but, interestingly, the two most promising analogues, bearing a 3,5-dimethylphenyl substituent at ring B, docked in a different orientation. This binding mode allows the hydrophobic moiety to be shielded from the aqueous environment by being buried between the deoxyribose belonging to the G(+1) guanine and Arg364 in the scissile strand and the surface of the protein and a hydrogen bond between the D-ring carbonyl and the basic amino acid. The discovery of this new binding mode and its associated higher inhibitory potency is a significant advance in the design of new topoisomerase 1 inhibitors. PMID:24830682

  7. Statistical properties of reversals and chrons in numerical dynamos and implications for the geodynamo

    NASA Astrophysics Data System (ADS)

    Lhuillier, Florian; Hulot, Gauthier; Gallet, Yves

    2013-07-01

    We analyse a series of very long runs (equivalent to up to 50 Myr) produced by chemically-driven dynamos. All runs assume homogeneous boundary conditions, an electrically conducting inner-core (except for one run) and only differ by the choice of the Rayleigh number Ra★. Introducing dynamo-based definitions of reversals, chrons and related concepts, such as "failed reversals" and "segments" (bounded by reversals or failed reversals), we investigate the distributions of chron and segment lengths, those of reversal and failed reversal durations, the way dipole field behaves through reversals and failed reversals, and the possible links between the axial dipole intensity and chron or segment lengths. We show that chron and segment lengths are very well described in terms of a Poisson process (with no occurrence of superchrons), while distributions of reversal and failed reversal durations are better fitted by log-normal distributions. We found that reversal rates generally increase in proportion to Rm-Rmc,Rm being the magnetic Reynolds number and Rmc a critical value. In contrast, reversal and failed reversal durations appear to be mainly controlled by the core's magnetic diffusion timescale. More generally, we show that much of the reversing behaviour of these dynamos can be understood by examining their signature in a (g10,g11,h11) phase-space plot. This reveals that the run with an insulating inner-core is very different and has only two distinct modes of opposite polarity, which we argue is the reason it displays less reversals and failed reversals, and has a clear tendency to produce an intensity "overshoot" and some systematic pattern in the dipole pole behaviour through reversals and failed reversals. This contrasts with conducting inner-core runs, which display an additional central unstable mode, the importance of which increases with Rm, and which is responsible for the more complex reversing behaviour of these dynamos. Available paleomagnetic data suggest

  8. Inhibition of HIV-1 Reverse Transcriptase Dimerization by Small Molecules.

    PubMed

    Tintori, Cristina; Corona, Angela; Esposito, Francesca; Brai, Annalaura; Grandi, Nicole; Ceresola, Elisa Rita; Clementi, Massimo; Canducci, Filippo; Tramontano, Enzo; Botta, Maurizio

    2016-04-15

    Because HIV-1 reverse transcriptase is an enzyme whose catalytic activity depends on its heterodimeric structure, this system could be a target for inhibitors that perturb the interactions between the protein subunits, p51 and p66. We previously demonstrated that the small molecule MAS0 reduced the association of the two RT subunits and simultaneously inhibited both the polymerase and ribonuclease H activities. In this study, some analogues of MAS0 were rationally selected by docking studies and evaluated in vitro for their ability to disrupt dimeric assembly. Two inhibitors were identified with improved activity compared to MAS0. This study lays the basis for the rational design of more potent inhibitors of RT dimerization.

  9. Missions to Mars: Characterisation of Mars analogue rocks for the International Space Analogue Rockstore (ISAR)

    NASA Astrophysics Data System (ADS)

    Bost, Nicolas; Westall, Frances; Ramboz, Claire; Foucher, Frédéric; Pullan, Derek; Meunier, Alain; Petit, Sabine; Fleischer, Iris; Klingelhöfer, Göstar; Vago, Jorge L.

    2013-07-01

    Instruments for surface missions to extraterrestrial bodies should be cross-calibrated using a common suite of relevant materials. Such work is necessary to improve instrument performance and aids in the interpretation of in-situ measurements. At the CNRS campus in Orléans, the Observatoire des Sciences de l'Univers en région Centre (OSUC) has created a collection of well-characterised rocks and minerals for testing and calibrating instruments to be flown in space missions. The characteristics of the analogue materials are documented in an accompanying online database. In view of the recent and upcoming rover missions to Mars (NASA's 2011 Mars Science Laboratory (MSL) and ESA/Roscosmos' 2018 ExoMars), we are concentrating initially on materials of direct relevance to the red planet. The initial collection consists of 15 well-studied rock and mineral samples, including a variety of basalts (ultramafic, weathered, silicified, primitive), sediments (volcanic sands, chert, and a banded iron formation -BIF-), and the phyllosilicate nontronite (a clay). All the samples were characterised petrographically, petrologically, and geochemically using the types of analyses likely to be performed during in-situ missions, in particular ExoMars: hand specimen description; optical microscopy; mineralogical analysis by XRD, Raman and IR spectrometry; iron phase analysis by Mössbauer spectroscopy (MBS), elemental analysis by Energy-Dispersive X-ray spectroscopy (EDX), microprobe, Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES) and Mass Spectrometry (ICP-MS); and reduced carbon analysis by Raman spectrometry.

  10. Spin Labeling ESR Investigation of Covalently Bound Residues in Soil

    NASA Astrophysics Data System (ADS)

    Aleksandrova, Olga; Steinhoff, Heinz-Juergen; Klasmeier, Joerg; Schulz, Marcus; Matthies, Michael

    2013-04-01

    Organic xenobiotic chemicals, such as pesticides, biocides and veterinary pharmaceuticals, interact with soil, which results in the simultaneous formations of metabolites, mineralization products, and bound or non-extractable residues (NER). Substances or metabolites with reactive functional groups, such as aniline or phenol, have a tendency to give a larger proportion of NER. Despite numerous studies on NER, the majority of their chemical structures is still unknown. Reversible sequestration and irreversible formation of NER were also observed for veterinary antibiotic pharmaceuticals, after their application to soil with and without manure. For this purpose, we hypothesized a key role of specific functional groups of soil contaminants, via which contaminants are covalently bound to soil constituents, and advance a method of spin labeling ESR investigation of reaction products using a membrane method. Spin labels (SL) represent chemically stable paramagnetic molecules used as molecular labels and molecular probes for testing the covalent binding, structural properties, and molecular mobility of different physical, chemical, and biological systems. In the case of covalent binding of SL, their ESR spectra become broadened. We used stable nitroxide radicals (NR) as SL. These radicals modeled organic chemical contaminants and differed only in one functional group. The paramagnetic SL 4-Amino Tempo (4-amino-2,2,6,6-tetramethyl-1-piperidinylox) differed from Tempo (2,2,6,6-Tetramethylpiperidinooxy) in a substituent at the para-position of the piperidine ring, whereas Aniline Tempo (1-Piperidinyloxy, 2,2,6,-tetramethyl, 6-Aniline) differed from Tempo in an Aniline substituting one CH3 functional group. Before experimental analysis, we tested temporal changes in the concentration of both NR incubated with soil and found that the life-times of them in soil exceeded 3 days. We contaminated and labeled soil samples with NR, adding to soil the aqueous solution, which already

  11. Reverse genetics of avian metapneumoviruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An overview of avian metapneumovirus (aMPV) infection in turkeys and development of a reverse genetics system for aMPV subgroup C (aMPV-C) virus will be presented. By using reverse genetics technology, we generated recombinant aMPV-C viruses containing a different length of glycoprotein (G) gene or...

  12. Play: The Reversal Theory Perspective.

    ERIC Educational Resources Information Center

    Kerr, J. H.

    The intention of this theoretical paper is to present a reversal theory interpretation of play phenomena. Reversal theory, a developing theory in psychology, concerns the complex relationship between experience and motivation. One of the central charactieristics of the theory is that it attempts to understand why so much of human behavior is…

  13. Reverse Transfer Project, Summer 1986.

    ERIC Educational Resources Information Center

    Reis, Elizabeth

    In 1986, a Reverse Transfer Project was initiated at Moraine Valley Community College (MVCC) in order to promote the summer school attendance at MVCC of "reverse transfer" students (i.e., students who attended another institution during the regular academic year). A mailing, containing a cover letter, informational brochure, summer catalog, and…

  14. Preference Reversal in Multiattribute Choice

    ERIC Educational Resources Information Center

    Tsetsos, Konstantinos; Usher, Marius; Chater, Nick

    2010-01-01

    A central puzzle for theories of choice is that people's preferences between options can be reversed by the presence of decoy options (that are not chosen) or by the presence of other irrelevant options added to the choice set. Three types of reversal effect reported in the decision-making literature, the attraction, compromise, and similarity…

  15. Bioactivity of albumins bound to silver nanoparticles.

    PubMed

    Mariam, Jessy; Sivakami, S; Kothari, D C; Dongre, P M

    2014-06-01

    The last decade has witnessed a tremendous rise in the proposed applications of nanomaterials in the field of medicine due to their very attractive physiochemical properties and novel actions such as the ability to reach previously inaccessible targets such as brain. However biological activity of functional molecules bound to nanoparticles and its physiological consequences is still unclear and hence this area requires immediate attention. The functional properties of Human Serum Albumin (HSA) and Bovine Serum Albumin (BSA) bound to silver nanoparticles (~60 nm) have been studied under physiological environment. Esterase activity, binding of drugs (warfarin and ibuprofen), antioxidant activity and copper binding by albumins was evaluated. The catalytic efficiencies of HSA and BSA diminished upon binding to silver nanoparticles. Perturbation in binding of warfarin and ibuprofen, loss of free sulphydryls, antioxidant activity and enhancement of copper binding were observed in albumins bound to nanoparticles. These alterations in functional activity of nanoparticle bound albumins which will have important consequences should be taken into consideration while using nanoparticles for diagnostic and therapeutic purposes.

  16. Outward Bound as an Adjunct to Therapy.

    ERIC Educational Resources Information Center

    Chase, Nelson K.

    The Colorado Outward Bound School (COBS) provides successful adjunct programs for special populations undergoing therapy at the Adventure Home (Boulder, CO), the Juvenile Justice Program and the St. Luke's Hospital Alcoholism Recovery Unit (Denver, CO), and the Dartmouth-Hitchcock Medical Center Department of Psychiatry (Hanover, NH). The goals of…

  17. Lifetime of a Chemically Bound Helium Compound

    NASA Technical Reports Server (NTRS)

    Chaban, Galina M.; Lundell, Jan; Gerber, R. Benny; Kwak, Dochan (Technical Monitor)

    2001-01-01

    The rare-gas atoms are chemically inert, to an extent unique among all elements. This is due to the stable electronic structure of the atoms. Stable molecules with chemically bound rare-gas atoms are, however, known. A first such compound, XePtF6, W2S prepared in 1962 and since then a range of molecules containing radon, xenon and krypton have been obtained. Most recently, a first stable chemically bound compound of argon was prepared, leaving neon and helium as the only elements for which stable chemically bound molecules are not yet known. Electronic structure calculations predict that a metastable species HHeF exists, but significance of the result depends on the unknown lifetime. Here we report quantum dynamics calculations of the lifetime of HHeF, using accurate interactions computed from electronic structure theory. HHeF is shown to disintegrate by tunneling through energy barriers into He + HF and H + He + F the first channel greatly dominating. The lifetime of HHeF is more than 120 picoseconds, that of DHeF is 14 nanoseconds. The relatively long lifetimes are encouraging for the preparation prospects of this first chemically bound helium compound.

  18. College Bound Seniors, 1974-75.

    ERIC Educational Resources Information Center

    College Entrance Examination Board, New York, NY.

    Some one million college bound students, who were high school seniors during 1974-75 previously participated in the College Board's Admissions Testing Program (ATP), which included the Scholarship Aptitude Test (SAT), the Test of Standard Written English, the Student Descriptive Questionnaire, and the ATP Achievement Tests. These tests created a…

  19. Mean shift is a bound optimization.

    PubMed

    Fashing, Mark; Tomasi, Carlo

    2005-03-01

    We build on the current understanding of mean shift as an optimization procedure. We demonstrate that, in the case of piecewise constant kernels, mean shift is equivalent to Newton's method. Further, we prove that, for all kernels, the mean shift procedure is a quadratic bound maximization.

  20. Bounds on transverse momentum dependent distribution functions

    NASA Astrophysics Data System (ADS)

    Henneman, A.

    2001-01-01

    When more than one hadron takes part in a hard process, an extended set of quark distribution and fragmentation functions becomes relevant. In this talk, the derivation of Soffer-like bounds for these functions, in the case of a spin-1/2 target [1], is sketched and some of their aspects are discussed.

  1. Mentoring College Bound High School Seniors.

    ERIC Educational Resources Information Center

    Mowrer-Popiel, Elizabeth

    This article examines causes of the high rate of attrition of college freshmen during the first few weeks of school and describes a plan for mentorships between successful college students and college-bound secondary seniors prior to entrance into college. In discussing the challenges facing freshmen, the article suggests that they suffer stress…

  2. Bounded relative motion under zonal harmonics perturbations

    NASA Astrophysics Data System (ADS)

    Baresi, Nicola; Scheeres, Daniel J.

    2017-04-01

    The problem of finding natural bounded relative trajectories between the different units of a distributed space system is of great interest to the astrodynamics community. This is because most popular initialization methods still fail to establish long-term bounded relative motion when gravitational perturbations are involved. Recent numerical searches based on dynamical systems theory and ergodic maps have demonstrated that bounded relative trajectories not only exist but may extend up to hundreds of kilometers, i.e., well beyond the reach of currently available techniques. To remedy this, we introduce a novel approach that relies on neither linearized equations nor mean-to-osculating orbit element mappings. The proposed algorithm applies to rotationally symmetric bodies and is based on a numerical method for computing quasi-periodic invariant tori via stroboscopic maps, including extra constraints to fix the average of the nodal period and RAAN drift between two consecutive equatorial plane crossings of the quasi-periodic solutions. In this way, bounded relative trajectories of arbitrary size can be found with great accuracy as long as these are allowed by the natural dynamics and the physical constraints of the system (e.g., the surface of the gravitational attractor). This holds under any number of zonal harmonics perturbations and for arbitrary time intervals as demonstrated by numerical simulations about an Earth-like planet and the highly oblate primary of the binary asteroid (66391) 1999 KW4.

  3. Colorado Outward Bound School River Rafters' Manual.

    ERIC Educational Resources Information Center

    Leachman, Mark

    Instructional sequences, safety rules, duties of crew members, and procedures for Colorado Outward Bound School river rafting trips are summarized in this manual. Designed to acquaint instructors with the duties expected of them on the trips, the information in the manual is presented in outline form and is intended for those with prior river…

  4. Colorado Outward Bound School Rafting Manual.

    ERIC Educational Resources Information Center

    Brown, Al

    River rafting trips at the Colorado Outward Bound School (COBS) present participants with an opportunity for developing self-confidence, self-awareness, and concern for others through challenging and adventuresome group effort, combined with a program of instruction in rafting skills, safety consciousness, and awareness of the natural environment.…

  5. Bound Indoleacetic Acid in Avena Coleoptiles 1

    PubMed Central

    Winter, Alan; Thimann, Kenneth V.

    1966-01-01

    When C14 carboxyl indoleacetic acid (IAA) is transported through Avena coleoptile sections a fraction of the activity becomes bound. The nature of this bound IAA has been investigated. Upon extraction with solvents and chromatography a substance having the RF of IAA in 4 solvents was detected. No evidence could be found for the formation of indoleacetyl conjugates. In pea stem sections subjected to a similar experimental regime good evidence was obtained for the occurrence of conjugates. When IAA was supplied exogenously to coleoptile sections floating in solutions the occurrence of conjugates was shown to be dependent on the presence of the primary leaf. In its absence no conjugates could be detected. On grinding coleoptile sections and subsequent centrifugation at 240 × g the radioactivity was found to be in the tissue fraction as opposed to the supernatant. The radioactivity cannot be removed from the tissue by extraction with water, buffer solution or treatment with ribonuclease. It is readily removed by 10% urea, crystalline trypsin and chymotrypsin. It is therefore concluded that IAA becomes bound to a protein. Bound IAA does not appear to be able to cause growth in Avena coleoptile sections. PMID:16656259

  6. Towards a New Generation of Outward Bound.

    ERIC Educational Resources Information Center

    Martin, Andrew

    2000-01-01

    Outward Bound Czech Republic developed a course for international participants in which everybody is simultaneously an actor and viewer in a 2-week theater play. A five-stage process of developing "dramaturgy" allows instructors to adapt the scenario to participant needs and thus enhance the likelihood of challenge and transfer of…

  7. [Oxazaphosphorinane drugs. New analogues, metabolic studies, and therapeutic approaches].

    PubMed

    Misiura, Konrad

    2004-01-01

    Recent studies on oxazaphosphorinane drugs, with the main focus on those carried out in Poland, are briefly reviewed. Research leading to the introduction of the new antitumor drug (S)-(-)-bromofosfamide are presented. The utility of phosphorus nuclear magnetic resonance in studies of ifosfamide metabolism and an application of analogues of the final, active metabolite of this drug in gene therapy are shown.

  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. 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…

  10. 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.

  11. A Laboratory Analogue for the Study of Peer Sexual Harassment

    ERIC Educational Resources Information Center

    Mitchell, Damon; Hirschman, Richard; Angelone, D. J.; Lilly, Roy S.

    2004-01-01

    The purpose of this study was to develop a laboratory analogue for the study of peer sexual harassment, and to examine person and situational factors associated with male on female peer sexual harassment. One hundred twenty-two male participants were given the opportunity to tell jokes to a female confederate from a joke list that included…

  12. 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.

  13. Fluorescence Studies Of A Cholesterol-Analogue Probe

    NASA Astrophysics Data System (ADS)

    Drew, Jacinta; Szabo, Arthur G.; Morand, Peter

    1988-06-01

    A novel cholesterol-analogue probe1,2 with a diene-(2-naphthyl) fluorophore in the sidechain (Figure 1), hereafter referred to as DN-Chol, has had its steady-state and time-resolved fluorescence properties characterized in solvents and in various viscosity mineral oils.

  14. 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.

  15. Cyclization of nucleotide analogues as an obstacle to polymerization

    NASA Technical Reports Server (NTRS)

    Hill, A. R. Jr; Nord, L. D.; Orgel, L. E.; Robins, R. K.

    1988-01-01

    Cyclization of activated nucleotide analogues by intramolecular phosphodiester-bond formation is likely to compete very effectively with template-directed condensation except in the cases of ribo- and arabinonucleotides. This could have excluded derivatives of most sugars from growing polyribonucleotide chains and thus reduced chain-termination in prebiotic polynucleotide synthesis.

  16. Synthesis of (+)-crocacin D and simplified bioactive analogues.

    PubMed

    Pasqua, Adele E; Ferrari, Frank D; Crawford, James J; Whittingham, William G; Marquez, Rodolfo

    2015-03-01

    The total synthesis of (+)-crocacin D has been achieved in 15 steps (9 isolated intermediates) and 14% overall yield from commercially available starting materials and using (+)-crocacin C as a key intermediate. A number of simplified analogues and their biological activities are also reported.

  17. 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).

  18. 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.

  19. Vitamin D analogues: Potential use in cancer treatment.

    PubMed

    Duffy, Michael J; Murray, Alyson; Synnott, Naoise C; O'Donovan, Norma; Crown, John

    2017-04-01

    The vitamin D receptor (VDR) is a member of the thyroid-steroid family of nuclear transcription factors. Following binding of the active form of vitamin D, i.e., 1,25(OH)2D3 (also known as calcitriol) and interaction with co-activators and co-repressors, VDR regulates the expression of several different genes. Although relatively little work has been carried out on VDR in human cancers, several epidemiological studies suggest that low circulating levels of vitamin D are associated with both an increased risk of developing specific cancer types and poor outcome in patients with specific diagnosed cancers. These associations apply especially in colorectal and breast cancer. Consistent with these findings, calcitriol as well as several of its synthetic analogues have been shown to inhibit tumor cell growth in vitro and in diverse animal model systems. Indeed, some of these vitamin D analogues with low calcemic inducing activity (e.g., EB1089, inecalcitol, paricalcitol) have progressed to clinical trials in patients with cancer. Preliminary results from these trials suggest that these vitamin D analogues have minimal toxicity, but clear evidence of efficacy remains to be shown. Although evidence of efficacy for mono-treatment with vitamin D analogues is currently lacking, several studies have reported that supplementation with calcitriol or the presence of high endogenous circulating levels of vitamin D enhances response to standard therapies.

  20. Synthesis of chlorins, bacteriochlorins and their tetraaza analogues

    NASA Astrophysics Data System (ADS)

    Dudkin, S. V.; Makarova, E. A.; Lukyanets, E. A.

    2016-07-01

    The currently known methods for the synthesis of hydrogenated derivatives of synthetic porphyrins — chlorins, bacteriochlorins, isobacteriochlorins and their tetraaza analogues — are considered. Reactions involving quasi-isolated double bonds including reduction, oxidative addition and cycloaddition are presented. Examples of direct synthesis of these macroheterocycles are given. The bibliography includes 168 references.

  1. Conformational behavior of flavin adenine dinucleotide: conserved stereochemistry in bound and free states.

    PubMed

    Kuppuraj, Gopi; Kruise, Dennis; Yura, Kei

    2014-11-26

    Metabolic enzymes utilize the cofactor flavin adenine dinucleotide (FAD) to catalyze essential biochemical reactions. Because these enzymes have been implicated in disease pathways, it will be necessary to target them via FAD-based structural analogues that can either activate/inhibit the enzymatic activity. To achieve this, it is important to explore the conformational space of FAD in the enzyme-bound and free states. Herein, we analyze X-ray crystallographic data of the enzyme-bound FAD conformations and sample conformations of the molecule in explicit water by molecular dynamics (MD) simulations. Enzyme-bound FAD conformations segregate into five distinct groups based on dihedral angle principal component analysis (PCA). A notable feature in the bound FADs is that the adenine base and isoalloxazine ring are oppositely oriented relative to the pyrophosphate axis characterized by near trans hypothetical dihedral angle "δV" values. Not surprisingly, MD simulations in water show final compact but not perfectly stacked ring structures in FAD. Simulation data did not reveal noticeable changes in overall conformational dynamics of the dinucleotide in reduced and oxidized forms and in the presence and/or absence of ions. During unfolding-folding dynamics, the riboflavin moiety is more flexible than the adenosine monophosphate group in the molecule. Conversely, the isoalloxazine ring is more stable than the variable adenine base. The pyrophosphate group depicts an unusually highly organized fluctuation illustrated by its dihedral angle distribution. Conformations sampled from enzymes and MD are quantified. The extent to which the protein shifts the distribution from the unbound state is discussed in terms of prevalent FAD shapes and dihedral angle population.

  2. Classical Analog to Entanglement Reversibility

    NASA Astrophysics Data System (ADS)

    Chitambar, Eric; Fortescue, Ben; Hsieh, Min-Hsiu

    2015-08-01

    In this Letter we study the problem of secrecy reversibility. This asks when two honest parties can distill secret bits from some tripartite distribution pX Y Z and transform secret bits back into pX Y Z at equal rates using local operation and public communication. This is the classical analog to the well-studied problem of reversibly concentrating and diluting entanglement in a quantum state. We identify the structure of distributions possessing reversible secrecy when one of the honest parties holds a binary distribution, and it is possible that all reversible distributions have this form. These distributions are more general than what is obtained by simply constructing a classical analog to the family of quantum states known to have reversible entanglement. An indispensable tool used in our analysis is a conditional form of the Gács-Körner common information.

  3. Transition States and transition state analogue interactions with enzymes.

    PubMed

    Schramm, Vern L

    2015-04-21

    Enzymatic transition states have lifetimes of a few femtoseconds (fs). Computational analysis of enzyme motions leading to transition state formation suggests that local catalytic site motions on the fs time scale provide the mechanism to locate transition states. An experimental test of protein fs motion and its relation to transition state formation can be provided by isotopically heavy proteins. Heavy enzymes have predictable mass-altered bond vibration states without altered electrostatic properties, according to the Born-Oppenheimer approximation. On-enzyme chemistry is slowed in most heavy proteins, consistent with altered protein bond frequencies slowing the search for the transition state. In other heavy enzymes, structural changes involved in reactant binding and release are also influenced. Slow protein motions associated with substrate binding and catalytic site preorganization are essential to allow the subsequent fs motions to locate the transition state and to facilitate the efficient release of products. In the catalytically competent geometry, local groups move in stochastic atomic motion on the fs time scale, within transition state-accessible conformations created by slower protein motions. The fs time scale for the transition state motions does not permit thermodynamic equilibrium between the transition state and stable enzyme states. Isotopically heavy enzymes provide a diagnostic tool for fast coupled protein motions to transition state formation and mass-dependent conformational changes. The binding of transition state analogue inhibitors is the opposite in catalytic time scale to formation of the transition state but is related by similar geometries of the enzyme-transition state and enzyme-inhibitor interactions. While enzymatic transition states have lifetimes as short as 10(-15) s, transition state analogues can bind tightly to enzymes with release rates greater than 10(3) s. Tight-binding transition state analogues stabilize the rare but

  4. 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

  5. α-MSH analogue attenuates blood pressure elevation in DOCA-salt hypertensive mice.

    PubMed

    Rinne, Petteri; Penttinen, Anna-Maija; Nordlund, Wendy; Ahotupa, Markku; Savontaus, Eriika

    2013-01-01

    Melanocyte-stimulating hormones, α-, β- and γ-MSH, regulate important physiological functions including energy homeostasis, inflammation and sodium metabolism. Previous studies have shown that α-MSH increases sodium excretion and promotes vascular function in rodents, but it is unexplored whether these characteristics of α-MSH could translate into therapeutic benefits in the treatment of hypertension. Therefore, we first assessed the diuretic and natriuretic properties of the stable α-MSH analogue [Nle(4), D-Phe(7)]-α-MSH (NDP-α-MSH) and investigated whether it has protective effects in deoxycorticosterone acetate (DOCA)-salt hypertensive mice. Adult male C57Bl/6N mice were subjected to DOCA-salt treatment and randomized to receive intraperitoneal injections of either saline as vehicle or NDP-α-MSH (0.3 mg/kg/day for 14 days) starting 7 days after the DOCA-salt treatment. Systemic hemodynamics, serum and urine electrolytes, and oxidative stress markers were assessed in control sham-operated and DOCA-salt mice. NDP-α-MSH elicited marked diuretic and natriuretic responses that were reversible with the MC3/4 receptor antagonist SHU9119. Chronic NDP-α-MSH treatment attenuated blood pressure elevation in DOCA-salt mice without affecting the blood pressure of normotensive control animals. Owing to the enhanced sodium excretion, NDP-α-MSH-treated mice were protected from DOCA-salt-induced hypernatremia. DOCA-salt treatment mildly increased oxidative stress at the tissue level, but NDP-α-MSH had no significant effects on the oxidative stress markers. In conclusion, treatment with NDP-α-MSH increases urinary sodium excretion and protects against DOCA-salt-induced hypertension. These findings point to the potential future use of α-MSH analogues in the treatment of hypertension.

  6. Sample Complexity Bounds for Differentially Private Learning

    PubMed Central

    Chaudhuri, Kamalika; Hsu, Daniel

    2013-01-01

    This work studies the problem of privacy-preserving classification – namely, learning a classifier from sensitive data while preserving the privacy of individuals in the training set. In particular, the learning algorithm is required in this problem to guarantee differential privacy, a very strong notion of privacy that has gained significant attention in recent years. A natural question to ask is: what is the sample requirement of a learning algorithm that guarantees a certain level of privacy and accuracy? We address this question in the context of learning with infinite hypothesis classes when the data is drawn from a continuous distribution. We first show that even for very simple hypothesis classes, any algorithm that uses a finite number of examples and guarantees differential privacy must fail to return an accurate classifier for at least some unlabeled data distributions. This result is unlike the case with either finite hypothesis classes or discrete data domains, in which distribution-free private learning is possible, as previously shown by Kasiviswanathan et al. (2008). We then consider two approaches to differentially private learning that get around this lower bound. The first approach is to use prior knowledge about the unlabeled data distribution in the form of a reference distribution chosen independently of the sensitive data. Given such a reference , we provide an upper bound on the sample requirement that depends (among other things) on a measure of closeness between and the unlabeled data distribution. Our upper bound applies to the non-realizable as well as the realizable case. The second approach is to relax the privacy requirement, by requiring only label-privacy – namely, that the only labels (and not the unlabeled parts of the examples) be considered sensitive information. An upper bound on the sample requirement of learning with label privacy was shown by Chaudhuri et al. (2006); in this work, we show a lower bound. PMID:25285183

  7. 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.

  8. 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.

  9. Sulphamoylated 2-Methoxyestradiol Analogues Induce Apoptosis in Adenocarcinoma Cell Lines

    PubMed Central

    Visagie, Michelle; Theron, Anne; Mqoco, Thandi; Vieira, Warren; Prudent, Renaud; Martinez, Anne; Lafanechère, Laurence; Joubert, Annie

    2013-01-01

    2-Methoxyestradiol (2ME2) is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1–25 μM) was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues. PMID:24039728

  10. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    PubMed

    Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David

    2017-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT2a,b,c and NEα2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT2a,c receptors as compared to MDMA.

  11. Cysteine analogues potentiate glucose-induced insulin release in vitro

    SciTech Connect

    Ammon, H.P.; Hehl, K.H.; Enz, G.; Setiadi-Ranti, A.; Verspohl, E.J.

    1986-12-01

    In rat pancreatic islets, cysteine analogues, including glutathione, acetylcysteine, cysteamine, D-penicillamine, L-cysteine ethyl ester, and cysteine-potentiated glucose (11.1 mM) induced insulin secretion in a concentration-dependent manner. Their maximal effects were similar and occurred at approximately 0.05, 0.05, 0.1, 0.5, 1.0, 1.0 mM, respectively. At substimulatory glucose levels (2.8 mM), insulin release was not affected by these compounds. In contrast, thiol compounds, structurally different from cysteine and its analogues, such as mesna, tiopronin, meso-2,3-dimercaptosuccinic acid (DMSA), dimercaprol (BAL), beta-thio-D-glucose, as well as those cysteine analogues that lack a free-thiol group, including L-cystine, cystamine, D-penicillamine disulfide, S-carbocysteine, and S-carbamoyl-L-cysteine, did not enhance insulin release at stimulatory glucose levels (11.1 mM); cystine (5 mM) was inhibitory. These in vitro data indicate that among the thiols tested here, only cysteine and its analogues potentiate glucose-induced insulin secretion, whereas thiols that are structurally not related to cysteine do not. This suggests that a cysteine moiety in the molecule is necessary for the insulinotropic effect. For their synergistic action to glucose, the availability of a sulfhydryl group is also a prerequisite. The maximal synergistic action is similar for all cysteine analogues tested, whereas the potency of action is different, suggesting similarity in the mechanism of action but differences in the affinity to the secretory system.

  12. Reverse osmosis reverses conventional wisdom with Superfund cleanup success

    SciTech Connect

    Collins, M. ); Miller, K. )

    1994-09-01

    Although widely recognized as the most efficient means of water purification, reverse osmosis has not been considered effective for remediating hazardous wastewater. Scaling and fouling, which can cause overruns and downtime, and require membrane replacement, have inhibited success in high-volume wastewater applications. Despite this background, a reverse osmosis technology developed in Europe recently was used successfully to treat large volumes of contaminated water at a major Superfund site in Texas. The technology's success there may increase the chances for reverse osmosis to find wider use in future cleanups and other waste treatment applications.

  13. Stability of carbonaceous dust analogues and glycine under UV irradiation and electron bombardment.

    PubMed

    Maté, Belén; Tanarro, Isabel; Moreno, Miguel A; Jiménez-Redondo, Miguel; Escribano, Rafael; Herrero, Víctor J

    2014-01-01

    The effect of UV photon (120-200 nm) and electron (2 keV) irradiation of analogues of interstellar carbonaceous dust and of glycine were investigated by means of IR spectroscopy. Films of hydrogenated amorphous carbon (HAC), taken as dust analogues, were found to be stable under UV photon and electron bombardment. High fluences of photons and electrons, of the order of 10(19) cm(-2), were needed for a film depletion of a few percent. UV photons were energetically more effective than electrons for depletion and led to a certain dehydrogenation of the HAC samples, whereas electrons led seemingly to a gradual erosion with no appreciable changes in the hydrocarbon structure. The rates of change observed may be relevant over the lifetime of a diffuse cloud, but cannot account for the rapid changes in hydrocarbon IR bands during the evolution of some proto-planetary nebulae. Glycine samples under the same photon and electron fluxes decay at a much faster rate, but tend usually to an equilibrium value different from zero, especially at low temperatures. Reversible reactions re-forming glycine, or the build-up of less transparent products, could explain this behavior. CO2 and methylamine were identified as UV photoproducts. Electron irradiation led to a gradual disappearance of the glycine layers, also with formation of CO2. No other reaction products were clearly identified. The thicker glycine layers (a few hundred nm) were not wholly depleted, but a film of the order of the electron penetration depth (80 nm), was totally destroyed with an electron fluence of -1 x 10(18) cm(-2). A 60 nm ice layer on top of glycine provided only partial shielding from the 2 keV electrons. From an energetic point of view, 2 keV electrons are less efficient than UV photons and, according to literature data, much less efficient than MeV protons for the destruction of glycine. The use of keV electrons to simulate effects of cosmic rays on analogues of interstellar grains should be taken with

  14. The Geomagnetic Field During a Reversal

    NASA Technical Reports Server (NTRS)

    Heirtzler, James R.

    2003-01-01

    By modifying the IGRF it is possible to learn what may happen to the geomagnetic field during a geomagnetic reversal. If the entire IGRF reverses then the declination and inclination only reverse when the field strength is zero. If only the dipole component of the IGRF reverses a large geomagnetic field remains when the dipole component is zero and he direction of the field at the end of the reversal is not exactly reversed from the directions at the beginning of the reversal.

  15. Muraymycins, novel peptidoglycan biosynthesis inhibitors: synthesis and SAR of their analogues.

    PubMed

    Yamashita, Ayako; Norton, Emily; Petersen, Peter J; Rasmussen, Beth A; Singh, Guy; Yang, Youjin; Mansour, Tarek S; Ho, Douglas M

    2003-10-06

    A series of Muraymycin analogues was synthesized. These analogues showed excellent antimicrobial activity against gram-positive organisms. These analogues also showed excellent inhibitory activity against the target peptidoglycan biosynthesis enzyme MraY, the cell membrane associated transglycosylase responsible for the formation of Lipid II.

  16. Analogue modelling of inclined, brittle-ductile transpression: Testing analytical models through natural shear zones (external Betics)

    NASA Astrophysics Data System (ADS)

    Barcos, L.; Díaz-Azpiroz, M.; Balanyá, J. C.; Expósito, I.; Jiménez-Bonilla, A.; Faccenna, C.

    2016-07-01

    The combination of analytical and analogue models gives new opportunities to better understand the kinematic parameters controlling the evolution of transpression zones. In this work, we carried out a set of analogue models using the kinematic parameters of transpressional deformation obtained by applying a general triclinic transpression analytical model to a tabular-shaped shear zone in the external Betic Chain (Torcal de Antequera massif). According to the results of the analytical model, we used two oblique convergence angles to reproduce the main structural and kinematic features of structural domains observed within the Torcal de Antequera massif (α = 15° for the outer domains and α = 30° for the inner domain). Two parallel inclined backstops (one fixed and the other mobile) reproduce the geometry of the shear zone walls of the natural case. Additionally, we applied digital particle image velocimetry (PIV) method to calculate the velocity field of the incremental deformation. Our results suggest that the spatial distribution of the main structures observed in the Torcal de Antequera massif reflects different modes of strain partitioning and strain localization between two domain types, which are related to the variation in the oblique convergence angle and the presence of steep planar velocity - and rheological - discontinuities (the shear zone walls in the natural case). In the 15° model, strain partitioning is simple and strain localization is high: a single narrow shear zone is developed close and parallel to the fixed backstop, bounded by strike-slip faults and internally deformed by R and P shears. In the 30° model, strain partitioning is strong, generating regularly spaced oblique-to-the backstops thrusts and strike-slip faults. At final stages of the 30° experiment, deformation affects the entire model box. Our results show that the application of analytical modelling to natural transpressive zones related to upper crustal deformation

  17. 34 CFR 645.12 - What services may regular Upward Bound and Upward Bound Math-Science projects provide?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What services may regular Upward Bound and Upward Bound Math-Science projects provide? 645.12 Section 645.12 Education Regulations of the Offices of the... services may regular Upward Bound and Upward Bound Math-Science projects provide? Any project...

  18. 34 CFR 645.12 - What services may regular Upward Bound and Upward Bound Math-Science projects provide?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false What services may regular Upward Bound and Upward Bound Math-Science projects provide? 645.12 Section 645.12 Education Regulations of the Offices of the... services may regular Upward Bound and Upward Bound Math-Science projects provide? Any project...

  19. 34 CFR 645.12 - What services may regular Upward Bound and Upward Bound Math-Science projects provide?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false What services may regular Upward Bound and Upward Bound Math-Science projects provide? 645.12 Section 645.12 Education Regulations of the Offices of the... services may regular Upward Bound and Upward Bound Math-Science projects provide? Any project...

  20. 34 CFR 645.12 - What services may regular Upward Bound and Upward Bound Math-Science projects provide?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false What services may regular Upward Bound and Upward Bound Math-Science projects provide? 645.12 Section 645.12 Education Regulations of the Offices of the... services may regular Upward Bound and Upward Bound Math-Science projects provide? Any project...

  1. Cryo-EM reveals the conformation of a substrate analogue in the human 20S proteasome core

    NASA Astrophysics Data System (ADS)

    da Fonseca, Paula C. A.; Morris, Edward P.

    2015-07-01

    The proteasome is a highly regulated protease complex fundamental for cell homeostasis and controlled cell cycle progression. It functions by removing a wide range of specifically tagged proteins, including key cellular regulators. Here we present the structure of the human 20S proteasome core bound to a substrate analogue inhibitor molecule, determined by electron cryo-microscopy (cryo-EM) and single-particle analysis at a resolution of around 3.5 Å. Our map allows the building of protein coordinates as well as defining the location and conformation of the inhibitor at the different active sites. These results open new prospects to tackle the proteasome functional mechanisms. Moreover, they also further demonstrate that cryo-EM is emerging as a realistic approach for general structural studies of protein-ligand interactions.

  2. Observation by sup 13 C NMR of the EPSP synthase tetrahedral intermediate bound to the enzyme active site

    SciTech Connect

    Anderson, K.S.; Sammons, R.D.; Leo, G.C.; Sikorski, J.A. ); Benesi, A.J.; Johnson, K.A. )

    1990-02-13

    Direct observation of the tetrahedral intermediate in the EPSP synthase reaction pathway was provided by {sup 13}C NMR by examining the species bound to the enzyme active site under internal equilibrium conditions and using (2-{sup 13}C)PEP as a spectroscopic probe. The tetrahedral center of the intermediate bound to the enzyme gave a unique signal appearing at 104 ppm. Separate signals were observed for free EPSP and EPSP bound to the enzyme in a ternary complex with phosphate. These peak assignments account for the quantitation of the species bound to the enzyme and liberated upon quenching with either triethylamine or base. A comparison of quenching with acid, base, or triethylamine was conducted. After long times of incubation during the NMR measurement, a signal at 107 ppm appeared. The compound giving rise to this resonance was isolated and identified as an EPSP ketal. The rate of formation of the EPSP ketal was very slow establishing that it is a side product of the normal enzymatic reaction. To look for additional signals that might arise from a covalent adduct which has been postulated to arise from reaction of enzyme with PEP, and NMR experiment was performed with an analogue of S3P lacking the 4- and 5-hydroxyl groups. All of these results reaffirm identification of the tetrahedral species as the only observable intermediate in the EPSP synthase reaction.

  3. Supercritical fluid reverse micelle separation

    DOEpatents

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  4. Supercritical fluid reverse micelle separation

    DOEpatents

    Fulton, John L.; Smith, Richard D.

    1993-01-01

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W.sub.o that determines the maximum size of the reverse micelles. The maximum ratio W.sub.o of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions.

  5. Aerodynamics of intermittent bounds in flying birds

    NASA Astrophysics Data System (ADS)

    Tobalske, Bret W.; Hearn, Jason W. D.; Warrick, Douglas R.

    Flap-bounding is a common flight style in small birds in which flapping phases alternate with flexed-wing bounds. Body lift is predicted to be essential to making this flight style an aerodynamically attractive flight strategy. To elucidate the contributions of the body and tail to lift and drag during the flexed-wing bound phase, we used particle image velocimetry (PIV) and measured properties of the wake of zebra finch (Taeniopygia guttata, N = 5), flying at 6-10 m s- 1 in a variable speed wind tunnel as well as flow around taxidermically prepared specimens (N = 4) mounted on a sting instrumented with force transducers. For the specimens, we varied air velocity from 2 to 12 m s- 1 and body angle from -15∘ to 50∘. The wake of bounding birds and mounted specimens consisted of a pair of counterrotating vortices shed into the wake from the tail, with induced downwash in the sagittal plane and upwash in parasagittal planes lateral to the bird. This wake structure was present even when the tail was entirely removed. We observed good agreement between force measures derived from PIV and force transducers over the range of body angles typically used by zebra finch during forward flight. Body lift:drag (L:D) ratios averaged 1.4 in live birds and varied between 1 and 1.5 in specimens at body angles from 10∘ to 30∘. Peak (L:D) ratio was the same in live birds and specimens (1.5) and was exhibited in specimens at body angles of 15∘ or 20∘, consistent with the lower end of body angles utilized during bounds. Increasing flight velocity in live birds caused a decrease in CL and CD from maximum values of 1.19 and 0.95 during flight at 6 m s- 1 to minimum values of 0.70 and 0.54 during flight at 10 m s- 1. Consistent with delta-wing theory as applied to birds with a graduated-tail shape, trimming the tail to 0 and 50% of normal length reduced L:D ratios and extending tail length to 150% of normal increased L:D ratio. As downward induced velocity is present in the

  6. Aerodynamics of intermittent bounds in flying birds

    NASA Astrophysics Data System (ADS)

    Tobalske, Bret W.; Hearn, Jason W. D.; Warrick, Douglas R.

    2009-05-01

    Flap-bounding is a common flight style in small birds in which flapping phases alternate with flexed-wing bounds. Body lift is predicted to be essential to making this flight style an aerodynamically attractive flight strategy. To elucidate the contributions of the body and tail to lift and drag during the flexed-wing bound phase, we used particle image velocimetry (PIV) and measured properties of the wake of zebra finch ( Taeniopygia guttata, N = 5), flying at 6-10 m s-1 in a variable speed wind tunnel as well as flow around taxidermically prepared specimens ( N = 4) mounted on a sting instrumented with force transducers. For the specimens, we varied air velocity from 2 to 12 m s-1 and body angle from -15° to 50°. The wake of bounding birds and mounted specimens consisted of a pair of counter-rotating vortices shed into the wake from the tail, with induced downwash in the sagittal plane and upwash in parasagittal planes lateral to the bird. This wake structure was present even when the tail was entirely removed. We observed good agreement between force measures derived from PIV and force transducers over the range of body angles typically used by zebra finch during forward flight. Body lift:drag ( L: D) ratios averaged 1.4 in live birds and varied between 1 and 1.5 in specimens at body angles from 10° to 30°. Peak ( L: D) ratio was the same in live birds and specimens (1.5) and was exhibited in specimens at body angles of 15° or 20°, consistent with the lower end of body angles utilized during bounds. Increasing flight velocity in live birds caused a decrease in C L and C D from maximum values of 1.19 and 0.95 during flight at 6 m s-1 to minimum values of 0.70 and 0.54 during flight at 10 m s-1. Consistent with delta-wing theory as applied to birds with a graduated-tail shape, trimming the tail to 0 and 50% of normal length reduced L: D ratios and extending tail length to 150% of normal increased L: D ratio. As downward induced velocity is present in the

  7. Novel indole-based tambjamine-analogues induce apoptotic lung cancer cell death through p38 mitogen-activated protein kinase activation.

    PubMed

    Manuel-Manresa, Pilar; Korrodi-Gregório, Luís; Hernando, Elsa; Villanueva, Alberto; Martínez-García, David; Rodilla, Ananda M; Ramos, Ricard; Fardilha, Margarida; Moya, Juan; Quesada, Roberto; Soto-Cerrato, Vanessa; Perez-Tomas, Ricardo

    2017-04-10

    Lung cancer has become the leading killer cancer worldwide, due to late diagnosis and lack of efficient anticancer drugs. We have recently described novel natural-derived tambjamine analogues that are potent anion transporters capable of disrupting cellular ion balance, inducing acidification of the cytosol and hyperpolarization of cellular plasma membranes. Although these tambjamine analogues were able to compromise cell survival, their molecular mechanism of action remains largely unknown. Herein we characterize the molecular cell responses induced by highly active indole-based tambjamine analogues treatment in lung cancer cells. Expression changes produced after compounds treatment comprised genes related to apoptosis, cell cycle, growth factors and its receptors, protein kinases and topoisomerases, among others. Dysregulation of BCL2 and BIRC5/survivin genes suggested the apoptotic pathway as the induced molecular cell death mechanism. In fact, activation of several pro-apoptotic markers (caspase 9, caspase 3 and PARP) and reversion of the cytotoxic effect upon treatment with an apoptosis inhibitor (Z-VAD-FMK) were observed. Moreover, members of the Bcl-2 protein family suffered changes after tambjamine analogues treatment, with a concomitant protein decrease towards the pro-survival members. Besides this, it was observed cellular accumulation of ROS upon compound treatment and an activation of the stress-kinase p38 MAPK route that, when inhibited, reverted the cytotoxic effect of the tambjamine analogues. Finally, a significant therapeutic effect of these compounds was observed in subcutaneous and orthotopic lung cancer mice models. Taken together, these results shed light on the mechanism of action of novel cytotoxic anionophores and demonstrate the therapeutic effects against lung cancer.

  8. Reversers of the multidrug resistance transporter P-glycoprotein.

    PubMed

    Stein, Wilfred D

    2002-05-01

    Multidrug resistance can arise from the presence of the membrane-bound pump, P-glycoprotein, in a tumor. Major efforts have been made to develop inhibitors of this pump, and a number of promising blockers have reached late stages of clinical trials. The kinetics of the inhibition of P-glycoprotein is complex, with binding sites that can interact synergistically. Reversers of increased affinity and specificity could, in principle, be developed on the basis of these synergies, and offer some promise in cancer therapeutics.

  9. Scalable problems and memory bounded speedup

    NASA Technical Reports Server (NTRS)

    Sun, Xian-He; Ni, Lionel M.

    1992-01-01

    In this paper three models of parallel speedup are studied. They are fixed-size speedup, fixed-time speedup and memory-bounded speedup. The latter two consider the relationship between speedup and problem scalability. Two sets of speedup formulations are derived for these three models. One set considers uneven workload allocation and communication overhead and gives more accurate estimation. Another set considers a simplified case and provides a clear picture on the impact of the sequential portion of an application on the possible performance gain from parallel processing. The simplified fixed-size speedup is Amdahl's law. The simplified fixed-time speedup is Gustafson's scaled speedup. The simplified memory-bounded speedup contains both Amdahl's law and Gustafson's scaled speedup as special cases. This study leads to a better understanding of parallel processing.

  10. On generalized quasi-convex bounded sequences

    NASA Astrophysics Data System (ADS)

    Karakuş, Mahmut

    2016-08-01

    The space of all sequences a = (ak) for which ‖a ‖q= ∑k k |Δ2ak | +supk|ak | <∞ is denoted by q. Here, Δak = ak - ak+1 and Δmak = Δ(Δm-1ak) = Δm-1ak - Δm-1ak+1 with Δ0ak = ak, m ≥ 1. If a = (ak) ∈q then kΔak → 0 (k → ∞) and q ⊂ bv, the space of all sequences of bounded-variation, since ∑k | Δ ak | ≤ ∑k k | Δ2ak | In this study, we give a generalization of quasi-convex bounded sequences.

  11. Mutual Information Rate and Bounds for It

    PubMed Central

    Baptista, Murilo S.; Rubinger, Rero M.; Viana, Emilson R.; Sartorelli, José C.; Parlitz, Ulrich; Grebogi, Celso

    2012-01-01

    The amount of information exchanged per unit of time between two nodes in a dynamical network or between two data sets is a powerful concept for analysing complex systems. This quantity, known as the mutual information rate (MIR), is calculated from the mutual information, which is rigorously defined only for random systems. Moreover, the definition of mutual information is based on probabilities of significant events. This work offers a simple alternative way to calculate the MIR in dynamical (deterministic) networks or between two time series (not fully deterministic), and to calculate its upper and lower bounds without having to calculate probabilities, but rather in terms of well known and well defined quantities in dynamical systems. As possible applications of our bounds, we study the relationship between synchronisation and the exchange of information in a system of two coupled maps and in experimental networks of coupled oscillators. PMID:23112809

  12. Bounded excursion stable gravastars and black holes

    SciTech Connect

    Rocha, P; Da Silva, M F; Wang, Anzhong; Santos, N O E-mail: yasuda@on.br E-mail: mfasnic@gmail.com E-mail: anzhong_wang@baylor.edu

    2008-06-15

    Dynamical models of prototype gravastars were constructed in order to study their stability. The models are the Visser-Wiltshire three-layer gravastars, in which an infinitely thin spherical shell of stiff fluid divides the whole spacetime into two regions, where the internal region is de Sitter, and the external one is Schwarzschild. It is found that in some cases the models represent the 'bounded excursion' stable gravastars, where the thin shell is oscillating between two finite radii, while in other cases they collapse until the formation of black holes occurs. In the phase space, the region for the 'bounded excursion' gravastars is very small in comparison to that of black holes, but not empty. Therefore, although the possibility of the existence of gravastars cannot be excluded from such dynamical models, our results indicate that, even if gravastars do indeed exist, that does not exclude the possibility of the existence of black holes.

  13. Is Fusion Inhibited for Weakly Bound Nuclei?

    SciTech Connect

    Takahashi, J.; Munhoz, M.; Szanto, E.M.; Carlin, N.; Added, N.; Suaide, A.A.; de Moura, M.M.; Liguori Neto, R.; Szanto de Toledo, A.; Canto, L.F.

    1997-01-01

    Complete fusion of light radioactive nuclei is predicted to be hindered at near-barrier energies. This feature is investigated in the case of the least bound stable nuclei. Evaporation residues resulting from the {sup 6,7}Li+{sup 9}Be and {sup 6,7}Li+{sup 12}C fusion reactions have been measured in order to study common features in reactions involving light weakly bound nuclei. The experimental excitation functions revealed that the fusion cross section is significantly smaller than the total reaction cross section and also smaller than the fusion cross section expected from the available systematics. A clear correlation between the fusion probability and nucleon (cluster) separation energy has been established.The results suggest that the breakup process has a strong influence on the hindrance of the fusion cross section. {copyright} {ital 1996} {ital The American Physical Society}

  14. Performance bound for quantum absorption refrigerators

    NASA Astrophysics Data System (ADS)

    Correa, Luis A.; Palao, José P.; Adesso, Gerardo; Alonso, Daniel

    2013-04-01

    An implementation of quantum absorption chillers with three qubits has been recently proposed that is ideally able to reach the Carnot performance regime. Here we study the working efficiency of such self-contained refrigerators, adopting a consistent treatment of dissipation effects. We demonstrate that the coefficient of performance at maximum cooling power is upper bounded by 3/4 of the Carnot performance. The result is independent of the details of the system and the equilibrium temperatures of the external baths. We provide design prescriptions that saturate the bound in the limit of a large difference between the operating temperatures. Our study suggests that delocalized dissipation, which must be taken into account for a proper modeling of the machine-baths interaction, is a fundamental source of irreversibility which prevents the refrigerator from approaching the Carnot performance arbitrarily closely in practice. The potential role of quantum correlations in the operation of these machines is also investigated.

  15. Extremum seeking with bounded update rates

    SciTech Connect

    Scheinker, Alexander; Krstić, Miroslav

    2013-11-16

    In this work, we present a form of extremum seeking (ES) in which the unknown function being minimized enters the system’s dynamics as the argument of a cosine or sine term, thereby guaranteeing known bounds on update rates and control efforts. We present general n-dimensional optimization and stabilization results as well as 2D vehicle control, with bounded velocity and control efforts. For application to autonomous vehicles, tracking a source in a GPS denied environment with unknown orientation, this ES approach allows for smooth heading angle actuation, with constant velocity, and in application to a unicycle-type vehicle results in control ability as if the vehicle is fully actuated. Our stability analysis is made possible by the classic results of Kurzweil, Jarnik, Sussmann, and Liu, regarding systems with highly oscillatory terms. In our stability analysis, we combine the averaging results with a semi-global practical stability result under small parametric perturbations developed by Moreau and Aeyels.

  16. Tsirelson's bound and supersymmetric entangled states

    PubMed Central

    Borsten, L.; Brádler, K.; Duff, M. J.

    2014-01-01

    A superqubit, belonging to a (2|1)-dimensional super-Hilbert space, constitutes the minimal supersymmetric extension of the conventional qubit. In order to see whether superqubits are more non-local than ordinary qubits, we construct a class of two-superqubit entangled states as a non-local resource in the CHSH game. Since super Hilbert space amplitudes are Grassmann numbers, the result depends on how we extract real probabilities and we examine three choices of map: (1) DeWitt (2) Trigonometric and (3) Modified Rogers. In cases (1) and (2), the winning probability reaches the Tsirelson bound pwin=cos2π/8≃0.8536 of standard quantum mechanics. Case (3) crosses Tsirelson's bound with pwin≃0.9265. Although all states used in the game involve probabilities lying between 0 and 1, case (3) permits other changes of basis inducing negative transition probabilities. PMID:25294964

  17. Reinforcement Learning with Bounded Information Loss

    NASA Astrophysics Data System (ADS)

    Peters, Jan; Mülling, Katharina; Seldin, Yevgeny; Altun, Yasemin

    2011-03-01

    Policy search is a successful approach to reinforcement learning. However, policy improvements often result in the loss of information. Hence, it has been marred by premature convergence and implausible solutions. As first suggested in the context of covariant or natural policy gradients, many of these problems may be addressed by constraining the information loss. In this paper, we continue this path of reasoning and suggest two reinforcement learning methods, i.e., a model-based and a model free algorithm that bound the loss in relative entropy while maximizing their return. The resulting methods differ significantly from previous policy gradient approaches and yields an exact update step. It works well on typical reinforcement learning benchmark problems as well as novel evaluations in robotics. We also show a Bayesian bound motivation of this new approach [8].

  18. Circular dichroism study of the interaction between mutagens and bilirubin bound to different binding sites of serum albumins

    NASA Astrophysics Data System (ADS)

    Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

    Although recent investigations have shown that bilirubin not only has a negative role in the organism but also exhibits significant antimutagenic properties, the mechanisms of interactions between bilirubin and mutagens are not clear. In this study, interaction between bilirubin bound to different binding sites of mammalian serum albumins with structural analogues of the mutagens 2-aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were investigated by circular dichroism and absorption spectroscopy. Homological human and bovine serum albumins were used as chiral matrices, which preferentially bind different conformers of bilirubin in the primary binding sites and make it observable by circular dichroism. These molecular systems approximated a real system for the study of mutagens in blood serum. Differences between the interaction of bilirubin bound to primary and to secondary binding sites of serum albumins with mutagens were shown. For bilirubin bound to secondary binding sites with low affinity, partial displacement and the formation of self-associates were observed in all studied mutagens. The associates of bilirubin bound to primary binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7-trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact with bilirubin bound to primary sites of human and bovine serum albumins due to the spatial hindrance of the albumins binding domains. The spatial arrangement of the bilirubin bound to serum albumin along with the studied mutagens was modelled using ligand docking, which revealed a possibility of an arrangement of the both bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding site of human serum albumin.

  19. Circular dichroism study of the interaction between mutagens and bilirubin bound to different binding sites of serum albumins.

    PubMed

    Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

    2014-05-21

    Although recent investigations have shown that bilirubin not only has a negative role in the organism but also exhibits significant antimutagenic properties, the mechanisms of interactions between bilirubin and mutagens are not clear. In this study, interaction between bilirubin bound to different binding sites of mammalian serum albumins with structural analogues of the mutagens 2-aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were investigated by circular dichroism and absorption spectroscopy. Homological human and bovine serum albumins were used as chiral matrices, which preferentially bind different conformers of bilirubin in the primary binding sites and make it observable by circular dichroism. These molecular systems approximated a real system for the study of mutagens in blood serum. Differences between the interaction of bilirubin bound to primary and to secondary binding sites of serum albumins with mutagens were shown. For bilirubin bound to secondary binding sites with low affinity, partial displacement and the formation of self-associates were observed in all studied mutagens. The associates of bilirubin bound to primary binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7-trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact with bilirubin bound to primary sites of human and bovine serum albumins due to the spatial hindrance of the albumins binding domains. The spatial arrangement of the bilirubin bound to serum albumin along with the studied mutagens was modelled using ligand docking, which revealed a possibility of an arrangement of the both bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding site of human serum albumin.

  20. Synthesis and antioxidant activity of peptide-based ebselen analogues.

    PubMed

    Satheeshkumar, Kandhan; Mugesh, Govindasamy

    2011-04-18

    A series of di- and tripeptide-based ebselen analogues has been synthesized. The compounds were characterized by (1)H, (13)C, and (77)Se NMR spectroscopy and mass spectral techniques. The glutathione peroxidase (GPx)-like antioxidant activity has been studied by using H(2)O(2) , tert-butyl hydroperoxide (tBuOOH), and cumene hydroperoxide (Cum-OOH) as substrates, and glutathione (GSH) as a cosubstrate. Although all the peptide-based compounds have a selenazole ring similar to that of ebselen, the GPx activity of these compounds highly depends on the nature of the peptide moiety attached to the nitrogen atom of the selenazole ring. It was observed that the introduction of a phenylalanine (Phe) amino acid residue in the N-terminal reduces the activity in all three peroxide systems. On the other hand, the introduction of aliphatic amino acid residues such as valine (Val) significantly enhances the GPx activity of the ebselen analogues. The difference in the catalytic activity of dipeptide-based ebselen derivatives can be ascribed mainly to the change in the reactivity of these compounds toward GSH and peroxide. Although the presence of the Val-Ala-CO(2) Me moiety facilitates the formation of a catalytically active selenol species, the reaction of ebselen analogues that has a Phe-Ile-CO(2) Me residue with GSH does not generate the corresponding selenol. To understand the antioxidant activity of the peptide-based ebselen analogues in the absence of GSH, these compounds were studied for their ability to inhibit peroxynitrite (PN)-mediated nitration of bovine serum albumin (BSA) and oxidation of dihydrorhodamine 123. In contrast to the GPx activity, the PN-scavenging activity of the Phe-based peptide analogues was found to be comparable to that of the Val-based compounds. However, the introduction of an additional Phe residue to the ebselen analogue that had a Val-Ala dipeptide significantly reduced the potency of the parent compound in PN-mediated nitration.

  1. 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

  2. A bound particle coupled to two thermostats

    NASA Astrophysics Data System (ADS)

    Fogedby, Hans C.; Imparato, Alberto

    2011-05-01

    We consider a harmonically bound Brownian particle coupled to two distinct heat reservoirs at different temperatures. We show that the presence of a harmonic trap does not change the large deviation function from the case of a free Brownian particle discussed by Derrida and Brunet and Visco. Likewise, the Gallavotti-Cohen fluctuation theorem related to the entropy production at the heat sources remains in force. We support the analytical results with numerical simulations.

  3. Multipartite secret key distillation and bound entanglement

    SciTech Connect

    Augusiak, Remigiusz; Horodecki, Pawel

    2009-10-15

    Recently it has been shown that quantum cryptography beyond pure entanglement distillation is possible and a paradigm for the associated protocols has been established. Here we systematically generalize the whole paradigm to the multipartite scenario. We provide constructions of new classes of multipartite bound entangled states, i.e., those with underlying twisted Greenberger-Horne-Zeilinger (GHZ) structure and nonzero distillable cryptographic key. We quantitatively estimate the key from below with the help of the privacy squeezing technique.

  4. Improvement of cosmological neutrino mass bounds

    NASA Astrophysics Data System (ADS)

    Giusarma, Elena; Gerbino, Martina; Mena, Olga; Vagnozzi, Sunny; Ho, Shirley; Freese, Katherine

    2016-10-01

    The most recent measurements of the temperature and low-multipole polarization anisotropies of the cosmic microwave background from the Planck satellite, when combined with galaxy clustering data from the Baryon Oscillation Spectroscopic Survey in the form of the full shape of the power spectrum, and with baryon acoustic oscillation measurements, provide a 95% confidence level (C.L.) upper bound on the sum of the three active neutrinos ∑mν<0.183 eV , among the tightest neutrino mass bounds in the literature, to date, when the same data sets are taken into account. This very same data combination is able to set, at ˜70 % C.L., an upper limit on ∑mν of 0.0968 eV, a value that approximately corresponds to the minimal mass expected in the inverted neutrino mass hierarchy scenario. If high-multipole polarization data from Planck is also considered, the 95% C.L. upper bound is tightened to ∑mν<0.176 eV . Further improvements are obtained by considering recent measurements of the Hubble parameter. These limits are obtained assuming a specific nondegenerate neutrino mass spectrum; they slightly worsen when considering other degenerate neutrino mass schemes. Low-redshift quantities, such as the Hubble constant or the reionization optical depth, play a very important role when setting the neutrino mass constraints. We also comment on the eventual shifts in the cosmological bounds on ∑mν when possible variations in the former two quantities are addressed.

  5. Efficiency bounds for nonequilibrium heat engines

    SciTech Connect

    Mehta, Pankaj; Polkovnikov, Anatoli

    2013-05-15

    We analyze the efficiency of thermal engines (either quantum or classical) working with a single heat reservoir like an atmosphere. The engine first gets an energy intake, which can be done in an arbitrary nonequilibrium way e.g. combustion of fuel. Then the engine performs the work and returns to the initial state. We distinguish two general classes of engines where the working body first equilibrates within itself and then performs the work (ergodic engine) or when it performs the work before equilibrating (non-ergodic engine). We show that in both cases the second law of thermodynamics limits their efficiency. For ergodic engines we find a rigorous upper bound for the efficiency, which is strictly smaller than the equivalent Carnot efficiency. I.e. the Carnot efficiency can be never achieved in single reservoir heat engines. For non-ergodic engines the efficiency can be higher and can exceed the equilibrium Carnot bound. By extending the fundamental thermodynamic relation to nonequilibrium processes, we find a rigorous thermodynamic bound for the efficiency of both ergodic and non-ergodic engines and show that it is given by the relative entropy of the nonequilibrium and initial equilibrium distributions. These results suggest a new general strategy for designing more efficient engines. We illustrate our ideas by using simple examples. -- Highlights: ► Derived efficiency bounds for heat engines working with a single reservoir. ► Analyzed both ergodic and non-ergodic engines. ► Showed that non-ergodic engines can be more efficient. ► Extended fundamental thermodynamic relation to arbitrary nonequilibrium processes.

  6. Experimental and Theoretical Studies of the Structures and Interactions of Vancomycin Antibiotics with Cell Wall Analogues

    SciTech Connect

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

    2008-10-01

    Surface-induced dissociation (SID) of the singly protonated complex of vancomycin antibiotic with cell wall peptide analogue (Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala) was studied using a 6 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) specially configured for SID experiments. The binding energy between the vancomycin and the peptide was obtained from the RRKM modeling of the time- and energy resolved fragmentation efficiency curves (TFECs) of the precursor ion and its fragments. Electronic structure calculations of the geometries, proton affinities and binding energies were performed for several model systems including vancomycin (V), vancomycin aglycon (VA), Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala, and non-covalent complexes of VA with N-acetyl-D-Ala-D-Ala and Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala at the B3LYP/6-31G(d) level of theory. Comparison between the experimental and computational results suggests that the most probable structure of the complex observed in our experiments corresponds to the neutral peptide bound to the vancomycin protonated at the secondary amino group of the N-methyl-leucine residue. The experimental binding energy of 30.9 ± 1.8 kcal/mol is in good agreement with the binding energy of 29.3 ± 2.5 kcal/mol calculated for the model system representing the preferred structure of the complex.

  7. Ricin A-chain structural determinant for binding substrate analogues: a molecular dynamics simulation analysis.

    PubMed

    Olson, M A

    1997-01-01

    Ricin A-chain is a cytotoxic protein that attacks ribosomes by hydrolyzing a specific adenine base from a highly conserved, single-stranded rRNA hairpin containing the tetraloop sequence GAGA. Molecular-dynamics simulation methods are used to analyze the structural determinant for three substrate analogues bound to the ricin A-chain molecule. Simulations were applied to the binding of the dinucleotide adenyl-3',5'-guanosine employing the x-ray crystal structure of the ricin complex and a modeled CGAGAG hexanucleotide loop taken from the NMR solution structure of a 29-mer oligonucleotide hairpin. A third simulation model is also presented describing a conformational search of the docked 29-mer structure by using a simulated-annealing method. Analysis of the structural interaction energies for each model shows the overall binding dominated by nonspecific interactions, which are mediated by specific arginine contracts from the highly basic region on the protein surface. The tetraloop conformation of the 29-mer was found to make specific interactions with conserved protein residues, in a manner that favored the GAGA sequence. A comparison of the two docked loop conformations with the NMR structure revealed significant positional deviations, suggesting that ricin may use an induced fit mechanism to recognize and bind the rRNA substrate. The conserved Tyr-80 may play an important conformational entropic role in the binding and release of the target adenine in the active site.

  8. Immunometric assay of BN 52080, a heptapeptide C-terminal analogue of sorbin.

    PubMed

    Ezan, E; Tarrade, T; Cazenave, C; Ardouin, T; Genet, R; Grassi, J; Grognet, J M; Pradelles, P

    1995-01-01

    A novel type of enzyme immunometric assay has been developed for a heptapeptide, BN 52080. This compound is a short C-terminal analogue of sorbin and is under clinical evaluation for treatment of chronic diarrhea. In this solid-phase immobilized epitope immunoassay (SPIE-IA), the peptide is first immunologically bound to polyclonal antibodies adsorbed to a solid phase and then, after covalent immobilization with glutaraldehyde, is released from the antibody paratope by NaOH. The peptide linked to the solid phase is further quantified with a tracer consisting of the same antibodies purified by affinity chromatography and coupled to acetylcholinesterase. This assay has a detection limit of 10 pg/ml and is therefore five times more sensitive than competitive enzyme immunoassay using the same antibodies and BN 52080 coupled to acetylcholinesterase as tracer. The assay is specific and allows direct measurement of peptide in human plasma after subcutaneous or intravenous administration of 200 micrograms of BN 52080 to volunteers.

  9. Structures of Thermoactinomyces vulgaris R-47 alpha-amylase II complexed with substrate analogues.

    PubMed

    Yokota, T; Tonozuka, T; Shimura, Y; Ichikawa, K; Kamitori, S; Sakano, Y

    2001-03-01

    The structures of Thermoactinomyces vulgaris R-47 alpha-amylase II mutant (d325nTVA II) complexed with substrate analogues, methyl beta-cyclodextrin (m beta-CD) and maltohexaose (G6), were solved by X-ray diffraction at 3.2 A and 3.3 A resolution, respectively. In d325nTVA II-m beta-CD complex, the orientation and binding-position of beta-CD in TVA II were identical to those in cyclodextin glucanotransferase (CGTase). The active site residues were essentialy conserved, while there are no residues corresponding to Tyr89, Phe183, and His233 of CGTase in TVA II. In d325nTVA II-G6 complex, the electron density maps of two glucosyl units at the non-reducing end were disordered and invisible. The four glucosyl units of G6 were bound to TVA II as in CGTase, while the others were not stacked and were probably flexible. The residues of TVA II corresponding to Tyr89, Lys232, and His233 of CGTase were completely lacking. These results suggest that the lack of the residues related to alpha-glucan and CD-stacking causes the functional distinctions between CGTase and TVA II.

  10. Of Models and Machines: Implementing Bounded Rationality.

    PubMed

    Dick, Stephanie

    2015-09-01

    This essay explores the early history of Herbert Simon's principle of bounded rationality in the context of his Artificial Intelligence research in the mid 1950s. It focuses in particular on how Simon and his colleagues at the RAND Corporation translated a model of human reasoning into a computer program, the Logic Theory Machine. They were motivated by a belief that computers and minds were the same kind of thing--namely, information-processing systems. The Logic Theory Machine program was a model of how people solved problems in elementary mathematical logic. However, in making this model actually run on their 1950s computer, the JOHNNIAC, Simon and his colleagues had to navigate many obstacles and material constraints quite foreign to the human experience of logic. They crafted new tools and engaged in new practices that accommodated the affordances of their machine, rather than reflecting the character of human cognition and its bounds. The essay argues that tracking this implementation effort shows that "internal" cognitive practices and "external" tools and materials are not so easily separated as they are in Simon's principle of bounded rationality--the latter often shaping the dynamics of the former.

  11. Reverse engineering quantum field theory

    NASA Astrophysics Data System (ADS)

    Oeckl, Robert

    2012-12-01

    An approach to the foundations of quantum theory is advertised that proceeds by "reverse engineering" quantum field theory. As a concrete instance of this approach, the general boundary formulation of quantum theory is outlined.

  12. Dielectrophoresis of reverse phase emulsions.

    PubMed

    Flores-Rodriguez, N; Bryning, Z; Markx, G H

    2005-08-01

    Reverse miniemulsions, emulsions of droplets of size 200 nm-1 microm of a polar liquid dispersed in an apolar continuous liquid phase, exhibit strong electrokinetic responses in low-frequency electric fields. The electrokinetic behaviour of a reverse miniemulsion, previously developed for use as electronic paper, has been investigated under static and flow conditions, in uniform and non-uniform electric fields. Results reveal that when using frequencies lower than 10 Hz strong aggregation of the droplets occurs. In uniform electric fields, under static conditions, droplets reversibly aggregate into honeycomb-like or irregular aggregates. Under flow conditions, droplets aggregate into approximately equidistant streams. In non-uniform electric fields the droplets reversibly aggregate in high-field regions, and can be guided along regions of high field strength in a flow. The potential of the technique for the formation of structured materials is discussed.

  13. Structural Insight into Methyl-Coenzyme M Reductase Chemistry Using Coenzyme B Analogues

    SciTech Connect

    Cedervall, Peder E.; Dey, Mishtu; Pearson, Arwen R.; Ragsdale, Stephen W.; Wilmot, Carrie M.

    2010-09-07

    Methyl-coenzyme M reductase (MCR) catalyzes the final and rate-limiting step in methane biogenesis: the reduction of methyl-coenzyme M (methyl-SCoM) by coenzyme B (CoBSH) to methane and a heterodisulfide (CoBS-SCoM). Crystallographic studies show that the active site is deeply buried within the enzyme and contains a highly reduced nickel-tetrapyrrole, coenzyme F430. Methyl-SCoM must enter the active site prior to CoBSH, as species derived from methyl-SCoM are always observed bound to the F430 nickel in the deepest part of the 30 {angstrom} long substrate channel that leads from the protein surface to the active site. The seven-carbon mercaptoalkanoyl chain of CoBSH binds within a 16 {angstrom} predominantly hydrophobic part of the channel close to F430, with the CoBSH thiolate lying closest to the nickel at a distance of 8.8 {angstrom}. It has previously been suggested that binding of CoBSH initiates catalysis by inducing a conformational change that moves methyl-SCoM closer to the nickel promoting cleavage of the C-S bond of methyl-SCoM. In order to better understand the structural role of CoBSH early in the MCR mechanism, we have determined crystal structures of MCR in complex with four different CoBSH analogues: pentanoyl, hexanoyl, octanoyl, and nonanoyl derivatives of CoBSH (CoB5SH, CoB6SH, CoB8SH, and CoB9SH, respectively). The data presented here reveal that the shorter CoB5SH mercaptoalkanoyl chain overlays with that of CoBSH but terminates two units short of the CoBSH thiolate position. In contrast, the mercaptoalkanoyl chain of CoB6SH adopts a different conformation, such that its thiolate is coincident with the position of the CoBSH thiolate. This is consistent with the observation that CoB6SH is a slow substrate. A labile water in the substrate channel was found to be a sensitive indicator for the presence of CoBSH and HSCoM. The longer CoB8SH and CoB9SH analogues can be accommodated in the active site through exclusion of this water. These analogues

  14. Bound to be different: neurotransmitter transporters meet their bacterial cousins.

    PubMed

    Henry, L Keith; Meiler, Jens; Blakely, Randy D

    2007-12-01

    The neurotransmitter transporters belonging to the solute carrier 6 (SLC6) family, including the gamma-aminobutyric acid (GAT), norepinephrine (NET), serotonin (SERT) and dopamine (DAT) transporters are extremely important drug targets of great clinical relevance. These Na+, Cl(-)-dependent transporters primarily function following neurotransmission to reset neuronal signaling by transporting neurotransmitter out of the synapse and back into the pre-synaptic neuron. Recent studies have tracked down an elusive binding site for Cl(-) that facilitates neurotransmitter transport using structural differences evident with bacterial family members (e.g., the Aquifex aeolicus leucine transporter LeuT Aa) that lack Cl(-) dependence. Additionally, the crystal structures of antidepressant-bound LeuT Aa reveals a surprising mode of drug interaction that may have relevance for medication development. The study of sequence and structural divergence between LeuT Aa and human SLC6 family transporters can thus inform us as to how and why neurotransmitter transporters evolved a reliance on extracellular Cl(-) to propel the transport cycle; what residue changes and helical rearrangements give rise to recognition of different substrates; and how drugs such as antidepressants, cocaine, and amphetamines halt (or reverse) the transport process.

  15. Deciphering records of geomagnetic reversals

    NASA Astrophysics Data System (ADS)

    Valet, Jean-Pierre; Fournier, Alexandre

    2016-06-01

    Polarity reversals of the geomagnetic field are a major feature of the Earth's dynamo. Questions remain regarding the dynamical processes that give rise to reversals and the properties of the geomagnetic field during a polarity transition. A large number of paleomagnetic reversal records have been acquired during the past 50 years in order to better constrain the structure and geometry of the transitional field. In addition, over the past two decades, numerical dynamo simulations have also provided insights into the reversal mechanism. Yet despite the large paleomagnetic database, controversial interpretations of records of the transitional field persist; they result from two characteristics inherent to all reversals, both of which are detrimental to an ambiguous analysis. On the one hand, the reversal process is rapid and requires adequate temporal resolution. On the other hand, weak field intensities during a reversal can affect the fidelity of magnetic recording in sedimentary records. This paper is aimed at reviewing critically the main reversal features derived from paleomagnetic records and at analyzing some of these features in light of numerical simulations. We discuss in detail the fidelity of the signal extracted from paleomagnetic records and pay special attention to their resolution with respect to the timing and mechanisms involved in the magnetization process. Records from marine sediments dominate the database. They give rise to transitional field models that often lead to overinterpret the data. Consequently, we attempt to separate robust results (and their subsequent interpretations) from those that do not stand on a strong observational footing. Finally, we discuss new avenues that should favor progress to better characterize and understand transitional field behavior.

  16. Reverse Current in Solar Flares

    NASA Technical Reports Server (NTRS)

    Knight, J. W., III

    1978-01-01

    An idealized steady state model of a stream of energetic electrons neutralized by a reverse current in the pre-flare solar plasma was developed. These calculations indicate that, in some cases, a significant fraction of the beam energy may be dissipated by the reverse current. Joule heating by the reverse current is a more effective mechanism for heating the plasma than collisional losses from the energetic electrons because the Ohmic losses are caused by thermal electrons in the reverse current which have much shorter mean free paths than the energetic electrons. The heating due to reverse currents is calculated for two injected energetic electron fluxes. For the smaller injected flux, the temperature of the coronal plasma is raised by about a factor of two. The larger flux causes the reverse current drift velocity to exceed the critical velocity for the onset of ion cyclotron turbulence, producing anomalous resistivity and an order of magnitude increase in the temperature. The heating is so rapid that the lack of ionization equilibrium may produce a soft X-ray and EUV pulse from the corona.

  17. One algorithm for branch and bound method for solving concave optimization problem

    NASA Astrophysics Data System (ADS)

    Andrianova, A. A.; Korepanova, A. A.; Halilova, I. F.

    2016-11-01

    The article describes the algorithm for branch and bound method for solving the concave programming problem, which is based on the idea of similarity the necessary and sufficient conditions of optimum for the original problem and for a convex programming problem with another feasible set and reverse the sign of the objective function. To find the feasible set of the equivalent convex programming problem we construct an algorithm using the idea of the branch and bound method. We formulate various branching techniques and discusses the construction of the lower objective function evaluations for the node of the decision tree. The article discusses the results of experiments of this algorithm for some famous test problems of a particular form.

  18. Quantitation of chlorpromazine-bound calmodulin during chlorpromazine inhibition of gravitropism

    NASA Technical Reports Server (NTRS)

    Roux, S. J.; Biro, R. L.

    1982-01-01

    The regulatory protein, calmodulin (CaM), controls the activity of a plasma membrane localized ATPase in plants which serves to pump calcium out of cells. Recent data are consistent with the hypothesis that activation of this pump is one of the early steps necessary for gravitropism. Chlorpromazine (CPZ), a CaM antagonist, reversibly inhibits gravitropism in oat coleoptiles at concentrations which permit normal growth rates. C-14-labeled CPZ was used to photo-affinity label endogenous CaM in vivo to learn whether the drug is actually binding to some portion of endogenous CaM when it inhibits gravitropism. Under conditions in which CPZ inhibits gravitropism for over an hour, at least 11% of the CaM in gravitropically stimulated coleoptiles is bound to CPZ. In a given CPZ experiment the degree of inhibition of gravitropism correlates well with the amount of CaM bound to CPZ.

  19. Synthetic silvestrol analogues as potent and selective protein synthesis inhibitors.

    PubMed

    Liu, Tao; Nair, Somarajan J; Lescarbeau, André; Belani, Jitendra; Peluso, Stéphane; Conley, James; Tillotson, Bonnie; O'Hearn, Patrick; Smith, Sherri; Slocum, Kelly; West, Kip; Helble, Joseph; Douglas, Mark; Bahadoor, Adilah; Ali, Janid; McGovern, Karen; Fritz, Christian; Palombella, Vito J; Wylie, Andrew; Castro, Alfredo C; Tremblay, Martin R

    2012-10-25

    Misregulation of protein translation plays a critical role in human cancer pathogenesis at many levels. Silvestrol, a cyclopenta[b]benzofuran natural product, blocks translation at the initiation step by interfering with assembly of the eIF4F translation complex. Silvestrol has a complex chemical structure whose functional group requirements have not been systematically investigated. Moreover, silvestrol has limited development potential due to poor druglike properties. Herein, we sought to develop a practical synthesis of key intermediates of silvestrol and explore structure-activity relationships around the C6 position. The ability of silvestrol and analogues to selectively inhibit the translation of proteins with high requirement on the translation-initiation machinery (i.e., complex 5'-untranslated region UTR) relative to simple 5'UTR was determined by a cellular reporter assay. Simplified analogues of silvestrol such as compounds 74 and 76 were shown to have similar cytotoxic potency and better ADME characteristics relative to those of silvestrol.

  20. 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.