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Sample records for fviia analogue nn1731

  1. Effects of a recombinant FVIIa analogue, NN1731, on blood loss and survival after liver trauma in the pig

    DEFF Research Database (Denmark)

    Zaar, M; Secher, N H; Johansson, P I

    2009-01-01

    BACKGROUND: We considered whether haemorrhage after a liver trauma would be reduced by early administration of a pro-haemostatic agent and evaluated the effect of i.v. vs i.m. administration of the coagulation factor VIIa analogue NN1731 on haemorrhage after a liver trauma in the pig. METHODS......: The pharmacokinetics of i.v. and i.m. NN1731 was evaluated in eight minipigs, and the effects of dose and administration route of NN1731 (i.v. 180 microg kg(-1), n=6; i.m. 540 microg kg(-1), n=4, or 2000 microg kg(-1), n=6) vs vehicle (n=16) were studied on a liver laceration injury in pigs. To simulate a pre......-hospital setting, the administration of NN1731 was delayed by 1 min for i.m. administration and 7 min for i.v. administration, at which time fluid resuscitation also began. RESULTS: In the minipigs, NN1731 exposure was similar after i.v. 180 microg kg(-1) and i.m. 540 microg kg(-1), with a bioavailability...

  2. Design, synthesis and biological activity of novel peptidyl benzyl ketone FVIIa inhibitors

    DEFF Research Database (Denmark)

    Storgaard, Morten; Henriksen, Signe Teuber; Zaragoza, Florencio

    2011-01-01

    Herein is described the synthesis of a novel class of peptidyl FVIIa inhibitors having a C-terminal benzyl ketone group. This class is designed to be potentially suitable as stabilization agents of liquid formulations of rFVIIa, which is a serine protease used for the treatment of hemophilia...

  3. Effects of sucrose on rFVIIa aggregation and methionine oxidation

    DEFF Research Database (Denmark)

    Soenderkaer, Susanne; Carpenter, John F; van de Weert, Marco

    2004-01-01

    The aim of this study was to characterize the effects of sucrose on the stability of recombinant factor VIIa (rFVIIa), with special emphasis on aggregation and methionine oxidation, as well as to investigate the impact of various environmental conditions on the rFVIIa conformation. The stability ...

  4. Acidosis and Correction of Acidosis Does Not Affect rFVIIa Function in Swine

    Science.gov (United States)

    2012-12-15

    acidosis) with a decrease in respiration (respiratory aci- dosis ) successfully lowered arterial pH to 7.1 (Table 2). Bicarbonate infusion with...coagulation after rFVIIa infusions was not different between the control and aci- dosis groups, or between the acidosis and aci- dosis -corrected...in normal, aci- dosis and acidosis-corrected swine for both HCl- and hemorrhage/respiratory-induced aci- dosis (Figure 2). Infusions of rFVIIa led to

  5. The effect of GlycoPEGylation on the physical stability of human rFVIIa with increasing calcium chloride concentration

    DEFF Research Database (Denmark)

    Plesner, Bitten; Westh, Peter; Hvidt, Søren

    2011-01-01

    The effects of calcium chloride on the structural, kinetic and thermal stability of recombinant human factor VIIa (rFVIIa) were investigated using rFVIIa and two GlycoPEGylated recombinant human FVIIa derivatives, a linear 10 kDa PEG and a branched 40 kDa PEG, respectively. Three different CaCl(2...... scanning calorimetry (DSC) and circular dichroism (CD), and aggregation behaviour, measured by light scattering (LS), were affected by the increasing calcium concentration. Increasing the CaCl(2) concentration from 10mM to 35 mM resulted in a decrease in the apparent unfolding temperature, T(m), of r......FVIIa compounds was practically independent of the CaCl(2) concentration. From the obtained results, it is concluded that GlycoPEGylation postpones the calcium induced thermal destabilisation of rFVIIa, and a much higher calcium concentration also postpones the thermally induced aggregation of r...

  6. Economical comparison of APCC vs. rFVIIa for mild-to-moderate bleeding episodes in haemophilia patients with inhibitors.

    Science.gov (United States)

    Hay, J W; Zhou, Z Y

    2011-09-01

    To construct a cost-minimization model comparing activated prothrombin complex concentrates (APCC) vs. recombinant factor VIIa (rFVIIa) in haemophilia patients with inhibitors from a US third party payer perspective. A literature-based decision model was used to model inhibitor treatment costs and outcomes. As existing clinical trials fail to demonstrate differences in the relative efficacy or safety of APCC vs. rFVIIa, we assumed the same efficacy for both products in the base-case. Regimens of APCC (75 IU kg⁻¹ × 2 doses) and rFVIIa (90 μg kg⁻¹× 3 doses) were assumed according to manufacturer recommendations. If the first-line treatment failed, patients chose to continue the current treatment or switch to another drug. All costs were adjusted to 2009 US dollars. Sensitivity analyses on the infusion frequency, efficacy, unit price, switch rate, re-bleed rate and body weight were performed to assess model robustness. In the base-case, the total medical cost to treat a bleed with APCC or rFVIIa as first-line medication was US$25,969 and US$35,838, respectively. One-way sensitivity analyses showed that results were insensitive to the efficacy of rFVIIa, unit price of APCC or rFVIIa, switch rate, re-bleed rate or body weight. The rFVIIa will reach cost neutrality when the efficacy of APCC is as low as 60%, or rFVIIa is infused only twice for each line, or APCC is infused three times for each line. Two-way sensitivity analyses showed that results were quite sensitive to the assumed infusion frequency for both products. First-line APCC compared with rFVIIa can be a cost-saving alternative for home treatment of mild-to-moderate bleeds in haemophilia patients with inhibitors.

  7. Secondary prophylaxis with rFVIIa in hemophilia and inhibitors: Recommendations from an Experts Committee from Argentina

    Directory of Open Access Journals (Sweden)

    Raúl Pérez Bianco

    2010-06-01

    Full Text Available Secondary prophylaxis with rFVIIa has been the subject of several publications in the past few years. However, there is no general consensus on how this treatment should be put into practice, as publications have been very heterogeneous in the dosing schedule they report. Furthermore, the mechanism of action of rFVIIa and its short half life have been used as arguments against its role in prophylaxis. There have been a series of recent publications that show that rFVIIa can traffic through the intact endothelium and be stored in the subendothelium of several organs for a prolonged period of time. In order to consensuate the role of rFVIIa in prophylaxis, a group of experts from Argentina, resumed available information regarding pharmacology and clinical experience with this treatment, and developed a series of recommendations to use this drug in the prophylaxis setting.

  8. Animal models of FVIIa gene expression: their role in the future development of haemophilia treatment.

    Science.gov (United States)

    Obergfell, A; Nichols, T; Ezban, M

    2010-03-01

    The development of inhibitors to replacement factor therapy is a serious complication in the treatment of patients with haemophilia and requires use of bypassing agents to prevent uncontrolled bleeding. The efficacy of recombinant factor VIIa (rFVIIa) as a bypassing agent in patients with haemophilia has been demonstrated in case studies and clinical trials. However, the perception of a short plasma half-life and consequent need for repeated daily injections means that long-term prophylaxis could potentially be limiting. Canine haemophilia models using a gene transfer approach have been used to evaluate the continuous expression of FVIIa in dogs. These studies show improvement in measurable bleeding parameters that have important clinical ramifications for patients with haemophilia. The combination of gene transfer as the method of delivery and FVII as the transgene overcomes issues associated with the short plasma half-life of rFVIIa, and represents a potentially attractive novel approach to haemostasis in patients with haemophilia and other platelet disorders.

  9. Determination of FVIIa-sTF Inhibitors in Toxic Microcystis Cyanobacteria by LC-MS Technique.

    Science.gov (United States)

    Anas, Andrea Roxanne J; Nakajima, Anna; Naruse, Chiaki; Tone, Mineka; Asukabe, Hirohiko; Harada, Ken-ichi

    2015-12-30

    The blood coagulation cascade involves the human coagulation factors thrombin and an activated factor VII (fVIIa). Thrombin and fVIIa are vitamin-K-dependent clotting factors associated with bleeding, bleeding complications and disorders. Thrombin and fVIIa cause excessive bleeding when treated with vitamin-K antagonists. In this research, we explored different strains of toxic Microcystis aeruginosa and cyanobacteria blooms for the probable fVIIa-soluble Tissue Factor (fVIIa-sTF) inhibitors. The algal cells were subjected to acidification, and reverse phase (ODS) chromatography-solid phase extraction eluted by water to 100% MeOH with 20%-MeOH increments except for M. aeruginosa NIES-89, from the National Institute for Environmental Studies (NIES), which was eluted with 5%-MeOH increments as an isolation procedure to separate aeruginosins 89A and B from co-eluting microcystins. The 40%-80% MeOH fractions of the cyanobacterial extract are active against fVIIa-sTF. The fVIIa-sTF active fractions from cultured cyanobacteria and cyanobacteria blooms were subjected to liquid chromatography-mass spectrometry (LC-MS). The 60% MeOH fraction of M. aeruginosa K139 exhibited an m/z 603 [M + H]⁺ attributed to aeruginosin K139, and the 40% MeOH fraction of M. aeruginosa NIES-89 displayed ions with m/z 617 [M - SO3 + H]⁺ and m/z [M + H]⁺ 717, which attributed to aeruginosin 89. Aeruginosins 102A/B and 298A/B were also observed from other toxic strains of M. aeruginosa with positive fVIIa-sTF inhibitory activity. The active fractions contained cyanobacterial peptides of the aeruginosin class as fVIIa-sTF inhibitors detected by LC-MS.

  10. The kidneys play an important role in the clearance of rFVIIa in rats

    DEFF Research Database (Denmark)

    Vestergaard, Bill; Appa, Rupa S.; Lykkesfeldt, Jens

    2014-01-01

    study was to evaluate the importance of the kidneys in the clearance process of rFVIIa after iv administration to rats using a nephrectomy model. MATERIALS AND METHODS: A nephrectomized rat model was established and validated using inulin, a compound primarily cleared by the kidneys, as a test substance...... of mixed effects methods, where a pharmacokinetic model was used to simultaneously model all data from healthy, sham operated, and nephrectomized rats. RESULTS: Nephrectomized animals showed stable rectal temperature, SpO2 and pulse and as expected, clearance of inulin was essentially abolished compared...

  11. Secondary prophylaxis with rFVIIa in hemophilia and inhibitors: Recommendations from an Experts Committee from Argentina Profilaxis secundaria con rFVIIa en pacientes con hemofilia e inhibidores: Recomendaciones de un comité de expertos de Argentina

    Directory of Open Access Journals (Sweden)

    Raúl Pérez Bianco

    2010-06-01

    Full Text Available Secondary prophylaxis with rFVIIa has been the subject of several publications in the past few years. However, there is no general consensus on how this treatment should be put into practice, as publications have been very heterogeneous in the dosing schedule they report. Furthermore, the mechanism of action of rFVIIa and its short half life have been used as arguments against its role in prophylaxis. There have been a series of recent publications that show that rFVIIa can traffic through the intact endothelium and be stored in the subendothelium of several organs for a prolonged period of time. In order to consensuate the role of rFVIIa in prophylaxis, a group of experts from Argentina, resumed available information regarding pharmacology and clinical experience with this treatment, and developed a series of recommendations to use this drug in the prophylaxis setting.La profilaxis secundaria con factor VII activado recombinante (rFVIIa ha sido objeto de varias publicaciones en los últimos años. Sin embargo, no existe un consenso general sobre cómo este tratamiento debe ser puesto en práctica, dado que las publicaciones han sido muy heterogéneas respecto del régimen de dosificación que publican. Además, el mecanismo de acción del rFVIIa y su vida media corta se han utilizado como argumentos en contra de su papel en la profilaxis. Ha habido una serie de publicaciones recientes que muestran que el rFVIIa puede atravesar el endotelio intacto y almacenarse en el subendotelio de diversos órganos durante un período prolongado de tiempo. Con el fin de consensuar el papel de rFVIIa en la profilaxis, un grupo de expertos de Argentina, ha recopilado la información disponible sobre la farmacología y la experiencia clínica con este tratamiento, y desarrolló una serie de recomendaciones para utilizar este fármaco en el ámbito de profilaxis.

  12. Complementary effect of fibrinogen and rFVIIa on clotting ex vivo in Bernard-Soulier syndrome and combined use during three deliveries

    DEFF Research Database (Denmark)

    Palsson, Ragnar; Vidarsson, Brynjar; Gudmundsdottir, Brynja R

    2014-01-01

    coagulation profile of a pregnant woman with BSS before and after spiking ex vivo with different concentrations of recombinant activated factor VII (rFVIIa) and fibrinogen. As experiments suggested improved clotting with clinically applicable concentrations of both agents in a complementary manner...

  13. Local pulmonary administration of factor VIIa (rFVIIa in diffuse alveolar hemorrhage (DAH – a review of a new treatment paradigm

    Directory of Open Access Journals (Sweden)

    Nielsen JD

    2012-03-01

    Full Text Available Lars Heslet1, Jørn Dalsgaard Nielsen2, Steen Nepper-Christensen31Serendex ApS, Parkovsvej 20, Gentofte, DK 2820 Denmark; 2Department of Hematology, University Hospital of Copenhagen, Rigshospitalet, Denmark; 3Department of Otolaryngology/Head and Neck Surgery, University Hospital of Copenhagen, Rigshospitalet, DenmarkBackground: Diffuse alveolar hemorrhage (DAH is a clinical syndrome with typical symptoms dyspnea and hemoptysis. DAH is a complication of specific diseases, in some cases with acute catastrophic hemoptysis, while other patients present low grade alveolar bleeding with a need of chronic transfusion as in pulmonary hemosiderosis.Methods: Current literature in the PubMed database and other sources was reviewed in order to evaluate the current treatment recommendations, efficacy of this treatment, and finally the risk of complications after off-label use of rFVIIa in respect to DAH.Objectives: (i To elucidate the clinical aspects of alveolar hemorrhage, (ii to develop a simple diagnostic algorithm in order to separate DAH from other important pulmonary diseases with similar clinical picture and comparably high mortality. Such an algorithm has important therapeutic consequences because these diseases: acute lung injury (ALI, acute respiratory distress syndrome (ARDS and bronchiolitis obliterans organizing pneumonia (BOOP have different therapies, (iii to evaluate and discuss whether local pulmonary administration may improve outcome and reduce mortality in DAH, and (iv to suggest a treatment schedule.Results: Hitherto the diagnosis and treatment of DAH has been based on anecdotal reports. The treatment has relied on different unspecific treatment modalities based on a mixture of treatment of the underlying disease and treatment without evidence targeted to stop the alveolar bleeding. However, recently a number of publications have advocated the use of intrapulmonary rFVIIa. Even in severe bleeding DAH has been shown to respond promptly

  14. BALANOL ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to a solid phase methodology for the preparation of a combinatorial library of structural analogues of the natural product balanol (ophiocordin, azepinostatin), which is a protein kinase C (PKC) and protein kinase A (PKA) inhibitor. The method comprises solid-phase s...... be immobilised to the polymer support either as the monoallyl ester or as the internal anhydride. The libraries produced by the method are especially suited for high throughput screening of potential drug candidates for the treatment of mammals, especially humans....

  15. Analogue computing methods

    CERN Document Server

    Welbourne, D

    1965-01-01

    Analogue Computing Methods presents the field of analogue computation and simulation in a compact and convenient form, providing an outline of models and analogues that have been produced to solve physical problems for the engineer and how to use and program the electronic analogue computer. This book consists of six chapters. The first chapter provides an introduction to analogue computation and discusses certain mathematical techniques. The electronic equipment of an analogue computer is covered in Chapter 2, while its use to solve simple problems, including the method of scaling is elaborat

  16. Assessment of individual dose utilization vs. physician prescribing recommendations for recombinant activated factor VII (rFVIIa) in paediatric and adult patients with congenital haemophilia and alloantibody inhibitors (CHwI): the Dosing Observational Study in Hemophilia (DOSE).

    Science.gov (United States)

    Gruppo, R A; Kessler, C M; Neufeld, E J; Cooper, D L

    2013-07-01

    Recent data from the Dosing Observational Study in Hemophilia diary study has described home treatment with recombinant activated factor VII (rFVIIa) in congenital haemophilia with inhibitors (CHwI). The current analysis compares prescribed and patient/caregiver-reported rFVIIa administration in paediatric and adult CHwI patients in this study. Patients with ≥ 4 bleeding episodes within a 3-month period prescribed rFVIIa as first-line therapy for bleeding episodes were eligible. Patients/caregivers completed a diary for ≥ 90 days or until the patient experienced four bleeds. Initial, total and mean rFVIIa doses reported for each bleeding episode were calculated and compared with the physician-prescribed doses. Of 52 enrolled patients (25 children; 27 adults), 39 (75%) completed the study. Children and adults had similar mean durations of bleeding episodes. Both patient groups were administered higher initial rFVIIa doses for joint bleeds than prescribed: median (range) 215.2 (74.1-400.0) mcg kg(-1) vs. 200.0 (61.0-270.0) mcg kg(-1) for children, and 231.3 (59.3-379.7) mcg kg(-1) vs. 123.0 (81.0-289.0) mcg kg(-1) for adults. The median infused dose for joint bleeds was higher in adults than children (175.2 vs. 148.0 mcg kg(-1) ), but children received significantly more doses per joint bleed than adults (median 6.5 vs. 3.0). The median total dose per joint bleed was higher in children than adults (1248.7 vs. 441.6). For children and adults, both initial and additional doses administered for bleeds were higher than prescribed. Children received higher total doses per bleed due to an increased number of infusions per bleed.

  17. Recombinant Activated Factor VIIa (rFVIIa) Treatment in Very-Low-Birth-Weight (VLBW) Premature Infants with Acute Pulmonary Hemorrhage: A Single-Center, Retrospective Study.

    Science.gov (United States)

    Cosar, Hese; Isik, Halil; Cakır, Salih Cagrı; Yar, Nese; Goksen, Bulent; Tokbay, Hakan; Kertmen, Hasan; Erdoğan, Nihal; Durak, Ikbal

    2017-02-01

    We aimed to evaluate the efficacy of intravenous administration of recombinant activated factor VIIa (rFVIIa) for acute pulmonary hemorrhage treatment in very-low-birth-weight (VLBW) premature infants. This study was carried out retrospectively in premature infants with pulmonary hemorrhage that were ≤30 weeks gestational age or premature infants with pulmonary hemorrhage who were hospitalized in our neonatal intensive care unit between 01 January 2013 and 31 December 2015 were evaluated. Group 1 (n = 21) received rFVIIa support within the first 30 min of pulmonary hemorrhage plus conventional treatment, while Group 2 (n = 21) received conventional treatment only. The number of patients whose pulmonary hemorrhage was stopped within the first 2 h was significantly higher in Group 1 than Group 2 (n = 14 vs n = 4; p = 0.002). After pulmonary hemorrhage, hemoglobin values of Group 1 were higher than Group 2 (11.12 ± 1.06 vs 10.14 ± 1.59 g/dL; p = 0.024). Erythrocyte suspension (1.43 ± 4.51 vs 5.71 ± 7.46 mL/kg; p = 0.030) and fresh frozen plasma use (5.71 ± 8.10 vs 19.52 ± 12.44 mL/kg; p premature infants.

  18. Analogue MIMO Detection

    Directory of Open Access Journals (Sweden)

    McNamara Darren

    2006-01-01

    Full Text Available In this contribution we propose an analogue receiver that can perform turbo detection in MIMO systems. We present the case for a receiver that is built from nonlinear analogue devices, which perform detection in a "free-flow" network (no notion of iterations. This contribution can be viewed as an extension of analogue turbo decoder concepts to include MIMO detection. These first analogue implementations report reductions of few orders of magnitude in the number of required transistors and in consumed energy, and the same order of improvement in processing speed. It is anticipated that such analogue MIMO decoder could bring about the same advantages, when compared to traditional digital implementations.

  19. Carcinogenicity of insulin analogues

    NARCIS (Netherlands)

    Braak, Sebastiaan Johannes ter

    2015-01-01

    There is epidemiological evidence that the use of some insulin analogues by diabetic patients is correlated with an increased cancer risk. In vitro exposure experiments revealed that insulin glargine (LANTUS) was the only commercial insulin analogue with an increased mitogenic potential. In the huma

  20. Survey of analogue spacetimes

    CERN Document Server

    Visser, Matt

    2013-01-01

    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 introductory chapter, I shall provide a few simple examples of analogue spacetimes as general background for the rest of the contributions.

  1. Synthesis of Tonghaosu Analogues

    Institute of Scientific and Technical Information of China (English)

    SUN Hai; LIN Yingjie; WU Yulin; WU Yikang

    2009-01-01

    Several new analogues of natural antifeedant tonghaosu were synthesized via m-CPBA (m-chloroperoxybenzoic acid) oxidation of corresponding 3-(a-furyl)propanols, Luche reduction of the resulting enone, epoxidation, acid-mediated spiroketalization, and radical mediated dehydration.

  2. ACTINOMYCIN D ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to new compounds being structurally and functionally similar to Actinomycin D and to combinatorial libraries of such compounds. The Actinomycin D analogues according to the present invention comprise two linear or cyclic peptide moieties constituted by $g...

  3. ACTINOMYCIN D ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to new compounds being structurally and functionally similar to Actinomycin D and to combinatorial libraries of such compounds. The Actinomycin D analogues according to the present invention comprise two linear or cyclic peptide moieties constituted by $g...

  4. Gastric inhibitory polypeptide analogues

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2002-01-01

    of GIP and GLP-1 receptors, the incretin effect is essential for normal glucose tolerance. In patients with type 2 diabetes mellitus it turns out that the incretin effect is severely impaired or abolished. The explanation seems to be that both the secretion of GLP-1 and the effect of GIP are impaired...... (whereas both the secretion of GIP and the effect of GLP-1 are near normal). The impaired GLP-1 secretion is probably a consequence of diabetic metabolic disturbances. The known genetic variations in the GIP receptor sequence are not associated with type 2 diabetes mellitus, but a defective insulinotropic...... and its analogues are attractive as therapeutic agents for type 2 diabetes mellitus, analogues of GIP are unlikely to be effective. On the other hand, GIP seems to play an important role in lipid metabolism, promoting the disposal of ingested lipids, and mice with a targeted deletion of the GIP receptor...

  5. Aspartame and Its Analogues

    Science.gov (United States)

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

    1981-04-01

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

  6. Quantum analogue computing.

    Science.gov (United States)

    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.

  7. Analogue Methods in Palaeoecology: Using the analogue Package

    OpenAIRE

    Simpson, Gavin L.

    2007-01-01

    Palaeoecology is an important branch of ecology that uses the subfossil remains of organisms preserved in lake, ocean and bog sediments to inform on changes in ecosystems and the environment through time. The analogue package contains functions to perform modern analogue technique (MAT) transfer functions, which can be used to predict past changes in the environment, such as climate or lake-water pH from species data. A related technique is that of analogue matching, which is concerned with i...

  8. Vorticity in analogue gravity

    CERN Document Server

    Cropp, Bethan; Turcati, Rodrigo

    2015-01-01

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

  9. NASA/ESMD Analogue Mission Plans

    Science.gov (United States)

    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.

  10. Cobalamin analogues in humans

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Obeid, Rima; Herrmann, Wolfgang

    2013-01-01

    BACKGROUND: Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin...... of CorA. METHODS: HC-CorA were quantified in paired samples of cord serum from newborns and serum from mothers (n = 69). RESULTS: The CorA-concentration was higher in cord serum (median = 380, range: 41-780 pmol/L) than in serum from the mothers (median = 160, range: 64-330 pmol/L), (p...-analysis showed CorA-peaks with retention times of 13.5, 14,5 and 16.5 min in samples from both the mother and cord serum. The peak with retention time 16.5 min constituted 24% (mother) and 45% (cord serum) of the total amount CorA, and eluted as does dicyanocobinamide. CONCLUSION: Our results support that CorA...

  11. Introduction to electronic analogue computers

    CERN Document Server

    Wass, C A A

    1965-01-01

    Introduction to Electronic Analogue Computers, Second Revised Edition is based on the ideas and experience of a group of workers at the Royal Aircraft Establishment, Farnborough, Hants. This edition is almost entirely the work of Mr. K. C. Garner, of the College of Aeronautics, Cranfield. As various advances have been made in the technology involving electronic analogue computers, this book presents discussions on the said progress, including some acquaintance with the capabilities of electronic circuits and equipment. This text also provides a mathematical background including simple differen

  12. Menstrual regulation with prostaglandin analogues.

    Science.gov (United States)

    Hagenfeldt, K; Bygdeman, M

    1981-01-01

    The development of generally applicable, simple non-surgical methods for menstrual regulation has been desired for a long time. Such an approach to fertility control depends on the availability of a suitable therapeutic agent that should be effective, reliable, simple to administer and free from disturbing side effects. The classical prostaglandins have shown the capability but are unsuitable mainly due to high incidence of side effects. Most of these drawbacks seem to be overcome when prostaglandin analogues are used; however, vaginal administration caused appreciable pain in 10-30% of women, and so severely limits self-administration of these analogues.

  13. Analogue Methods in Palaeoecology: Using the analogue Package

    Directory of Open Access Journals (Sweden)

    Gavin L. Simpson

    2007-08-01

    Full Text Available Palaeoecology is an important branch of ecology that uses the subfossil remains of organisms preserved in lake, ocean and bog sediments to inform on changes in ecosystems and the environment through time. The analogue package contains functions to perform modern analogue technique (MAT transfer functions, which can be used to predict past changes in the environment, such as climate or lake-water pH from species data. A related technique is that of analogue matching, which is concerned with identifying modern sites that are floristically and faunistically similar to fossil samples. These techniques, and others, are increasingly being used to inform public policy on environmental pollution and conservation practices. These methods and other functionality in analogue are illustrated using the Surface Waters Acidification Project diatom:pH training set and diatom counts on samples of a sediment core from the Round Loch of Glenhead, Galloway, Scotland. The paper is aimed at palaeoecologists who are familiar with the techniques described but not with R.

  14. Novel acetylcholine and carbamoylcholine analogues

    DEFF Research Database (Denmark)

    Hansen, Camilla Petrycer; Jensen, Anders Asbjørn; Christensen, Jeppe K.

    2008-01-01

    A series of carbamoylcholine and acetylcholine analogues were synthesized and characterized pharmacologically at neuronal nicotinic acetylcholine receptors (nAChRs). Several of the compounds displayed low nanomolar binding affinities to the alpha 4beta 2 nAChR and pronounced selectivity for this ...

  15. Measuring Mental Imagery with Visual Analogue Scales.

    Science.gov (United States)

    Quilter, Shawn M.; Band, Jennie P.; Miller, Gary M.

    1999-01-01

    Investigates some of the psychometric characteristics of the results from visual-analogue scales used to measure mental imagery. Reports that the scores from visual-analogue scales are positively related to scores from longer pencil-and-paper measures of mental imagery. Implications and limitations for the use of visual-analogue scales to measure…

  16. A Short Term Analogue Memory

    DEFF Research Database (Denmark)

    Shah, Peter Jivan

    1992-01-01

    A short term analogue memory is described. It is based on a well-known sample-hold topology in which leakage currents have been minimized partly by circuit design and partly by layout techniques. Measurements on a test chip implemented in a standard 2.4 micron analogue CMOS process show a droop...... rate of 0.075mV per second with a 1pF hold capacitor. This is equivalent to a retention time of approximately 1½ minute with 10 bits accuracy, assuming a full scale of +/-3.5V. It is expected that this can be improved by more than an order of magnitude by improving the layout of the hold capacitor...

  17. Neuronal Analogues of Conditioning Paradigms

    Science.gov (United States)

    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

  18. Substrate analogues for isoprenoid enzymes

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Antimicrobial evaluation of mangiferin analogues

    Directory of Open Access Journals (Sweden)

    Singh S

    2009-01-01

    Full Text Available The naturally occurring xanthone glycoside mangiferin has been isolated by column chromatography from the ethanol extract of stem bark of Mangifera indica. Mangiferin was further converted to 5-(N-phenylaminomethylenomangiferin, 5-(N-p-chlorophenylaminomethyleno mangiferin, 5-(N-2-methylphenylaminomethyleno mangiferin, 5-(N-p-methoxyphenylaminomethyleno mangiferin, 5-(N,N-diphenylaminomethyleno mangiferin, 5-(N--napthylaminomethyleno mangiferin and 5-(N-4-methylphenylaminomethyleno mangiferin. Mangiferin and its analogues were characterized by melting point and R f value determination and through spectral technique like UV, IR, and NMR spectral analysis. The synthesized compounds were screened for antimicrobial activity.

  20. Antimicrobial Evaluation of Mangiferin Analogues

    Science.gov (United States)

    Singh, S. K.; Kumar, Y.; Kumar, S. Sadish; Sharma, V. K.; Dua, K.; Samad, A.

    2009-01-01

    The naturally occurring xanthone glycoside mangiferin has been isolated by column chromatography from the ethanol extract of stem bark of Mangifera indica. Mangiferin was further converted to 5-(N-phenylaminomethyleno)mangiferin, 5-(N-p-chlorophenylaminomethyleno) mangiferin, 5-(N-2-methylphenylaminomethyleno) mangiferin, 5-(N-p-methoxyphenylaminomethyleno) mangiferin, 5-(N, N-diphenylaminomethyleno) mangiferin, 5-(N--napthylaminomethyleno) mangiferin and 5-(N-4-methylphenylaminomethyleno) mangiferin. Mangiferin and its analogues were characterized by melting point and Rf value determination and through spectral technique like UV, IR, and NMR spectral analysis. The synthesized compounds were screened for antimicrobial activity. PMID:20490307

  1. Ecstasy analogues found in cacti.

    Science.gov (United States)

    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."

  2. A graphical approach to analogue behavioural modelling

    OpenAIRE

    Moser, Vincent; Nussbaum, Pascal; Amann, Hans-Peter; Astier, Luc; Pellandini, Fausto

    2007-01-01

    In order to master the growing complexity of analogue electronic systems, modelling and simulation of analogue hardware at various levels is absolutely necessary. This paper presents an original modelling method based on the graphical description of analogue electronic functional blocks. This method is intended to be automated and integrated into a design framework: specialists create behavioural models of existing functional blocks, that can then be used through high-level selection and spec...

  3. What Can We Learn From Analogue Experiments?

    CERN Document Server

    Thebault, Karim P Y

    2016-01-01

    In 1981 Unruh proposed that fluid mechanical experiments could be used to probe key aspects of the quantum phenomenology of black holes. In particular, he claimed that an analogue to Hawking radiation could be created within a fluid mechanical `dumb hole', with the event horizon replaced by a sonic horizon. Since then an entire sub-field of `analogue gravity' has been created. In 2016 Steinhauer reported the experimental observation of quantum Hawking radiation and its entanglement in a Bose-Einstein condensate analogue black hole. What can we learn from such analogue experiments? In particular, in what sense can they provide evidence of novel phenomena such as black hole Hawking radiation?

  4. The Valles natural analogue project

    Energy Technology Data Exchange (ETDEWEB)

    Stockman, H.; Krumhansl, J.; Ho, C. [Sandia National Labs., Albuquerque, NM (United States); McConnell, V. [Alaska Univ., Fairbanks, AK (United States). Geophysical Inst.

    1994-12-01

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

  5. CO2 Capture with Enzyme Synthetic Analogue

    Energy Technology Data Exchange (ETDEWEB)

    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. The future of somatostatin analogue therapy.

    Science.gov (United States)

    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.

  7. Strategy and methodology of dynamical analogue prediction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In order to effectively improve numerical prediction level by using current models and data, the strategy and methodology of dynamical analogue prediction (DAP) is deeply studied in the present paper. A new idea to predict the prediction errors of dynamical model on the basis of historical analogue information is put forward so as to transform the dynamical prediction problem into the estimation problem of prediction errors. In terms of such an idea, a new prediction method of final analogue correction of errors (FACE) is developed. Furthermore, the FACE is applied to extra-seasonal prediction experiments on an operational atmosphere-ocean coupled general circulation model. Prediction results of summer mean circulation and total precipitation show that the FACE can to some extent reduce prediction errors, recover prediction variances, and improve prediction skills. Besides, sensitive experiments also show that predictions based on the FACE are evidently influenced by the number of analogues, analogue-selected variables and analogy metric.

  8. Space analogue studies in Antarctica

    Science.gov (United States)

    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.

  9. Space analogue studies in Antarctica

    Science.gov (United States)

    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.

  10. Condensed matter analogues of cosmology

    Science.gov (United States)

    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

  11. Antimicrobial Activity of Resveratrol Analogues

    Directory of Open Access Journals (Sweden)

    Malik Chalal

    2014-06-01

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

  12. Total Synthesis of the Analogue of Icogenin

    Institute of Scientific and Technical Information of China (English)

    Shu Jie HOU; Peng XU; Liang ZHOU; De Quan YU; Ping Sheng LEI; Chuan Chun ZOU

    2006-01-01

    One of the analogues of icogenin, a natural furostanol saponin showing strong cytotoxic effect on cancer cell, was first synthesized via convergent strategy by using diosgenin and available monosaccharides as starting materials,

  13. Heterocyclic chalcone analogues as potential anticancer agents.

    Science.gov (United States)

    Sharma, Vikas; Kumar, Vipin; Kumar, Pradeep

    2013-03-01

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

  14. Second-Generation Fluorescent Quadracyclic Adenine Analogues

    DEFF Research Database (Denmark)

    Dumat, Blaise; Bood, Mattias; Wranne, Moa S.;

    2015-01-01

    Fluorescent base analogues comprise a group of increasingly important molecules for the investigation of nucleic acid structure, dynamics, and interactions with other molecules. Herein, we report on the quantum chemical calculation aided design, synthesis, and characterization of four new putativ...

  15. Sulfur analogues of psychotomimetic agents. Monothio analogues of mescaline and isomescaline.

    Science.gov (United States)

    Jacob, P; Shulgin, A T

    1981-11-01

    Two monothio analogues of mescaline and three monothio analogues of 2,3,4-trimethoxyphenethylamine (isomescaline) have been synthesized and characterized. Only the two mescaline analogues (3-and 4-thiomescaline) were found to be psychotomimetics in man, being 6 and 12 times more potent than mescaline, respectively. All five compounds can serve as substrates for bovine plasma monoamine oxidase in vitro, but no positive correlation is apparent between the extent of enzymatic degradation and human psychotomimetic potency.

  16. The structure activity relationship of discodermolide analogues.

    Science.gov (United States)

    Shaw, Simon J

    2008-03-01

    The marine polyketide discodermolide is a member of a class of natural products that stabilize microtubules. Many analogues have been synthesized suggesting that few changes can be made to the internal carbon backbone. Both ends of the molecule, however, can be modified. The majority of analogues have been generated via modification of the lactone region. This suggests that significant simplifications can be made in this region provided that the lactone moiety is maintained.

  17. Between Analogue and Digital Diagrams

    Directory of Open Access Journals (Sweden)

    Zoltan Bun

    2012-10-01

    Full Text Available This essay is about the interstitial. About how the diagram, as a method of design, has lead fromthe analogue deconstruction of the eighties to the digital processes of the turn of the millennium.Specifically, the main topic of the text is the interpretation and the critique of folding (as a diagramin the beginning of the nineties. It is necessary then to unfold its relationship with immediatelypreceding and following architectural trends, that is to say we have to look both backwards andforwards by about a decade. The question is the context of folding, the exchange of the analogueworld for the digital. To understand the process it is easier to investigate from the fields of artand culture, rather than from the intentionally perplicated1 thoughts of Gilles Deleuze. Both fieldsare relevant here because they can similarly be used as the yardstick against which the era itselfit measured. The cultural scene of the eighties and nineties, including performing arts, movies,literature and philosophy, is a wide milieu of architecture. Architecture responds parallel to itsera; it reacts to it, and changes with it and within it. Architecture is a medium, it has always beena medium, yet the relations are transformed. That’s not to say that technical progress, for exampleusing CAD-software and CNC-s, has led to the digital thinking of certain movements ofarchitecture, (it is at most an indirect tool. But the ‘up-to-dateness’ of the discipline, however,a kind of non-servile reading of an ‘applied culture’ or ‘used philosophy’2 could be the key.(We might recall here, parenthetically, the fortunes of the artistic in contemporary mass society.The proliferation of museums, the magnification of the figure of the artist, the existence of amassive consumption of printed and televised artistic images, the widespread appetite for informationabout the arts, all reflect, of course, an increasingly leisured society, but also relateprecisely to the fact

  18. Reduced peptide bond pseudopeptide analogues of neurotensin.

    Science.gov (United States)

    Doulut, S; Rodriguez, M; Lugrin, D; Vecchini, F; Kitabgi, P; Aumelas, A; Martinez, J

    1992-01-01

    Pseudopeptide analogues of the C-terminal hexapeptide of neurotensin (H-Arg-Arg-Pro-Tyr-Ile-Leu-OH) were obtained by replacing each peptide bond by the reduced peptide bond CH2NH. The resulting analogues were then examined for their ability to inhibit binding of labeled neurotensin to new-born mouse brain membranes and for stimulation of guinea pig ileum contraction. Replacement of the Ile12-Leu13, Tyr11-Ile12, Pro10-Tyr11 and Lys9-Pro10 peptide bonds resulted in about 2000-, 3400-, 200- and 3400-fold losses, respectively, in binding affinity and 400-, 750-, 250- and 300-fold losses, respectively, in biological activity. Replacement of both Arg8 and Arg9 by lysine led to an analogue exhibiting the same pharmacological profile as the C-terminal hexapeptide of neurotensin. Interestingly, replacement of the Lys8-Lys9 peptide bond by the CH2NH bond produced an analogue exhibiting the same affinity for neurotensin receptors, but 10 times more potent in stimulating guinea pig ileum contraction. N-terminal protected analogues (by the Boc group) showed decreased potency as compared with their amino-free corresponding compounds.

  19. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem

    2016-02-04

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

  20. Synthesis and anticancer evaluation of spermatinamine analogues.

    Science.gov (United States)

    Moosa, Basem A; Sagar, Sunil; Li, Song; Esau, Luke; Kaur, Mandeep; Khashab, Niveen M

    2016-03-15

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcysteine carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines, that is, cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5-10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Geomagnetic properties of Proxima Centauri b analogues

    CERN Document Server

    Zuluaga, Jorge I

    2016-01-01

    The recent discovery of a planet around the closest star, Proxima Centauri, could represent a quantum leap on the testability of models in exoplanet sciences. Unlike any other discovered exoplanet, models of planetary processes in Proxima b could be contrasted against near future telescopic observations and far future in-situ measurements. In this paper we study the geomagnetic properties of Proxima b analogues, namely, solid planets with masses close but larger than Earth's mass, periods of rotation of several days and habitable surface conditions. Assuming different planetary masses, bulk compositions and periods of rotations, we calculate for each planetary analogue its radius, heat flux, time of inner core formation, dynamo lifetime and minimum dipole magnetic moment. We find that most ($\\gtrsim$70\\%) Proxima b analogues develop intrinsic dynamos that last at least 3 Gyr, although only half of them are older than the present age of the host star ($4-6$ Gyr). Relying in our planetary evolution models, we p...

  2. Benzoylphenylurea sulfur analogues with potent antitumor activity.

    Science.gov (United States)

    Hallur, Gurulingappa; Jimeno, Antonio; Dalrymple, Susan; Zhu, Tao; Jung, M Katherine; Hidalgo, Manuel; Isaacs, John T; Sukumar, Saraswati; Hamel, Ernest; Khan, Saeed R

    2006-04-06

    A novel series of BPU analogues were synthesized and evaluated for antitumor activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up to 10-fold increased potency, when compared to 1 (NSC-639829), against cancer cell lines. 6n was more effective than 1 in causing apoptosis of MCF-7 cells. When compared to other drugs with a similar mechanism of action, 6n retained significant ability to inhibit tubulin assembly, with an IC(50) of 2.1 microM.

  3. Analogue alternative the electronic analogue computer in Britain and the USA, 1930-1975

    CERN Document Server

    Small, James S

    2013-01-01

    We are in the midst of a digital revolution - until recently, the majority of appliances used in everyday life have been developed with analogue technology. Now, either at home or out and about, we are surrounded by digital technology such as digital 'film', audio systems, computers and telephones. From the late 1940s until the 1970s, analogue technology was a genuine alternative to digital, and the two competing technologies ran parallel with each other. During this period, a community of engineers, scientists, academics and businessmen continued to develop and promote the analogue computer.

  4. Solanapyrone analogues from a Hawaiian fungicolous fungus

    Science.gov (United States)

    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...

  5. Dumb holes: analogues for black holes.

    Science.gov (United States)

    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.

  6. Prussian Blue Analogues of Reduced Dimensionality

    NARCIS (Netherlands)

    Gengler, Regis Y. N.; Toma, Luminita M.; Pardo, Emilio; Lloret, Francesc; Ke, Xiaoxing; Van Tendeloo, Gustaaf; Gournis, Dimitrios; Rudolf, Petra

    2012-01-01

    Mixed-valence polycyanides (Prussian Blue analogues) possess a rich palette of properties spanning from room-temperature ferromagnetism to zero thermal expansion, which can be tuned by chemical modifications or the application of external stimuli (temperature, pressure, light irradiation). While mol

  7. Synthesis and antimicrobial activity of squalamine analogue.

    Science.gov (United States)

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

    2000-08-01

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

  8. Prussian Blue Analogues of Reduced Dimensionality

    NARCIS (Netherlands)

    Gengler, Regis Y. N.; Toma, Luminita M.; Pardo, Emilio; Lloret, Francesc; Ke, Xiaoxing; Van Tendeloo, Gustaaf; Gournis, Dimitrios; Rudolf, Petra

    2012-01-01

    Mixed-valence polycyanides (Prussian Blue analogues) possess a rich palette of properties spanning from room-temperature ferromagnetism to zero thermal expansion, which can be tuned by chemical modifications or the application of external stimuli (temperature, pressure, light irradiation). While

  9. A great disappearing act: the electronic analogue computer

    OpenAIRE

    Bissell, C.C.

    2004-01-01

    One historian of technology has called the analogue computer 'one of the great disappearing acts of the Twentieth Century'. This paper will look briefly at the origins, development and decline of the electronic analogue computer ..

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

    Science.gov (United States)

    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.

  11. Analogue VLSI for probabilistic networks and spike-time computation.

    Science.gov (United States)

    Murray, A

    2001-02-01

    The history and some of the methods of analogue neural VLSI are described. The strengths of analogue techniques are described, along with residual problems to be solved. The nature of hardware-friendly and hardware-appropriate algorithms is reviewed and suggestions are offered as to where analogue neural VLSI's future lies.

  12. A q-analogue of the four functions theorem

    OpenAIRE

    Christofides, Demetres

    2009-01-01

    In this article we give a proof of a q-analogue of the celebrated four functions theorem. This analogue was conjectured by Bjorner and includes as special cases both the four functions theorem and also Bjorner's q-analogue of the FKG inequality.

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

    Science.gov (United States)

    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.

  14. Confirmation via Analogue Simulation: A Bayesian Analysis

    CERN Document Server

    Dardashti, Radin; Thebault, Karim P Y; Winsberg, Eric

    2016-01-01

    Analogue simulation is a novel mode of scientific inference found increasingly within modern physics, and yet all but neglected in the philosophical literature. Experiments conducted upon a table-top 'source system' are taken to provide insight into features of an inaccessible 'target system', based upon a syntactic isomorphism between the relevant modelling frameworks. An important example is the use of acoustic 'dumb hole' systems to simulate gravitational black holes. In a recent paper it was argued that there exists circumstances in which confirmation via analogue simulation can obtain; in particular when the robustness of the isomorphism is established via universality arguments. The current paper supports these claims via an analysis in terms of Bayesian confirmation theory.

  15. Spectroscopic study of solar twins and analogues

    CERN Document Server

    Datson, Juliet; Portinari, Laura

    2014-01-01

    Context. Many large stellar surveys have been and are still being carried out, providing huge amounts of data, for which stellar physical parameters will be derived. Solar twins and analogues provide a means to test the calibration of these stellar catalogues because the Sun is the best-studied star and provides precise fundamental parameters. Solar twins should be centred on the solar values. Aims. This spectroscopic study of solar analogues selected from the Geneva-Copenhagen Survey (GCS) at a resolution of 48,000 provides effective temperatures and metallicities for these stars. We test whether our spectroscopic parameters, as well as the previous photometric calibrations, are properly centred on the Sun. In addition, we search for more solar twins in our sample. Methods. The methods used in this work are based on literature methods for solar twin searches and on methods we developed in previous work to distinguish the metallicity-temperature degeneracies in the differential comparison of spectra of solar ...

  16. Optimization of propafenone analogues as antimalarial leads.

    Science.gov (United States)

    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.

  17. Holographic Fluids with Vorticity and Analogue Gravity

    CERN Document Server

    Leigh, Robert G; Petropoulos, P Marios

    2012-01-01

    We study holographic three-dimensional fluids with vorticity in local equilibrium and discuss their relevance to analogue gravity systems. The Fefferman-Graham expansion leads to the fluid's description in terms of a comoving and rotating Papapetrou-Randers frame. A suitable Lorentz transformation brings the fluid to the non-inertial Zermelo frame, which clarifies its interpretation as moving media for light/sound propagation. We apply our general results to the Lorentzian Kerr-AdS_4 and Taub-NUT-AdS_4 geometries that describe fluids in cyclonic and vortex flows respectively. In the latter case we associate the appearance of closed timelike curves to analogue optical horizons. In addition, we derive the classical rotational Hall viscosity of three-dimensional fluids with vorticity. Our formula remarkably resembles the corresponding result in magnetized plasmas.

  18. Polyamine analogues targeting epigenetic gene regulation.

    Science.gov (United States)

    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

  19. The Brookhaven electron analogue, 1953--1957

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Synthesis of constrained analogues of tryptophan

    Directory of Open Access Journals (Sweden)

    Elisabetta Rossi

    2015-10-01

    Full Text Available 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.

  1. Electromagnetic wave analogue of electronic diode

    OpenAIRE

    Shadrivov, Ilya V.; Powell, David A.; Kivshar, Yuri S.; Fedotov, Vassili A.; Zheludev, Nikolay I.

    2010-01-01

    An electronic diode is a nonlinear semiconductor circuit component that allows conduction of electrical current in one direction only. A component with similar functionality for electromagnetic waves, an electromagnetic isolator, is based on the Faraday effect of the polarization state rotation and is also a key component of optical and microwave systems. Here we demonstrate a chiral electromagnetic diode, which is a direct analogue of an electronic diode: its functionality is underpinned by ...

  2. Synthesis of a Cyclic Analogue of Galardin

    Institute of Scientific and Technical Information of China (English)

    马大为; 吴问根; 钱静; 郎深慧; 叶其壮

    2001-01-01

    A cyclic analogue 4 of galardin,a known MMP inhibitor,is designed to improve its selectivity.The synthesis of 4starts from dimethyl(S)-malate using diaselective alkylation and subsequent cyclization and amide formation as key steps.The compound 4 showed MMP inhibitory activity on all MMPs tested with IC50 ranging from 20.1 μM to 104 μM.

  3. Benchmarking analogue models of brittle thrust wedges

    Science.gov (United States)

    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

  4. Electromagnetic wave analogue of electronic diode

    OpenAIRE

    Shadrivov, Ilya V.; Powell, David A.; Kivshar, Yuri S.; Fedotov, Vassili A.; Zheludev, Nikolay I.

    2010-01-01

    An electronic diode is a nonlinear semiconductor circuit component that allows conduction of electrical current in one direction only. A component with similar functionality for electromagnetic waves, an electromagnetic isolator, is based on the Faraday effect of the polarization state rotation and is also a key component of optical and microwave systems. Here we demonstrate a chiral electromagnetic diode, which is a direct analogue of an electronic diode: its functionality is underpinned by ...

  5. Thymidine analogues for tracking DNA synthesis.

    Science.gov (United States)

    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.

  6. Thymidine Analogues for Tracking DNA Synthesis

    Directory of Open Access Journals (Sweden)

    Brenton L. Cavanagh

    2011-09-01

    Full Text Available 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.

  7. Analogue to Digital and Digital to Analogue Converters (ADCs and DACs): A Review Update

    CERN Document Server

    Pickering, J

    2015-01-01

    This is a review paper updated from that presented for CAS 2004. Essentially, since then, commercial components have continued to extend their performance boundaries but the basic building blocks and the techniques for choosing the best device and implementing it in a design have not changed. Analogue to digital and digital to analogue converters are crucial components in the continued drive to replace analogue circuitry with more controllable and less costly digital processing. This paper discusses the technologies available to perform in the likely measurement and control applications that arise within accelerators. It covers much of the terminology and 'specmanship' together with an application-oriented analysis of the realisable performance of the various types. Finally, some hints and warnings on system integration problems are given.

  8. The Greenland analogue project. Yearly report 2010

    Energy Technology Data Exchange (ETDEWEB)

    Harper, J.; Brinkerhoff, D.; Johnson, J. [University of Montana, Missoula (United States); Ruskeeniemi, T.; Engstroem, J.; Kukkonen, I. [Geological Survey of Finland (Finland)] [and others

    2012-04-15

    A four-year field and modelling study of the Greenland ice sheet and subsurface conditions, Greenland Analogue Project (GAP), has been initiated collaboratively by SKB, Posiva and NWMO to advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository. The study site encompasses a land terminus portion of the Greenland ice sheet, east of Kangerlussuaq, and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project begins in 2009 and is scheduled for completion in 2012. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with cold climate conditions and glacial cycles, and their impact on the long-term performance of deep geological repositories for spent nuclear fuel, will be significantly improved by studying a modern analogue. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a better understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. This report was produced by the GAP team members and presents an overview of the activities within the GAP during the interval January 1 to December 31, 2010, as well as research results obtained during this time frame. Research for the GAP is ongoing, and additional results related to the data presented here may become available in the future and will be presented in subsequent annual reports. (orig.)

  9. Synthesis and study of ceramide analogues

    OpenAIRE

    Školová, Barbora

    2015-01-01

    Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of inorganic and organic chemistry Candidate: Mgr. Barbora Školová Supervisor: doc. PharmDr. Kateřina Vávrová, Ph.D. Title of doctoral thesis: Synthesis and study of ceramide analogues Ceramides (Cer) together with free fatty acids and cholesterol form intercellular lamellar space of the uppermost skin layer (stratum corneum, SC). This lipid matrix presents the proper skin barrier - it protects organism against out...

  10. Analogues of Euler and Poisson Summation Formulae

    Indian Academy of Sciences (India)

    Vivek V Rane

    2003-08-01

    Euler–Maclaurin and Poisson analogues of the summations $\\sum_{a < n ≤ b}(n)f(n), \\sum_{a < n ≤ b}d(n) f(n), \\sum_{a < n ≤ b}d(n)(n) f(n)$ have been obtained in a unified manner, where (()) is a periodic complex sequence; () is the divisor function and () is a sufficiently smooth function on [, ]. We also state a generalised Abel's summation formula, generalised Euler's summation formula and Euler's summation formula in several variables.

  11. Analogue cosmology in a hadronic fluid

    Directory of Open Access Journals (Sweden)

    Bilić Neven

    2014-01-01

    Full Text Available Analog gravity models of general relativity seem promising routes to providing laboratory tests of the foundation of quantum field theory in curved space-time. In contrast to general relativity, where geometry of a spacetime is determined by the Einstein equations, in analog models geometry and evolution of analog spacetime are determined by the equations of fluid mechanics. In this paper we study the analogue gravity model based on massless pions propagating in a expanding hadronic fluid. The analog expanding spacetime takes the form of an FRW universe, with the apparent and trapping horizons defined in the standard way.

  12. Technical Considerations in Magnetic Analogue Models

    CERN Document Server

    Adams, Patrick W M

    2016-01-01

    The analogy between vorticity and magnetic fields has been a subject of interest to researchers for a considerable period of time, mainly because of the structural similarities between the systems of equations that govern the evolution of the two fields. We recently presented the analysis of magnetic fields and hydrodynamics vorticity fields and argued for a formal theory of analogue magnetism. This article provides in depth technical details of the relevant considerations for the simulation procedures and extends the analyses to a range of fluids.

  13. Satellite television analogue and digital reception techniques

    CERN Document Server

    Benoit, Herve

    1999-01-01

    Satellite television is part of the lives of millions of television viewers worldwide and its influence is set to increase significantly with the launch of digital satellite television services.This comprehensive reference book, written by the author of the highly successful 'Digital Television', provides a technical overview of both analogue and digital satellite TV. Written concisely and thoroughly, it covers all aspects of satellite TV necessary to understand its operation and installation. It also covers the evolution of satellite television, and contains a detailed glossary of tec

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

    Energy Technology Data Exchange (ETDEWEB)

    Kovach, L.A.; Ott, W.R. [Nuclear Regulatory Commission, Washington, DC (United States)

    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.

  15. Self-Powered Analogue Smart Skin.

    Science.gov (United States)

    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.

  16. Long-term predictions using natural analogues

    Energy Technology Data Exchange (ETDEWEB)

    Ewing, R.C. [Univ. of New Mexico, Albuquerque, NM (United States)

    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.

  17. Dynamic Analogue Initialization for Ensemble Forecasting

    Institute of Scientific and Technical Information of China (English)

    LI Shan; RONG Xingyao; LIU Yun; LIU Zhengyu; Klaus FRAEDRICH

    2013-01-01

    This paper introduces a new approach for the initialization of ensemble numerical forecasting:Dynamic Analogue Initialization (DAI).DAI assumes that the best model state trajectories for the past provide the initial conditions for the best forecasts in the future.As such,DAI performs the ensemble forecast using the best analogues from a full size ensemble.As a pilot study,the Lorenz63 and Lorenz96 models were used to test DAI's effectiveness independently.Results showed that DAI can improve the forecast significantly.Especially in lower-dimensional systems,DAI can reduce the forecast RMSE by ~50% compared to the Monte Carlo forecast (MC).This improvement is because DAI is able to recognize the direction of the analysis error through the embedding process and therefore selects those good trajectories with reduced initial error.Meanwhile,a potential improvement of DAI is also proposed,and that is to find the optimal range of embedding time based on the error's growing speed.

  18. Space Analogue Environments: Are the Populations Comparable?

    Science.gov (United States)

    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

  19. Dipeptide analogues containing 4-ethoxy-3-pyrrolin-2-ones

    DEFF Research Database (Denmark)

    Hosseini, Masood; Kringelum, Henriette; Murray, A.;

    2006-01-01

    Pyrrolidine-2,4-diones (1) are naturally occurring analogues of amino acids. We herein present a facile synthesis of N-acylated, O-alkylated pyrrolin-2-ones (2) in high yield and excellent enantiopurity. Molecular mechanics calculations suggest that the resulting dipeptide analogues adopt a linea...

  20. Black Hole Analogue in Bose–Einstein Condensation

    Indian Academy of Sciences (India)

    Tangmei He

    2014-09-01

    We have proposed a black hole analogue in a Bose–Einstein condensation. By introducing the Painlevé co-ordinates and using K–G equations, we have obtained the critical temperature of the black hole analogue in a Bose–Einstein condensation.

  1. A Comparison of Two Types of Counseling Analogues

    Science.gov (United States)

    Helms, Janet E.

    1976-01-01

    Subjects' attraction to the counselor, self-reported and physiological anxiety, and susceptibility to persuasion were compared using two types of counseling analogues, quasi-counseling and vicarious-participation. Participants in the quasi-counseling analogue were significantly more attracted to the counselor than were vicarious-participation…

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

    Science.gov (United States)

    Stichter, Janine Peck

    2001-01-01

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

  3. Synthesis of an Orthogonal Topological Analogue of Helicene

    DEFF Research Database (Denmark)

    Wixe, Torbjörn; Wallentin, Carl‐Johan; Johnson, Magnus T.

    2013-01-01

    The synthesis of an orthogonal topological pentamer analogue of helicene is presented. This analogue forms a tubular structure with its aromatic systems directed parallel to the axis of propagation, which creates a cavity with the potential to function as a host molecule. The synthetic strategy r...

  4. Insulin analogues and severe hypoglycaemia in type 1 diabetes

    DEFF Research Database (Denmark)

    Kristensen, P L; Hansen, L S; Jespersen, M J

    2012-01-01

    The effect of insulin analogues on glycaemic control is well-documented, whereas the effect on avoidance of severe hypoglycaemia remains tentative. We studied the frequency of severe hypoglycaemia in unselected patients with type 1 diabetes treated with insulin analogues, human insulin, or mixed...

  5. Derivatisable Cyanobactin Analogues: A Semisynthetic Approach.

    Science.gov (United States)

    Oueis, Emilia; Adamson, Catherine; Mann, Greg; Ludewig, Hannes; Redpath, Philip; Migaud, Marie; Westwood, Nicholas J; Naismith, James H

    2015-12-01

    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.

  6. Electromagnetic wave analogue of electronic diode

    CERN Document Server

    Shadrivov, Ilya V; Kivshar, Yuri S; Fedotov, Vassili A; Zheludev, Nikolay I

    2010-01-01

    An electronic diode is a nonlinear semiconductor circuit component that allows conduction of electrical current in one direction only. A component with similar functionality for electromagnetic waves, an electromagnetic isolator, is based on the Faraday effect of the polarization state rotation and is also a key component of optical and microwave systems. Here we demonstrate a chiral electromagnetic diode, which is a direct analogue of an electronic diode: its functionality is underpinned by an extraordinary strong nonlinear wave propagation effect in the same way as electronic diode function is provided by a nonlinear current characteristic of a semiconductor junction. The effect exploited in this new electromagnetic diode is an intensity-dependent polarization change in an artificial chiral metamolecule. This microwave effect exceeds a similar optical effect previously observed in natural crystals by more than 12 orders of magnitude and a direction-dependent transmission that differing by a factor of 65.

  7. Helical chirality induction of expanded porphyrin analogues

    Indian Academy of Sciences (India)

    Jun-Ichiro Setsune

    2012-11-01

    Expanded porphyrin analogues with unique figure-eight conformation were prepared by way of useful pyrrole intermediates such as bis(azafulvene)s and 2-borylpyrrole. Supramolecular chirogenesis of cyclooctapyrrole O1 with 32-cycloconjugation was successfully applied to determine absolute configuration of chiral carboxylic acids. Dinuclear CuII complex of cyclooctapyrrole O2 with interrupted -conjugation was resolved by HPLC into enantiomers and their helical handedness was determined by theoretical simulation of their CD spectral pattern. Enantioselective induction of helicity in the metal helicate formation in the presence of a chiral promoter was demonstrated by using ()-(+)-1-(1-phenyl)ethylamine that favoured , helicity. Dinuclear CoII complexes of cyclotetrapyrroletetrapyridine O3 were found to be substitution labile and pick up amino acid anions in water. Those amino acid complexes of O3Co2 were rendered to adopt a particular unidirectional helical conformation preferentially depending on the ligated amino acid anion.

  8. New pentamidine analogues in medicinal chemistry.

    Science.gov (United States)

    Porcheddu, A; Giacomelli, G; De Luca, L

    2012-01-01

    Sixty years after its introduction, 1,5-bis(4-amidinophenoxy)pentane (Pentamidine) is still one of the most used drugs for the treatment of the first stage of Human African trypanosomiasis and other neglected diseases such as malaria and leishmaniasis. These protozoan infections are prevalent in the poorest world areas such as sub-saharian and developing countries, however the increasing immigration from these countries to the richest part of the world and the overlap of HIV with parasitic infections result in a growing number of cases in developed nations. A great effort has been made to develop new generations of diamidines for the treatment of these infections transmitted by insects. This review summarises the synthesis and evaluation of pentamidine analogues reported in the last years in the effort to find new drugs with better pharmaceutical activity, higher lipophilicity and lower citotoxycicty.

  9. Gravitational analogue of the Witten effect

    Energy Technology Data Exchange (ETDEWEB)

    Foda, O. (International Centre for Theoretical Physics, Trieste (Italy))

    1985-07-22

    In the presence of massive fermions, and assuming a non-vanishing theta-parameter as the only source of CP violation, the Witten effect (a shift in the electric charge of a magnetic monopole due to CP non-conservation) is shown to follow from an anomalous chiral commutator. Next, given the gravitational contribution to the chiral anomaly, the corresponding anomalous commutator for Dirac fermion currents in a gravitational background is derived. From that, we infer the equivalence of a thetaR tildeR term in the lagrangian to a shift in the mass parameter of the NUT metric, in proportion to theta. This is interpreted as the gravitational analogue of the Witten effect. Its relevance to certain Kaluza-Klein monopoles is briefly discussed.

  10. Analogue Divider by Averaging a Triangular Wave

    Science.gov (United States)

    Selvam, Krishnagiri Chinnathambi

    2017-08-01

    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.

  11. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, W.R.; Mazurek, M.; Waber, H.N. [Univ. of Berne (Switzerland). Institutes of Geology, Mineralogy and Petrology, Rock-Water Interaction Group (GGWW); Arlinger, J.; Erlandson, A.C.; Hallbeck, L.; Pedersen, K. [Goeteborg University (Sweden). Dept. of General and Marine Microbiology; Boehlmann, W.; Fritz, P.; Geyer, S.; Geyer, W.; Hanschman, G.; Kopinke, F.D.; Poerschmann, J. [Umweltforschungszentrum Leipzig-Halle (Germany); Chambers, A.V.; Haworth, A.; Ilett, D.; Linklater, C.M.; Tweed, C.J. [AEA Technology plc, Harwell (United Kingdom); Chenery, S.R.N.; Kemp, S.J.; Milodowski, A.E.; Pearce, J.M.; Reeder, S.; Rochelle, C.A.; Smith, B.; Wetton, P.D.; Wragg, J. [British Geological Survey, Keyworth (United Kingdom); Clark, I.D. [Univ. of Ottawa (Canada). Dept. of Geology; Hodginson, E.; Hughes, C.R. [Univ. of Manchester (United Kingdom). Dept. of Earth Sciences; Hyslop, E.K. [British Geological Survey, Edinburgh (United Kingdom); Karlsson, F. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Khoury, H.N.; Salameh, E. [Univ. of Jordan, Amman (Jordan); Lagerblad, B. [Cement Institute, Stockholm (Sweden); Longworth, G. [Univ. of Manchester (United Kingdom). Dept. of Geology; Pitty, A.F. [Private consultant, Norwich (United Kingdom); Savage, D. [QuantiSci Ltd, Melton Mowbray (United Kingdom); Smellie, J.A.T. [ed.] [Conterra AB, Uppsala (Sweden)

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH){sub 2} type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the `alkali disturbed zone` of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  12. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, W.R.; Mazurek, M.; Waber, H.N. [Univ. of Berne (Switzerland). Institutes of Geology, Mineralogy and Petrology, Rock-Water Interaction Group (GGWW); Arlinger, J.; Erlandson, A.C.; Hallbeck, L.; Pedersen, K. [Goeteborg Univ. (Sweden). Dept. of General and Marine Microbiology; Boehlmann, W.; Fritz, P.; Geyer, S.; Geyer, W.; Hanschman, G.; Kopinke, F.D.; Poerschmann, J. [Umweltforschungszentrum Leipzig-Halle (Germany); Chambers, A.V.; Haworth, A.; Ilett, D.; Linklater, C.M.; Tweed, C.J. [AEA Technology plc, Harwell (United Kingdom); Chenery, S.R.N.; Kemp, S.J.; Milodowski, A.E.; Pearce, J.M.; Reeder, S.; Rochelle, C.A.; Smith, B.; Wetton, P.D.; Wragg, J. [British Geological Survey, Keyworth (United Kingdom); Clark, I.D. [Univ. of Ottawa (Canada). Dept. of Geology; Hodginson, E.; Hughes, C.R. [Univ. of Manchester (United Kingdom). Dept. of Earth Sciences; Hyslop, E.K. [British Geological Survey, Edinburgh (United Kingdom); Karlsson, F. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Khoury, H.N.; Salameh, E. [Univ. of Jordan, Amman (Jordan); Lagerblad, B. [Cement Inst., Stockholm (Sweden); Longworth, G. [Univ. of Manchester (United Kingdom). Dept. of Geology; Pitty, A.F. [Private consultant, Norwich (United Kingdom); Savage, D. [QuantiSci Ltd, Melton Mowbray (United Kingdom); Smellie, J.A.T. [ed.] [Conterra AB, Uppsala (Sweden)

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH){sub 2} type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the `alkali disturbed zone` of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  13. Current european regulatory perspectives on insulin analogues

    Directory of Open Access Journals (Sweden)

    Enzmann Harald G

    2011-07-01

    Full Text Available Abstract 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.

  14. Terrestrial analogues for lunar impact melt flows

    Science.gov (United States)

    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.

  15. Natural analogues of nuclear waste glass corrosion.

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  17. Analogue to Digital and Digital to Analogue (AD/DA) Conversion Techniques: An Overview

    CERN Document Server

    CERN. Geneva

    2002-01-01

    The basic ideas behind modern Analogue to Digital and Digital to Analogue (AD/DA) conversion methods will be introduced: a general view of the importance of these devices will be given, along with the digital representation of time-varying, real-world analogue signals. Some CERN applications will be outlined. The variety of conversion methods, their limitations, error sources and measurement methods will form the major part of this presentation. A review of the technological progress in this field over the last 30 years will be presented, concluding with the present 'state of the art' and a quick look at what is just around the corner. This Technical Training Seminar is in the framework of the FEED-2002 Lecture Series, and it is a prerequisite to attending to any of the FEED-2002 Terms. FEED-2002 is a two-term course that will review the techniques dealing with closed loop systems, focussing on time-invariant linear systems. (free attendance, no registration required) More information on the FEED-2002 ...

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

    Science.gov (United States)

    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.

  19. The Greenland Analogue Project. Yearly Report 2009

    Energy Technology Data Exchange (ETDEWEB)

    2010-12-15

    A deep geological repository for spent nuclear fuel needs to be designed to keep used nuclear fuel isolated from mankind and the environment for a million years. Within this time frame glacial conditions are expected in regions that have been glaciated in the past two to ten million years. Climate induced changes such as the growth of ice sheets and permafrost will influence and alter the ground surface and subsurface environment, including its hydrology, which may impact repository safety. Glaciation impact assessments have to-date used over-simplified models and conservative assumptions, for example in the representation of ice sheet hydrology, that do not reflect the complexity of natural systems and processes. This is largely due to lack of direct observations of such processes from existing ice sheets, which if more readily available could help reduce uncertainties and provide a strong scientific basis for the treatment of glacial impacts in safety assessments. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with glacial cycles and their impact on the long-term performance of deep geological repositories for spent nuclear fuel will be significantly improved by studying a modern analogue. To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of

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

    Science.gov (United States)

    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

  1. A Low-cost Multi-channel Analogue Signal Generator

    CERN Document Server

    Müller, F; The ATLAS collaboration; Shen, W; Stamen, R

    2009-01-01

    A scalable multi-channel analogue signal generator is presented. It uses a commercial low-cost graphics card with multiple outputs in a standard PC as signal source. Each color signal serves as independent channel to generate an analogue signal. A custom-built external PCB was developed to adjust the graphics card output voltage levels for a specific task, which needed differential signals. The system furthermore comprises a software package to program the signal shape. The signal generator was successfully used as independent test bed for the ATLAS Level-1 Trigger Pre-Processor, providing up to 16 analogue signals.

  2. Developing Skin Analogues for a Robotic Octopus

    Institute of Scientific and Technical Information of China (English)

    Jinping Hou; Richard H.C.Bonser; George Jeronimidis

    2012-01-01

    In order to fabricate a biomimetic skin for an octopus inspired robot,a new process was developed based on mechanical properties measured from real octopus skin.Various knitted nylon textiles were tested and the one of 10-denier nylon was chosen as reinforcement.A combination of Ecoflex 0030 and 0010 silicone rubbers was used as matrix of the composite to obtain the right stiffness for the skin-analogue system.The open mould fabrication process developed allows air bubble to escape easily and the artificial skin produced was thin and waterproof.Material properties of the biomimetic skin were characterised using static tensile and instrumented scissors cutting tests.The Young's moduli of the artificial skin are 0.08 MPa and 0.13 MPa in the longitudinal and transverse directions,which are much lower than those of the octopus skin.The strength and fracture toughness of the artificial skin,on the other hand are higher than those of real octopus skins.Conically-shaped skin prototypes to be used to cover the robotic arm unit were manufactured and tested.The biomimetic skin prototype was stiff enough to maintain it conical shape when filled with water.The driving force for elongation was reduced significantly compared with previous prototypes.

  3. A positive Grassmannian analogue of the permutohedron

    CERN Document Server

    Williams, Lauren K

    2015-01-01

    The classical permutohedron Perm is the convex hull of the points (w(1),...,w(n)) in R^n where w ranges over all permutations in the symmetric group. This polytope has many beautiful properties -- for example it provides a way to visualize the weak Bruhat order: if we orient the permutohedron so that the longest permutation w_0 is at the "top" and the identity e is at the "bottom," then the one-skeleton of Perm is the Hasse diagram of the weak Bruhat order. Equivalently, the paths from e to w_0 along the edges of Perm are in bijection with the reduced decompositions of w_0. Moreover, the two-dimensional faces of the permutohedron correspond to braid and commuting moves, which by the Tits Lemma, connect any two reduced expressions of w_0. In this note we introduce some polytopes Br(k,n) (which we call bridge polytopes) which provide a positive Grassmannian analogue of the permutohedron. In this setting, BCFW bridge decompositions of reduced plabic graphs play the role of reduced decompositions. We define Br(k,...

  4. Insulin, insulin analogues and diabetic retinopathy.

    Science.gov (United States)

    Chantelau, Ernst; Kimmerle, Renate; Meyer-Schwickerath, Rolf

    2008-02-01

    Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g. IGF-1. In this review we address the role insulin has in the natural evolution of diabetic retinopathy. On the one hand, chronic deficiency of insulin and IGF-1 at the retina is thought to cause capillary degeneration, with subsequent ischaemia. On the other hand, acute abundance of (exogenously administered) insulin and IGF-1 enhances ischaemia-induced VEGF expression. A critical ratio of tissue VEGF-susceptibility: VEGF-availability triggers vascular proliferation (i.e. of micro-aneurysms and/or abnormal vessels). The patent-protected insulin analogues Lispro, Glulisine, Aspart, Glargine and Detemir are artificial insulin derivatives with altered biological responses compared to natural insulin (e.g. divergent insulin and /or IGF-1 receptor-binding characteristics, signalling patterns, and mitogenicity). Their safety profiles concerning diabetic retinopathy remain to be established by randomised controlled trials. Anecdotal reports and circumstantial evidence suggest that Lispro and Glargine might worsen diabetic retinopathy.

  5. Automated Layout Generation of Analogue and Mixed-Signal ASIC's

    DEFF Research Database (Denmark)

    Bloch, Rene

    The research and development carried out in this Ph.D. study focusses on two key areas of the design flow for analogue and mixed-signal integrated circuit design, the mixed-signal floorplanning and the analogue layout generation.A novel approach to floorplanning is presented which provides true...... flow.A new design flow for automated layout generation of general analogue integrated circuits is presented. The design flow provides an automated design path from a sized circuit schematic to the final layout containing the placed, but unrouted, devices of the circuit. The analogue circuit layout...... interactive floorplanning capabilities due to a new implementation variant of a Genetic Algorithm. True interactive floorplanning allows the designer to communicate with existing floorplans during optimization. By entering the "ideas" and expertise of the designer into the optimization algorithm the automated...

  6. From BPA to its analogues: Is it a safe journey?

    Science.gov (United States)

    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?

  7. Doing it with Mirrors Classical analogues for Black Hole radiation

    CERN Document Server

    Srinivasan, K

    1998-01-01

    We construct analogues for the quantum phenomena of black hole radiation in the context of {\\it classical field theory}. Hawking radiation from a (radially) collapsing star is mathematically equivalent to radiation from a mirror moving along a specific trajectory in Minkowski spacetime. We construct a classical analogue for this quantum phenomenon and use it to construct a classical analogue for black hole radiation. The radiation spectrum in quantum field theory has the power spectrum as its classical analogue. Monochromatic light is continually reflected off a moving mirror or the silvered surface of a collapsing star.The reflected light is fourier analysed by the observer and the power spectrum is constructed. For a mirror moving along the standard black hole trajectory,it is seen that the power spectrum has a ``thermal'' nature. Mirror-observer configurations like an inertial mirror observed in an accelerated observer's frame and an accelerated mirror observed in a Rindler frame are investigated and condi...

  8. Analogue gravitational phenomena in Bose-Einstein condensates

    CERN Document Server

    Finazzi, Stefano

    2012-01-01

    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...

  9. Solistatinol, a novel phenolic compactin analogue from Penicillium solitum

    DEFF Research Database (Denmark)

    Larsen, Thomas Ostenfeld; Lange, Lene; Schnorr, Kirk

    2007-01-01

    Solistatinol, a novel phenolic compactin analogue, has been isolated from Penicillium solitum using a UV-guided strategy. The structure and relative stereochemistry were determined by NMR spectroscopy and mass spectrometry. The absolute stereochemistry was determined by chemical degradation...

  10. Sulphur Spring: Busy Intersection and Possible Martian Analogue

    Science.gov (United States)

    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.

  11. Analogue and Mixed-Signal Integrated Circuits for Space Applications

    CERN Document Server

    2014-01-01

    The purpose of AMICSA 2014 (organised in collaboration of ESA and CERN) is to provide an international forum for the presentation and discussion of recent advances in analogue and mixed-signal VLSI design techniques and technologies for space applications.

  12. Insulin analogues in pregnancy and specific congenital anomalies

    DEFF Research Database (Denmark)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa

    2016-01-01

    in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small...... included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate...... samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies. Copyright © 2015 John Wiley & Sons, Ltd....

  13. Synthesis of Novel Isoxazole-contained Analogues of Losartan

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A series of novel isoxazole-contained analogues of Losartan were designed and synthesized with 1,3-DC reaction. The regioselectivity of the reaction was discussed and the compounds are potential antihypertensive.

  14. A q-Analogue of the Dirichlet L-Function

    Institute of Scientific and Technical Information of China (English)

    Min-Soo Kim; Jin-Woo Son

    2002-01-01

    In this paper, we will treat some interesting formulae which are slightly different from Kim's results by more or less the same method in [4-9]. At first, we consider a new definition of a q-analogue of Bernoulli numbers and polynomials.We construct a q-analogue of the Riemann ζ-function, Hurwitz ζ-function, and Dirichlet L-series. Also, we investigate the relation between the q-analogue of generalized Bernoulli numbers and the generalized Euler numbers. As an application, we prove that the q-analogue of Bernoulli numbers occurs in the coefficients of some Stirling type series for the p-adic analytic q-log-gamma function.

  15. Current prodrug strategies for improving oral absorption of nucleoside analogues

    Directory of Open Access Journals (Sweden)

    Youxi Zhang

    2014-04-01

    Full Text Available Nucleoside analogues are first line chemotherapy in various severe diseases: AIDS (acquired immunodeficiency disease syndrome, cytomegalovirus infections, cancer, etc. However, many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability. In order to get around this drawback, prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug. Alternatively, prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues. Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1. The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport, but is readily degraded to the parent drug once at the target. This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.

  16. Trustworthiness and Influence: A Reexamination in an Extended Counseling Analogue.

    Science.gov (United States)

    Rothmeier, Rosemarie C.; Dixon, David N.

    1980-01-01

    The study demonstrated that: (1) interviewer trustworthiness can be manipulated in an analogue interview setting; and (2) interviewer trustworthiness is related to interpersonal influence in the interview setting. Findings follow a pattern of outcomes predicted by cognitive dissonance theory. (Author)

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

    Directory of Open Access Journals (Sweden)

    Silje Anda

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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).

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

    Science.gov (United States)

    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.

  1. Analogue Signal Processing: Collected Papers 1994-95

    DEFF Research Database (Denmark)

    1996-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995....

  2. Analogue Signal Processing: Collected Papers 1996-97

    DEFF Research Database (Denmark)

    1997-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of the Department of Information Technology, Technical University of Denmark, in 1996 and 1997.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of the Department of Information Technology, Technical University of Denmark, in 1996 and 1997....

  3. Analogue Signal Processing: Collected Papers 1994-95

    DEFF Research Database (Denmark)

    1996-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995....

  4. Analogue and digital linear modulation techniques for mobile satellite

    Science.gov (United States)

    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.

  5. An azumamide C analogue without the zinc-binding functionality

    DEFF Research Database (Denmark)

    Villadsen, Jesper; Kitir, Betül; Wich, Kathrine;

    2014-01-01

    + - coordinating moiety. Herein, we describe the synthesis of an azumamide analogue lacking its native Zn 2+ -binding group and evaluation of its inhibitory activity against recombinant human HDAC1 – 11. Furthermore, kinetic investigation of the inhibitory mechanism of both parent natural product and synthetic...... analogue against HDAC3-NCoR2 is reported as well as their activity against Burkitt's lymphoma cell proliferation....

  6. A new antiproliferative noscapine analogue: chemical synthesis and biological evaluation

    OpenAIRE

    Ghaly, Peter E.; Abou El-Magd, Rabab M.; Churchill, Cassandra D. M.; Tuszynski, Jack A.; West, F. G.

    2016-01-01

    Noscapine, a naturally occurring opium alkaloid, is a widely used antitussive medication. Noscapine has low toxicity and recently it was also found to possess cytotoxic activity which led to the development of many noscapine analogues. In this paper we report on the synthesis and testing of a novel noscapine analogue. Cytotoxicity was assessed by MTT colorimetric assay using SKBR-3 and paclitaxel-resistant SKBR-3 breast cancer cell lines using different concentrations for both noscapine and t...

  7. Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers

    Science.gov (United States)

    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

  8. Molecular Biodynamers: Dynamic Covalent Analogues of Biopolymers.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Sakilam Satishkumar

    2015-10-01

    Full Text Available 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-oxytris(dimethylaminophosphonium 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.

  11. Novel purine nucleoside analogues for hematological malignancies.

    Science.gov (United States)

    Korycka, Anna; Lech-Marańda, Ewa; Robak, Tadeusz

    2008-06-01

    Recently, the search for more effective and safer antineoplastic agents has led to synthesis and introduction into preclinical and clinical studies of a few new purine nucleoside analogues (PNA). Three of them: clofarabine (CAFdA), nelarabine, and forodesine (immucillin H, BCX-1777), despite belonging to the same group of drugs such as PNA, have shown some differences concerning their active forms, metabolic properties and mechanism of action. However, all these drugs have demonstrated promising activity in patients with relapsed and refractory acute lymphoblastic leukemia (ALL). CAFdA was approved for the therapy of relapsed or refractory ALL in the third line of treatment. It has proved promising in pediatric patients as well as in some patients who are able to proceed to allogenic hematopietic stem cell transplantation (HSCT). Moreover, the drug exhibits an efficacy in acute myeloid leukemia (AML), blast crisis of chronic myelogenous leukemia (CML-BP) and myelodysplastic syndrome (MDS). Nelarabine is recommended for T-ALL and T-cell lymphoblastic lymphoma (T-LBL) with the overall response rates ranging from 11 to 60%. However, the use of the drug is limited by potentially severe neurotoxicity. Forodesine is a purine nucleoside phosphorylase (PNP) inhibitor and it has shown activity in relapsed and refractory T- and B-cells leukemias as well as in cutaneous T-cell lymphoma (CTCL). Recently patented, a few of inventions in the field of pharmaceutical preparation of new PNA have also been published. Great hopes are currently set on the use of these drugs in the treatment of lymphoid and myeloid malignancies in adult and in pediatric patients, however ongoing studies will help to define their role in the standard therapy.

  12. Habitability & Astrobiology Research in Mars Terrestrial Analogues

    Science.gov (United States)

    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

  13. Role of PDI in regulating tissue factor: FVIIa activity.

    Science.gov (United States)

    Popescu, Narcis I; Lupu, Cristina; Lupu, Florea

    2010-04-01

    Cell exposed tissue factor (TF) is generally in a low procoagulant ("cryptic") state, and requires an activation step (decryption) to exhibit its full procoagulant potential. Recent data suggest that TF decryption may be regulated by the redox environment through the oxidoreductase activity of protein disulfide isomerase (PDI). In this article we review PDI contribution to different models of TF decryption, namely the disulfide switch model and the phosphatidylserine dynamics, and hypothesize on PDI contribution to TF self-association and association with lipid domains. Experimental evidence debate the disulfide switch model of TF decryption and its regulation by PDI. More recently we showed that PDI oxidoreductase activity regulates the phosphatidylserine equilibrium at the plasma membrane. Interestingly, PDI reductase activity could maintain TF in the reduced monomeric form, while also maintaining low exposure of PS, both states correlated with low procoagulant function. In contrast, PDI inhibition or oxidants may promote the adverse effects with a net increase in coagulation. The relative contribution of disulfide isomerization and PS exposure needs to be further analyzed to understand the redox control of TF procoagulant function. For the moment however TF regulation remains cryptic.

  14. Terrestrial research in Mars analogue environments

    Science.gov (United States)

    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

  15. Iron isotopes in an Archean ocean analogue

    Science.gov (United States)

    Busigny, Vincent; Planavsky, Noah J.; Jézéquel, Didier; Crowe, Sean; Louvat, Pascale; Moureau, Julien; Viollier, Eric; Lyons, Timothy W.

    2014-05-01

    Iron isotopes have been extensively used to trace the history of microbial metabolisms and the redox evolution of the oceans. Archean sedimentary rocks display greater variability in iron isotope ratios and more markedly negative values than those deposited in the Proterozoic and Phanerozoic. This increased variability has been linked to changes in either water column iron cycling or the extent of benthic microbial iron reduction through time. We tested these contrasting scenarios through a detailed study of anoxic and ferruginous Lac Pavin (France), which can serve as a modern analogue of the Archean ocean. A depth-profile in the water column of Lac Pavin shows a remarkable increase in dissolved Fe concentration (0.1-1200 μM) and δ56Fe values (-2.14‰ to +0.31‰) across the oxic-anoxic boundary to the lake bottom. The largest Fe isotope variability is found at the redox boundary and is related to partial oxidation of dissolved ferrous iron, leaving the residual Fe enriched in light isotopes. The analysis of four sediment cores collected along a lateral profile (one in the oxic layer, one at the redox boundary, one in the anoxic zone, and one at the bottom of the lake) indicates that bulk sediments, porewaters, and reactive Fe mostly have δ56Fe values near 0.0 ± 0.2‰, similar to detrital iron. In contrast, pyrite δ56Fe values in sub-chemocline cores (60, 65, and 92 m) are highly variable and show significant deviations from the detrital iron isotope composition (δ56Fepyrite between -1.51‰ and +0.09‰; average -0.93‰). Importantly, the pyrite δ56Fe values mirror the δ56Fe of dissolved iron at the redox boundary—where near quantitative sulfate and sulfide drawdown occurs—suggesting limited iron isotope fractionation during iron sulfide formation. This finding has important implications for the Archean environment. Specifically, this work suggests that in a ferruginous system, most of the Fe isotope variability observed in sedimentary pyrites can

  16. Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives.

    Science.gov (United States)

    Monte, A P; Waldman, S R; Marona-Lewicka, D; Wainscott, D B; Nelson, D L; Sanders-Bush, E; Nichols, D E

    1997-09-12

    hallucinogens, that such compounds must be full agonists at the 5-HT2A receptor subtype. In contrast to the 2,5-dimethoxy-substituted phenethylamines, where rigidification of the methoxy groups had no deleterious effect on activity, the loss of activity in the 3,4,5-trioxygenated mescaline analogues may suggest that the 3 and 5 methoxy groups must remain conformationally mobile to enable receptor activation.

  17. Incorporation of tryptophan analogues into the lantibiotic nisin.

    Science.gov (United States)

    Zhou, Liang; Shao, Jinfeng; Li, Qian; van Heel, Auke J; de Vries, Marcel P; Broos, Jaap; Kuipers, Oscar P

    2016-05-01

    Lantibiotics are posttranslationally modified peptides with efficient inhibitory activity against various Gram-positive bacteria. In addition to the original modifications, incorporation of non-canonical amino acids can render new properties and functions to lantibiotics. Nisin is the most studied lantibiotic and contains no tryptophan residues. In this study, a system was constructed to incorporate tryptophan analogues into nisin, which included the modification machinery (NisBTC) and the overexpression of tryptophanyl-tRNA synthetase (TrpRS). Tryptophan and three different tryptophan analogues (5-fluoroTrp (5FW), 5-hydroxyTrp (5HW) and 5-methylTrp (5MeW)) were successfully incorporated at four different positions of nisin (I1W, I4W, M17W and V32W). The incorporation efficiency of tryptophan analogues into mutants I1W, M17W and V32W was over 97 %, while the mutant I4W showed relatively low incorporation efficiency (69-93 %). The variants with 5FW showed relatively higher production yield, while 5MeW-containing variants showed the lowest yield. The dehydration efficiency of serines or threonines was affected by the tryptophan mutants of I4W and V32W. The affinity of the peptides for the cation-ion exchange and reverse phase chromatography columns was significantly reduced when 5HW was incorporated. The antimicrobial activity of IIW and its 5FW analogue both decreased two times compared to that of nisin, while that of its 5HW analogue decreased four times. The 5FW analogue of I4W also showed two times decreased activity than nisin. However, the mutant M17W and its 5HW analogue both showed 32 times reduced activity relative to that of nisin.

  18. Insulin analogues and cancer: a note of caution

    Directory of Open Access Journals (Sweden)

    Joseph A.M.J.L. eJanssen

    2014-05-01

    Full Text Available Abstract In view of the lifelong exposure and large patient populations involved, insulin analogues with an increased mitogenic effect in comparison to human insulin may potentially constitute a major health problem, since these analogues may possibly induce the growth of pre-existing neoplasms. At present, the available data suggest that insulin analogues are safe. In line with these findings, we observed that serum of diabetic patients treated with insulin analogues, compared to that of diabetic patients treated with human insulin, did not induce an increased phosphorylation of tyrosine residues of the insulin-like growth factor-I receptor (IGF-IR. However, the classical model of the IGF-IR signaling may be insufficient to explain (all mitogenic effects of insulin analogues since also non-canonical signaling pathways of the IGF-IR may play a major role in this respect. Although phosphorylation of tyrosine residues of the IGF-IR is generally considered to be the initial activation step within the intracellular IGF-IR signaling pathway, it has been found that cells undergo a signaling switch under hyperglycemic conditions. After this switch, a completely different mechanism is utilized to activate the mitogenic (mitogen-activated protein kinase (MAPK pathways of the IGF-IR that is independent from tyrosine phosphorylation of the IGF-IR. At present it is unknown whether activation of this alternative intracellular pathway of the IGF-IR occurs during hyperglycemia in vivo and whether it is stronger in patients treated with (some insulin analogues than in patients treated with human insulin. In addition, it is unknown whether the insulin receptors (IRs also undergo a signaling switch during hyperglycemia. This should be investigated in future studies. Finally, relative overexpression of IR isoform A (IR-A in (pre cancer tissues may play a key role in the development and progression of human cancers during treatment with insulin (analogues. Further

  19. MARKOV GRAPHS OF ONE–DIMENSIONAL DYNAMICAL SYSTEMS AND THEIR DISCRETE ANALOGUES AND THEIR DISCRETE ANALOGUES

    Directory of Open Access Journals (Sweden)

    SERGIY KOZERENKO

    2016-04-01

    Full Text Available One feature of the famous Sharkovsky’s theorem is that it can be proved using digraphs of a special type (the so–called Markov graphs. The most general definition assigns a Markov graph to every continuous map from the topological graph to itself. We show that this definition is too broad, i.e. every finite digraph can be viewed as a Markov graph of some one–dimensional dynamical system on a tree. We therefore consider discrete analogues of Markov graphs for vertex maps on combinatorial trees and characterize all maps on trees whose discrete Markov graphs are of the following types: complete, complete bipartite, the disjoint union of cycles, with every arc being a loop.

  20. Engineering of insulin receptor isoform-selective insulin analogues.

    Directory of Open Access Journals (Sweden)

    Tine Glendorf

    Full Text Available BACKGROUND: The insulin receptor (IR exists in two isoforms, A and B, and the isoform expression pattern is tissue-specific. The C-terminus of the insulin B chain is important for receptor binding and has been shown to contact the IR just adjacent to the region where the A and B isoforms differ. The aim of this study was to investigate the importance of the C-terminus of the B chain in IR isoform binding in order to explore the possibility of engineering tissue-specific/liver-specific insulin analogues. METHODOLOGY/PRINCIPAL FINDINGS: Insulin analogue libraries were constructed by total amino acid scanning mutagenesis. The relative binding affinities for the A and B isoform of the IR were determined by competition assays using scintillation proximity assay technology. Structural information was obtained by X-ray crystallography. Introduction of B25A or B25N mutations resulted in analogues with a 2-fold preference for the B compared to the A isoform, whereas the opposite was observed with a B25Y substitution. An acidic amino acid residue at position B27 caused an additional 2-fold selective increase in affinity for the receptor B isoform for analogues bearing a B25N mutation. Furthermore, the combination of B25H with either B27D or B27E also resulted in B isoform-preferential analogues (2-fold preference even though the corresponding single mutation analogues displayed no differences in relative isoform binding affinity. CONCLUSIONS/SIGNIFICANCE: We have discovered a new class of IR isoform-selective insulin analogues with 2-4-fold differences in relative binding affinities for either the A or the B isoform of the IR compared to human insulin. Our results demonstrate that a mutation at position B25 alone or in combination with a mutation at position B27 in the insulin molecule confers IR isoform selectivity. Isoform-preferential analogues may provide new opportunities for developing insulin analogues with improved clinical benefits.

  1. Central effects of angiotensin II, its fragment and analogues.

    Science.gov (United States)

    Georgiev, V P; Klousha, V E; Petkov, V D; Markovska, V L; Svirskis, S V; Mountsinietse, R K; Anouans, Z E

    1984-01-01

    The effects of the octapeptide angiotensin II (AT II), its fragment Ile8 AT3-8 and the analogues Sar1 Ala8 AT II, Ala8 AT II and Ile8 AT II were studied with respect to: the level of biogenic amines (DA, 5-HT and their metabolites HVA and 5-HIAA) in the forebrain; the behaviour of the animals--haloperidol catalepsy, apomorphine stereotypy, unconditioned jumping reaction (UJR), convulsive threshold. Good correlation was found between the biochemical and behavioural effects. The fragment of AT II where phenylalanine is substituted at the C-terminal by Ile reduces the haloperidol-increased content of HVA, potentiates apomorphine stereotypy and reduces catalepsy, whereas the AT II analogues (where the C-terminal phenylalanine is substituted by Ala, and the N-terminal--by Sar) potentiate the effect of haloperidol increasing the HVA content, reduce apomorphine stereotypy and potentiate catalepsy; saralasine independently applied induces brief catalepsy; AT II, its fragment and analogues inhibit UJR, in combination with amphetamine and PTZ this effect becomes deeper; the duration of hexobarbital sleep is increased. The peptides investigated increase the convulsive threshold. The results show that the hexapeptide fragment has preserved the effects of AT II, whereas in the analogues (with changed C- and N-terminals) they are changed. The results obtained may be explained with the modulating influence of AT II-receptors on the DA-ergic receptors in the brain structures with which AT II and its fragment and analogues enter in contact.

  2. Analogue earthquakes and seismic cycles: experimental modelling across timescales

    Science.gov (United States)

    Rosenau, Matthias; Corbi, Fabio; Dominguez, Stephane

    2017-05-01

    Earth deformation is a multi-scale process ranging from seconds (seismic deformation) to millions of years (tectonic deformation). Bridging short- and long-term deformation and developing seismotectonic models has been a challenge in experimental tectonics for more than a century. Since the formulation of Reid's elastic rebound theory 100 years ago, laboratory mechanical models combining frictional and elastic elements have been used to study the dynamics of earthquakes. In the last decade, with the advent of high-resolution monitoring techniques and new rock analogue materials, laboratory earthquake experiments have evolved from simple spring-slider models to scaled analogue models. This evolution was accomplished by advances in seismology and geodesy along with relatively frequent occurrences of large earthquakes in the past decade. This coincidence has significantly increased the quality and quantity of relevant observations in nature and triggered a new understanding of earthquake dynamics. We review here the developments in analogue earthquake modelling with a focus on those seismotectonic scale models that are directly comparable to observational data on short to long timescales. We lay out the basics of analogue modelling, namely scaling, materials and monitoring, as applied in seismotectonic modelling. An overview of applications highlights the contributions of analogue earthquake models in bridging timescales of observations including earthquake statistics, rupture dynamics, ground motion, and seismic-cycle deformation up to seismotectonic evolution.

  3. Controlled analogue experiments on propagation of seismic electromagnetic signals

    Institute of Scientific and Technical Information of China (English)

    HUANG Qinghua

    2005-01-01

    This study presented a method of laboratory analogue experiments based on a geographical scaling model and a waveguide model to investigate the characteristics of the propagation of seismic electromagnetic signals in the crust and the atmosphere. Some controlled experiments were done to evaluate the possible influence on the experimental results from the background electromagnetic field, geographical conditions, boundary effects, the source of electromagnetic signals (position, magnitude, and frequency), and media conductivity. The reliability and the extensibility of the above analogue experimental method were also investigated. This study indicated that such kind of analogue experimental method provided an intuitionistic way of studying the propagation of seismic electromagnetic signals, which is one of the most difficult research topics in seismo-electro- magnetism.

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

    Science.gov (United States)

    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.

  5. Synthesis and cytotoxic activities of semisynthetic zearalenone analogues.

    Science.gov (United States)

    Tadpetch, Kwanruthai; Kaewmee, Benyapa; Chantakaew, Kittisak; Kantee, Kawalee; Rukachaisirikul, Vatcharin; Phongpaichit, Souwalak

    2016-08-01

    Zearalenone is a β-resorcylic acid macrolide with various biological activities. Herein we report the synthesis and cytotoxic activities of 34 zearalenone analogues against human oral epidermoid carcinoma (KB) and human breast adenocarcinoma (MCF-7) cells as well as noncancerous Vero cells. Some zearalenone analogues showed moderately enhanced cytotoxic activities against the two cancer cell lines. We have discovered the potential lead compounds with diminished or no cytotoxicity to Vero cells. Preliminary structure-activity relationship studies revealed that the double bond at the 1' and 2' positions of zearalenone core was crucial for cytotoxic activities on both cell lines. In addition, for zearalenol analogues, the unprotected hydroxyl group at C-2 and an alkoxy substituent at C-4 played key roles on cytotoxic effects of both cell lines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Synthesis and Biological Evaluation of New (-)-Englerin Analogues.

    Science.gov (United States)

    López-Suárez, Laura; Riesgo, Lorena; Bravo, Fernando; Ransom, Tanya T; Beutler, John A; Echavarren, Antonio M

    2016-05-01

    We report the synthesis and biological evaluation of a series of (-)-englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth-inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC).

  7. Analogue peptides for the immunotherapy of human acute myeloid leukemia.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Synthesis and cytotoxic activity of novel curcumin analogues

    Institute of Scientific and Technical Information of China (English)

    Qin Zhang; Yao Fu; Hao Wei Wang; Tao Gong; Yong Qin; Zhi Rong Zhang

    2008-01-01

    Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues (1A-1C, 1E) with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.

  10. The Immucillins: Design, Synthesis and Application of Transition- State Analogues.

    Science.gov (United States)

    Evans, Gary B; Schramm, Vern L; Tyler, Peter C

    2015-01-01

    Transition-state analysis based on kinetic isotope effects and computational chemistry provides electrostatic potential maps to serve as blueprints for the design and chemical synthesis of transition-state analogues. The utility of these molecules is exemplified by potential clinical applications toward leukemia, autoimmune disorders, gout, solid tumors, bacterial quorum sensing and bacterial antibiotics. In some cases, transition-state analogues have chemical features that have allowed them to be repurposed for new indications, including potential antiviral use. Three compounds from this family have entered clinical trials. The transition-state analogues bind to their target proteins with high affinity and specificity. The physical and structural properties of binding teach valuable and often surprising lessons about the nature of tight-binding inhibitors.

  11. Ensemble meteorological reconstruction using circulation analogues of 1781–1785

    Directory of Open Access Journals (Sweden)

    P. Yiou

    2013-09-01

    Full Text Available This paper uses a method of atmospheric flow analogues to reconstruct an ensemble of atmospheric variables (namely sea-level pressure, surface temperature and wind speed between 1781 and 1785. The properties of this ensemble are investigated and tested against observations of temperature. The goal of the paper is to assess whether the atmospheric circulation during the Laki volcanic eruption (in 1783 and the subsequent winter were similar to the conditions that prevailed in the winter 2009/2010 and during spring 2010. We find that the three months following the Laki eruption in June 1783 barely have analogues in 2010. The cold winter of 1783/1784 yields circulation analogues in 2009/2010. Our analysis suggests that it is unlikely that the Laki eruption was responsible for the cold winter of 1783/1784, of the relatively short memory of the atmospheric circulation.

  12. Gold Nanoparticles Decorated with Mannose-6-phosphate Analogues

    Directory of Open Access Journals (Sweden)

    Stéphanie Combemale

    2014-01-01

    Full Text Available Herein, the preparation of neoglycoconjugates bearing mannose-6-phosphate analogues is described by: (a synthesis of a cyclic sulfate precursor to access the carbohydrate head-group by nucleophilic displacement with an appropriate nucleophile; (b introduction of spacers on the mannose-6-phosphate analogues via Huisgen’s cycloaddition, the Julia reaction, or the thiol-ene reaction under ultrasound activation. With the resulting compounds in hand, gold nanoparticles could be functionalized with various carbohydrate derivatives (glycoconjugates and then tested for angiogenic activity. It was observed that the length and flexibility of the spacer separating the sugar analogue from the nanoparticle have little influence on the biological response. One particular nanoparticle system substantially inhibits blood vessel growth in contrast to activation by the corresponding monomeric glycoconjugate, thereby demonstrating the importance of multivalency in angiogenic activity.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 =4.

  15. Analogue Kerr-like geometries in a MHD inflow

    CERN Document Server

    Noda, Sousuke; Takahashi, Masaaki

    2016-01-01

    We present a model of the analogue black hole in magnetohydrodynamic (MHD) flow. For a two dimensional axisymmetric stationary trans-magnetosonic inflow with a sink, using the dispersion relation of the MHD waves, we introduce the effective geometries for magnetoacoustic waves propagating in the MHD flow. Investigating the properties of the effective potentials for magnetoacoustic rays, we find that the effective geometries can be classified into five types which include analogue spacetimes of the Kerr black hole, ultra spinning stars with ergoregions and spinning stars without ergoregions. We address the effects of the magnetic pressure and the magnetic tension on each magnetoacoustic geometries.

  16. Naturally occurring crystalline phases: analogues for radioactive waste forms

    Energy Technology Data Exchange (ETDEWEB)

    Haaker, R.F.; Ewing, R.C.

    1981-01-01

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included.

  17. Synthesis and evaluation of heterocyclic analogues of bromoxynil.

    Science.gov (United States)

    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

  18. Five new discodermolide analogues from the marine sponge Discodermia species.

    Science.gov (United States)

    Gunasekera, Sarath P; Paul, Gopal K; Longley, Ross E; Isbrucker, Richard A; Pomponi, Shirley A

    2002-11-01

    Discodermolide (1) and five new discodermolide analogues trivially named 2-epi-discodermolide (2), 2-des-methyldiscodermolide (3), 5-hydroxymethyldiscodermolate (4), 19-des-aminocarbonyldiscodermolide (5), and 9(13)-cyclodiscodermolide (6) have been isolated from marine sponges belonging to the genus Discodermia collected from the Caribbean Sea. The isolation, structure elucidation, and biological activities of 2-6 are described. The natural analogues, which were isolated in trace amounts, exhibited significant variation of cytotoxicity against the cultured murine P-388 leukemia and A-549 human adenocarcinoma cells and suggested the importance of the C(7) through C(17) moiety for potency against cultured tumor cell lines.

  19. Synthesis of Novel 1,3-Dioxolane Nucleoside Analogues

    Institute of Scientific and Technical Information of China (English)

    蔡冬梅; 林昆华; 李明宗; 温集武; 李鸿艳; 尤田耙

    2004-01-01

    Novel 1,3-dioxolane C-nucleoside analogues of tiazofurin 2-(2-hydroxymethyl-1,3-dioxolan-4-yl)-1,3-thiazole-4-carboxamide as well as N-nucleoside analogues of substituted imidazoles 1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-4-nitroimidazole and 1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-4,5-dicyanoimidazole were synthesized frommethyl acrylate through a multistep procedure. Their structures were confirmed by IR, 1H NMR, 13C NMR spectra and elemental analysis.

  20. Analogue Building Blocks Based on Digital CMOS Gates

    DEFF Research Database (Denmark)

    Mucha, Igor

    1996-01-01

    Low-performance analogue circuits built of digital MOS gates are presented. Depending on the threshold voltages of the technology used the final circuits can be operated using low supply voltages. The main advantage using the proposed circuits is the simplicity and ultimate compatibility with the......Low-performance analogue circuits built of digital MOS gates are presented. Depending on the threshold voltages of the technology used the final circuits can be operated using low supply voltages. The main advantage using the proposed circuits is the simplicity and ultimate compatibility...

  1. Analogues of estradiol as potential breast tumor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, R.E.; Rzeszotarski, W.J.; Ferriera, N.L.; Jagoda, E.M.; Reba, R.C.; Eckelman, W.C.

    1984-01-01

    The radioiodinated analogue of estradiol, 11..beta..-methoxy-17..cap alpha..-(/sup 125/I)iodovinylestradiol (MIVE/sub 2/), has been shown to be a good candidate for the imaging of estrogen dependent breast tumors. Although there has been no extensive study on the sensitivity of radiotracers of this type, the authors have not observed localization of the radiotracer in metastatic lesions containing less than 20 fmole estrogen receptor/mg protein or in bone metasteses. In order to improve the sensitivity, they have examined several structural analogues of moxestrol (the parent structure for MIVE/sub 2/) for affinity to the ER isolated from immature rat uterus. The 11..beta..-ethyl analogue (EEE/sub 2/) of ethynyl estradiol (EE/sub 2/) exhibits the highest affinity with the 11..beta..-methyl analogue second best. Although the lipophilicity is also very high this compound should not be much more lipophilic than 16-iodoestradiol or MIVE/sub 2/ since the introduction of iodine increases the log P by greater than 1. The distribution of the tritiated derivative of EEE/sub 2/ is under study.

  2. Synthesis of pyrophosphonic acid analogues of farnesyl pyrophosphate

    NARCIS (Netherlands)

    Valentijn, A.R.P.M.; Berg, O. van den; Marel, G.A. van der; Cohen, L.H.; Boom, J.H. van

    1995-01-01

    The synthesis of four new analogues (i.e. 3-6) of farnesyl pyrophosphate (FPP), which may function as inhibitor of squalene synthase, is described. Compounds 3 and 4 were readily accessible by reaction of farnesal with diethyl phosphite or dimethyl lithiomethylphosphonate, respectively, followed by

  3. Simulated Milky Way analogues: implications for dark matter direct searches

    NARCIS (Netherlands)

    Bozorgnia, N.; Calore, F.; Schaller, M.; Lovell, M.; Bertone, G.; Frenk, C.S.; Crain, R.A.; Navarro, J.F.; Schaye, J.; Theuns, T.

    2016-01-01

    We study the implications of galaxy formation on dark matter direct detection using high resolution hydrodynamic simulations of Milky Way-like galaxies simulated within the EAGLE and APOSTLE projects. We identify Milky Way analogues that satisfy observational constraints on the Milky Way rotation

  4. Cytotoxicity of natural ginseng glycosides and semisynthetic analogues

    NARCIS (Netherlands)

    Atopkina, LN; Malinovskaya, GV; Elyakov, GB; Uvarova, NI; Woerdenbag, HJ; Koulman, A; Potier, P

    1999-01-01

    The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were ac

  5. Aromaticity in Polyacene Analogues of Inorganic Ring Compounds

    CERN Document Server

    Chattaraj, P K; Chattaraj, Pratim Kumar; Roy, Debesh Ranjan

    2006-01-01

    The aromaticity in the polyacene analogues of several inorganic ring compounds (BN-acenes, CN-acenes, BO-acenes and Na6-acenes) is reported here for the first time. Conceptual density functional theory based reactivity descriptors and the nucleus independent chemical shift (NICS) values are used in this analysis.

  6. Synthesis of 4” manipulated Lewis X trisaccharide analogues

    Directory of Open Access Journals (Sweden)

    Christopher J. Moore

    2012-07-01

    Full Text Available Three analogues of the Lex trisaccharide antigen (β-D-Galp(1→4[α-L-Fucp(1→3]-D-GlcNAcp in which the galactosyl residue is modified at O-4 as a methyloxy, deoxychloro or deoxyfluoro, were synthesized. We first report the preparation of the modified 4-OMe, 4-Cl and 4-F trichloroacetimidate galactosyl donors and then report their use in the glycosylation of an N-acetylglucosamine glycosyl acceptor. Thus, we observed that the reactivity of these donors towards the BF3·OEt2-promoted glycosylation at O-4 of the N-acetylglucosamine glycosyl acceptors followed the ranking 4-F > 4-OAc ≈ 4-OMe > 4-Cl. The resulting disaccharides were deprotected at O-3 of the glucosamine residue and fucosylated, giving access to the desired protected Lex analogues. One-step global deprotection (Na/NH3 of the protected 4”-methoxy analogue, and two-step deprotections (removal of a p-methoxybenzyl with DDQ, then Zemplén deacylation of the 4”-deoxychloro and 4”-deoxyfluoro protected Lex analogues gave the desired compounds in good yields.

  7. BlockLevel Bayesian Diagnosis of Analogue Electronic Circuits

    NARCIS (Netherlands)

    Krishnan, Shaji; Krishnan, Shaji; Kerkhoff, Hans G.; Doornbosch, Klaas D.; Brand, Rudi

    2010-01-01

    Daily experience with product designers, test and diagnosis engineers it is realized that the depth of interaction among them, ought to be high for successful diagnosis of analogue circuits. With this knowledge in mind, a responsibility was undertaken to choose a popular diagnostic method and define

  8. Design and Synthesis of Muramyl Dipeptide Cyclic Analogue

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A new conformationally restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our "Meshed-Bag Gathered-Bunch" method with a combination of Fmoc, allyl and N-1-(4,4-dimethyl-2,6-dioxocyclo-hexylidene)ethyl chemical protection strategy.

  9. Reproducibility along a 10 cm vertical visual analogue scale.

    OpenAIRE

    Dixon, J. S.; Bird, H A

    1981-01-01

    Reproducibility along a vertical 10 cm visual analogue scale (VAS) was investigated. Eight normal volunteers attempted to duplicate a set of marked VAS. There was a tendency to estimate too high on the scale, and reproducibility was found to be variable along its length. This indicates that the error involved in the use of VASs is even more complex than previously thought.

  10. Direct neutron decay of analogue resonances in 105Rh

    Institute of Scientific and Technical Information of China (English)

    Hu Bi-Tao; P.P.Zarubin; U.U.Juravlev

    2006-01-01

    A new method, while takes into account the contribution of direct neutron decay of analogue resonances to the isomeric ratio resulting from (p,n) reaction, is used to analyse the published experimental data for the reaction 104Ru(p,n)104Rh and also estimate a minimum probability of direct decay.

  11. A Macroscopic Analogue of the Nuclear Pairing Potential

    Science.gov (United States)

    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…

  12. Nucleic Acid Analogue Induced Transcription of Double Stranded DNA

    DEFF Research Database (Denmark)

    1998-01-01

    RNA is transcribed from a double stranded DNA template by forming a complex by hybridizing to the template at a desired transcription initiation site one or more oligonucleic acid analogues of the PNA type capable of forming a transcription initiation site with the DNA and exposing the complex...

  13. An Analysis of an Autoclitic Analogue in Pigeons

    Science.gov (United States)

    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…

  14. Combined treatment of somatostatin analogues with pegvisomant in acromegaly

    NARCIS (Netherlands)

    S.E. Franck (Sanne); A. Muhammad (Ammar); A-J. van der Lely (Aart-Jan); S.J.C.M.M. Neggers (Bas)

    2016-01-01

    textabstractTreatment of acromegaly with monotherapy long-acting somatostatin analogues (LA-SSA) as primary treatment or after neurosurgery can only achieve complete normalization of insulin-like growth factor I (IGF-I) in roughly 40 % of patients. Recently, one of the acromegaly consensus groups

  15. Combined treatment of somatostatin analogues with pegvisomant in acromegaly

    NARCIS (Netherlands)

    S.E. Franck; A. Muhammad; A-J. van der Lely (Aart-Jan); S.J.C.M.M. Neggers (Bas)

    2016-01-01

    textabstractTreatment of acromegaly with monotherapy long-acting somatostatin analogues (LA-SSA) as primary treatment or after neurosurgery can only achieve complete normalization of insulin-like growth factor I (IGF-I) in roughly 40 % of patients. Recently, one of the acromegaly consensus groups ha

  16. Are Structural Analogues to Bisphenol A Safe Alternatives?

    DEFF Research Database (Denmark)

    Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Mikael

    2014-01-01

    Background: Bisphenol A (BPA) is a chemical with widespread human exposure suspected of causing low-dose effects. Thus, a need for developing alternatives to BPA exists. Structural analogues of BPA have already been detected in foods and humans. Due to the structural analogy of the alternatives, ...

  17. Cytotoxicity of natural ginseng glycosides and semisynthetic analogues

    NARCIS (Netherlands)

    Atopkina, LN; Malinovskaya, GV; Elyakov, GB; Uvarova, NI; Woerdenbag, HJ; Koulman, A; Potier, P

    The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were

  18. A highly efficient synthesis of itraconazole intermediates and their analogues

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Chong Il; Myoung, Young Chan; Choi, Ha Young; Kim, Seung Jin [Agency for Technology and Standards, Gwacheon (Korea, Republic of)

    1999-12-01

    Itraconazole is an important drug for oral treatment of histoplasmosis and blastomycosis. Itraconazole has been the targets of many synthetic efforts due to their diverse antifungal activities. In this study, an efficient synthetic route for Itraconazole intermediates has been developed using new procedures. Also, Itraconazole analogues introducing 2- and 3-methoxy group instead of Itraconazole intermediates with 4-methoxy group were synthesized.

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

    Science.gov (United States)

    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, DNA interaction and antimicrobial activities of three rimantadine analogues

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bing-Mi; Zhang, Jun [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Wang, Xin, E-mail: wangxinlnu@163.com [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Zhang, Li-Ping; Liu, Yang [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Niu, Hua-Ying [Jinan Dachpharm Development Co., Ltd., Jinan 250100 (China); Liu, Bin, E-mail: liubinzehao@163.com [Department of Pharmacy, Liaoning University, Shenyang 110036 (China)

    2015-03-15

    The interactions of three rimantadine analogues (RAs) with calf thymus deoxyribonucleic acid (ct-DNA) in buffer solution (pH 7.4) were investigated using berberine (BR) as a probe by various methods. Fluorescence studies revealed that the RAs interacted with DNA in vitro and the quenchings were all static. Furthermore, the binding modes of these compounds to DNA were disclosed as groove binding supported by absorption spectroscopy, viscosity measurement and denatured DNA experiment. The antimicrobial activities of the RAs were also evaluated in Staphylococcus aureus and Escherichia coli, and they all exhibited good bacteriostasic effects. The results might provide an important reference for investigation of the molecular mechanism associated with the DNA binding of the RAs. - Highlights: • Three rimantadine analogues were synthesized. • The RAs effectively quenched the intrinsic fluorescence of DNA via a static combination. • These analogues can bind to DNA via groove binding mode. • The antimicrobial activities of three analogues were also evaluated by the disk diffusion method.

  1. Click-based synthesis and proteomic profiling of lipstatin analogues

    OpenAIRE

    Ngai, Mun H.; Yang, Peng-Yu; Liu, Kai; Shen, Yuan; Wenk, Markus R; Yao, Shao Q.; Lear, Martin J.

    2010-01-01

    Using click chemistry to enable both structural diversity and proteome profiling within a natural product derived library, two out of nineteen lipstatin analogues showed similar activity to Orlistat against fatty acid synthase (FAS), but with an improved ability to induce tumour cell death.

  2. Solution-phase synthesis of a muramyl dipeptide analogue MDA

    Institute of Scientific and Technical Information of China (English)

    Nan Zhao; Yao Ma; Gang Liu

    2011-01-01

    The solution-phase synthesis of a muramyl dipeptide (MDP) analogue of Nα- [4-chlorocinnamoyl-L-alanyl-D-isoglutaminyl]-L-lysine (MDA, 2) is reported that possesses the features of easy feasibility, safety and low cost in large scale of synthesis.

  3. Design and Synthesis of Muramyl Dipeptide Cyclic Analogue

    Institute of Scientific and Technical Information of China (English)

    SuoDeZHANG; GangLIU; 等

    2002-01-01

    A new conformationalloy restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our “Meshed-Bag Gathered-Bunch” method with a combination of Fmoc,ally and N-1-(4,4-dimethyl-2,6-dioxocyclo-hexylidene) ethyl chemical protection strategy.

  4. Charged Analogues of Henning Knutsen Type Solutions in General Relativity

    Science.gov (United States)

    Gupta, Y. K.; Kumar, Sachin; Pratibha

    2011-11-01

    In the present article, we have found charged analogues of Henning Knutsen's interior solutions which join smoothly to the Reissner-Nordstrom metric at the pressure free interface. The solutions are singularity free and analyzed numerically with respect to pressure, energy-density and charge-density in details. The solutions so obtained also present the generalization of A.L. Mehra's solutions.

  5. Synthesis of pyrophosphonic acid analogues of farnesyl pyrophosphate

    NARCIS (Netherlands)

    Valentijn, A.R.P.M.; Berg, O. van den; Marel, G.A. van der; Cohen, L.H.; Boom, J.H. van

    1995-01-01

    The synthesis of four new analogues (i.e. 3-6) of farnesyl pyrophosphate (FPP), which may function as inhibitor of squalene synthase, is described. Compounds 3 and 4 were readily accessible by reaction of farnesal with diethyl phosphite or dimethyl lithiomethylphosphonate, respectively, followed by

  6. The influence of no fault found in analogue CMOS circuits

    NARCIS (Netherlands)

    Wan, Jinbo; Kerkhoff, Hans G.

    2014-01-01

    The most difficult fault category in electronic systems is the “No Fault Found” (NFF). It is considered to be the most costly fault category in, for instance, avionics. The relatively few papers in this area rarely deal with analogue integrated systems. In this paper a simple simulation model has be

  7. Synthesis and Antioxidant Properties of Novel Silybin Analogues

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Eight novel silybin analogues (7a-h) were synthesized and their antioxidant properties including the capability of scavenging superoxide anion free radicals and the inhibitory effect on DPPH free radicals were determined. Several synthetic compounds showed comparable antioxidative effect to that of quercetin.

  8. Cytotoxicity of natural ginseng glycosides and semisynthetic analogues

    NARCIS (Netherlands)

    Atopkina, LN; Malinovskaya, GV; Elyakov, GB; Uvarova, NI; Woerdenbag, HJ; Koulman, A; Potier, P

    1999-01-01

    The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were ac

  9. Concise synthesis of new bridged-nicotine analogues

    DEFF Research Database (Denmark)

    Crestey, François; Hooyberghs, Geert; Kristensen, Jesper Langgaard

    2012-01-01

    This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively....

  10. Rubrene analogues with the aggregation-induced emission enhancement behaviour

    DEFF Research Database (Denmark)

    Zhang, Xiaoxu; Sørensen, Jakob Kryger; Fu, Xiaowei;

    2014-01-01

    In the light of the principle of aggregation-induced emission enhancement (AIEE), the rubrene analogue with orange light-emitting properties is designed and synthesized by substituting the phenyl side groups of rubrene with thienyl groups. To the best of our knowledge, this is the first report...

  11. Non-robust numerical simulations of analogue extension experiments

    Science.gov (United States)

    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

  12. Analogue Electrical Circuit for Simulation of the Duffing-Holmes Equation

    DEFF Research Database (Denmark)

    Tamaseviciute, E.; Tamasevicius, A.; Mykolaitis, G.

    2008-01-01

    An extremely simple second order analogue electrical circuit for simulating the two-well Duffing-Holmes mathematical oscillator is described. Numerical results and analogue electrical simulations are illustrated with the snapshots of chaotic waveforms, phase portraits (Lissajous figures...

  13. Synthesis and Characterization of the Tetrazole Analogues of α-Amino Acids

    Institute of Scientific and Technical Information of China (English)

    Yan Min HUO; Gen Hu LEI; Yin Mao WEI; Xiao Hui ZHENG

    2006-01-01

    The tetrazole analogues have been synthesized from fluorenylmethoxycarbonyl (Fmoc)protected amino acids by three steps. The structures of the analogues were characterized by HPLC-MS, 1H NMR and 13C NMR.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Alligator Rivers Analogue project. Application of scenario development method in evaluation of the Koongarra Analogue. Final Report - Volume 16

    Energy Technology Data Exchange (ETDEWEB)

    Skagius, K. [Kemakta Consultants co., Stockholm (Sweden); Wingefors, S. [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

    1992-12-31

    The study of natural analogues has been established as one of the most important methods for validation of concepts and models applied for the assessment of long-term performance of repositories for nuclear waste. The objectives of such studies range from detailed investigations of processes and features on a small scale to attempts of explaining the evolution of whole sites. For studies of specific processes it may well be as important to consider the larger scale settings as boundary conditions. This appreciation of context and an integrated view may be as important for evaluation of most natural analogues as for performance assessments. This is more evident the more the evaluation depends on a knowledge about the evolution of the natural analogue. The attempted formulation of scenarios of the Koongarra Analogue has been based on the external conditions and external features. A rapid weathering of the host rock, i.e. the chlorite schist, is assumed to have started around the onset of the Pleistocene Ice Age (ca 1.6 Ma BP). The eventual oxidation and mobilization of the uranium ore could then have occurred under unsaturated or saturated conditions. This leads to the following major scenarios: (1) Uranyl Phosphates formed under unsaturated conditions, with a periodical evolution of the dispersion fan in conjunction with alternating dry (glacial) and wet (interglacial) periods during the Pleistocene Ice Age; (2) Uranyl Phosphates formed under unsaturated conditions as a single event, taking place either early or late during the Pleistocene Ice Age; (3)Uranyl Phosphates formed under saturated conditions, in conjunction with periods of higher and lower flow due to the climatic cycling. Although the original objectives may not have been fully achieved, this work is believed to contribute to a better understanding of the Koongarra Analogue as well as to give a basis for further scenario work

  16. Phosphorylation of inositol 1,4,5-trisphosphate analogues by 3-kinase and dephosphorylation of inositol 1,3,4,5-tetrakisphosphate analogues by 5-phosphatase

    NARCIS (Netherlands)

    Dijken, Peter van; Lammers, Aleida A.; Ozaki, Shoichiro; Potter, Barry V.L.; Erneux, Christophe; Haastert, Peter J.M. van

    1994-01-01

    A series of P-32-labeled D-myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P-4] analogues was enzymically prepared from the corresponding D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] analogues using recombinant rat brain Ins(1,4,5)P-3 3-kinase and [gamma-P-32]ATP. Ins(1,4,5)P-3 analogues

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

    Science.gov (United States)

    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

  18. Synthesis and antioxidant activity of peptide-based ebselen analogues.

    Science.gov (United States)

    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.

  19. The analogue method for precipitation prediction: finding better analogue situations at a sub-daily time step

    Science.gov (United States)

    Horton, Pascal; Obled, Charles; Jaboyedoff, Michel

    2017-07-01

    Analogue methods (AMs) predict local weather variables (predictands) such as precipitation by means of a statistical relationship with predictors at a synoptic scale. The analogy is generally assessed on gradients of geopotential heights first to sample days with a similar atmospheric circulation. Other predictors such as moisture variables can also be added in a successive level of analogy. The search for candidate situations similar to a given target day is usually undertaken by comparing the state of the atmosphere at fixed hours of the day for both the target day and the candidate analogues. This is a consequence of using standard daily precipitation time series, which are available over longer periods than sub-daily data. However, it is unlikely for the best analogy to occur at the exact same hour for the target and candidate situations. A better analogue situation may be found with a time shift of several hours since a better fit can occur at different times of the day. In order to assess the potential for finding better analogues at a different hour, a moving time window (MTW) has been introduced. The MTW resulted in a better analogy in terms of the atmospheric circulation and showed improved values of the analogy criterion on the entire distribution of the extracted analogue dates. The improvement was found to increase with the analogue rank due to an accumulation of better analogues in the selection. A seasonal effect has also been identified, with larger improvements shown in winter than in summer. This may be attributed to stronger diurnal cycles in summer that favour predictors taken at the same hour for the target and analogue days. The impact of the MTW on the precipitation prediction skill has been assessed by means of a sub-daily precipitation series transformed into moving 24 h totals at 12, 6, and 3 h time steps. The prediction skill was improved by the MTW, as was the reliability of the prediction. Moreover, the improvements were greater for days

  20. New selenium-75 labeled radiopharmaceuticals: selenonium analogues of dopamine

    Energy Technology Data Exchange (ETDEWEB)

    Sadek, S.A.; Basmadjian, G.P.; Hsu, P.M.; Rieger, J.A.

    1983-07-01

    Selenium-75 labeled selenonium analogues of dopamine, (2-(3,4-dimethoxyphenyl)ethyl)dimethylselenonium iodide and its dihydroxy analogue, were prepared by reducing (/sup 75/Se)selenious acid with sodium borohydride at pH 6.0 and reacting the NaSeH produced with 1-(3,4-dimethoxyphenyl)-2-(p-toluenesulfonyloxy)ethane. Tissue distribution studies in rats given the /sup 75/Se-labeled selenonium agents intravenously demonstrated high initial heart uptake. Prolonged adrenal retention and high adrenal to blood ratio of compound 4 were observed. The high uptake and adrenal to blood ratio suggest the potential use of compound 4 as a radiopharmaceutical for the adrenal gland.

  1. The theory of Hawking radiation in laboratory analogues

    CERN Document Server

    Robertson, Scott

    2015-01-01

    Hawking radiation, despite being known to theoretical physics for nearly forty years, remains elusive and undetected. It also suffers, in its original context of gravitational black holes, from practical and conceptual difficulties. Of particular note is the trans-Planckian problem, which is concerned with the apparent origin of the radiation in absurdly high frequencies. In order to gain better theoretical understanding and, it is hoped, experimental verification of Hawking radiation, much study is being devoted to laboratory systems which use moving media to model the spacetime geometry of black holes, and which, by analogy, are also thought to emit Hawking radiation. These analogue systems typically exhibit dispersion, which regularizes the wave behaviour at the horizon at the cost of a more complicated theoretical framework. This tutorial serves as an introduction to Hawking radiation and its analogues, developing the moving medium analogy for black holes and demonstrating how dispersion can be incorporat...

  2. Basic entwinements: unassuming analogue inserts in basic digital modeling (courses)

    DEFF Research Database (Denmark)

    Wiesner, Thomas

    2012-01-01

    to diverse inter-active discussions and a more conscious re-plays of material transcending the dichotomies of digital/analogue. Keywords Simple didactics, analogue sketching, cognitive space awareness, digital modelling, bachelor first year, morphology of body and space, pataphysics...... of options for speedily produced material for various attuned and conscious, supplementary oblique architectural assessments. The simple procedure(s) advance a certain amount of beneficial cognitive complementarities: Beneficial interplay-changes between right and left brain concentrations; Change...... of tactility (whole hand gestures v/s mouse directed fixed “digits”); Fast production of simple material to re-assess various architectural spatial conditions; Fast toggling between scale/scaleless, conceptual-abstract/ and figurative/concrete; The fast exercises permit various interactive dealings, opening up...

  3. Noncommutative analogue Aharonov-Bohm effect and superresonance

    CERN Document Server

    Anacleto, M A; Passos, E

    2012-01-01

    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.

  4. Noncommutative analogue Aharonov-Bohm effect and superresonance

    Science.gov (United States)

    Anacleto, M. A.; Brito, F. A.; Passos, E.

    2013-06-01

    We consider the idea of modeling a rotating acoustic black hole by an idealized draining bathtub vortex which is a planar circulating flow phenomenon with a sink at the origin. We find the acoustic metric for this phenomenon from a noncommutative Abelian Higgs model. As such the acoustic metric not only describes a rotating acoustic black hole but also inherits the noncommutative characteristic of the spacetime. We address the issues of superresonance and analogue Aharonov-Bohm (AB) effect in this background. We mainly show that the scattering of planar waves by a draining bathtub vortex leads to a modified AB effect and due to spacetime noncommutativity, the phase shift persists even in the limit where the parameters associated with the circulation and draining vanish. Finally, we also find that the analogue AB effect and superresonance are competing phenomena at a noncommutative spacetime.

  5. Alligator rivers analogue project an OECD/NEA international project

    Energy Technology Data Exchange (ETDEWEB)

    Duerden, P.; Airey, P. [ANSTO, Menai (Australia); Pescatore, C. [OECD/NEA Issy-les-Moulineaux (France)

    1994-12-31

    The Koongarra uranium deposit in the Alligator Rivers Region of the Northern Territory of Australia was studied as a natural analogue of the far field behaviour of high level waste repositories following groundwater ingress. A number of mathematical modelling approaches were developed for processes as diverse as groundwater transport, host rock weathering, radionuclide sorption, evolution of the uranium dispersion fan and the distribution of uranium series nuclides between mineral assemblages in weathered host rock. Some of these models are relevant to performance assessment at the level of individual processes and subsystem performance. Through the project, new insights into the application of the natural analogue approach to the assessment of potential waste repository sites were obtained.

  6. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

    Energy Technology Data Exchange (ETDEWEB)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V. (Tulane Univ. School of Medicine, New Orleans, LA (USA))

    1989-08-01

    Metal complexes related to the cytotoxic complexes cisplatin (cis-diamminedichloroplatinum(II)) and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

  7. Acoustic clouds: standing sound waves around a black hole analogue

    CERN Document Server

    Benone, Carolina L; Herdeiro, Carlos; Radu, Eugen

    2014-01-01

    Under certain conditions sound waves in fluids experience an acoustic horizon with analogue properties to those of a black hole event horizon. In particular, a draining bathtub-like model can give rise to a rotating acoustic horizon and hence a rotating black hole (acoustic) analogue. We show that sound waves, when enclosed in a cylindrical cavity, can form stationary waves around such rotating acoustic black holes. These acoustic perturbations display similar properties to the scalar clouds that have been studied around Kerr and Kerr-Newman black holes; thus they are dubbed acoustic clouds. We make the comparison between scalar clouds around Kerr black holes and acoustic clouds around the draining bathtub explicit by studying also the properties of scalar clouds around Kerr black holes enclosed in a cavity. Acoustic clouds suggest the possibility of testing, experimentally, the existence and properties of black hole clouds, using analog models.

  8. Optical analogue of relativistic Dirac solitons in binary waveguide arrays

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Truong X., E-mail: truong.tran@mpl.mpg.de [Department of Physics, Le Quy Don University, 236 Hoang Quoc Viet str., 10000 Hanoi (Viet Nam); Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen (Germany); Longhi, Stefano [Department of Physics, Politecnico di Milano and Istituto di Fotonica e Nanotecnologie del Consiglio Nazionale delle Ricerche, Piazza L. da Vinci 32, I-20133 Milano (Italy); Biancalana, Fabio [Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen (Germany); School of Engineering and Physical Sciences, Heriot-Watt University, EH14 4AS Edinburgh (United Kingdom)

    2014-01-15

    We study analytically and numerically an optical analogue of Dirac solitons in binary waveguide arrays in the presence of Kerr nonlinearity. Pseudo-relativistic soliton solutions of the coupled-mode equations describing dynamics in the array are analytically derived. We demonstrate that with the found soliton solutions, the coupled mode equations can be converted into the nonlinear relativistic 1D Dirac equation. This paves the way for using binary waveguide arrays as a classical simulator of quantum nonlinear effects arising from the Dirac equation, something that is thought to be impossible to achieve in conventional (i.e. linear) quantum field theory. -- Highlights: •An optical analogue of Dirac solitons in nonlinear binary waveguide arrays is suggested. •Analytical solutions to pseudo-relativistic solitons are presented. •A correspondence of optical coupled-mode equations with the nonlinear relativistic Dirac equation is established.

  9. Analogue transformations in physics and their application to acoustics.

    Science.gov (United States)

    García-Meca, C; Carloni, S; Barceló, C; Jannes, G; Sánchez-Dehesa, J; Martínez, A

    2013-01-01

    Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation techniques to other branches of physics is often constrained by the structure of the field equations. We develop here a complete transformation method using the idea of analogue spacetimes. The method is general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an "analogue transformation acoustics" formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give explicit designs of a dynamic compressor, a spacetime cloak for acoustic waves and a carpet cloak for a moving aircraft.

  10. New Immunosuppressive Sphingoid Base and Ceramide Analogues in Wild Cordyceps.

    Science.gov (United States)

    Mi, Jia-Ning; Han, Yuwei; Xu, Yingqiong; Kou, Junping; Wang, Jing-Rong; Jiang, Zhi-Hong

    2016-12-14

    A comprehensive identification of sphingoid bases and ceramides in wild Cordyceps was performed by integrating a sequential chromatographic enrichment procedure and an UHPLC-ultrahigh definition-Q-TOF-MS based sphingolipidomic approach. A total of 43 sphingoid bases and 303 ceramides were identified from wild Cordyceps, including 12 new sphingoid base analogues and 159 new ceramide analogues based on high-resolution MS and MS/MS data, isotope distribution, matching with the comprehensive personal sphingolipid database, confirmation by sphingolipid standards and chromatographic retention time rule. The immunosuppressive bioassay results demonstrated that Cordyceps sphingoid base fraction exhibits more potent immunosuppressive activity than ceramide fraction, elucidating the immunosuppressive ingredients of wild Cordyceps. This study represented the most comprehensive identification of sphingoid bases and ceramides from a natural source. The findings of this study provided an insight into therapeutic application of wild Cordyceps.

  11. Anisotropic metamaterial as an analogue of a black hole

    Energy Technology Data Exchange (ETDEWEB)

    Fernández-Núñez, Isabel; Bulashenko, Oleg, E-mail: oleg.bulashenko@ub.edu

    2016-01-08

    Propagation of light in a metamaterial medium which mimics curved spacetime and acts like a black hole is studied. We show that for a particular type of spacetimes and wave polarization, the time dilation appears as dielectric permittivity, while the spatial curvature manifests as magnetic permeability. The optical analogue to the relativistic Hamiltonian which determines the ray paths (null geodesics) in the anisotropic metamaterial is obtained. By applying the formalism to the Schwarzschild metric, we compare the ray paths with full-wave simulations in the equivalent optical medium. - Highlights: • Optical analogue to the static anisotropic spacetime metric obeying rotational symmetries is studied. • Explicit expressions for the permittivity and permeability tensors are obtained. • Explicit expression for the optical Hamiltonian is found. • Ray paths are compared with full-wave simulations for the Schwarzschild metric in anisotropic and isotropic cases.

  12. Insulin analogues display atypical differentiative activities in skin keratinocytes.

    Science.gov (United States)

    Solomon Zemler, Ravid; Weingarten, Galina; Sarfstein, Rive; Laron, Zvi; Werner, Haim; Wertheimer, Efrat

    2015-02-01

    We have previously shown that both insulin and IGF1 lead to increased proliferation of keratinocytes. However, whereas insulin supports keratinocytes differentiation, IGF1 inhibits this process. The aim of the present study was to examine the proliferative and differentiative effects of insulin analogues (glargine, detemir, lispro and aspart) in primary keratinocytes in comparison with insulin and IGF1. Primary keratinocytes cultures were produced from newborn BALB/c mice skin. Proliferation rates were assessed by [(3)H]-thymidine incorporation and XTT assays and differentiation was evaluated by Western blots analysis. Insulin receptor and IGF1 receptor phosphorylation was assessed by immunoprecipitation assays. Treatment with glargine or detemir resulted in an insulin-like effect on the differentiation process whereas lispro and aspart treatment led to an IGF1-like effect. In addition, treatment of keratinocytes with aspart led to a rapid phosphorylation of the IGF1 receptor. Our study provides evidence that insulin analogues elicit atypical actions in the skin.

  13. Liquid Crystal Analogue of Abrikosov Vortex Flow in Superconductors

    CERN Document Server

    Tanaka, A; Hayakawa, R

    1996-01-01

    We extend the correspondence between the Renn-Lubensky Twist-Grain-Boundary-A phase in chiral liquid crystals and the Abrikosov mixed state in superconductors to dynamical aspects. We find that for a TGB sample with free boundaries, an external electric field applied along the helical axis induces a uniform translational motion of the grain boundary system - an analogue of the well-known mixed state flux flow. Likewise, an analogue of the mixed state Nernst effect is found. In much the same way in which the flux flow carries intercore electric fields generating Joule heat in an otherwise dissipation-free system, the grain boundary flow carries along polarized charges, resulting in a finite electric conductivity in a ferroelectric.

  14. Anti-cancer activities of diospyrin, its derivatives and analogues

    KAUST Repository

    Sagar, Sunil

    2010-09-01

    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  15. Tunneling approach and thermality in dispersive models of analogue gravity

    CERN Document Server

    Belgiorno, F; Piazza, F Dalla

    2014-01-01

    We set up a tunneling approach to the analogue Hawking effect in the case of models of analogue gravity which are affected by dispersive effects. An effective Schroedinger-like equation for the basic scattering phenomenon IN->P+N*, where IN is the incident mode, P is the positive norm reflected mode, and N* is the negative norm one, signalling particle creation, is derived, aimed to an approximate description of the phenomenon. Horizons and barrier penetration play manifestly a key-role in giving rise to pair-creation. The non-dispersive limit is also correctly recovered. Drawbacks of the model are also pointed out and a possible solution ad hoc is suggested.

  16. Modelling a river catchment using an electrical circuit analogue

    Directory of Open Access Journals (Sweden)

    C. G. Collier

    1998-01-01

    Full Text Available An electrical circuit analogue of a river catchment is described from which is derived an hydrological model of river flow called the River Electrical Water Analogue Research and Development (REWARD model. The model is based upon an analytic solution to the equation governing the flow of electricity in an inductance-capacitance-resistance (LCR circuit. An interpretation of L, C and R in terms of catchment parameters and physical processes is proposed, and tested for the River Irwell catchment in northwest England. Hydrograph characteristics evaluated using the model are compared with observed hydrographs, confirming that the modelling approach does provide a reliable framework within which to investigate the impact of variations in model input data.

  17. Analogue Wormholes and Black Hole LASER Effect in Hydrodynamics

    CERN Document Server

    Peloquin, Cédric; Philbin, Thomas; Rousseaux, Germain

    2015-01-01

    We numerically study water wave packets on a spatially varying counter-current in the presence of surface tension. Depending on the details of the velocity profile, we show that traversable and bi-directional analogue wormholes exist in fluid mechanics. The limitations on traversability of wormholes in general relativity are absent here because of the dispersion of water waves and the ability to form flow profiles that are not solutions of Einstein's equations. We observe that negative energy can be trapped between analogue horizons forming a LASER-like cavity. Six horizons are involved in the trapping cavity because of the existence of two dispersive scales, in contrast to previous treatments which considered two horizons and one dispersive scale.

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

    Science.gov (United States)

    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. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Neutral Diboron Analogues of Archetypal Aromatic Species by Spontaneous Cycloaddition.

    Science.gov (United States)

    Arrowsmith, Merle; Böhnke, Julian; Braunschweig, Holger; Celik, Mehmet Ali; Claes, Christina; Ewing, William C; Krummenacher, Ivo; Lubitz, Katharina; Schneider, Christoph

    2016-09-05

    Among the numerous routes organic chemists have developed to synthesize benzene derivatives and heteroaromatic compounds, transition-metal-catalyzed cycloaddition reactions are the most elegant. In contrast, cycloaddition reactions of heavier alkene and alkyne analogues, though limited in scope, proceed uncatalyzed. In this work we present the first spontaneous cycloaddition reactions of lighter alkene and alkyne analogues. Selective addition of unactivated alkynes to boron-boron multiple bonds under ambient conditions yielded diborocarbon equivalents of simple aromatic hydrocarbons, including the first neutral 6 π-aromatic diborabenzene compound, a 2 π-aromatic triplet biradical 1,3-diborete, and a phosphine-stabilized 2 π-homoaromatic 1,3-dihydro-1,3-diborete. DFT calculations suggest that all three compounds are aromatic and show frontier molecular orbitals matching those of the related aromatic hydrocarbons, C6 H6 and C4 H4 (2+) , and homoaromatic C4 H5 (+) .

  20. Basic entwinements: unassuming analogue inserts in basic digital modeling (courses)

    DEFF Research Database (Denmark)

    Wiesner, Thomas

    2012-01-01

    to diverse inter-active discussions and a more conscious re-plays of material transcending the dichotomies of digital/analogue. Keywords Simple didactics, analogue sketching, cognitive space awareness, digital modelling, bachelor first year, morphology of body and space, pataphysics...... between the various intentions and the student’s actual grasp of the many basic architectural element’s interplays of form and space can become apparent. To alleviate, calibrate and cognitively fine-tune the potential for more acute and lasting cognitive understandings of (scaled) body and space...... of options for speedily produced material for various attuned and conscious, supplementary oblique architectural assessments. The simple procedure(s) advance a certain amount of beneficial cognitive complementarities: Beneficial interplay-changes between right and left brain concentrations; Change...

  1. Matrices with restricted entries and q-analogues of permutations

    CERN Document Server

    Lewis, Joel Brewster; Morales, Alejandro H; Panova, Greta; Sam, Steven V; Zhang, Yan

    2010-01-01

    We study the functions that count matrices of given rank over a finite field with specified positions equal to zero. We show that these matrices are $q$-analogues of permutations with certain restricted values. We obtain a simple closed formula for the number of invertible matrices with zero diagonal, a $q$-analogue of derangements, and a curious relationship between invertible skew-symmetric matrices and invertible symmetric matrices with zero diagonal. In addition, we provide recursions to enumerate matrices and symmetric matrices with zero diagonal by rank, and we frame some of our results in the context of Lie theory. Finally, we provide a brief exposition of polynomiality results for enumeration questions related to those mentioned, and give several open questions.

  2. Stark absorption spectroscopy of peridinin and allene-modified analogues

    Energy Technology Data Exchange (ETDEWEB)

    Kusumoto, Toshiyuki; Horibe, Tomoko [Department of Physics and CREST-JST, Graduated School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Kajikawa, Takayuki; Hasegawa, Shinji [Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Gakuen 2-1, Sanda, Hyogo 669-1337 (Japan); Iwashita, Takashi [Suntory Institute for Bioorganic Research, Wakayamadai 1-1-1, Shimamoto, Mishimagunn, Osaka 618-8503 (Japan); Cogdell, Richard J. [Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8QQ, Scotland (United Kingdom); Birge, Robert R.; Frank, Harry A. [Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269-3060 (United States); Katsumura, Shigeo [Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Gakuen 2-1, Sanda, Hyogo 669-1337 (Japan); Hashimoto, Hideki, E-mail: hassy@sci.osaka-cu.ac.jp [Department of Physics and CREST-JST, Graduated School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan)

    2010-07-19

    Stark absorption spectra of peridinin (Per) and five allene-modified analogues and their angular dependence as a function of an externally applied electric field were measured in methyl methacrylate polymer at 77 K. In all cases, the energetically lowest absorption band has a significant change of static dipole-moment upon photoexcitation ({Delta}{mu}). In particular, Per has the largest value of |{Delta}{mu}|. The angles between {Delta}{mu} and the transition dipole-moment of all the analogues were determined. It is suggested that the allene group in Per plays a key role as the electron donor in the charge transfer process following photoexcitation. The results of MNDO-PSDCI calculations support this idea.

  3. Establishment of antenna membrane states FEM on analogue method

    Institute of Scientific and Technical Information of China (English)

    JIANG Wen-hui; CAO Xi-bin; ZHAO Yang

    2008-01-01

    On the basis of choosing the basic element as the bar and choosing the basic mesh as the triangle as well as supposing the conditions of the element,the membrane states of an antenna reflector were researched by the analogue method,because the membrane effect Was not omitted during the ending deployment process of the radial rib antenna.The expressions of the bar element's section area and density were obtained.while the expression of the stress state during the ending deployment process of antenna was attained.During the establishment process of the analogue method,the analysis method of the net shell structure was employed.Moreover,during the backward deduction of membrane stress,the continuation method Was adopted.Because the expression of the membrane stress state can realize the analysis on the antenna membrane state.this research has great significance of theoretical direction to the normal operation of the space deployable antenna.

  4. Geoscience in Support of a Mars Methane Analogue Mission

    Science.gov (United States)

    Boivin, Alexandre

    The Mars Methane Analogue Mission, funded by the Canadian Space Agency through its Analogue Missions program, simulates a Mars rover mission whose purpose is to detect, analyse, and determine the source of methane emissions on the planet's surface. As part of this project, both an electromagnetic induction sounder (EMIS) and a high-resolution triangulation-based 3D laser scanner were tested in the field to demonstrate the benefit of including these instruments on future rover missions. EMIS data was inverted in order to derive information on the conductivity and magnetic susceptibility of the near subsurface. 3D laser scanner data was processed with fracture detection as a goal in order to simplify the search for areas of potential methane seepage. Both instruments were found to be very valuable for future rover missions of this type.

  5. Some fluorescence properties of dimethylaminochalcone and its novel cyclic analogues

    Science.gov (United States)

    Tomečková, Vladimíra; Poškrobová, Martina; Štefanišinová, Miroslava; Perjési, Pál

    2009-12-01

    This paper demonstrates the basic character (polarity, solubility, colour, absorption and fluorescence quantum yield) of synthetic dimethylaminochalcone ( 1) and its cyclic analogues measured in toluene, chloroform, dimethylsulfoxide and ethanol, which have been studied by absorption and fluorescence spectroscopy. The biologically active dye 4'-dimethylaminochalcone ( 1b) and its less flexible analogues 4-dimethylaminoindanone ( 2b), -tetralone ( 3b), and -benzosuberone ( 4b) are lipophilic molecules that displayed the best solubility in toluene and chloroform. The highest fluorescence and quantum yields of compounds 1 and 2 have been obtained in DMSO and chloroform. Quenching effect of fluorescence compounds ( 1- 4) has been studied in the mixture of the most polar organic solvents DMSO and water. In the presence of water, fluorescence of compound 1 has been quenched the best from all studied chalcones and emission maxima of molecules 1- 4 have been shifted to the longer wavelengths. Quenching effect of fluorescence by water was in order 1 > 2 > 3 > 4.

  6. (18)F-labelled metomidate analogues as adrenocortical imaging agents.

    Science.gov (United States)

    Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Långström, Bengt

    2009-05-01

    Two- and one-step syntheses of (18)F-labelled analogues of metomidate, such as 2-[(18)F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[(18)F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[(18)F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[(18)F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[(18)F]fluoroethyl 4-methylbenzenesulfonate or 3-[(18)F]fluoropropyl 4-methylbenzenesulfonate. These were used as (18)F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46+/-3% and 79+/-30%, respectively. Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

  7. Analogue Square Root Calculator Circuit Designed With Logarithmic Amplifiers

    OpenAIRE

    2016-01-01

    In many applications, it has been necessary to calculate square roots of some numbers which are correspond to some voltages values. In this study such an analogue calculator has been designed and simulated in computer medium. Circuit consist of one logarithmic and one antilogarithmic amplifier connected in cascade. The component values of circuit chosen so that the output voltage of circuit is equal to square root of input voltage. The performance of designed circuit is investigated by applyi...

  8. Antimicrobial Activity of Xanthohumol and Its Selected Structural Analogues

    OpenAIRE

    Monika Stompor; Barbara Żarowska

    2016-01-01

    The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus). The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, fungi (Alternaria sp.), and yeasts (Rhodotorula rubra, Candida albicans) revealed that compounds with at least one hydroxyl group—...

  9. Synthesis of phosphonate and phostone analogues of ribose-1-phosphates

    Directory of Open Access Journals (Sweden)

    Pitak Nasomjai

    2009-07-01

    Full Text Available The synthesis of phosphonate analogues of ribose-1-phosphate and 5-fluoro-5-deoxyribose-1-phosphate is described. Preparations of both the α- and β-phosphonate anomers are reported for the ribose and 5-fluoro-5-deoxyribose series and a synthesis of the corresponding cyclic phostones of each α-ribose is also reported. These compounds have been prepared as tools to probe the details of fluorometabolism in S. cattleya.

  10. Synthesis of phosphonate and phostone analogues of ribose-1-phosphates.

    Science.gov (United States)

    Nasomjai, Pitak; O'Hagan, David; Slawin, Alexandra M Z

    2009-07-27

    The synthesis of phosphonate analogues of ribose-1-phosphate and 5-fluoro-5-deoxyribose-1-phosphate is described. Preparations of both the alpha- and beta-phosphonate anomers are reported for the ribose and 5-fluoro-5-deoxyribose series and a synthesis of the corresponding cyclic phostones of each alpha-ribose is also reported. These compounds have been prepared as tools to probe the details of fluorometabolism in S. cattleya.

  11. Projected Future Climate Analogues and Climate "Velocities" in North America

    Science.gov (United States)

    Shafer, S. L.; Bartlein, P. J.

    2014-12-01

    Future climate changes may have significant effects on many North American ecosystems. One way of assessing the potential impacts of future climate change is to use future climate analogues of present climate to evaluate the spatial extent and rates of future climate change. We used a set of Coupled Model Intercomparison Project phase 5 (CMIP5) coupled atmosphere-ocean general circulation model (AOGCM) future climate simulations (2006-2100) produced under representative concentration pathway scenario RCP8.5. We regridded these data to a 10-km equal-area grid of North America. Modern climate data (1961-1990 30-year mean) were interpolated to the same 10-km grid. The projected future climate data were analyzed using 10-year mean values of monthly and seasonal temperature and precipitation and a set of derived annual bioclimatic variables (e.g., growing degree days) considered to be ecologically significant. Potential future climate analogues were calculated for each grid cell using Euclidean distances to identify similar climates occurring elsewhere in North America. We identify regions that are projected to retain climates similar to present in the future (e.g., parts of the southeastern United States) and regions where present climates are projected to become less common or to disappear in the future (e.g., high elevation sites in western North America). We also calculate the rates of change in locations of similar climates (i.e., climate analogue velocities) and compare our results with simulated paleoclimate velocities over the past 22 kyr (from TraCE-21ka transient climate simulations for 22 ka-present). We discuss the implications of these results for conservation and natural resource management in North America. We also describe a web application being developed to allow researchers, decision makers, and members of the public, to visualize, explore, and use the climate analogue data.

  12. Combinatorial Solid-Phase Synthesis of Balanol Analogues

    DEFF Research Database (Denmark)

    Nielsen, John; Lyngsø, Lars Ole

    1996-01-01

    The natural product balanol has served as a template for the design and synthesis of a combinatorial library using solid-phase chemistry. Using a retrosynthetic analysis, the structural analogues have been assembled from three relatively accessible building blocks. The solid-phase chemistry inclu...... including MSNT-mediated esterification of both support-bound alcohols and carboxylic acids has been implemented successfully. Copyright (C) 1996 Elsevier Science Ltd....

  13. Combinatorial Solid-Phase Synthesis of Balanol Analogues

    DEFF Research Database (Denmark)

    Nielsen, John; Lyngsø, Lars Ole

    1996-01-01

    The natural product balanol has served as a template for the design and synthesis of a combinatorial library using solid-phase chemistry. Using a retrosynthetic analysis, the structural analogues have been assembled from three relatively accessible building blocks. The solid-phase chemistry inclu...... including MSNT-mediated esterification of both support-bound alcohols and carboxylic acids has been implemented successfully. Copyright (C) 1996 Elsevier Science Ltd....

  14. Differential membrane fluidization by active and inactive cannabinoid analogues.

    Science.gov (United States)

    Mavromoustakos, T; Papahatjis, D; Laggner, P

    2001-06-06

    The effects of the two cannabinomimetic drugs (-)-2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy-6H-dibenzo[b,d]pyranyl-2-(hexyl)-1,3-dithiolane (AMG-3) and its pharmacologically less active 1-methoxy analogue (AMG-18) on the thermotropic and structural properties of dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC) liposomes have been studied by X-ray diffraction and differential scanning calorimetry (DSC). DSC data revealed that the incorporation of the drugs affect differently the thermotropic properties of DPPC. The presence of the more active drug distinctly broadened and attenuated both the pretransition and main phase transition of DPPC bilayers, while the inactive analogue had only minor effects. Small and wide angle X-ray diffraction data showed that the two cannabinoids have different effects on the lipid phase structures and on the hydrocarbon chain packing. The pharmacologically active analogue, AMG-3, was found to efficiently fluidize domains of the lipids in the L(beta)' gel phase, and to perturb the regular multibilayer lattice. In the liquid crystalline L(alpha) phase, AMG-3 was also found to cause irregularities in packing, suggesting that the drug induces local curvature. At the same concentration, the inactive AMG-18 had only minor structural effects on the lipids. At about 10-fold or higher concentrations, AMG-18 was found to produce similar but still less pronounced effects in comparison to those observed by AMG-3. The dose-dependent, different thermotropic and structural effects by the two cannabinoid analogues suggest that these may be related to their biological activity.

  15. Ungeremine and Its hemisynthesized analogues as bactericides against Flavobacterium columnare.

    Science.gov (United States)

    Schrader, Kevin K; Avolio, Fabiana; Andolfi, Anna; Cimmino, Alessio; Evidente, Antonio

    2013-02-13

    The Gram-negative bacterium Flavobacterium columnare is the cause of columnaris disease, which can occur in channel catfish ( Ictalurus punctatus ). In a previous study, the betaine-type alkaloid ungeremine, 1, obtained from Pancratium maritimum L. was found to have strong antibacterial activity against F. columnare. In this study, analogues of 1 were evaluated using a rapid bioassay for activity against F. columnare to determine if the analogues might provide greater antibacterial activity and to determine structure-activity relationships of the test compounds. Several ungeremine analogues were prepared by hydrochlorination of the alkaloid and by selenium dioxide oxidation of both lycorine, 7, and pseudolycorine, 8, which yielded the isomer of ungeremine, 3, and zefbetaine, 4, respectively. The treatment of lycorine with phosphorus oxychloride allowed the synthesis of an anhydrolycorine lactam, 5, showing, with respect to 1, the deoxygenation and oxygenation of C-2 and C-7 of the C and B rings, respectively. The results of the structure-activity relationship studies showed that the aromatization of the C ring and the oxidation to an azomethine group of C-7 of the B ring are structural features important for antibacterial activity. In addition, the position of the oxygenation of the C ring as well as the presence of the 1,3-dioxole ring joined to the A ring of the pyrrolo[de]phenanthridine skeleton also plays a significant role in imparting antibacterial activity. On the basis of 24-h 50% inhibition concentration (IC(50)) results, ungeremine hydrochloride, 2, was similar in toxicity to 1, whereas 5 had the lowest activity. Analogue 2 is soluble in water, which may provide the benefit for use as an effective feed additive or therapeutant compared to ungeremine.

  16. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Melis, Marleen; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, V 220, Rotterdam (Netherlands); Boerman, Otto C. [Radboud University Hospital, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2010-05-15

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  17. Sums of multiplicative characters analogue of Kloosterman sums

    CERN Document Server

    Xi, Ping

    2010-01-01

    Let $q$ be a positive integer, $\\chi$ a nontrivial character mod $q$. In this paper the authors prove some estimates for the character sum which is analogue of incomplete Kloostermann sums\\[\\sum_{\\substack{a\\in\\mathcal{I}\\\\ \\gcd(a,q)=1}}\\chi(ma+n\\overline{a}),\\] where $\\overline{a}$ is the multiplicative inverse of $a\\bmod q$, and $\\mathcal{I}$ is a subinterval of $[x+1,x+q]$ for certain integer $x.$

  18. Active postoperative acromegaly: sustained remission after discontinuation of somatostatin analogues

    Science.gov (United States)

    Cardenas-Salas, Jersy

    2016-01-01

    Summary In patients with active acromegaly after pituitary surgery, somatostatin analogues are effective in controlling the disease and can even be curative in some cases. After treatment discontinuation, the likelihood of disease recurrence is high. However, a small subset of patients remains symptom-free after discontinuation, with normalized growth hormone (GH) and insulin-like growth factor (IGF1) levels. The characteristics of patients most likely to achieve sustained remission after treatment discontinuation are not well understood, although limited evidence suggests that sustained remission is more likely in patients with lower GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on an MRI scan and/or in patients who receive long-term treatment. In this report, we describe the case of a 56-year-old female patient treated with lanreotide Autogel for 11 years. Treatment was successfully discontinued, and the patient is currently disease-free on all relevant parameters (clinical, biochemical and tumour status). The successful outcome in this case adds to the small body of literature suggesting that some well-selected patients who receive long-term treatment with somatostatin analogues may achieve sustained remission. Learning points: The probability of disease recurrence is high after discontinuation of treatment with somatostatin analogues. Current data indicate that remission after treatment discontinuation may be more likely in patients with low GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on MRI, and/or in patients receiving prolonged treatment. This case report suggests that prolonged treatment with somatostatin analogues can be curative in carefully selected patients. PMID:27933171

  19. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2005-10-01

    Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

  20. Evaluation of anti-HIV-1 mutagenic nucleoside analogues.

    Science.gov (United States)

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-02

    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.

  1. 3D-QSAR Studies of Dimethoxyphenoxyphenoxy pyrimidines and Analogues

    Institute of Scientific and Technical Information of China (English)

    李爱秀; 王瑾玲; 苏华庆; 缪方明

    2000-01-01

    Three-dimensional quantitative structure-activity relationships (3DQSAR) of a series of dimethoxyphenoxyphenoxypyrimidines and analogues which are known to be photosystem Ⅱ (PS Ⅱ )inhibitors have been studied using comparative molecular field analysis (CoMFA) method. The results suggest that the steric and electronic properties of substitutes at m-position on the end phenyl ring have important influence on the Hill reaction inhibition.

  2. Do film soundtracks contain nonlinear analogues to influence emotion?

    OpenAIRE

    Daniel T. Blumstein; Davitian, Richard; Kaye, Peter D.

    2010-01-01

    A variety of vertebrates produce nonlinear vocalizations when they are under duress. By their very nature, vocalizations containing nonlinearities may sound harsh and are somewhat unpredictable; observations that are consistent with them being particularly evocative to those hearing them. We tested the hypothesis that humans capitalize on this seemingly widespread vertebrate response by creating nonlinear analogues in film soundtracks to evoke particular emotions. We used lists of highly rega...

  3. Dimerization and DNA recognition rules of mithramycin and its analogues.

    Science.gov (United States)

    Weidenbach, Stevi; Hou, Caixia; Chen, Jhong-Min; Tsodikov, Oleg V; Rohr, Jürgen

    2016-03-01

    The antineoplastic and antibiotic natural product mithramycin (MTM) is used against cancer-related hypercalcemia and, experimentally, against Ewing sarcoma and lung cancers. MTM exerts its cytotoxic effect by binding DNA as a divalent metal ion (Me(2+))-coordinated dimer and disrupting the function of transcription factors. A precise molecular mechanism of action of MTM, needed to develop MTM analogues selective against desired transcription factors, is lacking. Although it is known that MTM binds G/C-rich DNA, the exact DNA recognition rules that would allow one to map MTM binding sites remain incompletely understood. Towards this goal, we quantitatively investigated dimerization of MTM and several of its analogues, MTM SDK (for Short side chain, DiKeto), MTM SA-Trp (for Short side chain and Acid), MTM SA-Ala, and a biosynthetic precursor premithramycin B (PreMTM B), and measured the binding affinities of these molecules to DNA oligomers of different sequences and structural forms at physiological salt concentrations. We show that MTM and its analogues form stable dimers even in the absence of DNA. All molecules, except for PreMTM B, can bind DNA with the following rank order of affinities (strong to weak): MTM=MTM SDK>MTM SA-Trp>MTM SA-Ala. An X(G/C)(G/C)X motif, where X is any base, is necessary and sufficient for MTM binding to DNA, without a strong dependence on DNA conformation. These recognition rules will aid in mapping MTM sites across different promoters towards development of MTM analogues as useful anticancer agents.

  4. Matrix diffusion model. In situ tests using natural analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rasilainen, K. [VTT Energy, Espoo (Finland)

    1997-11-01

    Matrix diffusion is an important retarding and dispersing mechanism for substances carried by groundwater in fractured bedrock. Natural analogues provide, unlike laboratory or field experiments, a possibility to test the model of matrix diffusion in situ over long periods of time. This thesis documents quantitative model tests against in situ observations, done to support modelling of matrix diffusion in performance assessments of nuclear waste repositories. 98 refs. The thesis includes also eight previous publications by author.

  5. Spin Alignment in Analogues of The Local Sheet

    Science.gov (United States)

    Conidis, George J.

    2016-10-01

    Tidal torque theory and simulations of large scale structure predict spin vectors of massive galaxies should be coplanar with sheets in the cosmic web. Recently demonstrated, the giants (K s Torque Theory. However, the giants in the Local Sheet encircling the Local Group display a distinctly different arrangement, suggesting that the mass asymmetry of the Local Group or its progenitor torqued them from their primordial spin directions. To investigate the origin of the spin alignment of giants locally, analogues of the Local Sheet were identified in the SDSS DR9. Similar to the Local Sheet, analogues have an interacting pair of disk galaxies isolated from the remaining sheet members. Modified sheets in which there is no interacting pair of disk galaxies were identified as a control sample. Galaxies in face-on control sheets do not display axis ratios predominantly weighted toward low values, contrary to the expectation of tidal torque theory. For face-on and edge-on sheets, the distribution of axis ratios for galaxies in analogues is distinct from that in controls with a confidence of 97.6% & 96.9%, respectively. This corroborates the hypothesis that an interacting pair can affect spin directions of neighbouring galaxies.

  6. Natural analogue studies as supplements to biomineralization research

    Energy Technology Data Exchange (ETDEWEB)

    McNeil, M.B. [Nuclear Regulatory Commission, Washington, DC (United States)

    1995-09-01

    Chemical reactions can alter the chemistry and crystal structure of solid objects over archeological or geological times, while preserving external physical shapes. The reactions resulting in these structures offer natural analogues to laboratory experiments in biomineralization and to biologically influenced alteration of nuclear waste packages, and thus, they offer the only available way of validating models that purport waste package behavior over archaeological or geological times. Potential uses of such analogues in the construction and validation of hypothetical mechanisms of microbiological corrosion and biomineralization are reviewed. Evidence from such analogues suggests that biofilms can control materials alteration in ways usually overlooked. The newly hypothesized mechanisms involve control by biofilms of the cation flow near the solid surface and offer plausible mechanisms for the formation of mixed-cation minerals under conditions that would lead to dealloying in abiotic experiments; they also account for the formation of unusual minerals [such as posnjakite, Cu{sub 4}SO{sub 4}(OH){sub 6{center_dot}}H{sub 2}O] and mineral morphologies unusual in corrosion [malachite, Cu{sub 2}CO{sub 3}(OH){sub 2}, rarely forms botryoidally under corrosion conditions and its occasional presence on archaeological objects that appear to have undergone microbiological corrosion may be related to biofilm phenomena].

  7. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G. Saulnier and W. Statham

    2006-04-16

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. The Pena Blanca Natural Analogue Performance Assessment Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash-flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following analogous characteristics as compared to the Yucca Mountain repository site: (1) Analogous source--UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geology--(i.e. fractured, welded, and altered rhyolitic ash-flow tuffs); (3) Analogous climate--Semiarid to arid; (4) Analogous setting--Volcanic tuffs overlie carbonate rocks; and (5) Analogous geochemistry--Oxidizing conditions Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table.

  8. Simulated Milky Way analogues: implications for dark matter direct searches

    CERN Document Server

    Bozorgnia, Nassim; Schaller, Matthieu; Lovell, Mark; Bertone, Gianfranco; Frenk, Carlos S; Crain, Robert A; Navarro, Julio F; Schaye, Joop; Theuns, Tom

    2016-01-01

    We study the implications of galaxy formation on dark matter direct detection using high resolution hydrodynamic simulations of Milky Way-like galaxies simulated within the EAGLE and APOSTLE projects. We identify Milky Way analogues that satisfy observational constraints on the Milky Way rotation curve and total stellar mass. We then extract the dark matter density and velocity distribution in the Solar neighbourhood for this set of Milky Way analogues, and use them to analyse the results of current direct detection experiments. For most Milky Way analogues, the event rates in direct detection experiments obtained from the best fit Maxwellian distribution (with peak speed of 223 - 289 km/s) are similar to those obtained directly from the simulations. As a consequence, the allowed regions and exclusion limits set by direct detection experiments in the dark matter mass and spin-independent cross section plane shift by a few GeV compared to the Standard Halo Model, at low dark matter masses. For each dark matter...

  9. Four-quadrant analogue multiplier using operational amplifier

    Science.gov (United States)

    Riewruja, Vanchai; Rerkratn, Apinai

    2011-04-01

    A method to realise a four-quadrant analogue multiplier using general-purpose operational amplifiers (opamps) as only the active elements is described in this article. The realisation method is based on the quarter-square technique, which utilises the inherent square-law characteristic of class AB output stage of the opamp. The multiplier can be achieved from the proposed structure with using either bipolar or complementary metal-oxide-semiconductor (CMOS) opamps. The operation principle of the proposed multiplier has been confirmed by PSPICE analogue simulation program. Simulation results reveal that the principle of proposed scheme provides an adequate performance for a four-quadrant analogue multiplier. Experimental implementations of the proposed multiplier using bipolar and CMOS opamps are performed to verify the circuit performances. Measured results of the experimental proposed schemes based on the use of bipolar and CMOS opamps with supply voltage ±2.4 V show the worst-case relative errors of 0.32% and 0.47%, and the total harmonic distortions of 0.47% and 0.98%, respectively.

  10. Design and synthesis of biotin analogues reversibly binding with streptavidin.

    Science.gov (United States)

    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.

  11. The UVB1 Vitamin D analogue inhibits colorectal carcinoma progression.

    Science.gov (United States)

    Ferronato, María Julia; Alonso, Eliana Noelia; Gandini, Norberto Ariel; Fermento, María Eugenia; Villegas, María Emilia; Quevedo, Mario Alfredo; Arévalo, Julián; López Romero, Alejandro; Rivadulla, Marcos Lois; Gómez, Generosa; Fall, Yagamare; Facchinetti, María Marta; Curino, Alejandro Carlos

    2016-10-01

    Vitamin D has been shown to display a wide variety of antitumour effects, but their therapeutic use is limited by its severe side effects. We have designed and synthesized a Gemini vitamin D analogue of calcitriol (UVB1) which has shown to display antineoplastic effects on different cancer cell lines without causing hypercalcemia. The aim of this work has been to investigate, by employing in silico, in vitro, and in vivo assays, whether UVB1 inhibits human colorectal carcinoma progression. We demonstrated that UVB1 induces apoptotic cell death and retards cellular migration and invasion of HCT116 colorectal carcinoma cells. Moreover, the analogue reduced the tumour volume in vivo, and modulated the expression of Bax, E-cadherin and nuclear β-catenin in tumour animal tissues without producing toxic effects. In silico analysis showed that UVB1 exhibits greater affinity for the ligand binding domain of vitamin D receptor than calcitriol, and that several characteristics in the three-dimensional conformation of VDR may influence the biological effects. These results demonstrate that the Gemini vitamin D analogue affects the growth of the colorectal cancer and suggest that UVB1 is a potential chemotherapeutic agent for treatment of this disease.

  12. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis

    Directory of Open Access Journals (Sweden)

    Natalia M. Branis

    2015-01-01

    Full Text Available Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35–7.45, bicarbonate 16 mmol/L (22–29 mmol/L, and anion gap 19 mmol/L (8–16 mmol/L. Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  13. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis.

    Science.gov (United States)

    Branis, Natalia M; Wittlin, Steven D

    2015-01-01

    Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA) after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35-7.45), bicarbonate 16 mmol/L (22-29 mmol/L), and anion gap 19 mmol/L (8-16 mmol/L). Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA) availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  14. Antimicrobial evaluation of mangiferin and its synthesized analogues

    Institute of Scientific and Technical Information of China (English)

    Shashi Kant Singh; Rupali M Tiwari; Saurabh K Sinha; Chhanda C Danta; Satyendra K Prasad

    2012-01-01

    Objective: To isolate the mangiferin from Mangifera indica (M. indica) and assess the antimicrobial activity of different analogues synthesized from mangiferin. Methods: Mangiferin was isolated by column chromatography from the ethanolic extract of stem bark of M. indica. Mangiferin was further converted to 5-(N-phenylamino methyleno) mangiferin, 5-(N-p-chlorophenylamino methyleno) mangiferin, 5-(N-2-methyl phenylamino methyleno) mangiferin, 5-(N-p-methoxy phenylamino methyleno) mangiferin, 5-(N, N-diphenylamino methyleno) mangiferin, 5-(N-α-napthylamino methyleno) mangiferin and 5-(N-4-methyl phenylamino methyleno) mangiferin. Mangiferin and its analogues were characterized by melting point and Rf value determination and through spectral technique like UV, IR, and NMR spectral analysis. The antimicrobial effect of mangiferin and its derivatives was studied according to the disc diffusion method. Results: The solutions of mangiferin and its derivatives in polyethylene glycol-400 showed an activity with regard to four bacterial species-Bacillus pumilus (B. pumilus), Bacillus cereus (B. cereus) and Salmonella virchow (S. virchow) and two fungal species-Thermoascus (T. aurantiacus) and Aspergillus flavus (A. flavus). Conclusion: The present study aurantiacus confirms the antimicrobial activity of different analogues of mangiferin which could be further processed for the development of a potential antimicrobial agent.

  15. Do film soundtracks contain nonlinear analogues to influence emotion?

    Science.gov (United States)

    Blumstein, Daniel T; Davitian, Richard; Kaye, Peter D

    2010-12-23

    A variety of vertebrates produce nonlinear vocalizations when they are under duress. By their very nature, vocalizations containing nonlinearities may sound harsh and are somewhat unpredictable; observations that are consistent with them being particularly evocative to those hearing them. We tested the hypothesis that humans capitalize on this seemingly widespread vertebrate response by creating nonlinear analogues in film soundtracks to evoke particular emotions. We used lists of highly regarded films to generate a set of highly ranked action/adventure, dramatic, horror and war films. We then scored the presence of a variety of nonlinear analogues in these film soundtracks. Dramatic films suppressed noise of all types, contained more abrupt frequency transitions and musical sidebands, and fewer noisy screams than expected. Horror films suppressed abrupt frequency transitions and musical sidebands, but had more non-musical sidebands, and noisy screams than expected. Adventure films had more male screams than expected. Together, our results suggest that film-makers manipulate sounds to create nonlinear analogues in order to manipulate our emotional responses.

  16. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G.J. Saulnier Jr; W. Statham

    2006-03-10

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 {+-} 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory

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

    Science.gov (United States)

    Koyi, Hemin

    2015-04-01

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

  18. Mechanical behaviour of granular materials used in analogue modelling: insights from grain characterisation, ring-shear tests and analogue experiments

    Science.gov (United States)

    Panien, Marion; Schreurs, Guido; Pfiffner, Adrian

    2006-09-01

    The mechanical behaviour of several dry granular materials is investigated through ring-shear tests, grain characterisation, and simple analogue experiments analysed by X-ray computed tomography. An improved knowledge of granular materials is essential to determine their suitability as analogues for upper crustal rocks in experimental models and to compare analogue and numerical experiments. The ring-shear tests show that the granular materials have an elastic/frictional plastic behaviour with strain-hardening preceding failure at peak strength, followed by strain softening until a dynamic-stable value is reached. This is similar to the behaviour exhibited by experimentally deformed rocks. The physical characteristics of the grains determine the amount of diffuse deformation before failure, the percentage of strain softening and act on the thickness of the shear zones before broadening. Initial shear zone width in extensional and contractional experiments is between 11 and 16 times the mean grain size. The angle of internal friction defining one of the mechanical properties of granular materials and thus fault dip is not only related to physical characteristics of the grains and to the handling technique used (e.g. sieving or pouring), but also to the overburden and to the experimental setup used.

  19. Quantitative comparisons of analogue models of brittle wedge dynamics

    Science.gov (United States)

    Schreurs, Guido

    2010-05-01

    Analogue model experiments are widely used to gain insights into the evolution of geological structures. In this study, we present a direct comparison of experimental results of 14 analogue modelling laboratories using prescribed set-ups. A quantitative analysis of the results will document the variability among models and will allow an appraisal of reproducibility and limits of interpretation. This has direct implications for comparisons between structures in analogue models and natural field examples. All laboratories used the same frictional analogue materials (quartz and corundum sand) and prescribed model-building techniques (sieving and levelling). Although each laboratory used its own experimental apparatus, the same type of self-adhesive foil was used to cover the base and all the walls of the experimental apparatus in order to guarantee identical boundary conditions (i.e. identical shear stresses at the base and walls). Three experimental set-ups using only brittle frictional materials were examined. In each of the three set-ups the model was shortened by a vertical wall, which moved with respect to the fixed base and the three remaining sidewalls. The minimum width of the model (dimension parallel to mobile wall) was also prescribed. In the first experimental set-up, a quartz sand wedge with a surface slope of ˜20° was pushed by a mobile wall. All models conformed to the critical taper theory, maintained a stable surface slope and did not show internal deformation. In the next two experimental set-ups, a horizontal sand pack consisting of alternating quartz sand and corundum sand layers was shortened from one side by the mobile wall. In one of the set-ups a thin rigid sheet covered part of the model base and was attached to the mobile wall (i.e. a basal velocity discontinuity distant from the mobile wall). In the other set-up a basal rigid sheet was absent and the basal velocity discontinuity was located at the mobile wall. In both types of experiments

  20. Properties of granular analogue model materials: A community wide survey

    Science.gov (United States)

    Klinkmüller, M.; Schreurs, G.; Rosenau, M.; Kemnitz, H.

    2016-08-01

    We report the material properties of 26 granular analogue materials used in 14 analogue modelling laboratories. We determined physical characteristics such as bulk density, grain size distribution, and grain shape, and performed ring shear tests to determine friction angles and cohesion, and uniaxial compression tests to evaluate the compaction behaviour. Mean grain size of the materials varied between c. 100 and 400 μm. Analysis of grain shape factors shows that the four different classes of granular materials (14 quartz sands, 5 dyed quartz sands, 4 heavy mineral sands and 3 size fractions of glass beads) can be broadly divided into two groups consisting of 12 angular and 14 rounded materials. Grain shape has an influence on friction angles, with most angular materials having higher internal friction angles (between c. 35° and 40°) than rounded materials, whereas well-rounded glass beads have the lowest internal friction angles (between c. 25° and 30°). We interpret this as an effect of intergranular sliding versus rolling. Most angular materials have also higher basal friction angles (tested for a specific foil) than more rounded materials, suggesting that angular grains scratch and wear the foil. Most materials have an internal cohesion in the order of 20-100 Pa except for well-rounded glass beads, which show a trend towards a quasi-cohesionless (C < 20 Pa) Coulomb-type material. The uniaxial confined compression tests reveal that rounded grains generally show less compaction than angular grains. We interpret this to be related to the initial packing density after sifting, which is higher for rounded grains than for angular grains. Ring-shear test data show that angular grains undergo a longer strain-hardening phase than more rounded materials. This might explain why analogue models consisting of angular grains accommodate deformation in a more distributed manner prior to strain localisation than models consisting of rounded grains.

  1. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

    Directory of Open Access Journals (Sweden)

    Kinga Majchrzak

    Full Text Available BACKGROUND: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6 on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. RESULTS: OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6 disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6 were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs

  2. Radio-protective effect of some new curcumin analogues.

    Science.gov (United States)

    El-Gazzar, Marwa G; Zaher, Nashwa H; El-Hossary, Ebaa M; Ismail, Amel F M

    2016-09-01

    In the present study, novel symmetrical curcumin analogues (2-7) have been synthesized by substituting the phenolic OH of curcumin with different linkers providing additional keto-enol tautomerism, very essential for radioprotective activity. The structures of the synthesized compounds (2-7) were elucidated by elemental analysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data and were found consistent with the assigned structures. The curative effect of these new compounds, against the oxidative stress due to exposure of rats to the whole body γ-irradiation (7Gy) was investigated. Gamma-irradiated rats exhibited elevations of ALT, AST activities, urea, creatinine, triglycerides, total cholesterol, malondialdehyde (MDA), nitric oxide (NO), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Nuclear Factor-kappa B (NF-κB) levels. Contrariwise, the total protein, albumin, total calcium level, SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Treatment of gamma-irradiated rats with the new curcumin analogues (2-7) showed significant amelioration in the in-vivo antioxidant status, liver and kidney functions, as well as the anti-inflammatory markers (IL-6, TNF-α and NF-κB). Inhibition of NF-κB could be responsible for the improvement of the antioxidant and anti-inflammatory status in gamma-irradiated animals, by down-regulation of IL-1β and TNF-α level. In conclusion, the new curcumin analogues (2-7) exhibited post-protective effect on gamma-irradiation, by NF-κB inhibition.

  3. Quinazoline antifolates inhibiting thymidylate synthase: 4-thio-substituted analogues.

    Science.gov (United States)

    Thornton, T J; Jones, T R; Jackman, A L; Flinn, A; O'Connor, B M; Warner, P; Calvert, A H

    1991-03-01

    We report the synthesis of four new 4-thio-5,8-dideazafolic acid analogues and a 4-(methylthio) analogue structurally related to the thymidylate synthase (TS) inhibitor N10-propargyl-5,8-dideazafolic acid. Three N10-propargyl-4-thio-5,8-dideazafolic acid analogues had C2 amino, hydrogen, and methyl substituents. A 4-thio and a 4-(methylthio) compound each with hydrogen at C2 and ethyl at N10 were also synthesized. In general, the synthetic route involved thionation of the appropriate 4-oxoquinazoline; the sulfur thus introduced was then protected by methylation. Further protection with a pivaloyl group was required for the quinazoline bearing a 2-amino substituent. The protected quinazolines were treated with N-bromosuccinimide and the resulting 6-(bromomethyl) compounds were then coupled to the appropriate N-monoalkylated diethyl N-(4-aminobenzoyl)-L-glutamate in N,N-dimethylacetamide with calcium carbonate as base. The 4-thio-5,8-dideazafolic acids were obtained by removal of the methylthio group with sodium hydrosulfide, followed by deprotection of the carboxyl groups with cold dilute alkali. For the compound containing a pivaloyl protecting group, hot dilute alkali was used. To obtain the 5,8-dideazafolic acid containing a 4-(methylthio) substituent, the corresponding diester was treated with lithium hydroxide which selectively deprotected the carboxyl groups. The five compounds were tested as inhibitors of L1210 TS. It was found that replacement of the 4-oxygen of the quinazoline moiety by sulfur did not alter the TS inhibition. However, the introduction of a methylthio substituent at position 4 severely impaired TS inhibition. All 4-thio compounds were less cytotoxic to L1210 cells in culture than their 4-oxo counterparts.

  4. Stimulated Raman adiabatic passage analogues in classical physics

    Energy Technology Data Exchange (ETDEWEB)

    Rangelov, A A [University of Kassel, Heinrich-Plett-Str. 40, D-34132 Kassel (Germany); Vitanov, N V [Department of Physics, Sofia University, James Bourchier 5 blvd., 1164 Sofia (Bulgaria); Shore, B W [618 Escondido Cir., Livermore, CA (United States)

    2009-03-14

    Stimulated Raman adiabatic passage (STIRAP) is a well-established technique for producing coherent population transfer in a three-state quantum system. We here exploit the resemblance between the Schroedinger equation for such a quantum system and the Newton equation of motion for a classical system undergoing torque to discuss several classical analogues of STIRAP, notably the motion of a moving charged particle subject to the Lorentz force of a quasistatic magnetic field, the orientation of a magnetic moment in a slowly varying magnetic field and the Coriolis effect. Like STIRAP, these phenomena occur for counterintuitive motion of the torque and are robustly insensitive to small changes in the interaction properties.

  5. Towards bottom-up nanopatterning of Prussian blue analogues

    Directory of Open Access Journals (Sweden)

    Virgile Trannoy

    2014-10-01

    Full Text Available Ordered nanoperforated TiO2 monolayers fabricated through sol–gel chemistry were used to grow isolated particles of Prussian blue analogues (PBA. The elaboration of the TiO2/CoFe PBA nanocomposites involves five steps. The samples were characterized by scanning electron microscopy (SEM, atomic force microscopy (AFM, infrared spectroscopy and X-ray photoelectron spectroscopy (XPS all along the synthesis process. Selected physico-chemical parameters have been varied in order to determine the key steps of the synthesis process and to optimize it. This study is an important step towards the full control of the fabrication process.

  6. Pena Blanca Natural Analogue Project: Summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, S.; Goldstein, S.; Dobson, P.F.; Goodell, P.; Ku, T.-L.; Abdel-Fattah, A.; Saulnier, G.; Fayek, M.; de la Garza, R.

    2011-02-01

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill cores. Data from site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  7. Application of FPGA's in Flexible Analogue Electronic Image Generator Design

    Directory of Open Access Journals (Sweden)

    Peter Kulla

    2006-01-01

    Full Text Available This paper focuses on usage of the FPGAs (Field Programmable Gate Arrays Xilinx as a part of our more complex workdedicated to design of flexible analogue electronic images generator for application in TV measurement technique or/and TV servicetechnique or/and education process. The FPGAs performs here the role of component colour R, G, B, synchronization and blanking signals source. These signals are next processed and amplified in other parts of the generator as NTSC/PAL source encoder and RF modulator. The main aim of this paper is to show the possibilities how with suitable development software use a FPGAs in analog TV technology.

  8. Are structural analogues to bisphenol A a safe alternative?

    DEFF Research Database (Denmark)

    Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Gitte Alsing

    2013-01-01

    Bisphenol A (BPA) is often used in polycarbonate plastics, coatings of food and drink cans, and in thermal papers. Foods are thought to be a major human exposure route and human biomonitoring data suggest widespread exposure. BPA is suspected of contributing to effects such as increased birth...... weight, behavioral changes in children, cardiovascular disease, and diabetes. Regulatory initiatives and increased public awareness, related to the potential adverse effects of BPA, has led to an incitement to find alternative compounds. Structural analogues of BPA are available on the market, some...

  9. Synthesis, preliminary bioevaluation and computational analysis of caffeic acid analogues.

    Science.gov (United States)

    Liu, Zhiqian; Fu, Jianjun; Shan, Lei; Sun, Qingyan; Zhang, Weidong

    2014-05-16

    A series of caffeic acid amides were designed, synthesized and evaluated for anti-inflammatory activity. Most of them exhibited promising anti-inflammatory activity against nitric oxide (NO) generation in murine macrophage RAW264.7 cells. A 3D pharmacophore model was created based on the biological results for further structural optimization. Moreover, predication of the potential targets was also carried out by the PharmMapper server. These amide analogues represent a promising class of anti-inflammatory scaffold for further exploration and target identification.

  10. Pena blanca natural analogue project: summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Schon S [Los Alamos National Laboratory; Goldstein, Steven J [Los Alamos National Laboratory; Abdel - Fattah, Amr I [Los Alamos National Laboratory

    2010-12-08

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill core. Datafrom site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  11. [Visual analogue scale for measuring post-operative pain].

    Science.gov (United States)

    Rauh, Katja Halladin; Andersen, Rikke Søby; Rosenberg, Jacob

    2013-06-10

    All patients with pain who are admitted to hospitals in Denmark must be assessed for levels of pain. However, it is not certain how pain should be measured. One way to measure pain is to use a visual analogue scale (VAS). This article focuses on how the VAS should be used in clinical practice in the assessment of post-operative pain. Furthermore, other suitable methods are compared with VAS. VAS is particularly useful for clinical research, but for daily clinical practice it may be easier to use a numeric rating scale.

  12. Captopril analogues as metallo-β-lactamase inhibitors.

    Science.gov (United States)

    Yusof, Yusralina; Tan, Daniel T C; Arjomandi, Omid Khalili; Schenk, Gerhard; McGeary, Ross P

    2016-03-15

    A number of captopril analogues were synthesised and tested as inhibitors of the metallo-β-lactamase IMP-1. Structure-activity studies showed that the methyl group was unimportant for activity, and that the potencies of these inhibitors could be best improved by shortening the length of the mercaptoalkanoyl side-chain. Replacing the thiol group with a carboxylic acid led to complete loss of activity, and extending the length of the carboxylate group led to decreased potency. Good activity could be maintained by substituting the proline ring with pipecolic acid. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Stimulated emission in black holes and in analogue gravity

    Science.gov (United States)

    Belgiorno, F.; Cacciatori, S. L.

    2016-11-01

    Stimulated emission by black holes is discussed in light of the analogue gravity program. We first consider initial quantum states containing a definite number of particles, and then we take into account the case where the initial state is a coherent state. The latter case is particularly significant in the case where Hawking radiation is studied in dielectric black holes, and the emission is stimulated by a laser probe. We are particularly interested in the case of the electromagnetic field, for which examples of stimulated radiation are considered.

  14. The Canadian space agency planetary analogue materials suite

    Science.gov (United States)

    Cloutis, Edward A.; Mann, Paul; Izawa, Matthew R. M.; Applin, Daniel M.; Samson, Claire; Kruzelecky, Roman; Glotch, Timothy D.; Mertzman, Stanley A.; Mertzman, Karen R.; Haltigin, Timothy W.; Fry, Christopher

    2015-12-01

    The Canadian Space Agency (CSA) recently commissioned the development of a suite of over fifty well-characterized planetary analogue materials. These materials are terrestrial rocks and minerals that are similar to those known or suspected to occur on the lunar or martian surfaces. These include: Mars analogue sedimentary, hydrothermal, igneous and low-temperature alteration rock suites; lunar analogue basaltic and anorthositic rock suites; and a generic impactite rock suite from a variety of terrestrial impact structures. Representative thin sections of the materials have been characterized by optical microscopy and electron probe microanalysis (EPMA). Reflectance spectra have been collected in the ultraviolet, visible, near-infrared and mid-infrared, covering 0.2-25 μm. Thermal infrared emission spectra were collected from 5 to 50 μm. Raman spectra with 532 nm excitation, and laser-induced fluorescence spectra with 405 nm excitation were also measured. Bulk chemical analysis was carried out using X-ray fluorescence, with Fe valence determined by wet chemistry. Chemical and mineralogical data were collected using a field-portable Terra XRD-XRF instrument similar to CheMin on the MSL Curiosity rover. Laser-induced breakdown spectroscopy (LIBS) data similar to those measured by ChemCam on MSL were collected for powdered samples, cut slab surfaces, and as depth profiles into weathered surfaces where present. Three-dimensional laser camera images of rock textures were collected for selected samples. The CSA intends to make available sample powders (science community. Aiming to complement existing planetary analogue rock and mineral libraries, the CSA suite represents a new resource for planetary scientists and engineers. We envision many potential applications for these materials in the definition, development and testing of new analytical instruments for use in planetary missions, as well as possible calibration and ground-truthing of remote sensing data sets

  15. Histone Deacetylase Inhibitors: Synthesis of Tetrapeptide Analogue SAHA/TPX

    Directory of Open Access Journals (Sweden)

    Lynda Ekou

    2011-01-01

    Full Text Available The inhibition of HDAC (histone deacetylase activity by specific inhibitors induces growth arrest, differentiation and apoptosis of transformed or several cancer cells. Some of these inhibitors are in clinical trial at phase I or phase II. The discovery and development of specific HDAC inhibitors are helpful for cancer therapy. In this paper we describe the synthesis of simple inhibitor B hybrid analogue suberoylanilide hydroxamic acid (SAHA, trapoxin B (TPX B in as little as five steps. This compound is interesting lead for the design of potent inhibitors of histone deacetylase.

  16. Discodermolide analogues as the chemical component of combination bacteriolytic therapy.

    Science.gov (United States)

    Smith, Amos B; Freeze, B Scott; LaMarche, Matthew J; Sager, Jason; Kinzler, Kenneth W; Vogelstein, Bert

    2005-08-01

    The marine natural product (+)-discodermolide (1) and several simplified analogues of this microtubule-stabilizing agent have proven to be potent in vitro cell growth inhibitory agents in several human cancer cell lines. Here, we demonstrate the in vivo efficacy of discodermolide and several simplified congeners, both as stand-alone anti-tumor agents and, in the case of (+)-2,3-anhydrodiscodermolide (3), as a chemical component of the combination bacteriolytic therapy. A single intravenous injection of (+)-3 plus genetically modified Clostridium novyi-NT spores caused rapid and complete regressions of tumors in mice bearing HCT116 colorectal cancer xenografts.

  17. Coupling between mantle and surface processes: Insights from analogue modelling

    Science.gov (United States)

    Király, Ágnes; Sembroni, Andrea; Faccenna, Claudio; Funiciello, Francesca

    2014-05-01

    Thermal or density anomalies located beneath the lithosphere are thought to generate dynamic topography. Such a topographic signal compensates the viscous stresses originating from the anomaly driven mantle flow. It has been demonstrated that the erosion modulates the dynamic signal of topography changing the uplift rate by unload. The characteristic time for adjustments of dynamic topography due to surface erosion is likely similar to post-glacial rebound time (10000 - 50000 years). Here we present preliminary results of a new set of analogue models realized to study and quantify the contribution given by erosion to dynamic topography, during a process specifically driven by a positively buoyant deep anomaly. The adopted set up consists of a Plexiglas box (40x40x50 cm3) filled with glucose syrup as analogue upper mantle. A silicon plate positioned on the top of the syrup simulates the lithosphere. On the silicone plate is placed a thin layer of a high viscous glucose syrup which reproduces the upper, erodible layer of the crust. To simulate the positively buoyant anomaly we used an elastic, undeformable silicon ball free to rise by buoyancy in the syrup until the floating silicone plate is hit. The changes in topography have been monitored by using a 3D laser scan, while a side-view camera recorded the position of the rising ball in time. Data have been post-processed with image analysis techniques (e.g., Particle Image Velocimetry) in order to obtain the evolution of topography, uplift rate, erosion patterns of the top layer, bulge width and mantle circulation during the experiment. We ran experiments with and without the shallow, erodible crustal layer in order to quantify the effect of erosion on dynamic topography. Preliminary results showed that both the maximum topography and uplift rate are inversely proportional to the lithospheric thickness. The maximum uplift rate and the deformation of the lithospheric plate occurred just before the arrival of the

  18. Synthesis of a Nitro Analogue of Plakoric Acid

    Institute of Scientific and Technical Information of China (English)

    ZHANG,Qi; JIN,Hong-Xia; LIU,He-Hua; WU,Yi-Kang

    2006-01-01

    Synthesis of a nitro analogue of plakoric acid is presented. The peroxy bond was incorporated into the substrate structure through a boron trifluoride etherate catalyzed methoxy-hydroperoxy group partial exchange reaction in djethyl ether with urea-hydrogen peroxide complex (UHP, a commercially available solid reagent) as the source of the hydrogen peroxide. Under the given conditions, only one of the two methoxyl groups underwent the MeO-OOH exchange and the resulting hydroperoxy hemiketal proceeded directly to the end product through an intramolecular Michael addition of the hydroperoxyl group to the nitro group activated carbon-carbon double bond.

  19. Enantioselctive Syntheses of Sulfur Analogues of Flavan-3-Ols

    Directory of Open Access Journals (Sweden)

    Richard Lombardy

    2010-08-01

    Full Text Available The first enantioselective syntheses of sulfur flavan-3-ol analogues 1–8 have been accomplished, whereby the oxygen atom of the pyran ring has been replaced by a sulfur atom. The key steps were: (a Pd(0 catalyzed introduction of –S t-butyl group, (b Sharpless enantioselective dihydroxylation of the alkene, (c acid catalyzed ring closure to produce the thiopyran ring, and (d removal of benzyl groups using N,N-dimethylaniline and AlCl3. The compounds were isolated in high chemical and optical purity.

  20. Nonclassical mechanical states in an optomechanical micromaser analogue

    OpenAIRE

    Nation, P. D.

    2013-01-01

    Here we show that quantum states of a mechanical oscillator can be generated in an optomechanical analogue of the micromaser, in absence of any atom-like subsystem, thus exhibiting single-atom masing effects in a system composed solely of oscillator components. In the regime where the single-photon coupling strength is on the order of the cavity decay rate, a cavity mode with at most a single-excitation present gives rise to sub-Poissonian oscillator limit-cycles that generate quantum feature...

  1. Synthesis and Characterization of New Diketone Analogues of Podophyllotoxin

    Directory of Open Access Journals (Sweden)

    K. H. Hemakumar

    2008-01-01

    Full Text Available The new compounds 6,6a-dihydro-2,3-dimethoxy-9-nitro–11bH benzo [C]-fluoren 5,7-dione, 6,6a-dihydro-2,3-dimethoxy-9-chloro–11bH benzo[C]-fluoren-5,7-dione and 6,6a-dihydro-2,3-dimethoxy-9-fluoro–11bH benzo[C]-fluoren-5,7- dione were synthesized in high yields. They are analogues of naturally occurring lignan podophyllotoxin which exhibits anticancer activity. They are very essential to study anticancer activity.

  2. Astrobiology Field Research in Moon/Mars Analogue Environments: Preface

    Science.gov (United States)

    Foing, B. H.; Stoker, C.; Ehrenfreund, P.

    2011-01-01

    Extreme environments on Earth often provide similar terrain conditions to landing/operation sites on Moon and Mars. Several field campaigns (EuroGeoMars2009 and DOMMEX/ILEWG EuroMoonMars from November 2009 to March 2010) were conducted at the Mars Desert Research Station (MDRS) in Utah. Some of the key astrobiology results are presented in this special issue on Astrobiology field research in Moon/Mars analogue environments relevant to investigate the link between geology, minerals, organics and biota. Preliminary results from a multidisciplinary field campaign at Rio Tinto in Spain are presented.

  3. Enantioselective reduction of acetophenone analogues using carrot and celeriac enzymes system

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The enantioselective reduction of acetophenone analogues catalyzed by carrot and celeriac was performed in moderate conversions and excellent enantiomeric excesses.The steric factors and electronic effects of the substituents at the aromatic ring were found to significantly affect the efficiency of the enantioselective reduction of acetophenone analogues,while they had a little effect on the enantioselectivity of acetophenone analogues reduction.It was also found that the conversions of acetophenone anal...

  4. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studi......, the new fast-acting analogues have not achieved the expected commercial success, which emphasises the need for new strategies for basal insulin supplementation, exercise, diet and blood glucose monitoring....

  5. Semisynthetic analogues of the microtubule-stabilizing agent discodermolide: preparation and biological activity.

    Science.gov (United States)

    Gunasekera, Sarath P; Longley, Ross E; Isbrucker, Richard A

    2002-12-01

    A series of 12 semisynthetic discodermolide analogues, 2-13, have been prepared using natural (+)-discodermolide (1) and evaluated for in vitro cytotoxicity against cultured murine P-388 leukemia and A-549 human adenocarcinoma cells. These semisynthetic analogues showed a significant variation of cytotoxicity and confirmed the importance of the C-7 through C-19 molecular fragment for potency. Specifically, these analogues suggested the importance of the C-11 and C-17 hydroxyl groups and the C-13 double bond for the potency of discodermolide. The preparation, structure elucidation, and biological activity of these new analogues are described.

  6. THE OBJECTIVE ANALOGUE PREDICTION MODEL FOR TROPICAL CYCLONE TRACK WITH COMPREHENSIVE ASSESSMENT OF THE ENVIRONMENT

    Institute of Scientific and Technical Information of China (English)

    钟元

    2002-01-01

    An objective analogue prediction model for tropical cyclone (TC) track is put forward that comprehensively assesses the environmental field. With the parameters of the tropical cyclone and environmental field at initial and future time, objective analogue criteria are set up in the model. Analogous samples are recognized by comprehensive assessment of historical TC cases for similarity with multivariate criteria, using non-linear analogue indexes especially defined for the purpose. When the historical tracks are coordinateconverted and weighted with reference to analogue indexes, forecast tracks are determined. As shown in model verification and forecast experiments, the model has forecasting skill.

  7. Large scale biosynthesis of ganglioside analogues by RERF-LC-AI cells cultured in HYPERFlask.

    Science.gov (United States)

    Shimura, Yumiko; Suzuki, Junya; Muraoka, Miho; Kasuya, Maria Carmelita Zulueta; Matsuoka, Koji; Hatanaka, Kenichi

    2012-01-01

    The efficient production of ganglioside analogues was accomplished using RERF-LC-AI cells cultured in HYPERFlask (High Yield PERformance Flask). Eight kinds of ganglioside analogues (GM3, GM2, sialylparagloboside, GD3, di-sialylated lacto-N-tetraose, and another three kinds of analogues with intricate structures) were synthesized by the saccharide primer method using lung squamous-cell carcinoma line RERF-LC-AI and 12-azidododecyl β-lactoside primer. The yield for each analogue obtained using HYPERFlask was higher than yields obtained from 100-mm dishes.

  8. Synthesis, Physiochemical Properties, Photochemical Probe, and Antimicrobial Effects of Novel Norfloxacin Analogues

    National Research Council Canada - National Science Library

    Bakhotmah, Dina A; Abdul-Rahman, Reda M; Makki, Mohammad S; El-Zahabi, Mohamed A; Suliman, Mansor

    2011-01-01

    .... The present work aimed to synthesize novel norfloxacin analogues using modified Vilsmeier approach and conduct preliminary investigations for the evaluation of their physicochemical properties...

  9. Assessment of structurally diverse philanthotoxin analogues for inhibitory activity on ionotropic glutamate receptor subtypes

    DEFF Research Database (Denmark)

    Frølund, Sidsel; Bella, Angelo; Kristensen, Anders Skov;

    2010-01-01

    -electrode voltage-clamp electrophysiology employing Xenopus laevis oocytes expressing GluA1(i) AMPA or GluN1/2A NMDA receptors. Several of the analogues showed significantly increased inhibition of the GluN1/2A NMDA receptor. Thus, an analogue containing N-(1-naphtyl)acetyl group showed an IC(50) value of 47 n......M. For the diamino acid-based analogues, the optimal spacer length between two N-acyl groups was determined, resulting in an analogue with an IC(50) value of 106 nM....

  10. Synthesis of cyclic analogues of cholecystokinin highly selective for central receptors.

    Science.gov (United States)

    Rodriguez, M; Amblard, M; Galas, M C; Lignon, M F; Aumelas, A; Martinez, J

    1990-05-01

    Cyclic CCK analogues in which positions 28 and 31 have been replaced by lysine residues and whose side chains are bridged by a succinic moiety, were synthesized. They were tested for their ability to inhibit the binding of 125I-BH-CCK-8 to isolated rat pancreatic acini and to guinea pig brain membranes. These cyclic CCK-analogues were compared to the potent CCK analogue Boc-[Nle28,31]-CCK-7 and to Boc-Trp-Leu-Asp-Phe-NH2, analogue of CCK-4. These cyclic compounds appeared to be highly selective for central CCK receptors.

  11. Spin Alignment in Analogues of The Local Sheet

    CERN Document Server

    Conidis, George J

    2014-01-01

    Tidal torque theory and simulations of large scale structure predict spin vectors of massive galaxies should be coplanar with sheets in the cosmic web. Recently demonstrated, the giants (K$_{s}$ $\\leq$ -22.5 mag) in the Local Volume beyond the Local Sheet have spin vectors directed close to the plane of the Local Supercluster, supporting the predictions of Tidal Torque Theory. However, the giants in the Local Sheet encircling the Local Group display a distinctly different arrangement, suggesting that the mass asymmetry of the Local Group or its progenitor torqued them from their primordial spin directions. To investigate the origin of the spin alignment of giants locally, analogues of the Local Sheet were identified in the SDSS DR9. Similar to the Local Sheet, analogues have an interacting pair of disk galaxies isolated from the remaining sheet members. Modified sheets in which there is no interacting pair of disk galaxies were identified as a control sample. Galaxies in face-on control sheets do not display ...

  12. A selective phenelzine analogue inhibitor of histone demethylase LSD1.

    Science.gov (United States)

    Prusevich, Polina; Kalin, Jay H; Ming, Shonoi A; Basso, Manuela; Givens, Jeffrey; Li, Xin; Hu, Jianfei; Taylor, Martin S; Cieniewicz, Anne M; Hsiao, Po-Yuan; Huang, Rong; Roberson, Heather; Adejola, Nkosi; Avery, Lindsay B; Casero, Robert A; Taverna, Sean D; Qian, Jiang; Tackett, Alan J; Ratan, Rajiv R; McDonald, Oliver G; Feinberg, Andrew P; Cole, Philip A

    2014-06-20

    Lysine-specific demethylase 1 (LSD1) is an epigenetic enzyme that oxidatively cleaves methyl groups from monomethyl and dimethyl Lys4 of histone H3 (H3K4Me1, H3K4Me2) and can contribute to gene silencing. This study describes the design and synthesis of analogues of a monoamine oxidase antidepressant, phenelzine, and their LSD1 inhibitory properties. A novel phenelzine analogue (bizine) containing a phenyl-butyrylamide appendage was shown to be a potent LSD1 inhibitor in vitro and was selective versus monoamine oxidases A/B and the LSD1 homologue, LSD2. Bizine was found to be effective at modulating bulk histone methylation in cancer cells, and ChIP-seq experiments revealed a statistically significant overlap in the H3K4 methylation pattern of genes affected by bizine and those altered in LSD1-/- cells. Treatment of two cancer cell lines, LNCaP and H460, with bizine conferred a reduction in proliferation rate, and bizine showed additive to synergistic effects on cell growth when used in combination with two out of five HDAC inhibitors tested. Moreover, neurons exposed to oxidative stress were protected by the presence of bizine, suggesting potential applications in neurodegenerative disease.

  13. Active postoperative acromegaly: sustained remission after discontinuation of somatostatin analogues

    Directory of Open Access Journals (Sweden)

    Cristina Alvarez-Escola

    2016-11-01

    Full Text Available In patients with active acromegaly after pituitary surgery, somatostatin analogues are effective in controlling the disease and can even be curative in some cases. After treatment discontinuation, the likelihood of disease recurrence is high. However, a small subset of patients remains symptom-free after discontinuation, with normalized growth hormone (GH and insulin-like growth factor (IGF1 levels. The characteristics of patients most likely to achieve sustained remission after treatment discontinuation are not well understood, although limited evidence suggests that sustained remission is more likely in patients with lower GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on an MRI scan and/or in patients who receive long-term treatment. In this report, we describe the case of a 56-year-old female patient treated with lanreotide Autogel for 11 years. Treatment was successfully discontinued, and the patient is currently disease-free on all relevant parameters (clinical, biochemical and tumour status. The successful outcome in this case adds to the small body of literature suggesting that some well-selected patients who receive long-term treatment with somatostatin analogues may achieve sustained remission.

  14. [GnRH analogues for the treatment of fibroids].

    Science.gov (United States)

    Murillo, Ester Ortiz; Cano, Antonio

    2013-07-01

    Uterine fibroids are benign tumors that are very common in women and may present significant symptoms in 20%-50% of cases. When they require action, their traditional management has been surgery (hysterectomy or fibroidectomy); however medical alternatives have been proposed, given that surgery is associated with a certain morbidity and mortality and involves healthcare costs. Within the pharmacological management of uterine fibroids, GnRH analogues are the best known and most commonly used drugs, although their indications are limited by the side effects associated with long-term treatment. Their primary indication is based on preoperative treatment (to hysterectomy or fibroidectomy) and in selected cases of patients close to menopause or who want more conservative management. These analogues are able to significantly reduce the uterine volume, the size of the fibroid and their accompanying symptoms. Their main disadvantage, however, lies in the reversibility of their effect when treatment is discontinued, along with the side effects associated with hypoestrogenism, such as climacteric symptoms and loss of bone mass. "Add-back" therapies, which associate low-dose estrogens to aGnRH, allow for extended use thanks to decreased side effects without affecting the benefits. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  15. Thermal conductivity determination of cometary and asteroid material analogues

    Science.gov (United States)

    Banaszkiewicz, M.; Seweryn, K.; Wawrzaszek, R.

    Measurements of physical properties of surface and subsurface layers of planetary bodies often provide important information about the structure of the medium and processes that occur there Thermal properties of cometary nuclues subsurface material are crucial in determining the heat and gas transport Similarly asteroid s regolith is a buffering zone in heat transfer from to surface to from interior of a body There are space experiments planned to perform temperature and thermal conductivity measurements on a comet ROSETTA and one can easily foresee such measurements carried out by future robotic missions on Mars planetary satellites and asteroids In the paper we present the results of measurements carried out with a new type of thermal sensors The elementary cylindrical sensor is made of platinum wire resistance thermometer and isotan wire heating element that can operate independently By choosing these materials the problems of temperature measurement calibration and constant heating power are resolved We confront the results of measurements made for a number of sensors combined into a long cylinder in delrin basalt ice-dust mixture comet analogue and regolith-like material with models and show that agreement is very good Therefore we can recommend both the sensors and the method of data interpretation for the thermal conductivity determination as very useful tools in future space missions and in laboratory experiments on cometary and asteroid material analogues

  16. The molecular interactions of buspirone analogues with the serotonin transporter.

    Science.gov (United States)

    Jarończyk, Małgorzata; Chilmonczyk, Zdzisław; Mazurek, Aleksander P; Nowak, Gabriel; Ravna, Aina W; Kristiansen, Kurt; Sylte, Ingebrigt

    2008-10-15

    A major problem with the selective serotonin reuptake inhibitors (SSRIs) is the delayed onset of action. A reason for that may be that the initial SSRI-induced increase in serotonin levels activates somatodendritic 5-HT(1A) autoreceptors, causing a decrease in serotonin release in major forebrain areas. It has been suggested that compounds combining inhibition of the serotonin transport protein with antagonistic effects on the 5-HT(1A) receptor will shorten the onset time. The anxiolytic drug buspirone is known as 5-HT(1A) partial agonist. In the present work, we are studying the inhibition of the serotonin transporter protein by a series of buspirone analogues by molecular modelling and by experimental affinity measurements. Models of the transporter protein were constructed using the crystal structure of the Escherichia coli major facilitator family transporter-LacY and the X-ray structure of the neurotransmitter symporter family (NSS) transporter-LeuT(Aa) as templates. The buspirone analogues were docked into both SERT models and the interactions with amino acids within the protein were analyzed. Two putative binding sites were identified on the LeuT(Aa) based model, one suggested to be a high-affinity site, and the other suggested to be a low-affinity binding site. Molecular dynamic simulations of the LacY based model in complex with ligands did not induce a helical architecture of the LacY based model into an arrangement more similar to that of the LeuT(Aa) based model.

  17. Classical analogue of an interstellar travel through a hydrodynamic wormhole

    Science.gov (United States)

    Euvé, L.-P.; Rousseaux, G.

    2017-09-01

    The classical theory of space-time, namely general relativity, suggests but does not demonstrate the existence of so-called wormholes allowing for interstellar journeys. Alternative proposals such as quantum gravity theories are developed nowadays to allow for wormhole travels by assuming hypothetical trans-Planckian effects at tiny scales. Here we show experimentally that analogue traversable and bidirectional wormholes exist in hydrodynamics following a suggestion by Wheeler. Using a water channel, we sent free surface waves on a countercurrent in an analogue gravity setup aiming at showing that hydrodynamic wormhole travels are controlled by a cascade of dispersive scales including surface tension effects: the capillary wavelength plays the role of a Planckian scale below which long gravity waves are transformed into short capillary waves that are able to move at speeds higher than the "flow" of space-time. Whereas our results do not apply to putative astrophysical wormholes per se, we anticipate that they will trigger new ideas to explore quantum gravity physics.

  18. Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin.

    Science.gov (United States)

    Yadav, Babasaheb; Taurin, Sebastien; Rosengren, Rhonda J; Schumacher, Marc; Diederich, Marc; Somers-Edgar, Tiffany J; Larsen, Lesley

    2010-09-15

    A series of 18 heterocyclic cyclohexanone analogues of curcumin have been synthesised and screened for their activity in both adherent and non-adherent cancer cell models. Cytotoxicity towards MBA-MB-231 breast cancer cells, as well as ability to inhibit NF-kappaB transactivation in non-adherent K562 leukemia cells were investigated. Three of these analogues 3,5-bis(pyridine-4-yl)-1-methylpiperidin-4-one B1, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidin-4-one B10, and 8-methyl-2,4-bis((pyridine-4-yl)methylene)-8-aza-bicyclo[3.2.1]octan-3-one C1 showed potent cytotoxicity towards MBA-MB-231, MDA-MB-468, and SkBr3 cell lines with EC50 values below 1 microM and inhibition of NF-kappaB activation below 7.5 microM. The lead drug candidate, B10, was also able to cause 43% of MDA-MB-231 cells to undergo apoptosis after 18 h. This level of activity warrants further investigation for the treatment of ER-negative breast cancer and/or chronic myelogenous leukemia as prototypical cellular models for solid and liquid tumors.

  19. Drug-likeness of Phytic Acid and Its Analogues.

    Science.gov (United States)

    Joy, Amitha; Balaji, S

    2015-01-01

    Inositol hexakisphosphate is known to be the phosphorous reserve in plants particularly in the seeds. Though it has been known for its antinutrient properties for many years, recent research shed light to reveal it as a novel anticancer agent. Hence the present study investigates the drug-likeness of phytic acid and its analogues through bioinformatics methods. Two potential cancer drug targets such as mitogen activated kinase and inositol 1,4,5-triphosphate receptor are included in the study. Out of 50 selected analogues of phytic acid, 42 structures interact well with the chosen drug targets. The best interacting structures are 1-diphosinositol pentakisphosphate and 2,3,4,5,6-pentaphosphonooxycyclohexyl dihydrogen phosphate. For both of these structures, the negative binding energy obtained was -49.5 KJ/mol; this affirms the stability of the complex. ADME properties are also predicted to assess the drug-like properties of the compounds. The structure activity relationship model is generated for 12 compounds with experimental IC50 values.

  20. Analogues of atmospheric circulation to probe extreme and rare events

    Science.gov (United States)

    Yiou, P.

    2015-12-01

    Analogues of atmospheric circulation have had many applications, from weather prediction to the downscaling of climate variables. The main assumptions behind this methodology are that climate variables (such as temperature or precipitation) are linked a large-scale atmospheric predictand, which is usually taken as sea-level pressure, and that such predictands recur through time. They offer a possibility to estimate probability distributions of a climate variable, conditional to patterns of atmospheric circulation. In addition, this methodology allows the quantification of unusual weather patterns that have been observed. I will represent a way to use analogues of circulation for the detection/attribution of extreme events of precipitation and temperature. This approach will be illustrated on test cases, including the warm European winter of 2006/2007, the extremes of precipitation over Southern UK and northwestern France in January 2014, and the European summer of 2015. I will show how this analysis provides a low-cost estimate of the fraction of attributable risk (FAR) for extreme events that verify the above mentioned hypotheses. Such an analysis can be performed in continuous time with reanalysis data and meteorological observations.

  1. Analogue White Hole Horizon and its Impact on Sediment Transport

    CERN Document Server

    Chatterjee, Debasmita; Ghosh, Subir; Mazumder, B S

    2015-01-01

    Motivated by the ideas of analogue gravity, we have performed experiments in a flume where an analogue White Hole horizon is generated, in the form of a wave blocking region, by suitably tuned uniform fluid (water) flow and counter-propagating shallow water waves. We corroborate earlier experimental observations by finding a critical wave frequency for a particular discharge above which the waves are effectively blocked beyond the horizon. An obstacle, in the form of a bottom wave, is introduced to generate a sharp blocking zone. All previous researchers used this obstacle. A novel part of our experiment is where we do not introduce the obstacle and find that wave blocking still takes place, albeit in a more diffused zone. Lastly we replace the fixed bottom wave obstacle by a movable sand bed to study the sediment transport and the impact of the horizon or wave blocking phenomenon on the sediment profile. We find signatures of the wave blocking zone in the ripple pattern.

  2. A new antiproliferative noscapine analogue: chemical synthesis and biological evaluation.

    Science.gov (United States)

    Ghaly, Peter E; Abou El-Magd, Rabab M; Churchill, Cassandra D M; Tuszynski, Jack A; West, F G

    2016-06-28

    Noscapine, a naturally occurring opium alkaloid, is a widely used antitussive medication. Noscapine has low toxicity and recently it was also found to possess cytotoxic activity which led to the development of many noscapine analogues. In this paper we report on the synthesis and testing of a novel noscapine analogue. Cytotoxicity was assessed by MTT colorimetric assay using SKBR-3 and paclitaxel-resistant SKBR-3 breast cancer cell lines using different concentrations for both noscapine and the novel compound. Microtubule polymerization assay was used to determine the effect of the new compound on microtubules. To compare the binding affinity of noscapine and the novel compound to tubulin, we have done a fluorescence quenching assay. Finally, in silico methods using docking calculations were used to illustrate the binding mode of the new compound to α,β-tubulin. Our cytotoxicity results show that the new compound is more cytotoxic than noscapine on both SKBR-3 cell lines. This was confirmed by the stronger binding affinity of the new compound, compared to noscapine, to tubulin. Surprisingly, our new compound was found to have strong microtubule-destabilizing properties, while noscapine is shown to slightly stabilize microtubules. Our calculation indicated that the new compound has more binding affinity to the colchicine-binding site than to the noscapine site. This novel compound has a more potent cytotoxic effect on cancer cell lines than its parent, noscapine, and hence should be of interest as a potential anti-cancer drug.

  3. Martian Analogues Emissivity Spectra From the Berlin Emissivity Database (BED)

    Science.gov (United States)

    Maturilli, A.; Helbert, J.; Moroz, L.

    2006-12-01

    Remote sensing infrared spectroscopy is the principal field of investigation for planetary surfaces composition. Past, present and future missions to bodies in the solar system include in their payload instruments measuring the emerging radiation in the infrared range. For the interpretation of the measured data an emissivity spectral library of planetary analog materials is needed. The Berlin Emissivity Database (BED) currently contains emissivity spectra of plagioclase and potassium feldspars, low Ca and high Ca pyroxenes, olivine, elemental sulphur, and Martian analogue minerals, measured in the wavelength range from 7 to 22 microns as a function of particle size. For each sample we measured the spectra of four particle size separates ranging from 0 to 250 microns. The device we used is built at DLR (Berlin) and is coupled to a Fourier transform infrared spectrometer (Bruker IFS 88), purged with dry air and equipped with a cooled detector (MCT). All spectra were acquired with a spectral resolution of 4 cm-1. We present here the results of our analysis on well knew and characterized Martian analogue minerals: JSC Mars-1, Salten Skov, and Palagonite from Mauna Kea, Hawaii. We are currently working to upgrade our emissivity facility. A new spectrometer (Bruker VERTEX 80v) and new detectors will allow us to measure the emissivity of samples in the wavelength range from 1 to 50 microns, even in a vacuum environment.

  4. MDCK cystogenesis driven by cell stabilization within computational analogues.

    Directory of Open Access Journals (Sweden)

    Jesse A Engelberg

    2011-04-01

    Full Text Available The study of epithelial morphogenesis is fundamental to increasing our understanding of organ function and disease. Great progress has been made through study of culture systems such as Madin-Darby canine kidney (MDCK cells, but many aspects of even simple morphogenesis remain unclear. For example, are specific cell actions tightly coupled to the characteristics of the cell's environment or are they more often cell state dependent? How does the single lumen, single cell layer cyst consistently emerge from a variety of cell actions? To improve insight, we instantiated in silico analogues that used hypothesized cell behavior mechanisms to mimic MDCK cystogenesis. We tested them through in vitro experimentation and quantitative validation. We observed novel growth patterns, including a cell behavior shift that began around day five of growth. We created agent-oriented analogues that used the cellular Potts model along with an Iterative Refinement protocol. Following several refinements, we achieved a degree of validation for two separate mechanisms. Both survived falsification and achieved prespecified measures of similarity to cell culture properties. In silico components and mechanisms mapped to in vitro counterparts. In silico, the axis of cell division significantly affects lumen number without changing cell number or cyst size. Reducing the amount of in silico luminal cell death had limited effect on cystogenesis. Simulations provide an observable theory for cystogenesis based on hypothesized, cell-level operating principles.

  5. Analogue Missions on Earth, a New Approach to Prepare Future Missions on the Moon

    Science.gov (United States)

    Lebeuf, Martin

    Human exploration of the Moon is a target by 2020 with an initial lunar outpost planned in polar regions. Current architectures maintain a capability for sorties to other latitudes for science activities. In the early stages of design of lunar outpost infrastructure and science activity planning, it has been recognized that analogue missions could play a major role in Moon mission design. Analogue missions, as high fidelity simulations of human and robotic surface operations, can help field scientists and engineers develop and test strategies as well as user requirements, as they provide opportunities to groundtruth measurements, and for the team to share understanding of key science needs and key engineering trades. These types of missions also provide direct training in planning science operations, and in team building and communication. The Canadian Space Agency's Exploration Core Program targets the development of technology infrastructure elements in key areas of science, technology and robotics in preparation for its role in the future exploration of the Moon and Mars. Within this Program, Analogue Missions specifically target the operations requirements and lessons learned that will reduce costs and lower the risk of planetary surface missions. Analogue missions are simulations of planetary surface operations that take place at analogue sites on Earth. A terrestrial analogue site resembles in some key way: eg. geomorphologically or geochemically, a surface environment of another planet. An analogue mission can, therefore, be defined as an integrated set of activities that represent (or simulate) entire mission designs or narrowly focus on specific aspects of planned or potential future planetary exploration missions. Within the CSA's Exploration Core Program, Analogue Missions facilitate the maturation of science instruments and mission concepts by integrating ongoing space instrument and technology development programs with science and analogue elements. As

  6. In vitro structure-activity relationship of Re-cyclized octreotide analogues

    Energy Technology Data Exchange (ETDEWEB)

    Dannoon, Shorouk F. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Ma Lixin [Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Gallazzi, Fabio [Structural Biology Core, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: lewismic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: jurissons@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States)

    2010-07-15

    Introduction: Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods: Various octreotide analogue sequences and coordination systems (e.g., S{sub 2}N{sub 2} and S{sub 3}N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with {sup 111}In-DOTA-Tyr{sup 3}-octreotide in AR42J rat pancreatic tumor cells yielded IC{sub 50} values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr{sup 3}-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. Results: Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr{sup 3}-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions: Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS{sub 3} and N{sub 2}S{sub 2} coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of {sup 99m}Tc-cyclized analogue 4.

  7. Climate Analogues for agricultural impact projection and adaptation – a reliability test

    Directory of Open Access Journals (Sweden)

    Swen P.M. Bos

    2015-10-01

    Full Text Available The climate analogue approach is often considered a valuable tool for climate change impact projection and adaptation planning, especially for complex systems that cannot be modelled reliably. Important examples are smallholder farming systems using agroforestry or other mixed-cropping approaches. For the projected climate at a particular site of interest, the analogue approach identifies locations where the current climate is similar to these projected conditions. By comparing baseline-analogue site pairs, information on climate impacts and opportunities for adaptation can be obtained. However, the climate analogue approach is only meaningful, if climate is a dominant driver of differences between baseline and analogue site pairs. For a smallholder farming setting on Mt. Elgon in Kenya, we tested this requirement by comparing yield potentials of maize and coffee (obtained from the IIASA Global Agro-ecological Zones dataset among 50 close analogue sites for different future climate scenarios and models, and by comparing local ecological knowledge and farm characteristics for one baseline-analogue pair.Yield potentials among the 50 closest analogue locations varied strongly within all climate scenarios, hinting at factors other than climate as major drivers of what the analogue approach might interpret as climate effects. However, on average future climatic conditions seemed more favourable to maize and coffee cultivation than current conditions. The detailed site comparison revealed substantial differences between farms in important characteristics, such as farm size and presence of cash crops, casting doubt on the usefulness of the comparison for climate change analysis. Climatic constraints were similar between sites, so that no apparent lessons for adaptation could be derived. Pests and diseases were also similar, indicating that climate change may not lead to strong changes in biotic constraints at the baseline site in the near future. From

  8. Natural analogue studies for the safety case development of radioactive waste disposal in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Kyung-Woo [Korea Institute of Nuclear Safety, 305-338 Daejeon (Korea, Republic of); Baik, Min-Hoon [Korea Atomic Energy Research Institute, 305-353 Daejeon (Korea, Republic of)

    2014-07-01

    The natural analogue study is an analogy approach to investigate natural occurrences of materials, conditions and processes that are similar to those known or predicted to occur in some part of a radioactive waste disposal system. Countries considering the disposal of radioactive waste have been working on their domestic natural analogue studies for developing the safety case and improving the disposal safety. Natural analogue study can effectively be applied to the understanding of a long-term behavior of the post-closure repository, the provision of quantitative data required for the safety assessment models, and the supplementary safety indicator to prove the safety of deep geological disposal. Therefore the natural analogue studies play an important role in the safety case which requires a multiple lines of evidence including the safety assessment for the geological disposal of radioactive wastes. In this study, current status of foreign natural analogue studies was investigated by summarizing their results related with repository materials, radionuclide migration and retardation. Main results, issues, and their applicability of the foreign natural analogue studies were also analyzed. The results of natural analogue studies in Korea were categorized and summarized according to the studies on the uranium ore bodies, rocks, groundwater, and archeological artifacts. Although so many studies on the natural analogue have been carried out during last several decades in Korea, their results have not been actively applied to the safety assessment and safety case development for radioactive waste disposal. Therefore, applicable methods of natural analogues were summarized and a methodology for improving their applicability was examined. Additionally, in order to improve the application of these results from natural analogue studies, build-up of a natural analogue information database was in progress and its status will be presented. (authors)

  9. Magnetic fabric analyses in analogue models of clays

    Science.gov (United States)

    García-Lasanta, Cristina; Román-Berdiel, Teresa; Izquierdo-Llavall, Esther; Casas-Sainz, Antonio

    2017-04-01

    Anisotropy of magnetic susceptibility (AMS) studies in sedimentary rocks subjected to deformation indicate that magnetic fabrics orientation can be conditioned by multiple factors: sedimentary conditions, magnetic mineralogy, successive tectonic events, etc. All of them difficult the interpretation of the AMS as a marker of the deformation conditions. Analogue modeling allows to isolate the variables that act in a geological process and to determine the factors and in which extent they influence in the process. This study shows the magnetic fabric analyses applied to several analogue models developed with common commercial red clays. This material resembles natural clay materials that, despite their greater degree of impurities and heterogeneity, have been proved to record a robust magnetic signal carried by a mixture of para- and ferromagnetic minerals. The magnetic behavior of the modeled clay has been characterized by temperature dependent magnetic susceptibility curves (from 40 to 700°C). The measurements were performed combining a KLY-3S Kappabridge susceptometer with a CS3 furnace (AGICO Inc., Czech Republic). The obtained results indicate the presence of an important content of hematite as ferromagnetic phase, as well as a remarkable paramagnetic fraction, probably constituted by phyllosilicates. This mineralogy is common in natural materials such as Permo-Triassic red facies, and magnetic fabric analyses in these natural examples have given consistent results in different tectonic contexts. In this study, sedimentary conditions and magnetic mineralogy are kept constant and the influence of the tectonic regime in the magnetic fabrics is analyzed. Our main objective is to reproduce several tectonic contexts (strike-slip and compression) in a sedimentary environment where material is not yet compacted, in order to determine how tectonic conditions influence the magnetic fabric registered in each case. By dispersing the clays in water and after allowing their

  10. A desymmetrization route to fused Troger's base analogues: synthesis, isolation, and characterization of the first anti-anti diastereomer of a fused tris-Troger's base analogue.

    Science.gov (United States)

    Hansson, Anna; Wixe, Torbjörn; Bergquist, Karl-Erik; Wärnmark, Kenneth

    2005-05-12

    A desymmetrization route to fused Troger's base analogues was developed. In this way, the synthesis of the first example of an anti-anti diastereomer of a fused tris-Troger's base analogue was accomplished. The resulting compound 5b is a nonlinear symmetric regioisomer obtained from p-bromoaniline in 7% yield. The corresponding syn-anti diastereomer 5a was obtained in 4% yield.

  11. The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor.

    Directory of Open Access Journals (Sweden)

    Bryan L Roth

    Full Text Available In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS-2-(ethylamino-2-(3-methoxyphenylcyclohexanone and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenylcyclohexanamine and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenylcyclohexyl]piperidine and 1-[1-(4-methoxyphenylcyclohexyl]piperidine, were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

  12. Synthesis of the 4’-desmethoxy analogue of RU79115

    Directory of Open Access Journals (Sweden)

    MICHEL KLICH

    2004-11-01

    Full Text Available The synthesis, and biological activity in vitro of the 4’-desmethoxy analogue (3 of RU 79115 (2 is described. Comparison of the biological activity of the two analogues clearly indicated the importance of the 4’-methoxy group in conferring good gyrase B inhibitory activity as well as antibacterial activity.

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

    Science.gov (United States)

    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.

  14. Lactococcus lactis as expression host for the biosynthetic incorporation of tryptophan analogues into recombinant proteins

    NARCIS (Netherlands)

    El Khattabi, Mohamed; van Roosmalen, Maarten L.; Jager, Dennis; Metselaar, Heidi; Permentier, Hjalmar; Leenhouts, Kees; Broos, Jaap

    2008-01-01

    Incorporation of Trp (tryptophan) analogues into a protein may facilitate its structural analysis by spectroscopic techniques. Development of a biological system for the biosynthetic incorporation of such analogues into proteins is of considerable importance. The Gram-negative Escherichia coli is th

  15. Acetylated analogues of the microtubule-stabilizing agent discodermolide: preparation and biological activity.

    Science.gov (United States)

    Gunasekera, S P; Longley, R E; Isbrucker, R A

    2001-02-01

    A series of eight discodermolide acetates have been prepared using natural (+)-discodermolide and evaluated for in vitro cytotoxicity against the cultured murine P-388 leukemia cells. The acetylated analogues showed a significant variation of cytotoxicity and suggested the importance of C-11 and C-17 hydroxyl groups for potency. The preparation and structure elucidation of the new analogues are described.

  16. Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists

    DEFF Research Database (Denmark)

    Crestey, François; Jensen, Anders A.; Borch, Morten

    2013-01-01

    The synthesis of a new series of Erythrina alkaloid analogues and their pharmacological characterization at various nicotine acetylcholine receptor (nAChR) subtypes are described. The compounds were designed to be simplified analogues of aromatic erythrinanes with the aim of obtaining subtype...

  17. How Analogue Research Can Advance Descriptive Evaluation Theory: Understanding (and Improving) Stakeholder Dialogue

    Science.gov (United States)

    Campbell, Bernadette; Mark, Melvin M.

    2015-01-01

    Evaluation theories can be tested in various ways. One approach, the experimental analogue study, is described and illustrated in this article. The approach is presented as a method worthy to use in the pursuit of what Alkin and others have called descriptive evaluation theory. Drawing on analogue studies conducted by the first author, we…

  18. Making Connections in Math: Activating a Prior Knowledge Analogue Matters for Learning

    Science.gov (United States)

    Sidney, Pooja G.; Alibali, Martha W.

    2015-01-01

    This study investigated analogical transfer of conceptual structure from a prior-knowledge domain to support learning in a new domain of mathematics: division by fractions. Before a procedural lesson on division by fractions, fifth and sixth graders practiced with a surface analogue (other operations on fractions) or a structural analogue (whole…

  19. On Using Current Steering Logic in Mixed Analogue-digital Circuits

    DEFF Research Database (Denmark)

    Lehmann, Torsten

    1998-01-01

    The authors investigate power supply noise in mixed analogue-digital circuits, arising from communication between the analogue and digital parts of the circuit. Current steering techniques and proper buffering are used to show which noise currents can be reduced and which cannot. In addition...

  20. Synthesis of Benzofuran Analogue of Go6976, an Isoform Selective Protein Kinase C Inhibitor

    Institute of Scientific and Technical Information of China (English)

    MA, Da-Wei; ZHANG, Xin-Rong; WU, Shi-Hui; TAO, Feng-Gang

    2001-01-01

    Based on the structure of Go6976, a known isoform-selective protein kinase C inhibitor, a benzofuran analogue (1) was designed. This analogue was synthesized by coupling of benzofuran 3-acetic acid and 8-oxo-tryptamine and subsequent intramolecular Dieckmann condensation, alkylation, oxidative photocyclization and cyanation reaction of mesylate.

  1. New analogues of ACPD with selective activity for group II metabotropic glutamate receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Madsen, U; Mikiciuk-Olasik, E

    1997-01-01

    In this study we have determined the pharmacology of a series of 1-aminocyclopentane-1,3-dicarboxylic acid (1,3-ACPD) analogues at cloned metabotropic glutamic acid (mGlu) receptors. The new analogues comprise the four possible stereoisomers of 1-amino-1-carboxycyclopentane-3-acetic acid (1,3-homo...

  2. Structure-activity relationships of analogues of thapsigargin modified at O-11 and O-12

    DEFF Research Database (Denmark)

    Nielsen, S F; Thastrup, Ole; Pedersen, R;

    1995-01-01

    A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant ...

  3. Biological evaluation of Tyr6 and Ser7 modified drosocin analogues

    NARCIS (Netherlands)

    Visser, P.C. de; Hooft, P.A.V. van; Vries, A.-M. de; Jong, A. de; Marel, G.A. van der; Overkleeft, H.S.; Noort, D.

    2005-01-01

    An array of analogues of the cationic antimicrobial peptide drosocin was synthesized containing substitutions of Tyr6 and Ser7 in order to increase the proteolytic stability. Stabilizing the N-terminus with unnatural amino acids increased the serum stability of analogues by almost a factor 30 over a

  4. Insulin analogues in pregnancy and specific congenital anomalies; a literature review

    NARCIS (Netherlands)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa; Morgan, Margery; de Jong-van den Berg, Lolkje T W; Wang, Hao

    2016-01-01

    BACKGROUND: Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. METHODS: We performed a literature search for

  5. One-pot synthesis and biological evaluation of aspergillamides and analogues

    NARCIS (Netherlands)

    Beck, Barbara; Hess, Sibylle; Dömling, Alexander

    2000-01-01

    A one-pot total synthesis of aspergillamide and analogues by a solution phase Ugi multi component reaction (MCR) is described. The reaction is easily performed in 96-well plates and offers a facile access to diverse aspergillamide analogue compound libraries. The antibiotic and cytotoxic activity of

  6. Low-cost SI-POF analogue TIA and equaliser

    Science.gov (United States)

    Lope, Ignacio; García del Pozo, Jose Maria; Mateo, Javier; Urdangarín, Julen; Celma, Santiago

    2012-11-01

    This article proposes the two first blocks of an analogue front-end suitable for plastic optical fibre systems suitable for the standard IEEE 1394. These blocks consist of a preamplifier followed by an equaliser which employs low-cost commercial components and are designed with two different bipolar technologies. With a supply voltage of 3.3 V, the front-end consumes 396 mW. The total gain is 70 dBΩ and it operates at up to 800 Mb/s. At this bit rate, with fibre lengths of up to 30 m, the circuit has a BER ≤ 10-12 and a maximum jitter of 170 psrms.

  7. Does an all-sulphur analogue of heptamolybdate exist?

    Indian Academy of Sciences (India)

    Bikshandarkoil R Srinivasan

    2004-08-01

    The complexes [MoX4]2- (M = Mo; X = O or S) exist as the monomeric tetrahedral species in aqueous alkaline solutions. Acidification of tetraoxomolybdate results in the condensation of the tetrahedral units via a series of polyoxomolybdates leading to the ultimate formation of the trioxide MoO3. Heptamolybdate [Mo7O24]6- is the first major polyanion of the acidification reaction. In contrast, acidification of tetrathiomolybdates leads to the formation of amorphous molybdenum trisulphide via a dinuclear Mo(V) complex. The formation of the dinuclear Mo(V) complex precludes the formation of any higher nuclearity Mo(VI)-S complexes in aqueous solution. Thus it is shown that the all-sulphur analogue of heptamolybdate [Mo7S2]6- does not exist in alkaline medium and also cannot be isolated from aqueous acidic medium.

  8. Quasinormal modes and classical wave propagation in analogue black holes

    CERN Document Server

    Berti, E; Lemos, J P S; Berti, Emanuele; Cardoso, Vitor; Lemos, Jose' P. S.

    2004-01-01

    Many properties of black holes can be studied using acoustic analogues in the laboratory through the propagation of sound waves. We investigate in detail sound wave propagation in a rotating acoustic (2+1)-dimensional black hole, which corresponds to the ``draining bathtub'' fluid flow. We compute the quasinormal mode frequencies of this system and discuss late-time power-law tails. Due to the presence of an ergoregion, waves in a rotating acoustic black hole can be superradiantly amplified. We also compute reflection coefficients and instability timescales for the acoustic black hole bomb, the equivalent of the Press-Teukolsky black hole bomb. Finally we discuss quasinormal modes and late-time tails in a non-rotating canonical acoustic black hole, corresponding to an incompressible, spherically symmetric (3+1)-dimensional fluid flow.

  9. Intertial Frame Dragging in an Acoustic Analogue spacetime

    CERN Document Server

    Chakraborty, Chandrachur; Majumdar, Parthasarathi

    2015-01-01

    We report an incipient exploration of the Lense-Thirring precession effect in a rotating {\\it acoustic analogue black hole} spacetime. An exact formula is deduced for the precession frequency of a gyroscope due to inertial frame dragging, close to the ergosphere of a `Draining Bathtub' acoustic spacetime which has been studied extensively for acoustic Hawking radiation of phonons and also for `superresonance'. The formula is verified by embedding the two dimensional spatial (acoustic) geometry into a three dimensional one where the similarity with standard Lense-Thirring precession results within a strong gravity framework is well known. Prospects of experimental detection of this new `fixed-metric' effect in acoustic geometries, are briefly discussed.

  10. Novel Conformationally Constrained Analogues of Agomelatine as New Melatoninergic Ligands

    Directory of Open Access Journals (Sweden)

    Marouan Rami

    2012-12-01

    Full Text Available Novel conformationally restricted analogues of agomelatine were synthesized and pharmacologically evaluated at MT1 and MT2 melatoninergic receptors. Replacement of the N-acetyl side chain of agomelatine by oxathiadiazole-2-oxide (compound 3, oxadiazole-5(4H-one (compound 4, tetrazole (compound 5, oxazolidinone (compound 7a, pyrrolidinone (compound 7b, imidazolidinedione (compound 12, thiazole (compounds 13 and 14 and isoxazole moieties (compound 15 led to a decrease of the melatoninergic binding affinities, particularly at MT1. Compounds 7a and 7b exhibiting nanomolar affinity towards the MT2 receptors subtypes have shown the most interesting pharmacological results of this series with the appearance of a weak MT2-selectivity.

  11. Glutathione analogue sorbents selectively bind glutathione S-transferase isoenzymes.

    Science.gov (United States)

    Castro, V M; Kelley, M K; Engqvist-Goldstein, A; Kauvar, L M

    1993-06-01

    Novel affinity sorbents for glutathione S-transferases (GSTs) were created by binding glutathione (GSH) analogues to Sepharose 6B. The GSH molecule was modified at the glycine moiety and at the group attached to the sulphur of cysteine. When tested by affinity chromatography in a flow-through microplate format, several of these sorbents selectively bound GST isoenzymes. gamma E-C(Hx)-phi G (glutathione with a hexyl moiety bound to cysteine and phenylglycine substituted for glycine) specifically bound rat GST 7-7, the Pi-class isoenzyme, from liver, kidney and small intestine. gamma E-C(Bz)-beta A (benzyl bound to cysteine and beta-alanine substituted for glycine) was highly selective for rat subunits 3 and 4, which are Mu-class isoenzymes. By allowing purification of the isoenzymes under mild conditions that preserve activity, the novel sorbents should be useful in characterizing the biological roles of GSTs in both normal animal and cancer tissues.

  12. Anisotropic metamaterial as an analogue of a black hole

    CERN Document Server

    Fernández-Núñez, Isabel

    2016-01-01

    Propagation of light in a metamaterial medium which mimics curved spacetime and acts like a black hole is studied. We show that in a particular type of spacetimes, the time and space metric coefficients may correspond to different properties of the medium. For a TE wave, the time dilation appears as dielectric permittivity, while the spatial curvature manifests as magnetic permeability, and vice versa for a TM wave. We obtain the optical analogue to the relativistic Hamiltonian which determines the ray paths (null geodesics) in the anisotropic metamaterial. By applying the formalism to the Schwarzschild metric, we compare the ray paths with full-wave simulations in the effective medium and obtain a very good correspondence. As an interesting feature we find that light does not propagate in the direction of the wave normal, there is an angle between the wave velocity and the ray velocity.

  13. Database of optical properties of cosmic dust analogues (DOP)

    CERN Document Server

    Ilyin, V N; Babenko, V A; Beletsky, S A; Henning, T; Jäger, C; Khlebtsov, N G; Litvinov, P V; Mutschke, H; Tishkovets, V P; Waters, L B F M; Henning, Th.

    2003-01-01

    We present a database containing information on different aspects of calculation and usage of the optical properties of small non-spherical particles -- cosmic dust analogues. The main parts of the DOP are a review of available methods of the light scattering theory, collection of light scattering codes, special computational tools, a graphic library of the optical properties (efficiencies, albedo, asymmetry factors, etc.), a database of the optical constants for astronomy, a bibliographic database of light scattering works, and links to related Internet resources. The general purpose of the DOP having the address http://www.astro.spbu.ru/DOP is twofold -- to help scientists to apply the light scattering theory in astronomy and to give students and beginners a possibility quickly to get necessary knowledge on the subject.

  14. Visual vertigo analogue scale: an assessment questionnaire for visual vertigo.

    Science.gov (United States)

    Dannenbaum, Elizabeth; Chilingaryan, Gevorg; Fung, Joyce

    2011-01-01

    A common symptom for people with vestibulopathy is dizziness induced by dynamic visual input, known as visual vertigo (VV). The goal of this study is to present a novel method to assess VV, using a nine-item analog scale. The subjects rated the intensity of their dizziness on each item of the Visual Vertigo Analogue Scale (VVAS), which represented a daily situation typically inducing VV. The questionnaire was completed by participants with vestibulopathy (n=102) and by subjects receiving out-patient orthopaedic physiotherapy (n=102). The dizziness handicap inventory (DHI) was also completed by the vestibulopathic group. The Cronbach's Alpha index indicated the VVAS is internally consistent and reliable (Cronbach's Alpha=0.94). The study also found that the VVAS severity scores from vestibular and a non-vestibular population were significantly different (Wilcoxon-Mann Whitney test p scale may be useful in providing a quantitative evaluation scale of visual vertigo.

  15. Dynamic Analysis of Yinggehai Basin through Analogue Modeling

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The Yinggehai basin lies in the northwestern shelf of the South China Sea. The maximum depth of the Cenozoic sediments is 17 km. Present gas exploration was mainly in the Neogene strata. But it is estimated that the Paleoceue sediments (~8 km in thickness) has productive potential.So research on the Paleogene rifting structure will greatly enlarge the exploration area. 3D scaled sandbox is the analogue model for the Yinggehai basin. Comparing modeling with the basin by the positions and movement of depocenters, the geometric similarity, we aim to summarize the dynamic situation of Yinggehai basin during the rifting stage and to cast an objective prediction on the structures in the areas without data.

  16. Solar analogues and Solar twins in the HARPS archive

    CERN Document Server

    Datson, Juliet; Portinari, Laura

    2014-01-01

    We present 63 Solar analogues and twins for which high S/N archival data are available for the HARPS high resolution spectrograph at the ESO 3.6m telescope. We perform a differential analysis of these stellar spectra relative to the Solar spectrum, similar to previous work using ESO 2.2m/FEROS data, and expand our analysis by introducing a new method to test the temperature and metallicity calibration of Sun-like stars in the Geneva-Copenhagen-Survey (GCS). The HARPS data are significantly better than the FEROS data, with improvements in S/N, spectral resolution, and number of lines we can analyse. We confirm the offsets to the photometric scale found in our FEROS study. We confirm 3 Solar twins found in the FEROS data as Solar twins in the HARPS data, as well as identify 6 new twins.

  17. The Mojave vadose zone: a subsurface biosphere analogue for Mars.

    Science.gov (United States)

    Abbey, William; Salas, Everett; Bhartia, Rohit; Beegle, Luther W

    2013-07-01

    If life ever evolved on the surface of Mars, it is unlikely that it would still survive there today, but as Mars evolved from a wet planet to an arid one, the subsurface environment may have presented a refuge from increasingly hostile surface conditions. Since the last glacial maximum, the Mojave Desert has experienced a similar shift from a wet to a dry environment, giving us the opportunity to study here on Earth how subsurface ecosystems in an arid environment adapt to increasingly barren surface conditions. In this paper, we advocate studying the vadose zone ecosystem of the Mojave Desert as an analogue for possible subsurface biospheres on Mars. We also describe several examples of Mars-like terrain found in the Mojave region and discuss ecological insights that might be gained by a thorough examination of the vadose zone in these specific terrains. Examples described include distributary fans (deltas, alluvial fans, etc.), paleosols overlain by basaltic lava flows, and evaporite deposits.

  18. Toward the analogue of thermally generated electromagnetic fields

    CERN Document Server

    Osano, Bob

    2016-01-01

    Magnetic and vorticity fields evolution equations are known to obey the same equation when effects of dissipation and sources terms are negligible. We investigate the analogy between the two fields for non-vanishing dissipation and sources. In addition to the Reynolds (Re)and Prandtl (Pr_M) numbers, we define a new number (S_M) that is given by the ratio of the diffusive term to the Biermann battery term and which allows for a different classification of magnetised fluid behaviour. Numerical simulations of the two fields are then carried out given a parameter space made of Reynolds, Prandtl and Source numbers. We find it appropriate to present and discuss the findings against Prandtl numbers given that these provide the link between viscous and magnetic diffusion. Our simulations indicate that there exists a range of Prandtl numbers for which the fields remain analogues which raises the important question of how far the analogy goes.

  19. Solar analogues in open clusters: The case of M67

    CERN Document Server

    Biazzo, K; Bonifacio, P; Randich, S; Bedin, L R

    2009-01-01

    Solar analogues are fundamental targets for a better understanding of our Sun and our Solar System. Usually, this research is limited to field stars, which offer several advantages and limitations. In this work, we present the results of a research of solar twins performed for the first time in a open cluster, namely M67. Our analysis allowed us to find five solar twins and also to derive a solar colour of (B-V)0=0.649+/-0.016 and a cluster distance modulus of 9.63+/-0.08. This study encourages us to apply the same method to other open clusters, and to do further investigations for planet search in the solar twins we find.

  20. Procedures for monitoring recombinant erythropoietin and analogues in doping control.

    Science.gov (United States)

    Segura, Jordi; Pascual, José A; Gutiérrez-Gallego, Ricardo

    2007-08-01

    The present report summarizes the main analytical strategies developed to identify the presence of recombinant erythropoietin (EPO) administered as a doping agent. Indirect evidence is based on the analysis of blood parameters (haemoglobin, haematocrit, reticulocytes, macrocytes, etc.) and serum markers (concentration of EPO and serum transferrin receptors, etc.). The problem of intertechnique comparison for reliable results evaluation is emphasized, especially for serum markers. Charge differences between isoforms of recombinant EPO and native urinary EPO are the grounds for the isoelectric focusing-double blotting-chemiluminescence detection method presently approved for doping control. Works addressing its advantages and limitations are presented and commented on. The chemical bases of the differential detection are highlighted and some future approaches for detection are also presented. The appearance and detectability of EPO analogues and mimetics susceptible for abuse are also addressed.

  1. Antineoplastic activity of didemnin congeners: nordidemnin and modified chain analogues.

    Science.gov (United States)

    Jouin, P; Poncet, J; Dufour, M N; Aumelas, A; Pantaloni, A; Cros, S; François, G

    1991-02-01

    Nordidemnin (2), a natural analogue of the marine cyclodepsipeptide didemnin B (1b), showed cytotoxic activity against L1210 leukemia and antineoplastic activity against P388 leukemia as well as B16 melanoma; nordidemnin (2) was as active as didemnin B (1b). The influence of synthetic modifications in the linear peptidic chain on in vitro and in vivo activity was also studied. Replacement of the terminal lactyl residue by mandelyl and 3-(p-hydroxyphenyl)propionyl residues in compounds 3 and 4, respectively, did not affect the cytotoxic activity against L1210 leukemia (ID50 of 1.1 nM and 1.2 nM, respectively) or the in vivo activity against P388 leukemia. Unlike these aromatic substituants, the lipophilic palmityl residue induced a dramatic loss in cytotoxic activity. The inverted chirality of the MeLeu joining residue in compound 6 caused a marked reduction in the in vitro activity.

  2. Structure-activity study of pentamidine analogues as antiprotozoal agents.

    Science.gov (United States)

    Bakunova, Svetlana M; Bakunov, Stanislav A; Patrick, Donald A; Kumar, E V K Suresh; Ohemeng, Kwasi A; Bridges, Arlene S; Wenzler, Tanja; Barszcz, Todd; Jones, Susan Kilgore; Werbovetz, Karl A; Brun, Reto; Tidwell, Richard R

    2009-04-09

    Diamidine 1 (pentamidine) and 65 analogues (2-66) have been tested for in vitro antiprotozoal activities against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani, and for cytotoxicity against mammalian cells. Dications 32, 64, and 66 exhibited antitrypanosomal potencies equal or greater than melarsoprol (IC(50) = 4 nM). Nine congeners (2-4, 12, 27, 30, and 64-66) were more active against P. falciparum than artemisinin (IC(50) = 6 nM). Eight compounds (12, 32, 33, 44, 59, 62, 64, and 66) exhibited equal or better antileishmanial activities than 1 (IC(50) = 1.8 microM). Several congeners were more active than 1 in vivo, curing at least 2/4 infected animals in the acute mouse model of trypanosomiasis. The diimidazoline 66 was the most promising compound in the series, showing excellent in vitro activities and high selectivities against T. b. rhodesiense, P. falciparum, and L. donovani combined with high antitrypanosomal efficacy in vivo.

  3. Synthesis and antiprotozoal activity of pyridyl analogues of pentamidine.

    Science.gov (United States)

    Bakunova, Svetlana M; Bakunov, Stanislav A; Wenzler, Tanja; Barszcz, Todd; Werbovetz, Karl A; Brun, Reto; Tidwell, Richard R

    2009-08-13

    A series of novel pyridyl analogues 1-18 of antiprotozoal drug 1,5-bis(4-amidinophenoxy)pentane (pentamidine) has been synthesized and tested for in vitro activities against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani, and for cytotoxicity against mammalian cells. Antiprotozoal properties of compounds 1-18 depended on the placement of cationic moieties on the pyridine rings as well as the nature of substituents on the amidine groups. Diamidine 6 with cationic moieties adjacent to pyridine nitrogen atoms was the most promising compound in the series showing superior in vitro activities against T. brucei rhodesiense, P. falciparum, and L. donovani compared to pentamidine. An oral prodrug of diamidine 6, diamidoxime 9, administered at 25 mg/kg daily for 4 days, exhibited excellent antitrypanosomal efficacy in vivo curing all infected animals in the STIB900 acute mouse model of trypanosomiasis.

  4. A Study of Secondary Ion Triple Bond Analogues.

    Science.gov (United States)

    1980-08-20

    into the formation of cluster ions have measured secondary energy spectra (35-42] and the effects of surface adsorbed gases on secondary yields [43,44...GeCI’ Cl:Ge 0.13 GaTe Te:GaP 0.1 SnAs a Sn:GaAs 0.08 SiBr+ Br:Si < 0.02 Sicl+ CI:Si < 0.01 SiSb- Sb:Si c GeAs As :Ge d Gap Ge: GaP e InSe - Se:InPh f... GaSe Se:GaAs f GeBr Br:Ge f GeSb Sb :Ge f SiAS Si: GaAs 9 a Not a triple bond analogue b ’to Ge detected, (signal < "cps) c Large SiSb- signal, implant

  5. An Analog Analogue of a Digital Quantum Computation

    CERN Document Server

    Farhi, E; Farhi, Edward; Gutmann, Sam

    1998-01-01

    We solve a problem, which while not fitting into the usual paradigm, can be viewed as a quantum computation. Suppose we are given a quantum system described by an N dimensional Hilbert space with a Hamiltonian of the form $E |w >$ is an unknown (normalized) state. We show how to discover $| w >$ by adding a Hamiltonian (independent of $| w >$) and evolving for a time proportional to $N^{1/2}/E$. We show that this time is optimally short. This process is an analog analogue to Grover's algorithm, a computation on a conventional (!) quantum computer which locates a marked item from an unsorted list of N items in a number of steps proportional to $N^{1/2}$.

  6. Simulated Milky Way analogues: implications for dark matter indirect searches

    CERN Document Server

    Calore, F; Lovell, M; Bertone, G; Schaller, M; Frenk, C S; Crain, R A; Schaye, J; Theuns, T; Trayford, J W

    2015-01-01

    We study high-resolution hydrodynamic simulations of Milky Way type galaxies obtained within the "Evolution and Assembly of GaLaxies and their Environments" (EAGLE) project, and identify the those that best satisfy observational constraints on the Milky Way total stellar mass, rotation curve, and galaxy shape. Contrary to mock galaxies selected on the basis of their total virial mass, the Milky Way analogues so identified consistently exhibit very similar dark matter profiles inside the solar circle, therefore enabling more accurate predictions for indirect dark matter searches. We find in particular that high resolution simulated haloes satisfying observational constraints exhibit, within the inner few kiloparsecs, dark matter profiles shallower than those required to explain the so-called Fermi GeV excess via dark matter annihilation.

  7. Modelling the warm interglacials: analogues of MIS1

    Science.gov (United States)

    Herold, N.; Yin, Q. Z.; Karami, M. P.; Berger, A.

    2012-04-01

    Determining interglacial diversity, primarily as a function of duration, intensity and unique climate responses to Earth's orbital variations has become a focal point for researchers trying to better understand our current interglacial. Numerous interglacials have been espoused as Marine Isotopic Stage (MIS) 1 analogues or windows into the future of Holocene climate based on their astronomical characteristics, seasonal insolation patterns or their similarity with predicted anthropogenic warming. However, to date there has been little quantitative study of the climate of these interglacials within a physically robust framework. Here we examine the climate response to peak interglacial forcing during MIS1, 5, 9, 11 and 19 using the Community Climate System Model 3. We determine which interglacial provides the closest analogue to peak MIS1 conditions as well as the mechanisms which dominate the surface climate responses of these interglacials. Considering the differences in astronomical parameters and greenhouse gases we discount MIS5 and 9 as analogues to peak MIS1 conditions due to their significant warmth and stronger precipitation and vegetation responses. Conversely, based on seasonal and hemispheric averages of surface temperature, precipitation and sea-ice cover, MIS11 and 19 are most similar to MIS1, with MIS11 actually exhibiting a higher affinity particularly during boreal summer. This is attributed to a greater similarity in the seasonal and latitudinal distribution of insolation over middle latitude Eurasia and North America, which are the regions most sensitive to insolation change given the absence of ice-sheet dynamics in our model. Global ocean overturning circulation during MIS11 is also closer to MIS1 than circulation during MIS19 is, due predominantly to differences in Weddell Sea bottom water formation. Thus, under the assumption of present-day ice-sheets MIS11 appears to be the better climatic analogue to peak MIS1 conditions. In addition to the

  8. Characterizing the magnetic fields of the first tau Sco analogues

    CERN Document Server

    Kochukhov, V Petit O; Marcolino, W L F; Wade, G A; Ignace, R

    2011-01-01

    The B0.2 V magnetic star tau Sco stands out from the larger population of massive OB stars due to its high X-ray activity, peculiar wind diagnostics and complex magnetic field. Recently, Petit et al. 2011 presented the discovery of the first two tau Sco analogues -- HD 66665 and HD 63425, identified by the striking similarity of their UV spectra to that of tau Sco. ESPaDOnS and Narval spectropolarimetric observations were obtained by the Magnetism in Massive Stars CFHT and TBL Large Programs, in order to characterize the stellar and magnetic properties of these stars. A magnetic field of similar surface strength was found on both stars, reinforcing the connection between the presence of a magnetic field and wind peculiarities. We present additional phase-resolved observations secured by the MiMeS collaboration for HD 66665 in order to measure its magnetic geometry, and correlate that geometry with diagnostics of mass-loss.

  9. All-dielectric metasurface analogue of electromagnetically induced transparency.

    Science.gov (United States)

    Yang, Yuanmu; Kravchenko, Ivan I; Briggs, Dayrl P; Valentine, Jason

    2014-12-16

    Metasurface analogues of electromagnetically induced transparency (EIT) have been a focus of the nanophotonics field in recent years, due to their ability to produce high-quality factor (Q-factor) resonances. Such resonances are expected to be useful for applications such as low-loss slow-light devices and highly sensitive optical sensors. However, ohmic losses limit the achievable Q-factors in conventional plasmonic EIT metasurfaces to values dielectric silicon-based metasurfaces. Due to extremely low absorption loss and coherent interaction of neighbouring meta-atoms, a Q-factor of 483 is observed, leading to a refractive index sensor with a figure-of-merit of 103. Furthermore, we show that the dielectric metasurfaces can be engineered to confine the optical field in either the silicon resonator or the environment, allowing one to tailor light-matter interaction at the nanoscale.

  10. Nitrooxymethyl-substituted analogues of celecoxib: synthesis and pharmacological characterization.

    Science.gov (United States)

    Boschi, Donatella; Lazzarato, Loretta; Rolando, Barbara; Filieri, Andrea; Cena, Clara; Di Stilo, Antonella; Fruttero, Roberta; Gasco, Alberto

    2009-03-01

    Nitrooxymethyl-substituted analogues of celecoxib were synthesized and tested for their cyclooxygenase (COX)-inhibiting, vasodilator, and anti-aggregatory activities, as well as for their metabolic stability in human serum and whole blood. The results showed their potency and selectivity in inhibiting the COX isoforms, evaluated in whole human blood, as well as their anti-aggregatory activity to depend closely on the position at which the NO-donor moiety is introduced. All products dilated rat aorta strips precontracted with phenylephrine in a dose-dependent manner through a cGMP-dependent mechanism. They were stable in human serum while, in blood, they were metabolically transformed, principally to the related alcohols.

  11. Nitrooxymethyl-substituted analogues of rofecoxib: synthesis and pharmacological characterization.

    Science.gov (United States)

    Boschi, Donatella; Cena, Clara; Di Stilo, Antonella; Rolando, Barbara; Manzini, Paola; Fruttero, Roberta; Gasco, Alberto

    2010-05-01

    Nitrooxymethyl-substituted derivatives of Rofecoxib were synthesized and tested for their cyclooxygenase (COX)-inhibiting activity in whole human blood, vasodilator potency on rat aorta strips, and for their capacity of inhibiting platelet aggregation of human platelet-rich plasma. The results show that their potency and selectivity in inhibiting COX isoforms, as well as their anti-aggregatory properties, are closely dependent on the position at which the NO-donor nitrooxymethyl function is introduced into the Rofecoxib scaffold. All the products were capable of dilating rat aorta strips precontracted with phenylephrine in a dose-dependent manner, through a cGMP-dependent mechanism. Compound 10 emerged as a quite potent COX-2-selective inhibitor endowed with good vasodilator activity. Interestingly, compound 19 behaved as a potent selective COX-1 inhibitor, and displayed good vasodilator and anti-aggregatory properties. The hydroxymethyl derivatives, potential metabolites of the nitrooxymethyl analogues, were similarly studied for a comparison.

  12. Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues.

    Science.gov (United States)

    Beedie, Shaunna L; Peer, Cody J; Pisle, Steven; Gardner, Erin R; Mahony, Chris; Barnett, Shelby; Ambrozak, Agnieszka; Gütschow, Michael; Chau, Cindy H; Vargesson, Neil; Figg, William D

    2015-10-01

    Thalidomide has demonstrated clinical activity in various malignancies affecting immunomodulatory and angiogenic pathways. The development of novel thalidomide analogs with improved efficacy and decreased toxicity is an ongoing research effort. We recently designed and synthesized a new class of compounds, consisting of both tetrafluorinated thalidomide analogues (Gu973 and Gu998) and tetrafluorobenzamides (Gu1029 and Gu992). In this study, we demonstrate the antiangiogenic properties of these newly synthesized compounds. We examined the specific antiangiogenic characteristics in vitro using rat aortic rings with carboxyamidotriazole as a positive control. In addition, further in vitro efficacy was evaluated using human umbilical vein endothelial cells (HUVEC) and PC3 cells treated with 5 and 10 μmol/L doses of each compound. All compounds were seen to reduce microvessel outgrowth in rat aortic rings as well as to inhibit HUVECs to a greater extent, at lower concentrations than previously tested thalidomide analogs. The antiangiogenic properties of the compounds were also examined in vivo in fli1:EGFP zebrafish embryos, where all compounds were seen to inhibit the extent of outgrowth of newly developing blood vessels. In addition, Gu1029 and Gu973 reduced the anti-inflammatory response in mpo:GFP zebrafish embryos, whereas Gu998 and Gu992 showed no difference. The compounds' antitumor effects were also explored in vivo using the human prostate cancer PC3 xenograft model. All four compounds were also screened in vivo in chicken embryos to investigate their teratogenic potential. This study establishes these novel thalidomide analogues as a promising immunomodulatory class with anticancer effects that warrant further development to characterize their mechanisms of action.

  13. Design of Thymidine Analogues Targeting Thymidilate Kinase of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Luc Calvin Owono Owono

    2013-01-01

    Full Text Available We design here new nanomolar antituberculotics, inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt, by means of structure-based molecular design. 3D models of TMPKmt-inhibitor complexes have been prepared from the crystal structure of TMPKmt cocrystallized with the natural substrate deoxythymidine monophosphate (dTMP (1GSI for a training set of 15 thymidine analogues (TMDs with known activity to prepare a QSAR model of interaction establishing a correlation between the free energy of complexation and the biological activity. Subsequent validation of the predictability of the model has been performed with a 3D QSAR pharmacophore generation. The structural information derived from the model served to design new subnanomolar thymidine analogues. From molecular modeling investigations, the agreement between free energy of complexation (ΔΔGcom and Ki values explains 94% of the TMPKmt inhibition (pKi=-0.2924ΔΔGcom+3.234;R2=0.94 by variation of the computed ΔΔGcom and 92% for the pharmacophore (PH4 model (pKi=1.0206×pKipred-0.0832,  R2=0.92. The analysis of contributions from active site residues suggested substitution at the 5-position of pyrimidine ring and various groups at the 5′-position of the ribose. The best inhibitor reached a predicted Ki of 0.155 nM. The computational approach through the combined use of molecular modeling and PH4 pharmacophore is helpful in targeted drug design, providing valuable information for the synthesis and prediction of activity of novel antituberculotic agents.

  14. Comparison of Two Kinds of 64Cu Labelled Octreotide Analogues

    Directory of Open Access Journals (Sweden)

    HAN Zhen-yi1;LIANG Ji-xin1;HU Ji2;LUO Hong-yi1;QING Jing2;CHEN Yu-qing2;LI Guang2;LI Hong-yu1,2

    2016-10-01

    Full Text Available Octreotide analogues DOTA-TOC and DOTA-TATE were labeled with 64Cu. The influences of the ratio of peptide mass to 64Cu activity, pH value, temperature and reaction time on labeling yield were investigated. The optimum labeling was determined. In vitro stability tests in saline and 10% bovine serum had been carried out. Biodistribution of the two radiolabelled compounds in normal mice and Micro PET imaging in nude mice bearing U87MG tumor had been evaluated. The results showed that the labeling yields of 64Cu-DOTA-TOC and 64Cu-DOTA-TATE were higher than 95%. Two kinds of octreotide analogues labeled with 64Cu were quite stable in saline and decomposed slowly in 10% bovine serum at 37 ℃. Biodistribution results in normal mice showed that two 64Cu labelled tracers had similar profiles. Both of the compounds washed out from the blood quickly. High uptake of radioactivity in liver and kidneys indicated the tracers were excreted via both hepatobiliary system and renal system. At the same time, compared to 64Cu-DOTA-TOC, higher radioactivity accumulation of 64Cu-DOTA-TATE in liver and kidneys was observed. Micro PET images of U87MG tumor-bearing nude mice with 64Cu-DOTA-TOC and 64Cu-DOTA-TATE showed the tumors very clearly. The radioactivity uptake of 64Cu-DOTA-TATE in tumor was higher than that of 64Cu-DOTA-TOC. This work has paved the way for further preclinical and clinical application of 64Cu-DOTA-TOC and 64Cu-DOTA-TATE as PET tumor imaging agents.

  15. Identification of pyridine analogues as new predator-derived kairomones

    Directory of Open Access Journals (Sweden)

    Julien eBrechbühl

    2015-07-01

    Full Text Available In the wild, animals have developed survival strategies relying on their senses. The individual ability to identify threatening situations is crucial and leads to increase in the overall fitness of the species. Rodents, for example have developed in their nasal cavities specialized olfactory neurons implicated in the detection of volatile cues encoding for impending danger such as predator scents or alarm pheromones. In particular, the neurons of the Grueneberg ganglion (GG, an olfactory subsystem, are implicated in the detection of danger cues sharing a similar chemical signature, a heterocyclic sulfur- or nitrogen-containing motif. Here we used a from the wild to the lab approach to identify new molecules that are involuntarily emitted by predators and that initiate fear-related responses in the recipient animal, the putative prey. We collected urines from carnivores as sources of predator scents and first verified their impact on the blood pressure of the mice. With this approach, the urine of the mountain lion emerged as the most potent source of chemical stress. We then identified in this biological fluid, new volatile cues with characteristic GG-related fingerprints, in particular the methylated pyridine structures, 2,4-lutidine and its analogues. We finally verified their encoded danger quality and demonstrated their ability to mimic the effects of the predator urine on GG neurons, on mice blood pressure and in behavioral experiments. In summary, we were able to identify here, with the use of an integrative approach, new relevant molecules, the pyridine analogues, implicated in interspecies danger communication.

  16. Functional and structural characteristics of anticancer peptide Pep27 analogues

    Directory of Open Access Journals (Sweden)

    Seo Youn-Kyung

    2005-07-01

    Full Text Available Abstract Background A secreted peptide Pep27 initiates the cell death program in S. pneumoniae through signal transduction. This study was undertaken to evaluate the relation between the structure and cytotoxic activity of Pep27 and its analogues on cancer cells. Results Pep27anal2 characterized substituting (2R→W, (4E→W, (11S→W and (13Q→W in native Pep27, exhibited greater hydrophobicity and anticancer activity than Pep27 and other analogues. The IC50 values of Pep27anal2 were approximately 10 – 30 μM in a number of cell lines (AML-2, HL-60, Jurkat, MCF-7 and SNU-601. Confocal microscopy showed that Pep27anal2-FITC was localized in the plasma membrane, and then moving from the membrane to subcellular compartments with the initiation of membrane blebbing. Flow cytometric analysis using propidium iodide and Annexin V also revealed that Pep27anal2 induced apoptosis with minor membrane damage. Electron microscopy revealed that Pep27 induced apoptosis in Jurkat cells. The anticancer activity of Pep27anal2 was neither abrogated by pan-caspase inhibitor (Z-VAD-fmk nor related to cytochrome c release from mitochondria. The 3D solution structures of these two Pep27 peptides revealed that both form a random coil conformation in water; however, they adopted stable α-helical conformations in solutions. Conclusion The results indicate that Pep27anal2 can penetrate the plasma membrane, and then induce apoptosis in both caspase-and cytochrome c-independent manner. The hydrophobicity of Pep27anal2 appears to play an important role in membrane permeabilization and/or anticancer properties. The structure-functional relationships of these peptides are also discussed. It is proposed that Pep27anal2 is a potential candidate for anticancer therapeutic agents.

  17. The importance of analogue zeitgebers to reduce digital addictive tendencies in the 21st century

    Directory of Open Access Journals (Sweden)

    Christian Montag

    2015-12-01

    Full Text Available Analogue zeitgebers such as wristwatches and alarm clocks are essential for structuring everyday life. Since the dawn of the digital revolution – particularly since the advent of the smartphone – mobile phones have increasingly replaced analogue zeitgebers as a means of telling time. This functionality may prove problematic, in that it may contribute to the overuse of digital media (e.g. when checking the time turns into extended use of other smartphone utilities, including Internet-based applications. Of N = 3084 participants, 45% reported wearing a wristwatch and 67% used an analogue alarm clock. We observed that participants who reported using analogue zeitgebers used their mobile-/smartphone significantly less. Use of analogue zeitgebers may prove a practical tool for therapeutic and preventative interventions for problematic Internet use in an increasingly digital age.

  18. Looking at the carcinogenicity of human insulin analogues via the intrinsic disorder prism.

    Science.gov (United States)

    Redwan, Elrashdy M; Linjawi, Moustafa H; Uversky, Vladimir N

    2016-03-17

    Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and cancer risk, the currently used therapeutic insulin analogues raised serious concerns due to their potential roles in cancer initiation and/or progression. It is possible that structural variations in some of the insulin analogues are responsible for the appearance of new oncogenic species with high binding affinity to the insulin-like growth factor 1 (IGF1) receptor. The question we are trying to answer in this work is: are there any specific features of the distribution of intrinsic disorder propensity within the amino acid sequences of insulin analogues that may provide an explanation for the carcinogenicity of the altered insulin protein?

  19. Memory amplification for trauma: Investigating the role of analogue PTSD symptoms in the laboratory.

    Science.gov (United States)

    Oulton, Jacinta M; Takarangi, Melanie K T; Strange, Deryn

    2016-08-01

    Victims of trauma often remember their experience as being more traumatic later, compared to immediately after, the event took place. This finding-the "memory amplification effect"-is associated with increased re-experiencing symptoms. However, the effect has been found almost exclusively in field-based studies. We examined whether the effect could be replicated in the laboratory. In two studies, we exposed participants to negative photographs and assessed their memory for the photographs and analogue PTSD symptoms on two occasions. In Study 1, analogue symptoms at follow-up were positively associated with remembering more negative photos over time. In Study 2, we focused on "memory amplifiers": people whose memory of the photos amplified over time. Consistent with field research, analogue re-experiencing symptoms were associated with memory amplification. Overall, our findings confirm that analogue PTSD symptoms are also associated with an amplified memory for a trauma analogue.

  20. Antifungal agents. 4. Chemical modification of antibiotics from Polyangium cellulosum var. fulvum. Ester and amide analogues of ambruticin.

    Science.gov (United States)

    Connor, D T; von Strandtmann, M

    1979-09-01

    A series of ester and amide analogues of ambruticin (1) was prepared. The analogues were tested against Histoplasma capsulatum, Microsporum fulvum, Candida albicans and Streptococcus pyogenes. Structure-activity relationships are described.

  1. Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core

    OpenAIRE

    Kraft, Matthew B.; Poudel, Yam B.; Kedei, Noemi; Lewin, Nancy E.; Peach, Megan L.; Blumberg, Peter M.; Keck, Gary E.

    2014-01-01

    A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biolog...

  2. Insulin analogues may accelerate progression of diabetic retinopathy after impairment of inner blood-retinal barrier.

    Science.gov (United States)

    Kaya, Abdullah; Kar, Taner; Aksoy, Yakup; Özalper, Veysel; Başbuğ, Barbaros

    2013-12-01

    Diabetic retinopathy regresses after spontaneous infarction or surgical ablation of pituitary gland. Growth hormone deficiency seems to be a protective factor for development of diabetic retinopathy in dwarfs. Despite the same glycemic control, development of diabetic retinopathy is significantly higher in pubertal subjects than pre-pubertal subjects. These evidences indicate a strong relationship between growth hormone and progression of diabetic retinopathy. Insulin like growth factor-1 (IGF-1) is the most important mediator of effects of growth hormone (GH). It stimulates IGF-1 receptor. Insulin analogues also stimulate IGF-1 receptor. Therefore insulin analogues may show similar effects like growth hormone and deteriorate diabetic retinopathy. However we suggest that impairment degree of inner blood-retinal barrier should be considered for this claim. We hypothesize that insulin analogues have dual effects (beneficial and worsening) depending on stage of impairment of inner blood-retinal barrier. Insulin analogues protect pericytes and blood-retinal barrier by decreasing blood glucose level. Analogues may pass into the retinal tissue in very low amounts when inner blood-retinal barrier is intact. Therefore, insulin analogues may not deteriorate diabetic retinopathy but also have beneficial effect by protecting blood-retinal barrier at this stage. However, they may pass into the retinal tissue in much more amounts when inner blood-retinal barrier impairs. Analogues may deteriorate cellular composition of retina through stimulation of IGF-1 receptors. A number of different cell types, including glia, retinal pigment epithelial cells and fibroblast-like cells have been identified in diabetic epiretinal tissues. Insulin analogues may cause proliferation in these cells. A type of glial cell named Non-astrocytic Inner Retinal Glia-like (NIRG) cell was identified to be stimulated and proliferate by IGF-1. IGF has been reported to generate traction force in retinal

  3. Rough Precipitation Forecasts based on Analogue Method: an Operational System

    Science.gov (United States)

    Raffa, Mario; Mercogliano, Paola; Lacressonnière, Gwendoline; Guillaume, Bruno; Deandreis, Céline; Castanier, Pierre

    2017-04-01

    In the framework of the Climate KIC partnership, has been funded the project Wat-Ener-Cast (WEC), coordinated by ARIA Technologies, having the goal to adapt, through tailored weather-related forecast, the water and energy operations to the increased weather fluctuation and to climate change. The WEC products allow providing high quality forecast suited in risk and opportunities assessment dashboard for water and energy operational decisions and addressing the needs of sewage/water distribution operators, energy transport & distribution system operators, energy manager and wind energy producers. A common "energy water" web platform, able to interface with newest smart water-energy IT network have been developed. The main benefit by sharing resources through the "WEC platform" is the possibility to optimize the cost and the procedures of safety and maintenance team, in case of alerts and, finally to reduce overflows. Among the different services implemented on the WEC platform, ARIA have developed a product having the goal to support sewage/water distribution operators, based on a gradual forecast information system ( at 48hrs/24hrs/12hrs horizons) of heavy precipitation. For each fixed deadline different type of operation are implemented: 1) 48hour horizon, organisation of "on call team", 2) 24 hour horizon, update and confirm the "on call team", 3) 12 hour horizon, secure human resources and equipment (emptying storage basins, pipes manipulations …). More specifically CMCC have provided a statistical downscaling method in order to provide a "rough" daily local precipitation at 24 hours, especially when high precipitation values are expected. This statistical technique consists of an adaptation of analogue method based on ECMWF data (analysis and forecast at 24 hours). One of the most advantages of this technique concerns a lower computational burden and budget compared to running a Numerical Weather Prediction (NWP) model, also if, of course it provides only this

  4. Biphasic Insulin Analogues in Type 2 Diabetes: Expert Panel Recommendations

    Directory of Open Access Journals (Sweden)

    Sema Akalın

    2011-09-01

    Full Text Available Recently, the prevalence of type 2 diabetes has reached pandemic levels all over the world, and the problem is still growing. Type 2 diabetes is a progressive disease, in which insulin resistance and decrease in beta cell function accompany obesity. Early disorder, which ensues in clinical progression of the disease, is the defect of early phase insulin secretion. Patients have already lost approximately half of their beta cell reserve at the time of diagnosis. Aims of type 2 diabetes treatment are to eliminate hyperglycemia caused by insufficient insulin secretion and/or insulin resistance, to slow down beta cell destruction/depletion, to improve concomitant metabolic problems and to prevent complications. In treatment algorithms, insulin is evaluated as a replacement therapy at the following stage after life style changes (medical nutrition therapy, exercise and oral anti-diabetic drugs (OADs options. Since beta cell depletion is present at initial stages of the disease, it transforms insulin therapy into an earlier approach in treatment stages. Premixed insulin forms are one of the proposed treatment options in patients with hyperglycemia that is not controlled by OADs. These types of insulins are developed to meet both basal and postprandial insulin requirements of patients. Currently, premixed human insulin forms are replaced by analogue insulin forms, which can mimic the physiological secretion in more acceptable manner. Biphasic analogue insulin is one of the readily available pre-mixed analogue insulin forms, an example of this, Biphasic Insulin aspart 30 which is the one of the premixed analoge insulin forms, contains 30% insulin aspart and 70% protaminated insulin aspart. Consensus recommending the individualized approach in insulin therapy implies that physicians should have more detailed information about the use of different insulin forms. Although a global consensus report about initiation, titration and intensification and the use

  5. Analogue Models Of Volcanic Spreading At Mt. Vesuvius

    Science.gov (United States)

    De Matteo, Ada; Castaldo, Raffaele; D'Auria, Luca; James, Michael; Lane, Steve; Massa, Bruno; Pepe, Susi; Tizzani, Pietro

    2015-04-01

    Somma-Vesuvius is a quiescent strato-volcano of the Neapolitan district, southern Italy, for which various geophysical and geological evidences (e.g. geodetic measurements, geological and structural data, seismic profiles interpretations and surface deformation analysis with Differential Interferometric Synthetic Aperture Radar (DInSAR)) indicate ongoing spreading deformation. In this research we investigate the spreading deformation and associated surface deformation pattern by performing analogue experiments and comparing the results with actual ground deformation as measured using DInSAR data recorded between 1992 and 2010. Somma-Vesuvius consists of a volcanic cone (Gran Cono) lying within an asymmetric caldera (Somma). The Somma caldera is the result of at least 7 Plinian eruptions, the last of which was the 79 CE. Pompeii eruption. The current cone of Mt. Vesuvius grew within the caldera in the following centuries as the effect of continued explosive and effusive activity of the volcano. The volcano lies on a substratum consisting of a Mesozoic carbonatic basement, overlapped by Holocene clastic sediments and volcanic rocks. Our analogue models were built to simulate the shape of the Somma-Vesuvius top a scale of about 1:100000, emplaced on a sand layer (brittle behaviour) laid on a silicone layer (ductile behaviour). Models are based on the Fluid-dynamics Dimensionless Analysis (FDA), according to the Buckingham-Π theorem. In this context, we considered few dimensionless parameters that allowed the setting of a reliable scaled model. To represent the complex Somma-Vesuvius geometry, an asymmetric model was built by setting a truncated cone (mimicking the topography of Somma edifice) topped by another small cone (mimicking the Gran Cono) shifted off the axis of the main cone. Different experiments were carried out in which the thickness of the basal sand layer and of the silicone one were varied. To quantify the vertical and horizontal displacements the

  6. Quality of shrimp analogue product as affected by addition of modified potato starch.

    Science.gov (United States)

    Remya, S; Basu, S; Venkateshwarlu, G; Mohan, C O

    2015-07-01

    The present study was aimed to investigate the effects of addition of modified potato starch on the biochemical and textural properties of shrimp analogue/imitation shrimp, a popular value-added product prepared from surimi. Three batches of shrimp analogues were prepared with 0 % (NPS), 50 % (CPS) and 100 % (MPS) of modified starch incorporation and various quality attributes were monitored at regular intervals during frozen storage (-20 °C). Loss of myofibrillar protein was least for the shrimp analogue sample added with 100 % modified potato starch. The expressible moisture content of MPS (2.48 %) was less affected by long term storage compared to CPS (3.38 %) and NPS (3.99 %). During extended low temperature storage, the textural quality of sea food analogue was highly influenced by the type of starch added to it. The percentage of modified potato starch added to shrimp analogue significantly (p ≤ 0.05) affected its hardness and fracturability. MPS samples did not show significant changes in hardness during storage as compared to other two samples. Springiness of shrimp analogue increased 2.57, 1.5 and 1.77 times with the storage period for samples with NPS, CPS and MPS, respectively. Addition of modified potato starch improved the sensory quality and textural properties of shrimp analogue and reduced the quality degradation during frozen storage as compared to NPS which contained only native potato starch.

  7. Uncovering mass segregation with galaxy analogues in dark-matter simulations

    Science.gov (United States)

    Joshi, Gandhali D.; Parker, Laura C.; Wadsley, James

    2016-10-01

    We investigate mass segregation in group and cluster environments by identifying galaxy analogues in high-resolution dark-matter simulations. Subhaloes identified by the Amiga's Halo Finder (AHF) and ROCKSTAR halo finders have similar mass functions, independent of resolution, but different radial distributions due to significantly different subhalo hierarchies. We propose a simple way to classify subhaloes as galaxy analogues. The radial distributions of galaxy analogues agree well at large halocentric radii for both AHF and ROCKSTAR but disagree near parent halo centres where the phase-space information used by ROCKSTAR is essential. We see clear mass segregation at small radii (within 0.5 rvir) with average galaxy analogue mass decreasing with radius. Beyond the virial radius, we find a mild trend where the average galaxy analogue mass increases with radius. These mass segregation trends are strongest in small groups and dominated by the segregation of low-mass analogues. The lack of mass segregation in massive galaxy analogues suggests that the observed trends are driven by the complex accretion histories of the parent haloes rather than dynamical friction.

  8. Comparative transport efficiencies of urea analogues through urea transporter UT-B.

    Science.gov (United States)

    Zhao, Dan; Sonawane, N D; Levin, Marc H; Yang, Baoxue

    2007-07-01

    Expression of urea transporter UT-B confers high urea permeability to mammalian erythrocytes. Erythrocyte membranes also permeate various urea analogues, suggesting common transport pathways for urea and structurally similar solutes. In this study, we examined UT-B-facilitated passage of urea analogues and other neutral small solutes by comparing transport properties of wildtype to UT-B-deficient mouse erythrocytes. Stopped-flow light-scattering measurements indicated high UT-B permeability to urea and chemical analogues formamide, acetamide, methylurea, methylformamide, ammonium carbamate, and acrylamide, each with P(s)>5.0 x 10(-6) cm/s at 10 degrees C. UT-B genetic knockout and phloretin treatment of wildtype erythrocytes similarly reduced urea analogue permeabilities. Strong temperature dependencies of formamide, acetamide, acrylamide and butyramide transport across UT-B-null membranes (E(a)>10 kcal/mol) suggested efficient diffusion of these amides across lipid bilayers. Urea analogues dimethylurea, acryalmide, methylurea, thiourea and methylformamide inhibited UT-B-mediated urea transport by >60% in the absence of transmembrane analogue gradients, supporting a pore-blocking mechanism of UT-B inhibition. Differential transport efficiencies of urea and its analogues through UT-B provide insight into chemical interactions between neutral solutes and the UT-B pore.

  9. Efficacy of Antimicrobials on Bacteria Cultured in a Spaceflight Analogue

    Science.gov (United States)

    Nickerson, CA; Wotring, Virginia; Barrila, Jennifer; Crabbe, Aurelie; Castro, Sarah; Davis, Richard; Rideout, April; McCarthy, Breanne; Ott, C. Mark

    2014-01-01

    As humans travel in space, they will interact with microbial flora from themselves, other crewmembers, their food, and the environment. While evaluations of microbial ecology aboard the Mir and ISS suggest a predominance of common environmental flora, the presence of (and potential for) infectious agents has been well documented. Likewise, pathogens have been detected during preflight monitoring of spaceflight food, resulting in the disqualification of that production lot from flight. These environmental and food organisms range from the obligate pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium), which has been responsible for disqualification and removal of food destined for ISS and has previously been reported from Shuttle crew refuse, to the opportunistic pathogen Staphylococcus aureus, isolated numerous times from ISS habitable compartments and the crew. Infectious disease events have affected spaceflight missions, including an upper respiratory infection that delayed the launch of STS-36 and an incapacitating Pseudomonas aeruginosa urinary tract infection of a crewmember during Apollo 13. These observations indicate that the crew has the potential to be exposed to obligate and opportunistic pathogens. This risk of exposure is expected to increase with longer mission durations and increased use of regenerative life support systems. As antibiotics are the primary countermeasure after infection, determining if their efficacy during spaceflight missions is comparable to terrestrial application is of critical importance. The NASA Rotating Wall Vessel (RWV) culture system has been successfully used as a spaceflight culture analogue to identify potential alterations in several key microbial characteristics, such as virulence and gene regulation, in response to spaceflight culture. We hypothesized that bacteria cultured in the low fluid shear RWV environment would demonstrate changes in efficacy of antibiotics compared to higher fluid shear controls

  10. The Greenland Analogue Project (GAP). Literature review of hydrogeology/ hydrogeochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Wallroth, Thomas; Lokrantz, Hanna; Rimsa, Andrius (Bergab Consulting Geologists, Goeteborg (Sweden))

    2010-09-15

    This report is produced as part of the Greenland Analogue Project (GAP), carried out as a collaboration project with the Canadian Nuclear Waste Management Organization (NWMO), Posiva Oy and the Swedish Nuclear Fuel and Waste Management Co (SKB). The overall aim of the project is to improve the current understanding of hydrogeological and hydrogeochemical processes associated with continental-scale glacial periods including with the presence of permafrost and the advance/retreat of ice sheets. The project will focus on studying how an ice sheet affects groundwater flow and water chemistry around a deep geological repository in crystalline bedrock. The Greenland Analogue Project consists of three active sub-projects (A-C) with individual objectives. Field studies are conducted in the Kangerlussuaq region, in central Western Greenland. Sub-projects A and B collectively aim at improving the understanding of ice sheet hydrology by combining investigations on surface water processes with ice sheet drilling and instrumentation. In sub-project C, the penetration of glacial melt water into the bedrock, groundwater flow and the chemical composition of water will be studied. Main planned activities in sub-project C include drilling of a deep borehole in front of the ice sheet, in which different downhole surveys, sampling and monitoring will be carried out. The primary aim of this report is to review available information about hydrogeology and hydrogeochemistry in central Western Greenland, with special emphasis on the area around Kangerlussuaq. The relevant information about this area is however very limited, and it was decided to extend the review to briefly include studies made in other regions with similar conditions in terms of geology, climate and glaciology. The number of published studies made in other areas with glaciers, ice sheets or permafrost is very large, and the review and list of references in this report is far from complete. It is also obvious that both

  11. Insights into magma depth under resurgent domes from analogue modelling

    Science.gov (United States)

    Brothelande, Elodie; Merle, Olivier

    2014-05-01

    Post-collapse resurgence is a common process observed in many calderas, yet the mechanisms of this phenomenon are still poorly known. Whereas most models account for circular doming, deviations from circular shape is common in nature, reflecting either the shape of the underlying reservoir or the influence of regional structures. We conducted a series of scaled experiments to investigate the structural evolution of a resurgent dome in response to an elongated source. A sand-plaster mixture was chosen as the analogue for the brittle pile of volcanic rocks and silicone putty simulates the ductile behavior of the intruding magma. The uplift of the intrusion roof drives the resurgence. A set of 21 experiments have been conducted varying the thickness of the brittle overburden and the width of the silicone intrusion. Three types of extensional patterns associated with doming are observed: two lateral grabens, a single axial graben, and no graben. In the third type, the shape of the dome is significantly less elongated and extension is accommodated by two sets of normal faults, which are roughly concentric and radial from the center of the dome. These three extension modes are strongly related to the thickness of the brittle overburden. The "single axial graben" type, frequently observed in nature, corresponds to intermediate thicknesses. Results of experiments with a single graben show that the dome width is dependent on both tested parameters. In contrast, the graben width is strongly dependent on the overburden thickness whereas the intrusion width is of limited importance. As a significant result, the graben width shows an almost perfectly linear dependency upon the brittle overburden thickness. A simple geometrical model of the analogue system can be proposed, in which opposite master faults of the graben intersect at depth at the junction with the rising viscous intrusion. Geometric constants, or nearly so, such as the slope of the dome flanks and the dip of the

  12. Therapy of neuroendocrine tumors with radiolabeled somatostatin-analogues

    Energy Technology Data Exchange (ETDEWEB)

    De Jong, M.; Breeman, A.P.; Bernard, H.F.; Kooij, P.P.M.; Kwekkeboom, D.J.; Valkema, R. [Rotterdam University Hospital and Erasmus University, Rotterdam (Netherlands). Internal Medicine; Van Eijck, C.H.J.; Slooter, G.D. [Basel Surgery, Basel (Switzerland). Dept. of Nuclear Medicine; Maecke, H.R.; Krenning, E.P. [Basel Kantonspital, Basel (Switzerland). Dept. of Nuclear Medicine

    1999-12-01

    Peptide receptor scintigraphy with the radioactive somatostatin-analogue ({sup 111}In-DTPA{sup 0})octreotide (DTPA=diethylenetriaminepentaacetic acid) is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumors. With this technique primary tumors and metastases of neuroendocrine cancers as well as of many other cancer types can be localised. A new application is the use of peptide receptor radionuclide therapy, administrating high doses of {sup 111}In- or {sup 90}Y-labeled octreotide-analogues. In the preclinical situation it was investigated on the radiotherapeutic effect of {sup 90}Y- and {sup 111}In-labeled (DOTA{sup 0}, Tyr{sup 3})octreotide (DOTA=tetraazacyclododecanetetraacetic acid) or ({sup 111}In-DTPA{sup 0})octreotide in Lewis rats bearing the somatostatin receptor-positive rat pancreatic tumor CA20948 in (A) the flank of (B) in the liver. Thirty end-stage patients with mostly neuroendocrine progressing tumors were treated with ({sup 111}In-DTPA{sup 0})octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase 1 trial. (A) Flank model: at least two 111MBq injections of ({sup 111}In-DOTA{sup 0}, Tyr{sup 3})octreotide were needed to reach tumor response, in 40% of the animals complete tumor remission was found after a follow-up period of 10 months. One or two injections of ({sup 90}Y-DOTA{sup 0}, Tyr{sup 3})octreotide yielded transient stable disease. (B) Liver model: it was found that peptide receptor radionuclide therapy is only effective if somatostatin receptors are present on the tumors, and is therefore receptor-mediated. High radioactive doses of 370 MBq ({sup 111}In-DTPA{sup 0})octreotide or 93 MBq ({sup 90}Y-DOTA{sup 0}, Tyr{sup 3})octreotide can inhibit the growth of somatostatin receptor-positive metastases. There were no major clinical side effects after up to 2 years treatment, except that a transient decline in platelet counts and lymphocyte subsets can occur

  13. Serotonin receptor binding affinities of several hallucinogenic phenylalkylamine and N,N-dimethyltryptamine analogues.

    Science.gov (United States)

    Glennon, R A; Liebowitz, S M; Mack, E C

    1978-08-01

    Hallucinogenic phenylalkylamine and N,N-dimethyltryptamine analogues are known to affect serotonergic systems both in vivo and in vitro. Using a rat stomach fundus model, the 5-HT receptor binding affinities of several of these analogues were determined and compared. The most behaviorally potent analogues examined, DOB, DOM, and 5-methoxy-N,N-dimethyltryptamine, were found to possess rather high affirmities (pA2 = 7.35, 7.12, and 7.08, respectively) for the 5-HT receptors of the model system.

  14. Polymerization of fluorescent analogue of plant actin in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Maize pollen actin has been labeled with Oregon Green 488 iodoacetamide. A yield of 3 mg fluorescent actin analogue has been obtained from 10 mg of maize pollen actin, which is 99% in purity and the dye/protein ratio is 72%. In the presence of Mg2+ and K+, the fluorescent actin analogue polymerized into filaments in vitro. Green fluorescent filaments were observed when the fluorescent actin was introduced into living plant cells by microinjection, indicating that the fluorescent actin analogue functions similarly to the native actin.

  15. Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

    Directory of Open Access Journals (Sweden)

    Patrick Rabe

    2014-08-01

    Full Text Available Tropodithietic acid (TDA is a structurally unique sulfur-containing antibiotic from the Roseobacter clade bacterium Phaeobacter inhibens DSM 17395 and a few other related species. We have synthesised several structural analogues of TDA and used them in bioactivity tests against Staphylococcus aureus and Vibrio anguillarum for a structure–activity relationship (SAR study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than the bioactivity of the natural product. The synthesis of this compound and of several analogues is presented and the bioactivity of the synthetic compounds is discussed.

  16. Simultaneous preparation of four truncated analogues of discodermolide by fluorous mixture synthesis.

    Science.gov (United States)

    Curran, Dennis P; Furukawa, Takashi

    2002-06-27

    [structure: see text] Four truncated analogues of the natural product discodermolide were synthesized in a single synthetic sequence. Precursors bearing four different groups at C22, each with a unique fluorous p-methoxybenzyl substituent on the C17 hydroxy group, were mixed and taken through an nine-step sequence. Demixing by fluorous chromatography followed by deprotection and purification provided the individual analogues in 3-7% overall yields and with a savings of 24 synthetic steps. Fluorous mixture synthesis is recommended as a new technique to make multiple natural product analogues in a single multistep synthesis.

  17. Design, synthesis and characterisation of gurmarin and melanocortin analogues of gurmarin

    DEFF Research Database (Denmark)

    Eliasen, Rasmus

    to the melanocortin 4 receptor had a binding affinity of 500 nM which is around ten-fold lower affinity than the endogenous agonist a-melanocyte stimulating hormone. Finally, it was demonstrated that it was possible to synthesise melanocortin analogues of the cyclic cystine knotted peptide kalata B1, a plant peptide......, the analogue was less potent than a-melanocortin stimulating hormone at activating the melanocortin 4 receptor. In addition, the analogues were shown to be highly resistant to proteolysis compared to a-melanocyte stimulating hormone. In summary, the possibility of grafting melanocortin binding sequences...

  18. Isolation and structural elucidation of a new tadalafil analogue in health supplements: bisprenortadalafil.

    Science.gov (United States)

    Lee, Ji Hyun; Park, Han Na; Ganganna, Bogonda; Jeong, Ji Hye; Park, Sung-Kwan; Lee, Jongkook; Baek, Sun Young

    2016-06-01

    A new tadalafil analogue was found, along with nortadalafil, using HPLC-DAD during the inspection of a health product sold without official approval. The analogue was separated using a semi-preparative HPLC system and its structure was determined by a combination of mass spectrometry and NMR spectroscopy. The compound was identified as a tadalafil analogue in which the N-methyl group of tadalafil was replaced with a tadalafil precursor moiety. Nuclear Overhauser effect spectroscopy experiments suggested a cis-relationship between the substituents on a piperidine ring in the tadalafil moiety.

  19. GnRH Analogues in the Prevention of Ovarian Hyperstimulation Syndrome

    Science.gov (United States)

    Alama, Pilar; Bellver, Jose; Vidal, Carmen; Giles, Juan

    2013-01-01

    The GnRH analogue (agonist and antagonist GnRH) changed ovarian stimulation. On the one hand, it improved chances of pregnancy to obtain more oocytes and better embryos. This leads to an ovarian hyper-response, which can be complicated by the ovarian hyperstimulation syndrome (OHSS). On the other hand, the GnRH analogue can prevent the incidence of OHSS: GnRH antagonist protocols, GnRH agonist for triggering final oocyte maturation, either together or separately, coasting, and the GnRH analogue may prove useful for avoiding OHSS in high-risk patients. We review these topics in this article. PMID:23825982

  20. Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

    DEFF Research Database (Denmark)

    Rabe, Patrick; Klapschinski, Tim A.; Brock, Nelson L.

    2014-01-01

    aureus and Vibrio anguillarum for a structure-activity relationship (SAR) study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than the bioactivity of the natural product. The synthesis of this compound and of several analogues......Tropodithietic acid (TDA) is a structurally unique sulfur-containing antibiotic from the Roseobacter clade bacterium Phaeobacter inhibens DSM 17395 and a few other related species. We have synthesised several structural analogues of TDA and used them in bioactivity tests against Staphylococcus...

  1. Electrospray ionization mass spectral characteristics and fragmentation mechanisms of Angiotensin II and its analogues

    Science.gov (United States)

    Li, Huihui; Yuan, Gu

    2006-05-01

    The characteristic fragmentation pathways of Angiotensin II and eight analogues were investigated by electrospray ionization tandem mass spectrometry. The main fragmentations involve the cleavages of the CCO and CONH bonds with the loss of water, ammonia or carbon monoxide and rearrangements involving hydrogen atoms, and the MS/MS spectra give significant sequence information of these octapeptides. In addition, the two members of the analogues with the same mass and different elemental composition can be distinguished by the MS/MS spectra of [M + H]+ and fragment ions. These results show that ESI tandem mass spectrometry is an excellent tool for the structural identification of Angiotensin II and its analogues.

  2. New synthetic strategies towards psammaplin A, access to natural product analogues for biological evaluation.

    Science.gov (United States)

    Baud, Matthias G J; Leiser, Thomas; Meyer-Almes, Franz-Josef; Fuchter, Matthew J

    2011-02-07

    New synthetic routes towards the natural product psammaplin A were developed with the particular view to preparing diverse analogues for biological assessment. These routes utilize cheap and commercially available starting materials, and allowed access to psammaplin A analogues not accessible via currently reported methods. Preliminary biological studies revealed these compounds to be the most potent non peptidic inhibitors of the enzyme histone deacetylase 1 (HDAC1, class I) discovered so far. Interestingly, psammaplin A and our synthetic analogues show class I selectivity in vitro, an important feature for the design and synthesis of future isoform selective inhibitors.

  3. Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid.

    Science.gov (United States)

    Rabe, Patrick; Klapschinski, Tim A; Brock, Nelson L; Citron, Christian A; D'Alvise, Paul; Gram, Lone; Dickschat, Jeroen S

    2014-01-01

    Tropodithietic acid (TDA) is a structurally unique sulfur-containing antibiotic from the Roseobacter clade bacterium Phaeobacter inhibens DSM 17395 and a few other related species. We have synthesised several structural analogues of TDA and used them in bioactivity tests against Staphylococcus aureus and Vibrio anguillarum for a structure-activity relationship (SAR) study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than the bioactivity of the natural product. The synthesis of this compound and of several analogues is presented and the bioactivity of the synthetic compounds is discussed.

  4. Synthesis of a des-B-ring bryostatin analogue leads to an unexpected ring expansion of the bryolactone core.

    Science.gov (United States)

    Kraft, Matthew B; Poudel, Yam B; Kedei, Noemi; Lewin, Nancy E; Peach, Megan L; Blumberg, Peter M; Keck, Gary E

    2014-09-24

    A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biological function in cells. These studies shed new light on the role of the bryostatin B-ring in conferring bryo-like biological function to bryostatin analogues.

  5. Encoding complexity within supramolecular analogues of frustrated magnets

    Science.gov (United States)

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

    2016-05-01

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

  6. Antimicrobial Activity of Xanthohumol and Its Selected Structural Analogues.

    Science.gov (United States)

    Stompor, Monika; Żarowska, Barbara

    2016-05-11

    The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus). The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, fungi (Alternaria sp.), and yeasts (Rhodotorula rubra, Candida albicans) revealed that compounds with at least one hydroxyl group-all of them have it at the C-4 position-demonstrated good activity. Our research showed that the strain S. aureus was more sensitive to chalcones than to the isomers in which the heterocyclic ring C is closed (flavanones). The strain R. rubra was moderately sensitive to only one compound: 4-hydroxy-4'-methoxychalcone 8. Loss of the hydroxyl group in the B-ring of 4'-methoxychalcones or its replacement by a halogen atom (-Cl, -Br), nitro group (-NO₂), ethoxy group (-OCH₂CH₃), or aliphatic substituent (-CH₃, -CH₂CH₃) resulted in the loss of antimicrobial activity towards both R. rubra yeast and S. aureus bacteria. Xanthohumol 1, naringenin 5, and chalconaringenin 7 inhibited growth of S. aureus, whereas 4-hydroxy-4'-methoxychalcone 8 was active towards two strains: S. aureus and R. rubra.

  7. Relationship Between Resistance Gene Analogue and Blast Resistance in Rice

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-min; FAN Cheng-ming; YANG Yan; HE Yue-qiu

    2009-01-01

    DNA fragments of 43 rice varieties were amplified with 11 pairs of primers designed based on resistance gene analogue (RGA) of plants, and the blast resistance of the varieties was identified by inoculation with 33 isolates of Magnaporthe grisea collected from Yunnan Province, China. Clustering results revealed a significant correlation between the blast resistance and DNA bands with a correlation coefficient of 0.6117 (α=0.01), indicating that the resistance analysis based on RGA-PCR clustering analysis coincided with that based on inoculation. The correlation coefficients, ranging from 0.1701 to 0.535, however, depended on the primers. Five pairs of primers, S1/AS3, S1 INV/S2 INV, XLRR For/XLRR Rev, Pto-Kin1 IN/Pto-Kin2 IN, and NLRR For/NLRR Rev might be applied for blast resistance identification in consideration of their band numbers and polymorphisms, and their correlation coefficients with blast resistance were 0.5305, 0.4898, 0.4059, 0.3719 and 0.3524, respectively. Besides, indica and japonica rice except two highly susceptible varieties, CO39 and Lijiangxintuanheigu, could be well classified by the 11 pairs of primers.

  8. Neurotoxicity Caused by the Treatment with Platinum Analogues

    Directory of Open Access Journals (Sweden)

    Sousana Amptoulach

    2011-01-01

    Full Text Available Platinum agents (cisplatin, carboplatin, and oxaliplatin are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.

  9. Selective affinity of pirenzepine analogues for subtypes of muscarinic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Stubbins, J.F.; Smith, J.D.; Liu, W.S.; Gulya, K.; Yamamura, H.I.

    1986-03-05

    Pirenzepine (PZ), telenzepine (TZ) and quinuclidinyl xanthene-9-carboxylate (QNX) are antimuscarinic agents containing a tricyclic ring system and a basic side chain that have been reported to have selective affinity for the M/sub 1/ subtype of receptor. They have prepared and examined seven new PZ analogues containing modifications in either the tricyclic ring system, the side-chain, or both. Affinity for M/sub 1/ type receptors was determined by displacement of specifically-bound (/sup 3/H)PZ from rat cerebral cortex homogenates. Affinity for M/sub 2/ type receptors was measured on rat heart homogenate using (/sup 3/H)(-)quinuclidinyl benzilate. The ratio of the K/sub i/'s for M/sub 1/ and M/sub 2/ receptors were calculated and compared to PZ. All of the compounds had a higher affinity for M/sub 1/ than M/sub 2/ receptors. Three of the compounds were comparable to PZ in selectivity, but the more selective compounds had a weaker affinity for M/sub 1/ receptors. TZ and QNX were less selective than PZ.

  10. Bioactive phenylpropanoid analogues from Piper betle L. var. haldia leaves.

    Science.gov (United States)

    Atiya, Akhtar; Sinha, Barij Nayan; Lal, Uma Ranjan

    2017-02-15

    Phytochemical analyses of the chloroform extract of Piper betle L. var. birkoli, Piperaceae, leaves led to the isolation of two new phenylpropanoid analogues: bis-chavicol dodecanoyl ester (2) and bis-hydroxychavicol dodecanoyl ester (3), along with one known compound: allyl-3-methoxy-4-hydroxybenzene (1) on the basis of spectroscopic data 1D ((1)H and (13)C) and 2D ((1)H-(1)H COSY and HMBC) NMR, as well as ESI-MS, FT-IR, HR-ESI-MS and LC-ESI-MS. Compound 2 and 3 exhibited excellent antioxidant DPPH radical scavenging activity with IC50 values of 12.67 μg/mL and 1.08 μg/mL compared to ascorbic acid as a standard antioxidant drug with IC50 value of 6.60 μg/mL. Evaluation of cytotoxic activity against two human oral cancer cell lines (AW13516 and AW8507) showed significant effect with GI50 values of 19.61 and 23.01 μg/mL for compound 2 and 10.25 and 13.12 μg/mL for compound 3, compared to Doxorubicin(®) as a standard cytotoxic drug with GI50 value of < 10 μg/mL.

  11. Nontoxic piperamides and their synthetic analogues as novel antifouling reagents

    KAUST Repository

    Huang, Xiang-Zhong

    2014-03-25

    Bioassay-guided isolation of an acetone extract from a terrestrial plant Piper betle produced four known piperamides with potent antifouling (AF) activities, as evidenced by inhibition of settlement of barnacle cypris larvae. The AF activities of the four piperamides and 15 synthesized analogues were compared and their structure-activity relationships were probed. Among the compounds, piperoleine B and 1-[1-oxo-7-(3′,4′-methylenedioxyphenyl)-6E-heptenyl]-piperidine (MPHP) showed strong activity against settlement of cyprids of the barnacle Balanus amphitrite, having EC50 values of 1.1 ± 0.3 and 0.5 ± 0.2 μg ml-1, respectively. No toxicity against zebra fish was observed following incubation with these two compounds. Besides being non-toxic, 91% of piperoleine B-treated cyprids and 84% of MPHP-treated cyprids at a concentration of 100 μM completed normal metamorphosis in recovery bioassays, indicating that the anti-settlement effect of these two compounds was reversible. Hydrolysis and photolysis experiments indicated that MPHP could be decomposed in the marine environment. It is concluded that piperamides are promising compounds for use in marine AF coatings. © 2014 © 2014 Taylor & Francis.

  12. Generalized uncertainty principle and analogue of quantum gravity in optics

    Science.gov (United States)

    Braidotti, Maria Chiara; Musslimani, Ziad H.; Conti, Claudio

    2017-01-01

    The design of optical systems capable of processing and manipulating ultra-short pulses and ultra-focused beams is highly challenging with far reaching fundamental technological applications. One key obstacle routinely encountered while implementing sub-wavelength optical schemes is how to overcome the limitations set by standard Fourier optics. A strategy to overcome these difficulties is to utilize the concept of a generalized uncertainty principle (G-UP) which has been originally developed to study quantum gravity. In this paper we propose to use the concept of G-UP within the framework of optics to show that the generalized Schrödinger equation describing short pulses and ultra-focused beams predicts the existence of a minimal spatial or temporal scale which in turn implies the existence of maximally localized states. Using a Gaussian wavepacket with complex phase, we derive the corresponding generalized uncertainty relation and its maximally localized states. Furthermore, we numerically show that the presence of nonlinearity helps the system to reach its maximal localization. Our results may trigger further theoretical and experimental tests for practical applications and analogues of fundamental physical theories.

  13. Digitally Programmable Analogue Circuits for Sensor Conditioning Systems

    Science.gov (United States)

    Zatorre, Guillermo; Medrano, Nicolás; Sanz, María Teresa; Aldea, Concepción; Calvo, Belén; Celma, Santiago

    2009-01-01

    This work presents two current-mode integrated circuits designed for sensor signal preprocessing in embedded systems. The proposed circuits have been designed to provide good signal transfer and fulfill their function, while minimizing the load effects due to building complex conditioning architectures. The processing architecture based on the proposed building blocks can be reconfigured through digital programmability. Thus, sensor useful range can be expanded, changes in the sensor operation can be compensated for and furthermore, undesirable effects such as device mismatching and undesired physical magnitudes sensor sensibilities are reduced. The circuits were integrated using a 0.35 μm standard CMOS process. Experimental measurements, load effects and a study of two different tuning strategies are presented. From these results, system performance is tested in an application which entails extending the linear range of a magneto-resistive sensor. Circuit area, average power consumption and programmability features allow these circuits to be included in embedded sensing systems as a part of the analogue conditioning components. PMID:22412331

  14. Antimicrobial Activity of Xanthohumol and Its Selected Structural Analogues

    Directory of Open Access Journals (Sweden)

    Monika Stompor

    2016-05-01

    Full Text Available The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus. The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of Gram-positive (Staphylococcus aureus and Gram-negative (Escherichia coli bacteria, fungi (Alternaria sp., and yeasts (Rhodotorula rubra, Candida albicans revealed that compounds with at least one hydroxyl group—all of them have it at the C-4 position—demonstrated good activity. Our research showed that the strain S. aureus was more sensitive to chalcones than to the isomers in which the heterocyclic ring C is closed (flavanones. The strain R. rubra was moderately sensitive to only one compound: 4-hydroxy-4’-methoxychalcone 8. Loss of the hydroxyl group in the B-ring of 4’-methoxychalcones or its replacement by a halogen atom (−Cl, −Br, nitro group (−NO2, ethoxy group (−OCH2CH3, or aliphatic substituent (−CH3, −CH2CH3 resulted in the loss of antimicrobial activity towards both R. rubra yeast and S. aureus bacteria. Xanthohumol 1, naringenin 5, and chalconaringenin 7 inhibited growth of S. aureus, whereas 4-hydroxy-4′-methoxychalcone 8 was active towards two strains: S. aureus and R. rubra.

  15. Scaling issues for analogue circuits using Double Gate SOI transistors

    Science.gov (United States)

    Lim, Tao Chuan; Armstrong, G. Alastair

    2007-02-01

    This work presents a systematic analysis on the impact of source-drain engineering using gate "non-overlapped" on the RF performance of nano-scaled fully depleted Double Gate SOI transistors, when used in the design of a typical two stage Operational Transconductance Amplifier (OTA). It is evident that for a gate length less than 40 nm, the incorporation of optimal source-drain engineering requiring a spacer length, which may exceed the length of the gate, is particularly beneficial in analogue applications. Lengthening the spacer reduces gate capacitance in the weak/moderate inversion region more than transconductance, improving cut-off frequency fT. This improvement is particularly significant in a circuit application where an optimal spacer of 1.5 times the gate length is proposed. This gate under-lapped concept with extended spacer can also significantly enhance DC gain of the OTA, by increasing the Early Voltage, while maximising the transconductance to current ratio in the weak to moderate inversion, close to threshold voltage. With optimally designed devices, the sensitivity of OTA circuit performance to doping profile is shown to be relatively low.

  16. Toward the validation of visual analogue scale for anxiety.

    Science.gov (United States)

    Facco, E; Zanette, G; Favero, L; Bacci, C; Sivolella, S; Cavallin, F; Manani, G

    2011-01-01

    Anxiety is a relevant problem in dental practice. The Visual Analogue Scale for Anxiety (VAS-A), introduced in dentistry in 1988, has not yet been validated in large series. The aim of this study is to check VAS-A effectiveness in more than 1000 patients submitted to implantology. The VAS-A and the Dental Anxiety Scale (DAS) were administered preoperatively to 1114 patients (459 males and 655 females, age 54.7 ± 13.1 years). Statistical analysis was conducted with Pearson correlation coefficient, the receiver operating characteristic (ROC) curve, and McNemar tests. A close correlation between DAS and VAS-A was found (r  =  0.57, P < .0001); the VAS-A thresholds of dental anxiety and phobia were 5.1 and 7.0 cm, respectively. Despite a significant concordance of tests in 800 cases (72%), disagreement was found in the remaining 314 cases (28%), and low DAS was associated with high VAS-A (230 cases) or vice versa (84 cases). Our study confirms that VAS-A is a simple, sensitive, fast, and reliable tool in dental anxiety assessment. The rate of disagreement between VAS-A and DAS is probably due to different test sensitivities to different components of dental anxiety. VAS-A can be used effectively in the assessment of dental patients, using the values of 5.1 cm and 7.0 cm as cutoff values for anxiety and phobia, respectively.

  17. Detecting Pyrolysis Products from Bacteria in a Mars Soil Analogue

    Science.gov (United States)

    Glavin, D. P.; Cleaves, H. J.; Schubert, M.; Aubrey, A.; Buch, A.; Mahaffy, P. R.; Bada, J. L.

    2004-01-01

    One of the primary objectives of the 1976 Viking missions was to determine whether organic compounds, possibly of biological origin, were present in the Martian surface soils. The Viking gas chromatography mass spectrometry (GCMS) instruments found no evidence for any organic compounds of Martian origin above a few parts per billion in the upper 10 cm of surface soil, suggesting the absence of a widely distributed Martian biota. However, it is now known that key organic compounds important to biology, such as amino acids, carboxylic acids and nucleobases, would likely have been missed by the Viking GCMS instruments. In this study, a Mars soil analogue that was inoculated with approx. 10 billion Escherichia coli cells was heated at 500 C under Martian ambient pressure to release volatile organic compounds from the sample. The pyrolysis products were then analyzed for amino acids and nucleobases using high performance liquid chromatography (HPLC) and GCMS. Our experimental results indicate that at the part per billion level, the degradation products generated from several million bacterial cells per gram of Martian soil would not have been detected by the Viking GCMS instruments. Upcoming strategies for Mars exploration will require in-situ analyses by instruments that can assess whether any organic compounds, especially those that might be associated with life, are present in Martian surface samples.

  18. Onboard Detection of Active Canadian Sulfur Springs: A Europa Analogue

    Science.gov (United States)

    Castano, Rebecca; Wagstaff, Kiri; Gleeson, Damhnait; Pappalardo, Robert; Chien, Steve; Tran, Daniel; Scharenbroich, Lucas; Moghaddam, Baback; Tang, Benyang; Bue, Brian; Doggett, Thomas; Mandl, Dan; Frye, Stuart

    2008-01-01

    We discuss a current, ongoing demonstration of insitu onboard detection in which the Earth Observing-1 spacecraft detects surface sulfur deposits that originate from underlying springs by distinguishing the sulfur from the ice-rich glacial background, a good analogue for the Europan surface. In this paper, we describe the process of developing the onboard classifier for detecting the presence of sulfur in a hyperspectral scene, including the use of a training/testing set that is not exhaustively labeled, i.e.not all true positives are marked, and the selection of 12, out of 242, Hyperion instrument wavelength bands to use in the onboard detector. This study aims to demonstrate the potential for future missions to capture short-lived science events, make decisions onboard, identify high priority data for downlink and perform onboard change detection. In the future, such capability could help maximize the science return of downlink bandwidth-limited missions, addressing a significant constraint in all deep-space missions.

  19. Design and synthesis of novel stiripentol analogues as potential anticonvulsants.

    Science.gov (United States)

    Aboul-Enein, Mohamed N; El-Azzouny, Aida A; Attia, Mohamed I; Maklad, Yousreya A; Amin, Kamilia M; Abdel-Rehim, Mohamed; El-Behairy, Mohammed F

    2012-01-01

    A series of stiripentol (STP) analogues namely, 2-[(1E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-ylidene]-N-(aryl/H)hydrazinecarboxamides 7a-h, (±)-(5RS)-N-(aryl/H)-(1,3-benzodioxol-5-yl)-3-tert-butyl-4,5-dihydro-1H-pyrazole-1-carboxamides (±)-8a-h, and (±)-[(5RS)-(1,3-benzodioxol-5-yl)-3-tert-butyl-4,5-dihydro-1H-pyrazol-1-yl](aryl)methanones (±)-13a-f was synthesized by adopting appropriate synthetic routes and was pharmacologically evaluated in the preliminary anticonvulsant screens. The selected bioactive new chemical entities were subjected to ED(50) determination and neurotoxicity evaluation. The most active congeners are 7h in MES screen and (±)-13b in scPTZ screen which displayed ED(50) values of 87 and 110 mg/kg, respectively, as compared to that of STP (ED(50) = 277.7 and 115 mg/kg in MES and scPTZ, respectively).

  20. Probing riboswitch-ligand interactions using thiamine pyrophosphate analogues.

    Science.gov (United States)

    Chen, Liuhong; Cressina, Elena; Dixon, Neil; Erixon, Karl; Agyei-Owusu, Kwasi; Micklefield, Jason; Smith, Alison G; Abell, Chris; Leeper, Finian J

    2012-08-14

    The Escherichia coli thiM riboswitch forms specific contacts with its natural ligand, thiamine pyrophosphate (TPP or thiamine diphosphate), allowing it to generate not only nanomolar binding affinity, but also a high degree of discrimination against similar small molecules. A range of synthetic TPP analogues have been used to probe each of the riboswitch-ligand interactions. The results show that the pyrimidine-sensing helix of thiM is exquisitely tuned to select for TPP by recognising the H-bonding donor and acceptors around its aminopyrimidine ring and also by forming π-stacking interactions that may be sensitive to the electronics of the ring. The central thiazolium ring of TPP appears to be more important for ligand recognition than previously thought. It may contribute to binding via long-range electrostatic interactions and/or by exerting an electron withdrawing effect on the pyrimidine ring, allowing its presence to be sensed indirectly and thereby allowing discrimination between thiamine (and its phosphate esters) and other aminopyrimidines found in vivo. The pyrophosphate moiety is essential for submicromolar binding affinity, but unexpectedly, it does not appear to be strictly necessary for modulation of gene expression.

  1. Analogue Realization of Fractional-Order Dynamical Systems

    Directory of Open Access Journals (Sweden)

    Ladislav Pivka

    2013-10-01

    Full Text Available As it results from many research works, the majority of real dynamical objects are fractional-order systems, although in some types of systems the order is very close to integer order. Application of fractional-order models is more adequate for the description and analysis of real dynamical systems than integer-order models, because their total entropy is greater than in integer-order models with the same number of parameters. A great deal of modern methods for investigation, monitoring and control of the dynamical processes in different areas utilize approaches based upon modeling of these processes using not only mathematical models, but also physical models. This paper is devoted to the design and analogue electronic realization of the fractional-order model of a fractional-order system, e.g., of the controlled object and/or controller, whose mathematical model is a fractional-order differential equation. The electronic realization is based on fractional-order differentiator and integrator where operational amplifiers are connected with appropriate impedance, with so called Fractional Order Element or Constant Phase Element. Presented network model approximates quite well the properties of the ideal fractional-order system compared with e.g., domino ladder networks. Along with the mathematical description, circuit diagrams and design procedure, simulation and measured results are also presented.

  2. A Nonsingular Brans Wormhole: An Analogue to Naked Black Holes

    CERN Document Server

    Bhattacharya, Amrita; Laserra, Ettore; Nandi, Kamal K

    2011-01-01

    In a recent paper, we showed the Jordan frame vacuum Brans Class I solution provided a wormhole analogue to Horowitz-Ross naked black hole in the wormhole range -3/2<{\\omega}<-4/3. Thereafter, the solution has been criticized by some authors that, because of the presence of singularity in that solution within this range, a wormhole interpretation of it is untenable. While the criticism is correct, we show here that (i) a singularity-free wormhole can actually be obtained from Class I solution by performing a kind of Wick rotation on it, resulting into what Brans listed as his independent Class II solution (ii) the Class II solution has all the necessary properties of a regular wormhole in a revised range -2<{\\omega}<-3/2 and finally, (iii) naked black holes, as described by Horowitz and Ross, are spacetimes where the tidal forces attain their maxima above the black hole horizon. We show that in the non-singular Class II spacetime this maxima is attained above the throat and thus can be treated as ...

  3. Conformational behavior of insect pheromones and analogues. Part II

    Science.gov (United States)

    Koča, Jaroslav; Carlsen, Per H. J.

    1992-04-01

    The conformational potential energy surface paths of the sex pheromone, Ipsenol, to the Bark Beetle, Ips typographus, and of a series of analogues have been elucidated using the program DAISY. The following structures were calculated: 2-methyl-6-methylene-7-octen-4-ol (Ipsenol, ( II)), 2-methyl-6-methylene-2,7-octadiene-4-ol acetate ( III), 2-methyl-6-methylene-3,7-octadien-2-ol ( IV), 2-methyl-6-methylene-1,7-octadien-3-ol ( V), 5-(3-furanyl)-2-methyl-1-penten-3-ol ( VI) and 1-(3-furanyl)-4-methyl-3-penten-2-ol ( VII). As a measure of the conformational flexibility of the molecules the flexibility coefficients, f, were determined. The f values for the molecules were determined to be: II, 0.145; III, 0.144; IV, 1.240; V, 0.133; VI, 0.825; and VII, 0.451. The molecular mechanics method was used for energy calculations in conjunction with DAISY. Low-energy conformations (conformational channels) together with energy barriers for conformational changes are presented.

  4. Structure, Stability and Interaction Studies on Nucleotide Analogue Systems

    Directory of Open Access Journals (Sweden)

    R. Kanakaraju

    2003-08-01

    Full Text Available Abstract: Most of the biological molecules have a good interaction with water molecules. The hydrogen bonding interactions with the structural analogues of nucleic acid phosphate group namely dimethyl phosphate anion (DMP and diethyl phosphate anion (DEP are studied employing the ab initio and density functional theory methods. Inspections have been made to locate the reactive sites for the interactions of isomeric forms of mono, di and tri hydrates of alkyl phosphate anion using the above theories. It reveals, water molecules have a very strong interaction with the phosphate group in both the molecules and their interactions induce the changes in the structural parameters of the PO4 group for both the DMP and DEP anions. The optimized structural parameters, total energy, dipole moment and rotational constants are calculated and are compared with the available experimental values. The chemical hardness and chemical potential for these complexes have been calculated at HF/6-31G* level of theory and discussed the conformational stability of these complexes.

  5. Bioactivity of permselective PVA hydrogels with mixed ECM analogues.

    Science.gov (United States)

    Nafea, Eman H; Poole-Warren, Laura A; Martens, Penny J

    2015-12-01

    The presentation of multiple biological cues, which simulate the natural in vivo cell environment within artificial implants, has recently been identified as crucial for achieving complex cellular functions. The incorporation of two or more biological cues within a largely synthetic network can provide a simplified model of multifunctional ECM presentation to encapsulated cells. Therefore, the aim of this study was to examine the effects of simultaneously and covalently incorporating two dissimilar biological molecules, heparin and gelatin, within a PVA hydrogel. PVA was functionalized with 7 and 20 methacrylate functional groups per chain (FG/c) to tailor the permselectivity of UV photopolymerized hydrogels. Both heparin and gelatin were covalently incorporated into PVA at an equal ratio resulting in a final PVA:heparin:gelatin composition of 19:0.5:0.5. The combination of both heparin and gelatin within a PVA network has proven to be stable over time without compromising the PVA base characteristics including its permselectivity to different proteins. Most importantly, this combination of ECM analogues supplemented PVA with the dual functionalities of promoting cellular adhesion and sequestering growth factors essential for cellular proliferation. Multi-functional PVA hydrogels with synthetically controlled network characteristics and permselectivity show potential in various biomedical applications including artificial cell implants.

  6. Bead-Based Microfluidic Sediment Analogues: Fabrication and Colloid Transport.

    Science.gov (United States)

    Guo, Yang; Huang, Jingwei; Xiao, Feng; Yin, Xiaolong; Chun, Jaehun; Um, Wooyong; Neeves, Keith B; Wu, Ning

    2016-09-13

    Mobile colloids can act as carriers for low-solubility contaminants in the environment. However, the dominant mechanism for this colloid-facilitated transport of chemicals is unclear. Therefore, we developed a bead-based microfluidic platform of sediment analogues and measured both single and population transport of model colloids. The porous medium is assembled through a bead-by-bead injection method. This approach has the versatility to build both electrostatically homogeneous and heterogeneous media at the pore scale. A T-junction at the exit also allowed for encapsulation and enumeration of colloids effluent at single particle resolution to give population dynamics. Tortuosity calculated from pore-scale trajectory analysis and its comparison with lattice Boltzmann simulations revealed that transport of colloids was influenced by the size exclusion effect. The porous media packed by positively and negatively charged beads into two layers showed distinctive colloidal particle retention and significant remobilization and re-adsorption of particles during water flushing. We demonstrated the potential of our method to fabricate porous media with surface heterogeneities at the pore scale. With both single and population dynamics measurement, our platform has the potential to connect pore-scale and macroscale colloid transport on a lab scale and to quantify the impact of grain surface heterogeneities that are natural in the subsurface environment.

  7. Potent Inhibition of Acid Ceramidase by Novel B-13 Analogues

    Directory of Open Access Journals (Sweden)

    Denny Proksch

    2011-01-01

    Full Text Available The lipid-signalling molecule ceramide is known to induce apoptosis in a variety of cell types. Inhibition of the lysosomal acid ceramidase can increase cellular ceramide levels and thus induce apoptosis. Indeed, inhibitors of acid ceramidase have been reported to induce cell death and to display potentiating effects to classical radio- or chemo therapy in a number of in vitro and in vivo cancer models. The most potent in vitro inhibitor of acid ceramidase, B-13, recently revealed to be virtually inactive towards lysosomal acid ceramidase in living cells. In contrast, a number of weakly basic B-13 analogues have been shown to accumulate in the acidic compartments of living cells and to efficiently inhibit lysosomal acid ceramidase. However, introduction of weakly basic groups at the ω-position of the fatty acid moiety of B-13 led to a significant reduction of potency towards acid ceramidase from cellular extracts. Herein, we report a novel B-13-derived scaffold for more effective inhibitors of acid ceramidase. Furthermore, we provide hints for an introduction of basic functional groups at an alternative site of the B-13 scaffold that do not interfere with acid ceramidase inhibition in vitro.

  8. Implementation of Power Efficient Flash Analogue-to-Digital Converter

    Directory of Open Access Journals (Sweden)

    Taninki Sai Lakshmi

    2014-01-01

    Full Text Available An efficient low power high speed 5-bit 5-GS/s flash analogue-to-digital converter (ADC is proposed in this paper. The designing of a thermometer code to binary code is one of the exacting issues of low power flash ADC. The embodiment consists of two main blocks, a comparator and a digital encoder. To reduce the metastability and the effect of bubble errors, the thermometer code is converted into the gray code and there after translated to binary code through encoder. The proposed encoder is thus implemented by using differential cascade voltage switch logic (DCVSL to maintain high speed and low power dissipation. The proposed 5-bit flash ADC is designed using Cadence 180 nm CMOS technology with a supply rail voltage typically ±0.85 V. The simulation results include a total power dissipation of 46.69 mW, integral nonlinearity (INL value of −0.30 LSB and differential nonlinearity (DNL value of −0.24 LSB, of the flash ADC.

  9. Superconducting Analogue of the Parafermion Fractional Quantum Hall States

    Directory of Open Access Journals (Sweden)

    Abolhassan Vaezi

    2014-07-01

    Full Text Available Read-Rezayi Z_{k} parafermion wave functions describe ν=2+(k/kM+2 fractional quantum Hall (FQH states. These states support non-Abelian excitations from which protected quantum gates can be designed. However, there is no experimental evidence for these non-Abelian anyons to date. In this paper, we study the ν=2/k FQH-superconductor heterostructure and find the superconducting analogue of the Z_{k} parafermion FQH state. Our main tool is the mapping of the FQH into coupled one-dimensional chains, each with a pair of counterpropagating modes. We show that by inducing intrachain pairing and charge preserving backscattering with identical couplings, the one-dimensional chains flow into gapless Z_{k} parafermions when k<4. By studying the effect of interchain coupling, we show that every parafermion mode becomes massive except for the two outermost ones. Thus, we achieve a fractional topological superconductor whose chiral edge state is described by a Z_{k} parafermion conformal field theory. For instance, we find that a ν=2/3 FQH in proximity to a superconductor produces a Z_{3} parafermion superconducting state. This state is topologically indistinguishable from the non-Abelian part of the ν=12/5 Read-Rezayi state. Both of these systems can host Fibonacci anyons capable of performing universal quantum computation through braiding operations.

  10. Synthesis and NMDA receptor affinity of fluorinated dioxadrol analogues.

    Science.gov (United States)

    Banerjee, Ashutosh; Schepmann, Dirk; Wünsch, Bernhard

    2010-06-01

    A series of dioxadrol analogues with fluorine substituents in position 4 of the piperidine ring has been synthesized and pharmacologically evaluated. The key step in the synthesis was the fluorination of diastereomeric piperidones 6a and 6c as well as diastereomeric alcohols 9a and 9c with DAST. The reaction of the alcohols 9a and 9c took place with inversion of configuration. After removal of the Cbz-protective group, the NMDA receptor affinities of the resulting secondary amines 8a, 8c, 12b, and 12d were investigated in receptor binding studies. It was shown that the like-configuration of the ring junction was crucial for high NMDA receptor affinity. An axially oriented fluorine atom in position 4 led to 2-(2,2-diphenyl-1,3-dioxolan-4-yl)-4-fluoropiperidine (12d, WMS-2517) with a K(i)-value of 27nM. The NMDA receptor affinity of 8c (WMS-2513) with an additional fluorine atom in equatorial 4-position was slightly reduced (K(i)=81 nM). Both fluorinated dioxadrol derivatives 8c and 12d showed high selectivity against sigma(1) and sigma(2) receptors as well as the polyamine binding site of NR2B receptors.

  11. Platonic solids generate their four-dimensional analogues

    CERN Document Server

    Dechant, Pierre-Philippe

    2013-01-01

    In this paper, we show how regular convex 4-polytopes - the analogues of the Platonic solids in four dimensions - can be constructed from three-dimensional considerations concerning the Platonic solids alone. Via the Cartan-Dieudonne theorem, the reflective symmetries of the Platonic solids generate rotations. In a Clifford algebra framework, the space of spinors generating such three-dimensional rotations has a natural four-dimensional Euclidean structure. The spinors arising from the Platonic Solids can thus in turn be interpreted as vertices in four-dimensional space, giving a simple construction of the 4D polytopes 16-cell, 24-cell, the F_4 root system and the 600-cell. In particular, these polytopes have `mysterious' symmetries, that are almost trivial when seen from the three-dimensional spinorial point of view. In fact, all these induced polytopes are also known to be root systems and thus generate rank-4 Coxeter groups, which can be shown to be a general property of the spinor construction. These cons...

  12. Digitally programmable analogue circuits for sensor conditioning systems.

    Science.gov (United States)

    Zatorre, Guillermo; Medrano, Nicolás; Sanz, María Teresa; Aldea, Concepción; Calvo, Belén; Celma, Santiago

    2009-01-01

    This work presents two current-mode integrated circuits designed for sensor signal preprocessing in embedded systems. The proposed circuits have been designed to provide good signal transfer and fulfill their function, while minimizing the load effects due to building complex conditioning architectures. The processing architecture based on the proposed building blocks can be reconfigured through digital programmability. Thus, sensor useful range can be expanded, changes in the sensor operation can be compensated for and furthermore, undesirable effects such as device mismatching and undesired physical magnitudes sensor sensibilities are reduced. The circuits were integrated using a 0.35 μm standard CMOS process. Experimental measurements, load effects and a study of two different tuning strategies are presented. From these results, system performance is tested in an application which entails extending the linear range of a magneto-resistive sensor. Circuit area, average power consumption and programmability features allow these circuits to be included in embedded sensing systems as a part of the analogue conditioning components.

  13. Digitally Programmable Analogue Circuits for Sensor Conditioning Systems

    Directory of Open Access Journals (Sweden)

    Santiago Celma

    2009-05-01

    Full Text Available This work presents two current-mode integrated circuits designed for sensor signal preprocessing in embedded systems. The proposed circuits have been designed to provide good signal transfer and fulfill their function, while minimizing the load effects due to building complex conditioning architectures. The processing architecture based on the proposed building blocks can be reconfigured through digital programmability. Thus, sensor useful range can be expanded, changes in the sensor operation can be compensated for and furthermore, undesirable effects such as device mismatching and undesired physical magnitudes sensor sensibilities are reduced. The circuits were integrated using a 0.35 mm standard CMOS process. Experimental measurements, load effects and a study of two different tuning strategies are presented. From these results, system performance is tested in an application which entails extending the linear range of a magneto-resistive sensor. Circuit area, average power consumption and programmability features allow these circuits to be included in embedded sensing systems as a part of the analogue conditioning components.

  14. Potential of carbon nanotube field effect transistors for analogue circuits

    KAUST Repository

    Hayat, Khizar

    2013-05-11

    This Letter presents a detailed comparison of carbon nanotube field effect transistors (CNFETs) and metal oxide semiconductor field effect transistors (MOSFETs) with special focus on carbon nanotube FET\\'s potential for implementing analogue circuits in the mm-wave and sub-terahertz range. The latest CNFET lithographic dimensions place it at-par with complementary metal oxide semiconductor in terms of current handling capability, whereas the forecasted improvement in the lithography enables the CNFETs to handle more than twice the current of MOSFETs. The comparison of RF parameters shows superior performance of CNFETs with a g m , f T and f max of 2.7, 2.6 and 4.5 times higher, respectively. MOSFET- and CNFET-based inverter, three-stage ring oscillator and LC oscillator have been designed and compared as well. The CNFET-based inverters are found to be ten times faster, the ring oscillator demonstrates three times higher oscillation frequency and CNFET-based LC oscillator also shows improved performance than its MOSFET counterpart.

  15. Upheaval Dome, An Analogue Site for Gale Center

    Science.gov (United States)

    Conrad, P. G.; Eignebrode, J. L.

    2011-01-01

    We propose Upheaval Dome in southeastern Utah as an impact analogue site on Earth to Mars Science Laboratory candidate landing site Gale Crater. The genesis of Upheaval Dome was a mystery for some time--originally thought to be a salt dome. The 5 km crater was discovered to possess shocked quartz and other shock metamorphic features just a few years ago, compelling evidence that the crater was formed by impact, although the structural geology caused Shoemaker and Herkenhoff to speculate an impact origin some 25 years earlier. The lithology of the crater is sedimentary. The oldest rocks are exposed in the center of the dome, upper Permian sandstones, and progressively younger units are well exposed moving outward from the center. These are Triassic sandstones, siltstones and shales, which are intruded by clastic dikes. There are also other clay-rich strata down section, as is the case with Gale Crater. There is significant deformation in the center of the crater, with folding and steeply tilted beds, unlike the surrounding Canyonlands area, which is relatively undeformed. The rock units are well exposed at Upheaval Dome, and there are shatter cones, impactite fragments, shocked quartz grains and melt rocks present. The mineral shock features suggest that the grains were subjected to dynamic pressures> 10 GPa.

  16. Modern freshwater microbialite analogues for ancient dendritic reef structures

    Science.gov (United States)

    Laval, B.; Cady, S. L.; Pollack, J. C.; McKay, C. P.; Bird, J. S.; Grotzinger, J. P.; Ford, D. C.; Bohm, H. R.

    2000-01-01

    Microbialites are organosedimentary structures that can be constructed by a variety of metabolically distinct taxa. Consequently, microbialite structures abound in the fossil record, although the exact nature of the biogeochemical processes that produced them is often unknown. One such class of ancient calcareous structures, Epiphyton and Girvanella, appear in great abundance during the Early Cambrian. Together with Archeocyathids, stromatolites and thrombolites, they formed major Cambrian reef belts. To a large extent, Middle to Late Cambrian reefs are similar to Precambrian reefs, with the exception that the latter, including terminal Proterozoic reefs, do not contain Epiphyton or Girvanella. Here we report the discovery in Pavilion Lake, British Columbia, Canada, of a distinctive assemblage of freshwater calcite microbialites, some of which display microstructures similar to the fabrics displayed by Epiphyton and Girvanella. The morphologies of the modern microbialites vary with depth, and dendritic microstructures of the deep water (> 30 m) mounds indicate that they may be modern analogues for the ancient calcareous structures. These microbialites thus provide an opportunity to study the biogeochemical interactions that produce fabrics similar to those of some enigmatic Early Cambrian reef structures.

  17. Pharmacologic profiles of investigational kisspeptin/metastin analogues, TAK-448 and TAK-683, in adult male rats in comparison to the GnRH analogue leuprolide.

    Science.gov (United States)

    Matsui, Hisanori; Masaki, Tsuneo; Akinaga, Yumiko; Kiba, Atsushi; Takatsu, Yoshihiro; Nakata, Daisuke; Tanaka, Akira; Ban, Junko; Matsumoto, Shin-ichi; Kumano, Satoshi; Suzuki, Atsuko; Ikeda, Yukihiro; Yamaguchi, Masashi; Watanabe, Tatsuya; Ohtaki, Tetsuya; Kusaka, Masami

    2014-07-15

    Kisspeptin/metastin, a hypothalamic peptide, plays a pivotal role in controlling gonadotropin-releasing hormone (GnRH) neurons, and we have shown that continuous subcutaneous administration of kisspeptin analogues suppresses plasma testosterone in male rats. This study examined pharmacologic profiles of investigational kisspeptin analogues, TAK-448 and TAK-683, in male rats. Both analogues showed high receptor-binding affinity and potent and full agonistic activity for rat KISS1R, which were comparable to natural peptide Kp-10. A daily subcutaneous injection of TAK-448 and TAK-683 (0.008-8μmol/kg) for consecutive 7 days initially induced an increase in plasma luteinizing hormone and testosterone levels; however, after day 7, plasma hormone levels and genital organ weights were reduced. Continuous subcutaneous administrations of TAK-448 (≥10pmol/h, ca. 0.7nmol/kg/day) and TAK-683 (≥30pmol/h, ca. 2.1nmol/kg/day) induced a transient increase in plasma testosterone, followed by abrupt reduction of plasma testosterone to castrate levels within 3-7 days. This profound testosterone-lowering effect was sustained throughout 4-week dosing periods. At those dose levels, the weights of the prostate and seminal vesicles were reduced to castrate levels. These suppressive effects of kisspeptin analogues were more rapid and profound than those induced by the GnRH agonist analogue leuprolide treatment. In addition, TAK-683 reduced plasma prostate specific antigen (PSA) in the JDCaP androgen-dependent prostate cancer rat model. Thus, chronic administration of kisspeptin analogues may hold promise as a novel therapeutic approach for suppressing reproductive functions and hormone-related diseases such as prostate cancer. Further studies are warranted to elucidate clinical significance of TAK-448 and TAK-683.

  18. Fetal bovine serum influences the stability and bioactivity of resveratrol analogues: A polyphenol-protein interaction approach.

    Science.gov (United States)

    Tang, Fen; Xie, Yixi; Cao, Hui; Yang, Hua; Chen, Xiaoqing; Xiao, Jianbo

    2017-03-15

    Fetal bovine serum (FBS) is a universal growth supplement of cell and tissue culture media. Herein, the influences of FBS on the stability and antioxidant activity of 21 resveratrol analogues were investigated using a polyphenol-protein interaction approach. The structure-stability relationships of resveratrol analogues in FBS showed a clear decrease in the stability of hydroxylated resveratrol analogues in the order: resorcinol-type>pyrogallol-type>catechol-type. The glycosylation and methoxylation of resveratrol analogues enhanced their stability. A linear relationship between the stability of resveratrol analogues in FBS and the affinity of resveratrol analogues-FBS interaction was found. The oxidation process is not the only factor governing the stability of resveratrol analogues in FBS. These results facilitated the insightful investigation of the role of polyphenol-protein interactions in serum, thereby providing some fundamental clues for future clinical research and pharmacological studies on natural small molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro

    Science.gov (United States)

    Dechristopher, Brian A.; Loy, Brian A.; Marsden, Matthew D.; Schrier, Adam J.; Zack, Jerome A.; Wender, Paul A.

    2012-09-01

    Bryostatin is a unique lead in the development of potentially transformative therapies for cancer, Alzheimer's disease and the eradication of HIV/AIDS. However, the clinical use of bryostatin has been hampered by its limited supply, difficulties in accessing clinically relevant derivatives, and side effects. Here, we address these problems through the step-economical syntheses of seven members of a new family of designed bryostatin analogues using a highly convergent Prins-macrocyclization strategy. We also demonstrate for the first time that such analogues effectively induce latent HIV activation in vitro with potencies similar to or better than bryostatin. Significantly, these analogues are up to 1,000-fold more potent in inducing latent HIV expression than prostratin, the current clinical candidate for latent virus induction. This study provides the first demonstration that designed, synthetically accessible bryostatin analogues could serve as superior candidates for the eradication of HIV/AIDS through induction of latent viral reservoirs in conjunction with current antiretroviral therapy.

  20. Transient High-Temperature Processing of Silicates in Fulgurites as Analogues for Meteorite and Impact Melts

    Science.gov (United States)

    Parnell, J.; Thackrey, S.; Muirhead, D. K.; Wright, A. J.

    2008-03-01

    A fulgurite from the Sahara yielded petrographic data valuable as an analogue for highly reduced meteorite and impact melts, including iron silicide formation, devolatilization features, zircon melting and extreme melt heterogeneity.

  1. A New and Efficient Synthetic Method and Antibacterial Activities of Oxazolidinone Analogues

    Institute of Scientific and Technical Information of China (English)

    De Sheng YU; Liang HUANG; Hui LIANG; Ping GONG

    2005-01-01

    A series of novel oxazolidinone analogues were prepared by a new and efficient synthetic method and their antibacterial activities were determined. These compounds were characterized by LC-MS and 1H NMR.

  2. Synthetic analogues of the microtubule-stabilizing agent (+)-discodermolide: preparation and biological activity.

    Science.gov (United States)

    Gunasekera, Sarath P; Mickel, Stuart J; Daeffler, Robert; Niederer, Daniel; Wright, Amy E; Linley, Patricia; Pitts, Tara

    2004-05-01

    A series of seven synthetic discodermolide analogues 2-8, which are minor side products generated during the final stages in the synthesis of (+)-discodermolide (1), have been purified and evaluated for in vitro cytotoxicity against A549, P388, MFC-7, NCI/ADR, PANC-1, and VERO cell lines. These synthetic analogues showed a significant variation of cytotoxicity and confirmed the importance of the C-7 hydroxy through C-17 hydroxy molecular fragment for potency. Specifically, these analogues suggested the relevance of the C-11 hydroxyl group, the C-13 double bond, and the C-16 (S) stereochemistry for the potency of (+)-discodermolide. The preparation, purification, structure elucidation, and biological activity of these new analogues are described.

  3. Synthesis and Antitumor Activity of C-2/C-10 Modified Analogues of Docetaxel

    Institute of Scientific and Technical Information of China (English)

    Wei Shuo FANG; Hong Yan LIU; Qi Cheng FANG

    2005-01-01

    Four 10-propionyl docetaxel analogues (11a-d) with 2α-amido substituents were prepared, and their antitumor activity against three solid tumor cell lines and their drug-resistant counterparts were determined.

  4. Synthesis and biochemical evaluation of benzoylbenzophenone thiosemicarbazone analogues as potent and selective inhibitors of cathepsin L

    DEFF Research Database (Denmark)

    Parker, Erica N; Song, Jiangli; Kishore Kumar, G D;

    2015-01-01

    studies on benzophenone thiosemicarbazone cathepsin inhibitors, a series of fourteen benzoylbenzophenone thiosemicarbazone analogues were designed, synthesized, and evaluated for their inhibitory activity against cathepsins L and B. Thiosemicarbazone inhibitors 3-benzoylbenzophenone thiosemicarbazone 1, 1......,3-bis(4-fluorobenzoyl)benzene thiosemicarbazone 8, and 1,3-bis(2-fluorobenzoyl)-5-bromobenzene thiosemicarbazone 32 displayed the greatest potency against cathepsin L with low IC50 values of 9.9nM, 14.4nM, and 8.1nM, respectively. The benzoylbenzophenone thiosemicarbazone analogues evaluated were...... selective in their inhibition of cathepsin L compared to cathepsin B. Thiosemicarbazone analogue 32 inhibited invasion through Matrigel of MDA-MB-231 breast cancer cells by 70% at 10μM. Thiosemicarbazone analogue 8 significantly inhibited the invasive potential of PC-3ML prostate cancer cells by 92% at 5μ...

  5. Ion channel stability and hydrogen bonding. Molecular modelling of channels formed by synthetic alamethicin analogues.

    Science.gov (United States)

    Breed, J; Kerr, I D; Molle, G; Duclohier, H; Sansom, M S

    1997-12-04

    Several analogues of the channel-forming peptaibol alamethicin have been demonstrated to exhibit faster switching between channel substates than does unmodified alamethicin. Molecular modelling studies are used to explore the possible molecular basis of these differences. Models of channels formed by alamethicin analogues were generated by restrained molecular dynamics in vacuo and refined by short molecular dynamics simulations with water molecules within and at either mouth of the channel. A decrease in backbone solvation was found to correlate with a decrease in open channel stability between alamethicin and an analogue in which all alpha-amino-isobutyric acid residues of alamethicin were replaced by leucine. A decrease in the extent of hydrogen-bonding at residue 7 correlates with lower open channel stabilities of analogues in which the glutamine at position 7 was replaced by smaller polar sidechains. These two observations indicate the importance of alamethicin/water H-bonds in stabilizing the open channel.

  6. Synthesis of 2-Substituted Hexahydro-1H-1,4-diazepine Analogues

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    2-substituted hexahydro-1H-1,4-diazepine analogues were synthesized starting from N,N?-dibenzyl-1,3-propylene diamine and methyl-2,3-dibromo propionate through nucleophilic substitution, reduction, chlorination and debenzylation.

  7. Synthesis and formulation studies of griseofulvin analogues with improved solubility and metabolic stability

    DEFF Research Database (Denmark)

    Petersen, Asger Bjørn; Andersen, Nikolaj Sten; Konotop, Gleb

    2017-01-01

    potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve...... the poor pharmacokinetic properties, 11 griseofulvin analogues were synthesized and evaluated for biological activity and physiological stabilities including SGF, plasma, and metabolic stability. Finally, the most promising compounds were investigated in respect to thermodynamic solubility and formulation...... studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral...

  8. The synthesis and activity in vitro of a series of 8-difluoromethoxy quinolones: Analogues of gemifloxacin

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    7-[4-(Aminomethyl)-3-(methoxyimino)pyrrolidin- 1-yl]-1-cyclopropyl-6-fluoro-8-difluoromethoxy- 1 ,4-dihydro-4-oxoquino-line-3-carboxylic acid and its analogues have been prepared and evaluated for antibacterial activityin vitro.

  9. [Luliberin analogues exhibiting a cytotoxic effect on tumor cells in vitro].

    Science.gov (United States)

    Burov, S V; Iablokova, T V; Dorosh, M Iu; Shkarubskaia, Z P; Blank, M; Epshteĭn, N; Fridkin, M

    2006-01-01

    Luliberin analogues modified at the N-terminus were synthesized to search for drugs exerting a cytotoxic effect on cells of hormone-dependent tumors. A synthetic scheme effective in the preparation of analogues containing fatty acid residues was proposed. The cytotoxic effect of the peptides was studied on a number of cell lines of human tumors in vitro. The dependence of the antitumor effect on the length of peptide chain, amino acid sequence, and structure of the N-terminal group was demonstrated. Modification with palmitic acid was found to result in highly active compounds in the case of analogues containing more than ten aa, whereas modifications with lauric, caproic, or trimethylacetic acid led to compounds with significantly lower activities. Analogues of luliberin containing a palmitic acid residue and effectively inhibiting the growth of tumor cells in vitro were synthesized.

  10. Elastic and anelastic anomalies in (Ca,Sr)TiO perovskites: Analogue behaviour for silicate perovskites

    OpenAIRE

    Walsh, J.W.; Taylor, P.A.; Buckley, A.; Darling, T.W.; Schreuer, J.; Carpenter, M.A.

    2008-01-01

    Elastic and anelastic anomalies in (Ca,Sr)TiO3 perovskites: Analogue behaviour for silicate perovskites UNITED KINGDOM (Walsh, J.W.) UNITED KINGDOM Received: 2007-10-30 Revised: 2008-02-18 Accepted: 2008-02-27

  11. Synthesis of Tetracycline Analogues and Test of Their Affinity of Synthetic Hydroxyapatite

    Institute of Scientific and Technical Information of China (English)

    LingLingWENG; GangLIN; 等

    2002-01-01

    Eight of new 5-oxo[1] benzopyrano [2,3-b] pyridines as the analogues of tetracycline, were designed and synthesized, and their affinity to the hydroxyapatite-the inorganic composition of bone were tested.

  12. Synthesis and antifungal activity of novel indole-replaced streptochlorin analogues.

    Science.gov (United States)

    Zhang, Ming-Zhi; Jia, Chen-Yang; Gu, Yu-Cheng; Mulholland, Nick; Turner, Sarah; Beattie, David; Zhang, Wei-Hua; Yang, Guang-Fu; Clough, John

    2017-01-27

    Based on examples of the successful applications in drug discovery of bioisosterism, a series of streptochlorin analogues in which indole has been replaced by other heterocycles has been designed and synthesized, as a continuation of our studies aimed at the discovery of novel streptochlorin analogues with improved antifungal activity. Biological testing showed that most of the indole-replaced streptochlorin analogues were inactive, though compound 6f had a broad spectrum of antifungal activity with significant activity against Alternaria solani. The SAR study demonstrated that indole ring is an essential moiety for the antifungal activity of streptochlorin analogues, promoting the idea of indole ring as a framework that might be exploited in the future. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. An analogue of the Hom functor and a generalized nuclear democracy theorem

    CERN Document Server

    Li, H

    1997-01-01

    We give an analogue of the Hom functor and prove a generalized form of the nuclear democracy theorem of Tsuchiya and Kanie by using a notion of tensor product for two modules for a vertex operator algebra.

  14. Alkaline phosphatase predicts response in polycystic liver disease during somatostatin analogue therapy: a pooled analysis

    NARCIS (Netherlands)

    Gevers, T.J.; Nevens, F.; Torres, V.E.; Hogan, M.C.; Drenth, J.P.

    2016-01-01

    BACKGROUND & AIMS: Somatostatin analogues reduce liver volumes in polycystic liver disease. However, patients show considerable variability in treatment responses. Our aim was to identify specific patient, disease or treatment characteristics that predict response in polycystic liver disease during

  15. Occurrence and profiles of bisphenol analogues in municipal sewage sludge in China.

    Science.gov (United States)

    Song, Shanjun; Song, Maoyong; Zeng, Luzhe; Wang, Thanh; Liu, Runzeng; Ruan, Ting; Jiang, Guibin

    2014-03-01

    Extensive use of bisphenol A and its analogues has caused increasing concern over the potential adverse health impacts of these chemicals. In this study, the presence and profiles of 13 bisphenols (BPs) were investigated in 52 municipal sewage sludge samples collected from 30 cities in China. Tetrabromobisphenol A was the most frequently observed analogue (geometric mean: 20.5 ng/g dw). Bisphenol A (4.69 ng/g dw), bisphenol S (3.02 ng/g dw), and bisphenol F (3.84 ng/g dw) were found with similar frequency. Other BP analogues such as tetrachlorobisphenol A, bisphenol AF, bisphenol E, and dihydroxybiphenyl were identified for the first time in sewage sludge in China. Significant correlations were found among BP concentrations, but no relationships were found with wastewater treatment plant characteristics. Profiles of the relative estradiol equivalents suggested that the estrogenic potential of BP mixtures may be associated with the occurrence and contributions of specific analogues.

  16. Mars Methane Analogue Mission (M3): Near Subsurface Electromagnetic Techniques and Analysis

    Science.gov (United States)

    Boivin, A.; Samson, C.; Holladay, J. S.; Cloutis, E. A.; Ernst, R. E.

    2012-03-01

    As part of the Canadian Space Agency's Mars Methane Analogue Mission, a micro-rover mission, an Electromagnetic Induction Sounder (EMIS) was used with the goal of demonstrating its value as a potential science instrument onboard future rovers.

  17. Synthesis, DNA binding and antitrypanosomal activity of benzimidazole analogues of DAPI.

    Science.gov (United States)

    Farahat, Abdelbasset A; Bennett-Vaughn, Cheree; Mineva, Ekaterina M; Kumar, Arvind; Wenzler, Tanja; Brun, Reto; Liu, Yang; Wilson, W David; Boykin, David W

    2016-12-15

    A series of novel benzimidazole diamidines were prepared from the corresponding dicyano analogues either by applying Pinner methodology (5a-c, 10 and 13a) or by making amidoximes intermediates that were reduced to the corresponding amidines (15a-c). The new amidines were evaluated in vitro against the protozoan parasite Trypanosoma brucei rhodesiense (T. b. r.). The thiophene analogue 5b and the N-methyl compound 15a showed superior antitrypanosomal activity compared to that of the parent I.

  18. Measuring the perception of symptom, drug use and allergen immunotherapy efficacy using the Visual Analogue Scale.

    Science.gov (United States)

    Ciprandi, Giorgio; Tosca, Maria Angela; Silvestri, Michela

    2014-02-01

    The availability of a simple and reliable tool for quantitatively measuring symptom perception is surely very important in the daily practice. Especially, this concept appears to be fundamental in doctor's office and at home, where there are no adequate resources. The Visual Analogue Scale is a very simple and popular tool that could be used by anyone anywhere. The advantage given by the Visual Analogue Scale consists in the translation of a subjective sensation in an objective measure provided by numbers.

  19. The PedsQL™ Present Functioning Visual Analogue Scales: preliminary reliability and validity

    OpenAIRE

    Varni James W; Burwinkle Tasha M; Eisen Sarajane; Sherman Sandra A

    2006-01-01

    Abstract Background The PedsQL™ Present Functioning Visual Analogue Scales (PedsQL™ VAS) were designed as an ecological momentary assessment (EMA) instrument to rapidly measure present or at-the-moment functioning in children and adolescents. The PedsQL™ VAS assess child self-report and parent-proxy report of anxiety, sadness, anger, worry, fatigue, and pain utilizing six developmentally appropriate visual analogue scales based on the well-established Varni/Thompson Pediatric Pain Questionnai...

  20. Ureido-modification of the resin-bound LHRH analogue with N,N'-carbonyldiimidazole

    Institute of Scientific and Technical Information of China (English)

    Yong Qing Gao; Ning Zhou; Yu Jian Lv; Mao Sheng Cheng; Ke Liang Liu

    2009-01-01

    The ureido-modification of the resin-bound a luteinizing hormone releasing hormone (LHRH) analogue was investigated by CDI-activating method. The amino group at the side chain of LHRH analogue could be transformed into various substituted urea moieties in high yields. However, its terminal amino group was partially converted to a hydantoin structure due to the attack of the N atom of the adjacent amide bond.

  1. Socio-Economic Analogues of the Gas Laws (Boyle's and Charles')

    OpenAIRE

    Angle, John

    2011-01-01

    Most social scientists would reject the possibility of socio-economic analogues of the gas laws (Boyle’s and Charles’) on verisimilitude grounds. The gas laws relate the variables temperature, pressure, and volume. The possibility of socio-economic analogues of the gas laws and their variables is suggested by the similarity of two mathematical models. One model is the Inequality Process (IP), a particle system model that explains a wide scope of socio-economic phenomena. The IP is isomorphic ...

  2. Synthesis and Insecticidal Activities of Novel Analogues of Chlorantraniliprole Containing Nitro Group

    Institute of Scientific and Technical Information of China (English)

    FENG Qi; WANG Ming-zhong; XIONG Li-xia; LIU Zhi-li; LI Zheng-ming

    2011-01-01

    Twelve novel analogues of chlorantraniliprole containing nitro group were synthesized,and their structures were characterized by 1H NMR and high-resolution mass spectrometry(HRMS).Their evaluated insecticidal activities against oriental armyworm(Mythimna separata) indicate that the nitro-containing analogues showed favorable insecticidal activities,while the activity of compounds 5g at 0.25 mg/L was 40%,but still lower than chlorantraniliprole.

  3. Synthesis and biological activity of new quinoxaline antibiotics of echinomycin analogues.

    Science.gov (United States)

    Kim, Yun Bong; Kim, Yong Hae; Park, Ju Youn; Kim, Soo Kie

    2004-01-19

    Novel quinoxaline antibiotics having the methylenedithioether bridge as an analogue of echinomycin have been synthesized by insertion of methylene moiety between -S-S- bond. The compound 1a shows remarkable cytotoxicities against human tumor various cell lines, and is active VRE (vancomycin-resistant enterococci) within MIC range 0.5-8 microg/mL. According to the eukaryotic or prokaryotic data, 1a might be a first analogue to replace echinomycin.

  4. Synthesis and biological evaluation of new salvinorin A analogues incorporating natural amino acids.

    Science.gov (United States)

    Fichna, Jakub; Lewellyn, Kevin; Yan, Feng; Roth, Bryan L; Zjawiony, Jordan K

    2011-01-01

    The synthesis and in vitro evaluation of a new series of salvinorin A analogues substituted at the C(2) position with natural amino acids is reported. Compound 12, containing Val, displayed high affinity and full agonist activity at the kappa-opioid receptor. Analogues with bulky and/or aromatic residues were inactive, showing the importance of size and electronegativity of C(2)-substituents for binding affinity of salvinorin A derivatives.

  5. Analogue Hawking Radiation in a dc-SQUID Array Transmission Line

    Science.gov (United States)

    Nation, P. D.; Blencowe, M. P.; Rimberg, A. J.; Buks, E.

    2009-08-01

    We propose the use of a superconducting transmission line formed from an array of direct-current superconducting quantum interference devices for investigating analogue Hawking radiation. Biasing the array with a space-time varying flux modifies the propagation velocity of the transmission line, leading to an effective metric with a horizon. Being a fundamentally quantum mechanical device, this setup allows for investigations of quantum effects such as backreaction and analogue space-time fluctuations on the Hawking process.

  6. The Algebra of a q-Analogue of Multiple Harmonic Series

    Directory of Open Access Journals (Sweden)

    Yoshihiro Takeyama

    2013-10-01

    Full Text Available We introduce an algebra which describes the multiplication structure of a family of q-series containing a q-analogue of multiple zeta values. The double shuffle relations are formulated in our framework. They contain a q-analogue of Hoffman's identity for multiple zeta values. We also discuss the dimension of the space spanned by the linear relations realized in our algebra.

  7. Endomorphin analogues with balanced affinity for both μ- and δ-opioid receptors

    Institute of Scientific and Technical Information of China (English)

    Liang Zhang; Lei Chang; Lei Lei Yu; Jin Chun Liu; Jia Jia Chen; Xiao Wen Li; Lawrence H. Lazarus; Ting You Li

    2011-01-01

    Analogues of endomorphin and tripeptides modified at positions 4 and 3, respectively, with various phenylalanine analogues were synthesized and their affinities for opioid receptors were evaluated. Most of the peptides exhibited potent μ-receptor affinity and selectivity, among them, compound 7 (Dmt-Pro-Tmp-Tmp-NH2) exhibited potent affinity for both μ- and δ-receptors (Kiμ = 0.47 nmol/L, Kiδ = 1.63 nmol/L).

  8. Insulin analogues in pregnancy and specific congenital anomalies: a literature review.

    Science.gov (United States)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa; Morgan, Margery; de Jong-van den Berg, Lolkje T W; Wang, Hao

    2016-05-01

    Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate was 4.84% and 4.29% among the foetuses of mothers using lispro and aspart. For glargine and detemir, the congenital anomaly rate was 2.86% and 3.47%, respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies.

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

    Science.gov (United States)

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

    2015-04-01

    contrasting minerals endowment. The Mogok-Mandalay-Mergui (MMM) Belt hosts crustal-melt S-type granites with significant tin-tungsten mineralization, and contains the historically major tungsten deposit of Mawchi. The Wuntho-Popa Arc comprises I-type granites and granodiorites with porphyry-type copper-gold and epithermal gold mineralization, and includes the world-class Monywa copper mine. Recent U-Pb radiometric age dating has shown the potential for the two belts to be both active from the Late Cretaceous to Eocene. The spatial juxtaposition of these two sub-parallel belts, the implication of contemporary magmatism, and their distinct but consistent metallogenic endowment bears strong similarities to the metallogenic belts of the South American Cordillera. Here we investigate whether they together represent the magmatic and metallogenic expression of an Andean-type setting in Myanmar during the subduction of Neo-Tethys. In this analogue the Wuntho-Popa Arc represents a proximal I-type magmatic belt sited immediately above the eastwards-verging Neo-Tethys subduction zone. Exhibiting porphyry-type copper-gold and epithermal gold mineralization, this would therefore be the Myanmar equivalent of the Andean coastal copper belts. Conversely, the parallel MMM Belt, comprised of more distal crustal-melt S-type tin granites, would have an analogue in the Bolivian tin belt.

  10. Surfactin analogues produced by Bacillus subtilis strains grown on rapeseed cake

    Science.gov (United States)

    Jajor, Paweł; Piłakowska-Pietras, Dorota; Krasowska, Anna; Łukaszewicz, Marcin

    2016-12-01

    Microbiologically produced surface acting compounds (biosurfactants) have very interesting properties with many potential industrial applications. Lipopeptides is a particularly promising group of biosurfactants in respect to the potentially huge number of various chemical structures. The chemical diversity results from fatty acid moiety (e.g. length, saturation, branching or hydroxylation) and type and sequence of the amino acids in the peptide chain. The limiting factor for the design and analysis of various lipopeptides is the ability of the targeted biosynthesis. Biosynthesis of particular lipopeptides may be potentially achieved by strain selection, culture conditions, or molecular engineering. The well-known lipopeptedes (surfactins, iturins, and fengycins) producer is B. subtilis. The aim of this study was to study targeted surfactin structural analogues biosynthesis in response to culture conditions in view of the design and production of tailor-made lipopeptides. Two B. subtilis strains (KB1 and #309) were tested for surfactin production. Both strains produced a mixture of five major surfactin analogues with the number of carbons in an alkyl chain ranging from 12 to 16. The two strains differed with respect to their oxygen demand for optimal surfactin biosynthesis (lower oxygen demand for KB1). The amount of air influenced the relative ratios of surfactin analogues. Lower oxygen amount decreased the share of C15 analogues while it increased the share of C12 analogues. Thus, the biosynthesis of a desired surfactin analogue may controlled by both strain and culture conditions.

  11. A photoactive isoprenoid diphosphate analogue containing a stable phosphonate linkage: synthesis and biochemical studies with prenyltransferases

    Science.gov (United States)

    DeGraw, Amanda J.; Zhao, Zongbao; Strickland, Corey L.; Taban, A. Huma; Hsieh, John; Michael, Jefferies; Xie, Wenshuang; Shintani, David; McMahan, Colleen; Cornish, Katrina; Distefano, Mark D.

    2008-01-01

    A number of biochemical processes rely on isoprenoids, including the post-translational modification of signaling proteins and the biosynthesis of a wide array of compounds. Photoactivatable analogues have been developed to study isoprenoid utilizing enzymes such as the isoprenoid synthases and prenyltransferases. While these initial analogues proved to be excellent structural analogues with good cross linking capability, they lack the stability needed when the goals include isolation of cross-linked species, tryptic digestion, and subsequent peptide sequencing. Here, the synthesis of a benzophenone-based farnesyl diphosphate analogue containing a stable phosphonophosphate group is described. Inhibition kinetics, photolabeling experiments, as well as x-ray crystallographic analysis with a protein prenyltransferase are described, verifying this compound as a good isoprenoid mimetic. In addition, the utility of this new analogue was explored by using it to photoaffinity label crude protein extracts obtained from Hevea brasiliensis latex. Those experiments suggest that a small protein, Rubber Elongation Factor, interacts directly with farnesyl diphosphate during rubber biosynthesis. These results indicate that this benzophenone-based isoprenoid analogue will be useful for identifying enzymes that utilize farnesyl diphosphate as a substrate. PMID:17477573

  12. Optoelectronic properties of higher acenes, their BN analogue and substituted derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Armaković, Stevan, E-mail: stevan.armakovic@df.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Physics, Trg Dositeja Obradovića 4, 21000, Novi Sad (Serbia); Armaković, Sanja J. [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000, Novi Sad (Serbia); Holodkov, Vladimir [Educons University, Faculty of Sport and Tourism - TIMS, Radnička 30a, 21000, Novi Sad (Serbia); Pelemiš, Svetlana [University of East Sarajevo, Faculty of Technology, Karakaj bb, 75400, Zvornik, Republic of Srpska, Bosnia and Herzegovina (Bosnia and Herzegovina)

    2016-02-15

    We have investigated optoelectronic properties of higher acenes: pentacene, hexacene, heptacene, octacene, nonacene, decacene and their boron-nitride (BN) analogues, within the framework of density functional theory (DFT). We have also investigated the optoelectronic properties of acenes modified by BN substitution. Calculated optoelectronic properties encompasses: oxidation and reduction potentials, electron and hole reorganization energies and energy difference between excited first singlet and triplet states ΔE(S{sub 1}−T{sub 1}). Oxidation and reduction potentials indicate significantly better stability of BN analogues, comparing with their all-carbon relatives. Although higher acenes possess lower electron and hole reorganization energies, with both best values much lower than 0.1 eV, their BN analogues also have competitive values of reorganization energies, especially for holes for which reorganization energy is also lower than 0.1 eV. On the other hand ΔE(S{sub 1}−T{sub 1}) is much better for BN analogues, having values that indicate that BN analogues are possible applicable for thermally activated delayed fluorescence. - Highlights: • Optoelectronic properties of structures based on higher acenes have been investigated. • Oxidation and reduction potentials together with reorganization energies are calculated. • TADF is analyzed through calculation of ΔE(S{sub 1}−T{sub 1}), which is much better for BN analogues. • Reorganization energies of acenes improve with the increase of number of benzene rings.

  13. Effects of metronidazole analogues on Giardia lamblia: experimental infection and cell organization.

    Science.gov (United States)

    Busatti, Haendel G N O; Alves, Ricardo J; Santana-Anjos, Karla G; Gil, Frederico F; Cury, Marcia C; Vannier-Santos, Marcos A; Gomes, Maria A

    2013-02-01

    The chemotherapeutic agents used for the treatment of giardiasis are often associated with adverse side effects and are refractory cases, due to the development of resistant parasites. Therefore the search for new drugs is required. We have previously reported the giardicidal effects of metronidazole (MTZ) and its analogues (MTZ-Ms, MTZ-Br, MTZ-N(3), and MTZ-I) on the trophozoites of Giardia lamblia. Now we evaluated the activity of some giardicidal MTZ analogues in experimental infections in gerbils and its effects on the morphology and ultrastructural organization of Giardia. The giardicidal activity in experimental infections showed ED(50) values significantly lower for MTZ-I and MTZ-Br when compared to MTZ. Transmission electron microscopy was employed to approach the mechanism(s) of action of MTZ analogues upon the protozoan. MTZ analogues were more active than MTZ in changing significantly the morphology and ultrastructure of the parasite. The analogues affected parasite cell vesicle trafficking, autophagy, and triggered differentiation into cysts. These results coupled with the excellent giardicidal activity and lower toxicity demonstrate that these nitroimidazole derivates may be important therapeutic alternatives for combating giardiasis. In addition, our results suggest a therapeutic advantage in obtaining synthetic metronidazole analogues for screening of activities against other infectious agents.

  14. Glucosamine and glucosamine-6-phosphate derivatives: catalytic cofactor analogues for the glmS ribozyme.

    Science.gov (United States)

    Posakony, Jeffrey J; Ferré-D'Amaré, Adrian R

    2013-05-17

    Two analogues of glucosamine-6-phosphate (GlcN6P, 1) and five of glucosamine (GlcN, 2) were prepared for evaluation as catalytic cofactors of the glmS ribozyme, a bacterial gene-regulatory RNA that controls cell wall biosynthesis. Glucosamine and allosamine with 3-azido substitutions were prepared by SN2 reactions of the respective 1,2,4,6-protected sugars; final acidic hydrolysis afforded the fully deprotected compounds as their TFA salts. A 6-phospho-2-aminoglucolactam (31) was prepared from glucosamine in a 13-step synthesis, which included a late-stage POCl3-phosphorylation. A simple and widely applicable 2-step procedure with the triethylsilyl (TES) protecting group was developed to selectively expose the 6-OH group in N-protected glucosamine analogues, which provided another route to chemical phosphorylation. Mitsunobu chemistry afforded 6-cyano (35) and 6-azido (36) analogues of GlcN-(Cbz), and the selectivity for the 6-position was confirmed by NMR (COSY, HMBC, HMQC) experiments. Compound 36 was converted to the fully deprotected 6-azido-GlcN (37) and 2,6-diaminoglucose (38) analogues. A 2-hydroxylamino glucose (42) analogue was prepared via an oxaziridine (41). Enzymatic phosphorylation of 42 and chemical phosphorylation of its 6-OH precursor (43) were possible, but 42 and the 6-phospho product (44) were unstable under neutral or basic conditions. Chemical phosphorylation of the previously described 2-guanidinyl-glucose (46) afforded its 6-phospho analogue (49) after final deprotection.

  15. Analogue Correction Method of Errors by Combining Statistical and Dynamical Methods

    Institute of Scientific and Technical Information of China (English)

    REN Hongli; CHOU Jifan

    2006-01-01

    Based on the atmospheric analogy principle, the inverse problem that the information of historical analogue data is utilized to estimate model errors is put forward and a method of analogue correction of errors (ACE) of model is developed in this paper. The ACE can combine effectively statistical and dynamical methods, and need not change the current numerical prediction models. The new method not only adequately utilizes dynamical achievements but also can reasonably absorb the information of a great many analogues in historical data in order to reduce model errors and improve forecast skill.Furthermore, the ACE may identify specific historical data for the solution of the inverse problem in terms of the particularity of current forecast. The qualitative analyses show that the ACE is theoretically equivalent to the principle of the previous analogue-dynamical model, but need not rebuild the complicated analogue-deviation model, so has better feasibility and operational foreground. Moreover, under the ideal situations, when numerical models or historical analogues are perfect, the forecast of the ACE would transform into the forecast of dynamical or statistical method, respectively.

  16. Analogue of Melanotan II (MTII): A Novel Melanotropin with Superpotent Action on Frog Skin.

    Science.gov (United States)

    Gao, Liqian; Yu, Zhiqiang; Meng, Dan; Zheng, Fang; Ong, Yong S; Miao, Peng; Lee, Su S; Wen, Longping

    2015-01-01

    An α-MSH peptide analogue, named MTII (Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]- NH2), is one of the most important ligands of melanotropic receptors but are relatively nonselective. In order to improve the melanotropic activities of the well-characterized MTII analogues, we report here a new analogue by modifying the core structure as well as the size of the cyclic region of MTII peptide. The analogue peptide, Ac-Nle-c[Asp-His-D-Phe-Lys-Trp-Gly-Lys]-OH (F Peptide), in which we replaced Arg at position 8 with Lys and added a Gly to position 10 of the MTII peptide sequence, was synthesized and used as a new melanotropic hormone in controlling rapid color changes in frogs by its actions on mobilizing pigment granule movements within chromatophores. The in vivo responses of chromatophores to MTII and the related analogue F Peptide were studied in frogs. The results show that the F Peptide was a superpotent agonist with similar melanotropic activity to the MTII peptide according to MTII peptide by in vivo studies. The analogue also exhibited ultraprolonged melanotropic activity. The F peptide can be useful in the study of numerous physiological processes, particularly when superpotent and prolonged melanotropic activity is desired.

  17. [Cloning, expressing of exendin-4 analogue and bioactivity analysis in vivo].

    Science.gov (United States)

    Li, Taiming; Gu, Chunjiao; Ge, Xiaoyu; Li, Zhezhe; Wang, Dan; Ma, Yanhong; Liu, Tao; Zhang, Meiyou; Li, Li; Liu, Jingjing

    2012-07-01

    To construct, express and purify Exendin-4 analogue and detect its biological activity in vivo. Insert gene sequence into fusion partner ofpED plasmid which is helped to purification, entitled the new recombinant plasmid 5 Exendin-4 analogue polypeptide gene and fusion partner gene was linked by acid hydrolysisgene, transformed to E. coli BL21 and the fusion protein was induced by lactose. After acid hydrolysis, the Exendin-4 analogue polypeptide separated from fusion chaperon. Anion charge chromatography were used to further purification. 6 to 8 week-old ICR mice were injected (s.c) with Exendin-4 analogue, blood glucose and plasma insulin level was detected in different period after oral glucose tolerance test. The results show that high expression of inclusion body was induced by lactose, which accounted for 40% of germ proteins, the Exendin-4 analogue was obtained with the purity of 91.8% after being purified by anion charge chromatography. Bioactivity assay showed that the level of blood glucose of mouse which treated with exendin-4 analogue was obviously decreased to normal (P < 0.01), and the level of plasma insulin was increased obviously (P < 0.01).

  18. GnRH analogue attenuated apoptosis of rat hippocampal neuron after ischemia-reperfusion injury.

    Science.gov (United States)

    Chu, Chenyu; Xu, Bainan; Huang, Weiquan

    2010-12-01

    The expression and new functions of reproductive hormones in organs beyond hypothalamus-pituitary-gonad axis have been reported. So far, there is no report about the protective effects of GnRH analogue to hippocampal neurons suffering from ischemia-reperfusion injury. Middle cerebral artery occlusion model together with TUNEL staining were made in vivo and oxygen-glucose deprivation model together with double staining of Annexin V/PI with flow cytometer were made in vitro to observe the anti-apoptotic effects of GnRH analogue to hippocampal neurons after ischemia-reperfusion injury. The results found that the number of TUNEL positive pyramidal neurons in CA1 region in GnRH analogue experiment group was less than that in control group in vivo; the percentage of apoptotic neurons in GnRH analogue experiment group was less than that in control group in vitro. These findings suggested that pretreatment with certain concentration of GnRH analogue could attenuate apoptosis of hippocampal neurons. GnRH analogue has the protective effects to neurons.

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

    Science.gov (United States)

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

    2012-08-01

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

  20. Computer-aided rational design of novel EBF analogues with an aromatic ring.

    Science.gov (United States)

    Wang, Shanshan; Sun, Yufeng; Du, Shaoqing; Qin, Yaoguo; Duan, Hongxia; Yang, Xinling

    2016-06-01

    Odorant binding proteins (OBPs) are important in insect olfactory recognition. These proteins bind specifically to insect semiochemicals and induce their seeking, mating, and alarm behaviors. Molecular docking and molecular dynamics simulations were performed to provide computational insight into the interaction mode between AgamOBP7 and novel (E)-β-farnesene (EBF) analogues with an aromatic ring. The ligand-binding cavity in OBP7 was found to be mostly hydrophobic due to the presence of several nonpolar residues. The interactions between the EBF analogues and the hydrophobic residues in the binding cavity increased in strength as the distance between them decreased. The EBF analogues with an N-methyl formamide or ester linkage had higher docking scores than those with an amide linkage. Moreover, delocalized π-π and electrostatic interactions were found to contribute significantly to the binding between the ligand benzene ring and nearby protein residues. To design new compounds with higher activity, four EBF analogues D1-D4 with a benzene ring were synthesized and evaluated based on their docking scores and binding affinities. D2, which had an N-methyl formamide group linkage, exhibited stronger binding than D1, which had an amide linkage. D4 exhibited particularly strong binding due to multiple hydrophobic interactions with the protein. This study provides crucial foundations for designing novel EBF analogues based on the OBP structure. Graphical abstract The design strategy of new EBF analogues based on the OBP7 structure.

  1. Aqueous chemistry of Ce(iv): estimations using actinide analogues.

    Science.gov (United States)

    Marsac, Rémi; Réal, Florent; Banik, Nidhu Lal; Pédrot, Mathieu; Pourret, Olivier; Vallet, Valérie

    2017-10-10

    The prediction of cerium (Ce) aqueous speciation is relevant in many research fields. Indeed, Ce compounds are used for many industrial applications, which may require the control of Ce aqueous chemistry for their synthesis. The aquatic geochemistry of Ce is also of interest. Due to its growing industrial use and its release into the environment, Ce is now considered as an emerging contaminant. Cerium is also used as a proxy of (paleo)redox conditions due to the Ce(iv)/Ce(iii) redox transition. Finally, Ce(iv) is often presented as a relevant analogue of tetravalent actinides (An(iv)). In the present study, quantum chemical calculations were conducted to highlight the similarities between the structures of Ce(iv) and tetravalent actinide (An(iv); An = Th, Pa, U, Np, Pu) aqua-ions, especially Pu(iv). The current knowledge of An(iv) hydrolysis, solubility and colloid formation in water was briefly reviewed but important discrepancies were observed in the available data for Ce(iv). Therefore, new estimations of the hydrolysis constants of Ce(iv) and the solubility of Ce(iv)-(hydr)oxides are proposed, by analogy with Pu(iv). By plotting pH-Eh (Pourbaix) diagrams, we showed that the pH values corresponding to the onset of Ce(iv) species formation (i.e. Ce(iv)-(hydr)oxide or dissolved Ce(iv)) agreed with various experimental results. Although further experimental studies are required to obtain a more accurate thermodynamic database, the present work might yet help to predict more accurately the Ce chemical behavior in aqueous solution.

  2. Design of potent substrate-analogue inhibitors of canine renin

    Science.gov (United States)

    Hui, K. Y.; Siragy, H. M.; Haber, E.

    1992-01-01

    Through a systematic study of structure-activity relationships, we designed potent renin inhibitors for use in dog models. In assays against dog plasma renin at neutral pH, we found that, as in previous studies of rat renin inhibitors, the structure at the P2 position appears to be important for potency. The substitution of Val for His at this position increases potency by one order of magnitude. At the P3 position, potency appears to depend on a hydrophobic side chain that does not necessarily have to be aromatic. Our results also support the approach of optimizing potency in a renin inhibitor by introducing a moiety that promotes aqueous solubility (an amino group) at the C-terminus of the substrate analogue. In the design of potent dog plasma renin inhibitors, the influence of the transition-state residue 4(S)-amino-3(S)-hydroxy-5-cyclohexylpentanoic acid (ACHPA)-commonly used as a substitute for the scissile-bond dipeptide to boost potency-is not obvious, and appears to be sequence dependent. The canine renin inhibitor Ac-paF-Pro-Phe-Val-statine-Leu-Phe-paF-NH2 (compound 15; IC50 of 1.7 nM against dog plasma renin at pH 7.4; statine, 4(S)-amino-3(S)-hydroxy-6-methylheptanoic acid; paF, para-aminophenylalanine) had a potent hypotensive effect when infused intravenously into conscious, sodium-depleted, normotensive dogs. Also, compound 15 concurrently inhibited plasma renin activity and had a profound diuretic effect.

  3. Laboratory and Field Spectroscopy of Moon analogue material

    Science.gov (United States)

    Offringa, Marloes; Foing, Bernard H.

    2016-07-01

    Samples derived from terrestrial analogue sites are studied to gain insight into lunar processes in their geological context (Foing, Stoker, Ehrenfreund, 2011). For this study samples from the volcanic region of the Eifel, Germany collected during our latest field campaigns in November 2015 and February 2016 (Foing et al., 2010), are analyzed with a variety of spectrometers. The aim is to obtain a database of analyzed samples that could be used as a reference for future in situ measurements. We also use a documented set of Moon-Mars relevant minerals curated at VU Amsterdam. We are using systematically for all samples UV-VIS and NIR reflectance spectrometers, and sporadically a Fourier Transform Infrared (FTIR) spectrometer, an X-Ray Fluorescence (XRF) spectrometer and a Raman laser spectrometer on control samples. Calibration of the UV-VIS and NIR reflectance spectrometers is the main focus of this research in order to obtain the clearest spectra. The calibration of the UV-VIS and NIR reflectance spectrometers requires the use of a good light source as well as suitable optical fibers to create a signal that covers the widest range in wavelengths available. To eliminate noise towards the edges of this range, multiple measurements are averaged and data is processed by dividing the signal by reference spectra. Obtained spectra can be tested for accuracy by comparing them with stationary laboratory spectrometers such as the FTIR spectrometer. The Raman, UV-VIS and NIR are also used in combination with the ExoGeoLab mock-up lander during field campaigns (Foing, Stoker, Ehrenfreund, 2011) also brought again to Eifel in February 2016, to prove the applicability of the equipment in the field. Acknowledgements: we thank Dominic Doyle for ESTEC optical lab support, Euan Monaghan (Leiden U) for FTIR measurement support, Wim van Westrenen for access to VU samples, Oscar Kamps (Utrecht U./ESTEC), Aidan Cowley (EAC) and Matthias Sperl (DLR) for support discussions

  4. Photoreactivity of condensed species on Titan's aerosols analogues

    Science.gov (United States)

    Fleury, Benjamin; Gudipati, Murthy; Carrasco, Nathalie

    2016-10-01

    Titan's aerosols formation is initiated in the upper atmospheric layers at about 1000 km by the dissociation and the ionization of N2 and CH4 by the VUV solar photons [1]. Then, they aggregate and sediment to the surface. The temperatures of the stratosphere and the troposphere [3] (measured by the HASI instrument onboard the Huygens probe [2]) allow the condensation of many volatile organics on the solid aerosols, forming organic ice coating on the aerosol polymers. We will present an experimental study simulating this process and discuss the photoreactivity of condensed species on Titan's aerosols analogues in the atmosphere and on the surface. We demonstrated experimentally that the organic aerosols, which cover the Titan's surface, drive the photoreactivity of condensed species such as acetylene when they are irradiated with long wavelength photons (λ > 300 nm). This result highlights that Titan's surface remains active despite the absorption of the most energetic photons by the atmosphere.AcknowledgmentsThis work is supported by NASA Solar System Workings grant " Photochemistry in Titan's Lower Atmosphere". The research work has been carried out at the Jet Propulsion Laboratory, California Institute of Technology under a contract with the National Aeronautics and Space Administration. NC acknowledges the European Research Council for their financial support (ERC Starting Grant PRIMCHEM, grant agreement n°636829).References[1] Waite, J. H., et al., The process of Tholin formation in Titan's upper atmosphere, (2007), Science 316, 870-875.[2] Fulchignoni, M., et al., In situ measurements of the physical characteristics of Titan's environment, (2005), Nature 438, 785-791[3] Lavvas, P., et al., Condensation in Titan's atmosphere at the Huygens landing site, (2011), Icarus 215, 732-750.

  5. Two-dimensional graphene analogues for biomedical applications.

    Science.gov (United States)

    Chen, Yu; Tan, Chaoliang; Zhang, Hua; Wang, Lianzhou

    2015-05-07

    The increasing demand of clinical biomedicine and fast development of nanobiotechnology has substantially promoted the generation of a variety of organic/inorganic nanosystems for biomedical applications. Biocompatible two-dimensional (2D) graphene analogues (e.g., nanosheets of transition metal dichalcogenides, transition metal oxides, g-C3N4, Bi2Se3, BN, etc.), which are referred to as 2D-GAs, have emerged as a new unique family of nanomaterials that show unprecedented advantages and superior performances in biomedicine due to their unique compositional, structural and physicochemical features. In this review, we summarize the state-of-the-art progress of this dynamically developed material family with a particular focus on biomedical applications. After the introduction, the second section of the article summarizes a range of synthetic methods for new types of 2D-GAs as well as their surface functionalization. The subsequent section provides a snapshot on the use of these biocompatible 2D-GAs for a broad spectrum of biomedical applications, including therapeutic (photothermal/photodynamic therapy, chemotherapy and synergistic therapy), diagnostic (fluorescent/magnetic resonance/computed tomography/photoacoustic imaging) and theranostic (concurrent diagnostic imaging and therapy) applications, especially on oncology. In addition, we briefly present the biosensing applications of these 2D-GAs for the detection of biomacromolecules and their in vitro/in vivo biosafety evaluations. The last section summarizes some critical unresolved issues, possible challenges/obstacles and also proposes future perspectives related to the rational design and construction of 2D-GAs for biomedical engineering, which are believed to promote their clinical translations for benefiting the personalized medicine and human health.

  6. Somatostatin analogue scintigraphy and tuberculosis: case report; Scintigraphie des analogues de la somatostatine et tuberculose: a propos d'un cas

    Energy Technology Data Exchange (ETDEWEB)

    Biancheri, I.; Rudenko, B.; Vautrin, P.; Raddoul, J.; Lamfichek, N. [Centre Hospitalier General Andre Boulloche, 25 - Montbeliard (France); Kantelip, B.; Mantion, G. [Centre Hospitalier Universitaire Jean Minjoz, 25 - Besancon (France)

    2005-05-15

    Scintigraphy using a radiolabelled somatostatin analogue (111 In-pentetreotide) is useful in the detection of neuroendocrine tumors. But this radiopharmaceutical accumulates also in solid tumours or in inflammatory diseases such as granulomatosis. We present a case of 111 In-pentetreotide uptake in a tuberculous adenopathy. (author)

  7. Synthesis and Bioactivities of Andrographolide Derivatives: New (-)-Limonidilactone Analogues%Synthesis and Bioactivities of Andrographolide Derivatives: New (-)-Limonidilactone Analogues

    Institute of Scientific and Technical Information of China (English)

    徐海伟; 姜平娟; 李伟义; 王俊峰; 刘宏民

    2011-01-01

    In this study, a novel route to (-)-limonidilactone analogues 10, 11 by way of stereoselective reaction of andrographolide (5) from 8, 9 was reported. The anti-tumor and a-glucosidsae inhibition activities of some synthetic compounds were screened.

  8. Alligator Rivers Analogue project. Radionuclide transport. Final Report - Volume 14

    Energy Technology Data Exchange (ETDEWEB)

    Golian, C. [Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW (Australia); Lever, D.A.; Baker, A.J.; Connell, L.D. [AEA Decommissioning and Radwaste, Harwell (United Kingdom); Bennett, D.G.; Read, D. [WS Atkins Science and Technology Epsom Surrey (United Kingdom); Lindgreen, M.; Pers, K.; Skagius, K. [Kemakta Consultants co., Stockholm (Sweden); Murakami, T.; Ohnuki, T. [Japan Atomic Energy Research Institute, Tokai-mura, IBARAKI (Japan)

    1992-12-31

    The Koongarra orebody and its associated dispersion fan are examined as a geological analogue for the transport of radionuclides from waste repositories. The aim is to build a consistent picture of the transport that has been taking place in the orebody and the important processes controlling the retardation of uranium series isotopes and to test models of radionuclide transport. A particularly distinctive feature of the Koongarra system is the strong seasonal dependence of the groundwater flow. However, the Koongarra system is similar to a radioactive waste disposal system in that mobilization of uranium is taking place as a result of the infiltration of groundwaters that are in gross chemical disequilibrium with the mineralogy of the primary ore body. There are considerable differences between the Koongarra uranium orebody and a radioactive waste repository, particularly a deep waste repository. The Koongarra system is shallow, affected by seasonal hydrogeological changes as well as climatic variations on a longer timescale and transport is taking place in a zone of active weathering. Some of these features make the Koongarra system harder to characterise than a deep repository. However, there are nevertheless many analogies between the processes occurring at Koongarra and those occurring around a deep or shallow waste repository. The difficulties encountered because of the heterogeneity of the Koongarra weathered zone mirror those to be addressed in assessing radionuclide transport in repository systems. The {sup 234}U/{sup 238}U activity ratios in rock samples from the dispersion fan decrease in the direction of groundwater transport, whereas in many other systems it has been reported that {sup 234}U is preferentially mobile relative to {sup 238}U (Osmond and Cowart, 1982; Osmond et al., 1983). As most uranium resides in the rock rather than in the groundwater, the net recoil flux of uranium daughter radionuclides is usually from the rock to the groundwater

  9. Response of Staphylococcus Aureus to a Spaceflight Analogue

    Science.gov (United States)

    Castro, S. L.; Ott, C. M.

    2010-01-01

    The decreased gravity of the spaceflight environment creates quiescent, low fluid shear conditions. This environment can impart considerable effects on the physiology of microorganisms as well as their interactions with potential hosts. Using the rotating wall vessel (RWV), as a spaceflight analogue, the consequence of low fluid shear culture on microbial pathogenesis has provided a better understanding of the risks to the astronaut crew from infectious microorganisms. While the outcome of low fluid shear culture has been investigated for several bacterial pathogens, little has been done to understand how this environmental factor affects Staphylococcus aureus. S. aureus is an opportunistic human pathogen which presents a high level of infection risk to the crew, as it has been isolated from both the space shuttle and International Space Station. Given that approximately forty percent of the population are carriers of the bacteria, eradication of this organism from in flight environments is impractical. These reasons have lead to us to assess the response of S. aureus to a reduced fluid shear environment. Culture in the RWV demonstrated that S. aureus grown under the low-shear condition had lower cell concentrations after 10 hours when compared to the control culture. Furthermore, the low-shear cultured bacteria displayed a reduction in carotenoid production, pigments responsible for their yellow/gold coloration. When exposed to various environmental stressors, post low-shear culture, a decrease in the ability to survive oxidative assault was observed compared to control cultures. The low fluid shear environment also resulted in a decrease in hemolysin secretion, a staphylococcal toxin responsible for red blood cell lysis. When challenged by the immune components present in human whole blood, low-shear cultured S. aureus demonstrated significantly reduced survival rates as compared to the control culture. Assays to determine the duration of these alterations

  10. Emotions and Habitability study in Moon Mars Analogue.

    Science.gov (United States)

    Mertens, Alexandre; Lia Schlacht, Irene

    Euro Moon Mars mission have been conducted by students and field researchers in the Mars Desert Research Station (MDRS) a habitat installed by the Mars Society (MS) in the Utah desert. The campaign was supported by ILEWG International Lunar Exploration Working Group, ESTEC, NASA Ames, and partners. It investigated human aspects of isolation in a Mars analogue base. The project is in line with the ILEWG which coordinates several MDRS missions, and contributes to the preparation of future Mars sample return missions. The objective is to study and improve the habitat dynamics in a closed and small environment. Investigation cover different fields as emotional, sociological and psychological aspects and a food study but also habitability aspects. The study has been conducted by asking to the crew members to perform task and fill in questionnaires before, during and after the simulation. Video recovering, pictures and heart rate counting will also be used. One of the main study subject, conducted by Bernard Rimé, concerns the sharing of emotions in an isolated environ-e ment. Another is "Mars Habitability Experiment", which responsible is Irene Schlacht, will try to determine whether humans need variability of stimuli such as it happens in the natural environment -e.g. seasonal changing -to gain efficiency, reliability and well-being. This study have been conducted from February 19 to April 19 on two crews presenting different aspects that could lead to various behaviours. The first crew is made of people from different countries that don't know each other very well. On the opposite, the second crew members have the same cultural background -they come from the same country, university -and they know each other for at least six months. This allow studying how the extreme conditions of the isolation affect the crew efficiency, creativity and sanity according to its homogeneity. Report on the science and technical results, and implications for Earth-Mars comparative stud

  11. Response of Staphylococcus Aureus to a Spaceflight Analogue

    Science.gov (United States)

    Castro, S. L.; Ott, C. M.

    2010-01-01

    The decreased gravity of the spaceflight environment creates quiescent, low fluid shear conditions. This environment can impart considerable effects on the physiology of microorganisms as well as their interactions with potential hosts. Using the rotating wall vessel (RWV), as a spaceflight analogue, the consequence of low fluid shear culture on microbial pathogenesis has provided a better understanding of the risks to the astronaut crew from infectious microorganisms. While the outcome of low fluid shear culture has been investigated for several bacterial pathogens, little has been done to understand how this environmental factor affects Staphylococcus aureus. S. aureus is an opportunistic human pathogen which presents a high level of infection risk to the crew, as it has been isolated from both the space shuttle and International Space Station. Given that approximately forty percent of the population are carriers of the bacteria, eradication of this organism from in flight environments is impractical. These reasons have lead to us to assess the response of S. aureus to a reduced fluid shear environment. Culture in the RWV demonstrated that S. aureus grown under the low-shear condition had lower cell concentrations after 10 hours when compared to the control culture. Furthermore, the low-shear cultured bacteria displayed a reduction in carotenoid production, pigments responsible for their yellow/gold coloration. When exposed to various environmental stressors, post low-shear culture, a decrease in the ability to survive oxidative assault was observed compared to control cultures. The low fluid shear environment also resulted in a decrease in hemolysin secretion, a staphylococcal toxin responsible for red blood cell lysis. When challenged by the immune components present in human whole blood, low-shear cultured S. aureus demonstrated significantly reduced survival rates as compared to the control culture. Assays to determine the duration of these alterations

  12. Demonstration of flow localization in analogue partially molten system

    Science.gov (United States)

    Takashima, S.; Kumagai, I.; Kurita, K.

    2003-04-01

    Melt migration in partially molten medium is conceptually classified into two contrasting models; homogeneous permeable flow and localized channeled flow. The transition from permeable flow to localized one is promoted with advance of melting and deformation of the medium. Kelemen et al(1995) and Spiegelmanet al(2001) modeled this process taking into accounts of compaction and dissolution. But the physics behind this transition is not yet clarified well. Here we explore rheological aspect of this problem based analogue experiments using deformable soft gel as a solid phase and would like to argue the role of self-organization in the flow development. In this presentation we show two kinds of experimental results which are mutually related. One is a demonstration of development of the channeled flow in a so-called Rayleigh-Taylor Instability experiments. Dense viscous fluid(glycerol solution) is poured at the top of the matrix fluid;homogeneous mixture of soft transparent gel and visocous fluid( the viscosity is controlled by adding methyl-cellulose) having equal density. Liquid fraction is varied for this matrix fluid to see how the fraction controls the development. At the intermediate gel fraction(between70% to about 40%) the dense fluid at first migrates through the grain boundary as permeable flow. But local heterogeneity in the gel fraction induces relative movement of solid phase, which in turns enhances the localization of the flow and deformation. We measured the motion of fluid phase and solid phase separately by adoting PIV/PTV methods. Calculated relative motion describes how flow localization has developed. The deformation-induced compaction plays an important role. The second experimental result is rheology of the dense suspension of soft gel and viscous fluid. At the intermediate gel fraction, the rheology is sensitive to the mixture state. Deformation of bulk sample depends on the internal melt distribution and the melt distribution depends on the

  13. Alligator Rivers Analogue project. Hydrogeological modelling. Final Report - Volume 6

    Energy Technology Data Exchange (ETDEWEB)

    Townley, L.R.; Trefry, M.G.; Barr, A.D. [CSIRO Div of Water Resources, PO Wembley, WA (Australia); Braumiller, S. [Univ of Arizona, Tucson, AZ (United States). Dept of Hydrology and Water Resources; Kawanishi, M. [Central Research Institute of Electric Power Industry, Abiko-Shi, Chiba-Ken (Japan)] [and others

    1992-12-31

    This volume describes hydrogeological modelling carried out as part of the Alligator Rivers Analogue Project. Hydrogeology has played a key integrating role in the Project, largely because water movement is believed to have controlled the evolution of the Koongarra uranium Orebody and therefore affects field observations of all types at all scales. Aquifer testing described uses the concept of transmissivity in its interpretation of aquifer response to pumping. The concept of an aquifer, a layer transmitting significant quantities of water in a mainly horizontal direction, seems hard to accept in an environment as heterogeneous as that at Koongarra. But modelling of aquifers both in one dimension and two dimensionally in plan has contributed significantly to our understanding of the site. A one-dimensional model with three layers (often described as a quasi two dimensional model) was applied to flow between the Fault and Koongarra Creek. Being a transient model, this model was able to show that reverse flows can indeed occur back towards the Fault, but only if there is distributed recharge over the orebody as well as a mechanism for the Fault, or a region near the Fault, to remove water from the simulated cross-section. The model also showed clearly that the response of the three-layered system, consisting of a highly weathered zone, a fractured transmissive zone and a less conductive lower schist zone, is governed mainly by the transmissivity and storage coefficient of the middle layer. The storage coefficient of the higher layer has little effect. A two-dimensional model in plan used a description of anisotropy to show that reverse flows can also occur even without a conducting Fault. Modelling of a three-dimensional region using discrete fractures showed that it is certainly possible to simulate systems like that observed at Koongarra, but that large amounts of data are probably needed to obtain realistic descriptions of the fracture networks. Inverse modelling

  14. Synthesis and Evaluation of a Library of Fluorescent Dipeptidomimetic Analogues as Substrates for Modified Bacterial Ribosomes.

    Science.gov (United States)

    Chowdhury, Sandipan Roy; Chauhan, Pradeep S; Dedkova, Larisa M; Bai, Xiaoguang; Chen, Shengxi; Talukder, Poulami; Hecht, Sidney M

    2016-05-03

    Described herein are the synthesis and photophysical characterization of a library of aryl-substituted oxazole- and thiazole-based dipeptidomimetic analogues, and their incorporation into position 66 of green fluorescent protein (GFP) in lieu of the natural fluorophore. These fluorescent analogues resemble the fluorophore formed naturally by GFP. As anticipated, the photophysical properties of the analogues varied as a function of the substituents at the para position of the phenyl ring. The fluorescence emission wavelength maxima of compounds in the library varied from ∼365 nm (near-UV region) to ∼490 nm (visible region). The compounds also exhibited a large range of quantum yields (0.01-0.92). The analogues were used to activate a suppressor tRNACUA and were incorporated into position 66 of GFP using an in vitro protein biosynthesizing system that employed engineered ribosomes selected for their ability to incorporate dipeptides. Four analogues with interesting photophysical properties and reasonable suppression yields were chosen, and the fluorescent proteins (FPs) containing these fluorophores were prepared on a larger scale for more detailed study. When the FPs were compared with the respective aminoacyl-tRNAs and the actual dipeptide analogues, the FPs exhibited significantly enhanced fluorescence intensities at the same concentrations. Part of this was shown to be due to the presence of the fluorophores as an intrinsic element of the protein backbone. There were also characteristic shifts in the emission maxima, indicating the environmental sensitivity of these probes. Acridon-2-ylalanine and oxazole 1a were incorporated into positions 39 and 66 of GFP, respectively, and were shown to form an efficient Förster resonance energy transfer (FRET) pair, demonstrating that the analogues can be used as FRET probes.

  15. Solution conformation of C-linked antifreeze glycoprotein analogues and modulation of ice recrystallization.

    Science.gov (United States)

    Tam, Roger Y; Rowley, Christopher N; Petrov, Ivan; Zhang, Tianyi; Afagh, Nicholas A; Woo, Tom K; Ben, Robert N

    2009-11-01

    Antifreeze glycoproteins (AFGPs) are a unique class of proteins that are found in many organisms inhabiting subzero environments and ensure their survival by preventing ice growth in vivo. During the last several years, our laboratory has synthesized functional C-linked AFGP analogues (3 and 5) that possess custom-tailored antifreeze activity suitable for medical, commercial, and industrial applications. These compounds are potent inhibitors of ice recrystallization and do not exhibit thermal hysteresis. The current study explores how changes in the length of the amide-containing side chain between the carbohydrate moiety and the polypeptide backbone in 5 influences ice recrystallization inhibition (IRI) activity. Analogue 5 (n = 3, where n is the number of carbons in the side chain) was a potent inhibitor of ice recrystallization, while 4, 6, and 7 (n = 4, 2, and 1, respectively) exhibited no IRI activity. The solution conformation of the polypeptide backbone in C-linked AFGP analogues 4-7 was examined using circular dichroism (CD) spectroscopy. The results suggested that all of the analogues exhibit a random coil conformation in solution and that the dramatic increase in IRI activity observed with 5 is not due to a change in long-range solution conformation. Variable-temperature (1)H NMR studies on truncated analogues 26-28 failed to elucidate the presence of persistent intramolecular bonds between the amide in the side chain and the peptide backbone. Molecular dynamics simulations performed on these analogues also failed to show persistent intramolecular hydrogen bonds. However, the simulations did indicate that the side chain of IRI-active analogue 26 (n = 3) adopts a unique short-range solution conformation in which it is folded back onto the peptide backbone, orienting the more hydrophilic face of the carbohydrate moiety away from the bulk solvent. In contrast, the solution conformation of IRI-inactive analogues 25, 27, and 28 had fully extended side chains

  16. A Sleeping Beauty DNA transposon-based genetic sensor for functional screening of vitamin D3 analogues

    DEFF Research Database (Denmark)

    Staunstrup, Nicklas Heine; Sharma, Nynne; Bak, Rasmus Otkjær;

    2011-01-01

    Analogues of vitamin D3 are extensively used in the treatment of various illnesses, such as osteoporosis, inflammatory skin diseases, and cancer. Functional testing of new vitamin D3 analogues and formulations for improved systemic and topical administration is supported by sensitive screening me...... analogues. The tri-cistronic genetic sensor encodes a drug-sensoring protein, a reporter protein expressed from an activated sensor-responsive promoter, and a resistance marker....

  17. Encapsulation of antiviral nucleotide analogues azidothymidine-triphosphate and cidofovir in poly(iso-butylcyanoacrylate) nanocapsules.

    Science.gov (United States)

    Hillaireau, H; Le Doan, T; Besnard, M; Chacun, H; Janin, J; Couvreur, P

    2006-10-31

    Nucleoside analogues are widely used in the treatment of various viral infections. However, the poor in vivo conversion of the nucleoside analogues like azidothymidine (AZT) into their active triphosphate nucleotide counterpart limits their pharmacological efficacy. This could be overcome by the direct administration of azidothymidine triphosphate (AZT-TP), but it requires an appropriate drug delivery approach. Besides nucleoside analogues, nucleotide analogues like cidofovir (CDV) are also used in the treatment of viral infections. CDV has raised recent interest because of its promising activity against smallpox, but its use is limited by its poor bioavailability and nephrotoxicity. Here again, a proper drug delivery system should address these issues. In this study, we investigated the encapsulation of the nucleotide analogues AZT-TP and CDV into poly(iso-butylcyanoacrylate) aqueous core nanocapsules, known to efficiently entrap oligonucleotides. We show here that the encapsulation of these mono-nucleotides is less efficient than with oligonucleotides and that a rapid release of AZT-TP from the nanocapsules occurred in vitro. This highlights the importance of the molecular weight of the entrapped molecules which, if they are too small, are diffusing through the thin polymer membrane of the nanocapsules. On the other hand, a good protection of the encapsulated AZT-TP was observed.

  18. Pharmacological characterisation of strychnine and brucine analogues at glycine and alpha7 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Jensen, Anders A; Gharagozloo, Parviz; Birdsall, Nigel J M; Zlotos, Darius P

    2006-06-06

    Strychnine and brucine from the plant Strychnos nux vomica have been shown to have interesting pharmacological effects on several neurotransmitter receptors, including some members of the superfamily of ligand-gated ion channels. In this study, we have characterised the pharmacological properties of tertiary and quaternary analogues as well as bisquaternary dimers of strychnine and brucine at human alpha1 and alpha1beta glycine receptors and at a chimera consisting of the amino-terminal domain of the alpha7 nicotinic receptor (containing the orthosteric ligand binding site) and the ion channel domain of the 5-HT3A serotonin receptor. Although the majority of the analogues displayed significantly increased Ki values at the glycine receptors compared to strychnine and brucine, a few retained the high antagonist potencies of the parent compounds. However, mirroring the pharmacological profiles of strychnine and brucine, none of the analogues displayed significant selectivity between the alpha1 and alpha1beta subtypes. The structure-activity relationships for the compounds at the alpha7/5-HT3 chimera were significantly different from those at the glycine receptors. Most strikingly, quaternization of strychnine and brucine with substituents possessing different steric and electronic properties completely eliminated the activity at the glycine receptors, whereas binding affinity to the alpha7/5-HT3 chimera was retained for the majority of the quaternary analogues. This study provides an insight into the structure-activity relationships for strychnine and brucine analogues at these ligand-gated ion channels.

  19. Synthesis and evaluation of novel analogues of mangiferin as potent antipyretic

    Institute of Scientific and Technical Information of China (English)

    Shashi Kant Singh; Saurabh K Sinha; SK Prasad; R Kumar; Bhawani S Bithu; S Sadish Kumar; P Singh

    2011-01-01

    Objective:To screen different analogues of mangiferin pharmacologically for antipyretic activity. Methods:The naturally occurring xanthone glycoside mangiferin was isolated by column chromatography from the ethanolic extract of stem bark ofMangifera indica. Mangiferin was further converted to5-(N-phenylamino methyleno) mangiferin,5-(N-p-chlorophenylamino methyleno) mangiferin,5-(N-2-methyl phenylamino methyleno) mangiferin, 5-(N-p-methoxy phenylamino methyleno) mangiferin,5-(N, N-diphenylamino methyleno) mangiferin,5-(N-α-napthylamino methyleno) mangiferin and5-(N-4-methyl phenylamino methyleno) mangiferin analogues. The synthesized compounds were further screened for antipyretic activity along with mangiferin at a dose level of 100 and 200 mg/kg. Mangiferin and its analogues were characterized by melting point andRfvalue determination and through spectral technique likeUV, IR, and NMR spectral analysis.Results: The antipyretic activity of mangiferin as well as all analogues was found to be more significant in at higher doseie.200mg/kg which was depicted through a decrease in rectal temperature up to3 h.Conclusions:The antipyretic activity of mangiferin and its analogues may be attributed to inhibition in synthesis ofTNF-α and anti-oxidant activity associated with amelioration of inflammatory actions of cytokines.

  20. Analogue correction method of errors and its applicatim to numerical weather prediction

    Institute of Scientific and Technical Information of China (English)

    Gao Li; Ren Hong-Li; Li Jian-Ping; Chou Ji-Fan

    2006-01-01

    In this paper,an analogue correction method of errors (ACE) based on a complicated atmospheric model is further developed and applied to numerical weather prediction (NWP).The analysis shows that the ACE can effectively reduce model errors by combining the statistical analogue method with the dynamical model together in order that the information of plenty of historical data is utilized in the current complicated NWP model.Furthermore.in the ACE.the differences of the similarities between different historical analogues and the current initial state are considered as the weights for estimating model errors.The results of daily,decad and monthly prediction experiments On a complicated T63 atmospheric model show that the performance of the ACE by correcting model errors based on the estimation of the errors of 4 historical analogue predictions is not only better than that of the scheme of only introducing the correction of the errors of every single analogue prediction,but is also better than that of the T63 model.