DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei, Yongbin; Jia, Yanmin, E-mail: wuzheng@zjnu.cn, E-mail: ymjia@zjnu.edu.cn; Wu, Jiang

A mutual enhancement action between the ferro-/piezoelectric polarization and the photoluminescent performance of rare earth Pr{sup 3+} doped (K{sub 0.5}Na{sub 0.5})NbO{sub 3} (KNN) lead-free ceramics is reported. After Pr{sup 3+} doping, the KNN ceramics exhibit the maximum enhancement of ∼1.2 times in the ferroelectric remanent polarization strength and ∼1.25 times in the piezoelectric coefficient d{sub 33}, respectively. Furthermore, after undergoing a ferro-/piezoelectric polarization treatment, the maximum enhancement of ∼1.3 times in photoluminescence (PL) was observed in the poled 0.3% Pr{sup 3+} doped sample. After the trivalent Pr{sup 3+} unequivalently substituting the univalent (K{sub 0.5}Na{sub 0.5}){sup +}, A-sites ionic vacancies willmore » occur to maintain charge neutrality, which may reduce the inner stress and ease the domain wall motions, yielding to the enhancement in ferro-/piezoelectric performance. The polarization-induced enhancement in PL is attributed to the decrease of crystal symmetry abound the Pr{sup 3+} ions after polarization. The dual-enhancement of the ferro-/piezoelectric and photoluminescent performance makes the Pr{sup 3+} doped KNN ceramic hopeful for piezoelectric/luminescent multifunctional devices.« less

Braccio di Ferro: a new haptic workstation for neuromotor rehabilitation.

PubMed

Casadio, Maura; Sanguineti, Vittorio; Morasso, Pietro G; Arrichiello, Vincenzo

2006-01-01

This technical note describes a new robotic workstation for neurological rehabilitation, shortly named Braccio di Ferro. It has been designed by having in mind the range of forces and the frequency bandwidth that characterize the interaction between a patient and a physical therapist, as well as a number of requirements that we think are essential for allowing a natural haptic interaction: back-driveability, very low friction and inertia, mechanical robustness, the possibility to operate in different planes, and an open software environment, which allows the operator to add new functionalities and design personalized rehabilitation protocols. Braccio di Ferro is an open system and, in the spirit of open source design, is intended to foster the dissemination of robot therapy. Moreover, its combination of features is not present in commercially available systems.

Le premier relaxeur ferroélectrique oxyfluoré

NASA Astrophysics Data System (ADS)

Ravez, J.; Simon, A.

1997-02-01

Une étude diélectrique fine du système BaTiO3-BaLiF3 a montré que les céramiques de composition Ba(Ti1 - xLix)O3 - 3xF3x présentent deux comportements différents: l'un de type ferroélectrique classique pour (0 ≤ x 0,04), l'autre de type relaxeur ferroélectrique pour (0,04 <>x<> 0,15). Ces derniers matériaux constituent les premiers relaxeurs ferroélectriques oxyfluorés et comportent les caractéristiques diélectriques typiques correspondantes: transition de phase diffuse, dispersion en fréquence, croissance de Tm (température du maximum de 'r) avec la fréquence, écart à la loi de Curie-Weiss, etc. C'est l'occupation des mêmes sites cristallographiques par des cations (Ti4+, Li+) et anions (O2 - , F - ) hétérovalents qui est à l'origine de telles propriétés. A fine dielectric study of the BaTiO3-BaLiF3 system has shown that ceramics with composition Ba(Ti1 - xLix)O3 - 3xF3x present two different behaviours: a classical ferroelectric one for (0 ≤ x 0.04), a ferroelectric relaxor one for (0.04 x 0.15). Such materials constitute the first oxyfluoride ferroelectric relaxors with corresponding typical dielectric characteristics: diffuse phase transition, frequency dispersion, increase of Tm (temperature of the maximum of 'r) with frequency, deviation from the Curie-Weiss law. The occupation of the same crystallographic sites by heterovalent cations (Ti4+, Li+) and anions (O2 - , F - ) is the cause of such properties.

Stability of Glass Fiber-Plastic Composites

DTIC Science & Technology

1974-11-01

investigated. 1. S-Glass The formation of S-g1ass 1s proprietary and differs between the two main sources ( Owens - Corning and Ferro Corporation) from...which samples were obtained for this research program. However, according to published work by Humphrey (8) of Owens - Corning , the approximate...of the glass fibers. S-glass fibers furnished by both Owens - Corning and Ferro Cor- poration were utilized and the results analyzed using scanning

Electrochemistry of 1,1'-bis(2,4-dialkylphosphetanyl)ferrocene and 1,1'-bis(2,5-dialkylphospholanyl)ferrocene ligands: free phosphines, metal complexes, and chalcogenides.

PubMed

Mandell, Chelsea L; Kleinbach, Shannon S; Dougherty, William G; Kassel, W Scott; Nataro, Chip

2010-10-18

The oxidative electrochemistries of a series of chiral bisphosphinoferrocene ligands, 1,1'-bis(2,4-dialkylphosphetanyl)ferrocene (FerroTANE) and 1,1'-bis(2,5-dialkylphospholanyl)ferrocene (FerroLANE), were examined. The reversibility of the oxidation is sensitive to the steric bulk of the alkyl groups. New transition metal compounds and phosphine chalcogenides of these ligands were prepared and characterized. X-ray crystal structures of 10 of these compounds are reported. The percent buried volume (%V(bur)) is a recently developed measurement based on crystallographic data that examines the steric bulk of N-heterocyclic carbene and phosphine ligands. The %V(bur) for the FerroTANE and FerroLANE structures with methyl or ethyl substituents suggests these ligands are similar in steric properties to 1,1'-bis(diphenylphosphino)ferrocene (dppf). In addition the %V(bur) has been found to correlate well with the Tolman cone angle for phosphine chalcogenides. The oxidative electrochemistries of the transition metal complexes occur at more positive potentials than the free ligands. While a similar positive shift is seen for the oxidative electrochemistries of the phosphine chalcogenides, the oxidation of the phosphine selenides does not occur at the iron center, but rather oxidation occurs at the selenium atoms.

K4[Fe(CN)6] immobilized anion sensitive protonated amine functionalized polysilsesquioxane films for ultra-low electrochemical detection of dsDNA.

PubMed

Silambarasan, Krishnamoorthy; Narendra Kumar, Alam Venugopal; Joseph, James

2016-03-14

Charge transport in polymeric films bound by redox reagents is a topic of current interest. The dynamics of electroinactive ions across the interface is studied by immobilizing ferrocyanide anion in a polysilsesquioxanes (PSQs) modified electrode. Redox reagents can stay in the polymeric film by either physical forces or electrostatic binding. The present work describes the immobilization of ferro/ferricyanide redox couples in PSQ films possessing protonated amine functional groups by electrostatic interactions. Charge transport in [Fe(CN)6](4-)-PSQs film was found to be anion dependent, and its formal potential value varied with the relative hydrophilic or hydrophobic nature of the anion used in the supporting electrolyte, unlike the observed dependence on solution cation for electrodes modified with metal hexacyanoferrates (Prussian Blue analogues). The [Fe(CN)6](4-) bound PSQs films were extensively characterized by varying different supporting electrolytes anions using cyclic voltammetry. The redox peak currents were linearly proportional to the square root of the scan rate, implying that the transport of charge carriers is accompanied with redox ion diffusion and electron hopping in a confined space. dsDNA molecules were found to interact with this polymer matrix through anionic phosphate groups. Both voltammetry and A.C. impedance spectroscopy studies revealed that these interactions could be exploited for the determination of ultra-low level (0.5 attomolar) of dsDNA present in aqueous solution.

Spin-Transfer-Torque Nano-Oscillators: Fabrication, Characterization and Dynamics

NASA Astrophysics Data System (ADS)

Costa, Jose Diogo Teixeira Barbosa

Este trabalho aborda algumas propriedades magneticas e estruturais de nanoparticulas de oxidos e oxidos-hidroxidos de ferro crescidos em matrizes hibridas orgânicas-inorgânicas. As matrizes hibridas, denominadas di-ureasils e obtidas pelo processo sol-gel, sao compostas por uma rede siliciosa ligada covalentemente por pontes ureia a cadeias orgânicas de diferente peso molecular. A estrutura local dos di-ureasils nao dopados esta modelada como grupos de dominios siliciosos com dimensoes nanometricas, estruturalmente correlacionados no seio de uma matriz rica em polimero. Neste trabalho mostra-se que os di-ureasils permitem o crescimento controlado de oxidos e oxidos-hidroxidos de ferro, incluindo a magnetite, maguemite, oxihidroxinitrato de ferro e ferrihidrite. O crescimento das nanoparticulas de ferrihidrite da-se em condicoes acidas a superficie dos dominios siliciosos, junto aos grupos carbonilo, que funcionam como pontos de nucleacao. Desse modo da-se uma nucleacao heterogenea, onde o tamanho das nanoparticulas depende da concentracao de ferro (entre 1 e 6% em massa), sendo a concentracao de particulas constante. As propriedades magneticas das nanoparticulas de ferrihidrite revelam a existencia de interaccoes antiferromagneticas e de momentos descompensados. A contribuicao destas duas componentes nas curvas de magnetizacao em funcao do campo magnetico pode ser separada usando um metodo aqui proposto, o que permite um adequado estudo da evolucao do momento magnetico com a temperatura. O estudo das propriedades magneticas dinâmicas das particulas de ferrihidrite, atraves de susceptibilidade ac, medidas de relaxacao e medidas de efeito Mossbauer, permitiu estudar a evolucao das interaccoes dipolares em funcao da concentracao de ferro, bem como determinar a distribuicao de barreiras de energia de anisotropia no caso em que essas interaccoes sao desprezaveis. E apresentado um novo metodo para comparacao desta distribuicao com a distribuicao de tamanhos, que permitiu concluir que os momentos magneticos descompensados estao aleatoriamente distribuidos em volume. Usando baixas concentracoes de agua, foi possivel crescer fases de oxihidroxinitrato de ferro com diferentes graus de cristalinidade, sendo algumas precursoras da ferrihidrite (como observado noutros trabalhos) e sendo outras novas fases. O crescimento de nanoparticulas de maguemite e magnetite acontece apos incorporacao de ioes de Fe2+ e Fe3+ seguidos de tratamento basico e termico. Estes sistemas apresentam propriedades magneticas tipicas de nanoparticulas superparamagneticas sem interaccoes dipolares. As propriedades magneticas dependem criticamente da existencia de grupos isocianato livres, que actuarao como pontos de nucleacao. None

Facile Synthesis of Radial-Like Macroporous Superparamagnetic Chitosan Spheres with In-Situ Co-Precipitation and Gelation of Ferro-Gels

PubMed Central

Yang, Chih-Hui; Wang, Chih-Yu; Huang, Keng-Shiang; Yeh, Chen-Sheng; Wang, Andrew H. -J.; Wang, Wei-Ting; Lin, Ming-Yu

2012-01-01

Macroporous chitosan spheres encapsulating superparamagnetic iron oxide nanoparticles were synthesized by a facile and effective one-step fabrication process. Ferro-gels containing ferrous cations, ferric cations and chitosan were dropped into a sodium hydroxide solution through a syringe pump. In addition, a sodium hydroxide solution was employed for both gelation (chitosan) and co-precipitation (ferrous cations and ferric cations) of the ferro-gels. The results showed that the in-situ co-precipitation of ferro-ions gave rise to a radial morphology with non-spheroid macro pores (large cavities) inside the chitosan spheres. The particle size of iron oxide can be adjusted from 2.5 nm to 5.4 nm by tuning the concentration of the sodium hydroxide solution. Using Fourier Transform Infrared Spectroscopy and X-ray diffraction spectra, the synthesized nanoparticles were illustrated as Fe3O4 nanoparticles. In addition, the prepared macroporous chitosan spheres presented a super-paramagnetic behaviour at room temperature with a saturation magnetization value as high as ca. 18 emu/g. The cytotoxicity was estimated using cell viability by incubating doses (0∼1000 µg/mL) of the macroporous chitosan spheres. The result showed good viability (above 80%) with alginate chitosan particles below 1000 µg/mL, indicating that macroporous chitosan spheres were potentially useful for biomedical applications in the future. PMID:23226207

Calculations of Exchange Bias in Thin Films with Ferromagnetic/Antiferromagnetic Interfaces

NASA Astrophysics Data System (ADS)

Koon, N. C.

1997-06-01

A microscopic explanation of exchange bias in thin films with compensated ferro/antiferromagnetic interfaces is presented. Full micromagnetic calculations show the interfacial exchange coupling to be relatively strong with a perpendicular orientation between the ferro/antiferromagnetic axis directions, similar to the classic ``spin-flop'' state in bulk antiferromagnets. With reasonable parameters the calculations predict bias fields comparable to those observed and provide a possible explanation for both anomalous high field rotational hysteresis and recently discovered ``positive'' exchange bias.

Concomitant degradation of bisphenol A during ultrasonication and Fenton oxidation and production of biofertilizer from wastewater sludge.

PubMed

Mohapatra, D P; Brar, S K; Tyagi, R D; Surampalli, R Y

2011-09-01

Degradation of bisphenol A (BPA), an endocrine disruptor, from wastewater sludge (WWS) has attracted great interest recently. In the present study, the effects of different pre-treatment methods, including ultrasonication (US), Fenton's oxidation (FO) and ferro-sonication (FS) was assessed in terms of increase in solubilization of WWS and simultaneous degradation of BPA. Among US, FO and FS pre-treatment, higher suspended solids (SS), volatile suspended solids (VSS), chemical oxygen demand (COD) and soluble organic carbon (SOC) solubilization (39.7%, 51.2%, 64.5% and 17.6%, respectively) was observed during a ferro-sonication pre-treatment process carried out for 180 min, resulting in higher degradation of BPA (82.7%). In addition, the effect of rheological parameters (viscosity and particle size) and zeta potential on the degradation of BPA in raw and different pre-treated sludges were also investigated. The results showed that a decrease in viscosity and particle size and an increase in zeta potential resulted in higher degradation of BPA. BPA degradation by laccases produced by Sinorhizobium meliloti in raw and pre-treated sludge was also determined. Higher activity of laccases (207.9 U L(-1)) was observed in ferro-sonicated pre-treated sludge (180 min ultrasonic time), resulting in higher removal of BPA (0.083 μg g(-1)), suggesting concomitant biological degradation of BPA. Copyright © 2011 Elsevier B.V. All rights reserved.

Evaluation of microsilica admixture for production of high strength concrete.

DOT National Transportation Integrated Search

1990-08-01

This study consisted of a laboratory evaluation of the effect of microsilica on the physical properties of both plastic and hardened portland cement concrete. Microsilica (silica fume) is a by-product of the industrial manufacture of ferro silicon an...

Manganese in Air: Associations in Residents with Tremor and Motor Function

EPA Science Inventory

Objective: An environmental study examined air manganese (Mn) exposed residents of two towns in Ohio: Marietta (near a ferro-manganese smelter) and East Liverpool (EL)(adjacent to an open-storage ore packaging facility). Air Mn inhalation is associated with neuropsychological/neu...

Ferro and antiferro orbital ordering in Fe{sub 0.5}Mn{sub 0.5}V{sub 2}O{sub 4}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dey, Dibyendu, E-mail: dibyendu@phy.iitkgp.ernet.in; Taraphder, A.; Maitra, T.

2016-05-23

Using density functional theory calculations, we have investigated the orbital ordering in Fe{sub 0.5}Mn{sub 0.5}V{sub 2}O{sub 4} where Fe and V sites are orbitally active. Our first principles study within GGA+U and GGA+U+SO shows ferro-orbital ordering of d{sub x2−y2} orbital at all Fe sites, whereas A-type antiferro-orbital ordering at V sites where one 3d electron occupies d{sub xy} orbital at every V site and another electron occupies either 1/√2 (d{sub xz} + d{sub yz}) or 1/√2 (d{sub xz} - d{sub yz}) orbital alternatively along c axis. Insulating nature and the orbital ordering of this compound are found to be correlationmore » driven while the effect of spin-orbit interaction on orbital ordering is not significant.« less

The role of electronic dopant on full band in-plane RKKY coupling in armchair graphene nanoribbons-magnetic impurity system

NASA Astrophysics Data System (ADS)

Hoi, Bui Dinh; Yarmohammadi, Mohsen

2018-05-01

Motivated by the growing interest in solving the obstacles of spintronics applications, we study the Ruderman-Kittel-Kasuya-Yosida (RKKY) effective pairwise interaction between magnetic impurities interacting through the π -electrons embedded in both electronically doped-semiconducting and metallic armchair graphene nanoribbons. In terms of the Green's function formalism, treated in a tight-binding approximation with hopping beyond Dirac cone approximation, the RKKY coupling is an attraction or a repulsion depending on the magnetic impurities distances. Our results show that the RKKY coupling in semiconducting nanoribbons is much more affected by doping than metallic ones. Furthermore, we found that the RKKY coupling increases with ribbon width, while there exist some critical electronic concentrations in RKKY interaction oscillations. On the other hand, we find an unusual incoming wave-vector direction for electrons which describes more clearly the ferro- and antiferromagnetic spin configurations in such system. Also, the RKKY coupling at low and high-temperature regions has been addressed for both ferro- and antiferromagnetic spin arrangements.

Lithium-bearing fluor-arfvedsonite from Hurricane Mountain, New Hampshire: A crystal-chemical study

USGS Publications Warehouse

Hawthorne, F.C.; Oberti, R.; Ottolini, L.; Foord, E.E.

1996-01-01

The structures of two crystals of Li-bearing fluor-arfvedsonite (1) (K0.32Na0.68)Na2(Li0.48Fe 2+2.83Mn2+0.10Zn 0.06Fe3+1.46Ti0.07) (Si7.88Al0.12)O22[Fu1.15(OH) 0.85] and (2) (K0.25Na0.75)Na2(Li0.48Fe 2+2.84Mn2+0.11Zn 0.05Fe3+1.45Ti0.07)(Si 7.89Al0.11)O22[F1.35(OH) 0.65] from a granitic pegmatite, Hurricane Mountain, New Hampshire, have been refined to R indices of 1.5(1.6)% based on 1380(1387) reflections measured with MoK?? X-radiation. The unit cell parameters are (1) a 9.838(4), b 17.991(6), c 5.315(2) A??, 103.78(3)??, V 913.7 A??3 and (2) a 9.832(3), b 17.990(7), c 5.316(3) A??, ?? 103.79(3)??, V 913.2 A??3. Site-scattering refinement shows Li to be completely ordered at the M(3) site in these crystals. The amphibole composition is intermediate between fluor-arfvedsonite and fluor-ferro-leakeite with a small component (???10%) of fluor-ferro-ferri-nybo??ite. These amphibole crystals project into miarolitic cavities in a pegmatitic phase of a riebeckite granite. The early-crystallizing amphibole is close to fluor-ferro-leakeite in composition, but becomes progressively depleted in Li and F as crystals project out into miarolitic cavities; the final amphibole to crystallize is a fibrous Li-poor riebeckite. Li plays a significant role in late-stage fractionation involving the crystallization of alkali amphibole in peralkaline granitic environments.

Bioaccessibility studies of ferro-chromium alloy particles for a simulated inhalation scenario: a comparative study with the pure metals and stainless steel.

PubMed

Midander, Klara; de Frutos, Alfredo; Hedberg, Yolanda; Darrie, Grant; Wallinder, Inger Odnevall

2010-07-01

The European product safety legislation, REACH, requires that companies that manufacture, import, or use chemicals demonstrate safe use and high level of protection of their products placed on the market from a human health and environmental perspective. This process involves detailed assessment of potential hazards for various toxicity endpoints induced by the use of chemicals with a minimum use of animal testing. Such an assessment requires thorough understanding of relevant exposure scenarios including material characteristics and intrinsic properties and how, for instance, physical and chemical properties change from the manufacturing phase, throughout use, to final disposal. Temporary or permanent adverse health effects induced by particles depend either on their shape or physical characteristics, and/or on chemical interactions with the particle surface upon human exposure. Potential adverse effects caused by the exposure of metal particles through the gastrointestinal system, the pulmonary system, or the skin, and their subsequent potential for particle dissolution and metal release in contact with biological media, show significant gaps of knowledge. In vitro bioaccessibility testing at conditions of relevance for different exposure scenarios, combined with the generation of a detailed understanding of intrinsic material properties and surface characteristics, are in this context a useful approach to address aspects of relevance for accurate risk and hazard assessment of chemicals, including metals and alloys and to avoid the use of in vivo testing. Alloys are essential engineering materials in all kinds of applications in society, but their potential adverse effects on human health and the environment are very seldom assessed. Alloys are treated in REACH as mixtures of their constituent elements, an approach highly inappropriate because intrinsic properties of alloys generally are totally different compared with their pure metal components. A large research effort was therefore conducted to generate quantitative bioaccessibility data for particles of ferro-chromium alloys compared with particles of the pure metals and stainless steel exposed at in vitro conditions in synthetic biological media of relevance for particle inhalation and ingestion. All results are presented combining bioaccessibility data with aspects of particle characteristics, surface composition, and barrier properties of surface oxides. Iron and chromium were the main elements released from ferro-chromium alloys upon exposure in synthetic biological media. Both elements revealed time-dependent release processes. One week exposures resulted in very small released particle fractions being less than 0.3% of the particle mass at acidic conditions and less than 0.001% in near pH-neutral media. The extent of Fe released from ferro-chromium alloy particles was significantly lower compared with particles of pure Fe, whereas Cr was released to a very low and similar extent as from particles of pure Cr and stainless steel. Low release rates are a result of a surface oxide with passive properties predominantly composed of chromium(III)-rich oxides and silica and, to a lesser extent, of iron(II,III)oxides. Neither the relative bulk alloy composition nor the surface composition can be used to predict or assess the extent of metals released in different synthetic biological media. Ferro-chromium alloys cannot be assessed from the behavior of their pure metal constituents. (c) 2009 SETAC.

Synthesis, Structure and Thermal Behavior of Oxalato-Bridged Rb+ and H3O+ Extended Frameworks with Different Dimensionalities

PubMed Central

Kherfi, Hamza; Hamadène, Malika; Guehria-Laïdoudi, Achoura; Dahaoui, Slimane; Lecomte, Claude

2010-01-01

Correlative studies of three oxalato-bridged polymers, obtained under hydrothermal conditions for the two isostructural compounds {Rb(HC2O4)(H2C2O4)(H2O)2}∞1, 1, {H3O(HC2O4)(H2C2O4).2H2O}∞1, 2, and by conventional synthetic method for {Rb(HC2O4)}∞3, 3, allowed the identification of H-bond patterns and structural dimensionality. Ferroïc domain structures are confirmed by electric measurements performed on 3. Although 2 resembles one oxalic acid sesquihydrate, its structure determination doesn’t display any kind of disorder and leads to recognition of a supramolecular network identical to hybrid s-block series, where moreover, unusual H3O+ and NH4+ similarity is brought out. Thermal behaviors show that 1D frameworks with extended H-bonds, whether with or without a metal center, have the same stability. Inversely, despite the dimensionalities, the same metallic intermediate and final compounds are obtained for the two Rb+ ferroïc materials.

Changes in Magnetic Mineralogy Through a Depth Sequence of Hydrocarbon Contaminated Sediments

NASA Astrophysics Data System (ADS)

Ameen, N. N.; Klüglein, N.; Appel, E.; Petrovsky, E.; Kappler, A.

2013-12-01

Sediments, soils and groundwater can act as a natural storage for many types of pollution. This study aims to investigate ferro(i)magnetic phase formation and transformation in the presence of organic contaminants (hydrocarbons) and its relation to bacterial activity, in particular in the zone of fluctuating water levels. The work extends previous studies conducted at the same site. The study area is a former military air base at Hradčany, Czech Republic (50°37'22.71"N, 14°45'2.24"E). Due to leaks in petroleum storage tanks and jet fuelling stations over years of active use the site was heavily contaminated with petroleum hydrocarbons, until the base was closed in 1991. This site is one of the most important sources of high quality groundwater in the Czech Republic. During remediation processes the groundwater level in the sediments fluctuated, driving the hydrocarbon contaminants to lower depth levels along with the groundwater and leading to magnetite formation (Rijal et al., Environ.Pollut., 158, 1756-1762, 2010). In our study we drilled triplicate cores at three locations which were studied earlier. Magnetic susceptibility (MS) profiles combined with other magnetic properties were analyzed to obtain the ferro(i)magnetic concentration distributions along the depth sections. Additionally the sediment properties, hydrocarbon content and bacterial activity were studied. The triplicate cores were used to statistically discriminate outliers and to recognize significant magnetic signatures with depth. The results show that the highest concentration of ferrimagnetic phases (interpreted as newly formed magnetite) exists at the probable top of the groundwater fluctuation (GWF) zone. For example at one of the sites this zone is found between 1.4-1.9 m depth (groundwater table at ~2.3 m depth). High S-ratio and the correlation of ARM with MS values confirm the contribution of magnetite for the ferro(i)magnetic enhancement in the GWF zone. In the previous studies the MS signals revealed small-scale isolated features, but with the use of triplicate cores significant trends of MS could be identified, showing an increase from the lowermost position of the groundwater table upward. Bacterial activity is likely responsible for magnetite formation in this depth range as indicated by most probable number (MPN) results of iron-reducing bacteria.

Durcissement superficiel de la fonte grise Ft25 induit par un traitement de surface dans le moule

NASA Astrophysics Data System (ADS)

Bouitna, Mohamed; Boutarek-Zaourar, Naïma; Mansour, Samir; Chentouf, Samir Mourad; Mossang, Eric

2018-02-01

L'objectif de cette étude est la consolidation en surface de la fonte grise lamellaire Ft25 par un dépôt riche en manganèse en développant une méthode combinant en une seule opération l'élaboration et le traitement de surface dans le moule. Les effets de la granulométrie du ferro-manganèse (80 % Mn + 20 % Fe), ainsi que l'épaisseur des pièces en fontes sur les couches formées ont été étudiés. On a retenu trois granulométries du ferro-manganèse de 0,18 mm, 0,25 mm et 0,5 mm pour le traitement des pièces en fontes présentant des épaisseurs de 25 mm, 100 mm et 200 mm. Parmi les résultats obtenus, on distingue une consolidation des propriétés en surface induite par la formation d'une couche riche en manganèse continue et homogène. L'effet de la granulométrie du ferro-manganèse sur l'épaisseur de la couche traitée a été mis en évidence. La variation de l'épaisseur des couches formées diminue avec l'augmentation de la granulométrie du ferro-manganèse. Pour une pièce de 100 mm d'épaisseur, la couche formée est estimée à 350 μm pour une granulométrie de 0,18 alors qu'elle n'est que de 180 μm pour une granulométrie de 0,5. L'effet de l'épaisseur de la pièce n'est en revanche pas assez prononcé sur la taille des couches formées. Une amélioration nette de la résistance, à l'usure de la fonte traitée en relation avec les transformations en surface, a été mise en évidence.

Broken symmetries, non-reciprocity, and multiferroicity

DOE PAGES

Cheong, Sang-Wook; Talbayev, Diyar; Kiryukhin, Valery; ...

2018-04-03

The interplay of space and time symmetries, ferroic properties, chirality and notions of reciprocity determines many of the technologically important properties of materials such as optical diode effect, e.g., in polar ferromagnet FeZnMo 3O 8. Here, we illustrate these concepts, including the non-reciprocal directional dichroism, through a number of practical examples. In particular, the conditions for non-reciprocity of ferro-rotational order are discussed and the possible use of linear optical gyration is suggested as a way to detect ferro-rotational domains. In addition, we provide the means to achieve high-temperature optical diode effect and elucidate multiferroic behaviors as a result of helicalmore » vs. cycloidal spins. Finally, we identify different entities behaving similarly under all symmetry operations, which are useful to understand non-reciprocity and multiferroicity in various materials intuitively.« less

Broken symmetries, non-reciprocity, and multiferroicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheong, Sang-Wook; Talbayev, Diyar; Kiryukhin, Valery

The interplay of space and time symmetries, ferroic properties, chirality and notions of reciprocity determines many of the technologically important properties of materials such as optical diode effect, e.g., in polar ferromagnet FeZnMo 3O 8. Here, we illustrate these concepts, including the non-reciprocal directional dichroism, through a number of practical examples. In particular, the conditions for non-reciprocity of ferro-rotational order are discussed and the possible use of linear optical gyration is suggested as a way to detect ferro-rotational domains. In addition, we provide the means to achieve high-temperature optical diode effect and elucidate multiferroic behaviors as a result of helicalmore » vs. cycloidal spins. Finally, we identify different entities behaving similarly under all symmetry operations, which are useful to understand non-reciprocity and multiferroicity in various materials intuitively.« less

Fluor-ferro-leakeite, NaNa2(FC2+2Fe3+2Li)Si8O22F2, a new alkali amphibole from the Canada Pinabete pluton, Questa, New Mexico, U.S.A.

USGS Publications Warehouse

Hawthorne, F.C.; Oberti, R.; Ungaretti, L.; Ottolini, L.; Grice, Joel D.; Czamanske, G.K.

1996-01-01

Fluor-ferro-leakeite is a new amphibole species from the Canada Pinabete pluton, Questa, New Mexico, U.S.A.; it occurs in association with quartz, alkali feldspar, acmite, ilmenite, and zircon. It forms as anhedral bluish black crystals elongated along c and up to 1 mm long. It is brittle, H = 6, Dmeas = 3.37 g/cm3, Dcalc = 3.34 g/cm3. In plane-polarized light, it is strongly pleochroic, X = very dark indigo blue, Y = gray blue, Z = yellow green; X ??? c = 10?? (in ??obtuse), Y = b, Z ??? a = 4?? (in ?? obtuse), with absorption X > Y > Z. Fluor-ferro-leakeite is biaxial positive, ?? = 1.675(2), ??= 1.683(2), ?? = 1.694(1); 2V = 87(2)??; dispersion is not visible because of the strong absorption. Fluor-ferro-leakeite is monoclinic, space group C2/m, a = 9.792(1), b = 17.938(1), c = 5.3133(4) A??, ??= 103.87(7)??, V = 906.0(1) A??3, Z = 2. The ten strongest X-ray diffraction lines in the powder pattern are [d(I,hkl)]: 2.710(100,151), 2.536(92,202), 3.404(57,131), 4.481(54,040), 8.426(45,110), 2.985(38,241), 2.585(38,061), 3.122(29,310), 2.165(26,261), and 1.586(25,403). Analysis by a combination of electron microprobe, ion microprobe, and crystal-structure refinement (Hawthorne et al. 1993) gives SiO2 51.12, Al2O3 1.13, TiO2 0.68, Fe2O3 16.73, FeO 8.87, MgO 2.02, MnO 4.51, ZnO 0.57, CaO 0.15, Na2O 9.22, K2O 1.19, Li2O 0.99, F 2.87, H2Ocalc 0.60, sum 99.44 wt%. The formula unit, calculated on the basis of 23 O atoms, is (K0.23Na0.76)(Na1.97Ca0.03)(Mg 0.46Fe2+1.4Mn2+0.59Zn0.07Fe3+1.93-Ti 0.08Al0.02Li0.61])(Si7.81Al 0.19)O22(F1.39OH0.61). A previous crystal-structure refinement (Hawthorne et al. 1993) shows Li to be completely ordered at the M3 site. Fluor-ferro-leakeite, ideally NaNa2(Fe2+2Fe3+2Li)Si8O22F2, is related to leakeite, NaNa2(Mg2Fe3+3Li)Si 8O22(OH)2, by the substitutions Fe2+ ??? Mg and F ??? OH.

Ferro- and piezoelectric properties of polar-axis-oriented CaBi4Ti4O15 films

NASA Astrophysics Data System (ADS)

Kato, Kazumi; Fu, Desheng; Suzuki, Kazuyuki; Tanaka, Kiyotaka; Nishizawa, Kaori; Miki, Takeshi

2004-05-01

Polar-axis-oriented CaBi4Ti4O15 (CBTi144) films were fabricated on Pt foils using a complex metal alkoxide solution. The 500-nm-thick film showed the columnar structure and consisted of well-developed grains. The a/b-axis orientation of the ferroelectric films is considered to be associated with the preferred orientation of Pt foil. The film showed good ferro- and piezoelectric properties. The Pr and Ec were 25 μC/cm2 and 306 kV/cm, respectively, at an applied voltage of 115 V. The d33 was characterized as 30 pm/V by piezoresponse force microscopy. The values were twice as large as those of the CBTi144 thin film with random orientation. The polar-axis-oriented CBTi144 films would open up possibilities for devices as Pb-free piezoelectric materials.

Design and analysis of a low actuation voltage electrowetting-on-dielectric microvalve for drug delivery applications.

PubMed

Samad, Mst Fateha; Kouzani, Abbas Z

2014-01-01

This paper presents a low actuation voltage microvalve with optimized insulating layers that manipulates a conducting ferro-fluid droplet by the principle of electrowetting-on-dielectric (EWOD). The proposed EWOD microvalve contains an array of chromium (Cr) electrodes on the soda-lime glass substrate, covered by both dielectric and hydrophobic layers. Various dielectric layers including Su-8 2002, Polyvinylidenefluoride (PVDF) and Cyanoethyl pullulan (CEP), and thin (50 nm) hydrophobic Teflon and Cytonix are used to analyze the EWOD microvalves at different voltages. The Finite Element Method (FEM) based software, Coventorware is used to carry out the simulation analysis. It is observed that the EWOD microvalve having a CEP dielectric layer with dielectric constant of about 20 and thickness of 1 μm, and a Cytonix hydrophobic layer with thickness of 50 nm operated the conducting ferro-fluid droplet at the actuation voltage as low as 7.8 V.

Metamagnetism in hydrophobically induced carboxylate (phenylmalonate)-bridged copper(II) layers.

PubMed

Pasán, Jorge; Sanchiz, Joaquín; Ruiz-Pérez, Catalina; Campo, Javier; Lloret, Francesc; Julve, Miguel

2006-07-21

Self-assembly of copper(l) ions, phenylmalonate and pyrimidine yields the layered compound [Cu(pym)(Phmal)n (1) where intralayer ferro- and interlayer antiferromagnetic interactions occur with three-dimensional antiferromagnetic ordering at T(c) = 2.15 K.

75 FR 41143 - Silicon Metal from the People's Republic of China: Preliminary Results and Preliminary Rescission...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-15

.... Court of Appeals for the Federal Circuit's decision in Sigma Corp. v. United States, 117 F.3d 1401, 1407... (Mega Projects) Ltd., and Saturn Ferro Alloys Private Ltd., Indian producers of merchandise that is...

Ligand effects on the ferro- to antiferromagnetic exchange ratio in bis(o-semiquinonato)copper(II).

PubMed

Ovcharenko, Victor I; Gorelik, Elena V; Fokin, Sergey V; Romanenko, Galina V; Ikorskii, Vladimir N; Krashilina, Anna V; Cherkasov, Vladimir K; Abakumov, Gleb A

2007-08-29

Heterospin complexes [Cu(SQ)2Py].C7H8, Cu(SQ)2DABCO, and [Cu(SQ)2NIT-mPy].C6H6, where Cu(SQ)2 is bis(3,6-di-tert-butyl-o-benzosemiquinonato)copper(II), DABCO is 1,4-diazabicyclo(2,2,2)octane, and NIT-mPy is the nitronyl nitroxide 2-(pyridin-3-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, have been synthesized. The molecules of these complexes have a specific combination of the intramolecular ferro- and antiferromagnetic exchange interactions between the odd electrons of Cu(II) and SQ ligands, characterized by large exchange coupling parameters |J| approximately 100-300 cm(-1). X-ray and magnetochemical studies of a series of mixed-ligand compounds revealed that an extra ligand (Py, NIT-mPy, or DABCO) coordinated to the metal atom produces a dramatic effect on the magnetic properties of the complex, changing the multiplicity of the ground state. Quantum chemical analysis of magnetostructural correlations showed that the energy of the antiferromagnetic exchange interaction between the odd electrons of the SQ ligands in the Cu(SQ)2 bischelate is extremely sensitive to both the nature of the extra ligand and structural distortions of the coordination unit, arising from extra ligand coordination.

Bona-fide method for the determination of short range order and transport properties in a ferro-aluminosilicate slag

PubMed Central

Karalis, Konstantinos T.; Dellis, Dimitrios; Antipas, Georgios S. E.; Xenidis, Anthimos

2016-01-01

The thermodynamics, structural and transport properties (density, melting point, heat capacity, thermal expansion coefficient, viscosity and electrical conductivity) of a ferro-aluminosilicate slag have been studied in the solid and liquid state (1273–2273 K) using molecular dynamics. The simulations were based on a Buckingham-type potential, which was extended here, to account for the presence of Cr and Cu. The potential was optimized by fitting pair distribution function partials to values determined by Reverse Monte Carlo modelling of X-ray and neutron diffraction experiments. The resulting short range order features and ring statistics were in tight agreement with experimental data and created consensus for the accurate prediction of transport properties. Accordingly, calculations yielded rational values both for the average heat capacity, equal to 1668.58 J/(kg·K), and for the viscosity, in the range of 4.09–87.64 cP. The potential was consistent in predicting accurate values for mass density (i.e. 2961.50 kg/m3 vs. an experimental value of 2940 kg/m3) and for electrical conductivity (5.3–233 S/m within a temperature range of 1273.15–2273.15 K). PMID:27455915

Adult Education and Theological Interpretations.

ERIC Educational Resources Information Center

Jarvis, Peter, Ed.; Walters, Nicholas, Ed.

The following chapters are included in this book: "Learning as a Religious Phenomenon?" (Jarvis); "Truth, Belief, and Knowledge" (Clark); "The Authority of the Word" (Ferro); "The Priesthood of the Teacher--Language and the Teaching of the Word" (McCaffry); "Teaching--Catechism, Preaching, and Indoctrination" (Willis); "Meaning, Being, and…

Ferromagnetism in a hexagonal PrRh3 with 4f2 configuration

NASA Astrophysics Data System (ADS)

Park, G. B.; Yamane, Y.; Onimaru, T.; Umeo, K.; Takabatake, T.

2018-05-01

Electrical resistivity ρ , magnetization M and specific heat C are reported for polycrystalline samples of the hexagonal system PrRh3. The magnetic susceptibility M/B obeys the Curie-Weiss law with the effective magnetic moment μeff = 3.88 μB/Pr and the paramagnetic Curie temperature θp = +2.9 K, which indicates ferro-type magnetic interaction between the trivalent Pr ions. A cusp in C(T) at 3.0 K coincides with a bend in ρ (T). Applying magnetic fields, the peak broadens and shifts to higher temperatures. The field dependence indicates a ferro-type magnetic order. The magnetic entropy Sm is (1/3)Rln2 at TC = 3.0 K, suggesting that part of the Pr ions take part in the magnetic order. A broad tail of the magnetic specific heat Cm observed above TC may result from short-range correlations and/or fluctuations of the active magnetic dipole and quadrupoles in the ground state doublet.

A thermodynamically consistent model of magneto-elastic materials under diffusion at large strains and its analysis

NASA Astrophysics Data System (ADS)

Roubíček, Tomáš; Tomassetti, Giuseppe

2018-06-01

A theory of elastic magnets is formulated under possible diffusion and heat flow governed by Fick's and Fourier's laws in the deformed (Eulerian) configuration, respectively. The concepts of nonlocal nonsimple materials and viscous Cahn-Hilliard equations are used. The formulation of the problem uses Lagrangian (reference) configuration while the transport processes are pulled back. Except the static problem, the demagnetizing energy is ignored and only local non-self-penetration is considered. The analysis as far as existence of weak solutions of the (thermo) dynamical problem is performed by a careful regularization and approximation by a Galerkin method, suggesting also a numerical strategy. Either ignoring or combining particular aspects, the model has numerous applications as ferro-to-paramagnetic transformation in elastic ferromagnets, diffusion of solvents in polymers possibly accompanied by magnetic effects (magnetic gels), or metal-hydride phase transformation in some intermetallics under diffusion of hydrogen accompanied possibly by magnetic effects (and in particular ferro-to-antiferromagnetic phase transformation), all in the full thermodynamical context under large strains.

Magnon condensation and spin superfluidity

NASA Astrophysics Data System (ADS)

Bunkov, Yury M.; Safonov, Vladimir L.

2018-04-01

We consider the Bose-Einstein condensation (BEC) of quasi-equilibrium magnons which leads to spin superfluidity, the coherent quantum transfer of magnetization in magnetic material. The critical conditions for excited magnon density in ferro- and antiferromagnets, bulk and thin films, are estimated and discussed. It was demonstrated that only the highly populated region of the spectrum is responsible for the emergence of any BEC. This finding substantially simplifies the BEC theoretical analysis and is surely to be used for simulations. It is shown that the conditions of magnon BEC in the perpendicular magnetized YIG thin film is fulfillied at small angle, when signals are treated as excited spin waves. We also predict that the magnon BEC should occur in the antiferromagnetic hematite at room temperature at much lower excited magnon density compared to that of ferromagnetic YIG. Bogoliubov's theory of Bose-Einstein condensate is generalized to the case of multi-particle interactions. The six-magnon repulsive interaction may be responsible for the BEC stability in ferro- and antiferromagnets where the four-magnon interaction is attractive.

Facile Access to Graphene Oxide from Ferro-Induced Oxidation

NASA Astrophysics Data System (ADS)

Yu, Chao; Wang, Cai-Feng; Chen, Su

2016-01-01

Methods allowing the oxidation of graphite to graphene oxide (GO) are vital important for the production of graphene from GO. This oxidation reaction has mainly relied on strong acid strategy for 174 years, which circumvents issues associated with toxicity of reagent and product, complex post-treatment, high cost and waste generation. Here, we report a green route for performing this oxidization reaction via a ferro-induced strategy, with use of water, potassium ferrate (Fe(VI)) and hydrogen peroxide (H2O2) as reagents, to produce about 65% yield of GO (vs. 40% for Hummers’ method, the most commonly used concentrated acid strategy) and non-toxic by-products. Moreover, GO produced from this new method shows equivalent performance to those reported previously. This H2SO4-free strategy makes it possible to process graphite into GO in a safe, low-cost, time-saving, energy-efficient and eco-friendly pathway, opening a promising avenue for the large-scale production of GO and GO-based materials.

Facile Access to Graphene Oxide from Ferro-Induced Oxidation.

PubMed

Yu, Chao; Wang, Cai-Feng; Chen, Su

2016-01-28

Methods allowing the oxidation of graphite to graphene oxide (GO) are vital important for the production of graphene from GO. This oxidation reaction has mainly relied on strong acid strategy for 174 years, which circumvents issues associated with toxicity of reagent and product, complex post-treatment, high cost and waste generation. Here, we report a green route for performing this oxidization reaction via a ferro-induced strategy, with use of water, potassium ferrate (Fe(VI)) and hydrogen peroxide (H2O2) as reagents, to produce about 65% yield of GO (vs. 40% for Hummers' method, the most commonly used concentrated acid strategy) and non-toxic by-products. Moreover, GO produced from this new method shows equivalent performance to those reported previously. This H2SO4-free strategy makes it possible to process graphite into GO in a safe, low-cost, time-saving, energy-efficient and eco-friendly pathway, opening a promising avenue for the large-scale production of GO and GO-based materials.

Facile Access to Graphene Oxide from Ferro-Induced Oxidation

PubMed Central

Yu, Chao; Wang, Cai-Feng; Chen, Su

2016-01-01

Methods allowing the oxidation of graphite to graphene oxide (GO) are vital important for the production of graphene from GO. This oxidation reaction has mainly relied on strong acid strategy for 174 years, which circumvents issues associated with toxicity of reagent and product, complex post-treatment, high cost and waste generation. Here, we report a green route for performing this oxidization reaction via a ferro-induced strategy, with use of water, potassium ferrate (Fe(VI)) and hydrogen peroxide (H2O2) as reagents, to produce about 65% yield of GO (vs. 40% for Hummers’ method, the most commonly used concentrated acid strategy) and non-toxic by-products. Moreover, GO produced from this new method shows equivalent performance to those reported previously. This H2SO4-free strategy makes it possible to process graphite into GO in a safe, low-cost, time-saving, energy-efficient and eco-friendly pathway, opening a promising avenue for the large-scale production of GO and GO-based materials. PMID:26818784

Ab-initio study of pressure evolution of structural, mechanical and magnetic properties of cementite (Fe3C) phase

NASA Astrophysics Data System (ADS)

Gorai, S.; Ghosh, P. S.; Bhattacharya, C.; Arya, A.

2018-04-01

The pressure evolution of phase stability, structural and mechanical properties of Fe3C in ferro-magnetic (FM) and high pressure non magnetic (NM) phase is investigated from first principle calculations. The 2nd order FM to NM phase transition of Fe3C is identified around 60 GPa. Pressure (or density) variation of sound velocities from our ab-initio calculated single crystal elastic constants are determined to predict these parameters at Earth's outer core pressure.

Application of ultradisperse magnetic adsorbents for removal of small concentrations of pollutants from large volumes of water

NASA Astrophysics Data System (ADS)

Nechitailo, Galina S.; Kuznetsov, Anatoli; Kuznetsov, Oleg

2016-07-01

Pollution of natural bodies of water (rivers, lakes, ground water, etc) is unfortunately very common, both from natural sources like volcanic activity; and, even more importantly, from human activity, including disposal of industrial and municipal waste, mining, etc. Many toxic substances are harmful for humans and other organisms even in very low concentrations (e.g., less than 1 µg/L of cadmium is harmful, for Hg it is 0.5 µg/L, for phenol - 1 µg/L), and can remain in water for decades or longer. Cleaning large volumes of water even from low concentrations of pollutants is a challenging technological task and is very expensive. We propose to use suspension of ultradisperse magnetic adsorbents, for example, nanostructured ferro-carbon particles, produced by plasmachemical technique, for removing small concentrations of pollutants from large volumes of water. The suspension is introduced into the water. Due to their small sizes and densities similar to water (we measured the density of FC-4 ferro-carbon to be about 1 g/cm3; presumably due to porosity) the particles do not sediment for a long time (hours, days or longer), move due to Brownian motion and adsorb a variety of substances from the water. The particle surface can be modified to provide selectivity of the adsorption. Sorption capacities of ferro-carbon adsorbents is in dozens of percent. Therefore, to collect 1 kg of a pollutant, 2 to 20 kg of the adsorbents is required. Then the particles with the adsorbed contaminant can be collected (e.g., downstream of the river) using a variety of magnetic traps. The traps can consist of ferromagnetic wires and permanent magnets, a variety of simple and inexpensive designs are available. As a model system, the kinetics of adsorption of a highly diluted (0.002 mg/ml) aqueous solution of a low molecular weight compound (toluidine blue) by a small concentration of a ferro-carbon powder (FC-4) was studied by spectrophotometry. Before each measurement, the particles with the adsorbed toluidine blue were removed from the solution by magnetic separation. The sorbent was proven to have high sorption capacity and rapid adsorption kinetics for toluidine blue. These experiments demonstrated the validity of the method, where a small concentration of a pollutant was successfully collected from a large volume of water. By varying the ratio of the sorbent/pollutant, it is possible to optimize the sorbent use and the time required to adsorb all pollutant present in the treated water. A variety of magnetically controlled sorbents can be designed and used in this method, from broad-spectrum adsorbing sorbents to sorbents specifically targeting a particular pollutant. These sorbents can be used either individually or as mixtures of sorbents with different properties, depending on the desired purification goals. Simplicity and scalability of this method allow a variety of ecological applications, as well as industrial ones, from process water purification to wastewater treatment.

Elephant Dung and Ferro Fluid

ERIC Educational Resources Information Center

Andrews, Jackie

2007-01-01

Over the last couple of years, the author has produced six series of 15-minute studio-based programmes for Teachers' TV (the government-funded digital channel for UK teachers) entitled "Resource Review", totalling about 100 programmes. Each consists of three panellists evaluating three teaching resources for primary or secondary level…

11. VIEW OF STARBOARD ELEVATION OF STERN (WITHOUT SCALE STICK), ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. VIEW OF STARBOARD ELEVATION OF STERN (WITHOUT SCALE STICK), SHOWING WHEELHOUSE, DUCKTAIL, AND RUDDER ASSEMBLY; CRANE AT LEFT POSITIONED FOR REMOVAL OF WHEELHOUSE; UNFINISHED FERRO-CONCRETE HULL OF UNKNOWN VESSEL IN BACKGROUND - Bugeye "Louise Travers", Intersection of Routes 2 & 4, Solomons, Calvert County, MD

Systematic Review of the Cost Effectiveness of Insulin Analogues in Type 1 and Type 2 Diabetes Mellitus.

PubMed

Shafie, Asrul Akmal; Ng, Chin Hui; Tan, Yui Ping; Chaiyakunapruk, Nathorn

2017-02-01

Insulin analogues have a pharmacokinetic advantage over human insulin and are increasingly used to treat diabetes mellitus. A summary of their cost effectiveness versus other available treatments was required. Our objective was to systematically review the published cost-effectiveness studies of insulin analogues for the treatment of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). We searched major databases and health technology assessment agency reports for economic evaluation studies published up until 30 September 2015. Two reviewers performed data extraction and assessed the quality of the data using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines. Seven of the included studies assessed short-acting insulin analogues, 12 assessed biphasic insulin analogues, 30 assessed long-acting insulin analogues and one assessed a combination of short- and long-acting insulin analogues. Only 17 studies involved patients with T1DM, all were modelling studies and 12 were conducted in Canada. The incremental cost-effectiveness ratios (ICERs) for short-acting insulin analogues ranged from dominant to $US435,913 per quality-adjusted life-year (QALY) gained, the ICERs for biphasic insulin analogues ranged from dominant to $US57,636 per QALY gained and the ICERs for long-acting insulin analogues ranged from dominant to $US599,863 per QALY gained. A total of 15 studies met all the CHEERS guidelines reporting quality criteria. Only 26 % of the studies assessed heterogeneity in their analyses. Current evidence indicates that insulin analogues are cost effective for T1DM; however, evidence for their use in T2DM is not convincing. Additional evidence regarding compliance and efficacy is required to support the broader use of long-acting and biphasic insulin analogues in T2DM. The value of insulin analogues depends strongly on reductions in hypoglycaemia event rates and its efficacy in lowering glycated haemoglobin (HbA 1c ).

NASA/ESMD Analogue Mission Plans

NASA Technical Reports Server (NTRS)

Hoffman, Stephen J.

2007-01-01

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

Process for guidance, containment, treatment, and imaging in a subsurface environment utilizing ferro-fluids

DOEpatents

Moridis, George J.; Oldenburg, Curtis M.

2001-01-01

Disclosed are processes for monitoring and control of underground contamination, which involve the application of ferrofluids. Two broad uses of ferrofluids are described: (1) to control liquid movement by the application of strong external magnetic fields; and (2) to image liquids by standard geophysical methods.

77 FR 17013 - Sodium Hexametaphosphate From the People's Republic of China: Preliminary Results of Second...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-23

... Review Final. We did not value phosphate rock or ferro-phosphorous using Thai import statistics. Regarding phosphate rock, Petitioners proposed that the Department value phosphate rock using Thai... rock using HTS 2510.10.10 (``Natural Calcium Phosphates * * * Unground''), from Indonesia.\\26\\ For...

Change of Auger-electron emission from Ni-Pd alloys under magnetic phase transition

NASA Astrophysics Data System (ADS)

Elovikov, S. S.; Zykova, E. Y.; Gvozdover, R. S.; Colligon, J. S.; Yurasova, V. E.

2006-04-01

The change of Auger-electron emission from polycrystals of disordered ferromagnetic NiPd 3 and Ni 3 Pd alloys, under ferro- to paramagnetic transition, has been studied experimentally. It has been shown that the intensity of the Auger-lines, which are formed because of transition of valent zone 3d 3/2 and 3d 5/2 electrons, has local maxima near the Curie point T C for the alloys. Thus, the sensitivity of Auger-electron emission to a magnetic state of the alloy has been established.

Recent Advances In Radar Polarimetry And Polarimetric SAR Interferometry

DTIC Science & Technology

2007-02-01

Workshop, ESA SERRÍN, Frascati, Italy, January 2003. [69] EUSAR 2000 Procs, VDE Verlag, Offenbach, ISBN: 3-8007-2544-4, Munich, Germany, May 2000. [70...EUSAR 2002 Procs, VDE Verlag, Offenbach, ISBN: 3-8007-2697-1, Cologne, Germany, June 2002. [71] Ferro-Famil, L. and E. Pottier, 2000, "Description of

Solving Cubic Equations by Polynomial Decomposition

ERIC Educational Resources Information Center

Kulkarni, Raghavendra G.

2011-01-01

Several mathematicians struggled to solve cubic equations, and in 1515 Scipione del Ferro reportedly solved the cubic while participating in a local mathematical contest, but did not bother to publish his method. Then it was Cardano (1539) who first published the solution to the general cubic equation in his book "The Great Art, or, The Rules of…

Détection infrarouge par ferroélectriques en couche mince

NASA Astrophysics Data System (ADS)

Audaire, L.; Agnèse, P.; Rambaud, Ph.; Pirot, M.

1994-07-01

Ferroelectric materials are used in solid-state infrared detectors. The thermal scene is focused on a 2D staring array, the pyroelectric charge variations or the permittivity variations are read by an electronic circuit implemented in the focal plane. Various developments have been carried out and led to user friendly sensors which are now available in several laboratories and even as commercialized products in England and USA, but also in France. Les matériaux ferroélectriques sont utilisés en tant que détecteurs thermiques pour la prise de vue en infrarouge. L'optique projette l'image thermique de la scène sur une matrice de détecteurs et la variation de polarisation ou la variation de permittivité sont lues par une électronique intégrée au plan focal. Le travail de recherche et de développement a débouché sur des senseurs simples d'emploi qui commencent à être disponibles sur catalogues, en Angleterre et aux Etats-Unis, mais également en France.

Ferro-Lattice-Distortions and Charge Fluctuations in Superconducting LaO 1- x F x BiS 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Athauda, Anushika; Hoffmann, Christina; Aswartham, Saicharan

2017-05-15

Competing ferroelectric and charge density wave states have been proposed to exist in the electron–phonon coupled LaO1-xFxBiS2 superconductor. The lattice instability is proposed to arise from unstable phonon modes that can break the crystal symmetry. Using single crystal diffraction, a superlattice pattern is observed, that arises from coherent in-plane displacements of the sulfur atoms in the BiS2 superconducting planes. The distortions morph into coordinated ferrodistortive patterns with displacements in the x- and y-directions, that alternate along the c-axis. Diffuse scattering is observed along the (H0L) plane due to stacking faults but not along the (HH0) plane. The ferro-distortive pattern remainsmore » in the superconducting state upon fluorine doping, but the displacements are diminished in magnitude. Moreover, we find that the in-plane distortions give rise to disorder where the (00L) reflections become quite broad. It is possible that charge carriers can get trapped in the lattice deformations reducing the effective number of carriers available for pairing.« less

Towards Lead-Free Piezoceramics: Facing a Synthesis Challenge

PubMed Central

Villafuerte-Castrejón, María Elena; Morán, Emilio; Reyes-Montero, Armando; Vivar-Ocampo, Rodrigo; Peña-Jiménez, Jesús-Alejandro; Rea-López, Salvador-Oliver; Pardo, Lorena

2016-01-01

The search for electroceramic materials with enhanced ferro-pyro-piezoelectric properties and revealing the perovskite type structure has been the objective of a significant number of manuscripts reported in the literature. This has been usually carried out by proposing the synthesis and processing of new compounds and solid solution series. In this work, several methods to obtain ferro-pyro-piezoelectric families of materials featuring the well-known ABO3 perovskite structure (or related) such as BaTiO3, Ba1–xCaxTi1–yZryO3, (Bi0.5Na0.5)TiO3, (K0.5Na0.5)NbO3 and their solid solutions with different cations either in the A or B positions, are presented. For this kind of materials, the challenge for obtaining a single phase compound with a specific grain size and morphology and, most importantly, with the adequate stoichiometry, will also be discussed. The results reviewed herein will be discussed in terms of the tendency of working with softer conditions, i.e., lower temperature and shorter reaction times, also referred to as soft-chemistry. PMID:28787822

Effect of pressure on magnetic properties of mixed ferro-ferrimagnet (Ni0.38Mn0.62)3[Cr(CN)6]2.zH2O

NASA Astrophysics Data System (ADS)

Zentková, M.; Mihalik, M.; Arnold, Z.; Kamarád, J.

2010-01-01

We present the results of magnetization measurements performed on the ferro-ferrimagnetic (Ni0.38Mn0.62)3[Cr(CN)6]2.zH2O molecule-based magnet under pressures up to 0.8 GPa. Both antiferromagnetic JAF and ferromagnetic interaction JF are present in this magnet and temperature dependence of magnetization μ(T) exhibits the compensation temperature Tcomp at which the sign of the magnetization is reversed. Our results indicate that JAF dominates. The Curie temperature TC of the magnet increases with applied pressure, dTC/dp = 10.6 KGPa-1, due to strengthened JAF. The increase of the JAF is attributed to the enhanced value of the single electron overlapping integral S and the energy gap Δ of the mixed molecular orbitals t2g (Mn2+) and t2g (CrIII) induced by pressure. Magnetization processes are also affected by pressure: magnetization saturates at higher magnetic field and saturated magnetization is reduced. The compensation temperature Tcomp decreases under pressure.

Grain growth kinetics in pyrolite material under lower mantle condition: Implications for the rheology of the lower mantle

NASA Astrophysics Data System (ADS)

Imamura, M.; Kubo, T.; Takumi, K.

2016-12-01

Rheology of the lower mantle largely depends on the grain-size evolution in constituent minerals. The pioneering work on the grain growth kinetics in MgSiO3 bridgmanite and MgO periclase (Yamazaki et al., 1996) has raised the problem that the grain growth rate is too slow to explain the lower-mantle viscosity. This inconsistency may arise from effects of elastic stress due to the eutectoid transformation (e.g., Solomatov et al., 2002) and it may be difficult to extrapolate the slow kinetics obtained to geological timescales. We conducted grain growth experiments in pyrolitic material at 25-27 GPa, and 1600-1950°C for 30-3000 min using Kawai-type high pressure apparatus at Kyushu University. Four phases of bridgmanite, ferro-priclase, Ca-perovskite and majoritic garnet were present in recovered samples annealed at 25 GPa. To avoid the effects of the eutectoid texture, we took the grain growth data only from the sample exhibiting relatively homogeneous equi-granular texture. That was achieved after annealing for 30 minutes at 1800-1950°C (use these grain sizes as d0), and not achieved even after annealing for 3000 minutes at 1600°C. We preliminarily obtained kinetic parameters of n=4.9 and H* 420 kJ/mol for bridgmanite, and n=4.7 and H* 160 kJ/mol for ferro-pericalse. The ratio of grain sizes of bridgmanite and ferro-periclase is almost constant during the grain growth process. These results indicate faster kinetics compared to the previous study, and can be reasonably interpreted as the grain growth occurred by Ostwald ripening. On the other hand, three phases without majoritic garnet were present at higher pressure of 27 GPa and 1800°C, in which the grain size was slightly larger probably due to the smaller proportion of the secondary phases. When extrapolating the grain growth kinetics obtained in the four phases, the grain size of bridgmanite is roughly estimated to be 4-50 µm at 800-1200°C and 200-600 µm at 1600-2000°C in 108 years. These grain sizes may explain the lower-mantle viscosity in diffusion creep regime if we consider the effects of deformation-induced grain growth in convecting mantle (Hiraga et al., 2010).

A comparative study of ultrasonication, Fenton's oxidation and ferro-sonication treatment for degradation of carbamazepine from wastewater and toxicity test by Yeast Estrogen Screen (YES) assay.

PubMed

Mohapatra, D P; Brar, S K; Tyagi, R D; Picard, P; Surampalli, R Y

2013-03-01

A comparative study of ultrasonication (US), Fenton's oxidation (FO) and ferro-sonication (FS) (combination of ultrasonication and Fenton's oxidation) advanced oxidation processes (AOPs) for degradation of carbamazepine (CBZ) from wastewater (WW) is reported for the first time. CBZ is a worldwide used antiepileptic drug, found as a persistent emerging contaminant in many wastewater treatment plants (WWTPs) effluents and other aquatic environments. The oxidation treatments of WW caused an effective removal of the drug. Among the various US, FO and FS pre-treatments carried out, higher soluble chemical oxygen demand (SCOD) and soluble organic carbon (SOC) increment (63 to 86% and 21 to 34%, respectively) was observed during FO pre-treatment process, resulting in higher removal of CBZ (84 to 100%) from WW. Furthermore, analysis of by-products formed during US, FO and FS pre-treatment in WW was carried out by using laser diode thermal desorption-atmospheric pressure chemical ionization (LDTD-APCI) coupled to tandem mass spectrometry (MS/MS). LDTD-APCI-MS/MS analysis indicated formation of two by-products, such as epoxycarbamazepine and hydroxycarbamazepine due to the reaction of hydroxyl radicals (OH) with CBZ during the three types of pre-treatment processes. In addition, the estrogenic activity of US, FO and FS pre-treated sample with CBZ and its by-products was carried out by Yeast Estrogen Screen (YES) assay method. Based upon the YES test results, none of the pre-treated samples showed estrogenic activity. Copyright © 2012 Elsevier B.V. All rights reserved.

The Mineralogy and Geochemistry of Manganese Nodules From the Southern Ocean

DTIC Science & Technology

1968-02-01

accumulations. Quartz, plagioclase, montmorillonite , and phillipsite are almost invariably present, while clinoptilolite ii and amphibole occur less... Montmorillonite Diffraction Data ........... 125 16. Phillipsite Diffraction Data .. ......... ... 126 17. Sources of X-ray Diffraction Data...concretion. (Crust from ELTANIN 5-4; nucleus probably phillipsite- montmorillonite ; glacial erratics incorporated in ferro- manganese oxide crust.) 0 cm I

Cubic Polynomials with Real or Complex Coefficients: The Full Picture

ERIC Educational Resources Information Center

Bardell, Nicholas S.

2016-01-01

The cubic polynomial with real coefficients has a rich and interesting history primarily associated with the endeavours of great mathematicians like del Ferro, Tartaglia, Cardano or Vieta who sought a solution for the roots (Katz, 1998; see Chapter 12.3: The Solution of the Cubic Equation). Suffice it to say that since the times of renaissance…

Genie in a blotter: A comparative study of LSD and LSD analogues' effects and user profile.

PubMed

Coney, Leigh D; Maier, Larissa J; Ferris, Jason A; Winstock, Adam R; Barratt, Monica J

2017-05-01

This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them. An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues. Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD. LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement. Copyright © 2017 John Wiley & Sons, Ltd.

Etude de la structure électronique et magnétique de CrO_2

NASA Astrophysics Data System (ADS)

Matar, S.; Demazeau, G.; Sticht, J.; Eyert, V.; Kübler, J.

1992-03-01

The electronic and magnetic properties of CrO2 were investigated using the self-consistent A.S.W. method in a new approach to study the evolution of its magnetic properties at deceasing volume and to assess recent photoemission results on thin films. The results show that a magnetic transition of ferro Rightarrow antiferromagnetic type is likely to be induced under pressure. Experimental results could be explained by a compression of the CrO6 octahedron within the cell. Les propriétés électroniques de CrO2 ont été déterminées par la méthode auto-cohérente de l'onde sphérique augmentée : A.S.W. Cette étude est menée dans le cadre d'une nouvelle approche visant à définir lévolution de ses propriétés magnétiques à volume décroissant d'une part et à élucider les résultats expérimentaux récents de photoémission sur couches minces d'autre part. Les résultats des calculs montrent qu'une transition magnétique de type ferro Rightarrow antiferromagnétique est susceptible d'être induite sous l'effet de la pression. Les résultats expérimentaux pourraient être interprétés par une compression de l'octaèdre CrO6 au sein de la maille.

Nanometric study of nickel oxide prepared by sol gel process

NASA Astrophysics Data System (ADS)

Dessai, R. Raut; Desa, J. A. E.; Sen, D.; Babu, P. D.

2018-04-01

Nickel oxide nanopowder was synthesized by sol gel method using nickel nitrate as the starting material. Nickel oxide nanoparticles with a grain size of 15-90 nm have been studied by; small angle neutron scattering; scanning electron microscopy; and vibrating sample magnetometry. A combination of Ferro and paramagnetic behaviour of the particles after calcination at 800 °C is observed while for powder calcined at 400 °C, soft magnetic character with saturation is seen. The system of nanoparticles ofNiO embedded in a silica matrix is also studied for the structural change. Weak magnetic ordering is observed in this case with the likely-hood of particles being evenly distributed in the silica.

THE USE OF PANAX GINSENG AND ITS ANALOGUES AMONG PHARMACY CUSTOMERS IN ESTONIA: A CROSS-SECTIONAL STUDY.

PubMed

Volmer, Dasy; Raal, Ain; Kalle, Raivo; Sõukand, Renata

2016-01-01

The aim of the cross-sectional study was to evaluate the pattern of complementary self-treatment with P. ginseng and its analogues amongst pharmacy customers in Estonia. The study instrument consisted of multiple-choice items related to personal knowledge about and experience with the use of P. ginseng and its analogues. In total, 1233 customers participated in the study. Of study participants, 18.1% reported the use of P. ginseng and its analogues in their lives. P. ginseng preparations were used mostly according to the well- known indications (tiredness, weakness and decreased mental and physical capacity). Of P. ginseng users 44.3% reported positive treatment effects and 12.0% had experienced different side effects. With increase of age (p < 0.01) and at lower levels of education (p = 0.04), the use of ginseng or its analogues decreased. The better the users evaluated their health, the better they perceived the effect of P. ginseng preparations (p < 0.01). This study reported rather frequent use of P. ginseng and its analogues. P. ginseng could be seen in the treatment of conditions, where the use of local medicinal plants has not been established. Further research is needed to learn more about public knowledge and experiences about efficacy and safety of P. ginseng and its analogues.

Planetary habitability: lessons learned from terrestrial analogues

NASA Astrophysics Data System (ADS)

Preston, Louisa J.; Dartnell, Lewis R.

2014-01-01

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

Structure-activity relationships of the antimalarial agent artemisinin. 8. design, synthesis, and CoMFA studies toward the development of artemisinin-based drugs against leishmaniasis and malaria.

PubMed

Avery, Mitchell A; Muraleedharan, Kannoth M; Desai, Prashant V; Bandyopadhyaya, Achintya K; Furtado, Marise M; Tekwani, Babu L

2003-09-25

Artemisinin (1) and its analogues have been well studied for their antimalarial activity. Here we present the antimalarial activity of some novel C-9-modified artemisinin analogues synthesized using artemisitene as the key intermediate. Further, antileishmanial activity of more than 70 artemisinin derivatives against Leishmania donovani promastigotes is described for the first time. A comprehensive structure-activity relationship study using CoMFA is discussed. These analogues exhibited leishmanicidal activity in micromolar concentrations, and the overall activity profile appears to be similar to that against malaria. Substitution at the C-9beta position was shown to improve the activity in both cases. The 10-deoxo derivatives showed better activity compared to the corresponding lactones. In general, compounds with C-9alpha substitution exhibited lower antimalarial as well as antileishmanial activities compared to the corresponding C-9beta analogues. The importance of the peroxide group for the observed activity of these analogues against leishmania was evident from the fact that 1-deoxyartemisinin analogues did not exhibit antileishmanial activity. The study suggests the possibility of developing artemisinin analogues as potential drug candidates against both malaria and leishmaniasis.

The use and market for wood in the electrometallurgical industry

Treesearch

Jeffery L. Wartluft; Jeffery L. Wartluft

1971-01-01

Wood residues, particularly large chips, play an important role in the electric smelting of certain ferro-alloys. This is a report on the characteristics and growth potential of the market for wood in the electrometallurgicaI industry, including a brief account of how wood is used in electrometallurgical processes, a discussion of the preferred form of wood used, a...

Advanced Plasma Propulsion

DTIC Science & Technology

2011-11-01

within these cusps where electrons collide with the ceramic insulator lining the channel. In the MIT design, the overall magnetic field strength...allow compression of the anode spring (Sp), which holds the anode insulator (AI) flush with the base core (1). The anode stem and anode (A) are...case Aluminum bulk material 3 Insulator Cone HP-BN St. Gobain/ Ferro- Ceramic Grinding Inc. M1-M3 Permanent

Ferroelectric polarization induces electronic nonlinearity in ion-doped conducting polymers

PubMed Central

Fabiano, Simone; Sani, Negar; Kawahara, Jun; Kergoat, Loïg; Nissa, Josefin; Engquist, Isak; Crispin, Xavier; Berggren, Magnus

2017-01-01

Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) is an organic mixed ion-electron conducting polymer. The PEDOT phase transports holes and is redox-active, whereas the PSS phase transports ions. When PEDOT is redox-switched between its semiconducting and conducting state, the electronic and optical properties of its bulk are controlled. Therefore, it is appealing to use this transition in electrochemical devices and to integrate those into large-scale circuits, such as display or memory matrices. Addressability and memory functionality of individual devices, within these matrices, are typically achieved by nonlinear current-voltage characteristics and bistability—functions that can potentially be offered by the semiconductor-conductor transition of redox polymers. However, low conductivity of the semiconducting state and poor bistability, due to self-discharge, make fast operation and memory retention impossible. We report that a ferroelectric polymer layer, coated along the counter electrode, can control the redox state of PEDOT. The polarization switching characteristics of the ferroelectric polymer, which take place as the coercive field is overcome, introduce desired nonlinearity and bistability in devices that maintain PEDOT in its highly conducting and fast-operating regime. Memory functionality and addressability are demonstrated in ferro-electrochromic display pixels and ferro-electrochemical transistors. PMID:28695197

Life-Cycle environmental impact assessment of mineral industries

NASA Astrophysics Data System (ADS)

Hisan Farjana, Shahjadi; Huda, Nazmul; Parvez Mahmud, M. A.

2018-05-01

Mining is the extraction and processing of valuable ferro and non-ferro metals and minerals to be further used in manufacturing industries. Valuable metals and minerals are extracted from the geological deposits and ores deep in the surface through complex manufacturing technologies. The extraction and processing of mining industries involve particle emission to air or water, toxicity to the environment, contamination of water resources, ozone layer depletion and most importantly decay of human health. Despite all these negative impacts towards sustainability, mining industries are working throughout the world to facilitate the employment sector, economy and technological growth. The five most important miners in the world are South Africa, Russia, Australia, Ukraine, Guinea. The mining industries contributes to their GDP significantly. However, the most important issue is making the mining world sustainable thus reducing the emissions. To address the environmental impacts caused by the mining sectors, this paper is going to analyse the environmental impacts caused by the 5 major minerals extraction processes, which are bauxite, ilmenite, iron ore, rutile and uranium by using the life-cycle impact assessment technologies. The analysis is done here using SimaPro software version 8.4 using ReCipe, CML and Australian indicator method.

High Resolution Marine Magnetic Survey of Shallow Water Littoral Area

PubMed Central

Ginzburg, Boris; Cohen, Tsuriel Ram; Zafrir, Hovav; Alimi, Roger; Salomonski, Nizan; Sharvit, Jacob

2007-01-01

The purpose of this paper is to present a system developed for detection and accurate mapping of ferro-metallic objects buried below the seabed in shallow waters. The system comprises a precise magnetic gradiometer and navigation subsystem, both installed on a non-magnetic catamaran towed by a low-magnetic interfering boat. In addition we present the results of a marine survey of a near-shore area in the vicinity of Atlit, a town situated on the Mediterranean coast of Israel, about 15 km south of Haifa. The primary purpose of the survey was to search for a Harvard airplane that crashed into the sea in 1960. A magnetic map of the survey area (3.5 km2 on a 0.5 m grid) was created revealing the anomalies at sub-meter accuracy. For each investigated target location a corresponding ferro-metallic item was dug out, one of which turned to be very similar to a part of the crashed airplane. The accuracy of location was confirmed by matching the position of the actual dug artifacts with the magnetic map within a range of ± 1 m, in a water depth of 9 m. PMID:28903191

Plasma Wall interaction in the IGNITOR machine

NASA Astrophysics Data System (ADS)

Ferro, C.

1998-11-01

One of the critical issues in ignited machines is the management of the heat and particle exhaust without degradation of the plasma quality (pollution and confinement time) and without damage of the material facing the plasma. The IGNITOR machine has been conceived as a ``limiter" device, i.e., with the plasma leaning nearly on the entire surface of the first wall. Peak heat loads can easily be maintained at values lower than 1.35 MW/m^2 even considering displacements of the plasma column^1. This ``limiter" choice is based on the operational performances of high density, high field machines which suggests that intrinsic physics processes in the edge of the plasma are effective in spreading heat loads and maintaining the plasma pollution at a low level. The possibility of these operating scenarios has been demonstrated recently by different machines both in limiter and divertor configurations. The basis for the different physical processes that are expected to influence the IGNITOR edge parameters ^2 are discussed and a comparison with the latest experimental results is given. ^1 C. Ferro, G. Franzoni, R. Zanino, ENEA Internal Report RT/ERG/FUS/94/14. ^2 C. Ferro, R. Zanino, J. Nucl. Mater. 543, 176 (1990).

Synthesis and biological activity of analogues of the antimicrotubule agent N,beta,beta-trimethyl-L-phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N(1),3-dimethyl-L-valinamide (HTI-286).

PubMed

Zask, Arie; Birnberg, Gary; Cheung, Katherine; Kaplan, Joshua; Niu, Chuan; Norton, Emily; Suayan, Ronald; Yamashita, Ayako; Cole, Derek; Tang, Zhilian; Krishnamurthy, Girija; Williamson, Robert; Khafizova, Gulnaz; Musto, Sylvia; Hernandez, Richard; Annable, Tami; Yang, Xiaoran; Discafani, Carolyn; Beyer, Carl; Greenberger, Lee M; Loganzo, Frank; Ayral-Kaloustian, Semiramis

2004-09-09

Hemiasterlin, a tripeptide isolated from marine sponges, induces microtubule depolymerization and mitotic arrest in cells. HTI-286, an analogue from an initial study of the hemiasterlins, is presently in clinical trials. In addition to its potent antitumor effects, 2 has the advantage of circumventing the P-glycoprotein-mediated resistance that hampers the efficacy of other antimicrotubule agents such as paclitaxel and vincristine in animal models. This paper describes an in-depth study of the structure--activity relationships of analogues of 2, their effects on microtubule polymerization, and their in vitro and in vivo anticancer activity. Regions of the molecule necessary for potent activity are identified. Groups tolerant of modification, leading to novel analogues, are reported. Potent analogues identified through in vivo studies in tumor xenograft models include one superior analogue, HTI-042.

Investigations of mechanical, electronic, and magnetic properties of non-magnetic MgTe and ferro-magnetic Mg0.75 TM 0.25Te (TM = Fe, Co, Ni): An ab-initio calculation

NASA Astrophysics Data System (ADS)

Q, Mahmood; S, M. Alay-e.-Abbas; I, Mahmood; Mahmood, Asif; N, A. Noor

2016-04-01

The mechanical, electronic and magnetic properties of non-magnetic MgTe and ferro-magnetic (FM) Mg0.75 TM 0.25Te (TM = Fe, Co, Ni) in the zinc-blende phase are studied by ab-initio calculations for the first time. We use the generalized gradient approximation functional for computing the structural stability, and mechanical properties, while the modified Becke and Johnson local (spin) density approximation (mBJLDA) is utilized for determining the electronic and magnetic properties. By comparing the energies of non-magnetic and FM calculations, we find that the compounds are stable in the FM phase, which is confirmed by their structural stabilities in terms of enthalpy of formation. Detailed descriptions of elastic properties of Mg0.75 TM 0.25Te alloys in the FM phase are also presented. For electronic properties, the spin-polarized electronic band structures and density of states are computed, showing that these compounds are direct bandgap materials with strong hybridizations of TM 3d states and Te p states. Further, the ferromagnetism is discussed in terms of the Zener free electron model, RKKY model and double exchange model. The charge density contours in the (110) plane are calculated to study bonding properties. The spin exchange splitting and crystal field splitting energies are also calculated. The distribution of electron spin density is employed in computing the magnetic moments appearing at the magnetic sites (Fe, Co, Ni), as well as at the non-magnetic sites (Mg, Te). It is found that the p-d hybridization causes not only magnetic moments on the magnetic sites but also induces negligibly small magnetic moments at the non-magnetic sites.

Template properties of mutagenic cytosine analogues in reverse transcription

PubMed Central

Suzuki, Tetsuya; Moriyama, Kei; Otsuka, Chie; Loakes, David; Negishi, Kazuo

2006-01-01

We have studied the mutagenic properties of ribonucleotide analogues by reverse transcription to understand their potential as antiretroviral agents by mutagenesis of the viral genome. The templating properties of nucleotide analogues including 6-(β-D-ribofuranosyl)-3,4-dihydro-8H-pyrimido[4,5-c](1,2)oxazin-7-one, N4-hydroxycytidine, N4-methoxycytidine, N4-methylcytidine and 4-semicarbazidocytidine, which have been reported to exhibit ambiguous base pairing properties, were examined. We have synthesized RNA templates using T3 RNA polymerase, and investigated the specificity of the incorporation of deoxyribonucleoside triphosphates opposite these cytidine analogues in RNA by HIV and AMV reverse transcriptases. Except for N4-methylcytidine, both enzymes incorporated both dAMP and dGMP opposite these analogues in RNA. This indicates that they would be highly mutagenic if present in viral RNA. To study the basis of the differences among the analogues in the incorporation ratios of dAMP to dGMP, we have carried out kinetic analysis of incorporation opposite the analogues at a defined position in RNA templates. In addition, we examined whether the triphosphates of these analogues were incorporated competitively into RNA by human RNA polymerase II. Our present data supports the view that these cytidine analogues are mutagenic when incorporated into RNA, and that they may therefore be considered as candidates for antiviral agents by causing mutations to the retroviral genome. PMID:17130163

Synthesis, antimycobacterial evaluation and pharmacophore modeling of analogues of the natural product formononetin.

PubMed

Mutai, Peggoty; Pavadai, Elumalai; Wiid, Ian; Ngwane, Andile; Baker, Bienyameen; Chibale, Kelly

2015-06-15

The synthesis and antimycobacterial activity of formononetin analogues is hereby reported. Formononetin and its analogue 11E showed 88% and 95% growth inhibition, respectively, against the H37Rv strain of Mycobacterium tuberculosis. Pharmacophore modeling studies indicated that the presence of a hydroxyl group in formononetin and its analogues, is crucial for maintaining activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Polarization-Based Radar Detection in Sea Clutter

DTIC Science & Technology

2015-02-27

Boerner, "Introduction to Synthetic Aperture Radar (SAR) Polarimetry ," Wexford College Press, 2007. [7] E. Pottier, J. S. Lee, and L. Ferro...Application, US 20140169428 Al, December 10, 2013 T. Pratt, "Methods and Apparatus for Radio Frequency Polarimetry Sensing," non- provisional... Polarimetry ," submitted to IEEE Transactions on Instrumentation and Measurement, 2012 J. Mueller and T. Pratt, "A Radio Frequency Polarimetric Sensor for

TIBePO4 : un nouveau phosphate ferroélectrique

NASA Astrophysics Data System (ADS)

Wallez, G.; Jaulmes, S.; Elfakir, A.; Quarton, M.

1994-07-01

The thallium-beryllium monophosphate is related to the β-SiO2 tridymite structural kind. The phase II, stable at room temperature, is found to have orthorhombic symmetry mm2. It sustains a displacive transformation at 919 ^{circ}C leading to centric phase I with symmetry mmm. In the low-temperature form, the 6s^2 electron pair of TI+ cation is oriented along polar axis, inducing a significant distortion of the oxygen framework ; the ferroelectric nature of phase II is pointed out by the strong increase of the dielectric stiffness around Curie temperature. Phase transition results of bound rotations of PO4 and BeO4 tetrahedra, the rise of symmetry order leading to the loss of hybridization of the lone pair. According to the displacive transition mechanism, both thermal and dielectric properties show typical second order features. L'orthophosphate de thallium-béryllium cristallise selon le type structural " tridymite β-SiO2 déformée ". La phase II, stable à l'ambiante, présente une symétrie orthorhombique mm2 ; elle subit une transformation displacive à 919 ^circC vers la forme prototype I centrosymétrique (mmm). Dans la variété ferroélectrique, le doublet électronique 6s^2 de l'ion Tl^+, orienté selon l'axe polaire, provoque une importante déformation de la charpente oxygénée ; le caractère ferroélectrique est mis en évidence par le fort accroissement de la permittivité diélectrique au voisinage de la température de Curie. La transition procède par des rotations engrenées des tétraèdres PO4 et BeO4, l'accroissement de symétrie impliquant la déshybridation du doublet 6s^2. Observée sous ses aspects thermique et diélectrique, cette transition apparaît comme un phénomène du second ordre, conformément à son caractère displacif.

Synthesis of deuterium-labelled analogues of NLRP3 inflammasome inhibitor MCC950.

PubMed

Salla, Manohar; Butler, Mark S; Massey, Nicholas L; Reid, Janet C; Cooper, Matthew A; Robertson, Avril A B

2018-02-15

This study describes the syntheses of di, tetra and hexa deuterated analogues of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome inhibitor MCC950. In di and tetra deuterated analogues, deuteriums were incorporated into the 1,2,3,5,6,7-hexahydro-s-indacene moiety, whereas in the hexa deuterated MCC950 deuteriums were incorporated into the 2-(furan-3-yl)propan-2-ol moiety. The di deuterated MCC950 analogue was synthesised from 4-amino-3,5,6,7-tetrahydro-s-indacen-1(2H)-one 5. Tetra deuterated analogues were synthesised in 10 chemical steps starting with 5-bromo-2,3-dihydro-1H-inden-1-one 9, whereas the hexa deuterated analogue was synthesised in four chemical steps starting with ethyl-3-furoate 24. All of the compounds exhibited similar activity to MCC950 (IC 50  = 8 nM). These deuterated analogues are useful as internal standards in LC-MS analyses of biological samples from in vivo studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

ERIC Educational Resources Information Center

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…

Insulin analogues for type 1 diabetes in children and adolescents.

PubMed

Galli-Tsinopoulou, A; Stergidou, D

2012-12-01

Since insulin is the unique and life-long therapy in type 1 diabetes and classical insulin preparations have certain limitations due to their pharmacokinetic and pharmacodynamic properties, the new insulin analogues aim to eliminate these limitations. Five insulin analogues are commercially available and approved for individuals with type 1 diabetes: three rapid-acting (insulin lispro, insulin aspart and insulin glulisine) and two long-acting insulin analogues (insulin glargine and insulin detemir). According to several studies conducted in children with type 1 diabetes, insulin analogues, due to their structural alterations, offer flexibility, reduction of nocturnal hypoglycemic episodes and decrease in postprandial hyperglycemic events, resulting in improved quality of life for diabetic children and their families. However, diabetes control measured with glycosylated hemoglobin A1c has been reported to be similar to conventional insulin preparations. Evidence-based medical reports indicate that insulin analogues are safe and effective, and therefore approved for children even from the age of 2 years. Moreover, suspicions and reports on the association of insulin analogues with carcinogenesis have not been established, requiring further investigation. This review reports the properties and characteristics of insulin analogues, as well as the results of current studies concerning pediatric patients with type 1 diabetes. Copyright 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

Fetal bovine serum influences the stability and bioactivity of resveratrol analogues: A polyphenol-protein interaction approach.

PubMed

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.

Etudes diélectriques de la transition ferroélectrique induite par application d'un champ électrique dans les céramiques PbMg{1/3}Nb{2/3}O3 (PMN)

NASA Astrophysics Data System (ADS)

Chabin, M.; Malki, M.; Husson, E.; Morell, A.

1994-07-01

The evolution of the dielectric permittivity and loss factor under an external applied electric field has been studied in PbMg{1/3}Nb{2/3}O3 ceramics between 80 and 420 K. For a threshold field of 4 kV.cm^{-1}, it is possible to induce a ferroelectric transition from the average cubic phase to a macroscopically polar phase. The poling and depoling temperatures depend on the various combinations of thermal treatments and on the applied field strength. The transition between the nanopolar state and the macropolar state is discussed L'évolution de la permittivité diélectrique et du facteur de pertes diélectriques sous un champ électrique extérieur a été étudiée dans des céramiques de PbMg{1/3}Nb{2/3}O3 enre 80 et 420 K. Pour un champ de seuil de 4 kV.cm^{-1} il est possible d'induire une transition ferroélectrique de la phase cubique moyenne en une phase macroscopiquement polaire. Les températures de polarisation et de dépolarisation dépendent des différentes combinaisons de traitements thermiques et de la valeur du champ appliqué. La transition entre la phase constituée de nanodomaines polaires et la phase constituée de macrodomaines polaires est discutée.

Simple full micromagnetic model of exchange bias behavior in ferro/antiferromagnetic layered structures (abstract)

NASA Astrophysics Data System (ADS)

Koon, Norman C.

1997-04-01

It is shown using full micromagnetic relaxation calculations that exchange bias behavior is predicted for single-crystal ferro/antiferromagnetic layers with a fully compensated interface. The particular example most fully studied has a bcc/bct lattice structure with a fully compensated (110) interface plane. Only bilinear Heisenberg exchange was assumed, with anisotropy only in the antiferromagnet. In spite of the intuitive notion that exchange coupling between a ferromagnet and an antiferromagnet across a fully compensated plane of the antiferromagnet should be zero, we find strong coupling, comparable to the bilinear exchange, with a 90° angle between the ferromagnetic and antiferromagnetic axes of layers far from the interface in absence of an applied field. Even though the 90° coupling has characteristics resembling "biquadratic" exchange, it originates entirely from frustrated bilinear exchange. The development of exchange bias is found to originate from the formation of a domain wall in the antiferromagnet via the strong 90° exchange coupling and pinning of the wall by the magnetocrystalline anisotropy in the antiferromagnet. Because the large demagnetizing factor of the ferromagnet tends to confine its magnetization to the plane, the exchange bias is found to depend mainly on the strength and the symmetry of the in-plane component of anisotropy. Although little effort was made to analyze specific systems, the model reproduces many of the qualitative features observed in real exchange bias systems and gives reasonable semiquantitative estimates for the bias field when exchange and anisotropy values consistent with real systems are used.

Assessment of six dissimilarity metrics for climate analogues

NASA Astrophysics Data System (ADS)

Grenier, Patrick; Parent, Annie-Claude; Huard, David; Anctil, François; Chaumont, Diane

2013-04-01

Spatial analogue techniques consist in identifying locations whose recent-past climate is similar in some aspects to the future climate anticipated at a reference location. When identifying analogues, one key step is the quantification of the dissimilarity between two climates separated in time and space, which involves the choice of a metric. In this communication, spatial analogues and their usefulness are briefly discussed. Next, six metrics are presented (the standardized Euclidean distance, the Kolmogorov-Smirnov statistic, the nearest-neighbor distance, the Zech-Aslan energy statistic, the Friedman-Rafsky runs statistic and the Kullback-Leibler divergence), along with a set of criteria used for their assessment. The related case study involves the use of numerical simulations performed with the Canadian Regional Climate Model (CRCM-v4.2.3), from which three annual indicators (total precipitation, heating degree-days and cooling degree-days) are calculated over 30-year periods (1971-2000 and 2041-2070). Results indicate that the six metrics identify comparable analogue regions at a relatively large scale, but best analogues may differ substantially. For best analogues, it is also shown that the uncertainty stemming from the metric choice does generally not exceed that stemming from the simulation or model choice. A synthesis of the advantages and drawbacks of each metric is finally presented, in which the Zech-Aslan energy statistic stands out as the most recommended metric for analogue studies, whereas the Friedman-Rafsky runs statistic is the least recommended, based on this case study.

Comparison of insulin analogue B9AspB27Glu and soluble human insulin in insulin-treated diabetes.

PubMed

Kang, S; Owens, D R; Vora, J P; Brange, J

1990-02-10

Postprandial plasma glucose excursions and plasma levels of free insulin after subcutaneous bolus injection of a rapidly absorbed monomeric insulin analogue (B9AspB27Glu) or soluble human insulin ('Actrapid HM' U100) were studied in six insulin-treated diabetic subjects. 10 U actrapid or an equimolar amount of the analogue were injected, in random order with an interval of 1 week, immediately before a 500 kcal test meal. Basal insulin levels were similar on the 2 study days (mean 74.1 [SE 5.1] pmol/l, actrapid; 79.7 [13.0] pmol/l, analogue). After injection of actrapid plasma free insulin levels rose slowly, reaching a plateau by 105 min at 222 (19) pmol/l. Injection of the analogue resulted in a rapid early peak at 30 min (798 [112] pmol/l), and levels were significantly higher than those after actrapid between 15 and 210 min. The more physiological plasma insulin levels achieved with the analogue were accompanied by a substantial reduction in postprandial plasma glucose excursions; the integrated area under the incremental plasma glucose curve was 45% lower after the analogue than after actrapid.

Applications of Polarimetric and Interferometric SAR to Environmental Remote Sensing and its Activities: Recent Advances in Extrawideband Polarimetry, Interferometry and Polarimetric Interferometry in Synthetic Aperture Remote Sensing and its Applications

DTIC Science & Technology

2007-02-01

January 2003. [69] EUSAR 2000 Proceedings, VDE Verlag, Offenbach, ISBN: 3-8007-2544-4, Munich, Germany, May 2000. [70] EUSAR 2002 Proceedings... VDE Verlag, Offenbach, ISBN: 3-8007-2697-1, Cologne, Germany, June 2002. [71] Ferro-Famil, L. and E. Pottier, 2000, "Description of Dual Frequency

Computational study of the activity, dynamics, energetics and conformations of insulin analogues using molecular dynamics simulations: Application to hyperinsulinemia and the critical residue B26.

PubMed

Papaioannou, Anastasios; Kuyucak, Serdar; Kuncic, Zdenka

2017-09-01

Due to the increasing prevalence of diabetes, finding therapeutic analogues for insulin has become an urgent issue. While many experimental studies have been performed towards this end, they have limited scope to examine all aspects of the effect of a mutation. Computational studies can help to overcome these limitations, however, relatively few studies that focus on insulin analogues have been performed to date. Here, we present a comprehensive computational study of insulin analogues-three mutant insulins that have been identified with hyperinsulinemia and three mutations on the critical B26 residue that exhibit similar binding affinity to the insulin receptor-using molecular dynamics simulations with the aim of predicting how mutations of insulin affect its activity, dynamics, energetics and conformations. The time evolution of the conformers is studied in long simulations. The probability density function and potential of mean force calculations are performed on each insulin analogue to unravel the effect of mutations on the dynamics and energetics of insulin activation. Our conformational study can decrypt the key features and molecular mechanisms that are responsible for an enhanced or reduced activity of an insulin analogue. We find two key results: 1) hyperinsulinemia may be due to the drastically reduced activity (and binding affinity) of the mutant insulins. 2) Y26 B S and Y26 B E are promising therapeutic candidates for insulin as they are more active than WT-insulin. The analysis in this work can be readily applied to any set of mutations on insulin to guide development of more effective therapeutic analogues.

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

PubMed

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

2016-06-07

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

Synthetic and Medicinal Prospective of Structurally Modified Curcumins.

PubMed

Kumar, Bhupinder; Singh, Virender; Shankar, Ravi; Kumar, Kapil; Rawal, Ravindra K

2017-01-01

Curcumin, a natural yellow phenolic compound, is present in various types of herbs, particularly in Turmeric, Curcuma longa Linn. (Zingiberaceae family) rhizomes. Curcumin is a polyphenolic natural compound with diverse and attractive biological activities. In the last decade curcumine and its various synthetic analogues have been prepared and evaluated for various pharmacological activities that prove it as a lead molecule against several biological targets. It is a natural antioxidant and exhibited many pharmacological activities such as anti-inflammatory, anti-microbial, anticancer, anti-Alzheimer in both preclinical and clinical studies. Moreover, Curcumin and its analogues have anti-tubercular, cardioprotective, anti-diabetic, hepatoprotective, neuroprotective, nephroprotective, antirheumatic and anti-viral activities. The substitutions of 1,6-heptadiene linkage moiety via carbonyl group sustituion and addition of heterocyclic linker; isoxazole, 1H-pyrazole, cyclopentanone, piperidin-4-one, N-methylpiperidin-4-one enhance biological activities. The structure activity relationship of various curcumin analogues is studied for medicinal purposes and it reveals that monocarbonyl linkage analogues have anticancer properties. The current review gives an insight of the history, chemistry, analogues and most interesting in vitro and in vivo studies on the biological effects of Curcumin and its analogues.

A Cross-Sectional Survey of the Association between Bilateral Topical Prostaglandin Analogue Use and Ocular Adnexal Features

PubMed Central

Shah, Mamta; Lee, Grace; Lefebvre, Daniel R.; Kronberg, Benjamin; Loomis, Stephanie; Brauner, Stacey C.; Turalba, Angela; Rhee, Douglas J.; Freitag, Suzanne K.; Pasquale, Louis R.

2013-01-01

We studied the relation between prostaglandin analogue use and ocular adnexal features. We used a prospective, cross-sectional study involving 157 current, 15 past, and 171 never users of prostaglandin analogues. Patients 50 years of age or older and without conditions affecting ocular adnexal anatomy underwent glaucoma medication use history, external digital photography and systematic external adnexal exam. Two masked readers assessed the digital photos for upper lid dermatochalasis and lower lid steatoblepharon using a validated grading scheme. Another masked clinical examiner also assessed upper lid ptosis, levator muscle function, and inferior scleral show. We performed ordinal logistic regression analysis accounting for multiple covariates to assess the relation between prostaglandin analogue use and adnexal features. Multivariable analyses indicated there was a 230-fold increased risk of incremental involution of dermatochalasis (odds ratio (OR)  =  2.30; 95% confidence interval (CI) 1.43–3.69; p = 5.44E-04) and a 249-fold increased risk of incremental loss of lower lid steatoblepharon (OR  =  2.49; 95% CI, 1.54–4.03; p =  1.98E-04) associated with current prostaglandin analogue use (bimatoprost 0.03%, travoprost 0.005%, or latanoprost 0.004%) versus prostaglandin analogue never or past users. Upper lid ptosis (OR  =  4.04; 95% CI, 2.43–6.72; p = 7.37E-08), levator dysfunction (OR =  7.51; 95% CI, 3.39–16.65; p = 6.74E-07) and lower lid retraction (OR = 2.60; 95% CI, 1.58–4.28; p = 1.72E-04) were highly associated with current prostaglandin analogue use versus prostaglandin analogue never or past users. The associations between prostaglandin analogue use and deepening of the upper lid sulci and between prostaglandin analogue use and loss of inferior periorbital fat are confirmed in this multivariable analysis. The associations between prostaglandin analogue use and levator muscle dysfunction and between prostaglandin analogue use and upper lid ptosis represent significant side effects that could impact visual function in glaucoma patients. PMID:23650502

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

ERIC Educational Resources Information Center

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…

Fungal growth inhibitory properties of new phytosphingolipid analogues.

PubMed

Mormeneo, D; Manresa, A; Casas, J; Llebaria, A; Delgado, A

2008-04-01

To study the growth inhibitory properties of a series of phytosphingosine (PHS) and phytoceramide (PHC) analogues. A panel of two yeast (Candida albicans and Saccharomyces cerevisiae) and six moulds (Aspergillus repens, Aspergillus niger, Penicillium chrysogenum, Cladosporium cladosporioides, Arthroderma uncinatum and Penicillium funiculosum) has been used in this study. A series of new PHS and PHC analogues differing at the sphingoid backbone and the functional group at C1 position were synthesized. Among PHS analogues, 1-azido derivative 1c, bearing the natural D-ribo stereochemistry, showed a promising growth inhibitory profile. Among PHC analogues, compound 12, with a bulky N-pivaloyl group and a Z double bond at C3 position of the sphingoid chain, was the most active growth inhibitor. Minimal inhibitory concentration values were in the range of 23-48 micromol l(-1) for 1c and 44-87 micromol l(-1) for 12. Only scattered data on the antifungal activity of phytosphingolipids have been reported in the literature. This is the first time that a series of analogues of this kind are tested and compared to discern their structural requirements for antifungal activity.

Martian Feeling: An Analogue Study to Simulate a Round-Trip to Mars using the International Space Station

NASA Astrophysics Data System (ADS)

Felix, C. V.; Gini, A.

When talking about human space exploration, Mars missions are always present. It is clear that sooner or later, humanity will take this adventure. Arguably the most important aspect to consider for the success of such an endeavour is the human element. The safety of the crew throughout a Martian mission is a top priority for all space agencies. Therefore, such a mission should not take place until all the risks have been fully understood and mitigated. A mission to Mars presents unique human and technological challenges in terms of isolation, confinement, autonomy, reliance on mission control, communication delays and adaptation to different gravity levels. Analogue environments provide the safest way to simulate these conditions, mitigate the risks and evaluate the effects of long-term space travel on the crew. Martian Feeling is one of nine analogue studies, from the Mars Analogue Path (MAP) report [1], proposed by the TP Analogue group of ISU Masters class 2010. It is an integrated analogue study which simulates the psychological, physiological and operational conditions that an international, six-person, mixed gender crew would experience on a mission to Mars. Set both onboard the International Space Station (ISS) and on Earth, the Martian Feeling study will perform a ``dress rehearsal'' of a mission to Mars. The study proposes to test both human performance and operational procedures in a cost-effective manner. Since Low Earth Orbit (LEO) is more accessible than other space-based locations, an analogue studies in LEO would provide the required level of realism to a simulated transit mission to Mars. The sustained presence of microgravity and other elements of true spaceflight are features of LEO that are neither currently feasible nor possible to study in terrestrial analogue sites. International collaboration, economics, legal and ethical issues were considered when the study was proposed. As an example of international collaboration, the ISS would demonstrate an effective model for an international effort to send humans to Mars. The proposed starting date is the year 2017, before the planned retirement of the ISS, which is currently scheduled for 2020.

Combustion Synthesis Technology Applied to In-situ Resource Utilization

DTIC Science & Technology

2006-06-15

or bond energies. When both the precursor salts and the fuel are water soluble, a good homogenization can be achieved in the solution. In the...metallic compounds, e.g. Ni-Al. Steel processing additives, e.g. ferro-nitrides. Electrodes for electrolysis of corrosive media, e.g. TiN, TiB2...reactants; 4. Spreading of a molten phase; 5. Gasification of volatile impurities and reactants; 6. Chemical reaction with initial product formation; 7

Statistical Characterization of Altitude Matrices by Computer. Report 4. Frequency Distributions of Gradient.

DTIC Science & Technology

1977-01-01

balanced at the mean, with the central part steeper ( platykurtic : broad mode or truncated tails) -r flatter (leptokurtic: peaked mode or extended...and NUPUR, have negative kurtosis (they are platykurtic , with truncated tails and/or broad modes relative to their standard deviations) FERRO, on the...the other areas, and its gradients are platykurtic but almost unskewed. Hence the square root of sine transformation (Fig,15) and the log tangent

Trends in the use and cost of human and analogue insulins in a Colombian population, 2011-2015.

PubMed

Torres, D R; Portilla, A; Machado-Duque, M E; Machado-Alba, J E

2017-12-01

Diabetes mellitus is a common disease among the general population and imposes considerable costs on health care systems. Insulin is used to treat type 1 diabetes mellitus and as an adjuvant to oral agents in advanced stages of type 2 diabetes mellitus. The objective was to describe the trends in use and cost of human and analogue insulins for Colombian patients. Descriptive retrospective analysis of prescriptions of human and analogue insulins on a monthly basis for the period from July 1, 2011 to February 2, 2015. Information was collected for the database population of two insurance companies. Frequencies and proportions were calculated; estimated economic impact was expressed as net cost and cost per thousand inhabitants per day. During the observation period, there was continuous growth in use of insulin, mainly in analogue forms (34.0% growth). At the start of the study, 10.4% of subjects were using an analogue insulin; this figure was 62.6% at the end of the study. In 2012, the average cost per 1000 inhabitants/day was US$1.7 for analogue and US$0.8 for human insulins. At the end of the observation period these costs had risen to US$9.2 for analogue (441.1% increase) and fallen to US$0.5 for human insulin (58.3% decrease). There has been an increase in the unit cost and frequency of use of insulin analogues for anti-diabetic therapy in Colombian patients. Moreover, there is controversy over whether insulin analogues are a more cost-effective treatment than human insulins for the general diabetic population. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

In Silico Study and Cytotoxicity of the Synthesized Open-chain Analogues of Antimycin A3 Against HEP-2 Laryngeal Cancer Cells

PubMed Central

Arsianti, Ade; Fadilah, Fadilah; Kusmardi, Kusmardi; Sugiarta, Gede Y.; Tanimoto, Hiroki; Kakiuchi, Kiyomi

2017-01-01

Background: Laryngeal cancers affect one quarter of all head and neck cancers. Chemotherapy is a standard method in treatment laryngeal carcinoma. How-ever, cancer chemotherapy is often a failure due to the appearance of drug resistance. This fact suggests that the search for novel, safe, and more effective laryngeal cancer drugs are required. Antimycin A3 is a fit ligand of anti-apoptotic Bcl-2. While Bcl-2 is known to be over-expressed in laryngeal cancer cell, it is quite reasonable to expect an-timycin A3 and its analogue to induce apoptosis in those cells. Methods: With this viewpoint, we decided to conduct research that is aimed to evaluate cytotoxic activity of the synthesized open-chain analogues of antimycin A3 against HEP-2 laryngeal cancer cells, as well as to conduct in silico study of the analogues on receptor binding target Bcl-2 of laryngeal cancer. Results and Conclusion: Open-chain analogues of antimycin A3 were successfully syn-thesized in a good yield from Boc-L-Threonine by esterification, amidation, and Sharp-less asymmetric dihydroxylation. Consistent with in silico study, the analogues exhibited a greater anticancer activity against laryngeal HEP-2 cells than the original antimycin A3 with IC50 ranging of 31.6 µM to 46.3 µM. Our results clearly demonstrate that the open-chain analogues of an-timycin A3 as a promising candidates of new anti-laryngeal cancer agents.

The fracture toughness of borides formed on boronized cold work tool steels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sen, Ugur; Sen, Saduman

2003-06-15

In this study, the fracture toughness of boride layers of two borided cold work tool steels have been investigated. Boriding was carried out in a salt bath consisting of borax, boric acid, ferro-silicon and aluminum. Boriding was performed at 850 and 950 deg. C for 2 to 7 h. The presence of boride phases were determined by X-ray diffraction (XRD) analysis. Hardness and fracture toughness of borides were measured via Vickers indenter. Increasing of boriding time and temperature leads to reduction of fracture toughness of borides. Metallographic examination showed that boride layer formed on cold work tool steels was compactmore » and smooth.« less

Microstructural Investigation, Raman and Magnetic Studies on Chemically Synthesized Nanocrystalline Ni-Doped Gadolinium Oxide (Gd1.90Ni0.10O3- δ )

NASA Astrophysics Data System (ADS)

Sarkar, B. J.; Mandal, J.; Dalal, M.; Bandyopadhyay, A.; Satpati, B.; Chakrabarti, P. K.

2018-03-01

Nanocrystalline Ni-doped gadolinium oxide (Gd1.90Ni0.10O3- δ , GNO) is synthesized by co-precipitation method. The as-prepared sample is annealed in vacuum at 700°C for 6 h. Analyses of the x-ray diffractogram by Rietveld refinement method, transmission electron microscopy and Raman spectroscopy of GNO recorded at room temperature confirmed the pure crystallographic phase and complete substitution of Ni-ions in Gd2O3 lattice. Magnetization ( M) as a function of temperature ( T) and magnetic field ( H) is measured by a superconducting quantum interference device magnetometer, which suggests the presence of ferromagnetic/antiferromagnetic phases together with a paramagnetic phase. From the M-T curve it can be shown that the ferromagnetic phase dominates over para-/antiferromagnetic phases in the temperature range of 300-100 K, but from 100 K to 50 K, the antiferromagnetic phase dominates over ferro-/paramagnetic phases. Hysteresis loops recorded at different temperatures indicate the presence of weak ferro-/antiferromagnetism, which dominates in the low field region (˜ 4000 Oe), above which magnetization increases linearly. The sharp increase of magnetization in M-T curve observed in the temperature range of 50-5 K confirms the presence of dominating ferromagnetic plus paramagnetic phase over antiferromagnetic part. For the first time a combined formula generated from three-dimensional (3D) spin wave model and Johnston formula is proposed to analyze the coexistence of different magnetic phases in different temperature ranges. Interestingly, the combined formula successfully explains the co-existence of different magnetic phases along with their contribution at different temperatures. The onset of ferromagnetism in Gd1.90Ni0.10O3- δ is explained by oxygen vacancy mediated F-centre exchange (FCE) coupling mechanism.

Preparation and Characterization of BaTiO3-PbZrTiO3 Coating for Pyroelectric Energy Harvesting

NASA Astrophysics Data System (ADS)

Raghavendra, R. M.; Praneeth, K. P. S. S.; Dutta, Soma

2017-01-01

Harvesting energy from waste heat is a promising field of research as there are significant energy recovery opportunities from various waste thermal energy sources. The present study reports pyroelectric energy harvesting using thick film prepared from a (x)BaTiO3-(1 - x)PbZr0.52Ti0.48O3 (BT-PZT) solid solution. The developed BT-PZT system is engineered to tune the ferro to paraelectric phase transition temperature of it in-between the phase transition temperature of BaTiO3 (393 K) and PbZrTiO3 (573 K) with higher pyroelectric figure-of-merit (FOM). The temperature-dependent dielectric behavior of the material has revealed the ferro- to paraelectric phase transition at 427 K with a maximum dielectric constant of 755. The room-temperature (298 K) pyroelectric coefficient (Pi) of the material was obtained as 738.63 μC/m2K which has yielded a significantly high FOM of 1745.8 J m-3 K-2. The enhancement in pyroelectric property is attributed to the morphotopic phase transition between tetragonal and rhombohedral PZT phases in the BT-PZT system. The developed BT-PZT system is capable of generating a power output of 1.3 mW/m2 near the Curie temperature with a constant rate (0.11 K/s) of heating. A signal conditioning circuit has been developed to rectify the time-varying current and voltage signals obtained from the harvester during heating cycles. The output voltage generated by the pyroelectric harvester has been stored in a capacitor for powering wearable electronics.

Synthesis, biological evaluation and structure-activity relationship studies of isoflavene based Mannich bases with potent anti-cancer activity.

PubMed

Chen, Yilin; Cass, Shelley L; Kutty, Samuel K; Yee, Eugene M H; Chan, Daniel S H; Gardner, Christopher R; Vittorio, Orazio; Pasquier, Eddy; Black, David StC; Kumar, Naresh

2015-11-15

Phenoxodiol, an analogue of the isoflavone natural product daidzein, is a potent anti-cancer agent that has been investigated for the treatment of hormone dependent cancers. This molecular scaffold was reacted with different primary amines and secondary amines under different Mannich conditions to yield either benzoxazine or aminomethyl substituted analogues. These processes enabled the generation of a diverse range of analogues that were required for structure-activity relationship (SAR) studies. The resulting Mannich bases exhibited prominent anti-proliferative effects against SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines. Further cytotoxicity studies against MRC-5 normal lung fibroblast cells showed that the isoflavene analogues were selective towards cancer cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ring size of somatostatin analogues (ODT-8) modulates receptor selectivity and binding affinity

PubMed Central

Erchegyi, Judit; Grace, Christy Rani R.; Samant, Manoj; Cescato, Renzo; Piccand, Veronique; Riek, Roland; Reubi, Jean Claude; Rivier, Jean E.

2009-01-01

The synthesis, biological testing and NMR studies of several analogues of H-c[Cys3-Phe6-Phe7-dTrp8-Lys9-Thr10-Phe11-Cys14]-OH (ODT-8, a pan-somatostatin analogue) (1), have been performed to assess the effect of changing the stereochemistry and the number of the atoms in the disulfide bridge on binding affinity. Cysteine at positions 3 and/or 14 (SRIF numbering) were/was substituted with d-cysteine, Nor-cysteine, d-Nor-cysteine, Homo-cysteine and/or d-Homo-cysteine. The 3D structures of selected partially selective, bioactive analogues (3, 18, 19 and 21) were carried out in DMSO. Interestingly and not unexpectedly, the 3D structures of these analogues comprised the pharmacophore for which the analogues had the highest binding affinities (i.e., sst4 in all cases). PMID:18410084

Phytotoxicity of sarmentine isolated from long pepper (Piper longum) fruit.

PubMed

Huang, Huazhang; Morgan, Christy M; Asolkar, Ratnakar N; Koivunen, Marja E; Marrone, Pamela G

2010-09-22

Discovery of novel natural herbicides has become crucial to overcome increasing weed resistance and environmental issues. In this article, we describe the finding that a methanol extract of dry long pepper (Piper longum L.) fruits is phytotoxic to lettuce (Lactuca sativa L.) seedlings. The bioassay-guided fractionation and purification of the crude extract led to isolation of sarmentine (1), a known compound, as the active principle. Phytotoxicity of 1 was examined with a variety of seedlings of field crops and weeds. Results indicated that 1 was a contact herbicide and possessed broad-spectrum herbicidal activity. Moreover, a series of sarmentine analogues were then synthesized to study the structure-activity relationship (SAR). SAR studies suggested that phytotoxicity of sarmentine and its analogues was specific due to chemical structures, i.e., the analogues of the acid moiety of 1 were active, but the amine and its analogues were inactive; the ester analogues and amide analogues with a primary amine of 1 were also inactive. In addition, quantification of 1 from different resources of the dry P. longum fruits using liquid chromatography-mass spectrometry showed a wide variation, ranging from almost zero to 0.57%. This study suggests that 1 has potential as an active lead molecule for synthesized herbicides as well as for bioherbicides derived from natural resources.

Comparison of medication adherence in diabetes mellitus patients on human versus analogue insulins.

PubMed

Machado-Alba, Jorge Enrique; Medina-Morales, Diego Alejandro; Echeverri-Cataño, Luis Felipe

2017-02-01

Objetive: This study evaluated the results of treatment adherence scales in two cohorts of patients with diabetes mellitus treated either with human or analogue insulins. A cohort study was conducted in diabetes mellitus patients older than 18 that were being treated with human or analogue insulins. Two instruments were applied to each patient [medication possession ratio, Morisky-Green test] to evaluate treatment adherence. A total of 238 patients, were included. The majority (69.4%) of the subjects had human insulin and 30.6% had insulin analogue prescriptions. Out of the total, 163 (68.5%) cases were classified as adherent to therapy, according to the type of insulin, as follows: 69.9% for conventional and 65.3% for analogues; without differences between the groups (CI95%:0.450-1.458). The adherence to treatment was more probable in patients with elementary-secondary education (OR:2.341; CI95%:1.199-4.568) and less probable for those in the age range of 31-45 years (OR:0.427; CI95%:0.187-0.971). The results of this study show that there are no significant statistical differences in adherence when comparing human with analogue insulin therapy. Strategies to improve treatment adherence are particularly important since they improve the clinical results.

Towards depersonalized abacavir therapy: chemical modification eliminates HLA-B*57 : 01-restricted CD8+ T-cell activation.

PubMed

Naisbitt, Dean J; Yang, Emma L; Alhaidari, Mohammad; Berry, Neil G; Lawrenson, Alexandre S; Farrell, John; Martin, Philip; Strebel, Klaus; Owen, Andrew; Pye, Matthew; French, Neil S; Clarke, Stephen E; O'Neill, Paul M; Park, B Kevin

2015-11-28

Exposure to abacavir is associated with T-cell-mediated hypersensitivity reactions in individuals carrying human leukocyte antigen (HLA)-B57 : 01. To activate T cells, abacavir interacts directly with endogenous HLA-B57 : 01 and HLA-B57 : 01 expressed on the surface of antigen presenting cells. We have investigated whether chemical modification of abacavir can produce a molecule with antiviral activity that does not bind to HLA-B57 : 01 and activate T cells. An interdisciplinary laboratory study using samples from human donors expressing HLA-B57 : 01. Researchers were blinded to the analogue structures and modelling data. Sixteen 6-amino substituted abacavir analogues were synthesized. Computational docking studies were completed to predict capacity for analogue binding within HLA-B57 : 01. Abacavir-responsive CD8 clones were generated to study the association between HLA-B57 : 01 analogue binding and T-cell activation. Antiviral activity and the direct inhibitory effect of analogues on proliferation were assessed. Major histocompatibility complex class I-restricted CD8 clones proliferated and secreted IFNγ following abacavir binding to surface and endogenous HLA-B57 : 01. Several analogues retained antiviral activity and showed no overt inhibitory effect on proliferation, but displayed highly divergent antigen-driven T-cell responses. For example, abacavir and N-propyl abacavir were equally potent at activating clones, whereas the closely related analogues N-isopropyl and N-methyl isopropyl abacavir were devoid of T-cell activity. Docking abacavir analogues to HLA-B57 : 01 revealed a quantitative relationship between drug-protein binding and the T-cell response. These studies demonstrate that the unwanted T-cell activity of abacavir can be eliminated whilst maintaining the favourable antiviral profile. The in-silico model provides a tool to aid the design of safer antiviral agents that may not require a personalized medicines approach to therapy.

Synthesis of the biologically active natural product cyclodepsipeptides apratoxin A and its analogues.

PubMed

Doi, Takayuki

2014-01-01

This paper describes the synthetic studies conducted on a marine natural product, cyclodepsipeptide apratoxin A. Total synthesis of the oxazoline analogue of apratoxin A was achieved. The conversion of oxazoline to thioamide, as well as thioamide formation from a serine-derived compound, were both unsuccessful. However, thiazoline formation from a cysteine-derived compound led to the total synthesis of apratoxin A. An in vivo study on synthetic apratoxin A revealed that it has potent antitumor activity, but with significant toxicity. Solid-phase synthesis of apratoxin A was accomplished using a preformed thiazoline derivative as a coupling unit. This method was used to synthesize several azido-containing analogues as precursors of molecular probes, and these analogues exhibited potent biological activity.

Asymptotics of quasi-classical localized states in 2D system of charged hard-core bosons

NASA Astrophysics Data System (ADS)

Panov, Yu. D.; Moskvin, A. S.

2018-05-01

The continuous quasi-classical two-sublattice approximation is constructed for the 2D system of charged hard-core bosons to explore metastable inhomogeneous states analogous to inhomogeneous localized excitations in magnetic systems. The types of localized excitations are determined by asymptotic analysis and compared with numerical results. Depending on the homogeneous ground state, the excitations are the ferro and antiferro type vortices, the skyrmion-like topological excitations or linear domain walls.

Magnetic Microhelix Coil Structures

NASA Astrophysics Data System (ADS)

Smith, Elliot J.; Makarov, Denys; Sanchez, Samuel; Fomin, Vladimir M.; Schmidt, Oliver G.

2011-08-01

Together with the well-known ferro- and antiferromagnetic ordering, nature has created a variety of complex helical magnetic configurations. Here, we design and investigate three-dimensional microhelix coil structures that are radial-, corkscrew-, and hollow-bar-magnetized. The magnetization configurations of the differently magnetized coils are experimentally revealed by probing their specific dynamic response to an external magnetic field. Helix coils offer an opportunity to realize microscale geometries of the magnetic toroidal moment, observed so far only in bulk multiferroic materials.

REVIEWS OF TOPICAL PROBLEMS: Broken symmetry and magnetoacoustic effects in ferroand antiferromagnetics

NASA Astrophysics Data System (ADS)

Turov, Evgenii A.; Shavrov, Vladimir G.

1983-07-01

This review of some aspects of the magnetoacoustics of ferro- and antiferromagnetic materials has been written in connection with the 25th anniversary of the rise of this field of physics of magnetic phenomena. Primary attention is paid to relatively new problems that have not been reflected in the existing monographs and reviews. The topic is a group of linear magnetoacoustic effects that manifest spontaneous symmetry breaking caused by magnetic ordering in a system of two coupled fields: the magnetization field M (r) and the deformation field uij(r). To some extent these effects are analogous to the Higgs effect in the theory of elementary particles (the Higgs mechanism of the origin of the mass of a particle) or the Meissner effect in the theory of superconductivity. A direct analog of the stated effects is the so-called magnetoelastic gap in the magnon spectrum, while an analog of an accompanying effect is the softening of the quasiacoustic modes interacting with it (up to the vanishing of the corresponding dynamic elastic moduli). However, a characteristic feature of such effects in crystalline (anisotropic) magnetic materials is that they are manifested mainly near points of magnetic (spin-reorientation) phase transitions. This review treats the coupled magnetoelastic waves in ferro- and antiferromagnetic materials of different types that show phase transitions with respect to temperature, magnetic field, or pressure.

Guest Programmable Multistep Spin Crossover in a Porous 2-D Hofmann-Type Material.

PubMed

Murphy, Michael J; Zenere, Katrina A; Ragon, Florence; Southon, Peter D; Kepert, Cameron J; Neville, Suzanne M

2017-01-25

The spin crossover (SCO) phenomenon defines an elegant class of switchable materials that can show cooperative transitions when long-range elastic interactions are present. Such materials can show multistepped transitions, targeted both fundamentally and for expanded data storage applications, when antagonistic interactions (i.e., competing ferro- and antiferro-elastic interactions) drive concerted lattice distortions. To this end, a new SCO framework scaffold, [Fe II (bztrz) 2 (Pd II (CN) 4 )]·n(guest) (bztrz = (E)-1-phenyl-N-(1,2,4-triazol-4-yl)methanimine, 1·n(guest)), has been prepared that supports a variety of antagonistic solid state interactions alongside a distinct dual guest pore system. In this 2-D Hofmann-type material we find that inbuilt competition between ferro- and antiferro-elastic interactions provides a SCO behavior that is intrinsically frustrated. This frustration is harnessed by guest exchange to yield a very broad array of spin transition characters in the one framework lattice (one- (1·(H 2 O,EtOH)), two- (1·3H 2 O) and three-stepped (1·∼2H 2 O) transitions and SCO-deactivation (1)). This variety of behaviors illustrates that the degree of elastic frustration can be manipulated by molecular guests, which suggests that the structural features that contribute to multistep switching may be more subtle than previously anticipated.

Probing the Nanodomain Origin and Phase Transition Mechanisms in (Un)Poled PMN-PT Single Crystals and Textured Ceramics

PubMed Central

Slodczyk, Aneta; Colomban, Philippe

2010-01-01

Outstanding electrical properties of solids are often due to the composition heterogeneity and/or the competition between two or more sublattices. This is true for superionic and superprotonic conductors and supraconductors, as well as for many ferroelectric materials. As in PLZT ferroelectric materials, the exceptional ferro- and piezoelectric properties of the PMN-PT ((1−x)PbMg1/3Nb2/3O3−xPbTiO3) solid solutions arise from the coexistence of different symmetries with long and short scales in the morphotropic phase boundary (MPB) region. This complex physical behavior requires the use of experimental techniques able to probe the local structure at the nanoregion scale. Since both Raman signature and thermal expansion behavior depend on the chemical bond anharmonicity, these techniques are very efficient to detect and then to analyze the subtitle structural modifications with an efficiency comparable to neutron scattering. Using the example of poled (field cooling or room temperature) and unpoled PMN-PT single crystal and textured ceramic, we show how the competition between the different sublattices with competing degrees of freedom, namely the Pb-Pb dominated by the Coulombian interactions and those built of covalent bonded entities (NbO6 and TiO6), determine the short range arrangement and the outstanding ferro- and piezoelectric properties. PMID:28883367

Porous polymer composite membrane based nanogenerator: A realization of self-powered wireless green energy source for smart electronics applications

NASA Astrophysics Data System (ADS)

Ghosh, Sujoy Kumar; Sinha, Tridib Kumar; Mahanty, Biswajit; Jana, Santanu; Mandal, Dipankar

2016-11-01

An efficient, flexible and unvaryingly porous polymer composite membrane based nanogenerator (PPCNG) without any electrical poling treatment has been realised as wireless green energy source to power up smart electronic gadgets. Owing to self-polarized piezo- and ferro-electretic phenomenon of in situ platinum nanoparticles (Pt-NPs) doped porous poly(vinylidenefluoride-co-hexafluoropropylene)-membrane, a simple, inexpensive and scalable PPCNG fabrication is highlighted. The molecular orientations of the -CH2/-CF2 dipoles that cause self-polarization phenomenon has been realized by angular dependent near edge X-ray absorption fine structure spectroscopy. The square-like hysteresis loop with giant remnant polarization, Pr ˜ 68 μC/cm2 and exceptionally high piezoelectric charge coefficient, d33 ˜ - 836 pC/N promises a best suited ferro- and piezo-electretic membrane. The PPCNG exhibits a high electrical throughput such as, ranging from 2.7 V to 23 V of open-circuit voltage (Voc) and 2.9 μA to 24.7 μA of short-circuit current (Isc) under 0.5 MPa to 4.3 MPa of imparted stress amplitude by periodic human finger motion. The harvested mechanical and subsequent electrical energy by PPCNG is shown to transfer wirelessly via visible and infrared transmitter-receiver systems, where 17% and 49% of wireless power transfer efficiency, respectively, has been realized to power up several consumer electronics.

Inhibitory effect of a toxic peptide isolated from a waterbloom of Microcystis sp. (Cyanobacteria) on iron uptake by rabbit reticulocytes.

PubMed

Rojas, M; Nuñez, M T; Zambrano, F

1990-01-01

The effect of a soluble toxin purified from the algae bloom of a eutrophic lake dominated by Microcystis on the receptor-mediated endocytosis of ferro-transferrin in rabbit reticulocytes was studied. The toxin was a very effective inhibitor of cell iron uptake. Kinetic studies using 125I, 59Fe-labeled transferrin indicated that the step of ferrotransferrin internalization was selectively inhibited by the toxin while the surface receptor-binding capacity, the externalization of previously internalized transferrin, and the cellular ATP levels were not affected. These findings indicate that the reduction of iron uptake caused by the toxin is due to inhibition of the internalization of surface-located transferrin-transferrin receptor complexes, perhaps due to a disruption of cytoskeleton integrity.

Molecular modeling of methyl-α-Neu5Ac analogues docked against cholera toxin--a molecular dynamics study.

PubMed

Blessy, J Jino; Sharmila, D Jeya Sundara

2015-02-01

Molecular modeling of synthetic methyl-α-Neu5Ac analogues modified in C-9 position was investigated by molecular docking and molecular dynamics (MD) simulation methods. Methyl-α-Neu5Ac analogues were docked against cholera toxin (CT) B subunit protein and MD simulations were carried out for three Methyl-α-Neu5Ac analogue-CT complexes (30, 10 and 10 ns) to estimate the binding activity of cholera toxin-Methyl-α-Neu5Ac analogues using OPLS_2005 force field. In this study, direct and water mediated hydrogen bonds play a vital role that exist between the methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ)-cholera toxin active site residues. The Energy plot, RMSD and RMSF explain that the simulation was stable throughout the simulation run. Transition of phi, psi and omega angle for the complex was calculated. Molecular docking studies could be able to identify the binding mode of methyl-α-Neu5Ac analogues in the binding site of cholera toxin B subunit protein. MD simulation for Methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ), Methyl-α-9-N-acetyl-9-deoxy-9-amino-Neu5Ac and Methyl-α-9-N-biphenyl-4-acetyl-deoxy-amino-Neu5Ac complex with CT B subunit protein was carried out, which explains the stable nature of interaction. These methyl-α-Neu5Ac analogues that have computationally acceptable pharmacological properties may be used as novel candidates for drug design for cholera disease.

Recent developments in naturally derived antimalarials: cryptolepine analogues.

PubMed

Wright, Colin W

2007-06-01

Increasing resistance of Plasmodium falciparum to commonly used antimalarial drugs has made the need for new agents increasingly urgent. In this paper, the potential of cryptolepine, an alkaloid from the West African shrub Cryptolepis sanguinolenta, as a lead towards new antimalarial agents is discussed. Several cryptolepine analogues have been synthesized that have promising in-vitro and in-vivo antimalarial activity. Studies on the antimalarial modes of action of these analogues indicate that they may have different or additional modes of action to the parent compound. Elucidation of the mode of action may facilitate the development of more potent antimalarial cryptolepine analogues.

[Splenic nodules and sickle cell anemia].

PubMed

Jouini, S; Sehili, S; Mokrani, A; Ayadi, K; Fakunle, Y; Daghfous, M H; Ladeb, M F

2001-11-01

We report 4 patients with sickle cell anemia presenting with intra-splenic benign nodules corresponding to islands of preserved tissue within splenic ferro-calcinosis. Ultrasound, CT and MRI findings were evaluated and compared to a follow-up study by ultrasound and CT done after 6 to 12 months. Ultrasound showed multiple well-defined rounded nodules appearing hypoechoic compared to the rest of the spleen that was hyperechoic. On CT, the nodules were homogenous, hypodense relative to the spleen, isodense to the liver in 3 cases and hypodense to the liver in 1 case. On MRI, the nodules appeared relatively hyperintense within low-signal-intensity spleens. The ultrasound and CT follow-up study demonstrated no remarkable change. In sickle cell patients, intra-splenic benign nodules corresponding to normal splenic tissue may be identified on imaging studies. The differential diagnosis is discussed.

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

PubMed

Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

1991-11-01

To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and 68.9 +/- 3.5 from 2.5 h onward; and hexameric insulin 20.7 +/- 1.9 from 0 to 2 h, 45.6 +/- 5.0 from 2.5 to 5 h, and 70.6 +/- 6.3 from 5 h onward. Association state is a major determinant of rates of absorption of insulin and insulin analogues. The lag phase and the subsequent increasing rate of subcutaneous soluble insulin absorption can be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process.

Absorption kinetics and action profiles of subcutaneously administered insulin analogues (AspB9GluB27, AspB10, AspB28) in healthy subjects.

PubMed

Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

1991-11-01

The subcutaneous absorption and resulting changes in plasma insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations after subcutaneous bolus injection of three soluble human insulin analogues (AspB9GluB27, monomeric; AspB28, mixture of monomers and dimers; and AspB10, dimeric) and soluble human insulin were evaluated. Fasting healthy male volunteers (n = 7) were studied on five occasions 1 wk apart randomly receiving 0.6 nmol.kg-1 s.c. 125I-labeled AspB10 or soluble human insulin (Novolin R, Novo, Copenhagen); 1st study and 0.6 nmol.kg-1 s.c. 125I-labeled AspB28, AspB9GluB27 or soluble human insulin (2nd study). Residual radioactivity at the injection site was measured over 8 h with frequent venous sampling for plasma immunoreactive insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations. The three analogues were absorbed 2-3 times faster than human insulin. The mean +/- SE time to 50% residual radioactivity was 94 +/- 6 min for AspB10 compared with 184 +/- 10 min for human insulin (P less than 0.001), 83 +/- 8 min for AspB28 (P less than 0.005), and 63 +/- 9 min for AspB9GluB27 (P less than 0.001) compared with 182 +/- 21 min for human insulin. delta Peak plasma insulin analogue levels were significantly higher after each analogue than after human insulin (P less than 0.005). With all three analogues, the mean hypoglycemic nadir occurred earlier at 61-65 min postinjection compared with 201-210 min for the reference human insulins (P less than 0.005). The magnitude of the hypoglycemic nadir was greater after AspB9GluB27 (P less than 0.05) and AspB28 (P less than 0.001) compared with human insulin. There was a significantly faster onset and offset of responses in C-peptide and intermediary metabolite levels after the analogues than after human insulin (P less than 0.05). The rapid absorption and biological actions of these analogues offer potential therapeutic advantages over the current short-acting neutral soluble insulins.

Rheological and physical characteristics of crustal-scaled materials for centrifuge analogue modelling

NASA Astrophysics Data System (ADS)

Waffle, Lindsay; Godin, Laurent; Harris, Lyal B.; Kontopoulou, M.

2016-05-01

We characterize a set of analogue materials used for centrifuge analogue modelling simulating deformation at different levels in the crust simultaneously. Specifically, we improve the rheological characterization in the linear viscoelastic region of materials for the lower and middle crust, and cohesive synthetic sands without petroleum-binding agents for the upper crust. Viscoelastic materials used in centrifuge analogue modelling demonstrate complex dynamic behaviour, so viscosity alone is insufficient to determine if a material will be an effective analogue. Two series of experiments were conducted using an oscillating bi-conical plate rheometer to measure the storage and loss moduli and complex viscosities of several modelling clays and silicone putties. Tested materials exhibited viscoelastic and shear-thinning behaviour. The silicone putties and some modelling clays demonstrated viscous-dominant behaviour and reached Newtonian plateaus at strain rates < 0.5 × 10-2 s-1, while other modelling clays demonstrated elastic-dominant power-law relationships. Based on these results, the elastic-dominant modelling clay is recommended as an analogue for basement cratons. Inherently cohesive synthetic sands produce fine-detailed fault and fracture patterns, and developed thrust, strike-slip, and extensional faults in simple centrifuge test models. These synthetic sands are recommended as analogues for the brittle upper crust. These new results increase the accuracy of scaling analogue models to prototype. Additionally, with the characterization of three new materials, we propose a complete lithospheric profile of analogue materials for centrifuge modelling, allowing future studies to replicate a broader range of crustal deformation behaviours.

Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6.

PubMed Central

Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

1989-01-01

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells. PMID:2548207

Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6.

PubMed

Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

1989-08-01

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.

Clinical study of a digital vs an analogue hearing aid.

PubMed

Bille, M; Jensen, A M; Kjaerbøl, E; Vesterager, V; Sibelle, P; Nielsen, H

1999-01-01

Digital signal processing in hearing instruments has brought new perspectives to the compensation of hearing impairment and may result in alleviation of the adverse effects of hearing problems. This study compares a commercially available digital signal processing hearing aid (HA) (Senso) with a modern analogue HA with programmable fitting (Logo). The HAs tested are identical in appearance and, in spite of a different mode of operation, the study design ensured blinding of the test subjects. Outcome parameters were: improvements in speech recognition score in noise (deltaSRSN) with the HAs; overall preference for HA; overall satisfaction; and various measures of HA performance evaluated by a self-assessment questionnaire. A total of 28 experienced HA users with sensorineural hearing impairment were included and 25 completed the trial. No significant differences were found in deltaSRSN between the two HAs. Eleven subjects indicated an overall preference for the digital HA, 10 preferred the analogue HA and 4 had no preference. Concerning overall satisfaction, 8 subjects rated the digital HA superior to the analogue one, whereas 7 indicated a superior rating for the analogue HA and 10 rated the HAs equal. Acceptability of noise from traffic was the only outcome parameter which gave a significant difference between the HAs in favour of the digital HA. It is concluded that there are no significant differences in outcome between the digital and analogue signal processing HAs tested by these experienced HA-users.

Activities of dl-α-Difluoromethylarginine and Polyamine Analogues against Cryptosporidium parvum Infection in a T-Cell Receptor Alpha-Deficient Mouse Model▿

PubMed Central

Yarlett, Nigel; Waters, W. Ray; Harp, James A.; Wannemuehler, Michael J.; Morada, Mary; Bellcastro, Josephine; Upton, Steve J.; Marton, Laurence J.; Frydman, Benjamin J.

2007-01-01

The in vivo effectiveness of a series of conformationally restricted polyamine analogues alone and selected members in combination with dl-α-difluoromethylarginine against Cryptosporidium parvum infection in a T-cell receptor alpha-deficient mouse model was tested. Polyamine analogues were selected from the extended bis(ethyl)-sym-homospermidine or bis(ethyl)-spermine backbone having cis or trans double bonds at the center of the molecule. The cis isomers were found to have significantly greater efficacy in both preventing and curing infection in a mouse model than the trans polyamine analogues when tested in a T-cell receptor alpha-deficient mouse model. When tested in combination with dl-α-difluoromethylarginine, the cis-restricted analogues were found to be more effective in preventing oocyst shedding. This study demonstrates the potential of polyamine analogues as anticryptosporidial agents and highlights the presence of multiple points in polyamine synthesis by this parasite that are susceptible to inhibition resulting in growth inhibition. PMID:17242149

FMR thermomagnetic studies up to 900 C of lunar soils and potential magnetic analogues. [Ferromagnetic Resonance studies

NASA Technical Reports Server (NTRS)

Morris, R. V.; Gibbons, R. V.; Hoerz, F.

1975-01-01

Using a recently developed furnace, ferromagnetic resonance (FMR) thermomagnetic studies up to 900 C were employed to measure the Curie points of the superparamagnetic (SP) and single domain (SD) particles in lunar soils and potential magnetic analogue materials. Based on measured Curie points of 775 C, the SP and SD particles in lunar soils 10084-853, 12070-29, 14161-46, and 67010-4 are essentially pure metallic Fe. Synthetic and terrestrial samples containing magnetite, titanomaghemites, and magnetite-like particles have measured Curie points below 600 C are thus not magnetic analogues of lunar soils.

Controlling of N-alkylpolyamine analogue metabolism by selective deuteration.

PubMed

Ucal, Sebahat; Häkkinen, Merja R; Alanne, Aino-Liisa; Alhonen, Leena; Vepsäläinen, Jouko; Keinänen, Tuomo A; Hyvönen, Mervi T

2018-02-14

Replacing protium with deuterium is an efficient method to modulate drug metabolism. N -alkylated polyamine analogues are polyamine antimetabolites with proven anticancer efficacy. We have characterized earlier the preferred metabolic routes of N 1 , N 12 -diethylspermine (DESpm), N 1 -benzyl- N 12 -ethylspermine (BnEtSpm) and N 1 , N 12 -dibenzylspermine (DBSpm) by human recombinant spermine oxidase (SMOX) and acetylpolyamine oxidase (APAO). Here, we studied the above analogues, their variably deuterated counterparts and their metabolites as substrates and inhibitors of APAO, SMOX, semicarbazide-sensitive amine oxidase (SSAO), diamine oxidase (DAO) and monoamine oxidases. We found that targeted deuteration efficiently redirected the preferable cleavage site and suppressed reaction rate by APAO and SMOX in vitro We found a three- to six-fold decline in V max with moderate variable effect on K m when deuterium was located at the preferred hydrogen abstraction site of the analogue. We also found some of the metabolites to be potent inhibitors of DAO and SSAO. Surprisingly, analogue deuteration did not markedly alter the anti-proliferative efficacy of the drugs in DU145 prostate cancer cells, while in mouse embryonic fibroblasts, which had higher basal APAO and SMOX activities, moderate effect was observed. Interestingly, the anti-proliferative efficacy of the analogues did not correlate with their ability to suppress polyamine biosynthetic enzymes, induce spermidine/spermine- N 1 -acetyltransferase or deplete intracellular polyamine levels, but correlated with their ability to induce SMOX. Our data show that selective deuteration of N -alkyl polyamine analogues enables metabolic switching, offering the means for selective generation of bioactive metabolites inhibiting, e.g. SSAO and DAO, thus setting a novel basis for in vivo studies of this class of analogues. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Exploration of charge states of balanol analogues acting as ATP-competitive inhibitors in kinases.

PubMed

Hardianto, Ari; Yusuf, Muhammad; Liu, Fei; Ranganathan, Shoba

2017-12-28

(-)-Balanol is an ATP mimic that inhibits protein kinase C (PKC) isozymes and cAMP-dependent protein kinase (PKA) with limited selectivity. While PKA is a tumour promoter, PKC isozymes act as tumour promoters or suppressors, depending on the cancer type. In particular, PKCε is frequently implicated in cancer promotion, making it a potential target for anticancer drugs. To improve isozyme selectivity of balanol, exhaustive structural and activity relationship (SAR) studies have been performed in the last two decades, but with limited success. More recently, fluorination on balanol has shown improved selectivity for PKCε, although the fluorine effect is not yet clearly understood. Understanding the origin to this fluorine-based selectivity will be valuable for designing better balanol-based ATP mimicking inhibitors. Computational approaches such as molecular dynamics (MD) simulations can decipher the fluorine effect, provided that correct charges have been assigned to a ligand. Balanol analogues have multiple ionisable functional groups and the effect of fluorine substitutions on the exact charge state of each analogue bound to PKA and to PKCε needs to be thoroughly investigated in order to design highly selective inhibitors for therapeutic applications. We explored the charge states of novel fluorinated balanol analogues using MD simulations. For different potential charge states of these analogues, Molecular Mechanics Generalized Born Surface Area (MMGBSA) binding energy values were computed. This study suggests that balanol and the most potent fluorinated analogue (5S fluorine substitution on the azepane ring), have charges on the azepane ring (N1), and the phenolic (C6''OH) and the carboxylate (C15''O 2 H) groups on the benzophenone moiety, when bound to PKCε as well as PKA. To the best our knowledge, this is the first study showing that the phenolate group is charged in balanol and its analogues binding to the ATP site of PKCε. Correct charge assignments of ligands are important to obtain predicted binding energy values from MD simulations that reflect experimental values. Both fluorination and the local enzymatic environment of the ATP site can influence the exact charge states of balanol analogues. Overall, this study is highly valuable for further rational design of potent balanol analogues selective to PKCε.

4-Alkylated homoibotenic acid (HIBO) analogues: versatile pharmacological agents with diverse selectivity profiles towards metabotropic and ionotropic glutamate receptor subtypes.

PubMed

Madsen, Ulf; Pickering, Darryl S; Nielsen, Birgitte; Bräuner-Osborne, Hans

2005-01-01

4-Alkylated analogues of homoibotenic acid (HIBO) have previously shown high potency and selectivity at ionotropic and metabotropic glutamic acid receptor (iGluR and mGluR) subtypes. Compounds with different selectivity profiles are valuable pharmacological tools for neuropharmacological studies, and the series of 4-alkyl-HIBO analogues have been extended in this paper in the search for versatile agents. Pharmacological characterization of five new analogues, branched and unbranched 4-alkyl-HIBO analogues, have been carried out. The present compounds are all weak antagonists at Group I mGluRs (mGluR1 and 5) presenting only small differences in potencies (Ki values ranging from 89 to 670 microM). Affinities were studied at native and cloned iGluRs, and the compounds described show preference for the AMPA receptor subtypes GluR1 and 2 over GluR3 and 4. However, compared to previous 4-alkyl-HIBO analogues, these compounds show a remarkably high affinity for the Kain preferring subtype GluR5. The observed GluR5 affinities were either similar or higher compared to their GluR1 and 2 affinity. Isopropyl-HIBO showed the highest affinity for GluR5 (Ki=0.16 microM), and represents a unique compound with high affinity towards the three subtypes GluR1, 2 and 5. In general, these compounds represent new selectivity profiles compared to previously reported Glu receptor analogues.

Surfactin analogues produced by Bacillus subtilis strains grown on rapeseed cake

NASA Astrophysics Data System (ADS)

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.

Structure activity relationship study of curcumin analogues toward the amyloid-beta aggregation inhibitor.

PubMed

Endo, Hitoshi; Nikaido, Yuri; Nakadate, Mamiko; Ise, Satomi; Konno, Hiroyuki

2014-12-15

Inhibition of the amyloid β aggregation process could possibly prevent the onset of Alzheimer's disease. In this article, we report a structure-activity relationship study of curcumin analogues for anti amyloid β aggregation activity. Compound 7, the ideal amyloid β aggregation inhibitor in vitro among synthesized curcumin analogues, has not only potent anti amyloid β aggregation effects, but also water solubility more than 160 times that of curcumin. In addition, new approaches to improve water solubility of curcumin-type compounds are proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of a digital and an optical analogue hand-held refractometer for the measurement of canine urine specific gravity.

PubMed

Paris, J K; Bennett, A D; Dodkin, S J; Gunn-Moore, D A

2012-05-05

Urine specific gravity (USG) is used clinically as a measure of urine concentration, and is routinely assessed by refractometry. A comparison between optical analogue and digital refractometers for evaluation of canine urine has not been reported. The aim of this study was to compare a digital and an optical analogue hand-held refractometer for the measurement of canine USG, and to assess correlation with urine osmolality. Prospective study. Free-catch urine samples were collected from 285 hospitalised adult dogs, and paired USG readings were obtained with a digital and an optical analogue refractometer. In 50 dogs, urine osmolality was also measured using a freezing point depression osmometer. There was a small but statistically significant difference between the two refractometers (P<0.001), with the optical analogue refractometer reading higher than the digital refractometer (mean difference 0.0006, sd 0.0012). Paired refractometer measurements varied by <0.002 in 91.5 per cent of cases. The optical analogue and digital refractometer readings showed excellent correlation with osmolality (r=0.980 and r=0.977, respectively, P<0.001 in both cases). Despite statistical significance, the difference between the two refractometers is unlikely to be clinically significant. Both instruments provide an accurate assessment of USG in dogs.

Electrolytic Reduction of Titania Slag in Molten Calcium Chloride Bath

NASA Astrophysics Data System (ADS)

Mohanty, Jayashree

2012-05-01

Ferro-titanium is prepared by direct electrolytic reduction of titania-rich slag obtained from plasma smelting of ilmenite in molten CaCl2. The product after electro-reduction is characterized by x-ray diffraction, scanning electron microscopy, and electron probe microanalysis. The electrolysis is carried out at a cell voltage of 3.0 V, taking graphite as the electrolysis cell as well as the anode, and a titania-rich slag piece wrapped by a nichrome wire is used as the cathode.

Non-Volatile Memory Technology Symposium 2001: Proceedings

NASA Technical Reports Server (NTRS)

Aranki, Nazeeh; Daud, Taher; Strauss, Karl

2001-01-01

This publication contains the proceedings for the Non-Volatile Memory Technology Symposium 2001 that was held on November 7-8, 2001 in San Diego, CA. The proceedings contains a a wide range of papers that cover current and new memory technologies including Flash memories, Magnetic Random Access Memories (MRAM and GMRAM), Ferro-electric RAM (FeRAM), and Chalcogenide RAM (CRAM). The papers presented in the proceedings address the use of these technologies for space applications as well as radiation effects and packaging issues.

Identification of human-selective analogues of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA)

PubMed Central

Tijono, S M; Guo, K; Henare, K; Palmer, B D; Wang, L-C S; Albelda, S M; Ching, L-M

2013-01-01

Background: Species selectivity of DMXAA (5,6-dimethylxanthenone-4-acetic acid, Vadimezan) for murine cells over human cells could explain in part the recent disappointing phase III trials clinical results when preclinical studies were so promising. To identify analogues with greater human clinical potential, we compared the activity of xanthenone-4-acetic acid (XAA) analogues in murine or human cellular models. Methods: Analogues with a methyl group systematically substituted at different positions of the XAA backbone were evaluated for cytokine induction in cultured murine or human leukocytes; and for anti-vascular effects on endothelial cells on matrigel. In vivo antitumour activity and cytokine production by stromal or cancer cells was measured in human A375 and HCT116 xenografts. Results: Mono-methyl XAA analogues with substitutions at the seventh and eighth positions were the most active in stimulating human leukocytes to produce IL-6 and IL-8; and for inhibition of tube formation by ECV304 human endothelial-like cells, while 5- and 6-substituted analogues were the most active in murine cell systems. Conclusion: Xanthenone-4-acetic acid analogues exhibit extreme species selectivity. Analogues that are the most active in human systems are inactive in murine models, highlighting the need for the use of appropriate in vivo animal models in selecting clinical candidates for this class of compounds. PMID:23481185

Human factors research as part of a Mars exploration analogue mission on Devon Island

NASA Astrophysics Data System (ADS)

Binsted, Kim; Kobrick, Ryan L.; Griofa, Marc Ó.; Bishop, Sheryl; Lapierre, Judith

2010-06-01

Human factors research is a critical element of space exploration as it provides insight into a crew's performance, psychology and interpersonal relationships. Understanding the way humans work in space-exploration analogue environments permits the development and testing of countermeasures for and responses to potential hazardous situations, and can thus help improve mission efficiency and safety. Analogue missions, such as the one described here, have plausible mission constraints and operational scenarios, similar to those that a real Mars crew would experience. Long duration analogue studies, such as those being conducted at the Flashline Mars Arctic Research Station (FMARS) on Devon Island, Canada, offer an opportunity to study mission operations and human factors in a semi-realistic environment, and contribute to the design of missions to explore the Moon and Mars. The FMARS XI Long Duration Mission (F-XI LDM) was, at four months, the longest designed analogue Mars mission conducted to date, and thus provides a unique insight into human factors issues for long-duration space exploration. Here, we describe the six human factors studies that took place during F-XI LDM, and give a summary of their results, where available. We also present a meta-study, which examined the impact of the human-factors research itself on crew schedule and workload. Based on this experience, we offer some lessons learnt: some aspects (perceived risk and crew motivation, for example) of analogue missions must be realistic for study results to be valid; human factors studies are time-consuming, and should be fully integrated into crew schedules; and crew-ground communication and collaboration under long-term exploration conditions can present serious challenges.

Prediction of Layer Thickness in Molten Borax Bath with Genetic Evolutionary Programming

NASA Astrophysics Data System (ADS)

Taylan, Fatih

2011-04-01

In this study, the vanadium carbide coating in molten borax bath process is modeled by evolutionary genetic programming (GEP) with bath composition (borax percentage, ferro vanadium (Fe-V) percentage, boric acid percentage), bath temperature, immersion time, and layer thickness data. Five inputs and one output data exist in the model. The percentage of borax, Fe-V, and boric acid, temperature, and immersion time parameters are used as input data and the layer thickness value is used as output data. For selected bath components, immersion time, and temperature variables, the layer thicknesses are derived from the mathematical expression. The results of the mathematical expressions are compared to that of experimental data; it is determined that the derived mathematical expression has an accuracy of 89%.

Effects of analogues of hydra peptide morphogen on DNA synthesis in the myocardium of newborn albino rats.

PubMed

Sazonova, E N; Yakovenko, I G; Kryzhanovskaya, S Yu; Budylev, A A; Timoshin, S S

2012-01-01

DNA-synthetic activity of myocardial cells was studied by (3)H-thymidine autoradiography in newborn albino rats after intraperitoneal injection of hydra peptide morphogen and its analogues. Administration of hydra peptide morphogen stimulated proliferative activity in the myocardium. Short analogues of hydra peptide morphogen, 6C and 3C peptides, produced a similar effect. Administration of arginine-containing analogue of hydra peptide morphogen significantly reduced the number of DNA-synthesizing nuclei in the ventricular myocardium of newborn albino rats. The role of the structure of the peptide molecule in the realization of the morphogenetic effects of hydra peptide morphogen is discussed.

Engineering Silicone Rubbers for In vitro Studies: Creating AAA Models and ILT Analogues with Physiological Properties

PubMed Central

Corbett, T.J.; Doyle, B.J.; Callanan, A.; Walsh, M.T.; McGloughlin, T.M

2010-01-01

Background In vitro studies of abdominal aortic aneurysm (AAA) have been widely reported. Frequently mock artery models with intraluminal thrombus (ILT) analogues are used to mimic the AAA in vivo. While the models used may be physiological, their properties are frequently either not reported or investigated. Method of Approach This study is concerned with the testing and characterisation of previously used vessel analogue materials and the development of new materials for the manufacture of AAA models. These materials were used in conjunction with a previously validated injection moulding technique to manufacture AAA models of ideal geometry. To determine the model properties (stiffness (β) and compliance) the diameter change of each AAA model was investigated under incrementally increasing internal pressures and compared to published in vivo studies to determine if the models behaved physiologically. A FEA study was implemented to determine if the pressure – diameter change behaviour of the models could be predicted numerically. ILT analogues were also manufactured and characterised. Ideal models were manufactured with ILT analogue internal to the aneurysm region and the effect of the ILT analogue on the model compliance and stiffness was investigated. Results The wall materials had similar properties to aortic tissue at physiological pressures (Einit 2.22MPa and 1.57MPa (aortic tissue: 1.8MPa)). ILT analogues had similar Young’s modulus to the medial layer of ILT (0.24 and 0.33MPa (ILT: 0.28MPa)). All models had aneurysm sac compliance in the physiological range (2.62 – 8.01×10-4/mmHg (AAA in vivo: 1.8 – 9.4×10-4/mmHg)). The necks of our AAA models had similar stiffness to healthy aortas (20.44 – 29.83 (healthy aortas in vivo: 17.5±5.5)). Good agreement was seen between the diameter changes due to pressurisation in the experimental and FEA wall models with a maximum error of 7.3% at 120mmHg. It was also determined that the inclusion of ILT analogue in the sac of our models could have an effect on the compliance of the model neck. Conclusions Ideal AAA models with physiological properties were manufactured. The behaviour of these models due to pressurisation was predicted using FEA, validating this technique for the future design of realistic, physiological AAA models. Addition of ILT analogues in the aneurysm sac was shown to affect neck behaviour. This could have implications for endovascular AAA repair due to the importance of the neck for stent-graft fixation. PMID:20524746

Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bajusz, S.; Janaky, T.; Csernus, V.J.

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Ofmore » the peptides prepared, (D-Mel{sup 6})LH-RH (SB-05) and (Ac-D-Nal(2){sup 1},D-Phe(pCl){sup 2},D-Pal(3){sup 3},Arg{sup 5},D-Mel{sup 6},D-Ala{sup 10})LH-RH (SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine) possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel{sup 6} analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.« less

Novel sst2-selective somatostatin agonists. Three-dimensional consensus structure by NMR

PubMed Central

Grace, Christy Rani R.; Erchegyi, Judit; Koerber, Steven C.; Reubi, Jean Claude; Rivier, Jean; Riek, Roland

2008-01-01

The three-dimensional NMR structures of six octapeptide agonist analogues of somatostatin (SRIF) in the free form are described. These analogues, with the basic sequence H-DPhe/Phe2-c[Cys3-Xxx7-DTrp8-Lys9-Thr10-Cys14]-Thr-NH2 (the numbering refers to the position in native SRIF), with Xxx7 being Ala/Aph, exhibit potent and highly selective binding to human SRIF type 2 (sst2) receptors. The backbone of these sst2-selective analogues have the usual type-II’ β-turn reported in the literature for sst2/3/5-subtype-selective analogues. Correlating biological results and NMR studies led to the identification of the side chains of DPhe2, DTrp8 and Lys9 as the necessary components of the sst2 pharmacophore. This is the first study to show that the aromatic ring at position 7 (Phe7) is not critical for sst2 binding and that it plays an important role in sst3 and sst5 binding. This pharmacophore is therefore different from that proposed by others for sst2/3/5 analogues. PMID:16854054

Design and preliminary structure-activity relationship of redox-silent semisynthetic tocotrienol analogues as inhibitors for breast cancer proliferation and invasion.

PubMed

Elnagar, Ahmed Y; Wali, Vikram B; Sylvester, Paul W; El Sayed, Khalid A

2010-01-15

Vitamin E (VE) is a generic term that represents a family of compounds composed of various tocopherol and tocotrienol isoforms. Tocotrienols display potent anti-angiogenic and antiproliferative activities. Redox-silent tocotrienol analogues also display potent anticancer activity. The ultimate objective of this study was to develop semisynthetically C-6-modified redox-silent tocotrienol analogues with enhanced antiproliferative and anti-invasive activities as compared to their parent compound. Examples of these are carbamate and ether analogues of alpha-, gamma-, and delta-tocotrienols (1-3). Various aliphatic, olefinic, and aromatic substituents were used. Steric limitation, electrostatic, hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) properties were varied at this position and the biological activities of these derivatives were tested. Three-dimensional quantitative structure-activity relationship (3D QSAR) studies were performed using Comparative Molecular Field (CoMFA) and Comparative Molecular Similarity Indices Analyses (CoMSIA) to better understand the structural basis for biological activity and guide the future design of more potent VE analogues. Copyright 2009 Elsevier Ltd. All rights reserved.

1,25-Dihydroxyvitamin D3 and its analogues increase catalase at the mRNA, protein and activity level in a canine transitional carcinoma cell line.

PubMed

Middleton, R P; Nelson, R; Li, Q; Blanton, A; Labuda, J A; Vitt, J; Inpanbutr, N

2015-12-01

Antioxidant enzymes, such as catalase, superoxide dismutases (SOD), MnSOD and Cu/ZnSOD, protect cells by scavenging reactive oxygen species (ROS). Numerous studies have reported the anti-cancer effects of 1,25-dihydroxyvitamin D3 (calcitriol) and its related analogues, seocalcitol and analogue V. In this study, canine bladder transitional cell carcinoma (cbTCC) cells were used to determine effects of calcitriol and its related analogues on antioxidant enzyme gene expression, protein expression and activity. Catalase mRNA was increased in response to calcitriol (10(-7) M), and seocalcitol (10(-7) and 10(-9) M). MnSOD mRNA was decreased in response to calcitriol at 10(-7) M. Catalase was significantly increased in response to calcitriol (10(-7) and 10(-9) M), and seocalcitol (10(-9) M). Catalase enzymatic activity increased in response to calcitriol, seocalcitol and analogue V (10(-9) M). In addition, global gene expression analysis identified the involvement of mitogen-activated protein kinase (MAPK) signalling in cbTCC's response to calcitriol and seocalcitol treatment.

A novel lunar bed rest analogue.

PubMed

Cavanagh, Peter R; Rice, Andrea J; Licata, Angelo A; Kuklis, Matthew M; Novotny, Sara C; Genc, Kerim O; Englehaupt, Ricki K; Hanson, Andrea M

2013-11-01

Humans will eventually return to the Moon and thus there is a need for a ground-based analogue to enable the study of physiological adaptations to lunar gravity. An important unanswered question is whether or not living on the lunar surface will provide adequate loading of the musculoskeletal system to prevent or attenuate the bone loss that is seen in microgravity. Previous simulations have involved tilting subjects to an approximately 9.5 degrees angle to achieve a lunar gravity component parallel to the long-axis of the body. However, subjects in these earlier simulations were not weight-bearing, and thus these protocols did not provide an analogue for load on the musculoskeletal system. We present a novel analogue which includes the capability to simulate standing and sitting in a lunar loading environment. A bed oriented at a 9.5 degrees angle was mounted on six linear bearings and was free to travel with one degree of freedom along rails. This allowed approximately 1/6 body weight loading of the feet during standing. "Lunar" sitting was also successfully simulated. A feasibility study demonstrated that the analogue was tolerated by subjects for 6 d of continuous bed rest and that the reaction forces at the feet during periods of standing were a reasonable simulation of lunar standing. During the 6 d, mean change in the volume of the quadriceps muscles was -1.6% +/- 1.7%. The proposed analogue would appear to be an acceptable simulation of lunar gravity and deserves further exploration in studies of longer duration.

3D-QSAR study and design of 4-hydroxyamino α-pyranone carboxamide analogues as potential anti-HCV agents

NASA Astrophysics Data System (ADS)

Li, Wenlian; Xiao, Faqi; Zhou, Mingming; Jiang, Xuejin; Liu, Jun; Si, Hongzong; Xie, Meng; Ma, Xiuting; Duan, Yunbo; Zhai, Honglin

2016-09-01

The three dimensional-quantitative structure activity relationship (3D-QSAR) study was performed on a series of 4-hydroxyamino α-pyranone carboxamide analogues using comparative molecular similarity indices analysis (COMSIA). The purpose of the present study was to develop a satisfactory model providing a reliable prediction based on 4-hydroxyamino α-pyranone carboxamide analogues as anti-HCV (hepatitis C virus) inhibitors. The statistical results and the results of validation of this optimum COMSIA model were satisfactory. Furthermore, analysis of the contour maps helped to provide guidelines for finding structural requirement. Therefore, the satisfactory results from this study may provide useful guidelines for drug development of anti-HCV inhibitors.

Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus.

PubMed

Hogan, Andrew E; Gaoatswe, Gadintshware; Lynch, Lydia; Corrigan, Michelle A; Woods, Conor; O'Connell, Jean; O'Shea, Donal

2014-04-01

Glucagon-like peptide 1 (GLP-1) is a gut hormone used in the treatment of type 2 diabetes mellitus. There is emerging evidence that GLP-1 has anti-inflammatory activity in humans, with murine studies suggesting an effect on macrophage polarisation. We hypothesised that GLP-1 analogue therapy in individuals with type 2 diabetes mellitus would affect the inflammatory macrophage molecule soluble CD163 (sCD163) and adipocytokine profile. We studied ten obese type 2 diabetes mellitus patients starting GLP-1 analogue therapy at a hospital-based diabetes service. We investigated levels of sCD163, TNF-α, IL-1β, IL-6, adiponectin and leptin by ELISA, before and after 8 weeks of GLP-1 analogue therapy. GLP-1 analogue therapy reduced levels of the inflammatory macrophage activation molecule sCD163 (220 ng/ml vs 171 ng/ml, p < 0.001). This occurred independent of changes in body weight, fructosamine and HbA1c. GLP-1 analogue therapy was associated with a decrease in levels of the inflammatory cytokines TNF-α (264 vs 149 pg/ml, p < 0.05), IL-1β (2,919 vs 748 pg/ml, p < 0.05) and IL-6 (1,379 vs 461 pg/ml p < 0.05) and an increase in levels of the anti-inflammatory adipokine adiponectin (4,480 vs 6,290 pg/ml, p < 0.002). In individuals with type 2 diabetes mellitus, GLP-1 analogue therapy reduces the frequency of inflammatory macrophages. This effect is not dependent on the glycaemic or body weight effects of GLP-1.

Interval-level measurement with visual analogue scales in Internet-based research: VAS Generator.

PubMed

Reips, Ulf-Dietrich; Funke, Frederik

2008-08-01

The present article describes VAS Generator (www.vasgenerator.net), a free Web service for creating a wide range of visual analogue scales that can be used as measurement devices in Web surveys and Web experimentation, as well as for local computerized assessment. A step-by-step example for creating and implementing a visual analogue scale with visual feedback is given. VAS Generator and the scales it generates work independently of platforms and use the underlying languages HTML and JavaScript. Results from a validation study with 355 participants are reported and show that the scales generated with VAS Generator approximate an interval-scale level. In light of previous research on visual analogue versus categorical (e.g., radio button) scales in Internet-based research, we conclude that categorical scales only reach ordinal-scale level, and thus visual analogue scales are to be preferred whenever possible.

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

PubMed

Usman, Afia; Ahmad, Masood

2016-09-01

Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful? Copyright © 2016. Published by Elsevier Ltd.

Harmony of computational quantum chemistry and experimental chemistry: Comprehensive DFT studies, microsynthesis, and characterization of mustard gas polysulfide analogues

NASA Astrophysics Data System (ADS)

Saeidian, Hamid; Faraz, Sajjad Mousavi; Mirjafary, Zohreh; Babri, Mehran

2018-05-01

After microsynthesis, structures of mustard gas polysulfide analogues were characterized using electron impact (EI) mass spectrometry. General EI fragmentation pathways for such compounds are proposed. The structure of sulfur mustard (HD) and its two other polysulfide analogues have been examined through B3LYP/6-311++G(2d, 2p) calculations. Geometrical analysis of HD shows that the calculated bond distances are satisfactorily comparable with experimental results. Calculated NMR chemical shifts for HD also were compared with experimental data, indicating good agreement both for 1H and 13C atoms. The vibrational frequencies of HD and polysulfide analogues have been precisely assigned. At the end, based on visual inspection of lowest unoccupied molecular orbitals and the relative difference in the total energies of their episulfonium ions, relative reactivity of HD and its polysulfide analogues were investigated.

Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin

PubMed Central

Holden, Sarah E; Poole, Chris D; Morgan, Christopher Ll

2011-01-01

Introduction Insulin analogues have become increasingly popular despite their greater cost compared with human insulin. The aim of this study was to calculate the incremental cost to the National Health Service (NHS) of prescribing analogue insulin preparations instead of their human insulin alternatives. Methods Open-source data from the four UK prescription pricing agencies from 2000 to 2009 were analysed. Cost was adjusted for inflation and reported in UK pounds at 2010 prices. Results Over the 10-year period, the NHS spent a total of £2732 million on insulin. The total annual cost increased from £156 million to £359 million, an increase of 130%. The annual cost of analogue insulin increased from £18.2 million (12% of total insulin cost) to £305 million (85% of total insulin cost), whereas the cost of human insulin decreased from £131 million (84% of total insulin cost) to £51 million (14% of total insulin cost). If it is assumed that all patients using insulin analogues could have received human insulin instead, the overall incremental cost of analogue insulin was £625 million. Conclusion Given the high marginal cost of analogue insulin, adherence to prescribing guidelines recommending the preferential use of human insulin would have resulted in considerable financial savings over the period. PMID:22021891

The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs.

PubMed

Adriaens, E; Dierckens, K; Bauters, T G; Nelis, H J; van Goethem, F; Vanparys, P; Remon, J P

2001-07-01

The objective of this study was to evaluate the mucosal toxicity of different benzalkonium chloride (BAC) analogues using slugs as the alternative test organism. The effect of different BAC analogues on the mucosal tissue of slugs was determined from the protein, lactate dehydrogenase, and alkaline phosphatase released from the foot mucosa after treatment. Additionally, mucus production and reduction in body weight of the slugs were measured. The eye irritation potency of the molecules was evaluated with the Bovine Corneal Opacity and Permeability (BCOP) assay. The antimicrobial activity of the different BAC analogues was also assessed. All BAC analogues induced severe damage to the mucosal epithelium of the slugs, and the irritation increased with decreasing alkyl chain length: BAC-C16 < BAC-C14 < BAC-C12 approximately BAC-mix. A similar ranking was obtained with the BCOP assay for eye irritation. The relative order of activities among the three BAC analogues was the same, i.e., BAC-C14 > or = BAC-C16 > BAC-C12. The BAC-C14 exhibited higher activity than the BAC-mix. The toxicity and activity of BAC analogues depend on the alkyl chain length. The use of BAC-C14 as a conservative agent in pharmaceutical preparations instead of the BAC-mix should be considered.

High levels of hair manganese in children living in the vicinity of a ferro-manganese alloy production plant.

PubMed

Menezes-Filho, José A; Paes, Ciro R; Pontes, Angela M de C; Moreira, Josino C; Sarcinelli, Paula N; Mergler, Donna

2009-11-01

Manganese (Mn) is an essential element, but an effective toxic at high concentrations. While there is an extensive literature on occupational exposure, few studies have examined adults and children living near important sources of airborne Mn. The objective of this study was to analyze hair Mn of children living in the vicinity of a ferro-manganese alloy production plant in the Great Salvador region, State of Bahia, Brazil and examine factors that influence this bioindicator of exposure. We examined 109 children in the age range of 1-10 years, living near the plant. Four separate housing areas were identified a priori on the bases of proximity to the emission sources and downwind location. A non-exposed group (n=43) of similar socio-economic status was also evaluated. Mn hair (MnH) concentration was measured by graphite atomic absorption spectrometry (GFAAS). Possible confounding hematological parameters were also assessed. Mean MnH concentration was 15.20 microg/g (1.10-95.50 microg/g) for the exposed children and 1.37 microg/g (0.39-5.58 microg/g) for the non-exposed. For the former, MnH concentrations were 7.95+/-1.40 microg/g (farthest from the plant), 11.81+/-1.11 microg/g (mid-region), 34.43+/-8.66 microg/g (closest to the plant) and 34.22+/-9.15 microg/g (directly downwind). Multiple regression analysis on log transformed MnH concentrations for the exposed children derived a model that explained 36.8% of the variability. In order of importance, area of children's residence, gender (girls>boys) and time of mother's residence in the area at the birth of the child, were significantly associated with MnH. Post hoc analyses indicated two groupings for exposure areas, with those living closest to and downwind of the plant displaying higher MnH concentrations compared to the others. The contribution of the time the mother lived in the community prior to the child's birth to the children's current MnH suggests that in utero exposure may play a role. A study of neurobehavioral performance with respect to Mn exposure in these children is currently underway.

Experimental Melting Study of Basalt-Peridotite Hybrid Source: Melting model of Hawaiian plume

NASA Astrophysics Data System (ADS)

Takahashi, E.; Gao, S.

2015-12-01

Eclogite component entrained in ascending plume is considered to be essentially important in producing flood basalts (e.g., Columbia River basalt, Takahashi et al., 1998 EPSL), alkalic OIBs (e.g., Kogiso et al.,2003), ferro-picrites (Tuff et al.,2005) and Hawaiian shield lavas (e.g., Hauri, 1996; Takahashi & Nakajima, 2002, Sobolev et al.,2005). Size of the entrained eclogite, which controls the reaction rates with ambient peridotite, however, is very difficult to constrain using geophysical observation. Among Hawaiian shield volcanoes, Koolau is the most enriched end-member in eclogite component (Frey et al, 1994). Reconstruction of Koolau volcano based on submarine study on Nuuanu landslide (AGU Monograph vol.128, 2002, Takahashi Garcia Lipman eds.) revealed that silica-rich tholeiite appeared only at the last stage (Makapuu stage) of Koolau volcano. Chemical compositions of lavas as well as isotopes change abruptly and coherently across a horizon (Shinozaki et al. and Tanaka et al. ibid.). Based on these observation, Takahashi & Nakajima (2002 ibid) proposed that the Makapuu stage lava in Koolau volcano was supplied from a single large eclogite block. In order to study melting process in Hawaiian plume, high-pressure melting experiments were carried out under dry and hydrous conditions with layered eclogite/peridotite starting materials. Detail of our experiments will be given by Gao et al (2015 AGU). Combined previous field observation with new set of experiments, we propose that variation in SiO2 among Hawaiian tholeiites represent varying degree of wall-rock interaction between eclogite and ambient peridotite. Makapuu stage lavas in Koolau volcano represents eclogite partial melts formed at ~3 GPa with various amount of xenocrystic olivines derived from Pacific plate. In other words, we propose that "primary magma" in the melting column of Hawaiian plume ranges from basaltic andesite to ferro-picrite depending on the lithology of the source. Solidus of peridotite lowers significantly due to FeO, TiO2, K2O from eclogites thus PMT of Hawaiian plume may be ~1450C which is siginificantly lower than current estimates (e.g., Herzberg, 2006).

Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: did we miss something in CPT analogue molecular targets for treating human disease such as cancer?

PubMed Central

Li, Fengzhi; Jiang, Tao; Li, Qingyong; Ling, Xiang

2017-01-01

Camptothecin (CPT) was discovered from plant extracts more than 60 years ago. Since then, only two CPT analogues (irinotecan and topotecan) have been approved for cancer treatment, although several thousand CPT derivatives have been synthesized and many of them were actively studied in our research community over the past 6+ decades. In this review article, we briefly summarize: (1) the discovery and early development of CPTs, (2) the recognized CPT mechanism of action (MOA), (3) the synthesis of CPT and CPT analogues, and (4) the structure-activity relationship (SAR) of CPT and its analogues. Next, we provide evidence that certain CPT analogues can exert improved efficacy with low toxicity independently of topoisomerase I (Top1) inhibition; instead, these CPT analogues use novel MOAs by targeting important cancer survival-associated oncogenic proteins and/or by bypassing various treatment-resistant mechanisms. We then present a comprehensive review of the most advanced CPT analogues in clinical development, with the goal of resolving why no new CPTs have been FDA approved for cancer treatment, beyond irinotecan and topotecan. We argue that new CPT Top1 inhibitor drugs are unlikely being found to be significantly better than irinotecan and/or topotecan in terms of the overall antitumor activity and toxicity. The significance of CPT analogues that possess novel MOAs has not been sufficiently recognized so far. In our opinion, this is a research area with great potential to make a breakthrough for development of the next generation of CPT analogues that possess high efficacy (due to novel targets) and low toxicity (due to low inhibition of Top1 activity/function) for effective treatment of human disease, including cancer. PMID:29312794

In vitro and in vivo potency of insulin analogues designed for clinical use.

PubMed

Vølund, A; Brange, J; Drejer, K; Jensen, I; Markussen, J; Ribel, U; Sørensen, A R; Schlichtkrull, J

1991-11-01

Analogues of human insulin designed to have improved absorption properties after subcutaneous injection have been prepared by recombinant DNA technology. Five rapidly absorbed analogues, being predominantly in mono- or di-meric states in the pharmaceutical preparation, and a hexameric analogue with very low solubility at neutral pH and slow absorption, were studied. Receptor binding assays with HEP-G2 cells showed overall agreement with mouse free adipocyte assays. Two analogues, B28Asp and A21Gly + B27Arg + B30Thr-NH2, had nearly the same molar in vitro potency as human insulin. Another two showed increased adipocyte potency and receptor binding, B10Asp 194% and 333% and A8His + B4His + B10Glu + B27His 575% and 511%, while B9Asp + B27Glu showed 29% and 18% and the B25Asp analogue only 0.12% and 0.05% potency. Bioassays in mice or rabbits of the analogues except B25Asp showed that they had the same in vivo potency as human insulin 1.00 IU = 6.00 nmol. Thus the variation had the same in vivo potency as human insulin 1.00 IU = 6.00 nmol. Thus the variation in in vivo potency reflects the differences in receptor binding affinity. Relative to human insulin a low concentration is sufficient for a high affinity analogue to produce a given receptor complex formation and metabolic response. In conclusion, human insulin and analogues with markedly different in vitro potencies were equipotent in terms of hypoglycaemic effect. This is in agreement with the concept that elimination of insulin from blood and its subsequent degradation is mediated by insulin receptors.

Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects.

PubMed

Kang, S; Creagh, F M; Peters, J R; Brange, J; Vølund, A; Owens, D R

1991-07-01

To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.

Rapid actions of calcitriol and its side chain analogues CB1093 and GS1500 on intracellular calcium levels in skeletal muscle cells: a comparative study

PubMed Central

Vazquez, Guillermo; Sellés, Juana; de Boland, Ana Russo; Boland, Ricardo

1999-01-01

The ability of synthetic analogues of the secosteroid hormone 1α,25-dihydroxy-vitamin-D3 [calcitriol, CT; 1,25(OH)2D3] to exert non-genomic (rapid) effects on target cells has been scarcely studied. To evaluate the pharmacological potential of the CT side-chain analogues CB1093 and GS1500, we compared their fast effects on intracellular calcium concentration ([Ca2+]i) in chick skeletal muscle cells with those elicited by the natural hormone.Both analogues, similarly to CT, specifically induced rapid (30–60 s) and sustained rises in [Ca2+]i levels. CB1093 and GS1500 were more potent than the natural hormone at concentrations as low as 10−13 M (4.5 fold stimulation) and 10−12 M (2.5 fold), respectively, whereas higher concentrations (10−9–10−8 M) of CT were more effective than the analogues in elevating [Ca2+]i. Cyclic AMP was markedly increased by both analogues pointing for a role of this messenger in the fast actions of the synthetic compounds.In Ca2+ free medium CT and analogues elicited a transient elevation in [Ca2+]i. The PLC inhibitors U73122 (2 μM) and neomycin (0.5 mM), as well as depletion of intracellular stores with thapsigargin (1 μM), completely prevented CB1093/GS1500-dependent changes in [Ca2+]i suggesting that, similarly to CT, these analogues mobilized Ca2+ from an IP3/thapsigargin-sensitive store.The voltage-dependent calcium channel (VDCC) blocker nifedipine (2 μM) reduced by 50–60% the influx phase of the [Ca2+]i response to CB1093 and GS1500, indicating that VDCC contributed partially to Ca2+ entry. The Ca2+ readdition protocol suggested that analogue-dependent activation of a SOC entry pathway accounted, to the same extent as for CT, for the remaining non-VDCC mediated Ca2+ influx. PMID:10372825

Human versus animal: contrasting decomposition dynamics of mammalian analogues in experimental taphonomy.

PubMed

Stokes, Kathryn L; Forbes, Shari L; Tibbett, Mark

2013-05-01

Taphonomic studies regularly employ animal analogues for human decomposition due to ethical restrictions relating to the use of human tissue. However, the validity of using animal analogues in soil decomposition studies is still questioned. This study compared the decomposition of skeletal muscle tissues (SMTs) from human (Homo sapiens), pork (Sus scrofa), beef (Bos taurus), and lamb (Ovis aries) interred in soil microcosms. Fixed interval samples were collected from the SMT for microbial activity and mass tissue loss determination; samples were also taken from the underlying soil for pH, electrical conductivity, and nutrient (potassium, phosphate, ammonium, and nitrate) analysis. The overall patterns of nutrient fluxes and chemical changes in nonhuman SMT and the underlying soil followed that of human SMT. Ovine tissue was the most similar to human tissue in many of the measured parameters. Although no single analogue was a precise predictor of human decomposition in soil, all models offered close approximations in decomposition dynamics. © 2013 American Academy of Forensic Sciences.

Synthesis of indolizidinone analogues of cytotoxic alkaloids: monocyclic precursors are also active.

PubMed

Boto, Alicia; Miguélez, Javier; Marín, Raquel; Díaz, Mario

2012-05-15

Readily available proline derivatives can be transformed in just two steps into analogues of cytotoxic phenanthroindolizidine alkaloids. The key step uses a sequential radical scission-oxidation-alkylation process, which yields 2-substituted pyrrolidine amides. A second process effects the cyclization to give the desired alkaloid analogues, which possess an indolizidine core. The major and minor isomers (dr 3:2 to 3:1) can be easily separated, allowing their use to study structure-activity relationships (SAR). The process is versatile and allows the introduction of aryl and heteroaryl groups (including biphenyl, halogenated phenyl, and pyrrole rings). Some of these alkaloid analogues displayed a selective cytotoxic activity against tumorogenic human neuronal and mammary cancer cells, and one derivative caused around 80% cell death in both tumor lines at micromolar doses. The cytotoxicity of some monocyclic precursors was also studied, being comparable or superior to the bicyclic derivatives. Copyright © 2012 Elsevier Ltd. All rights reserved.

The anti-inflammatory activity of dillapiole and some semisynthetic analogues.

PubMed

Parise-Filho, Roberto; Pastrello, Michelli; Pereira Camerlingo, Carla Emygdio; Silva, Gisele Juni; Agostinho, Leonardo Aguiar; de Souza, Thaís; Motter Magri, Fátima Maria; Ribeiro, Roberto Rodrigues; Brandt, Carlos Alberto; Polli, Michelle Carneiro

2011-11-01

Piper aduncum L. (Piperaceae) produces an essential oil (dillapiole) with great exploitative potential and it has proven effects against traditional cultures of phytopathogens, such as fungi, bacteria and mollusks, as well as analgesic action with low levels of toxicity. This study investigated the in vivo anti-inflammatory activity of dillapiole. Furthermore, in order to elucidate its structure-anti-inflammatory activity relationship (SAR), semisynthetic analogues were proposed by using the molecular simplification strategy. Dillapiole and safrole were isolated and purified using column chromatography. The semisynthetic analogues were obtained by using simple organic reactions, such as catalytic reduction and isomerization. All the analogues were purified by column chromatography and characterized by (1)H and (13)C NMR. The anti-inflammatory activities of dillapiole and its analogues were studied in carrageenan-induced rat paw edema model. Dillapiole and di-hydrodillapiole significantly (p<0.05) inhibited rat paw edema. All the other substances tested, including safrole, were less powerful inhibitors with activities inferior to that of indomethacin. These findings showed that dillapiole and di-hydrodillapiole have moderate anti-phlogistic properties, indicating that they can be used as prototypes for newer anti-inflammatory compounds. Structure-activity relationship studies revealed that the benzodioxole ring is important for biological activity as well as the alkyl groups in the side chain and the methoxy groups in the aromatic ring.

Protective effects of TRH and its analogues against various cytotoxic agents in retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells.

PubMed

Jaworska-Feil, L; Jantas, D; Leskiewicz, M; Budziszewska, B; Kubera, M; Basta-Kaim, A; Lipkowski, A W; Lason, W

2010-12-01

TRH (thyroliberin) and its analogues were reported to possess neuroprotective effects in cellular and animal experimental models of acute and chronic neurodegenerative diseases. In the present study we evaluated effects of TRH and its three stable analogues, montirelin (CG-3703), RGH-2202 and Z-TRH (N-(carbobenzyloxy)-pGlutamyl-Histydyl-Proline) on the neuronally differentiated human neuroblastoma SH-SY5Y cell line, which is widely accepted for studying potential neuroprotectants. We found that TRH and all the tested analogues at concentrations 0.1-50 μM attenuated cell damage induced by MPP(+) (2 mM), 3-nitropropionate (10 mM), hydrogen peroxide (0.5 mM), homocysteine (250 μM) and beta-amyloid (20μM) in retinoic acid differentiated SH-SY5Y cells. Furthermore, we demonstrated that TRH and its analogues decreased the staurosporine (0.5 μM)-induced LDH release, caspase-3 activity and DNA fragmentation, which indicate the anti-apoptotic proprieties of these peptides. The neuroprotective effects of TRH (10 μM) and RGH-2202 (10 μM) on St-induced cell death was attenuated by inhibitors of PI3-K pathway (wortmannin and LY294002), but not MAPK/ERK1/2 (PD98059 and U0126). Moreover, TRH and its analogues at neuroprotective concentrations (1 and 10 μM) increased expression of Bcl-2 protein, as confirmed by Western blot analysis. All in all, these results extend data on neuroprotective properties of TRH and its analogues and provide evidence that mechanism of anti-apoptotic effects of these peptides in SH-SY5Y cell line involves induction of PI3K/Akt pathway and Bcl-2. Furthermore, the data obtained on human cell line with a dopaminergic phenotype suggest potential utility of TRH and its analogues in the treatment of some neurodegenerative diseases including Parkinson's disease. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effect of non-Newtonian viscosity on the fluid-dynamic characteristics in stenotic vessels

NASA Astrophysics Data System (ADS)

Huh, Hyung Kyu; Ha, Hojin; Lee, Sang Joon

2015-08-01

Although blood is known to have shear-thinning and viscoelastic properties, the effects of such properties on the hemodynamic characteristics in various vascular environments are not fully understood yet. For a quantitative hemodynamic analysis, the refractive index of a transparent blood analogue needs to be matched with that of the flowing conduit in order to minimize the errors according to the distortion of the light. In this study, three refractive index-matched blood analogue fluids with different viscosities are prepared—one Newtonian and two non-Newtonian analogues—which correspond to healthy blood with 45 % hematocrit (i.e., normal non-Newtonian) and obese blood with higher viscosity (i.e., abnormal non-Newtonian). The effects of the non-Newtonian rheological properties of the blood analogues on the hemodynamic characteristics in the post-stenosis region of an axisymmetric stenosis model are experimentally investigated using particle image velocimetry velocity field measurement technique and pathline flow visualization. As a result, the centerline jet flow from the stenosis apex is suppressed by the shear-thinning feature of the blood analogues when the Reynolds number is smaller than 500. The lengths of the recirculation zone for abnormal and normal non-Newtonian blood analogues are 3.67 and 1.72 times shorter than that for the Newtonian analogue at Reynolds numbers smaller than 200. The Reynolds number of the transition from laminar to turbulent flow for all blood analogues increases as the shear-thinning feature increases, and the maximum wall shear stresses in non-Newtonian fluids are five times greater than those in Newtonian fluids. However, the shear-thinning effect on the hemodynamic characteristics is not significant at Reynolds numbers higher than 1000. The findings of this study on refractive index-matched non-Newtonian blood analogues can be utilized in other in vitro experiments, where non-Newtonian features dominantly affect the flow characteristics.

Type and location of fluorescent probes incorporated into the potent mu-opioid peptide [Dmt]DALDA affect potency, receptor selectivity and intrinsic efficacy.

PubMed

Schiller, P W; Berezowska, I; Weltrowska, G; Chen, H; Lemieux, C; Chung, N N

2005-06-01

The dermorphin-derived tetrapeptide H-Dmt-d-Arg-Phe-Lys-NH(2) (Dmt = 2',6'-dimethyltyrosine) ([Dmt(1)]DALDA) is a highly potent and selective mu-opioid agonist capable of crossing the blood-brain barrier and producing a potent, centrally mediated analgesic effect when given systemically. For the purpose of biodistribution studies by fluorescence techniques, [Dmt(1)]DALDA analogues containing various fluorescent labels [dansyl, anthraniloyl (atn), fluorescein, or 6-dimethylamino-2'-naphthoyl] in several different locations of the peptide were synthesized and characterized in vitro in the guinea-pig ileum and mouse vas deferens assays, and in mu-, delta- and kappa-opioid receptor-binding assays. The analogues showed various degrees of mu receptor-binding selectivity, but all of them were less mu-selective than the [Dmt(1)]DALDA parent peptide. Most analogues retained potent, full mu-agonist activity, except for one with fluorescein attached at the C-terminus (3a) (partial mu-agonist) and one containing beta-(6'-dimethylamino-2'-naphthoyl)alanine (aladan) in place of Phe(3) (4) (mu- and kappa-antagonist). The obtained data indicate that the receptor-binding affinity, receptor selectivity and intrinsic efficacy of the prepared analogues vary very significantly, depending on the type of fluorescent label used and on its location in the peptide. The results suggest that the biological activity profile of fluorescence-labeled peptide analogues should always be carefully determined prior to their use in biodistribution studies or other studies. One of the analogues containing the atn group (2a) proved highly useful in a study of cellular uptake and intracellular distribution by confocal laser scanning microscopy.

[Ocular Surface Evaluation in Patients Treated with Prostaglandin Analogues Considering Preservative Agent].

PubMed

Mlčáková, E; Mlčák, P; Karhanová, M; Langová, K; Marešová, K

The aim of this study was to evaluate the ocular surface in patients treated with prostaglandin analogues considering contained preservative agent. 60 patients with glaucoma or ocular hypertension treated with prostaglandin analogue monotherapy were enrolled in this observational study. 20 patients with glaucoma suspect or ocular hypertension without local or systemic glaucoma medication formed the control group. Demographic data and medical history were recorded for each participant. Patients filled in the Ocular surface disease index© (OSDI) questionnaire and underwent an ophthalmological examination including assessment of conjunctival hyperaemia according to Efron, tear film break up time (BUT) and fluorescein staining according to the Oxford grading scheme. Treated participants were divided into 3 groups according to the preservative contained in the currently used prostaglandin analogue: the preservative-free group (18 patients), the polyquaternium group (17 patients) and the benzalkonium chloride (BAK) group (25 patients). The control group had significantly lower fluorescein staining than the preservative-free group (p=0.001), the polyquaternium group (p=0.007) and the BAK group (p=0.002). The conjunctival hyperaemia was significantly lower in the preservative-free group compared to the polyquaternium group (p=0.011). There was no significant difference among the other groups. The difference neither in the OSDI score nor in the BUT was statistically important. This study confirmed that the ocular surface is worse in patients treated with prostaglandin analogue monotherapy than in people without glaucoma medication. A significant difference among treated patients depending on a preservative agent was not proved.Key words: benzalkonium chloride, glaucoma, ocular surface disease, preservatives, prostaglandin analogues.

Attributions about Perpetrators and Victims of Interpersonal Abuse: Results from an Analogue Study

ERIC Educational Resources Information Center

Langhinrichsen-Rohling, Jennifer; Shlien-Dellinger, Rania K.; Huss, Matthew T.; Kramer, Vertrie L.

2004-01-01

This analogue study (written vignettes and videotapes) examines the influence of victim-perpetrator relationship (spouse or acquaintance), sex of perceiver, and type of abuse (psychological vs. physical) on attributions about victims and perpetrators of domestic abuse. College student participants (73 men, 108 women) were randomly assigned to…

Approved Antiviral Drugs over the Past 50 Years

PubMed Central

2016-01-01

SUMMARY Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2′-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2′-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide. PMID:27281742

Can concreteness training buffer against the negative effects of rumination on PTSD? An experimental analogue study.

PubMed

Schaich, Anja; Watkins, Edward R; Ehring, Thomas

2013-12-01

Trauma-related rumination has been found to be an important maintaining factor for PTSD. On the background of the processing mode account of ruminative thinking, this study tested whether the relationship between rumination and analogue PTSD symptoms can be modified by training participants in a concrete mode of processing. Healthy participants were trained in either an abstract or a concrete style of processing. Afterwards, they watched a stressful film. The interactive effect of training condition and trait rumination on intrusive memories of the film was examined. Following abstract training, a positive relationship between trait rumination and intrusive memories of the film emerged. As hypothesized, this relationship disappeared following concrete training. include the lack of a no-training control group and the analogue paradigm used. The study provides preliminary evidence that the relationship between trait rumination and analogue PTSD symptoms can be modified. If replicated in future studies, it may be promising to examine the value of concreteness training for prevention and/or treatment of PTSD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structure-function correlation of chloroquine and analogues as transgene expression enhancers in nonviral gene delivery.

PubMed

Cheng, Jianjun; Zeidan, Ryan; Mishra, Swaroop; Liu, Aijie; Pun, Suzie H; Kulkarni, Rajan P; Jensen, Gregory S; Bellocq, Nathalie C; Davis, Mark E

2006-11-02

To understand how chloroquine (CQ) enhances transgene expression in polycation-based, nonviral gene delivery systems, a number of CQ analogues with variations in the aliphatic amino side chain or in the aromatic ring are synthesized and investigated. Our studies indicate that the aliphatic amino moiety of CQ is essential to provide increased gene expression. Further, the enhancements are more dramatically affected by changes to the aromatic ring and are positively correlated to the strength of intercalation between DNA and the CQ analogues. Quinacrine (QC), a CQ analogue with a fused acridinyl structure that can strongly intercalate DNA, enhances transfection similarly to CQ at a concentration 10 times lower, while N(4)-(4-pyridinyl)-N(1),N(1)-diethyl-1,4-pentanediamine (CP), a CQ analogue that has a weakly intercalating pyridinyl ring, shows no effect on gene expression. Subtle change on the 7-substituent of the chloroquine aromatic structure can also greatly affect the ability of the CQ analogues to enhance transgene expression. Transfection in the presence of N(4)-(7-trifluoromethyl-4-quinolinyl)-N(1),N(1)-diethyl-1,4-pentanediamin e (CQ7a) shows expression efficiency 10 times higher than in the presence of CQ at same concentration, while transfection in the presence of N(4)-(4-quinolinyl)-N(1),N(1)-diethyl-1,4-pentanediamine (CQ7b) does not reveal any enhancing effects on expression. Through a number of comparative studies with CQ and its analogues, we conclude that there are at least three mechanistic features of CQ that lead to the enhancement in gene expression: (i) pH buffering in endocytic vesicles, (ii) displacement of polycations from the nucleic acids in polyplexes, and (iii) alteration of the biophysical properties of the released nucleic acid.

Cross-reactivity of insulin analogues with three insulin assays.

PubMed

Dayaldasani, A; Rodríguez Espinosa, M; Ocón Sánchez, P; Pérez Valero, V

2015-05-01

Immunometric assays have recently shown higher specificity in the detection of human insulin than radioimmunoassays with almost no cross-reaction with proinsulin or C peptide. The introduction of the new insulin analogues on the market, however, has raised the need to define their cross-reactivity in these assays. Several studies have been published in this regard with different results. The analogues studied were insulins lispro, aspart, glargine, detemir, and glulisine. Insulin concentrations were measured in Immulite(®) 2000 and Advia Centaur(®) XP (Siemens Healthcare Diagnostics), and Elecsys(®) Modular Analytics E170 (Roche). All samples were processed 15 times in the same analytical run following a random sequence. Those samples which showed statistically and clinically significant changes in insulin concentration were reprocessed using increasing concentrations of analogue, and this was done twice, using two different serum pools, one with a low concentration of insulin and one with a high concentration of insulin. In the Elecsys(®) E170 analyser, glargine showed statistical changes (comparison of mean concentrations with p < 0.05) and clinically significant changes in measured insulin (percentage difference 986.2% > reference change value: 59.8%), and the interference increased with increasing concentrations of analogue; the differences were not significant in the case of the other analogues. In the Advia Centaur(®) and Immulite(®) 2000 only the results for glulisine did not present significance (percentage difference 44.7% < reference change value 103.5%). Increasing concentrations of aspart, glargine, and lispro showed increased interference in Immulite(®) 2000. In the Elecsys(®) E170 assay, relevant cross-reactivity was only detected with insulin glargine, whereas in the other analysers all analogues except glulisine showed significant interference. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

The Need for Analogue Missions in Scientific Human and Robotic Planetary Exploration

NASA Technical Reports Server (NTRS)

Snook, K. J.; Mendell, W. W.

2004-01-01

With the increasing challenges of planetary missions, and especially with the prospect of human exploration of the moon and Mars, the need for earth-based mission simulations has never been greater. The current focus on science as a major driver for planetary exploration introduces new constraints in mission design, planning, operations, and technology development. Analogue missions can be designed to address critical new integration issues arising from the new science-driven exploration paradigm. This next step builds on existing field studies and technology development at analogue sites, providing engineering, programmatic, and scientific lessons-learned in relatively low-cost and low-risk environments. One of the most important outstanding questions in planetary exploration is how to optimize the human and robotic interaction to achieve maximum science return with minimum cost and risk. To answer this question, researchers are faced with the task of defining scientific return and devising ways of measuring the benefit of scientific planetary exploration to humanity. Earth-based and spacebased analogue missions are uniquely suited to answer this question. Moreover, they represent the only means for integrating science operations, mission operations, crew training, technology development, psychology and human factors, and all other mission elements prior to final mission design and launch. Eventually, success in future planetary exploration will depend on our ability to prepare adequately for missions, requiring improved quality and quantity of analogue activities. This effort demands more than simply developing new technologies needed for future missions and increasing our scientific understanding of our destinations. It requires a systematic approach to the identification and evaluation of the categories of analogue activities. This paper presents one possible approach to the classification and design of analogue missions based on their degree of fidelity in ten key areas. Various case studies are discussed to illustrate the approach.

High stability and biological activity of the copper(II) complexes of alloferon 1 analogues containing tryptophan.

PubMed

Kadej, Agnieszka; Kuczer, Mariola; Czarniewska, Elżbieta; Urbański, Arkadiusz; Rosiński, Grzegorz; Kowalik-Jankowska, Teresa

2016-10-01

Copper(II) complex formation processes between the alloferon 1 (Allo1) (HGVSGHGQHGVHG) analogues where the tryptophan residue is introducing in the place His residue H1W, H6W, H9W and H12W have been studied by potentiometric, UV-visible, CD and EPR spectroscopic, and MS methods. For all analogues of alloferon 1 complex speciation have been obtained for a 1:1 metal-to-ligand molar ratio and 2:1 of H1W because of precipitation at higher (2:1, 3:1 and 4:1) ratios. At physiological pH7.4 and a 1:1 metal-to-ligand molar ratio the tryptophan analogues of alloferon 1 form the CuH -1 L and/or CuH -2 L complexes with the 4N binding mode. The introduction of tryptophan in place of histidine residues changes the distribution diagram of the complexes formed with the change of pH and their stability constants compared to the respective substituted alanine analogues of alloferon 1. The CuH -1 L, CuH -2 L and CuH -3 L complexes of the tryptophan analogues are more stable from 1 to 5 log units in comparison to those of the alanine analogues. This stabilization of the complexes may result from cation(Cu(II))-π and indole/imidazole ring interactions. The induction of apoptosis in vivo, in Tenebrio molitor cells by the ligands and their copper(II) complexes at pH7.4 was studied. The biological results show that copper(II) ions in vivo did not cause any apparent apoptotic features. The most active were the H12W peptide and Cu(II)-H12W complex formed at pH7.4. Copyright © 2016 Elsevier Inc. All rights reserved.

Probing the steric requirements of the γ-aminobutyric acid aminotransferase active site with fluorinated analogues of vigabatrin

PubMed Central

Juncosa, Jose I.; Groves, Andrew P.; Xia, Guoyao; Silverman, Richard B.

2012-01-01

We have synthesized three analogues of 4-amino-5-fluorohexanoic acids as potential inactivators of γ-aminobutyric acid aminotransferase (GABA-AT), which were designed to combine the potency of their shorter chain analogue, 4-amino-5-fluoropentanoic acid (AFPA), with the greater enzyme selectivity of the antiepileptic vigabatrin (Sabril®). Unexpectedly, these compounds failed to inactivate or inhibit the enzyme, even at high concentrations. On the basis of molecular modeling studies, we propose that the GABA-AT active site has an accessory binding pocket that accommodates the vinyl group of vigabatrin and the fluoromethyl group of AFPA, but is too narrow to support the extra width of one distal methyl group in the synthesized analogues. PMID:23306054

Algicidal Activity of Bacillamide Alkaloids and Their Analogues against Marine and Freshwater Harmful Algae.

PubMed

Wang, Bo; Tao, Yuanyuan; Liu, Qisheng; Liu, Na; Jin, Zhong; Xu, Xiaohua

2017-08-07

Harmful algal blooms have become a great challenge to global aquatic ecosystems over the past decades. Given their low toxicity, high selectivity, and environment-friendly properties, the use of natural products and their analogues as algicides has proven to be particularly efficient. In the present study, algicidal activity of naturally occurring bacillamides A-C, alkaloid ( 1 ), and neobacillamide A, as well as their synthetic analogues were investigated intensively. Bioassay results showed that, relative to natural bacillamide alkaloids, aniline-derived analogue ( 10d ) exhibited higher algicidal potential against three freshwater harmful algae Mycrocyctis aeruginosa, Scenedesmus obliquus, and Chlorella pyrenoidosa , suggesting that it could be used as a promising lead compound to develop novel algicide for controlling harmful algal blooms.

Algicidal Activity of Bacillamide Alkaloids and Their Analogues against Marine and Freshwater Harmful Algae

PubMed Central

Wang, Bo; Tao, Yuanyuan; Liu, Qisheng; Liu, Na; Jin, Zhong; Xu, Xiaohua

2017-01-01

Harmful algal blooms have become a great challenge to global aquatic ecosystems over the past decades. Given their low toxicity, high selectivity, and environment-friendly properties, the use of natural products and their analogues as algicides has proven to be particularly efficient. In the present study, algicidal activity of naturally occurring bacillamides A–C, alkaloid (1), and neobacillamide A, as well as their synthetic analogues were investigated intensively. Bioassay results showed that, relative to natural bacillamide alkaloids, aniline-derived analogue (10d) exhibited higher algicidal potential against three freshwater harmful algae Mycrocyctis aeruginosa, Scenedesmus obliquus, and Chlorella pyrenoidosa, suggesting that it could be used as a promising lead compound to develop novel algicide for controlling harmful algal blooms. PMID:28783131

Synthesis and Biological Evaluation of Carbocyclic Analogues of Pachastrissamine

PubMed Central

Kwon, Yongseok; Song, Jayoung; Bae, Hoon; Kim, Woo-Jung; Lee, Joo-Youn; Han, Geun-Hee; Lee, Sang Kook; Kim, Sanghee

2015-01-01

A series of carbocyclic analogues of naturally-occurring marine sphingolipid pachastrissamine were prepared and biologically evaluated. The analogues were efficiently synthesized via a tandem enyne/diene-ene metathesis reaction as a key step. We found that the analogue 4b exhibited comparable cytotoxicity and more potent inhibitory activity against sphingosine kinases, compared to pachastrissamine. Molecular modeling studies were conducted to provide more detailed insight into the binding mode of 4b in sphingosine kinase. In our docking model, pachastrissamine and 4b were able to effectively bind to the binding pocket of sphingosine kinase 1 as co-crystalized sphingosine. However, 4b showed a hydrophobic interaction with Phe192, which suggests that it contributes to its increased inhibitory activity against sphingosine kinase 1. PMID:25654428

Chromophoric Nucleoside Analogues: Synthesis and Characterization of 6-Aminouracil-Based Nucleodyes.

PubMed

Freeman, Noam S; Moore, Curtis E; Wilhelmsson, L Marcus; Tor, Yitzhak

2016-06-03

Nucleodyes, visibly colored chromophoric nucleoside analogues, are reported. Design criteria are outlined and the syntheses of cytidine and uridine azo dye analogues derived from 6-aminouracil are described. Structural analysis shows that the nucleodyes are sound structural analogues of their native nucleoside counterparts, and photophysical studies demonstrate that the nucleodyes are sensitive to microenvironmental changes. Quantum chemical calculations are presented as a valuable complementary tool for the design of strongly absorbing nucleodyes, which overlap with the emission of known fluorophores. Förster critical distance (R0) calculations determine that the nucleodyes make good FRET pairs with both 2-aminopurine (2AP) and pyrrolocytosine (PyC). Additionally, unique tautomerization features exhibited by 5-(4-nitrophenylazo)-6-oxocytidine (8) are visualized by an extraordinary crystal structure.

Strongly enhanced Fenton degradation of organic pollutants by cysteine: An aliphatic amino acid accelerator outweighs hydroquinone analogues.

PubMed

Li, Tuo; Zhao, Zhenwen; Wang, Quan; Xie, Pengfei; Ma, Jiahai

2016-11-15

Quinone-hydroquinone analogues have been proven to be efficient promoters of Fenton reactions by accelerating the Fe(III)/Fe(II) redox cycle along with self-destruction. However, so far there is little information on non-quinone-hydroquinone cocatalyst for Fenton reactions. This study found that cysteine, a common aliphatic amino acid, can strongly enhance Fenton degradation of organic pollutants by accelerating Fe(III)/Fe(II) redox cycle, as quinone-hydroquinone analogues do. Further, cysteine is superior to quinone-hydroquinone analogues in catalytic activity, H 2 O 2 utilization and atmospheric limits. The cocatalysis mechanism based on the cycle of cysteine/cystine was proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transport characteristics of endomorphin-2 analogues in brain capillary endothelial cells.

PubMed

Mallareddy, Jayapal Reddy; Tóth, Géza; Fazakas, Csilla; Molnár, Judit; Nagyőszi, Péter; Lipkowski, Andrzej W; Krizbai, István A; Wilhelm, Imola

2012-04-01

Because of their poor metabolic stability and limited blood-brain barrier permeability, endomorphins have a low analgesic efficacy when administered systemically. Therefore, it is of great importance to design analogues with improved peptidase resistance and better delivery to the central nervous system. Recently, novel endomorphin-2 analogues have been synthesized, which proved to bind with high affinity and selectivity to the μ-opioid receptors and showed proteolytic resistance. In this study, we have analysed the transport characteristics of endomorphin-2 and three of its analogues [Dmt-Pro-Phe-Phe-NH(2) , Tyr-(1S,2R)Acpc-Phe-Phe-NH(2) and Tyr-(1S,2R)Achc-Phe-Phe-NH(2) ] using an in vitro blood-brain barrier model. The lipophilicity of the analogues, as assessed by their octanol/water partition coefficients, was higher than that of endomorphin-2. The flux of all four peptides from the apical (blood) side to the basolateral (brain) side was not saturable in the 10nm-1mm concentration range, suggesting that a passive mechanism plays a major role in their transport. The permeability coefficient of the analogues was significantly higher than that of endomorphin-2, suggesting increased blood-brain barrier penetration properties. We conclude that because of their good peptidase resistance and improved transport through brain endothelial cells, these endomorphin-2 analogues will have better analgesic properties in vivo. © 2011 John Wiley & Sons A/S.

Rapid on-site detection of ephedrine and its analogues used as adulterants in slimming dietary supplements by TLC-SERS.

PubMed

Lv, Diya; Cao, Yan; Lou, Ziyang; Li, Shujin; Chen, Xiaofei; Chai, Yifeng; Lu, Feng

2015-02-01

Ephedrine and its analogues are in the list of prohibited substance in adulteration to botanical dietary supplements (BDS) for their uncontrollable stimulating side effects. However, they were always adulterated illegally in BDS to promote losing weight. In order to avoid detection, various kinds of ephedrine analogues were added rather than ephedrine itself. This has brought about great difficulties in authentication of BDS. In this study, we put forward for the first time a method which combined thin-layer chromatography (TLC) and surface-enhanced Raman scattering (SERS) to directly identify trace adulterant. Ephedrine, pseudoephedrine, methylephedrine, and norephedrine were mixed and used in this method to develop an analytical model. As a result, the four analogues were separated efficiently in TLC analysis, and trace-components and low-background SERS detection was realized. The limit of detection (LOD) of the four analogues was 0.01 mg/mL. Eight common Raman peaks (△υ = 620, 1003, 1030, 1159, 1181, 1205, 1454, 1603 cm(-1)) were extracted experimentally and statistically to characterize the common feature of ephedrine analogues. A TLC-SERS method coupled with common-peak model was adopted to examine nine practical samples, two of which were found to be adulterated with ephedrine analogues. Identification results were then confirmed by UPLC-QTOF/MS analysis. The proposed method was simple, rapid, and accurate and can also be employed to trace adulterant identification even when there are no available reference derivatives on-site or unknown types of ephedrine analogues are adulterated.

In silico and in vitro characterization of anti-amyloidogenic activity of vitamin K3 analogues for Alzheimer's disease.

PubMed

Huy, Pham Dinh Quoc; Yu, Yao-Chung; Ngo, Son Tung; Thao, Tran Van; Chen, Chin-Piao; Li, Mai Suan; Chen, Yi-Cheng

2013-04-01

Aggregation of amyloid-beta (Aβ) has been proposed as the main cause of Alzheimer's disease (AD). Vitamin K deficiency has been linked to the pathogenesis of AD. Therefore, 15 synthesized vitamin K3 (VK3) analogues were studied for their anti-amyloidogenic activity. Biological and spectroscopic assays were used to characterize the effect of VK3 analogues on amyloidogenic properties of Aβ, such as aggregation, free radical formation, and cell viability. Molecular dynamics simulation was used to calculate the binding affinity and mode of VK3 analogue binding to Aβ. Both numerical and experimental results showed that several VK3 analogues, including VK3-6, VK3-8, VK3-9, VK3-10, and VK3-224 could effectively inhibit Aβ aggregation and conformational conversion. The calculated inhibition constants were in the μM range for VK3-10, VK3-6, and VK3-9 which was similar to the IC50 of curcumin. Cell viability assays indicated that VK3-9 could effectively reduce free radicals and had a protective effect on cytotoxicity induced by Aβ. The results clearly demonstrated that VK3 analogues could effectively inhibit Aβ aggregation and protect cells against Aβ induced toxicity. Modified VK3 analogues can possibly be developed as effective anti-amyloidogenic drugs for the treatment of AD. VK3 analogues effectively inhibit Aβ aggregation and are highly potent as anti-amyloidogenic drugs for therapeutic treatment of AD. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparative positron-emission tomography (PET) imaging and phototherapeutic potential of 124I- labeled methyl- 3-(1'-iodobenzyloxyethyl)pyropheophorbide-a vs the corresponding glucose and galactose conjugates.

PubMed

Pandey, Suresh K; Sajjad, Munawwar; Chen, Yihui; Zheng, Xiang; Yao, Rutao; Missert, Joseph R; Batt, Carrie; Nabi, Hani A; Oseroff, Allan R; Pandey, Ravindra K

2009-01-22

In our present study, 3-(1(')-m-iodobenzyloxyethyl)pyropheophorbide-a methyl ester 1, 3-(1'-m-iodobenzyloxyethyl)-17(2)-{(2-deoxy)glucose}pyropheophorbide-a 2, and 3-(1'-m-iodobenzyloxyethyl)-17(2)-{(1-deoxy)galactose}pyropheophorbide-a 3 were synthesized and converted into the corresponding (124)I-labeled analogues by reacting the intermediate trimethyltin analogues with Na(124)I. Photosensitizers 1-3 were evaluated for the PDT efficacy in C3H mice bearing RIF tumors at variable doses and showed a significant long-term tumor cure. Among the compounds investigated, the non-carbohydrate analogue 1 was most effective. These results were in contrast to the in vitro data, where compared to the parent analogue the corresponding galactose and glucose derivatives showed enhanced cell kill. Among the corresponding (124)I-labeled analogues, excellent tumor images were obtained from compound 1 in both tumor models (RIF and Colon-26) and the best tumor contrast was observed at 72 h after injection. Conjugating a glucose moiety to photosensitizer 1 initially diminished its tumor uptake, whereas with time the corresponding galactose analogue showed improved tumor contrast.

Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal, and anti-HIV activities.

PubMed

Ahmed, Nafees; Brahmbhatt, Keyur G; Khan, Shabana I; Jacob, Melissa; Tekwani, Babu L; Sabde, Sudeep; Mitra, Debashis; Singh, Inder P; Khan, Ikhlas A; Bhutani, Kamlesh K

2013-04-01

Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC(50) 1.25 and 0.88 μM and chloroquine-resistant W2 strain with IC(50) 1.64 and 1.07 μM, respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC(50) 2.39 and 2.78 μM and IC(90) 11.27 and 12.76 μM, respectively. Three analogues 12c, 14c, and 14i were the most active against various pathogenic bacteria and fungi with IC(50) < 3.02 μM and MIC/MBC/MFC <6 μM. Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV-1. Our study demonstrated that the tricyclic guanidine compounds provide new structural class for broad spectrum activity. © 2012 John Wiley & Sons A/S.

Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal and anti-HIV activities.

PubMed

Ahmed, Nafees; Brahmbhatt, Keyur G; Khan, Shabana I; Jacob, Melissa; Tekwani, Babu L; Sabde, Sudeep; Mitra, Debashis; Singh, Inder Pal; Khan, Ikhlas A; Bhutani, Kamlesh K

2012-06-15

Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC 50 1.25 and 0.88 μM and chloroquine-resistant W2 strain with IC 50 1.64 and 1.07 μM, respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC 50 2.39 and 2.78 μM and IC 90 11.27 and 12.76 μM respectively. Three analogues 12c, 14c and 14i were the most active against various pathogenic bacteria and fungi with IC 50 <3.02 μM and MIC/MBC/MFC <6 μM. Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV-1. Our study demonstrated that the tricyclic guanidine compounds provide new structral class for broad spectrum activity. © 2012 John Wiley & Sons A/S. © 2012 John Wiley & Sons A/S.

Evaluation of the antidepressant therapeutic potential of isocyanine and pseudoisocyanine analogues of the organic cation decynium-22.

PubMed

Krause-Heuer, Anwen M; Fraser-Spears, Rheaclare; Dobrowolski, Jeremy C; Ashford, Mark E; Wyatt, Naomi A; Roberts, Maxine P; Gould, Georgianna G; Cheah, Wai-Ching; Ng, Clarissa K L; Bhadbhade, Mohan; Zhang, Bo; Greguric, Ivan; Wheate, Nial J; Kumar, Naresh; Koek, Wouter; Callaghan, Paul D; Daws, Lynette C; Fraser, Benjamin H

2017-09-08

Herein we describe the synthesis and evaluation of antidepressant properties of seven analogues (1-7) of the low affinity/high capacity transporter blocker decynium-22 (D-22). All analogues (1-7) were synthesized via base promoted coupling reactions between N-alkylated-2-methylquinolinium iodides or N-alkylated-4-methylquinolinium iodides and electrophilic N-alkylated-2-iodoquinolinium iodides. All final compounds were purified by re-crystallization or preparative HPLC and initial evaluation studies included; 1) screening for in vitro α1-adrenoceptor activity (a property that can lead to unwanted side-effects), 2) measuring antidepressant-like activity in a mouse tail suspension test (TST), and 3) measuring effects upon mouse locomotion. The results showed some analogues have lower affinities at α1-adrenoceptors compared to D-22 and showed antidepressant-like activity without the need for co-administration of SSRIs. Additionally, many analogues did not affect mouse locomotion to the same extent as D-22. Plans for additional evaluations of these promising analogues, including measurement of antidepressant-like activity with co-administration of selective serotonin re-uptake inhibitors (SSRIs), are outlined. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Quantum Monte Carlo simulation of the ferroelectric or ferrielectric nanowire with core shell morphology

NASA Astrophysics Data System (ADS)

Feraoun, A.; Zaim, A.; Kerouad, M.

2016-09-01

By using the Quantum Monte Carlo simulation; the electric properties of a nanowire, consisting of a ferroelectric core of spin-1/2 surrounded by a ferroelectric shell of spin-1/2 with ferro- or anti-ferroelectric interfacial coupling have been studied within the framework of the Transverse Ising Model (TIM). We have examined the effects of the shell coupling Js, the interfacial coupling JInt, the transverse field Ω, and the temperature T on the hysteresis behavior and on the electric properties of the system. The remanent polarization and the coercive field as a function of the transverse field and the temperature are examined. A number of characteristic behavior have been found such as the appearance of triple hysteresis loops for appropriate values of the system parameters.

Nano-FTIR Spectroscopy to Investigate the Silicate Mineralogy of Mercury Analogues: Supporting MERTIS Onboard BepiColombo Mission

NASA Astrophysics Data System (ADS)

Varatharajan, I.; Maturilli, A.; Helbert, J.; Ulrich, G.; Born, K.; Namur, O.; Kästner, B.; Hecht, L.; Charlier, B.; Hiesinger, H.

2018-05-01

Nano-FTIR Spectroscopy is used to investigate the silicate mineralogy of synthetic Mercury analogues produced under reduced conditions representing different Mercury terrains. The study will support MERTIS payload onboard BepiColombo mission.

Synthesis, HPLC measurement and bioavailability of the phenolic amide amkamide

USDA-ARS?s Scientific Manuscript database

Amkamide, oretamide, becatamide, enferamide and veskamide are phenolic amides whose analogues are found in plants. Recently, becatamide was reported to have very potent mitochondria protective activity. In this study, becatamide and analogues (amkamide, oretamide, enferamide and veskamide) were chem...

Temperature dependent magnon-phonon coupling in bcc Fe from theory and experiment.

PubMed

Körmann, F; Grabowski, B; Dutta, B; Hickel, T; Mauger, L; Fultz, B; Neugebauer, J

2014-10-17

An ab initio based framework for quantitatively assessing the phonon contribution due to magnon-phonon interactions and lattice expansion is developed. The theoretical results for bcc Fe are in very good agreement with high-quality phonon frequency measurements. For some phonon branches, the magnon-phonon interaction is an order of magnitude larger than the phonon shift due to lattice expansion, demonstrating the strong impact of magnetic short-range order even significantly above the Curie temperature. The framework closes the previous simulation gap between the ferro- and paramagnetic limits.

Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro

NASA Astrophysics Data System (ADS)

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(S)-Protopanaxadiol (PPD) analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs.

PubMed

Liu, Junhua; Wang, Xu; Liu, Peng; Deng, Rongxin; Lei, Min; Chen, Wantao; Hu, Lihong

2013-07-15

Novel 20(S)-protopanoxadiol (PPD) analogues were designed, synthesized, and evaluated for the chemosensitizing activity against a multidrug resistant (MDR) cell line (KBvcr) overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic substituted aliphatic amine at the 24-positions (groups V) effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as docetaxel (DOC), vincristine (VCR), and adriamycin (ADM). PPD derivatives 12 and 18 showed 1.3-2.6 times more effective reversal ability than verapamil (VER) for DOC and VCR. Importantly, no cytotoxicity was observed by the active PPD analogues (5μM) against both non-MDR and MDR cells, suggesting that PPD analogues serve as novel lead compounds toward a potent and safe resistance modulator. Moreover, a preliminary mechanism study demonstrated that the chemosensitizing activity of PPD analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Occurrence and profiles of bisphenol analogues in municipal sewage sludge in China.

PubMed

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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pharmacological characterisation of strychnine and brucine analogues at glycine and alpha7 nicotinic acetylcholine receptors.

PubMed

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.

Molecular Imaging and Radionuclide Therapy of Melanoma Targeting the Melanocortin 1 Receptor

PubMed Central

Zhang, Chengcheng; Lin, Kuo-Shyan; Bénard, François

2017-01-01

Melanoma is a deadly disease at late metastatic stage, and early diagnosis and accurate staging remain the key aspects for managing melanoma. The melanocortin 1 receptor (MC1 R) is overexpressed in primary and metastatic melanomas, and its endogenous ligand, the α-melanocyte-stimulating hormone (αMSH), has been extensively studied for the development of MC1 R-targeted molecular imaging and therapy of melanoma. Natural αMSH is not well suited for this purpose due to low stability in vivo. Unnatural amino acid substitutions substantially stabilized the peptide, while cyclization via lactam bridge and metal coordination further improved binding affinity and stability. In this study, we summarized the development and the in vitro and in vivo characteristics of the radiolabeled αMSH analogues, including 99mTc-, 111In-, 67 Ga-, or 125I-labeled αMSH analogues for imaging with single-photon emission computed tomography; 68Ga-, 64Cu-, or 18F-labeled αMSH analogues for imaging with positron emission tomography; and 188Re-, 177Lu-, 90Y-, or 212Pb-labeled αMSH analogues for radionuclide therapy. These radiolabeled αMSH analogues showed promising results with high tumor uptake and rapid normal tissue activity clearance in the preclinical model of B16F1 and B16F10 mouse melanomas. These results highlight the potential of using radiolabeled αMSH analogues in clinical applications for molecular imaging and radionuclide therapy of melanoma. PMID:29182034

The effects of DHEA, 3beta-hydroxy-5alpha-androstane-6,17-dione, and 7-amino-DHEA analogues on short term and long term memory in the mouse.

PubMed

Bazin, Marc-Antoine; El Kihel, Laïla; Boulouard, Michel; Bouët, Valentine; Rault, Sylvain

2009-11-01

Neurosteroids have been reported to modulate memory processes in rodents. Three analogues of dehydroepiandrosterone (DHEA), two of them previously described (7beta-aminoDHEA and 7beta-amino-17-ethylenedioxy-DHEA), and a new one (3beta-hydroxy-5alpha-androstane-6,17-dione) were synthesized, and their effects were evaluated on memory. This study examined their effects on long term and short term memory in male (6 weeks old) NMRI mice in comparison with the reference drug. Long term memory was assessed using the passive avoidance task and short term memory (spatial working memory) using the spontaneous alternation task in a Y maze. Moreover, the effects of DHEA and its analogues on spontaneous locomotion were measured. In all tests, DHEA and analogues were injected at three equimolar doses (0.300-1.350-6.075 microM/kg). DHEA and its three analogues administered immediately post-training at the highest doses (6.075 microM/kg, s.c.) improved retention in passive avoidance test. Without effect per se in the spatial working memory task, the four compounds failed to reverse scopolamine (1mg/kg, i.p.)-induced deficit in spontaneous alternation. These data suggested an action of DHEA and analogues in consolidation of long term memory particularly when emotional components are implied. Moreover, data indicated that pharmacological modulation of DHEA as performed in this study provides derivatives giving the same mnemonic profile than reference molecule.

The Effectiveness of Teaching Methods Used in Graphic Design Pedagogy in Both Analogue and Digital Education Systems

ERIC Educational Resources Information Center

Alhajri, Salman

2016-01-01

Purpose: this paper investigates the effectiveness of teaching methods used in graphic design pedagogy in both analogue and digital education systems. Methodology and approach: the paper is based on theoretical study using a qualitative, case study approach. Comparison between the digital teaching methods and traditional teaching methods was…

Dunkl-Darboux differential-difference operators

NASA Astrophysics Data System (ADS)

Khekalo, S. P.

2017-02-01

Using a natural generalization, we construct and study analogues of Dunkl differential-difference operators on the line. These analogues turn out to be closely connected with the so-called Burchnall- Chaundy-Adler-Moser polynomials and, therefore, with Darboux transforms. We find the eigenfunctions of these operators.

Conformational analysis of compstatin analogues with molecular dynamics simulations in explicit water.

PubMed

Tamamis, Phanourios; Skourtis, Spiros S; Morikis, Dimitrios; Lambris, John D; Archontis, Georgios

2007-09-01

The cyclic 13-residue peptide compstatin is a potential therapeutic agent against the unregulated activation of the complement system. A thorough knowledge of its structural and dynamical properties in solution may assist the design of improved complement inhibitors. NMR studies have suggested that the 5-8 segment of free compstatin folds into a critical for activity 5-8 beta turn and the rest of the peptide is mainly disordered. Earlier computational studies of compstatin analogues with a polar-hydrogen/generalized-Born approximation reproduced the 5-8 turn, but also indicated the formation of beta-hairpin or alpha-helical elements and the existence of interactions between certain charged or aromatic sidechains. However, these features are absent or partly present in the NMR spectra, due to extensive conformational averaging. In order to check the compstatin properties with a more rigorous model of the intra- and intermolecular interactions, we conduct here 98-ns all-atom/explicit-water simulations of three compstatin analogues with variable activity; a native analogue, the more active mutant V4W/H9A and the inactive mutant Q5G. The 5-8 beta-turn population is in good accord with NMR. For the systems studied here, the simulations suggest that the 5-8 turn population does not correlate strictly with activity, in agreement with earlier mutational studies. Furthermore, they show structural differences among the analogues outside the 5-8 region. The possible role of these differences in activity is discussed. The probability of beta-hairpin or alpha-helix elements is much smaller with respect to the polar-hydrogen/GB simulations, and the persistent Trp4-Trp7 or Asp6-Arg11 sidechain interactions of the earlier GB studies are not reproduced. The present simulations extend the NMR data and improve our understanding of the properties of compstatin and related analogues.

A Comparison of Gallium and Indium Alkoxide Complexes as Catalysts for Ring-Opening Polymerization of Lactide.

PubMed

Kremer, Alexandre B; Andrews, Ryan J; Milner, Matthew J; Zhang, Xu R; Ebrahimi, Tannaz; Patrick, Brian O; Diaconescu, Paula L; Mehrkhodavandi, Parisa

2017-02-06

The impact of the metal size and Lewis acidity on the polymerization activity of group 13 metal complexes was studied, and it was shown that, within the same ligand family, indium complexes are far more reactive and selective than their gallium analogues. To this end, gallium and aluminum complexes supported by a tridentate diaminophenolate ligand, as well as gallium complexes supported by N,N'-ethylenebis(salicylimine)(salen) ligands, were synthesized and compared to their indium analogues. Using the tridentate ligand set, it was possible to isolate the gallium chloride complexes 3 and (±)-4 and the aluminum analogues 5 and (±)-6. The alkoxygallium complex (±)-2, supported by a salen ligand, was also prepared and characterized and, along with the three-component system GaCl 3 /BnOH/NEt 3 , was tested for the ring-opening polymerization of lactide and ε-caprolactone. The polymerization rates and selectivities of both systems were significantly lower than those for the indium analogues. The reaction of (±)-2 with 1 equiv of lactide forms the first insertion product, which is stable in solution and can be characterized at room temperature. In order to understand the differences of the reactivity within the group 13 metal complexes, a Lewis acidity study using triethylphosphine oxide (the Gutmann-Beckett method) was undertaken for a series of aluminum, gallium, and indium halide complexes; this study shows that indium halide complexes are less Lewis acidic than their aluminum and gallium analogues. Density functional theory calculations show that the Mulliken charges for the indium complexes are higher than those for the gallium analogues. These data suggest that the impact of ligands on the reactivity is more significant than that of the metal Lewis acidity.

The development and validation of the Visual Analogue Self-Esteem Scale (VASES).

PubMed

Brumfitt, S M; Sheeran, P

1999-11-01

To develop a visual analogue measure of self-esteem and test its psychometric properties. Two correlational studies involving samples of university students and aphasic speakers. Two hundred and forty-three university students completed multiple measures of self-esteem, depression and anxiety as well as measures of transitory mood and social desirability (Study 1). Two samples of aphasic speakers (N = 14 and N = 20) completed the Visual Analogue Self-Esteem Scale (VASES), the Rosenberg (1965) self-esteem scale and measures of depression and anxiety. (Study 2). Study 1 found evidence of good internal and test-retest reliability, construct validity and convergent and discriminant validity for a 10-item VASES. Study 2 demonstrated good internal reliability among aphasic speakers. The VASES is a short and easy to administer measure of self-esteem that possesses good psychometric properties.

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

PubMed

Vora, J P; Owens, D R; Dolben, J; Atiea, J A; Dean, J D; Kang, S; Burch, A; Brange, J

1988-11-12

To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. Study in normal people at a diabetes research unit and a university department of medical physics. Seven healthy male volunteers aged 20-39 not receiving any other drugs. After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and more dramatic hypoglycaemic effect with the insulin analogue. The much faster absorption from subcutaneous tissue of the disubstituted monomeric insulin analogue compared with soluble insulin suggests that the analogue may be a potential candidate for rapid insulin delivery after subcutaneous bolus injection.

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

PubMed Central

Vora, J. P.; Owens, D. R.; Dolben, J.; Atiea, J. A.; Dean, J. D.; Kang, S.; Burch, A.; Brange, J.

1988-01-01

OBJECTIVE--To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. DESIGN--Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. SETTING--Study in normal people at a diabetes research unit and a university department of medical physics. SUBJECTS--Seven healthy male volunteers aged 20-39 not receiving any other drugs. INTERVENTIONS--After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. END POINT--To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and more dramatic hypoglycaemic effect with the insulin analogue. CONCLUSIONS--The much faster absorption from subcutaneous tissue of the disubstituted monomeric insulin analogue compared with soluble insulin suggests that the analogue may be a potential candidate for rapid insulin delivery after subcutaneous bolus injection. PMID:3145064

Synthesis and binding studies of some epibatidine analogues.

PubMed

Rádl, S; Hezký, P; Hafner, W; Budesínský, M; Hejnová, L

2000-01-03

A series of epibatidine analogues and their positional isomers bearing an 8-azabicyclo[3.2.1]octane moiety is described. Some of the compounds, especially those containing 8-azabicyclo[3.2.1]oct-2-ene moiety show high affinity for the nicotinic cholinergic receptor.

Structural, Biochemical, and Computational Studies Reveal the Mechanism of Selective Aldehyde Dehydrogenase 1A1 Inhibition by Cytotoxic Duocarmycin Analogues.

PubMed

Koch, Maximilian F; Harteis, Sabrina; Blank, Iris D; Pestel, Galina; Tietze, Lutz F; Ochsenfeld, Christian; Schneider, Sabine; Sieber, Stephan A

2015-11-09

Analogues of the natural product duocarmycin bearing an indole moiety were shown to bind aldehyde dehydrogenase 1A1 (ALDH1A1) in addition to DNA, while derivatives without the indole solely addressed the ALDH1A1 protein. The molecular mechanism of selective ALDH1A1 inhibition by duocarmycin analogues was unraveled through cocrystallization, mutational studies, and molecular dynamics simulations. The structure of the complex shows the compound embedded in a hydrophobic pocket, where it is stabilized by several crucial π-stacking and van der Waals interactions. This binding mode positions the cyclopropyl electrophile for nucleophilic attack by the noncatalytic residue Cys302, thereby resulting in covalent attachment, steric occlusion of the active site, and inhibition of catalysis. The selectivity of duocarmycin analogues for ALDH1A1 is unique, since only minor alterations in the sequence of closely related protein isoforms restrict compound accessibility. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Membrane-Targeting DCAP Analogues with Broad-Spectrum Antibiotic Activity against Pathogenic Bacteria

PubMed Central

2015-01-01

We performed a structure–activity relationship study of 2-((3-(3,6-dichloro-9H-carbazol-9-yl)-2-hydroxypropyl)amino)-2-(hydroxymethyl)propane-1,3-diol (DCAP), which is an antibacterial agent that disrupts the membrane potential and permeability of bacteria. The stereochemistry of DCAP had no effect on the biological activity of DCAP. The aromaticity and electronegativity of the chlorine-substituted carbazole was required for activity, suggesting that its planar and dipolar characteristics orient DCAP in membranes. Increasing the hydrophobicity of the tail region of DCAP enhanced its antibiotic activity. Two DCAP analogues displayed promising antibacterial activity against the BSL-3 pathogens Bacillus anthracis and Francisella tularensis. Codosing DCAP analogues with ampicillin or kanamycin increased their potency. These studies demonstrate that DCAP and its analogues may be a promising scaffold for developing chemotherapeutic agents that bind to bacterial membranes and kill strains of slow-growing or dormant bacteria that cause persistent infections. PMID:25941556

Triphenylbutanamines: Kinesin Spindle Protein Inhibitors with in Vivo Antitumor Activity†

PubMed Central

2012-01-01

The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-l-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most potent C-trityl analogues exhibit Kiapp ≤ 10 nM and GI50 ≈ 50 nM, comparable to results from the phase II clinical benchmark ispinesib. Crystallographic studies reveal that they adopt the same overall binding configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5. Evaluation of their druglike properties reveals favorable profiles for future development and, in the clinical candidate ispinesib, moderate hERG and CYP inhibition. One triphenylbutanamine analogue and ispinesib possess very good bioavailability (51% and 45%, respectively), with the former showing in vivo antitumor growth activity in nude mice xenograft studies. PMID:22248262

Policy issues in space analogues

NASA Astrophysics Data System (ADS)

Auger, Robin N.; Facktor, Debra D.

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

A differential scanning calorimetric study of the effects of metal ions, substrate/product, substrate analogues and chaotropic anions on the thermal denaturation of yeast enolase 1.

PubMed

Brewer, J M; Wampler, J E

2001-03-14

The thermal denaturation of yeast enolase 1 was studied by differential scanning calorimetry (DSC) under conditions of subunit association/dissociation, enzymatic activity or substrate binding without turnover and substrate analogue binding. Subunit association stabilizes the enzyme, that is, the enzyme dissociates before denaturing. The conformational change produced by conformational metal ion binding increases thermal stability by reducing subunit dissociation. 'Substrate' or analogue binding additionally stabilizes the enzyme, irrespective of whether turnover is occurring, perhaps in part by the same mechanism. More strongly bound metal ions also stabilize the enzyme more, which we interpret as consistent with metal ion loss before denaturation, though possibly the denaturation pathway is different in the absence of metal ion. We suggest that some of the stabilization by 'substrate' and analogue binding is owing to the closure of moveable polypeptide loops about the active site, producing a more 'closed' and hence thermostable conformation.

The effects of dissociation on information processing for analogue trauma and neutral stimuli: a laboratory study.

PubMed

Olsen, Shira A; Beck, J Gayle

2012-01-01

This study investigated the effects of high and low levels of dissociation on information processing for analogue trauma and neutral stimuli. Fifty-four undergraduate females who reported high and low levels of trait dissociation were presented with two films, one depicting traumatic events, the other containing neutral material. Participants completed a divided attention task (yielding a proxy measure of attention), as well as explicit memory (free-recall) and implicit memory (word-stem completion) tasks for both films. Results indicated that the high DES group showed less attention and had poorer recall for the analogue trauma stimuli, relative to the neutral stimuli and the low DES group. These findings suggest that high levels of trait dissociation are associated with reductions in attention and memory for analogue trauma stimuli, relative to neutral stimuli and relative to low trait dissociation. Implications for the role of cognitive factors in the etiology of negative post-trauma responses are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Computer-aided rational design of novel EBF analogues with an aromatic ring.

PubMed

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.

Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer.

PubMed

Thomas, T J; Thomas, Thresia

2018-03-13

Polyamine levels are elevated in breast tumors compared to those of adjacent normal tissues. The female sex hormone, estrogen is implicated in the origin and progression of breast cancer. Estrogens stimulate and antiestrogens suppress the expression of polyamine biosynthetic enzyme, ornithine decarboxylate (ODC). Using several bis(ethyl)spermine analogues, we found that these analogues inhibited the proliferation of estrogen receptor-positive and estrogen receptor negative breast cancer cells in culture. There was structure-activity relationship in the efficacy of these compounds in suppressing cell growth. The activity of ODC was inhibited by these compounds, whereas the activity of the catabolizing enzyme, spermidine/spermine N ¹-acetyl transferase (SSAT) was increased by 6-fold by bis(ethyl)norspermine in MCF-7 cells. In a transgenic mouse model of breast cancer, bis(ethyl)norspermine reduced the formation and growth of spontaneous mammary tumor. Recent studies indicate that induction of polyamine catabolic enzymes SSAT and spermine oxidase (SMO) play key roles in the anti-proliferative and apoptotic effects of polyamine analogues and their combinations with chemotherapeutic agents such as 5-fluorouracil (5-FU) and paclitaxel. Thus, polyamine catabolic enzymes might be important therapeutic targets and markers of sensitivity in utilizing polyamine analogues in combination with other therapeutic agents.

Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer

PubMed Central

Thomas, Thresia

2018-01-01

Polyamine levels are elevated in breast tumors compared to those of adjacent normal tissues. The female sex hormone, estrogen is implicated in the origin and progression of breast cancer. Estrogens stimulate and antiestrogens suppress the expression of polyamine biosynthetic enzyme, ornithine decarboxylate (ODC). Using several bis(ethyl)spermine analogues, we found that these analogues inhibited the proliferation of estrogen receptor-positive and estrogen receptor negative breast cancer cells in culture. There was structure-activity relationship in the efficacy of these compounds in suppressing cell growth. The activity of ODC was inhibited by these compounds, whereas the activity of the catabolizing enzyme, spermidine/spermine N1-acetyl transferase (SSAT) was increased by 6-fold by bis(ethyl)norspermine in MCF-7 cells. In a transgenic mouse model of breast cancer, bis(ethyl)norspermine reduced the formation and growth of spontaneous mammary tumor. Recent studies indicate that induction of polyamine catabolic enzymes SSAT and spermine oxidase (SMO) play key roles in the anti-proliferative and apoptotic effects of polyamine analogues and their combinations with chemotherapeutic agents such as 5-fluorouracil (5-FU) and paclitaxel. Thus, polyamine catabolic enzymes might be important therapeutic targets and markers of sensitivity in utilizing polyamine analogues in combination with other therapeutic agents. PMID:29533973

Molecular designing and in silico evaluation of darunavir derivatives as anticancer agents

PubMed Central

Mahto, Manoj kumar; Yellapu, Nanda Kumar; Kilaru, Ravendra Babu; Chamarthi, Naga Raju; Bhaskar, Matcha

2014-01-01

Darunavir is a synthetic nonpeptidic protease inhibitor which has been tested for anticancer properties. To deduce and enhance the anticancer activity of the Darunavir, we have modified its reactive moiety in an effective way. We designed 9 analogues in ChemBioOffice 2010 and minimized using the LigPrep tool of Schrödinger 2011. These analogues can obstruct the activity of other signalling pathways which are implicated in many tumors. Results of the QikProp showed that all the analogues lied in the specified range of all the pharmacokinetic (ADMET) properties required to become the successful drug. Docking study was performed to test its anticancer activity against the biomarkers of the five main types of cancers i.e. bone, brain, breast, colon and skin cancer. Grid was generated for each oncoproteins by specifying the active site amino acids. The binding model of best scoring analogue with each protein was assessed from their G-scores and disclosed by docking analysis using the XP visualizer tool. An analysis of the receptor-ligand interaction studies revealed that these nine Darunavir analogues are active against all cancer biomarkers and have the features to prove themselves as anticancer drugs, further to be synthesized and tested against the cell lines. PMID:24966524

Analogue scale modelling of extensional tectonic processes using a large state-of-the-art centrifuge

NASA Astrophysics Data System (ADS)

Park, Heon-Joon; Lee, Changyeol

2017-04-01

Analogue scale modelling of extensional tectonic processes such as rifting and basin opening has been numerously conducted. Among the controlling factors, gravitational acceleration (g) on the scale models was regarded as a constant (Earth's gravity) in the most of the analogue model studies, and only a few model studies considered larger gravitational acceleration by using a centrifuge (an apparatus generating large centrifugal force by rotating the model at a high speed). Although analogue models using a centrifuge allow large scale-down and accelerated deformation that is derived by density differences such as salt diapir, the possible model size is mostly limited up to 10 cm. A state-of-the-art centrifuge installed at the KOCED Geotechnical Centrifuge Testing Center, Korea Advanced Institute of Science and Technology (KAIST) allows a large surface area of the scale-models up to 70 by 70 cm under the maximum capacity of 240 g-tons. Using the centrifuge, we will conduct analogue scale modelling of the extensional tectonic processes such as opening of the back-arc basin. Acknowledgement This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number 2014R1A6A3A04056405).

Bisphenol AF and Bisphenol B Exert Higher Estrogenic Effects than Bisphenol A via G Protein-Coupled Estrogen Receptor Pathway.

PubMed

Cao, Lin-Ying; Ren, Xiao-Min; Li, Chuan-Hai; Zhang, Jing; Qin, Wei-Ping; Yang, Yu; Wan, Bin; Guo, Liang-Hong

2017-10-03

Numerous studies have indicated estrogenic disruption effects of bisphenol A (BPA) analogues. Previous mechanistic studies were mainly focused on their genomic activities on nuclear estrogen receptor pathway. However, their nongenomic effects through G protein-coupled estrogen receptor (GPER) pathway remain poorly understood. Here, using a SKBR3 cell-based fluorescence competitive binding assay, we found six BPA analogues bound to GPER directly, with bisphenol AF (BPAF) and bisphenol B (BPB) displaying much higher (∼9-fold) binding affinity than BPA. Molecular docking also demonstrated the binding of these BPA analogues to GPER. By measuring calcium mobilization and cAMP production in SKBR3 cells, we found the binding of these BPA analogues to GPER lead to the activation of subsequent signaling pathways. Consistent with the binding results, BPAF and BPB presented higher agonistic activity than BPA with the lowest effective concentration (LOEC) of 10 nM. Moreover, based on the results of Boyden chamber and wound-healing assays, BPAF and BPB displayed higher activity in promoting GPER mediated SKBR3 cell migration than BPA with the LOEC of 100 nM. Overall, we found two BPA analogues BPAF and BPB could exert higher estrogenic effects than BPA via GPER pathway at nanomolar concentrations.

Racial Differences in Risk-Taking Propensity on the Youth Version of the Balloon Analogue Risk Task (BART-Y)

ERIC Educational Resources Information Center

Collado, Anahi; Risco, Cristina M.; Banducci, Anne N.; Chen, Kevin W.; MacPherson, Laura; Lejuez, Carl W.

2017-01-01

Research indicates that White adolescents tend to engage in greater levels of risk behavior relative to Black adolescents. To better understand these differences, the current study examined real-time changes in risk-taking propensity (RTP). The study utilized the Balloon Analogue Risk Task-Youth Version (BART-Y), a well-validated real-time,…

Comparative study of the interactions between bisphenol-A and its endocrine disrupting analogues with bovine serum albumin using multi-spectroscopic and molecular docking studies.

PubMed

Ikhlas, Shoeb; Usman, Afia; Ahmad, Masood

2018-04-24

Interaction studies of bisphenol analogues; biphenol-A (BPA), bisphenol-B (BPB), and bisphenol-F (BPF) with bovine serum albumin (BSA) were performed using multi-spectroscopic and molecular docking studies at the protein level. The mechanism of binding of bisphenols with BSA was dynamic in nature. SDS refolding experiments demonstrated no stabilization of BSA structure denatured by BPB, however, BSA denatured by BPA and BPF was found to get stabilized. Also, CD spectra and molecular docking studies revealed that BPB bound more strongly and induced more conformational changes in BSA in comparison to BPA. Hence, this study throws light on the replacement of BPA by its analogues and whether the replacement is associated with a possible risk, raising a doubt that perhaps BPB is not a good substitute of BPA.

Glycaemic control and prevalence of hypoglycaemic events in children and adolescents with type 1 diabetes mellitus treated with insulin analogues.

PubMed

Plavšić, Ljiljana; Mitrović, Katarina; Todorović, Sladjana; Vuković, Rade; Milenković, Tatjana; Zdravković, Dragan

2014-09-01

An ideal insulin regimen for children and adolescents with type 1 diabetes mellitus (T1DM) should be physiological, flexibile and predictable, protecting against hypoglycaemia. The aim of this study was to evaluate the influence of insulin analogues on glycaemic control and the occurance of hypoglycaemic episodes in children and adolescents with T1DM. The study group consisted of 151 children and adolescents (90 boys, 61 girls) treated with human insulins for at least 12 months before introducing insulin analogues. All the patients were divided into two groups: the group I consisted of 72 (47.7%) patients treated with three injections of regular human insulin before meals and long-acting analogue (RHI/LA), and the group II of 79 (52.30%) patients treated with a combination of rapid-acting and long-acting analogue (RA/LA). The levels of glycated hemoglobin (HbA1c) and the number of hypoglycaemic episodes were assessed at the beginning of therapy with insulin analogues, and after 6 and 12 months. The mean HbA1c was significantly lower in the group I (RHI/LA) after 6 months (9.15% vs 8.20%, p < 0.001) and after 12 months (9.15% vs 8.13%, p < 0.001) as well as in the group II (RA/LA) after 6 months (9.40% vs 8.240%, p < 0.001) and after 12 months of insulin analogues treatment (9.40% vs 8.38%, p < 0.001). The frequency of severe hypoglycaemia was significantly lower in both groups after 6 months (in the group I from 61.1% to 4.2% and in the group II from 54.4% to 1.3%, p < 0.001), and after 12 months (in the group I from 61.1% to 1.4% and in the group II from 54.4% to 1.3%, p < 0.001). Significantly better HbA1c values and lower risk of severe hypoglycaemia were established in children and adolescents with T1DM treated with insulin analogues.

Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation.

PubMed

Grimm, Marcus O W; Thiel, Andrea; Lauer, Anna A; Winkler, Jakob; Lehmann, Johannes; Regner, Liesa; Nelke, Christopher; Janitschke, Daniel; Benoist, Céline; Streidenberger, Olga; Stötzel, Hannah; Endres, Kristina; Herr, Christian; Beisswenger, Christoph; Grimm, Heike S; Bals, Robert; Lammert, Frank; Hartmann, Tobias

2017-12-19

Alzheimer's disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol) on AD-relevant mechanisms. D₂ and D₃ analogues decreased Aβ-production and increased Aβ-degradation in neuroblastoma cells or vitamin D deficient mouse brains. Effects were mediated by affecting the Aβ-producing enzymes BACE1 and γ-secretase. A reduced secretase activity was accompanied by a decreased BACE1 protein level and nicastrin expression, an essential component of the γ-secretase. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention.

Human Factor Studies on a Mars Analogue During Crew 100b International Lunar Exploration Working Group EuroMoonMars Crew: Proposed New Approaches for Future Human Space and Interplanetary Missions.

PubMed

Rai, Balwant; Kaur, Jasdeep

2012-11-01

Knowing the risks, costs, and complexities associated with human missions to Mars, analogue research can be a great (low-risk) tool for exploring the challenges associated with the preparation for living, operating, and undertaking research in interplanetary missions. Short-duration analogue studies, such as those being accomplished at the Mars Desert Research Station (MDRS), offer the chance to study mission operations and human factors in a simulated environment, and therefore contribute to exploration of the Moon and Mars in planned future missions. This article is based upon previously published articles, abstracts, and presentations by a series of independent authors, human factor studies performed on mars analogue station by Crew 100B. The MDRS Crew 100B performed studies over 15 days providing a unique insight into human factor issues in simulated short-duration Mars mission. In this study, 15 human factors were evaluated and analyzed by subjective and objective means, and from the summary of results it was concluded that optimum health of an individual and the crew as a whole is a necessity in order to encourage and maintain high performance and the satisfaction of project goals.

Human Factor Studies on a Mars Analogue During Crew 100b International Lunar Exploration Working Group EuroMoonMars Crew: Proposed New Approaches for Future Human Space and Interplanetary Missions

PubMed Central

Rai, Balwant; Kaur, Jasdeep

2012-01-01

Knowing the risks, costs, and complexities associated with human missions to Mars, analogue research can be a great (low-risk) tool for exploring the challenges associated with the preparation for living, operating, and undertaking research in interplanetary missions. Short-duration analogue studies, such as those being accomplished at the Mars Desert Research Station (MDRS), offer the chance to study mission operations and human factors in a simulated environment, and therefore contribute to exploration of the Moon and Mars in planned future missions. This article is based upon previously published articles, abstracts, and presentations by a series of independent authors, human factor studies performed on mars analogue station by Crew 100B. The MDRS Crew 100B performed studies over 15 days providing a unique insight into human factor issues in simulated short-duration Mars mission. In this study, 15 human factors were evaluated and analyzed by subjective and objective means, and from the summary of results it was concluded that optimum health of an individual and the crew as a whole is a necessity in order to encourage and maintain high performance and the satisfaction of project goals. PMID:23181225

57Fe Mössbauer spectroscopy and electron paramagnetic resonance studies of human liver ferritin, Ferrum Lek and Maltofer®

NASA Astrophysics Data System (ADS)

Alenkina, I. V.; Oshtrakh, M. I.; Klencsár, Z.; Kuzmann, E.; Chukin, A. V.; Semionkin, V. A.

2014-09-01

A human liver ferritin, commercial Ferrum Lek and Maltofer® samples were studied using Mössbauer spectroscopy and electron paramagnetic resonance. Two Mössbauer spectrometers have been used: (i) a high velocity resolution (4096 channels) at 90 and 295 K, (ii) and a low velocity resolution (250 channels) at 20 and 40 K. It is shown that the three studied materials have different superparamagnetic features at various temperatures. This may be caused by different magnetic anisotropy energy barriers, sizes (volume), structures and compositions of the iron cores. The electron paramagnetic resonance spectra of the ferritin, Ferrum Lek and Maltofer® were decomposed into multiple spectral components demonstrating the presence of minor ferro- or ferrimagnetic phases along with revealing marked differences among the studied substances. Mössbauer spectroscopy provides evidences on several components in the measured spectra which could be related to different regions, layers, nanocrystallites, etc. in the iron cores that coincides with heterogeneous and multiphase models for the ferritin iron cores.

In Silico Molecular Interaction of Bisphenol Analogues with Human Nuclear Receptors Reveals their Stronger Affinity vs. Classical Bisphenol A.

PubMed

Sharma, Shikha; Ahmad, Shahzad; Faraz Khan, Mohemmed; Parvez, Suhel; Raisuddin, Sheikh

2018-06-21

Bisphenol A (BPA) is known for endocrine disrupting activity. In order to replace BPA a number of bisphenol analogues have been designed. However, their activity profile is poorly described and little information exists about their endocrine disrupting potential and interactions with nuclear receptors. An understanding of such interaction may unravel mechanism of their molecular action and provide valuable inputs for risk assessment. BPA binds and activates peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors (RXRs) which act as transcription factors and regulate genes involved in glucose, lipid, and cholesterol metabolism and adipogenesis. We studied binding efficiency of 18 bisphenol analogues and BPA with human PPARs and RXRs. Using Maestro Schrodinger 9.4, docking scores of bisphenols were compared with the known endogenous and exogenous ligands of hPPARs and hRXRs. BPA showed good binding efficiency. Several analogues also showed higher binding efficiency than BPA. BPPH which has high tendency to be absorbed in tissues showed the strongest binding with hPPARα, hPPARβ, hPPARγ and hRXRα whereas two of the most toxic bisphenols, BPM and BPAF showed strongest binding with hRXRβ and hRXRγ. Some of the bisphenol analogues showed a stronger binding affinity with PPAR and RXR compared to BPA implying that BPA substitutes may not be fully safe and chemico-biological interactions indicate their toxic potential. These results may also serve to plan further studies for determining safety profile of bisphenol analogues and be helpful in risk characterization.

Rapid and sensitive determination of nine bisphenol analogues, three amphenicol antibiotics, and six phthalate metabolites in human urine samples using UHPLC-MS/MS.

PubMed

Yao, Yuan; Shao, Yijun; Zhan, Ming; Zou, Xiaoli; Qu, Weidong; Zhou, Ying

2018-06-01

Bisphenol analogues, amphenicol antibiotics, and phthalate have widely aroused public concerns due to their adverse effects on human health. In this study, a rapid and sensitive method for determination of nine bisphenol analogues, three amphenicol antibiotics, and six phthalate metabolites in the urine based on ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry was developed and validated. The sample pretreatment condition on the base of mixed-mode anion-exchange (Oasis MAX) SPE was optimized to separate bisphenol analogues and amphenicol antibiotics from phthalate metabolites: the former were detected with a mobile phase of 0.1% ammonium water solution/methanol containing 0.1% ammonium water solution in negative mode, whereas the latter were determined with a mobile phase of 0.1% acetic acid solution/acetonitrile containing 0.1% acetic acid in negative mode. The limits of detection were less than 0.26 ng/mL for bisphenol analogues, 0.12 ng/mL for amphenicol antibiotics, and 0.14 ng/mL for phathalate metabolites. The recoveries of all target analytes in three fortification levels ranged from 72.02 to 117.64% with the relative standard deviations of no larger than 14.51%. The matrix effect was adjusted by isotopically labeled internal standards. This proposed method was successfully applied to analyze 40 actual urines and 13 out of 18 studied compounds were detected. Graphical abstract Simultaneous determination of nine bisphenol analogues, three amphenicol antibiotics, and six phthalate metabolites in human urine samples.

Therapeutic index of gramicidin S is strongly modulated by D-phenylalanine analogues at the beta-turn.

PubMed

Solanas, Concepción; de la Torre, Beatriz G; Fernández-Reyes, María; Santiveri, Clara M; Jiménez, M Angeles; Rivas, Luis; Jiménez, Ana I; Andreu, David; Cativiela, Carlos

2009-02-12

Analogues of the cationic antimicrobial peptide gramicidin S (GS), cyclo(Val-Orn-Leu-D-Phe-Pro)2, with d-Phe residues replaced by different (restricted mobility, mostly) surrogates have been synthesized and used in SAR studies against several pathogenic bacteria. While all D-Phe substitutions are shown by NMR to preserve the overall beta-sheet conformation, they entail subtle structural alterations that lead to significant modifications in biological activity. In particular, the analogue incorporating D-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) shows a modest but significant increase in therapeutic index, mostly due to a sharp decrease in hemolytic effect. The fact that NMR data show a shortened distance between the D-Tic aromatic ring and the Orn delta-amino group may help explain the improved antibiotic profile of this analogue.

Therapeutic index of gramicidin S is strongly modulated by d-phenylalanine analogues at the β-turn

PubMed Central

Solanas, Concepción; de la Torre, Beatriz G.; Fernández-Reyes, María; Santiveri, Clara M.; Jiménez, M. Ángeles; Rivas, Luis; Jiménez, Ana I.; Andreu, David; Cativiela, Carlos

2009-01-01

Analogues of the cationic antimicrobial peptide gramicidin S (GS), cyclo(Val-Orn-Leu-d-Phe-Pro)2, with d-Phe residues replaced by different (restricted mobility, mostly) surrogates have been synthesized and used in SAR studies against several pathogenic bacteria. While all d-Phe substitutions are shown by NMR to preserve the overall β-sheet conformation, they entail subtle structural alterations that lead to significant modifications in biological activity. In particular, the analogue incorporating d-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) shows a modest but significant increase in therapeutic index, mostly due to a sharp decrease in hemolytic effect. The fact that NMR data show a shortened distance between the d-Tic aromatic ring and the Orn δ-amino group may help explain the improved antibiotic profile of this analogue. PMID:19132829

Swift heavy ion irradiation of interstellar dust analogues. Small carbonaceous species released by cosmic rays

NASA Astrophysics Data System (ADS)

Dartois, E.; Chabot, M.; Pino, T.; Béroff, K.; Godard, M.; Severin, D.; Bender, M.; Trautmann, C.

2017-03-01

Context. Interstellar dust grain particles are immersed in vacuum ultraviolet (VUV) and cosmic ray radiation environments influencing their physicochemical composition. Owing to the energetic ionizing interactions, carbonaceous dust particles release fragments that have direct impact on the gas phase chemistry. Aims: The exposure of carbonaceous dust analogues to cosmic rays is simulated in the laboratory by irradiating films of hydrogenated amorphous carbon interstellar analogues with energetic ions. New species formed and released into the gas phase are explored. Methods: Thin carbonaceous interstellar dust analogues were irradiated with gold (950 MeV), xenon (630 MeV), and carbon (43 MeV) ions at the GSI UNILAC accelerator. The evolution of the dust analogues is monitored in situ as a function of fluence at 40, 100, and 300 K. Effects on the solid phase are studied by means of infrared spectroscopy complemented by simultaneously recording mass spectrometry of species released into the gas phase. Results: Specific species produced and released under the ion beam are analyzed. Cross sections derived from ion-solid interaction processes are implemented in an astrophysical context.

8-Amido-Bearing pseudomycin B (PSB) analogue: novel antifungal agents.

PubMed

Zhang, Y Z; Sun, X; Zeckner, D J; Sachs, R K; Current, W L; Chen, S H

2001-01-22

During the course of a structure-activity relationship (SAR) study on novel depsinonapeptide pseudomycin B, we synthesized a total of 12 8-amidopseudomycin analogues via standard two-step sequence from either ZPSB 2 or AllocPSB 3. A number of these amides exhibited good in vitro antifungal activities.

[Synthesis and cytotoxicity of novel phosphorusless analogues of edelfosine].

PubMed

Romanova, S G; Shtil', A A; Serebrennikova, G A

2008-01-01

Modified series of phosphorusless edelfosine analogues bearing the polar heads of aliphatic bases, N,N-dimethylethanolamine and N,N,N(1),N(1)-tetramethylethylenediamine, were synthesized, with the length of the spacer varying from three to four methylene units. The cytotoxic characteristics of the compounds synthesized were studied.

Synthesis and antioxidant activity of peptide-based ebselen analogues.

PubMed

Satheeshkumar, Kandhan; Mugesh, Govindasamy

2011-04-18

A series of di- and tripeptide-based ebselen analogues has been synthesized. The compounds were characterized by (1)H, (13)C, and (77)Se NMR spectroscopy and mass spectral techniques. The glutathione peroxidase (GPx)-like antioxidant activity has been studied by using H(2)O(2) , tert-butyl hydroperoxide (tBuOOH), and cumene hydroperoxide (Cum-OOH) as substrates, and glutathione (GSH) as a cosubstrate. Although all the peptide-based compounds have a selenazole ring similar to that of ebselen, the GPx activity of these compounds highly depends on the nature of the peptide moiety attached to the nitrogen atom of the selenazole ring. It was observed that the introduction of a phenylalanine (Phe) amino acid residue in the N-terminal reduces the activity in all three peroxide systems. On the other hand, the introduction of aliphatic amino acid residues such as valine (Val) significantly enhances the GPx activity of the ebselen analogues. The difference in the catalytic activity of dipeptide-based ebselen derivatives can be ascribed mainly to the change in the reactivity of these compounds toward GSH and peroxide. Although the presence of the Val-Ala-CO(2) Me moiety facilitates the formation of a catalytically active selenol species, the reaction of ebselen analogues that has a Phe-Ile-CO(2) Me residue with GSH does not generate the corresponding selenol. To understand the antioxidant activity of the peptide-based ebselen analogues in the absence of GSH, these compounds were studied for their ability to inhibit peroxynitrite (PN)-mediated nitration of bovine serum albumin (BSA) and oxidation of dihydrorhodamine 123. In contrast to the GPx activity, the PN-scavenging activity of the Phe-based peptide analogues was found to be comparable to that of the Val-based compounds. However, the introduction of an additional Phe residue to the ebselen analogue that had a Val-Ala dipeptide significantly reduced the potency of the parent compound in PN-mediated nitration. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluating three commonly used growth media for assessing fumonisin analogues FB1, FB2 and FB3 production by nine Fusarium verticillioides isolates.

PubMed

Schoeman, A; Flett, B C; Janse van Rensburg, B

2017-02-01

Maize is most often infected by the fumonisin-producing Fusarium verticillioides. Total fumonisins of natural infected grain is made up of FB 1 , FB 2 and FB 3 with FB 1 occurring naturally at higher levels. A maize plant can be infected with more than one F. verticillioides isolate, and finding a reliable method to elucidate the toxigenic potential of these isolates is important to extrapolate the possible fumonisin risk to consumers of grain. It is not clear whether F. verticillioides produces similar fumonisin levels, as well as fumonisin analogue ratios, across media. In this study, nine F. verticillioides isolates were subjected to three methods of fumonisin testing using liquid media, maize patties and a field trial (silk inoculation of grain) in Potchefstroom, South Africa. Spore concentrations of 1 × 10 6 conidia ml - 1 of each isolate were used to inoculate the different media and levels fumonisin analogues were measured using HPLC. Fumonisin production per isolate was highly variable and was influenced by the two-way interaction of F. verticillioides isolate × growth media. Total fumonisins produced in the liquid medium ranged from 0 to 21.3 ppm, on maize patties fumonisins they ranged from 0 to 21.5 ppm, and in the silk inoculation technique they ranged from 0 to 15.5 ppm. The fumonisin analogue FB 1 occurred at higher levels followed by FB 3 in both in vitro studies. In the silk inoculation technique, fumonisin analogue FB 2 was the second highest occurring analogue after FB 1 . Isolate GCI 282 produced higher FB 2 and FB 3 levels than FB 1 in the patties and grain, respectively. In order not to miscalculate the fumonisin and analogue ratio levels per F. verticillioides isolate, the growth medium will have to be optimised for each isolate and more than one growth medium used.

The monoamine oxidase inhibition properties of selected structural analogues of methylene blue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delport, Anzelle

The thionine dye, methylene blue (MB), is a potent inhibitor of monoamine oxidase (MAO) A, a property that may, at least in part, mediate its antidepressant effects in humans and animals. The central inhibition of MAO-A by MB has also been linked to serotonin toxicity (ST) which may arise when MB is used in combination with serotonergic drugs. Structural analogues and the principal metabolite of MB, azure B, have also been reported to inhibit the MAO enzymes, with all compounds exhibiting specificity for the MAO-A isoform. To expand on the structure-activity relationships (SARs) of MAO inhibition by MB analogues, themore » present study investigates the human MAO inhibition properties of five MB analogues: neutral red, Nile blue, new methylene blue, cresyl violet and 1,9-dimethyl methylene blue. Similar to MB, these analogues also are specific MAO-A inhibitors with cresyl violet (IC{sub 50} = 0.0037 μM), Nile blue (IC{sub 50} = 0.0077 μM) and 1,9-dimethyl methylene blue (IC{sub 50} = 0.018 μM) exhibiting higher potency inhibition compared to MB (IC{sub 50} = 0.07 μM). Nile blue also represents a potent MAO-B inhibitor with an IC{sub 50} value of 0.012 μM. From the results it may be concluded that non-thionine MB analogues (e.g. cresyl violet and Nile blue) also may exhibit potent MAO inhibition, a property which should be considered when using these compounds in pharmacological studies. Benzophenoxazines such as cresyl violet and Nile blue are, similar to phenothiazines (e.g. MB), representative of high potency MAO-A inhibitors with a potential risk of ST. - Highlights: • MB analogues, cresyl violet and Nile blue, are high potency MAO-A inhibitors. • Nile blue also represents a potent MAO-B inhibitor. • Potent MAO-A inhibition should alert to potential serotonin toxicity.« less

[Positioning of mRNA 3' of the a site bound codon on the human 80S ribosome].

PubMed

Molotkov, M V; Graĭfer, D M; Demeshkina, N A; Repkova, M N; Ven'iaminova, A G; Karpova, G G

2005-01-01

Short mRNA analogues carrying a UUU triplet at the 5'-termini and a perfluorophenylazide group at either the N7 atom of the guanosine or the C5 atom of the uridine 3' of the triplet were applied to study positioning of mRNA 3' of the A site codon. Complexes of 80S ribosomes with the mRNA analogues were obtained in the presence of tRNAPhe that directed UUU codon to the P site and consequently provided placement of the nucleotide with cross-linker in positions +9 or +12 with respect to the first nucleotide of the P site bound codon. Both types mRNA analogues cross-linked to the 18S rRNA and 40S proteins under mild UV-irradiation. Cross-linking patterns in the complexes where modified nucleotides of the mRNA analogues were in position +7 were analyzed for comparison (cross-linking to the 18S rRNA in such complexes has been studied previously). The efficiency of cross-linking to the ribosomal components depended on the nature of the modified nucleotide in the mRNA analogue and its position on the ribosome, extent of cross-linking to the 18S rRNA being decreased drastically when the modified nucleotide was moved from position +7 to position +12. The nucleotides of 18S rRNA cross-linked to mRNA analogues were determined. Modified nucleotides in positions +9 and +12 cross-linked to the invariant dinucleotide A1824/A1825 and to variable A1823 in the 3'-minidomain of 18S rRNA as well as to protein S15. The same ribosomal components have been found earlier to cross-link to modified mRNA nucleotides in positions from +4 to +7. Besides, all mRNA analogues cross-linked to the invariant nucleotide c1698 in the 3'-minidomain and to and the conserved region 605-620 closing helix 18 in the 5'-domain.

SERUM VITAMIN B12, IRON AND FOLIC ACID DEFICIENCIES IN OBESE INDIVIDUALS SUBMITTED TO DIFFERENT BARIATRIC TECHNIQUES.

PubMed

Silva, Rafaella de Andrade; Malta, Flávia Monteiro França; Correia, Maria Flora Ferreira Sampaio Carvalho; Burgos, Maria Goretti Pessoa de Araújo

Different surgical techniques to combat obesity combine malabsorption with restrictive procedures and can lead to metabolic problems, such as micronutrient deficiencies. Assess vitamin B12, iron and folic acid deficiencies associated with the lifestyle of obese individuals having been submitted to different bariatric techniques. A retrospective analysis was performed using the electronic charts of patients submitted to bariatric surgery involving adjustable gastric banding and Roux-en-Y gastric bypass at the São João Hospital Center in the city of Porto, Portugal, between 2005 and 2010. The following data were collected: surgical technique, sex, age, marital status, serum concentrations of vitamin B12, iron and folic acid and postoperative lifestyle. A 5% significance level was used for the statistical analysis (p<0.05). Among 286 individuals evaluated, females accounted for 90.9% of the overall sample (both techniques). Gastric banding was performed more (68.9%), but greater nutrient deficiencies were found following gastric bypass. Iron was the most prevalent deficiency (21.3%), followed by vitamin B12 (16.9%) and folic acid (4.5%). Mild to moderate alcohol intake, adherence to the diet and the use of multivitamins reduced the frequency, but did not avoid micronutrient deficiency. Vitamin B12, iron and folic acid deficiencies were found in the first and second year following the two bariatric techniques analyzed and were more frequent among individuals submitted to gastric bypass. As diferentes técnicas da cirurgia da obesidade combinam má absorção com procedimentos restritivos e podem levar à complicações metabólicas, entre as quais se destacam as deficiências de micronutrientes. Avaliar a deficiência de vitamina B12, ferro e ácido fólico e fatores associados ao estilo de vida de obesos submetidos a diferentes técnicas cirúrgicas. Análise retrospectiva dos prontuários eletrônicos de pacientes submetidos à cirurgia bariátrica pelas técnicas de banda gástrica ajustável e bypass gástrico em Y-de-Roux, no Centro Hospitalar de São João, E.P.E., Porto - Portugal, no período de 2005-2010. Foram coletadas: técnica cirúrgica, sexo, idade, estado civil, concentrações séricas de vitamina B12, ferro e ácido fólico e o estilo de vida no pós-operatório. Para análise estatística foi utilizado nível de significância de 5% (p< 0,05). Dentre os 286 indivíduos avaliados, houve predomínio do sexo feminino (90,9%) em ambas as técnicas cirúrgicas, sendo a banda gástrica a mais realizada (68,9%); no entanto maiores deficiências de micronutrientes foram detectadas após o bypass gástrico. A deficiência de micronutriente mais prevalente foi a de ferro (21,3%), seguida da vitamina B12 (16,9%) e do ácido fólico (4,5%). A ingestão de bebida alcoólica de leve-moderada, a adesão à dieta e o uso de polivitamínicos reduziu a frequência, mas não evitou a carência de micronutrientes. A deficiência de vitamina B12, ferro e ácido fólico foi observada durante o primeiro e o segundo anos após as duas técnicas avaliadas, sendo mais frequente nos pacientes submetidos ao bypass gástrico.

Conformationally Constrained Analogues of N'-(4-t-Butylbenzyl)-N-(4-Methylsulfonylaminobenzyl)Thiourea as TRPV1 Antagonists

PubMed Central

Ryu, HyungChul; Lim, Ju-Ok; Kang, Dong Wook; Pearce, Larry V.; Tran, Richard; Toth, Attila; Lee, Jeewoo; Blumberg, Peter M.

2012-01-01

A series of bicyclic analogues having indan and tetrahydronaphthalene templates in the A-region were designed as conformationally constrained analogues of our previously reported potent TRPV1 antagonists (1, 3). The activities for rat TRPV1 of the conformationally restricted analogues were moderately or markedly diminished, particularly in the case of the tetrahydronaphthalene analogues. The analysis indicated that steric constraints at the benzylic position in the bicyclic analogues were an important factor for their unfavorable interaction with the receptor. PMID:18406014

Weak arrest-like and field-driven first order magnetic phase transitions of itinerant Fe3Ga4 revealed by magnetization and magnetoresistance isotherms

NASA Astrophysics Data System (ADS)

Samatham, S. Shanmukharao; Suresh, K. G.

2017-01-01

The detailed magnetic study of complex 3d-electron based Fe3Ga4 is reported. It undergoes paramagnetic to antiferromagnetic (TN) and antiferromagnetic to ferromagnetic (TC) transitions respectively around 380 and 70 K. The thermal hysteresis of field-cooled cooling (FCC) and field-cooled warming (FCW) hints at first order phase transition below Curie temperature. A weak phase coexistence of ferro and antiferromagnetic phases is suggested by exploring the arrest-like first-order phenomenon. In the intermediate temperature range, field-driven metamagnetic transition from antiferro to ferromagnetic phase is confirmed. Further bringing the system very near to TN, field-induced transitions disappear and above TN predominant paramagnetic contribution is evident. The magnetic H-T phase diagram distinguishing different magnetic phases of Fe3Ga4 is obtained.

Monte Carlo and Ab-initio calculation of TM (Ti, V, Cr, Mn, Fe, Co, Ni) doped MgH2 hydride: GGA and SIC approximation

NASA Astrophysics Data System (ADS)

Salmani, E.; Laghrissi, A.; Laamouri, R.; Benchafia, E.; Ez-Zahraouy, H.; Benyoussef, A.

2017-02-01

MgH2: TM (TM: V, Cr, Mn, Fe, Co, Ni) based dilute magnetic semiconductors (DMS) are investigated using first principle calculations. Our results show that the ferromagnetic state is stable when TM introduces magnetic moments as well as intrinsic carriers in TM: Co, V, Cr, Ti; Mg0.95TM0.05H2. Some of the DMS Ferro magnets under study exhibit a half-metallic behavior, which make them suitable for spintronic applications. The double exchange is shown to be the underlying mechanism responsible for the magnetism of such materials. The exchange interactions obtained from first principle calculations and used in a classical Ising model by a Monte Carlo approach resulted in ferromagnetic states with Curie temperatures within the ambient conditions.

PEGylation, increasing specific activity and multiple dosing as strategies to improve the risk-benefit profile of targeted radionuclide therapy with 177Lu-DOTA-bombesin analogues

PubMed Central

2012-01-01

Background Radiolabelled bombesin (BN) conjugates are promising radiotracers for imaging and therapy of breast and prostate tumours, in which BN2/gastrin-releasing peptide receptors are overexpressed. We describe the influence of the specific activity of a 177Lu-DOTA-PEG5k-Lys-B analogue on its therapeutic efficacy and compare it with its non-PEGylated counterpart. Methods Derivatisation of a stabilised DOTA-BN(7–14)[Cha13,Nle14] analogue with a linear PEG molecule of 5 kDa (PEG5k) was performed by PEGylation of the ϵ-amino group of a β3hLys-βAla-βAla spacer between the BN sequence and the DOTA chelator. The non-PEGylated and the PEGylated analogues were radiolabelled with 177Lu. In vitro evaluation was performed in human prostate carcinoma PC-3 cells, and in vivo studies were carried out in nude mice bearing PC-3 tumour xenografts. Different specific activities of the PEGylated BN analogue and various dose regimens were evaluated concerning their therapeutic efficacy. Results The specificity and the binding affinity of the BN analogue for BN2/GRP receptors were only slightly reduced by PEGylation. In vitro binding kinetics of the PEGylated analogue was slower since steady-state condition was reached after 4 h. PEGylation improved the stability of BN conjugate in vitro in human plasma by a factor of 5.6. The non-PEGylated BN analogue showed favourable pharmacokinetics already, i.e. fast blood clearance and renal excretion, but PEGylation improved the in vivo behaviour further. One hour after injection, the tumour uptake of the PEG5k-BN derivative was higher compared with that of the non-PEGylated analogue (3.43 ± 0.63% vs. 1.88 ± 0.4% ID/g). Moreover, the increased tumour retention resulted in a twofold higher tumour accumulation at 24 h p.i., and increased tumour-to-non-target ratios (tumour-to-kidney, 0.6 vs. 0.4; tumour-to-liver, 8.8 vs. 5.9, 24 h p.i.). In the therapy study, both 177Lu-labelled BN analogues significantly inhibited tumour growth. The therapeutic efficacy was highest for the PEGylated derivative of high specific activity administered in two fractions (2 × 20 MBq = 40 MBq) at day 0 and day 7 (73% tumour growth inhibition, 3 weeks after therapy). Conclusions PEGylation and increasing the specific activity enhance the pharmacokinetic properties of a 177Lu-labelled BN-based radiopharmaceutical and provide a protocol for targeted radionuclide therapy with a beneficial anti-tumour effectiveness and a favourable risk-profile at the same time. PMID:22681935

Mid-Western US heavy summer-precipitation in regional and global climate models: the impact on model skill and consensus through an analogue lens

NASA Astrophysics Data System (ADS)

Gao, Xiang; Schlosser, C. Adam

2018-04-01

Regional climate models (RCMs) can simulate heavy precipitation more accurately than general circulation models (GCMs) through more realistic representation of topography and mesoscale processes. Analogue methods of downscaling, which identify the large-scale atmospheric conditions associated with heavy precipitation, can also produce more accurate and precise heavy precipitation frequency in GCMs than the simulated precipitation. In this study, we examine the performances of the analogue method versus direct simulation, when applied to RCM and GCM simulations, in detecting present-day and future changes in summer (JJA) heavy precipitation over the Midwestern United States. We find analogue methods are comparable to MERRA-2 and its bias-corrected precipitation in characterizing the occurrence and interannual variations of observed heavy precipitation events, all significantly improving upon MERRA precipitation. For the late twentieth-century heavy precipitation frequency, RCM precipitation improves upon the corresponding driving GCM with greater accuracy yet comparable inter-model discrepancies, while both RCM- and GCM-based analogue results outperform their model-simulated precipitation counterparts in terms of accuracy and model consensus. For the projected trends in heavy precipitation frequency through the mid twenty-first century, analogue method also manifests its superiority to direct simulation with reduced intermodel disparities, while the RCM-based analogue and simulated precipitation do not demonstrate a salient improvement (in model consensus) over the GCM-based assessment. However, a number of caveats preclude any overall judgement, and further work—over any region of interest—should include a larger sample of GCMs and RCMs as well as ensemble simulations to comprehensively account for internal variability.

Magnetic properties changes due to hydrocarbon contaminated groundwater table fluctuations

NASA Astrophysics Data System (ADS)

Ameen, Nawrass

2013-04-01

This study aims to understand the mechanisms and conditions which control the formation and transformation of ferro(i)magnetic minerals caused by hydrocarbon contaminated groundwater, in particular in the zone of fluctuating water levels. The work extends previous studies conducted at the same site. The study area is a former military air base at Hradčany, Czech Republic (50°37'22.71"N, 14°45'2.24"E). The site was heavily contaminated with petroleum hydrocarbons, due to leaks in petroleum storage tanks and jet fuelling stations over years of active use by the Soviet Union, which closed the base in 1991. The site is one of the most important sources of high quality groundwater in the Czech Republic. In a previous study, Rijal et al. (2010) concluded that the contaminants could be flushed into the sediments as the water level rose due to remediation processes leading to new formation of magnetite. In this previous study three different locations were investigated; however, from each location only one core was obtained. In order to recognize significant magnetic signatures versus depth three cores from each of these three locations were drilled in early 2012, penetrating the unsaturated zone, the groundwater fluctuation (GWF) zone and extending to about one meter below the groundwater level (~2.3 m depth at the time of sampling). Magnetic susceptibility (MS) profiles combined with other magnetic properties were analyzed to obtain a significant depth distribution of the ferro(i)magnetic concentration. Sediment properties, hydrocarbon content and bacterial activity were additionally studied. The results show that the highest ferrimagnetic mineral concentrations exist between 1.4-1.9 m depth from the baseline which is interpreted as the top of the GWF zone. Spikes of MS detected in the previous studies turned out to represent small-scale isolated features, but the trend of increasing MS values from the lowermost position of the groundwater table upward was verified. Mineral magnetic parameters indicate that magnetite is responsible for the MS signal which confirms the previous results (Rijal et al., 2010). The so far existing uncertainty of the groundwater level position could be solved. Bacterial activity is studied at particular depth horizons as it is assumed to be responsible for iron mineralogy changes. References: Rijal M.L., Appel E., Petrovský E. and Blaha U., 2010. Change of magnetic properties due to fluctuations of hydrocarbon contaminated groundwater in unconsolidated sediments. Environ.Pollut., 158, 1756-1762.

Monomeric insulins and their experimental and clinical implications.

PubMed

Brange, J; Owens, D R; Kang, S; Vølund, A

1990-09-01

Due to the inherent pharmacokinetic properties of available insulins, normoglycemia is rarely, if ever, achieved in insulin-dependent diabetic patients without compromising their quality of life. Subcutaneous insulin absorption is influenced by many factors, among which the associated state of insulin (hexameric) in pharmaceutical formulation may be of importance. This review describes the development of a series of human insulin analogues with reduced tendency to self-association that, because of more rapid absorption, are better suited to meal-related therapy. DNA technology has made it possible to prepare insulins that remain dimeric or even monomeric at high concentration by introducing one or a few amino acid substitutions into human insulin. These analogues were characterized and used for elucidating the mechanisms involved in subcutaneous absorption and were investigated in preliminary clinical studies. Their relative receptor binding and in vitro potency (free-fat cell assay), ranging from 0.05 to 600% relative to human insulin, were strongly correlated (r = 0.97). In vivo, most of the analogues exhibited approximately 100% activity, explainable by a dominating receptor-mediated clearance. This was confirmed by clamp studies in which correlation between receptor binding and clearance was observed. Thus, an analogue with reduced binding and clearance gives higher circulating concentrations, counterbalancing the reduced potency at the cellular level. Absorption studies in pigs revealed a strong inverse correlation (r = 0.96) between the rate of subcutaneous absorption and the mean association state of the insulin analogues. These studies also demonstrated that monomeric insulins were absorbed three times faster than human insulin. In healthy subjects, rates of disappearance from subcutis were two to three times faster for dimeric and monomeric analogues than for human insulin. Concomitantly, a more rapid rise in plasma insulin concentration and an earlier hypoglycemic response with the analogues were observed. The monomeric insulin had no lag phase and followed a monoexponential course throughout the absorption process. In contrast, two phases in rate of absorption were identified for the dimer and three for the normal hexameric human insulin. The initial lag phase and the subsequent accelerated absorption of soluble insulin can now be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process. In the light of these results, the effects of insulin concentration, injected volume, temperature, and massage on the absorption process are now also understood.(ABSTRACT TRUNCATED AT 400 WORDS)

Dielectric Characterization of a Nonlinear Optical Material

PubMed Central

Lunkenheimer, P.; Krohns, S.; Gemander, F.; Schmahl, W. W.; Loidl, A.

2014-01-01

Batisite was reported to be a nonlinear optical material showing second harmonic generation. Using dielectric spectroscopy and polarization measurements, we provide a thorough investigation of the dielectric and charge-transport properties of this material. Batisite shows the typical characteristics of a linear lossy dielectric. No evidence for ferro- or antiferroelectric polarization is found. As the second-harmonic generation observed in batisite points to a non-centrosymmetric structure, this material is piezoelectric, but most likely not ferroelectric. In addition, we found evidence for hopping charge transport of localized charge carriers and a relaxational process at low temperatures. PMID:25109553

Magnetic refrigeration apparatus with belt of ferro or paramagnetic material

DOEpatents

Barclay, John A.; Stewart, Walter F.; Henke, Michael D.; Kalash, Kenneth E.

1987-01-01

A magnetic refrigerator operating in the 12 to 77K range utilizes a belt which carries ferromagnetic or paramagnetic material and which is disposed in a loop which passes through the center of a solenoidal magnet to achieve cooling. The magnetic material carried by the belt, which can be blocks in frames of a linked belt, can be a mixture of substances with different Curie temperatures arranged such that the Curie temperatures progressively increase from one edge of the belt to the other. This magnetic refrigerator can be used to cool and liquefy hydrogen or other fluids.

Magnetic refrigeration apparatus with belt of ferro or paramagnetic material

DOEpatents

Barclay, J.A.; Stewart, W.F.; Henke, M.D.; Kalash, K.E.

1986-04-03

A magnetic refrigerator operating in the 12 to 77 K range utilizes a belt which carries ferromagnetic or paramagnetic material and which is disposed in a loop which passes through the center of a solenoidal magnet to achieve cooling. The magnetic material carried by the belt, which can be blocks in frames of a linked belt, can be a mixture of substances with different Curie temperatures arranged such that the Curie temperatures progressively increase from one edge of the belt to the other. This magnetic refrigerator can be used to cool and liquefy hydrogen or other fluids.

Metal hydride reasearch and development program at Brookhaven National Laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, J.R.; Reilly, J.J.

1978-01-01

A progress report is presented covering work performed in the hydrogen materials development program at Brookhaven National Laboratory (BNL) for FY78 which encompasses the time period from October 1, 1977 through September 30, 1978. The subjects to be discussed here concern properties of importance in the utilization of metal hydrides as energy storage media. Most of the areas of research were initiated prior to FY78, however all of the results contained in this manuscript were obtained during the aforementioned period of time. The following subjects will be discussed: the properties of ferro-titanium and chrome-titanium alloy hydrides.

Ferro- and antiferro-magnetism in (Np, Pu)BC

NASA Astrophysics Data System (ADS)

Klimczuk, T.; Shick, A. B.; Kozub, A. L.; Griveau, J.-C.; Colineau, E.; Falmbigl, M.; Wastin, F.; Rogl, P.

2015-04-01

Two new transuranium metal boron carbides, NpBC and PuBC, have been synthesized. Rietveld refinements of powder XRD patterns of {Np,Pu}BC confirmed in both cases isotypism with the structure type of UBC. Temperature dependent magnetic susceptibility data reveal antiferromagnetic ordering for PuBC below TN = 44 K, whereas ferromagnetic ordering was found for NpBC below TC = 61 K. Heat capacity measurements prove the bulk character of the observed magnetic transition for both compounds. The total energy electronic band structure calculations support formation of the ferromagnetic ground state for NpBC and the antiferromagnetic ground state for PuBC.

Preparation and Evaluation at the Delta Opioid Receptor of a Series of Linear Leu-Enkephalin Analogues Obtained by Systematic Replacement of the Amides

PubMed Central

2013-01-01

Leu-enkephalin analogues, in which the amide bonds were sequentially and systematically replaced either by ester or N-methyl amide bonds, were prepared using classical organic chemistry as well as solid phase peptide synthesis (SPPS). The peptidomimetics were characterized using competition binding, ERK1/2 phosphorylation, receptor internalization, and contractility assays to evaluate their pharmacological profile over the delta opioid receptor (DOPr). The lipophilicity (LogD7.4) and plasma stability of the active analogues were also measured. Our results revealed that the last amide bond can be successfully replaced by either an ester or an N-methyl amide bond without significantly decreasing the biological activity of the corresponding analogues when compared to Leu-enkephalin. The peptidomimetics with an N-methyl amide function between residues Phe and Leu were found to be more lipophilic and more stable than Leu-enkephalin. Findings from the present study further revealed that the hydrogen-bond donor properties of the fourth amide of Leu-enkephalin are not important for its biological activity on DOPr. Our results show that the systematic replacement of amide bonds by isosteric functions represents an efficient way to design and synthesize novel peptide analogues with enhanced stability. Our findings further suggest that such a strategy can also be useful to study the biological roles of amide bonds. PMID:23650868

Differential Top10 promoter regulation by six tetracycline analogues in plant cells

NASA Technical Reports Server (NTRS)

Love, John; Allen, George C.; Gatz, Christiane; Thompson, William F.; Brown, C. S. (Principal Investigator)

2002-01-01

The effects of five tetracycline analogues, anhydrotetracycline, doxycycline, minocycline, oxytetracycline, and tetracycline, on Top10 promoter activity in NT1 tobacco tissue culture cells have been analysed. The concentration that repressed Top10 promoter activity, the level of transgene repression and the kinetics of transgene de-repression were determined for each analogue, and could not be predicted from in vitro binding affinity to the tetracycline repressor or from comparison with animal cells. Doxycycline had the most potent effect on the Top10 promoter and completely inhibited transgene expression at 4 nmol l(-1). Tetracycline was the most versatile of the analogues tested; tetracycline inhibited the Top10 promoter at 10 nmol l(-1) and was easily washed out to restore Top10-driven expression in 12-24 h. A study was also made of the suitability for plant research of a novel tetracycline analogue, GR33076X. In animal cells, GR33076X de-repressed Top10 promoter activity in the presence of inhibitory concentrations of anhydrotetracycline. In NT1, it is shown that GR 33076X can antagonize repression of the Top10 promoter in the presence of tetracycline, but not of anhydrotetracycline or of doxycycline. Different tetracycline analogues can therefore be used to regulate the Top10 promoter in plant cells and this property may be exploited in planning an optimum course of transgene regulation.

Differential Top10 promoter regulation by six tetracycline analogues in plant cells.

PubMed

Love, John; Allen, George C; Gatz, Christiane; Thompson, William F

2002-09-01

The effects of five tetracycline analogues, anhydrotetracycline, doxycycline, minocycline, oxytetracycline, and tetracycline, on Top10 promoter activity in NT1 tobacco tissue culture cells have been analysed. The concentration that repressed Top10 promoter activity, the level of transgene repression and the kinetics of transgene de-repression were determined for each analogue, and could not be predicted from in vitro binding affinity to the tetracycline repressor or from comparison with animal cells. Doxycycline had the most potent effect on the Top10 promoter and completely inhibited transgene expression at 4 nmol l(-1). Tetracycline was the most versatile of the analogues tested; tetracycline inhibited the Top10 promoter at 10 nmol l(-1) and was easily washed out to restore Top10-driven expression in 12-24 h. A study was also made of the suitability for plant research of a novel tetracycline analogue, GR33076X. In animal cells, GR33076X de-repressed Top10 promoter activity in the presence of inhibitory concentrations of anhydrotetracycline. In NT1, it is shown that GR 33076X can antagonize repression of the Top10 promoter in the presence of tetracycline, but not of anhydrotetracycline or of doxycycline. Different tetracycline analogues can therefore be used to regulate the Top10 promoter in plant cells and this property may be exploited in planning an optimum course of transgene regulation.

Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation

PubMed Central

Winkler, Jakob; Lehmann, Johannes; Regner, Liesa; Nelke, Christopher; Janitschke, Daniel; Benoist, Céline; Streidenberger, Olga; Stötzel, Hannah; Endres, Kristina; Beisswenger, Christoph; Bals, Robert; Lammert, Frank; Hartmann, Tobias

2017-01-01

Alzheimer’s disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol) on AD-relevant mechanisms. D2 and D3 analogues decreased Aβ-production and increased Aβ-degradation in neuroblastoma cells or vitamin D deficient mouse brains. Effects were mediated by affecting the Aβ-producing enzymes BACE1 and γ-secretase. A reduced secretase activity was accompanied by a decreased BACE1 protein level and nicastrin expression, an essential component of the γ-secretase. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention. PMID:29257109

Lumbar spine radiography — poor collimation practices after implementation of digital technology

PubMed Central

Zetterberg, L G; Espeland, A

2011-01-01

Objectives The transition from analogue to digital radiography may have reduced the motivation to perform proper collimation, as digital techniques have made it possible to mask areas irradiated outside the area of diagnostic interest (ADI). We examined the hypothesis that collimation practices have deteriorated since digitalisation. Methods After defining the ADI, we compared the proportion of the irradiated field outside the ADI in 86 digital and 86 analogue frontal lumbar spine radiographs using the Mann–Whitney test. 50 digital images and 50 analogue images were from a Norwegian hospital and the remainder from a Danish hospital. Consecutive digital images were compared with analogue images (from the hospitals' archives) produced in the 4 years prior to digitalisation. Both hospitals' standard radiographic procedures remained unchanged during the study. For digital images, the irradiated field was assessed using non-masked raw-data images. Results The proportion of the irradiated field outside the ADI was larger in digital than in analogue images (mean 61.7% vs 42.4%, p<0.001), and also in a subsample of 39 image pairs that could be matched for patient age (p<0.001). The mean total field size was 46% larger in digital than in analogue images (791 cm2 vs 541 cm2). Conclusion Following the implementation of digital radiography, considerably larger areas were irradiated. This causes unnecessarily high radiation doses to patients. PMID:21606070

2-(2-Bromophenyl)-formononetin and 2-heptyl-formononetin are PPARγ partial agonists and reduce lipid accumulation in 3T3-L1 adipocytes.

PubMed

Andersen, Charlotte; Kotowska, Dorota; Tortzen, Christian G; Kristiansen, Karsten; Nielsen, John; Petersen, Rasmus Koefoed

2014-11-01

Isoflavones are bioactive compounds that have been shown to decrease lipid accumulation in vitro. However, the knowledge of the isoflavone formononetin is limited. The aim of the study was to assess the effects of formononetin and its two synthetic analogues, 2-(2-bromophenyl)-formononetin and 2-heptyl-formononetin, on lipid accumulation in 3T3-L1 adipocytes and investigate possible mechanisms. Formononetin and the two analogues were added day 0-8 or day 8-10 of the differentiation period, and lipid accumulation, glycerol release and gene expression were measured. Additionally, competitive peroxisome proliferator-activated receptor (PPAR)-γ binding assay, PPARγ transactivation assay and Western blot for phosphorylated AMP-activated protein kinase (AMPK) were performed. Chronic treatment (day 0-8) with formononetin increased lipid accumulation, whereas the two analogues decreased lipid accumulation partly due to decreased differentiation. The two analogues, but not formononetin, also decreased lipid content in mature adipocytes. 2-Heptyl-formononetin increased glycerol release and lipolytic gene expression and decreased lipogenic gene expression. Formononetin did not bind to or activate PPARγ whereas both analogues bound to the receptor and behaved as PPARγ partial agonists in the transactivation assay. Neither of the compounds affected phosphorylation of AMPK. In conclusion, the analogues of formononetin decreased lipid accumulation possibly in part by acting as PPARγ partial agonists. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis and evaluation of heterocyclic analogues of bromoxynil.

PubMed

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

2014-01-15

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

Developing Pantetheinase-Resistant Pantothenamide Antibacterials: Structural Modification Impacts on PanK Interaction and Mode of Action.

PubMed

Barnard, Leanne; Mostert, Konrad J; van Otterlo, Willem A L; Strauss, Erick

2018-05-11

Pantothenamides (PanAms) are analogues of pantothenate, the biosynthetic precursor of coenzyme A (CoA), and show potent antimicrobial activity against several bacteria and the malaria parasite in vitro. However, pantetheinase enzymes that normally degrade pantetheine in human serum also act on the PanAms, thereby reducing their potency. In this study, we designed analogues of the known antibacterial PanAm N-heptylpantothenamide (N7-Pan) to be resistant to pantetheinase by using three complementary structural modification strategies. We show that, while two of these are effective in imparting resistance, the introduced modifications have an impact on the analogues' interaction with pantothenate kinase (PanK, the first CoA biosynthetic enzyme), which acts as a metabolic activator and/or target of the PanAms. This, in turn, directly affects their mode of action. Importantly, we discover that the phosphorylated version of N7-Pan shows pantetheinase resistance and antistaphylococcal activity, providing a lead for future studies in the ongoing search of PanAm analogues that show in vivo efficacy.

Chemical construction and structural permutation of neurotoxic natural product, antillatoxin: importance of the three-dimensional structure of the bulky side chain

PubMed Central

INOUE, Masayuki

2014-01-01

Antillatoxin 1 is a unique natural product that displays potent neurotoxic and neuritogenic activities through activation of voltage-gated sodium channels. The peptidic macrocycle of 1 was attached to a side chain with an exceptionally high degree of methylation. In this review, we discuss the total synthesis and biological evaluation of 1 and its analogues. First we describe an efficient synthetic route to 1. This strategy enabled the unified preparation of nine side chain analogues. Structure-activity relationship studies of these analogues revealed that subtle side chain modification leads to dramatic changes in activity, and detailed structural analyses indicated the importance of the overall size and three dimensional shape of the side chain. Based on these data, we designed and synthesized a photoresponsive analogue, proving that the activity of 1 was modulated via a photochemical reaction. The knowledge accumulated through these studies will be useful for the rational design of new tailor-made molecules to control the function and behavior of ion channels. PMID:24522155

A Facile Semi-Synthetic Approach towards Halogen-Substituted Aminobenzoic Acid Analogues of Platensimycin.

PubMed

Qiu, Lin; Tian, Kai; Pan, Jian; Jiang, Lin; Yang, Hu; Zhu, Xiangcheng; Shen, Ben; Duan, Yanwen; Huang, Yong

2017-02-09

Platensimycin (PTM), produced by several strains of Streptomyces platensis, is a promising drug lead for infectious diseases and diabetes. The recent pilot-scale production of PTM from S. platensis SB12026 has set the stage for the facile semi-synthesis of a focused library of PTM analogues. In this study, gram-quantity of platensic acid (PTMA) was prepared by the sulfuric acid-catalyzed ethanolysis of PTM, followed by a mild hydrolysis in aqueous lithium hydroxide. Three PTMA esters were also obtained in near quantitative yields in a single step, suggesting a facile route to make PTMA aliphatic esters. 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU)-catalyzed coupling of PTMA and 33 aminobenzoates resulted in the synthesis of 28 substituted aminobenzoate analogues of PTM, among which 26 of them were reported for the first time. Several of the PTM analogues showed weak antibacterial activity against methicillin-resistant Staphylococcus aureus. Our study supported the potential utility to integrate natural product biosynthetic and semi-synthetic approaches for structure diversification.

Irinotecan-induced mucositis: the interactions and potential role of GLP-2 analogues.

PubMed

Mayo, Bronwen J; Stringer, Andrea M; Bowen, Joanne M; Bateman, Emma H; Keefe, Dorothy M

2017-02-01

A common side effect of irinotecan administration is gastrointestinal mucositis, often manifesting as severe diarrhoea. The damage to the structure and function of the gastrointestinal tract caused by this cytotoxic agent is debilitating and often leads to alterations in patients' regimens, hospitalisation or stoppage of treatment. The purpose of this review is to identify mechanisms of irinotecan-induced intestinal damage and a potential role for GLP-2 analogues for intervention. This is a review of current literature on irinotecan-induced mucositis and GLP-2 analogues mechanisms of action. Recent studies have found alterations that appear to be crucial in the development of severe intestinal mucositis, including early apoptosis, alterations in proliferation and cell survival pathways, as well as induction of inflammatory cascades. Several studies have indicated a possible role for glucagon-like peptide-2 analogues in treating this toxicity, due to its proven intestinotrophic, anti-apoptotic and anti-inflammatory effects in other models of gastrointestinal disease. This review provides evidence as to why and how this treatment may improve mucositis through the possible molecular crosstalk that may be occurring in models of severe intestinal mucositis.

Adjuvant role of vitamin B analogue (sulbutiamine) with anti-infective treatment in infection associated asthenia.

PubMed

Shah, Siddharth N

2003-09-01

Asthenic symptoms such as weakness accompany illness. This study investigates whether the centrally acting cholinergic agent, vitamin B analogue (sulbutiamine), is effective and acceptable in relieving these symptoms in infectious disease when combined with specific anti-infective treatment. In a prospective uncontrolled, non-randomised, commercial, observational study, 1772 patients with an infectious disease and asthenic symptoms, drawn from the practice of 350 randomly selected physicians throughout India, received vitamin B analogue (sulbutiamine) in addition to specific anti-infective treatment for 15 days. The primary outcome variable was complete resolution of asthenic symptoms with treatment. The number (%, 95% confidence interval) of patients with complete resolution of all asthenic symptoms was 916 (51.7, 49.4-54). In the remaining patients, severe asthenia was reduced but persisted in 11 (0.6, 0-26); and moderate asthenia in 94 (5.3, 0-17.6). The response was greater in patients with acute infection and symptoms more related to cerebral function. Side effects occurred in 10 (0.6%), patients and well being improved significantly. Vitamin B analogue (sulbutiamine) may be a useful adjunct to specific anti-infective treatment.

Design of novel analogues of short antimicrobial peptide anoplin with improved antimicrobial activity.

PubMed

Wang, Yang; Chen, Jianbo; Zheng, Xin; Yang, Xiaoli; Ma, Panpan; Cai, Ying; Zhang, Bangzhi; Chen, Yuan

2014-12-01

Currently, novel antibiotics are urgently required to combat the emergence of drug-resistant bacteria. Antimicrobial peptides with membrane-lytic mechanism of action have attracted considerable interest. Anoplin, a natural α-helical amphiphilic antimicrobial peptide, is an ideal research template because of its short sequence. In this study, we designed and synthesized a group of analogues of anoplin. Among these analogues, anoplin-4 composed of D-amino acids displayed the highest antimicrobial activity due to increased charge, hydrophobicity and amphiphilicity. Gratifyingly, anoplin-4 showed low toxicity to host cells, indicating high bacterial selectivity. Furthermore, the mortality rate of mice infected with Escherichia coli was significantly reduced by anoplin-4 treatment relative to anoplin. In conclusion, anoplin-4 is a novel anoplin analogue with high antimicrobial activity and enzymatic stability, which may represent a potent agent for the treatment of infection. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

Lobatamide C: total synthesis, stereochemical assignment, preparation of simplified analogues, and V-ATPase inhibition studies.

PubMed

Shen, Ruichao; Lin, Cheng Ting; Bowman, Emma Jean; Bowman, Barry J; Porco, John A

2003-07-02

The total synthesis and stereochemical assignment of the potent antitumor macrolide lobatamide C, as well as synthesis of simplified lobatamide analogues, is reported. Cu(I)-mediated enamide formation methodology has been developed to prepare the highly unsaturated enamide side chain of the natural product and analogues. A key fragment coupling employs base-mediated esterification of a beta-hydroxy acid and a salicylate cyanomethyl ester. Three additional stereoisomers of lobatamide C have been prepared using related synthetic routes. The stereochemistry at C8, C11, and C15 of lobatamide C was assigned by comparison of stereoisomers and X-ray analysis of a crystalline derivative. Synthetic lobatamide C, stereoisomers, and simplified analogues have been evaluated for inhibition of bovine chromaffin granule membrane V-ATPase. The salicylate phenol, enamide NH, and ortho-substitution of the salicylate ester have been shown to be important for V-ATPase inhibitory activity.

Combining molecular docking and QSAR studies for modeling the anti-tyrosinase activity of aromatic heterocycle thiosemicarbazone analogues

NASA Astrophysics Data System (ADS)

Dong, Huanhuan; Liu, Jing; Liu, Xiaoru; Yu, Yanying; Cao, Shuwen

2018-01-01

A collection of thirty-six aromatic heterocycle thiosemicarbazone analogues presented a broad span of anti-tyrosinase activities were designed and obtained. A robust and reliable two-dimensional quantitative structure-activity relationship model, as evidenced by the high q2 and r2 values (0.848 and 0.893, respectively), was gained based on the analogues to predict the quantitative chemical-biological relationship and the new modifier direction. Inhibitory activities of the compounds were found to greatly depend on molecular shape and orbital energy. Substituents brought out large ovality and high highest-occupied molecular orbital energy values helped to improve the activity of these analogues. The molecular docking results provided visual evidence for QSAR analysis and inhibition mechanism. Based on these, two novel tyrosinase inhibitors O04 and O05 with predicted IC50 of 0.5384 and 0.8752 nM were designed and suggested for further research.

The metabolism of the phosphonium analogue of choline in cultured cells. A useful nuclear-magnetic-resonance probe for membrane phosphatidylcholine.

PubMed Central

Sim, E; Pasternak, C A

1976-01-01

1. Replacement of choline by the phosphonium analogue does not affect the growth rate of P815Y, NIL, 3T3, and SV40/3T3 cells in culture. 2. The fatty acid composition of the resulting phosphonium phosphatidylcholine is similar to that of phosphatidylcholine. 3. The rate of synthesis and degradation of phosphatidylcholine and of the phosphonium analogue are similar. 4. Phospholipid-exchange protein does not distinguish between phosphatidylcholine and the phosphonium analogue. 5. By contrast, incorporation of phosphonium choline into sphingomyelin occurs to only a minor extent. 6. It is concluded that, since the enzymes involved in the turnover of phosphatidylcholine do not discriminate between quaternary N and quaternary P in the polar head-group region, phosphonium choline should prove to be a useful probe for 31P nuclear-magnetic-resonance (n.m.r.) studies of natural membranes. PMID:1275902

N-Guanidino Derivatives of 1,5-Dideoxy-1,5-imino-d-xylitol are Potent, Selective, and Stable Inhibitors of β-Glucocerebrosidase.

PubMed

Sevšek, Alen; Šrot, Luka; Rihter, Jakob; Čelan, Maša; van Ufford, Linda Quarles; Moret, Ed E; Martin, Nathaniel I; Pieters, Roland J

2017-04-06

A series of lipidated guanidino and urea derivatives of 1,5-dideoxy-1,5-imino-d-xylitol were prepared from d-xylose using a concise synthetic protocol. Inhibition assays with a panel of glycosidases revealed that the guanidino analogues display potent inhibition against human recombinant β-glucocerebrosidase with IC 50 values in the low nanomolar range. Related urea analogues of 1,5-dideoxy-1,5-imino-d-xylitol were also synthesized and evaluated in the same fashion and found to be selective for β-galactosidase from bovine liver. No inhibition of human recombinant β-glucocerebrosidase was observed for the urea analogues. Computational studies provided insight into the potent activity of analogues bearing the substituted guanidine moiety in the inhibition of lysosomal glucocerebrosidase (GBA). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spermidine/spermine N1-acetyltransferase (SSAT) activity in human small-cell lung carcinoma cells following transfection with a genomic SSAT construct.

PubMed

Murray-Stewart, Tracy; Applegren, Nancy B; Devereux, Wendy; Hacker, Amy; Smith, Renee; Wang, Yanlin; Casero, Robert A

2003-07-15

Spermidine/spermine N (1)-acetyltransferase (SSAT) activity is typically highly inducible in non-small-cell lung carcinomas in response to treatment with anti-tumour polyamine analogues, and this induction is associated with subsequent cell death. In contrast, cells of the small-cell lung carcinoma (SCLC) phenotype generally do not respond to these compounds with an increase in SSAT activity, and usually are only moderately affected with respect to growth. The goal of the present study was to produce an SSAT-overexpressing SCLC cell line to further investigate the role of SSAT in response to these anti-tumour analogues. To accomplish this, NCI-H82 SCLC cells were stably transfected with plasmids containing either the SSAT genomic sequence or the corresponding cDNA sequence. Individual clones were selected based on their ability to show induced SSAT activity in response to exposure to a polyamine analogue, and an increase in the steady-state SSAT mRNA level. Cells transfected with the genomic sequence exhibited a significant increase in basal SSAT mRNA expression, as well as enhanced SSAT activity, intracellular polyamine pool depletion and growth inhibition following treatment with the analogue N (1), N (11)-bis(ethyl)norspermine. Cells containing the transfected cDNA also exhibited an increase in the basal SSAT mRNA level, but remained phenotypically similar to vector control cells with respect to their response to analogue exposure. These studies indicate that both the genomic SSAT sequence and polyamine analogue exposure play a role in the transcriptional and post-transcriptional regulation and subsequent induction of SSAT activity in these cells. Furthermore, this is the first production of a cell line capable of SSAT protein induction from a generally unresponsive parent line.

Analyzing surface features on icy satellites using a new two-layer analogue model

NASA Astrophysics Data System (ADS)

Morales, K. M.; Leonard, E. J.; Pappalardo, R. T.; Yin, A.

2017-12-01

The appearance of similar surface morphologies across many icy satellites suggests potentially unified formation mechanisms. Constraining the processes that shape the surfaces of these icy worlds is fundamental to understanding their rheology and thermal evolution—factors that have implications for potential habitability. Analogue models have proven useful for investigating and quantifying surface structure formation on Earth, but have only been sparsely applied to icy bodies. In this study, we employ an innovative two-layer analogue model that simulates a warm, ductile ice layer overlain by brittle surface ice on satellites such as Europa and Enceladus. The top, brittle layer is composed of fine-grained sand while the ductile, lower viscosity layer is made of putty. These materials were chosen because they scale up reasonably to the conditions on Europa and Enceladus. Using this analogue model, we investigate the role of the ductile layer in forming contractional structures (e.g. folds) that would compensate for the over-abundance of extensional features observed on icy satellites. We do this by simulating different compressional scenarios in the analogue model and analyzing whether the resulting features resemble those on icy bodies. If the resulting structures are similar, then the model can be used to quantify the deformation by calculating strain. These values can then be scaled up to Europa or Enceladus and used to quantity the observed surface morphologies and the amount of extensional strain accommodated by certain features. This presentation will focus on the resulting surface morphologies and the calculated strain values from several analogue experiments. The methods and findings from this work can then be expanded and used to study other icy bodies, such as Triton, Miranda, Ariel, and Pluto.

The monoamine oxidase inhibition properties of selected structural analogues of methylene blue.

PubMed

Delport, Anzelle; Harvey, Brian H; Petzer, Anél; Petzer, Jacobus P

2017-06-15

The thionine dye, methylene blue (MB), is a potent inhibitor of monoamine oxidase (MAO) A, a property that may, at least in part, mediate its antidepressant effects in humans and animals. The central inhibition of MAO-A by MB has also been linked to serotonin toxicity (ST) which may arise when MB is used in combination with serotonergic drugs. Structural analogues and the principal metabolite of MB, azure B, have also been reported to inhibit the MAO enzymes, with all compounds exhibiting specificity for the MAO-A isoform. To expand on the structure-activity relationships (SARs) of MAO inhibition by MB analogues, the present study investigates the human MAO inhibition properties of five MB analogues: neutral red, Nile blue, new methylene blue, cresyl violet and 1,9-dimethyl methylene blue. Similar to MB, these analogues also are specific MAO-A inhibitors with cresyl violet (IC 50 =0.0037μM), Nile blue (IC 50 =0.0077μM) and 1,9-dimethyl methylene blue (IC 50 =0.018μM) exhibiting higher potency inhibition compared to MB (IC 50 =0.07μM). Nile blue also represents a potent MAO-B inhibitor with an IC 50 value of 0.012μM. From the results it may be concluded that non-thionine MB analogues (e.g. cresyl violet and Nile blue) also may exhibit potent MAO inhibition, a property which should be considered when using these compounds in pharmacological studies. Benzophenoxazines such as cresyl violet and Nile blue are, similar to phenothiazines (e.g. MB), representative of high potency MAO-A inhibitors with a potential risk of ST. Copyright © 2017 Elsevier Inc. All rights reserved.

Metric optimisation for analogue forecasting by simulated annealing

NASA Astrophysics Data System (ADS)

Bliefernicht, J.; Bárdossy, A.

2009-04-01

It is well known that weather patterns tend to recur from time to time. This property of the atmosphere is used by analogue forecasting techniques. They have a long history in weather forecasting and there are many applications predicting hydrological variables at the local scale for different lead times. The basic idea of the technique is to identify past weather situations which are similar (analogue) to the predicted one and to take the local conditions of the analogues as forecast. But the forecast performance of the analogue method depends on user-defined criteria like the choice of the distance function and the size of the predictor domain. In this study we propose a new methodology of optimising both criteria by minimising the forecast error with simulated annealing. The performance of the methodology is demonstrated for the probability forecast of daily areal precipitation. It is compared with a traditional analogue forecasting algorithm, which is used operational as an element of a hydrological forecasting system. The study is performed for several meso-scale catchments located in the Rhine basin in Germany. The methodology is validated by a jack-knife method in a perfect prognosis framework for a period of 48 years (1958-2005). The predictor variables are derived from the NCEP/NCAR reanalysis data set. The Brier skill score and the economic value are determined to evaluate the forecast skill and value of the technique. In this presentation we will present the concept of the optimisation algorithm and the outcome of the comparison. It will be also demonstrated how a decision maker should apply a probability forecast to maximise the economic benefit from it.

Effects of truncation of the peptide chain on the secondary structure and bioactivities of palmitoylated anoplin.

PubMed

Salas, Remmer L; Garcia, Jan Kathryne D L; Miranda, Ana Carmela R; Rivera, Windell L; Nellas, Ricky B; Sabido, Portia Mahal G

2018-06-01

Anoplin (GLLKRIKTLL-NH 2 ) is of current interest due to its short sequence and specificity towards bacteria. Recent studies on anoplin have shown that truncation and acylation compromises its antimicrobial activity and specificity, respectively. In this study, truncated analogues (pal-ano-9 to pal-ano-5) of palmitoylated anoplin (pal-anoplin) were synthesized to determine the effects of C-truncation on its bioactivities. Moreover, secondary structure of each analogue using circular dichroism (CD) spectroscopy was determined to correlate with bioactivities. Interestingly, pal-anoplin, pal-ano-9 and pal-ano-6 were helical in water, unlike anoplin. In contrast, pal-ano-8, pal-ano-7 and pal-ano-5, with polar amino acid residues at the C-terminus, were random coil in water. Nevertheless, all the peptides folded into helical structures in 30% trifluoroethanol/water (TFE/H 2 O) except for the shortest analogue pal-ano-5. Hydrophobicity played a significant role in the enhancement of activity against bacteria E. coli and S. aureus as all lipopeptides including the random coil pal-ano-5 were more active than the parent anoplin. Meanwhile, the greatest improvement in activity against the fungus C. albicans was observed for pal-anoplin analogues (pal-ano-9 and pal-ano-6) that were helical in water. Although, hydrophobicity is a major factor in the secondary structure and antimicrobial activity, it appears that the nature of amino acids at the C-terminus also influence folding of lipopeptides in water and its antifungal activity. Moreover, the hemolytic activity of the analogues was found to correlate with hydrophobicity, except for the least hemolytic, pal-ano-5. Since most of the analogues are more potent and shorter than anoplin, they are promising drug candidates for further development. Copyright © 2018. Published by Elsevier Inc.

Analogues of the Frog-skin Antimicrobial Peptide Temporin 1Tb Exhibit a Wider Spectrum of Activity and a Stronger Antibiofilm Potential as Compared to the Parental Peptide

NASA Astrophysics Data System (ADS)

Grassi, Lucia; Maisetta, Giuseppantonio; Maccari, Giuseppe; Esin, Semih; Batoni, Giovanna

2017-04-01

The frog skin-derived peptide Temporin 1Tb (TB) has gained increasing attention as novel antimicrobial agent for the treatment of antibiotic-resistant and/or biofilm-mediated infections. Nevertheless, such a peptide possesses a preferential spectrum of action against Gram-positive bacteria. In order to improve the therapeutic potential of TB, the present study evaluated the antibacterial and antibiofilm activities of two TB analogues against medically relevant bacterial species. Of the two analogues, TB_KKG6A has been previously described in the literature, while TB_L1FK is a new analogue designed by us through statistical-based computational strategies. Both TB analogues displayed a faster and stronger bactericidal activity than the parental peptide, especially against Gram-negative bacteria in planktonic form. Differently from the parental peptide, TB_KKG6A and TB_L1FK were able to inhibit the formation of Staphylococcus aureus biofilms by more than 50% at 12 μM, while only TB_KKG6A prevented the formation of Pseudomonas aeruginosa biofilms at 24 μM. A marked antibiofilm activity against preformed biofilms of both bacterial species was observed for the two TB analogues when used in combination with EDTA. Analysis of synergism at the cellular level suggested that the antibiofilm activity exerted by the peptide-EDTA combinations against mature biofilms might be due mainly to a disaggregating effect on the extracellular matrix in the case of S. aureus, and to a direct activity on biofilm-embedded cells in the case of P. aeruginosa. Both analogues displayed a low hemolytic effect at the active concentrations and, overall, TB_L1FK resulted less cytotoxic towards mammalian cells. Collectively, the results obtained demonstrated that subtle changes in the primary sequence of TB may provide TB analogues that, used alone or in combination with adjuvant molecules such as EDTA, exhibit promising features against both planktonic and biofilm cells of medically relevant bacteria.

Structure/function relationships of calcitonin analogues as agonists, antagonists, or inverse agonists in a constitutively activated receptor cell system.

PubMed

Pozvek, G; Hilton, J M; Quiza, M; Houssami, S; Sexton, P M

1997-04-01

The structure/function relationship of salmon calcitonin (sCT) analogues was investigated in heterologous calcitonin receptor (CTR) expression systems. sCT analogues with progressive amino-terminal truncations intermediate of sCT-(1-32) to sCT-(8-32) were examined for their ability to act as agonists, antagonists, or inverse agonists. Two CTR cell clones, B8-H10 and G12-E12, which express approximately 5 million and 25,000 C1b receptors/cell, respectively, were used for this study. The B8-H10 clone has an approximately 80-fold increase in basal levels of intracellular cAMP due to constitutive activation of the overexpressed receptor. In whole-cell competition binding studies, sCT-(1-32) was more potent than any of its amino-terminally truncated analogues in competition for 125I-sCT binding. In cAMP accumulation studies, sCT-(1-32) and modified analogues sCT-(2-32) and sCT-(3-32) had agonist activities. SDZ-216-710, with an amino-terminal truncation of four amino acids, behaved as a partial agonist/antagonist, whereas amino-terminal truncations of six or seven amino acid residues produced a 16-fold reduction in basal cAMP levels and attenuated the response to the agonist sCT-(1-32) in the constitutively active CTR system. This inverse agonist effect was insensitive to pertussis toxin inhibition. In contrast, the inverse agonist activity of these peptides was not observed in the nonconstitutively active CTR system, in which sCT analogues with amino-terminal truncations of four or more amino acids behaved as neutral competitive antagonists. These results suggest that the inverse agonist activity is mediated by stabilization of the inactive state of the receptor, which does not couple to G protein, and attenuates basal signaling initiated by ligand-independent activation of the effector adenylyl cyclase.

Systematic review and meta-analysis of short-acting insulin analogues in patients with diabetes mellitus.

PubMed

Plank, Johannes; Siebenhofer, Andrea; Berghold, Andrea; Jeitler, Klaus; Horvath, Karl; Mrak, Peter; Pieber, Thomas R

2005-06-27

This article compares the effect of treatment with short-acting insulin (SAI) analogues vs regular insulin on glycemic control, hypoglycemic episodes, quality of life, and diabetes-specific complications. Electronic searches (Cochrane Library, MEDLINE, and EMBASE) and additional searching (pharmaceutical companies, experts, approval agencies, abstracts of diabetology meetings) were performed. Two reviewers independently screened randomized controlled trials to determine inclusion. Forty-two randomized controlled trials that assessed the effect of SAI analogues vs regular insulin in 7933 patients with type 1 diabetes mellitus, type 2 diabetes mellitus, and gestational diabetes mellitus were identified. The weighted mean difference between hemoglobin A(1c) values obtained using SAI analogues and regular insulin was -0.12% (95% confidence interval [CI], -0.17% to -0.07%) for adult patients with type 1 diabetes mellitus and -0.02% (95% CI, -0.10% to 0.07%) for patients with type 2 diabetes mellitus. The standardized mean difference for overall hypoglycemia (episodes per patient per month) was -0.05 (95% CI, -0.22 to 0.11) and -0.04 (95% CI, -0.12 to 0.04) comparing SAI analogues with regular insulin in adult patients with type 1 and type 2 diabetes mellitus, respectively. No differences between treatments were observed in children with type 1 diabetes, pregnant women with type 1 diabetes mellitus, and women with gestational diabetes. Concerning quality of life, improvement was observed only in open-label studies in patients with type 1 diabetes mellitus. No differences were seen in a double-blinded study of patients with type 1 or in the studies of patients with type 2 diabetes mellitus. Our analysis suggests only a minor benefit to hemoglobin A(1c) values in adult patients with type 1 diabetes mellitus but no benefit in the remaining population with type 2 or gestational diabetes from SAI analogue treatment.

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

PubMed

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

2012-01-01

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

Aminopropyl carbazole analogues as potent enhancers of neurogenesis.

PubMed

Yoon, Hye Jin; Kong, Sun-Young; Park, Min-Hye; Cho, Yongsung; Kim, Sung-Eun; Shin, Jae-Yeon; Jung, Sunghye; Lee, Jiyoun; Farhanullah; Kim, Hyun-Jung; Lee, Jeewoo

2013-11-15

Neural stem cells are multipotent and self-renewing cells that can differentiate into new neurons and hold great promise for treating various neurological disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Small molecules that can trigger neurogenesis and neuroprotection are particularly useful not only because of their therapeutic implications but also because they can provide an invaluable tool to study the mechanisms of neurogenesis. In this report, we have developed and screened 25 aminopropyl carbazole derivatives that can enhance neurogenesis of cultured neural stem cells. Among these analogues, compound 9 demonstrated an excellent proneurogenic and neuroprotective activity with no apparent toxicity. We believe that compound 9 can serve as an excellent lead to develop various analogues and to study the underlying mechanisms of neurogenesis. Copyright © 2013 Elsevier Ltd. All rights reserved.

2-MeS-β,γ-CCl2-ATP is a Potent Agent for Reducing Intraocular Pressure†

PubMed Central

Eliahu, Shay; Martín-Gil, Alba; de Lara, María Jesús Perez; Pintor, Jesús; Camden, Jean; Weisman, Gary A.; Lecka, Joanna; Sévigny, Jean; Fischer, Bilha

2015-01-01

Extracellular nucleotides can modify the production or drainage of the aqueous humor via activation of P2 receptors and therefore affect the intraocular pressure (IOP). We have synthesized slowly hydrolyzable nucleoside di- and triphosphate analogues, 1, and 8–14. Analogues 8–14 were completely resistant to hydrolysis by alkaline phosphatase over 30 min at 37 °C. In human blood serum, analogues 8–14 exhibited high stability, e.g., analogues 9 and 10–14 were only 15% and 0% degraded after 24 h, respectively. Moreover, analogues 8–14 were highly stable at pH 1.4 (t1/21 h–30 days). Analogues 8–14 were agonists of the P2Y1 receptor (EC50 0.57–9.54μM). Ocular administration of most analogues into rabbits reduced IOP, e.g., analogue 9 reduced IOP by 32% (EC50 95.5 nM). Analogue 9 was more effective at reducing IOP than several common glaucoma drugs and represents a promising alternative to timolol maleate, which cannot be used for the treatment of patients suffering from asthma or cardiac problems. PMID:20337495

Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships.

PubMed

Sun, Wenlong; Zhuang, Chunlin; Li, Xia; Zhang, Bowei; Lu, Xinhua; Zheng, Zhihui; Dong, Yuesheng

2017-08-01

Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential therapies for diabetes and obesity have attracted much attention in recent years. Six varic acid analogues were isolated from two strains of fungi and evaluated for PTP1B inhibition activities. The structure-activity relationships were also characterized and predicted by molecular modeling. Further kinetic studies indicated the reversible and competitive inhibition manner of varic acid analogues. Trivaric acid showed insulin-sensitizing effect not only in vitro but also in vivo, representing a promising lead compound for further optimization. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Antihistaminic and antiserotonin properties of new complex tropine esters].

PubMed

Mashkovskiĭ, M D; Shvarts, G Ia

1979-01-01

The antihistaminic and antiserotonin properties of 16 new tropine esters, analogues of atropine, tropacin and tropaphen, were studied. All of them were found to lessen the spasmogenic effects of histamine and serotonin. The intensity of the antihistaminic and antiserotonin action of the drugs varied depending upon the structure of the radical at the alpha-carbon atom in the acidic part of the molecule. Both types of the activity are most marked in the desoxymethyl propyl and butyl analogues of atropine. The absence of the oxymethyl group at alpha-carbon in the series of atropine analogues is shown to facilitate the manifestation of the antihistaminic activity.

The effect of pre-existing vulnerability factors on a laboratory analogue trauma experience.

PubMed

Laposa, Judith M; Alden, Lynn E

2008-12-01

This study examined how pre-existing emotional and personality vulnerability factors affect responses to an analogue trauma experience. Sixty-eight undergraduate participants viewed a distressing film and completed measures of trait anxiety, intelligence, depression, trait dissociation, as well as changes in state anxiety, then recorded intrusions over the following week. Results revealed that trait anxiety, depression, trait dissociation, change in anxiety, and post-state anxiety were associated with intrusion frequency. Post-state anxiety mediated the relationship between trait anxiety, depression and trait dissociation, and intrusions. Implications for PTSD theories and laboratory trauma analogue research examining specific elements of cognitive models of PTSD are discussed.

Natural and Semisynthetic Analogues of Manadoperoxide B Reveal New Structural Requirements for Trypanocidal Activity

PubMed Central

Chianese, Giuseppina; Scala, Fernando; Calcinai, Barbara; Cerrano, Carlo; Dien, Henny A.; Kaiser, Marcel; Tasdemir, Deniz; Taglialatela-Scafati, Orazio

2013-01-01

Chemical analysis of the Indonesian sponge Plakortis cfr. lita afforded two new analogues of the potent trypanocidal agent manadoperoxide B (1), namely 12-isomanadoperoxide B (2) and manadoperoxidic acid B (3). These compounds were isolated along with a new short chain dicarboxylate monoester (4), bearing some interesting relationships with the polyketide endoperoxides found in this sponge. Some semi-synthetic analogues of manadoperoxide B (6–8) were prepared and evaluated for antitrypanosomal activity and cytotoxicity. These studies revealed crucial structure–activity relationships that should be taken into account in the design of optimized and simplified endoperoxyketal trypanocidal agents. PMID:23989650

Validity and reproducibility of cephalometric measurements obtained from digital photographs of analogue headfilms.

PubMed

Grybauskas, Simonas; Balciuniene, Irena; Vetra, Janis

2007-01-01

The emerging market of digital cephalographs and computerized cephalometry is overwhelming the need to examine the advantages and drawbacks of manual cephalometry, meanwhile, small offices continue to benefit from the economic efficacy and ease of use of analogue cephalograms. The use of modern cephalometric software requires import of digital cephalograms or digital capture of analogue data: scanning and digital photography. The validity of digital photographs of analogue headfilms rather than original headfilms in clinical practice has not been well established. Digital photography could be a fast and inexpensive method of digital capture of analogue cephalograms for use in digital cephalometry. The objective of this study was to determine the validity and reproducibility of measurements obtained from digital photographs of analogue headfilms in lateral cephalometry. Analogue cephalometric radiographs were performed on 15 human dry skulls. Each of them was traced on acetate paper and photographed three times independently. Acetate tracings and digital photographs were digitized and analyzed in cephalometric software. Linear regression model, paired t-test intergroup analysis and coefficient of repeatability were used to assess validity and reproducibility for 63 angular, linear and derivative measurements. 54 out of 63 measurements were determined to have clinically acceptable reproducibility in the acetate tracing group as well as 46 out of 63 in the digital photography group. The worst reproducibility was determined for measurements dependent on landmarks of incisors and poorly defined outlines, majority of them being angular measurements. Validity was acceptable for all measurements, and although statistically significant differences between methods existed for as many as 15 parameters, they appeared to be clinically insignificant being smaller than 1 unit of measurement. Validity was acceptable for 59 of 63 measurements obtained from digital photographs, substantiating the use of digital photography for headfilm capture and computer-aided cephalometric analysis.

Therapeutic uses of vitamin D analogues.

PubMed

Brown, A J

2001-11-01

The vitamin D endocrine system has been implicated in numerous biological activities throughout the body. The breadth and magnitude of vitamin D activity suggest potential therapeutic applications for the treatment of several diseases and disorders, including hyperproliferative diseases, immune dysfunction, endocrine disorders, and metabolic bone diseases. However, therapy using natural vitamin D hormone, 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) has been precluded in most cases because of the potent calcemic activity shown by this hormone. Newly developed vitamin D analogues with lower calcemic activity have been shown to retain many therapeutic properties of 1,25(OH)(2)D(3). Molecular studies discussed in this article provide insights into the unique target cell specificity afforded by these analogues. In particular, the importance of the nuclear vitamin D receptor (VDR), serum vitamin D-binding protein, 24-hydroxylase, and membrane receptor is noted because analogue selectivity, specificity, and potency are afforded through their molecular interactions. The nuclear VDR has been isolated from a variety of target cells and tissues, suggesting that vitamin D compounds may have therapeutic potential throughout several body systems. Five vitamin D analogues have been approved for use in patients: calcipotriol (Dovonex; Leo Pharmaceuticals, Copenhagen, Denmark) for the treatment of psoriasis, 19-nor-1,25(OH)(2)D(2) (Zemplar; Abbott Laboratories, Abbott Park, IL) for secondary hyperparathyroidism, doxercalciferol (Hectorol; Bone Care Int, Madison, WI) for reduction of elevated parathyroid hormone levels, 22-oxacalcitriol (Maxacalcitol; Chugai Pharmaceuticals, Tokyo, Japan), and alfacalcidol. Several other analogues are currently being tested in preclinical and clinical trials for the treatment of various types of cancer and osteoporosis, as well as immunosuppression. Understanding how analogues exert their selective actions may allow for the design of more effective and safer vitamin D compounds for the treatment of a wide range of clinical disorders.

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

PubMed Central

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

2012-01-01

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

NMR Insights into the Structure-Function Relationships in the Binding of Melanocortin Analogues to the MC1R Receptor.

PubMed

Morais, Maurício; Zamora-Carreras, Héctor; Raposinho, Paula D; Oliveira, Maria Cristina; Pantoja-Uceda, David; Correia, João D G; Jiménez, M Angeles

2017-07-15

Linear and cyclic analogues of the α-melanocyte stimulating hormone (α-MSH) targeting the human melanocortin receptor 1 (MC1R) are of pharmacological interest for detecting and treating melanoma. The central sequence of α-MSH (His-Phe-Arg-Trp) has been identified as being essential for receptor binding. To deepen current knowledge on the molecular basis for α-MSH bioactivity, we aimed to understand the effect of cycle size on receptor binding. To that end, we synthesised two macrocyclic isomeric α-MSH analogues, c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys]-Lys-NH₂ ( CycN-K6 ) and c[NH-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Lys-Lys]-NH₂ ( CycN-K7 ). Their affinities to MC1R receptor were determined by competitive binding assays, and their structures were analysed by ¹H and 13 C NMR. These results were compared to those of the previously reported analogue c[S-NO₂-C₆H₃-CO-His-DPhe-Arg-Trp-Cys]-Lys-NH₂ ( CycS-C6 ). The MC1R binding affinity of the 22-membered macrocyclic peptide CycN-K6 (IC 50 = 155 ± 16 nM) is higher than that found for the 25-membered macrocyclic analogue CycN-K7 (IC 50 = 495 ± 101 nM), which, in turn, is higher than that observed for the 19-membered cyclic analogue CycS-C6 (IC 50 = 1770 ± 480 nM). NMR structural study indicated that macrocycle size leads to changes in the relative dispositions of the side chains, particularly in the packing of the Arg side chain relative to the aromatic rings. In contrast to the other analogues, the 22-membered cycle's side chains are favorably positioned for receptor interaction.

Physical Properties of Granulates Used in Analogue Experiments of Caprock Failure and Sediment Remobilisation

NASA Astrophysics Data System (ADS)

Kukowski, N.; Warsitzka, M.; May, F.

2014-12-01

Geological systems consisting of a porous reservoir and a low-permeable caprock are prone to hydraulic fracturing, if pore pressure rises to the effective stress. Under certain conditions, hydraulic fracturing is associated with sediment remobilisation, e.g. sand injections or pipes, leading to reduced seal capacity of the caprock. In dynamically scaled analogue experiments using granular materials and air pressure, we intent to investigate strain patterns and deformation mechanisms during caprock failure and fluidisation of shallow over-pressured reservoirs. The aim of this study is to improve the understanding of leakage potential of a sealing formation and the fluidisation potential of a reservoir formation depending on rock properties and effective stress. For reliable interpretation of analogue experiments, physical properties of analogue materials, e.g. frictional strength, cohesion, density, permeability etc., have to be correctly scaled according to those of their natural equivalents. The simulation of caprock requires that the analogue material possess a low permeability and is capable to shear failure and tensional failure. In contrast, materials representing the reservoir have to possess high porosity and low shear strength. In order to find suitable analogue materials, we measured the stress-strain behaviour and the permeability of over 25 different types of natural and artificial granular materials, e.g. glass powder, siliceous microspheres, diatomite powder, loess, or plastic granulate. Here, we present data of frictional parameters, compressibility and permeability of these granular materials characterized as a function of sphericity, grain size, and density. The repertoire of different types of granulates facilitates the adjustment of accurate mechanical properties in the analogue experiments. Furthermore, conditions during seal failure and fluidisation can be examined depending on the wide range of varying physical properties.

Quantitative structure-activity relationship analysis of the pharmacology of para-substituted methcathinone analogues.

PubMed

Bonano, J S; Banks, M L; Kolanos, R; Sakloth, F; Barnier, M L; Glennon, R A; Cozzi, N V; Partilla, J S; Baumann, M H; Negus, S S

2015-05-01

Methcathinone (MCAT) is a potent monoamine releaser and parent compound to emerging drugs of abuse including mephedrone (4-CH3 MCAT), the para-methyl analogue of MCAT. This study examined quantitative structure-activity relationships (QSAR) for MCAT and six para-substituted MCAT analogues on (a) in vitro potency to promote monoamine release via dopamine and serotonin transporters (DAT and SERT, respectively), and (b) in vivo modulation of intracranial self-stimulation (ICSS), a behavioural procedure used to evaluate abuse potential. Neurochemical and behavioural effects were correlated with steric (Es ), electronic (σp ) and lipophilic (πp ) parameters of the para substituents. For neurochemical studies, drug effects on monoamine release through DAT and SERT were evaluated in rat brain synaptosomes. For behavioural studies, drug effects were tested in male Sprague-Dawley rats implanted with electrodes targeting the medial forebrain bundle and trained to lever-press for electrical brain stimulation. MCAT and all six para-substituted analogues increased monoamine release via DAT and SERT and dose- and time-dependently modulated ICSS. In vitro selectivity for DAT versus SERT correlated with in vivo efficacy to produce abuse-related ICSS facilitation. In addition, the Es values of the para substituents correlated with both selectivity for DAT versus SERT and magnitude of ICSS facilitation. Selectivity for DAT versus SERT in vitro is a key determinant of abuse-related ICSS facilitation by these MCAT analogues, and steric aspects of the para substituent of the MCAT scaffold (indicated by Es ) are key determinants of this selectivity. © 2014 The British Pharmacological Society.

Synthesis and Nicotinic Acetylcholine Receptor In Vitro and In Vivo Pharmacological Properties of 2'-Fluoro-3'-(substituted phenyl)deschloroepibatidine Analogues of 2'-Fluoro-3'-(4-nitrophenyl)deschloroepibatidine (4-Nitro-PFEB or RTI-7527-102)

PubMed Central

Ondachi, Pauline; Castro, Ana; Luetje, Charles W.; Damaj, M. Imad; Mascarella, S. Wayne; Navarro, Hernán A.; Carroll, F. Ivy

2012-01-01

Herein, we report the synthesis and nicotinic acetylcholine receptor (nAChR) in vitro and in vivo pharmacological properties of 2'-fluoro-3'-(substituted phenyl)deschloroepibatidines 5b–g, analogues of 3'-(4-nitrophenyl) compound 5a. All compounds had high affinity for the α4β2-nAChR and low affinity for α7-nAChR. Initial electrophysiological studies showed that all analogues were antagonists at α4β2-, α3β4-, and α7-nAChRs. The 4-carbamoylphenyl analogue 5g was highly selective for α4β2-nAChR over α3β4- and α7-nAChRs. All the analogues were antagonists of nicotine-induced antinociception in the tail-flick test. Molecular modeling docking studies using agonist-bound form of the X-ray crystal structure of the acetylcholine binding protein suggested several different binding modes for epibatidine, varenicline, and 5a–5g. In particular, a unique binding mode for 5g was suggested by these docking simulations. The high binding affinity, in vitro efficacy, and selectivity of 5g for α4β2-nAChR combined with its nAChR functional antagonist properties suggest that 5g will be a valuable pharmacological tool for studying the nAChR and may have potential as a pharmacotherapy for addiction and other CNS disorders. PMID:22742586

Quantitative structure–activity relationship analysis of the pharmacology of para-substituted methcathinone analogues

PubMed Central

Bonano, J S; Banks, M L; Kolanos, R; Sakloth, F; Barnier, M L; Glennon, R A; Cozzi, N V; Partilla, J S; Baumann, M H; Negus, S S

2015-01-01

Background and Purpose Methcathinone (MCAT) is a potent monoamine releaser and parent compound to emerging drugs of abuse including mephedrone (4-CH3 MCAT), the para-methyl analogue of MCAT. This study examined quantitative structure–activity relationships (QSAR) for MCAT and six para-substituted MCAT analogues on (a) in vitro potency to promote monoamine release via dopamine and serotonin transporters (DAT and SERT, respectively), and (b) in vivo modulation of intracranial self-stimulation (ICSS), a behavioural procedure used to evaluate abuse potential. Neurochemical and behavioural effects were correlated with steric (Es), electronic (σp) and lipophilic (πp) parameters of the para substituents. Experimental Approach For neurochemical studies, drug effects on monoamine release through DAT and SERT were evaluated in rat brain synaptosomes. For behavioural studies, drug effects were tested in male Sprague-Dawley rats implanted with electrodes targeting the medial forebrain bundle and trained to lever-press for electrical brain stimulation. Key Results MCAT and all six para-substituted analogues increased monoamine release via DAT and SERT and dose- and time-dependently modulated ICSS. In vitro selectivity for DAT versus SERT correlated with in vivo efficacy to produce abuse-related ICSS facilitation. In addition, the Es values of the para substituents correlated with both selectivity for DAT versus SERT and magnitude of ICSS facilitation. Conclusions and Implications Selectivity for DAT versus SERT in vitro is a key determinant of abuse-related ICSS facilitation by these MCAT analogues, and steric aspects of the para substituent of the MCAT scaffold (indicated by Es) are key determinants of this selectivity. PMID:25438806

Mineralisation of reconstituted collagen using polyvinylphosphonic acid/polyacrylic acid templating matrix protein analogues in the presence of calcium, phosphate and hydroxyl ions

PubMed Central

Kim, Young Kyung; Gu, Li-sha; Bryan, Thomas E.; Kim, Jong Ryul; Chen, Liang; Liu, Yan; Yoon, James C.; Breschi, Lorenzo; Pashley, David H.; Tay, Franklin R.

2010-01-01

The complex morphologies of mineralised collagen fibrils are regulated through interactions between the collagen matrix and non-collagenous extracellular proteins. In the present study, polyvinylphosphonic acid, a biomimetic analogue of matrix phosphoproteins, was synthesised and confirmed with FTIR and NMR. Biomimetic mineralisation of reconstituted collagen fibrils devoid of natural non-collagenous proteins was demonstrated with TEM using a Portland cement-containing resin composite and a phosphate-containing fluid in the presence of polyacrylic acid as sequestration, and polyvinylphosphonic acid as templating matrix protein analogues. In the presence of these dual biomimetic analogues in the mineralisation medium, intrafibrillar and extrafibrillar mineralisation via bottom-up nanoparticle assembly based on the nonclassical crystallisation pathway could be identified. Conversely, only large mineral spheres with no preferred association with collagen fibrils were observed in the absence of biomimetic analogues in the medium. Mineral phases were evident within the collagen fibrils as early as 4 hours after the initially-formed amorphous calcium phosphate nanoprecursors were transformed into apatite nanocrystals. Selected area electron diffraction patterns of highly mineralised collagen fibrils were nearly identical to those of natural bone, with apatite crystallites preferentially aligned along the collagen fibril axes. PMID:20621767

Synthesis of potent agonists of substance P by replacement of Met11 with Glu(OBzl) and N-terminal glutamine with Glp of the C-terminal hexapeptide and heptapeptide of substance P.

PubMed

Stavropoulos, G; Karagiannis, K; Anagnostides, S; Ministrouski, I; Selinger, Z; Chorev, M

1995-06-01

The analogues [Glp6,Glu(OBzl)11]SP(6-11) and [Glp5,Glu(OBzl)11]SP(5-11) of the C-terminal hexapeptide and heptapeptide of Substance P have been synthesized by conventional solution methods. In each analogue the N-terminal glutamine has been replaced by pyroglutamic acid, while the COOCH2C6H5 ester group has replaced the SCH3 group of the Met11 side chain. The in vitro activity of both analogues has been determined on three biological preparations: guinea pig ileum (GPI), rat vas deferens (RVD) and rat portal vein (RPV). The results showed that both analogues are highly potent and selective agonists on GPI through the NK-1 receptor. They are more potent than SP itself, with 1.54 and 1.25 respective values of relative potency on GPI. Their selectivity has been studied by utilizing atropine-treated guinea pig ileum (GPI+At). The analogues showed low activity on RVD and RPV tissues, which represent NK-2 and NK-3 monoreceptor assay, respectively.

Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial.

PubMed

Bourlière, Marc; Rabiega, Pascaline; Ganne-Carrie, Nathalie; Serfaty, Lawrence; Marcellin, Patrick; Barthe, Yoann; Thabut, Dominique; Guyader, Dominique; Hezode, Christophe; Picon, Magali; Causse, Xavier; Leroy, Vincent; Bronowicki, Jean Pierre; Carrieri, Patrizia; Riachi, Ghassan; Rosa, Isabelle; Attali, Pierre; Molina, Jean Michel; Bacq, Yannick; Tran, Albert; Grangé, Jean Didier; Zoulim, Fabien; Fontaine, Hélène; Alric, Laurent; Bertucci, Inga; Bouvier-Alias, Magali; Carrat, Fabrice

2017-03-01

Findings from uncontrolled studies suggest that addition of pegylated interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus (HBV) DNA might increase HBs antigen (HBsAg) clearance. We aimed to assess this strategy. In this randomised, controlled, open-label trial, we enrolled patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1 year from 30 hepatology tertiary care wards in France. Patients had to have an alanine aminotransferase concentration of less than or equal to five times the upper normal range, no hepatocellular carcinoma, and a serum α fetoprotein concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and a negative pregnancy test in women. Patients with contraindications to pegylated interferon were not eligible. A centralised randomisation used computer-generated lists of random permuted blocks of four with stratification by HBsAg titres (< or ≥2·25 log 10 IU/mL) to allocate patients (1:1) to receive a 48 week course of subcutaneous injections of 180 μg per week of pegylated interferon alfa-2a in addition to the nucleos(t)ide analogue regimen or to continue to receive nucleos(t)ide analogues only. The primary endpoint was HBsAg loss at week 96 by intention-to-treat analysis. This trial is closed and registered with ClinicalTrials.gov, number NCT01172392. Between Jan 20, 2011, and July 18, 2012, we randomly allocated 185 patients (92 [50%] to pegylated interferon and nucleos(t)ide analogues and 93 [50%] to nucleos(t)ide analogues alone). We excluded two patients from the pegylated interferon plus nucleos(t)ide analogues group from analyses because of withdrawal of consent (one patient) or violation of inclusion criteria (one patient). At week 96, loss of HBsAg was reported in seven (7·8%) of 90 patients in the pegylated interferon plus nucleos(t)ide analogues group versus three (3·2%) of 93 in the nucleos(t)ide analogues-alone group (difference 4·6% [95% CI -2·6 to 12·5]; p=0·15). 85 (94%) of 90 patients started pegylated interferon, three (4%) of whom had a dose reduction and 17 (20%) had an early discontinuation of pegylated interferon (seven [41%] for serious adverse events). Grade 3 and 4 adverse events were more frequent in the pegylated interferon plus nucleos(t)ide analogues group (26 [29%] grade 3 adverse events; 19 [21%] grade 4 adverse events) than in the nucleos(t)ide analogues-alone group (three [3%] grade 3; six [6%] grade 4). Addition of a 48 week course of pegylated interferon to nucleos(t)ide analogue therapy in patients with HBeAg-negative chronic hepatitis B with undetectable HBV DNA for a least 1 year was poorly tolerated and did not result in a significant increase of HBsAg clearance. Institut national de la santé et de la recherche médicale-Agence nationale de recherches sur le sida et les hépatites virales (France Recherche Nord&sud Sida-vih Hepatites). Copyright © 2017 Elsevier Ltd. All rights reserved.

Association of a Mixed Anxiety-Depression Syndrome and Symptoms of Major Depressive Disorder during Adolescence.

ERIC Educational Resources Information Center

Gerhardt, Cynthia A.; Compas, Bruce E.; Connor, Jennifer K.; Achenbach, Thomas M.

1999-01-01

Examined the relations between an empirically derived syndrome of Anxiety-Depression and an analogue measure of Major Depressive Disorder (MDD) in a longitudinal study of a nationally representative sample of 3,154 adolescents. Analyses indicated moderate correspondence between scores on the syndrome and symptoms of the MDD analogue. (SLD)

Development of novobiocin analogues that manifest anti-proliferative activity against several cancer cell lines.

PubMed

Burlison, Joseph A; Avila, Christopher; Vielhauer, George; Lubbers, Donna J; Holzbeierlein, Jeffrey; Blagg, Brian S J

2008-03-21

Recent studies have shown that the DNA gyrase inhibitor, novobiocin, binds to a previously unrecognized ATP-binding site located at the C-terminus of Hsp90 and induces degradation of Hsp90-dependent client proteins at approximately 700 microM. As a result of these studies, several analogues of the coumarin family of antibiotics have been reported and shown to exhibit increased Hsp90 inhibitory activity; however, the monomeric species lacked the ability to manifest anti-proliferative activity against cancer cell lines at concentrations tested. In an effort to develop more efficacious compounds that produce growth inhibitory activity against cancer cell lines, structure-activity relationships were investigated surrounding the prenylated benzamide side chain of the natural product. Results obtained from these studies have produced the first novobiocin analogues that manifest anti-proliferative activity against several cancer cell lines.

Assessment of cyanide contamination in soils with a handheld mid-infrared spectrometer.

PubMed

Soriano-Disla, José M; Janik, Leslie J; McLaughlin, Michael J

2018-02-01

We examined the feasibility of using handheld mid-infrared (MIR) Fourier-Transform infrared (FT-IR) instrumentation for detecting and analysing cyanide (CN) contamination in field contaminated soils. Cyanide spiking experiments were first carried out, in the laboratory, to test the sensitivity of infrared Fourier transform (DRIFT) spectrometry to ferro- and ferricyanide compounds across a range of reference soils and minerals. Both benchtop and handheld diffuse reflectance infrared spectrometers were tested. Excellent results were obtained for the reference soils and minerals, with the MIR outperforming the near-infrared (NIR) range. Spectral peaks characteristic of the -C≡N group were observed near 2062 and 2118cm -1 in the MIR region for the ferro- and ferricyanide compounds spiked into soils/minerals, respectively. In the NIR region such peaks were observed near 4134 and 4220cm -1 . Cyanide-contaminated samples were then collected in the field and analyzed with the two spectrometers to further test the applicability of the DRIFT technique for soils containing aged CN residues. The prediction of total CN in dry and ground contaminated soils using the handheld MIR instrument resulted in a coefficient of determination (R 2 ) of 0.88-0.98 and root mean square error of the cross-validation (RMSE) of 21-49mgkg -1 for a CN range of 0-611mgkg -1 . A major peak was observed in the MIR at about 2092cm -1 which was attributed to "Prussian Blue" (Fe 4 [Fe(CN) 6 ] 3 ·xH 2 O). These results demonstrate the potential of handheld DRIFT instrumentation as a promising alternative to the standard laboratory method to predict CN concentrations in contaminated field soils. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Mixed valent stannide EuRuSn 3 - Structure, magnetic properties, and Mössbauer spectroscopic investigation

NASA Astrophysics Data System (ADS)

Harmening, Thomas; Hermes, Wilfried; Eul, Matthias; Pöttgen, Rainer

2010-02-01

The stannide EuRuSn 3 was synthesized by induction melting of the elements in a sealed tantalum tube in a water-cooled quartz glass sample chamber. The structure was refined on the basis of single crystal X-ray diffractometer data (LaRuSn 3 type, Pm3¯n, a = 976.0(1) pm, wR2 = 0.0399, 317 F2 values, and 13 variables). EuRuSn 3 shows modified Curie-Weiss behaviour in the temperature range 50-305 K with an experimental magnetic moment of 7.34(1) μB per formula unit. Thus, the europium atoms are not in a purely divalent state. Low field susceptibility measurement indicates a ferro- or ferrimagnetic ordering at TC = 11.2(2) K and magnetization measurements indicate EuRuSn 3 as a non-collinear ferro- or ferrimagnet. 151Eu Mössbauer spectroscopic measurements suggested one europium site to be static mixed valent with a Eu 2+/Eu 3+ ratio close to one and the other site purely divalent. This was supported by substituting the Eu 3+ atoms with Y 3+ in a sample with a composition of Eu 0.7Y 0.3RuSn 3 ( a = 971.24(8) pm, wR2 = 0.0485, 313 F2 values, 14 variables). The 119Sn Mössbauer spectra show a pronounced Gol'danskii-Karyagin effect in the paramagnetic range and a magnetic hyperfine field distribution at 4.2 K, due to the complex magnetic structure. The influence of the valence electron concentration on the europium valence was tested via Ru/Pd substitution. A EuRu 0.8Pd 0.2Sn 3 sample shows almost purely divalent europium.

Computation-based virtual screening for designing novel antimalarial drugs by targeting falcipain-III: a structure-based drug designing approach.

PubMed

Kesharwani, Rajesh Kumar; Singh, Durg Vijay; Misra, Krishna

2013-01-01

Cysteine proteases (falcipains), a papain-family of enzymes of Plasmodium falciparum, are responsible for haemoglobin degradation and thus necessary for its survival during asexual life cycle phase inside the human red blood cells while remaining non-functional for the human body. Therefore, these can act as potential targets for designing antimalarial drugs. The P. falciparum cysteine proteases, falcipain-II and falcipain- III are the enzymes which initiate the haemoglobin degradation, therefore, have been selected as targets. In the present study, we have designed new leupeptin analogues and subjected to virtual screening using Glide at the active site cavity of falcipain-II and falcipain-III to select the best docked analogues on the basis of Glide score and also compare with the result of AutoDock. The proposed analogues can be synthesized and tested in vivo as future potent antimalarial drugs. Protein falcipain-II and falcipain-III together with bounds inhibitors epoxysuccinate E64 (E64) and leupeptin respectively were retrieved from protein data bank (PDB) and latter leupeptin was used as lead molecule to design new analogues by using Ligbuilder software and refined the molecules on the basis of Lipinski rule of five and fitness score parameters. All the designed leupeptin analogues were screened via docking simulation at the active site cavity of falcipain-II and falcipain-III by using Glide software and AutoDock. The 104 new leupeptin-based antimalarial ligands were designed using structure-based drug designing approach with the help of Ligbuilder and subjected for virtual screening via docking simulation method against falcipain-II and falcipain-III receptor proteins. The Glide docking results suggest that the ligands namely result_037 shows good binding and other two, result_044 and result_042 show nearly similar binding than naturally occurring PDB bound ligand E64 against falcipain-II and in case of falcipain-III, 15 designed leupeptin analogues having better binding affinity compared to the PDB bound inhibitor of falcipain-III. The docking simulation results of falcipain-III with designed leupeptin analogues using Glide compared with AutoDock and find 80% similarity as better binder than leupeptin. These results further highlight new leupeptin analogues as promising future inhibitors for chemotherapeutic prevention of malaria. The result of Glide for falcipain-III has been compared with the result of AutoDock and finds very less differences in their order of binding affinity. Although there are no extra hydrogen bonds, however, equal number of hydrogen bonds with variable strength as compared to leupeptin along with the enhanced hydrophobic and electrostatic interactions in case of analogues supports our study that it holds the ligand molecules strongly within the receptor. The comparative e-pharmacophoric study also suggests and supports our predictions regarding the minimum features required in ligand molecule to behave as falcipain- III inhibitors and is also helpful in screening the large database as future antimalarial inhibitors.

Effect of extrusion temperature and moisture content of corn flour on crystallinity and hardness of rice analogues

NASA Astrophysics Data System (ADS)

Budi, Faleh Setia; Hariyadi, Purwiyatno; Budijanto, Slamet; Syah, Dahrul

2015-12-01

Rice analogues are food products made of broken rice and/or any other carbohydrate sources to have similar texture and shape as rice. They are usually made by hot extrusion processing. The hot extrusion process may change the crystallinity of starch and influence the characteristic of rice analogues. Therefore, this research aimed to study the effect of moisture content of incoming dough and temperature of extrusion process on the crystallinity and hardness of resulting rice analogues. The dough's were prepared by mixing of corn starch-flour with ratio 10/90 (w/w) and moisture content of 35%, 40% and 45% (w/w) and extrusion process were done at temperature of 70, 80, 90°C by using of twin screw extruder BEX-DS-2256 Berto. The analyses were done to determine the type of crystal, degree of crystallinity, and hardness of the resulting rice analogues. Our result showed that the enhancement of extrusion temperature from 70 - 90°C increased degree of crystallinity from 5.86 - 15.00% to 10.70 - 18.87% and hardness from 1.71 - 4.36 kg to 2.05 - 5.70 kg. The raising of dough moisture content from 35 - 45% decreased degree of crystallinity from 15.00 - 18.87% to 5.86 - 10.70% and hardness from 4.36 - 5.70 kg to 1.71 - 2.05 kg. The increase of degree of crystallinity correlated positively with the increase of hardness of rice analogues (r = 0.746, p = 0.05).

(D-Phe/sup 12/)bombesin analogues: a new class of bombesin receptor antagonists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heinz-Erian, P.; Coy, D.H.; Tamura, M.

1987-03-01

Previous attempts to develop analogues of bombesin that function as specific receptor antagonists have been unsuccessful. Alteration of the histidine in luteinizing hormone releasing factor has resulted in analogues that function as competitive antagonists. In the present study the authors have used a similar strategy and altered the histidine in bombesin. (D-Phe/sup 12/)bombesin, (D-Phe/sup 12/,Leu/sup 14/)bombesin, and (Try/sup 4/, D-)je/sup 12/) bombesin did not stimulate amylase release from guinea pig pancreatic acini when present alone, but each analog inhibited bombesin-stimulated secretion. For each analog, detectable inhibition occurred at 1 ..mu..M and half-maximal inhibition at 4 ..mu..M. Each analog inhibited amylasemore » release by bombesin and other agonists that stimulate secretion by interacting with bombesin receptors. The analogues of bombesin did not alter stimulation by substance P or other agonists that interact with other receptors. The inhibition of the action of bombesin was competitive with Schild plots having slopes of 1.0. Each analog also inhibited binding of /sup 125/I-labeled (Try/sup 4/) bombesin but not /sup 125/I-labeled substance P. These results demonstrate that (D-Phe/sup 12/) analogues of bombesin function as bombesin receptor antagonists and are the only bombesin receptor antagonists that interact only with the bombesin receptor. Because of their specificity, these analogues may prove useful for defining the role of bombesin in various physiological or pathological processes.« less

Design of novel antimicrobial peptide dimer analogues with enhanced antimicrobial activity in vitro and in vivo by intermolecular triazole bridge strategy.

PubMed

Liu, Beijun; Huang, Haifeng; Yang, Zhibin; Liu, Beiyin; Gou, Sanhu; Zhong, Chao; Han, Xiufeng; Zhang, Yun; Ni, Jingman; Wang, Rui

2017-02-01

Currently, antimicrobial peptides have attracted considerable attention because of their broad-sprectum activity and low prognostic to induce antibiotic resistance. In our study, for the first time, a series of side-chain hybrid dimer peptides J-AA (Anoplin-Anoplin), J-RR (RW-RW), and J-AR (Anoplin-RW) based on the wasp peptide Anoplin and the arginine- and tryptophan-rich hexapeptide RW were designed and synthesized by click chemistry, with the intent to improve the antimicrobial efficacy of peptides against bacterial pathogens. The results showed that all dimer analogues exhibited up to a 4-16 fold increase in antimicrobial activity compared to the parental peptides against bacterial strains. Furthermore, the antimicrobial activity was confirmed by time-killing kinetics assay with two strains which showed that these dimer analogues at 1, 2×MIC were rapidly bactericidal and reduced the initial inoculum significantly during the first 2-6h. Notably, dimer peptides showed synergy and additivity effects when used in combination with conventional antibiotics rifampin or penicillin respectively against the multidrug-resistant strains. In the Escherichia coli-infected mouse model, all of hybrid dimer analogues had significantly lower degree of bacterial load than the untreated control group when injected once i.p. at 5mg/kg. In addition, the infected mice by methicillin-resistant (MRSA) strain could be effectively treated with J-RR. All of dimer analogues had membrane-active action mode. And the membrane-dependent mode of action signifies that peptides functions freely and without regard to conventional resistant mechanisms. Circular dichroism analyses of all dimer analogues showed a general predominance of α-helix conformation in 50% trifluoroethanol (TFE). Additionally, the acute toxicities study indicated that J-RR or J-AR did not show the signs of toxicity when adult mice exposed to concentration up to 120mg/kg. The 50% lethal dose (LD 50 ) of J-AA was 53.6mg/kg. In conclusion, to design and synthesize side chain-hybrid dimer analogues via click chemistry may offer a new strategy for antibacterial therapeutic option. Copyright © 2016 Elsevier Inc. All rights reserved.

Uncovering mass segregation with galaxy analogues in dark-matter simulations

NASA Astrophysics Data System (ADS)

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.

Imaging, biodistribution and therapy potential of halogenated tamoxifen analogues.

PubMed

Yang, D J; Li, C; Kuang, L R; Price, J E; Buzdar, A U; Tansey, W; Cherif, A; Gretzer, M; Kim, E E; Wallace, S

1994-01-01

Tamoxifen binds to estrogen receptors (ERs) and prevents breast cancer cell proliferation. This study is aimed at developing a ligand for imaging ER (+) breast tumors by positron emission tomography (PET) or single photon emission computed tomography (SPECT). [18F]-Labeled tamoxifen analogue ([18F]FTX) was prepared in 30-40% yield and [131I]-labeled tamoxifen analogue ([131I]ITX) was prepared in 20-25% yield. In mammary tumor-bearing rats, the biodistribution of [18F]FTX at 2 h showed a tumor uptake value (% injected dose/gram tissue) of 0.41 +/- 0.07; when rats were pretreated with diethylstilbestrol (DES), the value changed to 0.24 +/- 0.017. [131I]ITX at 6 h showed a tumor uptake value of 0.26 +/- 0.166; when rats were pretreated with DES, the value changed to 0.22 +/- 0.044. Priming tumor-bearing rats with estradiol, a tumor uptake value for [131I]ITX was increased to 0.48 +/- 0.107 at 6 h. In the [3H]estradiol receptor assay, tumors had a mean estrogen receptor density of 7.5 fmol/mg of protein. In gamma scintigraphic imaging studies with [131I]ITX, the rabbit uterus uptake can be blocked by pretreatment with DES. Both iodo-tamoxifen and tamoxifen reduced ER(+) breast tumor growth at the dose of 50 micrograms in tumor-bearing mice. The findings indicate that tamoxifen analogue uptake in tumors occurs via an ER-mediated process. Both analogues should have potential for diagnosing functioning ER(+) breast cancer.

Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues.

PubMed

Knapp, Levente; Szita, Bence; Kocsis, Kitti; Vécsei, László; Toldi, József

2017-01-01

The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified. In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested. The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level. The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening.

Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues

PubMed Central

Knapp, Levente; Szita, Bence; Kocsis, Kitti; Vécsei, László; Toldi, József

2017-01-01

Background The complex pathophysiology of migraine is not yet clearly understood; therefore, experimental models are essential for the investigation of the processes related to migraine headache, which include cortical spreading depression (CSD) and NO donor-induced neurovascular changes. Data on the assessment of drug efficacy in these models are often limited, which prompted us to investigate a novel combined migraine model in which an effective pharmacon could be more easily identified. Materials and methods In vivo electrophysiological experiments were performed to investigate the effect of nitroglycerin (NTG) on CSD induced by KCl application. In addition, sumatriptan and newly synthesized neuroactive substances (analogues of the neuromodulator kynurenic acid [KYNA]) were also tested. Results The basic parameters of CSDs were unchanged following NTG administration; however, propagation failure was decreased compared to the controls. Sumatriptan decreased the number of CSDs, whereas propagation failure was as minimal as in the NTG group. On the other hand, both of the KYNA analogues restored the ratio of propagation to the control level. Discussion The ratio of propagation appeared to be the indicator of the effect of NTG. This is the first study providing direct evidence that NTG influences CSD; furthermore, we observed different effects of sumatriptan and KYNA analogues. Sumatriptan changed the generation of CSDs, whereas the analogues acted on the propagation of the waves. Our experimental design overlaps with a large spectrum of processes present in migraine pathophysiology, and it can be a useful experimental model for drug screening. PMID:28053504

Misoprostol inhibits gastric mucosal release of endogenous prostaglandin E2 and thromboxane B2 in healthy volunteers.

PubMed Central

Mertz-Nielsen, A; Eskerod, O; Bukhave, K; Rask-Madsen, J

1995-01-01

Prostaglandin analogues of the E-series theoretically offer the ideal antiulcer drugs. Peptic ulcer healing with prostaglandin analogues is, however, no better than would be predicted from their ability to inhibit gastric acid secretion and they are less effective than histamine H2 receptor antagonists in preventing ulcer relapse. It could be that prostaglandin analogues inhibit gastric mucosal synthesis or release of endogenous eicosanoids, thereby abrogating their own effects. This study, therefore, examined how a single therapeutic dose (200 micrograms) of misoprostol, a synthetic analogue of prostaglandin E1, influences gastric mucosal release of endogenous prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and chemotactic leukotriene B4 (LTB4) during basal conditions and in response to gastric luminal acidification (0.1 M HCl; 5 ml/min for 10 minutes). Nine healthy volunteers were studied in a single blind, cross over design. In each subject misoprostol or placebo was instilled in randomised order into the stomach, which was subsequently perfused with isotonic mannitol. Misoprostol significantly decreased basal as well as acid stimulated output of PGE2 and TXB2, without affecting output of LTB4. These data show that misoprostol inhibits gastric mucosal synthesis of prostanoids. Decreased concentrations, or even a changed profile, of native eicosanoids modulating the release of inflammatory mediators from immune cells might explain why prostaglandin analogues have a comparatively poor clinical performance in ulcer healing and prevention. PMID:7737555

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

NASA Astrophysics Data System (ADS)

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

2000-10-01

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

Synthesis, SAR and molecular docking studies of benzo[d]thiazole-hydrazones as potential antibacterial and antifungal agents.

PubMed

Zha, Gao-Feng; Leng, Jing; Darshini, N; Shubhavathi, T; Vivek, H K; Asiri, Abdullah M; Marwani, Hadi M; Rakesh, K P; Mallesha, N; Qin, Hua-Li

2017-07-15

A series of new benzo[d]thiazole-hydrazones analogues were synthesized and screened for their in vitro antibacterial and antifungal activities. The results revealed that compounds 13, 14, 15, 19, 20, 28 and 30 exhibited superior antibacterial potency compared to the reference drug chloramphenicol and rifampicin. Compounds 5, 9, 10, 11, 12, 28 and 30 were found to be good antifungal activity compared to the standard drug ketoconazole. A preliminary study of the structure-activity relationship (SAR) revealed that the antimicrobial activity depended on the effect of different substituents on the phenyl ring. The electron donating (OH and OCH 3 ) groups presented in the analogues, increase the antibacterial activity (except compound 12), interestingly, while the electron withdrawing (Cl, NO 2 , F and Br) groups increase the antifungal activity (except compound 19 and 20). In addition, analogues containing thiophene (28) and indole (30) showed good antimicrobial activities. Whereas, aliphatic analogues (24-26) shown no activities in both bacterial and fungal stains even in high concentrations (100µg/mL). Molecular docking studies were performed for all the synthesized compounds of which compounds 11, 19 and 20 showed the highest glide G-score. Copyright © 2017 Elsevier Ltd. All rights reserved.

Toxicological Effects during and following Persistent Insulin-Induced Hypoglycaemia in Healthy Euglycaemic Rats.

PubMed

Jensen, Vivi F H; Mølck, Anne-Marie; Berthelsen, Line O; Alifrangis, Lene; Andersen, Lene; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid B

2017-07-01

New insulin analogues with a longer duration of action and a 'peakless' pharmacokinetic profile have been developed to improve efficacy, safety and convenience for patients with diabetes. During non-clinical development, according to regulatory guidelines, these analogues are tested in healthy euglycaemic rats rendering them persistently hypoglycaemic. Little is known about the effect of persistent (24 hr/day) insulin-induced hypoglycaemia (IIH) in rats, complicating interpretation of results in pre-clinical studies with new longer-acting insulin analogues. In this study, we investigated the effects of persistent IIH and their reversibility in euglycaemic rats. Histopathological changes in insulin-infused animals included partly reversible axonal and reversible myofibre degeneration in peripheral nerve and skeletal muscle tissue, respectively, as well as reversible pancreatic islet atrophy and partly reversible increase in unilocular adipocytes in brown adipose tissue. Additionally, results suggested increased gluconeogenesis. The observed hyperphagia, the pancreatic, peripheral nerve and skeletal muscle changes were considered related to the hypoglycaemia. Cessation of insulin infusion resulted in transient hyperglycaemia, decreased food consumption and body-weight loss before returning to control levels. The implications for the interpretation of non-clinical studies with long-acting insulin analogues are discussed. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Using stressful films to analyze risk factors for PTSD in analogue experimental studies--which film works best?

PubMed

Weidmann, Anke; Conradi, Ania; Groger, Kathrin; Fehm, Lydia; Fydrich, Thomas

2009-10-01

To understand mental disorders, analogue paradigms provide an indispensable contribution. In posttraumatic stress disorder (PTSD), the stressful film paradigm is a frequently used analogue approach: Films depicting traumatic events are shown to non-clinical participants in order to elicit stress responses analogue to responses to traumatic events in real life. Previous studies used a large variety of films, which is problematic with regard to the comparability of results. The main goal of this study was to identify a film clip that (a) consistently provokes stress reactions and (b) provokes reactions that are as similar as possible to traumatic stress. We randomly exposed 105 male and female participants to one of four stressful films, differing, e.g., in content and origin. Intrusive memories of the film, reported immediately after the film and during a diary phase of three days, as well as distress, heart rate, and several mood states were measured. A film clip depicting rape elicited the most consistent reactions that were characterized by a higher heart rate, more distress and more intrusive memories, compared to the other three clips. Intrusive memories across all films were especially related to an increase in heart rate and disgust in response to the film.

Intestinal P-glycoprotein inhibitors, benzoxanthone analogues.

PubMed

Chae, Song Wha; Lee, Jaeok; Park, Jung Hyun; Kwon, Youngjoo; Na, Younghwa; Lee, Hwa Jeong

2018-02-01

The inhibitors of P-glycoprotein (P-gp) which limits an access of exogenous compounds in the luminal membrane of the intestine have been studied to enhance the intestinal P-gp-mediated absorption of anticancer drugs. Inhibition of the efflux pump by synthesized benzoxanthone derivatives was investigated in vitro and in vivo. MCF-7/ADR cell line was used for cytotoxicity assay and [ 3 H]-daunomycin (DNM) accumulation/efflux study. Eight benzoxanthone analogues were tested for their effects on DNM cytotoxicity. Among them, three analogues were selected for the accumulation/efflux and P-gp ATPase studies. Paclitaxel (PTX), a P-gp substrate anticancer drug, was orally administered to rats with/without compound 1 (8,10-bis(thiiran-2-ylmethoxy)-7H-benzo[c]xanthen-7-one). The pharmacokinetic parameters of PTX in the presence/absence of compound 1 were evaluated from the plasma concentration-time profiles. Compound 1 increased the DNA accumulation to 6.5-fold and decreased the DNM efflux to approximately 1/2 in the overexpressing P-gp cell line. Relative bioavailability (RB) of PTX in rats was significantly increased up to 3.2-fold by compound 1 (0.5 or 2 mg/kg). Benzoxanthone analogue, compound 1 is strongly suggested to be a promising inhibitor of P-gp to improve an oral absorption of compounds for cancer therapy. © 2017 Royal Pharmaceutical Society.

Polarized Neutron Study of Ni-Mn-Ga Alloys: Site-Specific Spin Density Affected by Martensitic Transformation.

PubMed

Lázpita, P; Barandiarán, J M; Gutiérrez, J; Mondelli, C; Sozinov, A; Chernenko, V A

2017-10-13

Polarized neutron scattering has been used to obtain the magnetic moment at specific crystallographic sites of the austenitic and martensitic phases of two nonstoichiometric Ni-Mn-Ga single crystals with close composition. These alloys have been chosen because they exhibit different structures in the paramagnetic state and inverse positions of the respective martensitic transformation and Curie temperature. The diffraction analysis revealed a remarkable result: Despite the similar alloy composition, the magnetic moments of Mn are quite different for the two alloys at the same crystallographic position. Furthermore, such a difference enabled us to assess that the exchange coupling between Mn atoms switches from ferro- to antiferromagnetic at a distance between 2.92 and 3.32 Å in the martensite. These results are of great importance to guide first principles calculations that, up to now, have not been contrasted with experiments at the atomic level.

Polarized Neutron Study of Ni-Mn-Ga Alloys: Site-Specific Spin Density Affected by Martensitic Transformation

NASA Astrophysics Data System (ADS)

Lázpita, P.; Barandiarán, J. M.; Gutiérrez, J.; Mondelli, C.; Sozinov, A.; Chernenko, V. A.

2017-10-01

Polarized neutron scattering has been used to obtain the magnetic moment at specific crystallographic sites of the austenitic and martensitic phases of two nonstoichiometric Ni-Mn-Ga single crystals with close composition. These alloys have been chosen because they exhibit different structures in the paramagnetic state and inverse positions of the respective martensitic transformation and Curie temperature. The diffraction analysis revealed a remarkable result: Despite the similar alloy composition, the magnetic moments of Mn are quite different for the two alloys at the same crystallographic position. Furthermore, such a difference enabled us to assess that the exchange coupling between Mn atoms switches from ferro- to antiferromagnetic at a distance between 2.92 and 3.32 Å in the martensite. These results are of great importance to guide first principles calculations that, up to now, have not been contrasted with experiments at the atomic level.

Further aspects on cellular and cordless telephones and brain tumours.

PubMed

Hardell, Lennart; Mild, Kjell Hansson; Carlberg, Michael

2003-02-01

We included in a case-control study on brain tumours and mobile and cordless telephones 1,617 patients aged 20-80 years of both sexes diagnosed during January 1, 1997 to June 30, 2000. They were alive at the study time and had histopathology verified brain tumour. One matched control to each case was selected from the Swedish Population Register. The study area was the Uppsala-Orebro, Stockholm, Linköping and Göteborg medical regions of Sweden. Exposure was assessed by a questionnaire that was answered by 1,429 (88%) cases and 1,470 (91%) controls. In total use of analogue cellular telephones gave an increased risk with odds ratio (OR)=1.3, 95% confidence interval (CI)=1.04-1.6, whereas digital and cordless phones did not overall increase the risk significantly. Ipsilateral use of analogue phones gave OR=1.7, 95% CI=1.2-2.3, digital phones OR=1.3, 95% CI=1.02-1.8 and cordless phones OR=1.2, 95% CI=0.9-1.6. The risk for ipsilateral use was significantly increased for astrocytoma for all studied phone types, analogue phones OR=1.8,95% CI=1.1-3.2, digital phones OR=1.8, 95% CI=1.1-2.8, cordless phones OR=1.8, 95% CI=1.1-2.9. Use of a telephone on the opposite side of the brain was not associated with a significantly increased risk for brain tumours. Regarding anatomical area of the tumour and exposure to microwaves, the risk was increased for tumours located in the temporal area on the same side of the brain that was used during phone calls, significantly so for analogue cellular telephones OR=2.3, 95% CI=1.2-4.1. For acoustic neurinoma OR=4.4, 95% CI=2.1-9.2 was calculated among analogue cellular telephone users. When duration of use was analysed as a continuous variable in the total material, the risk increased per year for analogue phones with OR=1.04, 95% CI=1.01-1.08. For astrocytoma and ipsilateral use the trend was for analogue phones OR=1.10, 95% CI=1.02-1.19, digital phones OR=1.11, 95% CI=1.01-1.22, and cordless phones OR=1.09, 95% CI=1.01-1.19. There was a tendency of a shorter tumour induction period for ipsilateral exposure to microwaves than for contralateral, which may indicate a tumour promotor effect.

Design and Synthesis of Novel Arctigenin Analogues for the Amelioration of Metabolic Disorders

PubMed Central

2015-01-01

Analogues of the natural product (−)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (−)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure–activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes. PMID:25941553

Design and synthesis of novel arctigenin analogues for the amelioration of metabolic disorders.

PubMed

Duan, Shudong; Huang, Suling; Gong, Jian; Shen, Yu; Zeng, Limin; Feng, Ying; Ren, Wenming; Leng, Ying; Hu, Youhong

2015-04-09

Analogues of the natural product (-)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (-)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure-activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes.

The Oxidation of Iron: Experiment, Simulation, and Analysis in Introductory Chemistry

ERIC Educational Resources Information Center

Schubert, Frederic E.

2015-01-01

In this exercise, an actual chemical reaction, oxidation of iron in air, is studied along with a related analogue simulation of that reaction. The rusting of steel wool is carried out as a class effort. The parallel simulation is performed by students working in small groups. The analogue for the reacting gas is a countable set of discrete marble…

Sex Differences in a Human Analogue of the Radial Arm Maze: The ''17-Box Maze Test''

ERIC Educational Resources Information Center

Rahman, Q.; Abrahams, S.; Jussab, F.

2005-01-01

This study investigated sex differences in spatial memory using a human analogue of the Radial Arm Maze: a revision on the Nine Box Maze originally developed by Abrahams, Pickering, Polkey, and Morris (1997) called the 17-Box Maze Test herein. The task encourages allocentric spatial processing, dissociates object from spatial memory, and…

The Use of Trial-Based Functional Analysis in Public School Classrooms for Two Students with Developmental Disabilities

ERIC Educational Resources Information Center

Rispoli, Mandy J.; Davis, Heather S.; Goodwyn, Fara D.; Camargo, Siglia

2013-01-01

Analogue functional analyses are a well-researched means of determining behavioral function in research and clinical contexts. However, conducting analogue functional analyses in school settings can be problematic and may lead to inconclusive results. The purpose of this study was to compare the results of a trial-based functional analysis with…

Effect of restricted protein diet supplemented with keto analogues in end-stage renal disease: a systematic review and meta-analysis.

PubMed

Jiang, Zheng; Tang, Yi; Yang, Lichuan; Mi, Xuhua; Qin, Wei

2018-04-01

To evaluate the efficacy and safety of the restricted protein diet supplemented with keto analogues when applied in end-stage renal disease (ESRD). The Cochrane Library, PubMed, Embase, CBM and CENTRAL databases were searched and reviewed up to January 2017. Clinical trials were analyzed using RevMan 5.3 software. Five randomized controlled trials were selected and included in this study according to our inclusion and exclusion criteria. Changes in serum albumin, PTH, triglyceride, cholesterol, calcium, phosphorus, hemoglobin, Kt/v and CRP before and after treatment were analyzed. Meta-analysis results indicated that, compared with normal protein diet, low-protein diet (LPD) supplemented with keto analogues (sLPD) could improve serum albumin (P < 0.00001), hyperparathyroidism (P < 0.00001) and hyperphosphatemia (P = 0.008). No differences in triglyceride, cholesterol, hemoglobin, Kt/v and CRP were observed between different protein intake groups. Restricted protein diet supplemented with keto analogues (sLPD) may improve nutritional status and prevent hyperparathyroidism in ESRD patients. The current data were mainly obtained from short-term, single-center trails with small sample sizes and limited nutritional status indexes, indicating a need for further study.

Parturient perineal distensibility tolerance assessed by EPI-NO: an observational study.

PubMed

Nakamura, Mary Uchiyama; Sass, Nelson; Elito Júnior, Julio; Petricelli, Carla Dellabarba; Alexandre, Sandra Maria; Araujo Júnior, Edward; Zanetti, Miriam Raquel Diniz

2014-01-01

To determine how parturient women tolerate the use of a perineal distensibility assessment technique using the EPI-NO device. An observational study with a total of 227 full-term parturient women was performed. During the evaluation with EPI-NO, parturient patients were asked about their sensation of discomfort. The degree of discomfort was measured using the Visual Analogue Scale, with a score from zero to 10. The Mann-Whitney test was applied to assess perineal distensibility measured by EPI-NO and the degree of discomfort caused by the test according to parity. The relation between perineal distensibility and discomfort was analyzed by using the Spearman correlation test (r). The test with EPI-NO caused only slight discomfort (mean Visual Analogue Scale of 3.8), and primiparous women reported significantly greater discomfort (mean Visual Analogue Scale of 4.5) than did multiparous (mean Visual Analogue Scale=3.1), with p<0.001 women. A negative correlation was observed, in other words, the greater the perineal distensibility on the EPI-NO, the lower the pain reported by the patients (r=-0.424; p<0.001). The assessment of perineal distensibility with EPI-NO was well tolerated by the parturient women.

XAFS Study of the Ferro- and Antiferromagnetic Binuclear Copper(II) Complexes of Azomethine Based Tridentate Ligands

NASA Astrophysics Data System (ADS)

Vlasenko, Valery G.; Vasilchenko, Igor S.; Pirog, Irina V.; Shestakova, Tatiana E.; Uraev, Ali I.; Burlov, Anatolii S.; Garnovskii, Alexander D.

2007-02-01

Binuclear copper complexes are known to be models for metalloenzymes containing copper active sites, and some of them are of considerable interest due to their magnetic and charge transfer properties. The reactions of the complex formation of bibasic tridentate heterocyclic imines with copper acetate leads to two types of chelates with mono deprotonated ligands and with totally deprotonated ligands. Cu K-edge EXAFS has been applied to determine the local structure around the metal center in copper(II) azomethine complexes with five tridentate ligands: 1-(salycilideneimino)- or 1-(2-tosylaminobenzilideneimino)-2-amino(oxo, thio)benzimidazoles. It has been found that some of the chelates studied are bridged binuclear copper complexes, and others are mononuclear complexes. The copper-copper interatomic distances in the bridged binuclear copper complexes were found to be 2.85-3.01 Å. Variable temperature magnetic susceptibility data indicate the presence of both ferromagnetic and antiferromagnetic interactions within the dimer, the former is dominating at low temperatures and the latter at high temperatures.

Ferroelectric and optical properties of `Ba-doped' new double perovskites

NASA Astrophysics Data System (ADS)

Parida, B. N.; Panda, Niranjan; Padhee, R.; Parida, R. K.

2018-06-01

Solid solution of Pb1.5Ba0.5BiNbO6 ceramic is explored here to obtain its ferroelectric and optical properties. The polycrystalline sample was prepared by a standard solid state reaction route. Room temperature XRD and FTIR spectra of the compound exhibit an appreciable change in its crystal structure of Pb2BiNbO6 on addition of 'Ba' in A site. The surface morphology of the gold-plated sintered pellet sample recorded by SEM exhibits a uniform distribution of small grains with well-defined grain boundaries. Detailed studies on the nature of polarization and variation of dielectric constant, tangent loss with temperature as well as frequency indicate the existence of Ferro-electricity in the sample. Using UV-Vis spectroscopy, the optical band gap of the studied sample has been estimated as 2.1 eV, which is useful for photo catalytic devices. Photoluminescence analysis of the powder sample shows a strong red photoluminescence with blue excitation, which is basically useful for LED.

The unique karyotype of Henochilus wheatlandii, a critically endangered fish living in a fast-developing region in Minas Gerais State, Brazil.

PubMed

Silva, Priscilla C; Santos, Udson; Travenzoli, Natália M; Zanuncio, Jose C; Cioffi, Marcelo de B; Dergam, Jorge A

2012-01-01

Henochilus wheatlandii, the only species of this genus, is critically endangered and was considered extinct for over a century. The rediscovery of this fish in 1996 made it possible to study its phylogenetic relationships with other species in the subfamily Bryconinae. The aim of this study was to characterise the karyotype of H. wheatlandii. Standard staining, C-positive heterochromatin and nucleolar organiser region (NOR) banding, chromomycin A(3) staining, and fluorescent in situ hybridisation (FISH) using 5S rDNA and 18S rDNA probes were conducted on nineteen specimens collected in the Santo Antonio River, a sub-basin of the Doce River in Ferros municipality, Minas Gerais State, Brazil. Henochilus wheatlandii shared the same diploid number and chromosome morphology as other species of Bryconinae. However, its heterochromatin distribution patterns, NOR localisation, and FISH patterns revealed a cytogenetic profile unique among Neotropical Bryconinae, emphasizing the evolutionary uniqueness of this threatened species.

The Unique Karyotype of Henochilus wheatlandii, a Critically Endangered Fish Living in a Fast-Developing Region in Minas Gerais State, Brazil

PubMed Central

Silva, Priscilla C.; Santos, Udson; Travenzoli, Natália M.; Zanuncio, Jose C.; Cioffi, Marcelo de B.; Dergam, Jorge A.

2012-01-01

Henochilus wheatlandii, the only species of this genus, is critically endangered and was considered extinct for over a century. The rediscovery of this fish in 1996 made it possible to study its phylogenetic relationships with other species in the subfamily Bryconinae. The aim of this study was to characterise the karyotype of H. wheatlandii. Standard staining, C-positive heterochromatin and nucleolar organiser region (NOR) banding, chromomycin A3 staining, and fluorescent in situ hybridisation (FISH) using 5S rDNA and 18S rDNA probes were conducted on nineteen specimens collected in the Santo Antonio River, a sub-basin of the Doce River in Ferros municipality, Minas Gerais State, Brazil. Henochilus wheatlandii shared the same diploid number and chromosome morphology as other species of Bryconinae. However, its heterochromatin distribution patterns, NOR localisation, and FISH patterns revealed a cytogenetic profile unique among Neotropical Bryconinae, emphasizing the evolutionary uniqueness of this threatened species. PMID:22848754

Late Pleniglacial vegetation in eastern-central Europe: are there modern analogues in Siberia?

NASA Astrophysics Data System (ADS)

Magyari, Enikő Katalin; Kuneš, Petr; Jakab, Gusztáv; Sümegi, Pál; Pelánková, Barbora; Schäbitz, Frank; Braun, Mihály; Chytrý, Milan

2014-07-01

To characterize Late Pleniglacial (LPG: 26.5-15 ka cal BP) and particularly Last Glacial Maximum (LGM: 21 ± 2 ka cal BP) vegetation and climate, fossil pollen assemblages are often compared with modern pollen assemblages. Given the non-analogue climate of the LPG, a key question is how glacial pollen assemblages and thereby vegetation compare with modern vegetation. In this paper we present three LPG pollen records from the Carpathian Basin and the adjoining Carpathian Mountains to address this question and provide a concise compositional characterization of the LPG vegetation. Fossil pollen assemblages were compared with surface pollen spectra from the Altai-Sayan Mountains in southern Siberia. This area shows many similarities with the LPG vegetation of eastern-central Europe, and has long been considered as its best modern analogue. Ordination and analogue matching were used to characterize vegetation composition and find the best analogues. Our results show that few LPG pollen assemblages have statistically significant analogues in southern Siberia. When analogue pairings occur they suggest the predominance of wet and mesic grasslands and dry steppe in the studied region. Wooded vegetation types (continental and suboceanic hemiboreal forest, continental taiga) appear as significant analogues only in a few cases during the LGM and more frequently after 16 ka cal BP. These results suggest that the LPG landscape of the Carpathian Basin was dominated by dry steppe that occurred outside the river floodplains, while wet and mesic grasslands occurred in the floodplains and on other sites influenced by ground water. Woody vegetation mainly occurred in river valleys, on wet north-facing hillsides, and scattered trees were likely also present on the loess plateaus. The dominant woody species were Larix, Pinus sylvestris, Pinus mugo, Pinus cembra, Picea abies, Betula pendula/pubescens, Betula nana, Juniperus, Hippophaë rhamnoides, Populus, Salix and Alnus. The pollen records suggest uninterrupted presence of mesophilous temperate trees (Quercus, Ulmus, Corylus, Fagus and Fraxinus excelsior) in the Eastern Carpathian Mountains throughout the LPG. We demonstrate that the LPG vegetation in this area was characterized by increasing grass cover and high frequency of wildfires. We conclude that pollen spectra over represent trees in the forest-steppe landscape of the LPG, furthermore pollen-based quantitative climate reconstructions for the LPG are challenging in this area due to the scarcity of modern analogues.

Synthesis and characterization of mitoQ and idebenone analogues as mediators of oxygen consumption in mitochondria.

PubMed

Duveau, Damien Y; Arce, Pablo M; Schoenfeld, Robert A; Raghav, Nidhi; Cortopassi, Gino A; Hecht, Sidney M

2010-09-01

Analogues of mitoQ and idebenone were synthesized to define the structural elements that support oxygen consumption in the mitochondrial respiratory chain. Eight analogues were prepared and fully characterized, then evaluated for their ability to support oxygen consumption in the mitochondrial respiratory chain. While oxygen consumption was strongly inhibited by mitoQ analogues 2-4 in a chain length-dependent manner, modification of idebenone by replacement of the quinone methoxy groups by methyl groups (analogues 6-8) reduced, but did not eliminate, oxygen consumption. Idebenone analogues 6-8 also displayed significant cytoprotective properties toward cultured mammalian cells in which glutathione had been depleted by treatment with diethyl maleate. Copyright 2010 Elsevier Ltd. All rights reserved.

Photophysical Study of Novel Perylene Analogues for Biophysical Applications

NASA Astrophysics Data System (ADS)

Palos-Chávez, Jorge; Penick, Mark; Negrete, George; Brancaleon, Lorenzo

2011-03-01

Perylene and perylene derivatives have been shown to be useful in a variety of photoinitiated applications, such as molecular dyes, organic solar cells, etc. Recently we started the characterization of novel 3,9-perylene analogues which could potentially lead to the synthesis of novel molecules with improved ability to separate charges. We have characterized the basic photophysical properties of these molecules, and we are currently investigating the photochemistry that leads to photoproducts in chlorinated compounds. Spectroscopic measurements show the substantial changes in photophysical parameters consistent with the conversion of the original compounds into photoproducts. SEM and AFM imaging show that these photoproducts form ordered particles. Mass spectrometry studies have confirmed the presence of these photoproducts as well. Additional studies are underway concerning the use of these novel perylene analogues in binding to biological structures such as proteins. It is hoped that these compounds will prove useful for biophysical applications, specifically in studying the manipulation of protein conformation via physical methods. Supported by NIH/NIGMS MBRS RISE GM-60655.

Benzothiazole analogues: Synthesis, characterization, MO calculations with PM6 and DFT, in silico studies and in vitro antimalarial as DHFR inhibitors and antimicrobial activities.

PubMed

Thakkar, Sampark S; Thakor, Parth; Ray, Arabinda; Doshi, Hiren; Thakkar, Vasudev R

2017-10-15

Benzothiazole analogues are of interest due to their potential activity against malarial and microbial infections. In search of suitable antimicrobial and antimalarial agents, we report here the synthesis, characterization and biological activities of benzothiazole analogues (J 1-J 10). The molecules were characterized by IR, Mass, 1 H NMR, 13 C NMR and elemental analysis. The in vitro antimicrobial activity was investigated against pathogenic strains; the results were explained with the help of DFT and PM6 molecular orbital calculations. In vitro cytotoxicity and genotoxicity of the molecules were studied against S. pombe cells. In vitro antimalarial activity was studied. The active compounds J 1, J 2, J 3, J 5 and J 6 were further evaluated for enzyme inhibition efficacy against the receptor Pf-DHFR, computational and in vitro studies were carried out to examine their candidatures as lead dihydrofolate reductase inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Distribution of 137Cs, 90Sr and their chemical analogues in the components of an above-ground part of a pine in a quasi-equilibrium condition].

PubMed

Mamikhin, S V; Manakhov, D V; Shcheglov, A I

2014-01-01

The additional study of the distribution of radioactive isotopes of caesium and strontium and their chemical analogues in the above-ground components of pine in the remote from the accident period was carried out. The results of the research confirmed the existence of analogy in the distribution of these elements on the components of this type of wood vegetation in the quasi-equilibrium (relatively radionuclides) condition. Also shown is the selective possibility of using the data on the ash content of the components of forest stands of pine and oak as an information analogue.

Antimicrobial activity of antihypertensive food-derived peptides and selected alanine analogues.

PubMed

McClean, Stephen; Beggs, Louise B; Welch, Robert W

2014-03-01

This study evaluated four food-derived peptides with known antihypertensive activities for antimicrobial activity against pathogenic microorganisms, and assessed structure-function relationships using alanine analogues. The peptides (EVSLNSGYY, barley; PGTAVFK, soybean; TTMPLW, α-casein; VHLPP, α-zein) and the six alanine substitution peptides of PGTAVFK were synthesised, characterised and evaluated for antimicrobial activity using the bacteria, Escherichia coli, Staphylococcus aureus, and Micrococcus luteus and the yeast, Candida albicans. The peptides TTMPLW and PGTAVFK inhibited growth of all four microorganisms tested, with activities of a similar order of magnitude to ampicillin and ethanol controls. EVSLNSGYY inhibited the growth of the bacteria, but VHLPP showed no antimicrobial activity. The alanine analogue, PGAAVFK showed the highest overall antimicrobial activity and PGTAVFA showed no activity; overall, the activities of the analogues were consistent with their structures. Some peptides with antihypertensive activity also show antimicrobial activity, suggesting that food-derived peptides may exert beneficial effects via a number of mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Selection of an in vitro carcinogenicity test for derivatives of the carcinogen hexamethylphosphoramide.

PubMed Central

Ashby, J.; Styles, J. A.; Anderson, D.

1977-01-01

The demonstration that hexamethylphosphoramide (HMPA) possesses potent carcinogenic properties has raised doubts about the safety of exposure to other phosphoric amides. In order to define a suitable short-term test with which to evaluate such analogues, the response of the Salmonella typhimurium mutation assay of Ames and cell transformation assay of Styles to HMPA and 3 selected analogues has been studied. These analogues were the related leukaemogen phosphoramide, the putative non-carcinogen, phosphoric trianilide and N.N'N''-trimethylphosphorothioic triamide, a compound of unknown and hitherto unpredictable properties. While both tests found the trianilide negative, the Ames test failed to detect phosphoramide as positive and gave an erratic and predominantly negative response to HMPA. In contrast, the transformation assay found both phosphoramide and HMPA positive. This test response profile indicates that the transformation assay is the preferred test with which to evaluate analogues of HMPA for potential carcinogenicity. Some structural requirements for potential carcinogenicity within this class of compounds are tentatively deduced. PMID:337998

Structure-activity analysis and biological studies of chensinin-1b analogues.

PubMed

Dong, Weibing; Dong, Zhe; Mao, Xiaoman; Sun, Yue; Li, Fei; Shang, Dejing

2016-06-01

Chensinin-1b shows a potent and broad-spectrum bactericidal activity and no hemolytic activity and thus is a potential therapeutic agent against bacterial infection. The NMR structure of chensinin-1b consists of a partially α-helical region (residues 8-14) in a membrane-mimic environment that is distinct from other common antimicrobial peptides. However, further analysis of the structural features of chensinin-1b is required to better understand its bactericidal activity. In this study, a series of N- and C-terminally truncated or amino acid-substituted chensinin-1b analogues were synthesized. Next, the bactericidal activity and bacterial membrane effects of the analogues were investigated. The results indicated that the N-terminal residues play a more significant role than the C-terminal residues in the antimicrobial activity of chensinin-1b. The removal of five amino acids from the C-terminus of chensinin-1b did not affect its biological properties, but helix disruption significantly decreased bactericidal activity. The substitution of positively charged residues increased the helicity and antimicrobial activity of the peptide. We also identified a novel analogue [R(4),R(10)]C1b(3-13) that exhibited similar bactericidal properties with its parent peptide chensinin-1b. Electrostatic interactions between the selected analogues and lipopolysaccharides or cells were detected using isothermal titration calorimetry or zeta potential. The thermodynamic parameters ΔH and ΔS for [R(4),R(10)]C1b(3-13) were -20.48kcalmol(-1) and -0.0408kcalmol(-1)deg(-1), respectively. Chensinin-1b yielded similar results of -26.36kcalmol(-1) and -0.0559kcalmol(-1)deg(-1) for ΔH and ΔS, respectively. These results are consistence with their antimicrobial activities. Lastly, membrane depolarization studies showed that selected analogues exerted bactericidal activity by damaging the cytoplasmic membrane. Antimicrobial peptide chensinin-1b is a candidate for the development of new drugs and a template for the design of synthetic analogues. It mainly exhibits a random coil conformation in membrane environment, and in this manuscript, we characterized the structure of chensinin-1b using NMR spectroscopy, its structure is different than the structures of magainin 2, which has an α-helical conformation and indolicidin, which has a random coil structure. The structural features of chensinin-1b that are required for its potent bactericidal activity were also elucidated. Based on these data, we can fully understand the structure-activity relationship of such peptide and identified a novel analogue with properties that make it an attractive topic for future therapeutic research. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Hepcidin: an important iron metabolism regulator in chronic kidney disease.

PubMed

Antunes, Sandra Azevedo; Canziani, Maria Eugênia Fernandes

2016-01-01

Anemia is a common complication and its impact on morbimortality in patients with chronic kidney disease (CKD) is well known. The discovery of hepcidin and its functions has contributed to a better understanding of iron metabolism disorders in CKD anemia. Hepcidin is a peptide mainly produced by hepatocytes and, through a connection with ferroportin, it regulates iron absorption in the duodenum and its release of stock cells. High hepcidin concentrations described in patients with CKD, especially in more advanced stages are attributed to decreased renal excretion and increased production. The elevation of hepcidin has been associated with infection, inflammation, atherosclerosis, insulin resistance and oxidative stress. Some strategies were tested to reduce the effects of hepcidin in patients with CKD, however more studies are necessary to assess the impact of its modulation in the management of anemia in this population. Resumo Anemia é uma complicação frequente e seu impacto na morbimortalidade é bem conhecido em pacientes com doença renal crônica (DRC). A descoberta da hepcidina e de suas funções contribuíram para melhor compreensão dos distúrbios do metabolismo de ferro na anemia da DRC. Hepcidina é um peptídeo produzido principalmente pelos hepatócitos, e através de sua ligação com a ferroportina, regula a absorção de ferro no duodeno e sua liberação das células de estoque. Altas concentrações de hepcidina descritas em pacientes com DRC, principalmente em estádios mais avançados, são atribuídas à diminuição da excreção renal e ao aumento de sua produção. Elevação de hepcidina tem sido associada à ocorrência de infecção, inflamação, aterosclerose, resistência à insulina e estresse oxidativo. Algumas estratégias foram testadas para diminuir os efeitos da hepcidina em pacientes com DRC, entretanto, serão necessários mais estudos para avaliar o impacto de sua modulação no manejo da anemia nessa população.

Dronedarone: an amiodarone analogue.

PubMed

Doggrell, Sheila A; Hancox, Jules C

2004-04-01

Of the antiarrhythmic drugs in current use, amiodarone is one of the most effective and is associated with a comparatively low risk of drug-induced pro-arrhythmia, probably due to its multiple pharmacological actions on cardiac ion channels and receptors. However, amiodarone is associated with significant extra-cardiac side effects and this has driven development of amiodarone analogues. These analogues include short acting analogues (e.g., AT-2001) with similar acute effects to amiodarone, the thyroid receptor antagonist KB-130015 and dronedarone. Dronedarone, (SR-33589; Sanofi-Synthelabo), is a non-iodinated amiodarone derivative that inhibits Na +, K + and Ca 2+ currents. It is a potent inhibitor of the acetylcholine-activated K + current from atrial and sinoatrial nodal tissue, and inhibits the rapid delayed rectifier more potently than slow and inward rectifier K + currents and inhibits L-type calcium current. Dronedarone is an antagonist at alpha- and beta-adrenoceptors and unlike amiodarone, has little effect at thyroid receptors. Dronedarone is more potent than amiodarone in inhibiting arrhythmias and death in animal models of ischaemia- and reperfusion-induced arrhythmias. In the Dronedarone Atrial Fibrillation Study After Electrical Cardioversion (DAFNE) clinical trial, dronedarone 800 mg/day appeared to be effective and safe for the prevention of atrial fibrillation relapses after cardioversion. The Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease (ANDROMEDA) trial was stopped due to a potential increased risk of death in the dronedarone group. Trials of dronedarone in the maintenance of sinus rhythm in patients with atrial fibrillation and a safety and tolerability study in patients with an implantable cardioverter defibrillator are ongoing. Further experimental and clinical studies are required before we have a definitive answer to whether dronedarone has advantages over amiodarone and other amiodarone analogues.

Legumes and meat analogues consumption are associated with hip fracture risk independently of meat intake among Caucasian men and women: the Adventist Health Study-2.

PubMed

Lousuebsakul-Matthews, Vichuda; Thorpe, Donna L; Knutsen, Raymond; Beeson, W Larry; Fraser, Gary E; Knutsen, Synnove F

2014-10-01

In contrast to non-vegetarians, vegetarians consume more legumes and meat analogues as sources of protein to substitute for meat intake. The present study aimed to assess the association between foods with high protein content (legumes, meat, meat analogues) by dietary pattern (vegetarians, non-vegetarians) and hip fracture incidence, adjusted for selected lifestyle factors. A prospective cohort of Adventist Health Study-2 (AHS-2) enrollees who completed a comprehensive lifestyle and dietary questionnaire between 2002 and 2007. Every two years after enrolment, a short questionnaire on hospitalizations and selected disease outcomes including hip fractures was sent to these members. Respondents (n 33,208) to a baseline and a follow-up questionnaire. In a multivariable model, legumes intake of once daily or more reduced the risk of hip fracture by 64% (hazard ratio = 0·36, 95% CI 0·21, 0·61) compared with those with legumes intake of less than once weekly. Similarly, meat intake of four or more times weekly was associated with a 40% reduced risk of hip fracture (hazard ratio = 0·60, 95% CI 0·41, 0·87) compared with those whose meat intake was less than once weekly. Furthermore, consumption of meat analogues once daily or more was associated with a 49 % reduced risk of hip fracture (hazard ratio = 0·51, 95% CI 0·27, 0·98) compared with an intake of less than once weekly. Hip fracture incidence was inversely associated with legumes intake and, to a lesser extent, meat intake, after accounting for other food groups and important covariates. Similarly, a high intake of meat analogues was associated with a significantly reduced risk of hip fracture.

Applications of Ferro-Nanofluid on a Micro-Transformer

PubMed Central

Tsai, Tsung-Han; Kuo, Long-Sheng; Chen, Ping-Hei; Lee, Da-sheng; Yang, Chin-Ting

2010-01-01

An on-chip transformer with a ferrofluid magnetic core has been developed and tested. The transformer consists of solenoid-type coil and a magnetic core of ferrofluid, with the former fabricated by MEMS technology and the latter by a chemical co-precipitation method. The performance of the MEMS transformer with a ferrofluid magnetic core was measured and simulated with frequencies ranging from 100 kHz to 100 MHz. Experimental results reveal that the presence of the ferrofluid increases the inductance of coils and the coupling coefficient of transformer; however, it also increases the resistance owing to the lag between the external magnetic field and the magnetization of the material. PMID:22163647

Applications of ferro-nanofluid on a micro-transformer.

PubMed

Tsai, Tsung-Han; Kuo, Long-Sheng; Chen, Ping-Hei; Lee, Da-Sheng; Yang, Chin-Ting

2010-01-01

An on-chip transformer with a ferrofluid magnetic core has been developed and tested. The transformer consists of solenoid-type coil and a magnetic core of ferrofluid, with the former fabricated by MEMS technology and the latter by a chemical co-precipitation method. The performance of the MEMS transformer with a ferrofluid magnetic core was measured and simulated with frequencies ranging from 100 kHz to 100 MHz. Experimental results reveal that the presence of the ferrofluid increases the inductance of coils and the coupling coefficient of transformer; however, it also increases the resistance owing to the lag between the external magnetic field and the magnetization of the material.

A prospective randomised cross-over study of the effect of insulin analogues and human insulin on the frequency of severe hypoglycaemia in patients with type 1 diabetes and recurrent hypoglycaemia (the HypoAna trial): study rationale and design

PubMed Central

2012-01-01

Background Severe hypoglycaemia still represents a significant problem in insulin-treated diabetes. Most patients do not experience severe hypoglycaemia often. However, 20% of patients with type 1 diabetes experience recurrent severe hypoglycaemia corresponding to at least two episodes per year. The effect of insulin analogues on glycaemic control has been documented in large trials, while their effect on the frequency of severe hypoglycaemia is less clear, especially in patients with recurrent severe hypoglycaemia. The HypoAna Trial is designed to investigate whether short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing the occurrence of severe hypoglycaemic episodes in patients with recurrent hypoglycaemia. This paper reports the study design of the HypoAna Trial. Methods/design The study is a Danish two-year investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE), multicentre, cross-over trial investigating the effect of insulin analogues versus human insulin on the frequency of severe hypoglycaemia in subjects with type 1 diabetes. Patients are randomised to treatment with basal-bolus therapy with insulin detemir / insulin aspart or human NPH insulin / human regular insulin in random order. The major inclusion criterion is history of two or more episodes of severe hypoglycaemia in the preceding year. Discussion In contrast to almost all other studies in this field the HypoAna Trial includes only patients with major problems with hypoglycaemia. The HypoAna Trial will elucidate whether basal-bolus regimen with short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing occurrence of severe hypoglycaemic episodes in hypoglycaemia prone patients with type 1 diabetes. http://www.clinicaltrials.gov: NCT00346996. PMID:22727048

NMR studies of multiple conformations in complexes of Lactobacillus casei dihydrofolate reductase with analogues of pyrimethamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Birdsall, B.; Tendler, S.J.B.; Feeney, J.

1990-10-01

{sup 1}H and {sup 19}F NMR signals from bound ligands have been assigned in one- and two-dimensional NMR spectra of complexes of Lactobacillus casei dihydrofolate reductase with various pyrimethamine analogues. The signals were identified mainly by correlating signals from bound and free ligands by using 2D exchange experiments. Analogues with symmetrically substituted phenyl rings give rise to {sup 1}H signals from four nonequivalent aromatic protons, clearly indicating the presence of hindered rotation about the pyrimidine-phenyl bond. Analogues with symmetrically substituted phenyl rings give rise to {sup 1}H signals from four nonequivalent aromatic protons, clearly indicating the presence of hindered rotationmore » about the pyrimidine-phenyl bond. Analogues containing asymmetrically substituted aromatic rings exist as mixtures of two rotational isomers (an enantiomeric pair) because of this hindered rotation and the NMR spectra revealed that both isomers (forms A and B) bind to the enzyme with comparable, though unequal, binding energies. In this case two complete sets of bound proton signals were observed. The relative orientations of the two forms have been determined from NOE through-space connections between protons on the ligand and protein. Ternary complexes with NADP{sup {plus}} were also examined.« less

Efficient synthesis of RITA and its analogues: derivation of analogues with improved antiproliferative activity via modulation of p53/miR-34a pathway.

PubMed

Lin, Jinshun; Jin, Xiuli; Bu, Yiwen; Cao, Deliang; Zhang, Nannan; Li, Shangfu; Sun, Qinsheng; Tan, Chunyan; Gao, Chunmei; Jiang, Yuyang

2012-12-28

A novel approach to synthesize RITA by practical palladium-catalyzed C-C bond-forming Suzuki reactions at room temperature was developed, which was used for deriving a series of substituted tricyclic α-heteroaryl (furan/thiophene) analogues of RITA under mild conditions. These novel analogues showed notable antiproliferative activity against cancer cell lines with wild-type p53 (i.e., HCT116, A549, MCF-7 and K562), but much less activity in HCT116/p53(-/-) cells. In particular, compound 1f demonstrated promising antiproliferative activity compared to RITA, with IC(50) = 28 nM in MCF-7 vs. 54 nM for RITA, and cancer cell selectivity. Compound 1f markedly activated p53 in HCT116 cells at 100 nM, triggering apoptosis. Importantly, we found that both RITA and compound 1f induced G(0)/G(1) cell cycle arrest by up-regulating miR-34a, which in turn down-regulated the expression of cell cycle-related proteins CDK4 and E2F1. In summary, this study reports an effective synthetic approach for RITA and its analogues, and elucidates a novel antiproliferative mechanism of these compounds.

Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells

PubMed Central

Dugnani, Silvana; Calastretti, Angela; Spadoni, Gilberto; Bedini, Annalida; Rivara, Silvia; Mor, Marco; Canti, Gianfranco; Scaglione, Francesco; Bevilacqua, Annamaria

2017-01-01

Melatonin plays different physiological functions ranging from the regulation of circadian rhythms to tumor inhibition, owing to its antioxidant, immunomodulatory and anti-aging properties. Due to its pleiotropic functions, melatonin has been shown to elicit cytoprotective processes in normal cells and trigger pro-apoptotic signals in cancer cells. The therapeutic potential of melatonin analogues prompted us to investigate the in vitro and in vivo antitumor activity of new melatonin derivatives and explore the underlying molecular mechanisms. The experiments revealed that the new melatonin analogues inhibited the growth of melanoma and breast cancer cells in a dose- and time-dependent manner. In addition, our results indicated that melatonin derivative UCM 1037 could induce apoptosis in melanoma and breast cancer cells, as well as cell necrosis, in MCF-7. Together, apoptosis and necrosis could be two possible mechanisms to explain the cytotoxic effect of the melatonin analogue against cancer cells. The suppression of tumor growth by the melatonin analogues was further demonstrated in vivo in a xenograft mice model. A decrease in the activation of MAPK pathway was observed in all cancer cells following UCM 1037 treatment. Overall, this study describes a promising antitumor compound showing antiproliferative and cytotoxic activity in melanoma and breast cancer cells. PMID:28978121

Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells.

PubMed

Gatti, Giuliana; Lucini, Valeria; Dugnani, Silvana; Calastretti, Angela; Spadoni, Gilberto; Bedini, Annalida; Rivara, Silvia; Mor, Marco; Canti, Gianfranco; Scaglione, Francesco; Bevilacqua, Annamaria

2017-09-15

Melatonin plays different physiological functions ranging from the regulation of circadian rhythms to tumor inhibition, owing to its antioxidant, immunomodulatory and anti-aging properties. Due to its pleiotropic functions, melatonin has been shown to elicit cytoprotective processes in normal cells and trigger pro-apoptotic signals in cancer cells. The therapeutic potential of melatonin analogues prompted us to investigate the in vitro and in vivo antitumor activity of new melatonin derivatives and explore the underlying molecular mechanisms. The experiments revealed that the new melatonin analogues inhibited the growth of melanoma and breast cancer cells in a dose- and time-dependent manner. In addition, our results indicated that melatonin derivative UCM 1037 could induce apoptosis in melanoma and breast cancer cells, as well as cell necrosis, in MCF-7. Together, apoptosis and necrosis could be two possible mechanisms to explain the cytotoxic effect of the melatonin analogue against cancer cells. The suppression of tumor growth by the melatonin analogues was further demonstrated in vivo in a xenograft mice model. A decrease in the activation of MAPK pathway was observed in all cancer cells following UCM 1037 treatment. Overall, this study describes a promising antitumor compound showing antiproliferative and cytotoxic activity in melanoma and breast cancer cells.

Natural analogues for processes affecting disposal of high-level radioactive waste in the vadose zone

NASA Astrophysics Data System (ADS)

Stuckless, J. S.

2003-04-01

Natural analogues can contribute to understanding and predicting the performance of subsystems and processes affecting a mined geologic repository for high-level radioactive waste in several ways. Most importantly, analogues provide tests for various aspects of systems of a repository at dimensional scales and time spans that cannot be attained by experimental study. In addition, they provide a means for the general public to judge the predicted performance of a potential high-level nuclear waste repository in familiar terms such that the average person can assess the anticipated long-term performance and other scientific conclusions. Hydrologists working on the Yucca Mountain Project (currently the U.S. Department of Energy's Office of Repository Development) have modeled the flow of water through the vadose zone at Yucca Mountain, Nevada and particularly the interaction of vadose-zone water with mined openings. Analogues from both natural and anthropogenic examples confirm the prediction that most of the water moving through the vadose zone will move through the host rock and around tunnels. This can be seen both quantitatively where direct comparison between seepage and net infiltration has been made and qualitatively by the excellent degree of preservation of archaeologic artifacts in underground openings. The latter include Paleolithic cave paintings in southwestern Europe, murals and artifacts in Egyptian tombs, painted subterranean Buddhist temples in India and China, and painted underground churches in Cappadocia, Turkey. Natural analogues also suggest that this diversion mechanism is more effective in porous media than in fractured media. Observations from natural analogues are also consistent with the modeled decrease in the percentage of infiltration that becomes seepage with a decrease in amount of infiltration. Finally, analogues, such as tombs that have ben partially filled by mud flows, suggest that the same capillary forces that keep water in the rock around underground openings will draw water towards buried waste packages if they are encased in backfill. Analogue work in support of the U.S. repository program continues in the U.S. Geological Survey, in cooperation with the U.S. Department of Energy.

Non-robust numerical simulations of analogue extension experiments

NASA Astrophysics Data System (ADS)

Naliboff, John; Buiter, Susanne

2016-04-01

Numerical and analogue models of lithospheric deformation provide significant insight into the tectonic processes that lead to specific structural and geophysical observations. As these two types of models contain distinct assumptions and tradeoffs, investigations drawing conclusions from both can reveal robust links between first-order processes and observations. Recent studies have focused on detailed comparisons between numerical and analogue experiments in both compressional and extensional tectonics, sometimes involving multiple lithospheric deformation codes and analogue setups. While such comparisons often show good agreement on first-order deformation styles, results frequently diverge on second-order structures, such as shear zone dip angles or spacing, and in certain cases even on first-order structures. Here, we present finite-element experiments that are designed to directly reproduce analogue "sandbox" extension experiments at the cm-scale. We use material properties and boundary conditions that are directly taken from analogue experiments and use a Drucker-Prager failure model to simulate shear zone formation in sand. We find that our numerical experiments are highly sensitive to numerous numerical parameters. For example, changes to the numerical resolution, velocity convergence parameters and elemental viscosity averaging commonly produce significant changes in first- and second-order structures accommodating deformation. The sensitivity of the numerical simulations to small parameter changes likely reflects a number of factors, including, but not limited to, high angles of internal friction assigned to sand, complex, unknown interactions between the brittle sand (used as an upper crust equivalent) and viscous silicone (lower crust), highly non-linear strain weakening processes and poor constraints on the cohesion of sand. Our numerical-analogue comparison is hampered by (a) an incomplete knowledge of the fine details of sand failure and sand properties, and (b) likely limitations to the use of a continuum Drucker-Prager model for representing shear zone formation in sand. In some cases our numerical experiments provide reasonable fits to first-order structures observed in the analogue experiments, but the numerical sensitivity to small parameter variations leads us to conclude that the numerical experiments are not robust.

Role of the Zn1 and Zn2 sites in metallo-beta-lactamase L1.

PubMed

Hu, Zhenxin; Periyannan, Gopalraj; Bennett, Brian; Crowder, Michael W

2008-10-29

In an effort to probe the role of the Zn(II) sites in metallo-beta-lactamase L1, mononuclear metal ion containing and heterobimetallic analogues of the enzyme were generated and characterized using kinetic and spectroscopic studies. Mononuclear Zn(II)-containing L1, which binds Zn(II) in the consensus Zn1 site, was shown to be slightly active; however, this enzyme did not stabilize a nitrocefin-derived reaction intermediate that had been previously detected. Mononuclear Co(II)- and Fe(III)-containing L1 were essentially inactive, and NMR and EPR studies suggest that these metal ions bind to the consensus Zn2 site in L1. Heterobimetallic analogues (ZnCo and ZnFe) analogues of L1 were generated, and stopped-flow kinetic studies revealed that these enzymes rapidly hydrolyze nitrocefin and that there are large amounts of the reaction intermediate formed during the reaction. The heterobimetallic analogues were reacted with nitrocefin, and the reactions were rapidly freeze quenched. EPR studies on these samples demonstrate that Co(II) is 5-coordinate in the resting state, proceeds through a 4-coordinate species during the reaction, and is 5-coordinate in the enzyme-product complex. These studies demonstrate that the metal ion in the Zn1 site is essential for catalysis in L1 and that the metal ion in the Zn2 site is crucial for stabilization of the nitrocefin-derived reaction intermediate.

Developing Equipotent Teixobactin Analogues against Drug-Resistant Bacteria and Discovering a Hydrophobic Interaction between Lipid II and Teixobactin.

PubMed

Zong, Yu; Sun, Xiuyun; Gao, Hongying; Meyer, Kirsten J; Lewis, Kim; Rao, Yu

2018-04-26

Teixobactin, targeting lipid II, represents a new class of antibiotics with novel structures and has excellent activity against Gram-positive pathogens. We developed a new convergent method to synthesize a series of teixobactin analogues and explored structure-activity relationships. We obtained equipotent and simplified teixobactin analogues, replacing the l- allo-enduracididine with lysine, substituting oxygen to nitrogen on threonine, and adding a phenyl group on the d-phenylalanine. On the basis of the antibacterial activities that resulted from corresponding modifications of the d-phenylalanine, we propose a hydrophobic interaction between lipid II and the N-terminal of teixobactin analogues, which we map out with our analogue 35. Finally, a representative analogue from our series showed high efficiency in a mouse model of Streptococcus pneumoniae septicemia.

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

PubMed

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

2016-08-01

Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Experimental evaluation of shark detection rates by aerial observers.

PubMed

Robbins, William D; Peddemors, Victor M; Kennelly, Steven J; Ives, Matthew C

2014-01-01

Aerial surveys are a recognised technique to identify the presence and abundance of marine animals. However, the capability of aerial observers to reliably sight coastal sharks has not been previously assessed, nor have differences in sighting rates between aircraft types been examined. In this study we investigated the ability of observers in fixed-wing and helicopter aircraft to sight 2.5 m artificial shark analogues placed at known depths and positions. Initial tests revealed that the shark analogues could only be detected at shallow depths, averaging only 2.5 m and 2.7 m below the water surface for observers in fixed-wing and helicopter aircraft, respectively. We then deployed analogues at shallower depths along a 5 km-long grid, and assessed their sightability to aircraft observers through a series of transects flown within 500 m. Analogues were seen infrequently from all distances, with overall sighting rates of only 12.5% and 17.1% for fixed-wing and helicopter observers, respectively. Although helicopter observers had consistently higher success rates of sighting analogues within 250 m of their flight path, neither aircraft observers sighted more than 9% of analogues deployed over 300 m from their flight paths. Modelling of sighting rates against environmental and experimental variables indicated that observations were affected by distance, aircraft type, sun glare and sea conditions, while the range of water turbidities observed had no effect. We conclude that aerial observers have limited ability to detect the presence of submerged animals such as sharks, particularly when the sharks are deeper than ∼ 2.6 m, or over 300 m distant from the aircraft's flight path, especially during sunny or windy days. The low rates of detections found in this study cast serious doubts on the use of aerial beach patrols as an effective early-warning system to prevent shark attacks.

Experimental Evaluation of Shark Detection Rates by Aerial Observers

PubMed Central

Robbins, William D.; Peddemors, Victor M.; Kennelly, Steven J.; Ives, Matthew C.

2014-01-01

Aerial surveys are a recognised technique to identify the presence and abundance of marine animals. However, the capability of aerial observers to reliably sight coastal sharks has not been previously assessed, nor have differences in sighting rates between aircraft types been examined. In this study we investigated the ability of observers in fixed-wing and helicopter aircraft to sight 2.5 m artificial shark analogues placed at known depths and positions. Initial tests revealed that the shark analogues could only be detected at shallow depths, averaging only 2.5 m and 2.7 m below the water surface for observers in fixed-wing and helicopter aircraft, respectively. We then deployed analogues at shallower depths along a 5 km-long grid, and assessed their sightability to aircraft observers through a series of transects flown within 500 m. Analogues were seen infrequently from all distances, with overall sighting rates of only 12.5% and 17.1% for fixed-wing and helicopter observers, respectively. Although helicopter observers had consistently higher success rates of sighting analogues within 250 m of their flight path, neither aircraft observers sighted more than 9% of analogues deployed over 300 m from their flight paths. Modelling of sighting rates against environmental and experimental variables indicated that observations were affected by distance, aircraft type, sun glare and sea conditions, while the range of water turbidities observed had no effect. We conclude that aerial observers have limited ability to detect the presence of submerged animals such as sharks, particularly when the sharks are deeper than ∼2.6 m, or over 300 m distant from the aircraft's flight path, especially during sunny or windy days. The low rates of detections found in this study cast serious doubts on the use of aerial beach patrols as an effective early-warning system to prevent shark attacks. PMID:24498258

Mediation by SRIF1 receptors of the contractile action of somatostatin in rat isolated distal colon; studies using some novel SRIF analogues.

PubMed Central

McKeen, E S; Feniuk, W; Humphrey, P P

1994-01-01

1. The motor effects of somatostatin-14 (SRIF), and several SRIF peptide analogues were investigated on the rat isolated distal colon. The objective of these studies was to characterize the receptor mediating the contractile action of SRIF by comparing the relative agonist potencies of a range of SRIF analogues. 2. SRIF (1 nM-1 microM) produced concentration-dependent contractions with an EC50 value of approximately 10 nM. Contractile responses induced by SRIF were insensitive to atropine (1 microM) or naloxone (1 microM) but abolished by tetrodotoxin (1 microM). Somatostatin-28 (SRIF28), also induced concentration-dependent contractions and was equipotent with SRIF. Phosphoramidon (1 microM) and amastatin (10 microM) did not increase the potency of either SRIF or SRIF28. 3. The SRIF peptide analogues, octreotide, SRIF25, seglitide, angiopeptin and CGP23996 (1 nM-1 microM) produced contractile responses in the rat distal colon, each having similar potency and maximal activity relative to SRIF. The SSTR2 receptor-selective hexapeptide, BIM23027 (0.1 nM-1 microM), and the SRIF stereoisomer, D-Trp8-SRIF (0.1 nM-1 microM), were the most potent agonists examined being approximately 12 and 7 times more potent than SRIF, respectively. In contrast, the SSTR5 receptor-selective analogue, L362,855, was approximately 120 times weaker than SRIF, whilst the SSTR3 receptor-selective analogue, BIM23056, was inactive at concentrations up to 3 microM. 4. The putative SRIF receptor antagonist, (cyclo(7-aminoheptanoyl Phe-D-Trp-Lys-Thr[Bzl]))(CPP) (1 microM), had no agonist activity and had no effect on contractions induced by SRIF. 5. The contractile actions of BIM23027 and seglitide were subject to pronounced desensitization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7834217

Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

PubMed

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

2017-01-01

3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.

Multiple sensory modalities used by squid in successful predator evasion throughout ontogeny.

PubMed

York, Carly A; Bartol, Ian K; Krueger, Paul S

2016-09-15

Squid rely on multiple sensory systems for predator detection. In this study we examine the role of two sensory systems, the lateral line analogue and vision, in successful predator evasion throughout ontogeny. Squid Doryteuthis pealeii and Lolliguncula brevis were recorded using high-speed videography in the presence of natural predators under light and dark conditions with their lateral line analogue intact or ablated via a pharmacological technique. Paralarval squid showed reduced escape responses when ablated; however, no differences were found between light and dark conditions in non-ablated paralarvae, as was previously shown in juveniles and adults, indicating that the lateral line analogue is integral for predator detection early in life. However, vision does play a role in survival because ablated squid in dark conditions had lower levels of survival than all other treatments. Throughout ontogeny, squid oriented themselves anteriorly towards the oncoming predator, maximizing sensory input to the lateral line analogue system and providing better positioning for tail-first escape jetting, the preferred escape mode. Ablated juveniles and adults had lower response times, escape velocities and peak acceleration than non-ablated individuals, indicating that the lateral line analogue enables squid to respond quicker and with more powerful jets to a predator and maximize escape success. Our findings reveal that the lateral line analogue plays a role in predator detection and successful escape response at the earliest life stages, and continues to contribute to successful evasion by aiding visual cues in juvenile and adult squid. © 2016. Published by The Company of Biologists Ltd.

Customizing the management of chronic hepatitis B virus infection.

PubMed

Gish, Robert G; Perrillo, Robert P; Jacobson, Ira M

2007-08-01

As of October 2006, 6 medications are approved in the United States for the management of chronic hepatitis B virus (HBV) infection: 2 formulations of interferon and 4 oral nucleos(t)ide analogues. For the treating practitioner, tailoring the pharmaceutical regimen according to patient features and clinical circumstances can be a challenge. First-line therapeutic regimens for the management of HBV infection include monotherapy with a U.S. Food and Drug Administration-approved agent that has potent on-treatment viral response and low rates of resistance; in the future, these regimens may include a combination of more than one nucleos(t)ide analogue or a combination of a nucleos(t)ide analogue and pegylated interferon. The oral nucleos(t)ide analogues are generally better tolerated than interferon; however, they can be expensive when administered for lengthy periods and can also lead to medication resistance. Lamivudine, the first approved nucleoside analogue for the treatment of HBV infection, has a very high resistance profile; in fact, lamivudine exposure increases viral resistance to other commercially available nucleos(t)ide analogues: entecavir, telbivudine, and adefovir. For these reasons, the 2007 American Association for the Study of Liver Diseases (AASLD) guidelines no longer recommend lamivudine as first-line therapy for the management of HBV infection. A satellite symposium conducted during the 57th Annual Meeting of the AASLD in Boston, Massachusetts, presented approaches to customizing the management of chronic HBV infection. The presentation highlighted recent findings suggesting that early, profound, and sustained viral suppression improves the probability of sustained virologic response and reduces the likelihood of nucleos(t)ide resistance.

The impact of pre-existing anxiety on affective and cognitive processing of a Virtual Reality analogue trauma.

PubMed

Schweizer, Tina; Schmitz, Julian; Plempe, Laura; Sun, Dali; Becker-Asano, Christian; Leonhart, Rainer; Tuschen-Caffier, Brunna

2017-01-01

Dysfunctional processing of traumatic events may be in particular related to high trait anxiety as a pre-traumatic risk factor for the development of post-traumatic stress disorder (PTSD). However, as this has rarely been investigated in prospective, experimental studies, we aimed to analyse the association between high trait anxiety and affective as well as cognitive processing of stress using a new prospective Virtual Reality analogue trauma paradigm to overcome limitations of retrospective or current analogue designs. Individuals with high and low trait anxiety (N = 80) were exposed to a multi-sensory Virtual Reality emergency scenario while psychophysiological stress response, emotion regulation and intrusive memories were assessed. Our results showed that high trait anxiety individuals display increased (i) subjective stress responses, (ii) emotion dysregulation and (iii) intrusive memories upon VR analogue trauma exposure. In particular, our sample of high trait anxiety individuals displayed limited access to different emotion regulation strategies as well as increased worry and rumination regarding perceived intrusive memories. Considering the complex interplay of multiple risk factors, our findings suggests that peri-traumatic affective processing seems to mediate high trait anxiety and post-traumatic intrusive memories thereby pointing out the central role of peri-traumatic processes for intrusion development. In addition, HA as a modulating pre-traumatic risk factor might further increase the risk of later dysfunctional processing of an analogue trauma by interacting with factors of affective processing during analogue trauma exposure. Implications of these findings which may contribute to a higher risk to develop PTSD are discussed.

The impact of pre-existing anxiety on affective and cognitive processing of a Virtual Reality analogue trauma

PubMed Central

Schmitz, Julian; Plempe, Laura; Sun, Dali; Becker-Asano, Christian; Leonhart, Rainer; Tuschen-Caffier, Brunna

2017-01-01

Dysfunctional processing of traumatic events may be in particular related to high trait anxiety as a pre-traumatic risk factor for the development of post-traumatic stress disorder (PTSD). However, as this has rarely been investigated in prospective, experimental studies, we aimed to analyse the association between high trait anxiety and affective as well as cognitive processing of stress using a new prospective Virtual Reality analogue trauma paradigm to overcome limitations of retrospective or current analogue designs. Individuals with high and low trait anxiety (N = 80) were exposed to a multi-sensory Virtual Reality emergency scenario while psychophysiological stress response, emotion regulation and intrusive memories were assessed. Our results showed that high trait anxiety individuals display increased (i) subjective stress responses, (ii) emotion dysregulation and (iii) intrusive memories upon VR analogue trauma exposure. In particular, our sample of high trait anxiety individuals displayed limited access to different emotion regulation strategies as well as increased worry and rumination regarding perceived intrusive memories. Considering the complex interplay of multiple risk factors, our findings suggests that peri-traumatic affective processing seems to mediate high trait anxiety and post-traumatic intrusive memories thereby pointing out the central role of peri-traumatic processes for intrusion development. In addition, HA as a modulating pre-traumatic risk factor might further increase the risk of later dysfunctional processing of an analogue trauma by interacting with factors of affective processing during analogue trauma exposure. Implications of these findings which may contribute to a higher risk to develop PTSD are discussed. PMID:29287111

Innovations in Measuring Peer Conflict Resolution Knowledge in Children with LI: Exploring the Accessibility of a Visual Analogue Rating Scale

ERIC Educational Resources Information Center

Campbell, Wenonah N.; Skarakis-Doyle, Elizabeth

2011-01-01

This preliminary study explored peer conflict resolution knowledge in children with and without language impairment (LI). Specifically, it evaluated the utility of a visual analogue scale (VAS) for measuring nuances in such knowledge. Children aged 9-12 years, 26 with typically developing language (TLD) and 6 with LI, completed a training protocol…

The Development of the Text Reception Threshold Test: A Visual Analogue of the Speech Reception Threshold Test

ERIC Educational Resources Information Center

Zekveld, Adriana A.; George, Erwin L. J.; Kramer, Sophia E.; Goverts, S. Theo; Houtgast, Tammo

2007-01-01

Purpose: In this study, the authors aimed to develop a visual analogue of the widely used Speech Reception Threshold (SRT; R. Plomp & A. M. Mimpen, 1979b) test. The Text Reception Threshold (TRT) test, in which visually presented sentences are masked by a bar pattern, enables the quantification of modality-aspecific variance in speech-in-noise…

Influence of the juvenile hormone analogue, methoprene, on development of the southern pine beetle, Dendroctonus frontalis Zimm. (Col. Scolytidae)

Treesearch

J.W. Van Sambeek; J.R. Bridges

1980-01-01

To determine the effects of juvenoids on the development and sensitivity of the southern pine beetle (SPB) Dendroctonus frontalis Zimm, we treated last-instar larvae, pupae, and callow adults with methoprene, a potent juvenile hormone analogue. From this study we identified a number of juvenoid effects on SPB. Methoprene has the greatest effect on...

Collaborative Student Laboratory Exercise Using FT-IR Spectroscopy for the Kinetics Study of a Biotin Analogue

ERIC Educational Resources Information Center

Leong, Jhaque; Ackroyd, Nathan C.; Ho, Karen

2014-01-01

The synthesis of N-methoxycarbonyl-2-imidazolidone, an analogue of biotin, was conducted by organic chemistry students and confirmed using FT-IR and H NMR. Spectroscopy students used FT-IR to measure the rate of hydrolysis of the product and determined the rate constant for the reaction using the integrated rate law. From the magnitude of the rate…

Conformationally restrained aromatic analogues of fosmidomycin and FR900098.

PubMed

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

2007-07-01

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

U.S. Nuclear Regulatory Commission natural analogue research program

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1995-09-01

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

Steric parameters, molecular modeling and hydropathic interaction analysis of the pharmacology of para-substituted methcathinone analogues

PubMed Central

Sakloth, F; Kolanos, R; Mosier, P D; Bonano, J S; Banks, M L; Partilla, J S; Baumann, M H; Negus, S S; Glennon, R A

2015-01-01

Background and Purpose There is growing concern over the abuse of certain psychostimulant methcathinone (MCAT) analogues. This study extends an initial quantitative structure–activity relationship (QSAR) investigation that demonstrated important steric considerations of seven 4- (or para-)substituted analogues of MCAT. Specifically, the steric character (Taft's steric ES) of the 4-position substituent affected in vitro potency to induce monoamine release via dopamine and 5-HT transporters (DAT and SERT) and in vivo modulation of intracranial self-stimulation (ICSS). Here, we have assessed the effects of other steric properties of the 4-position substituents. Experimental Approach Definitive steric parameters that more explicitly focus on the volume, width and length of the MCAT 4-position substituents were assessed. In addition, homology models of human DAT and human SERT based upon the crystallized Drosophila DAT were constructed and docking studies were performed, followed by hydropathic interaction (HINT) analysis of the docking results. Key Results The potency of seven MCAT analogues at DAT was negatively correlated with the volume and maximal width of their 4-position substituents, whereas potency at SERT increased as substituent volume and length increased. SERT/DAT selectivity, as well as abuse-related drug effects in the ICSS procedure, also correlated with the same parameters. Docking solutions offered a means of visualizing these findings. Conclusions and Implications These results suggest that steric aspects of the 4-position substituents of MCAT analogues are key determinants of their action and selectivity, and that the hydrophobic nature of these substituents is involved in their potency at SERT. PMID:25522019

Synthesis of isocryptolepine analogues and their structure-activity relationship studies as antiplasmodial and antiproliferative agents.

PubMed

Aroonkit, Pasuk; Thongsornkleeb, Charnsak; Tummatorn, Jumreang; Krajangsri, Suppachai; Mungthin, Mathirut; Ruchirawat, Somsak

2015-04-13

Novel isocryptolepine analogues have been conveniently synthesized and evaluated for antimalarial and antiproliferative activities. We have found 3-fluoro-8-bromo-isocryptolepine (1n) to have the highest activities against chloroquine-resistant K1, chloroquine-sensitive 3D7, and chloroquine- and mefloquine-resistant SKF58 and SRIV35 strains. Several fluorine-substituted analogues (1b, 1n, and 1q) also showed excellent selectivities while maintaining good to excellent activities against all four Plasmodium falciparum strains. Additionally, antiproliferative properties of isocryptolepine derivatives against HepG2, HuCCA-1, MOLT-3 and A549 cancer cell lines are reported for the first time in this study. 2-Chloroisocryptolepine (1c) and benzo-fused-2-chloroisocryptolepine (1i) showed significant bioactivities whereas several novel fluorinated compounds and 2-chloro-8-bromoisocryptolepine (1f) displayed excellent selectivities. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Discovery and Pre-Clinical Characterization of Third-Generation 4-H Heteroaryldihydropyrimidine (HAP) Analogues as Hepatitis B Virus (HBV) Capsid Inhibitors.

PubMed

Qiu, Zongxing; Lin, Xianfeng; Zhang, Weixing; Zhou, Mingwei; Guo, Lei; Kocer, Buelent; Wu, Guolong; Zhang, Zhisen; Liu, Haixia; Shi, Houguang; Kou, Buyu; Hu, Taishan; Hu, Yimin; Huang, Mengwei; Yan, S Frank; Xu, Zhiheng; Zhou, Zheng; Qin, Ning; Wang, Yue Fen; Ren, Shuang; Qiu, Hongxia; Zhang, Yuxia; Zhang, Yi; Wu, Xiaoyue; Sun, Kai; Zhong, Sheng; Xie, Jianxun; Ottaviani, Giorgio; Zhou, Yuan; Zhu, Lina; Tian, Xiaojun; Shi, Liping; Shen, Fang; Mao, Yi; Zhou, Xue; Gao, Lu; Young, John A T; Wu, Jim Zhen; Yang, Guang; Mayweg, Alexander V; Shen, Hong C; Tang, Guozhi; Zhu, Wei

2017-04-27

Described herein are the discovery and structure-activity relationship (SAR) studies of the third-generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the first- and second-generation 4-H HAPs. X-ray crystallographic study of analogue 12 (HAP_R01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen bonding interactions with capsid protein and coordinated waters. The representative analogue 10 (HAP_R10) was extensively characterized in vitro (ADMET) and in vivo (mouse PK and PD) and subsequently selected for further development as oral anti-HBV infection agent.

Analogues of the muscarinic agent 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane]: synthesis and pharmacology.

PubMed

Nordvall, G; Sundquist, S; Glas, G; Gogoll, A; Nilvebrant, L; Hacksell, U

1992-05-01

A number of tetrahydrofuran analogues of 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane] (1) have been prepared with the aim to obtain information about the relative importance of each of the oxygens in 1 for efficacy and for selectivity. In addition, the dimethyl and desmethyl analogues of 1 were prepared. The new compounds were compared to cis- and trans-1 with regard to their ability to displace (-)-[3H]-3-quinuclidinyl benzilate ((-)-[3H]QNB) from muscarinic receptors in cerebral cortex, heart, parotid gland, and urinary bladder from guinea pigs. Functional studies were made on isolated guinea pig bladder and ileum. The new compounds exhibited both lower affinity and efficacy than cis-1. A conformational study was performed, and the effects of steric and electronic factors on the biological activity of the compounds are discussed.

Substituent Effects on Desferrithiocin and Desferrithiocin Analogue Iron Clearing and Toxicity Profiles

PubMed Central

Bergeron, Raymond J.; Wiegand, Jan; Bharti, Neelam; McManis, James S.

2012-01-01

Desferrithiocin (DFT, 1) is a very efficient iron chelator when given orally. However, it is severely nephrotoxic. Structure-activity studies with 1 demonstrated that removal of the aromatic nitrogen to provide desazadesferrithiocin (DADFT, 2) and introduction of either a hydroxyl group or a polyether fragment onto the aromatic ring resulted in orally active iron chelators that were much less toxic than 1. The purpose of the current study was to determine if a comparable reduction in renal toxicity could be achieved by performing the same structural manipulations on 1 itself. Accordingly, three DFT analogues were synthesized. Iron clearing efficiency and ferrokinetics were evaluated in rats and primates; toxicity assessments were carried out in rodents. The resulting DFT ligands demonstrated a reduction in toxicity that was equivalent to that of the DADFT analogues and presented with excellent iron clearing properties. PMID:22889170

Lysosome and HER3 (ErbB3) selective anticancer agent kahalalide F: semisynthetic modifications and antifungal lead-exploration studies.

PubMed

Shilabin, Abbas Gholipour; Kasanah, Noer; Wedge, David E; Hamann, Mark T

2007-09-06

Kahalalide F (1) shows remarkable antitumor activity against different carcinomas and has recently completed phase I clinical trials and is being evaluated in phase II clinical studies. The antifungal activity of this molecule has not been thoroughly investigated. In this report, we focused on acetylation and oxidation of the secondary alcohol of threonine, as well as reductive alkylation of the primary amine of ornithine, and each product was evaluated for improvements in antifungal activity. 1 and analogues do not exhibit antimalarial, antileishmania, or antibacterial activity; however, the antifungal activity against different strains of fungi was particularly significant. This series of compounds was highly active against Fusarium spp., which represents an opportunistic infection in humans and plants. The in vitro cytotoxicity for the new analogues of 1 was evaluated in the NCI 60 cell panel. Analogue 5 exhibited enhanced potency in several human cancer cell lines relative to 1.

Rapid One-step Enzymatic Synthesis and All-aqueous Purification of Trehalose Analogues.

PubMed

Meints, Lisa M; Poston, Anne W; Piligian, Brent F; Olson, Claire D; Badger, Katherine S; Woodruff, Peter J; Swarts, Benjamin M

2017-02-17

Chemically modified versions of trehalose, or trehalose analogues, have applications in biology, biotechnology, and pharmaceutical science, among other fields. For instance, trehalose analogues bearing detectable tags have been used to detect Mycobacterium tuberculosis and may have applications as tuberculosis diagnostic imaging agents. Hydrolytically stable versions of trehalose are also being pursued due to their potential for use as non-caloric sweeteners and bioprotective agents. Despite the appeal of this class of compounds for various applications, their potential remains unfulfilled due to the lack of a robust route for their production. Here, we report a detailed protocol for the rapid and efficient one-step biocatalytic synthesis of trehalose analogues that bypasses the problems associated with chemical synthesis. By utilizing the thermostable trehalose synthase (TreT) enzyme from Thermoproteus tenax, trehalose analogues can be generated in a single step from glucose analogues and uridine diphosphate glucose in high yield (up to quantitative conversion) in 15-60 min. A simple and rapid non-chromatographic purification protocol, which consists of spin dialysis and ion exchange, can deliver many trehalose analogues of known concentration in aqueous solution in as little as 45 min. In cases where unreacted glucose analogue still remains, chromatographic purification of the trehalose analogue product can be performed. Overall, this method provides a "green" biocatalytic platform for the expedited synthesis and purification of trehalose analogues that is efficient and accessible to non-chemists. To exemplify the applicability of this method, we describe a protocol for the synthesis, all-aqueous purification, and administration of a trehalose-based click chemistry probe to mycobacteria, all of which took less than 1 hour and enabled fluorescence detection of mycobacteria. In the future, we envision that, among other applications, this protocol may be applied to the rapid synthesis of trehalose-based probes for tuberculosis diagnostics. For instance, short-lived radionuclide-modified trehalose analogues (e.g., 18 F-modified trehalose) could be used for advanced clinical imaging modalities such as positron emission tomography-computed tomography (PET-CT).

Effect of insulin analogues on frequency of non-severe hypoglycaemia in patients with type 1 diabetes prone to severe hypoglycaemia: The HypoAna trial.

PubMed

Agesen, R M; Kristensen, P L; Beck-Nielsen, H; Nørgaard, K; Perrild, H; Christiansen, J S; Jensen, T; Hougaard, P; Parving, H H; Thorsteinsson, B; Tarnow, L; Pedersen-Bjergaard, U

2016-09-01

Insulin analogues reduce the risk of hypoglycaemia compared with human insulin in patients with type 1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night. This 2-year investigator-initiated multicentre, prospective, randomized, open, blinded endpoint (PROBE) trial involved patients with T1D and at least two episodes of severe hypoglycaemia during the previous year. Using a balanced crossover design, patients were randomized to basal-bolus therapy based on analogue (detemir/aspart) or human (NPH/regular) insulins. A total of 114 participants were included. Endpoints were the number of severe hypoglycaemic events and non-severe events, including documented symptomatic and asymptomatic episodes occurring during the day and at night (ClinicalTrials.gov number: NCT00346996). Analogue-based treatment resulted in a 6% (2-10%; P=0.0025) overall relative risk reduction of non-severe hypoglycaemia. This was due to a 39% (32-46%; P<0.0001) reduction of non-severe nocturnal hypoglycaemia, seen for both symptomatic (48% [36-57%]; P<0.0001) and asymptomatic (28% [14-39%]; P=0.0004) nocturnal hypoglycaemia episodes. No clinically significant differences in hypoglycaemia occurrence were observed between the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months. In T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non-severe nocturnal hypoglycaemia compared with human insulin. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Climate change in safety assessment of a surface disposal facility

NASA Astrophysics Data System (ADS)

Leterme, B.

2012-04-01

The Belgian Agency for Radioactive Waste and Enriched Fissile Materials (ONDRAF/NIRAS) aims to develop a surface disposal facility for LILW-SL in Dessel (North-East of Belgium). Given the time scale of interest for the safety assessment (several millennia), a number of parameters in the modelling chain near field - geosphere - biosphere may be influenced by climate change. The present study discusses how potential climate change impact was accounted for the following quantities: (i) near field infiltration through the repository earth cover, (ii) partial pressure of CO2 in the water infiltrating the cover and draining the concrete, and (iii) groundwater recharge in the vicinity of the site. For these three parameters, the impact of climate change is assessed using climatic analogue stations, i.e. stations presently under climatic conditions corresponding to a given climate state. Results indicate that : (i) Using Gijon (Spain) as representative analogue station for the next millennia, infiltration at the bottom of the soil layer towards the modules of the facility is expected to increase (from 346 to 413 mm/y) under a subtropical climate. Although no colder climate is foreseen in the next 10 000 years, the approach was also tested with analogue stations for a colder climate state. Using Sisimiut (Greenland) as representative analogue station, infiltration is expected to decrease (109 mm/y). (ii) Due to changes of the partial pressure of CO2 in the soil water, cement degradation is estimated to occur more rapidly under a warmer climate. (iii) A decrease of long-term annual average groundwater recharge by 12% was simulated using Gijon representative analogue (from 314 to 276 mm), although total rainfall was higher (947 mm) in the warmer climate compared to the current temperate climate (899 mm). For a colder climate state, groundwater recharge simulated for the representative analogue Sisimiut showed a decrease by 69% compared to current climate conditions. The advantages and weaknesses of using analogue stations are also discussed.

Some fluorescence properties of dimethylaminochalcone and its novel cyclic analogues

NASA Astrophysics Data System (ADS)

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.

Characterization of electronic structure and physicochemical properties of antiparasitic nifurtimox analogues: A theoretical study

NASA Astrophysics Data System (ADS)

Soriano-Correa, Catalina; Raya, A.; Esquivel, Rodolfo O.

American trypanosomiasis, also known as Chagas' disease, is caused by Trypanosoma cruzi (T. cruzi). It is well known that trypanosomes, and particularly T. cruzi, are highly sensitive towards oxidative stress, i.e., to compounds than are able to produce free radicals. Generally, nifurtimox (NFX) and benznidazol are most effective in the acute phase of the disease; therefore, nitroheterocycles constitute good models to design other nitrocompounds with specific biological characteristics. Thus, we have performed an ab initio study at the Hartree-Fock and Density Functional Theory levels of theory of several NFX analogues recently synthesized, to characterize them by obtaining their electronic, structural, and physicochemical properties, which might be linked to the observed antichagasic activity. The antitrypanosomal activity scale previously reported for the NFX analogues studied in this work is in good agreement with our theoretical results, from which we can conclude that the activity seems to be related to the reactivity along with the acidity observed for the most active molecules.

Effect of a long-acting analogue of somatostatin, SMS 201-995, on the development of intestinal tumours in azoxymethane-treated rats.

PubMed

Savage, A P; Matthews, J L; Adrian, T E; Ghatei, M A; Cooke, T; Bloom, S R

1987-04-01

The effect of daily parenteral administration of a long-acting analogue of somatostatin (SMS 201-995) on the development of intestinal tumours and the rate of crypt cell proliferation in azoxymethane-treated rats has been studied. SMS 201-995 had no significant effect on the number of colonic tumours induced. In the duodenum, SMS 201-995 administration was associated with a change in the number of tumours from 1.4/rat in saline-treated animals to 2.4/rat in animals treated for the last third of the study and 2.8/rat in animals treated with SMS for the entire duration of the study (P less than 0.02). SMS had no significant effect on the rate of cell proliferation in the duodenum, ileum or colon. The inhibition of release of gastrointestinal trophic hormones by this analogue of somatostatin thus does not appear to reduce the number of tumours in the intestine of azoxymethane-treated rats.

Structural and Biochemical Studies of Actin in Complex with Synthetic Macrolide Tail Analogues

DOE PAGES

Pereira, Jose H.; Petchprayoon, Chutima; Hoepker, Alexander C.; ...

2014-07-22

The actin filament-binding and filament-severing activities of the aplyronine, kabiramide, and reidispongiolide families of marine macrolides are located within the hydrophobic tail region of the molecule. Two synthetic tail analogues of aplyronine C (SF-01 and GC-04) are shown to bind to G-actin with dissociation constants of (285±33) and (132±13) nM, respectively. The crystal structures of actin complexes with GC-04, SF-01, and kabiramide C reveal a conserved mode of tail binding within the cleft that forms between subdomains (SD) 1 and 3. Our studies support the view that filament severing is brought about by specific binding of the tail region tomore » the SD1/SD3 cleft on the upper protomer, which displaces loop-D from the lower protomer on the same half-filament. With previous studies showing that the GC-04 analogue can sever actin filaments, it is argued that the shorter complex lifetime of tail analogues with F-actin would make them more effective at severing filaments compared with plasma gelsolin. In conclusion, structure-based analyses are used to suggest more reactive or targetable forms of GC-04 and SF-01, which may serve to boost the capacity of the serum actin scavenging system, to generate antibody conjugates against tumor cell antigens, and to decrease sputum viscosity in children with cystic fibrosis.« less

Effect of a synthetic indolicidin analogue on lipid peroxidation in thermal burns.

PubMed

Lazarenko, V A; Lyashev, Yu D; Shevchenko, N I

2014-08-01

Experimental simulation of burn was followed by accumulation of LPO products and suppression of antioxidant enzyme activity in the burn wound. Application of a synthetic analogue of indolicidin led to an increase in MDA and acylhydroperoxide concentrations in the burn wound on experimental day 1. Further application of the peptide in a dose of 100 mg/kg had no significant effect on the studied parameters, while the peptide in a dose of 500 mg/kg was followed by a decrease in the level of LPO products on days 10 and 14. Changes in antioxidant enzyme activities in rats treated with 500 mg/kg indolicidin analogue had a two-phase pattern: an increase on day 4 was followed by a decrease.

Antibacterial Optimization of 4-Aminothiazolyl Analogues of the Natural Product GE2270 A: Identification of the Cycloalkylcarboxylic Acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

LaMarche, Matthew J.; Leeds, Jennifer A.; Amaral, Kerri

4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for their activity against Gram positive bacterial infections. Optimization efforts focused on improving the physicochemical properties (e.g., aqueous solubility and chemical stability) of the 4-aminothiazolyl natural product template while improving the in vitro and in vivo antibacterial activity. Structure-activity relationships were defined, and the solubility and efficacy profiles were improved over those of previous analogues and 1. These studies identified novel, potent, soluble, and efficacious elongation factor-Tu inhibitors, which bear cycloalkylcarboxylic acid side chains, and culminated in the selection of development candidates amide 48 andmore » urethane 58.« less

Microbial production of four biodegradable siderophores under submerged fermentation.

PubMed

Fazary, Ahmed E; Al-Shihri, Ayed S; Alfaifi, Mohammad Y; Saleh, Kamel A; Alshehri, Mohammed A; Elbehairi, Serag Eldin I; Ju, Yi-Hsu

2016-07-01

Four siderophore analogues were isolated and purified from Escherichia coli, Bacillus spp. ST13, and Streptomyces pilosus microorganisms under some specific submerged fermentation conditions. In order to evaluate the highest production of this siderophore analogues through the growth, a rapid spectrophotometric screening semi-quantitative method was used, in which interestingly the analogues were isolated in its own form not its iron chelate. After chromatographic separation, the chemical structures of the isolated and purified siderophores were illustrated using detailed spectroscopic techniques. The biodegradation studies were done on that four novel isolated and purified siderophores following OECD protocols. In addition, the bioactivities of these siderophores and their iron complexes were examined and evaluated. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel nicotine analogues with potential anti-mycobacterial activity.

PubMed

Gandhi, Paresh T; Athmaram, Thimmasandra Narayanappa; Arunkumar, Gundaiah Ramesh

2016-04-15

Tuberculosis (TB) is the second leading lethal infectious disease in the world after acquired immuno deficiency (AIDs). We have developed a series of twenty-five novel nicotine analogues with de-addiction property and tested them for their activity against Mycobacterium tuberculosis (MTB). In an effort to increase the specificity of action and directing nicotine analogues to target MTB, four promising compounds were further optimized via molecular docking studies against the Dihydrofolate reductase of MTB. After lead optimization, one nicotine analogue [3-(5-(3fluorophenyl)nicotinoyl)-1-methylpyrrolidin-2-one] exhibited minimum inhibitory concentration of 1 μg/mL (2.86 nM) against M. tuberculosis (H37Rv strain), a human pathogenic strain of clinically significant importance. Pharmacokinetic analysis of [3-(5-(3fluorophenyl)nicotinoyl)-1methylpyrrolidin-2-one] with lowest MIC value via oral route in Wistar rats revealed that at a dosage of 5 mg/kg body weight gave a maximum serum drug concentration (Cmax) of 2.86 μg/mL, Tmax of one hour and a half-life (T1/2) of more than 24 h and Volume of distribution (Vd) of 27.36 L. Whereas the parenteral (intra venous) route showed a Cmax of 3.37 μg/mL, Tmax of 0.05 h, T1/2 of 24 h and Vd equivalent to 23.18 L. The acute oral toxicity and repeated oral toxicity studies in female Wistar rats had an LD50>2000 mg/kg body weight. Our data suggests that nicotine derivatives developed in the present study has good metabolic stability with tunable pharmacokinetics (PK) with therapeutic potential to combat MTB. However, further in vivo studies for anti-tuberculosis activity and elucidation of mode of action could result in more promising novel drug for treating MTB. To the best of our knowledge this is the first report revealing the anti-mycobacterial potential of nicotine analogue at potential therapeutic concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fields of application of continuous subcutaneous insulin infusion in the treatment of diabetes and implications in the use of rapid-acting insulin analogues.

PubMed

Pitocco, D; Rizzi, A; Scavone, G; Tanese, L; Zaccardi, F; Manto, A; Ghirlanda, G

2013-09-01

In western countries, diabetes mellitus, because of macrovascular and microvascular complications related to it, is still an important cause of death. Patients with type 1 diabetes mellitus (T1DM) have a six-time higher risk of mortality than healthy patients. Since the Diabetes Control and Complications Trial (DCCT) established how an intensive therapy is necessary to prevent diabetes mellitus complications, many studies have been conducted to understand which method is able to reach an optimal metabolic control. In the past 30 years continuous subcutaneous insulin infusion established/introduced as a validate alternative to multiple daily injections. Several trials demonstrated that, when compared to MDI, CSII brings to a better metabolic control, in terms of a reduction of glycated hemoglobin and blood glucose variability, hypoglycemic episodes and improvement in quality of life. Because of their pharmacokinetic and pharmacodynamic characteristics, rapid-action insulin analogues are imposed as best insulin to be used in CSII. The rapid onset and the fast reached peak make them better mimic the way how pancreas secretes insulin. CSII by pump is not free from issues. Catheter occlusions, blockages, clogs can arrest insulin administration. The consequent higher levels of glycemic values, can easily bring to the onset of ketoacidosis, with an high risk for patients' life. Aspart is a rapid analogue obtained by aminoacidic substitution. It is as effective as lispro and glulisine in gaining a good metabolic control and even better in reducing glucose variability. Some studies tried to compare rapid analogues in terms of stability. Obtained data are controversial. An in vivo study evidenced higher stability or glulisine, while studies in vitro highlighted a higher safety of aspart. Nowadays it is not possible to assess which analogues is safer. When the infusion set is changed every 48 hours equivalent rates of occlusions have been observed.

Isolation and structural identification of a novel minoxidil analogue in an illegal dietary supplement: triaminodil.

PubMed

Lee, Ji Hyun; Park, Han Na; Park, Hyoung Joon; Kim, Nam Sook; Park, Sung-Kwan; Lee, Jongkook; Baek, Sun Young

2018-01-01

A new minoxidil analogue was detected in an illegal dietary supplement advertised as a hair-growth treatment. The analogue was identified using ultra-performance liquid chromatography (UPLC), high-resolution mass spectrometry (LC-HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. The compound was structurally elucidated as a minoxidil analogue in which the piperidinyl group of minoxidil was replaced with a pyrrolidinyl group corresponding to a molecular formula of C 8 H 13 N 5 O. The new analogue has been named triaminodil. As this is the first report of the compound, there are no chemical, toxicology or pharmacological data available.

5'-Phosphorothiolate Dinucleotide Cap Analogues: Reagents for Messenger RNA Modification and Potent Small-Molecular Inhibitors of Decapping Enzymes.

PubMed

Wojtczak, Blazej A; Sikorski, Pawel J; Fac-Dabrowska, Kaja; Nowicka, Anna; Warminski, Marcin; Kubacka, Dorota; Nowak, Elzbieta; Nowotny, Marcin; Kowalska, Joanna; Jemielity, Jacek

2018-05-09

The 5' cap consists of 7-methylguanosine (m 7 G) linked by a 5'-5'-triphosphate bridge to messenger RNA (mRNA) and acts as the master regulator of mRNA turnover and translation initiation in eukaryotes. Cap analogues that influence mRNA translation and turnover (either as small molecules or as part of an RNA transcript) are valuable tools for studying gene expression, which is often also of therapeutic relevance. Here, we synthesized a series of 15 dinucleotide cap (m 7 GpppG) analogues containing a 5'-phosphorothiolate (5'-PSL) moiety (i.e., an O-to-S substitution within the 5'-phosphoester) and studied their biological properties in the context of three major cap-binding proteins: translation initiation factor 4E (eIF4E) and two decapping enzymes, DcpS and Dcp2. While the 5'-PSL moiety was neutral or slightly stabilizing for cap interactions with eIF4E, it significantly influenced susceptibility to decapping. Replacing the γ-phosphoester with the 5'-PSL moiety (γ-PSL) prevented β-γ-pyrophosphate bond cleavage by DcpS and conferred strong inhibitory properties. Combining the γ-PSL moiety with α-PSL and β-phosphorothioate (PS) moiety afforded first cap-derived hDcpS inhibitor with low nanomolar potency. Susceptibility to Dcp2 and translational properties were studied after incorporation of the new analogues into mRNA transcripts by RNA polymerase. Transcripts containing the γ-PSL moiety were resistant to cleavage by Dcp2. Surprisingly, superior translational properties were observed for mRNAs containing the α-PSL moiety, which were Dcp2-susceptible. The overall protein expression measured in HeLa cells for this mRNA was comparable to mRNA capped with the translation augmenting β-PS analogue reported previously. Overall, our study highlights 5'-PSL as a synthetically accessible cap modification, which, depending on the substitution site, can either reduce susceptibility to decapping or confer superior translational properties on the mRNA. The 5'-PSL-analogues may find application as reagents for the preparation of efficiently expressed mRNA or for investigation of the role of decapping enzymes in mRNA processing or neuromuscular disorders associated with decapping.

Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities of euglobals and their analogues.

PubMed

Bharate, Sandip B; Bhutani, Kamlesh K; Khan, Shabana I; Tekwani, Babu L; Jacob, Melissa R; Khan, Ikhlas A; Singh, Inder Pal

2006-03-15

In the present communication, naturally occurring phloroglucinol-monoterpene adducts, euglobals G1-G4 (3b/a and 4a/b) and 16 new analogues (13a/b-18a/b and 19-22) were synthesized by biomimetic approach. These synthetic compounds differ from natural euglobals in the nature of monoterpene and acyl functionality. All of these compounds were evaluated for their antibacterial, antifungal, antileishmanial and antimalarial activities. Analogue 17b possessed good antibacterial activity against methicillin-resistant Staphylococcus aureus, while analogues 19-22 possessed potent antifungal activity against Candida glabrata with IC50s ranging from 1.5 to 2.5 microg/mL. Euglobals along with all synthesized analogues exhibited antileishmanial activity. Amongst these, euglobal G2 (3a), G3 (4a) and analogues 13a and 14a showed potent antileishmanial activity with IC50s ranging from 2.8 to 3.9 microg/mL. Analogue 16a possessed antimalarial activity against chloroquine sensitive D6 clone of Plasmodium falciparum. None of the compounds showed toxicity against mammalian kidney fibroblasts (vero cells) upto the concentration of 4.76 microg/ml.

Novel Linear Lipopeptide Paenipeptins with Potential for Eradicating Biofilms and Sensitizing Gram-Negative Bacteria to Rifampicin and Clarithromycin.

PubMed

Moon, Sun Hee; Zhang, Xuan; Zheng, Guangrong; Meeker, Daniel G; Smeltzer, Mark S; Huang, En

2017-12-14

We report the structure-activity relationship analyses of 17 linear lipopeptide paenipeptin analogues. Analogues 7, 12, and 17 were more potent than the lead compound. Analogue 17 was active against carbapenem-resistant and polymyxin-resistant pathogens. This compound at 40 μg/mL resulted in 3 log and 2.6 log reductions of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, respectively, in catheter-associated biofilms in vitro. Analogue 17 showed little hemolysis at 32 μg/mL and lysed 11% of red blood cells at 64 μg/mL. Analogues 9 and 16 were nonhemolytic and retained potent P. aeruginosa-specific antimicrobial activity. These two analogues when used alone lacked activity against Acinetobacter baumannii and Klebsiella pneumoniae; however, analogue 9 and 16 at 4 μg/mL decreased the MIC of rifampicin and clarithromycin against the same pathogens from 16 to 32 μg/mL to nanomolar levels (sensitization factor: 2048-8192). Therefore, paenipeptins, alone or in combination with rifampicin or clarithromycin, are promising candidates for treating bacterial infections.

Secondary structure propensity and chirality of the amyloidophilic peptide p5 and its analogues impacts ligand binding - In vitro characterization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wall, Jonathan S.; Williams, Angela; Wooliver, Craig

Here, polybasic helical peptides, such as peptide p5, bind human amyloid extracts and synthetic amyloid fibrils. When radio labeled, peptide p5 has been shown to specifically bind amyloid in vivo thereby allowing imaging of the disease. Structural requirements for heparin and amyloid binding have been studied using analogues of p5 that modify helicity and chirality.

Lead optimization of antimalarial propafenone analogues.

PubMed

Lowes, David; Pradhan, Anupam; Iyer, Lalitha V; Parman, Toufan; Gow, Jason; Zhu, Fangyi; Furimsky, Anna; Lemoff, Andrew; Guiguemde, W Armand; Sigal, Martina; Clark, Julie A; Wilson, Emily; Tang, Liang; Connelly, Michele C; Derisi, Joseph L; Kyle, Dennis E; Mirsalis, Jon; Guy, R Kiplin

2012-07-12

Previously reported studies identified analogues of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are nontoxic and suppress parasitemia in vivo. Although these compounds possess potential for further preclinical development, they also carry some significant challenges.

Aspartame and Its Analogues

NASA Astrophysics Data System (ADS)

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

1981-04-01

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

Secondary structure propensity and chirality of the amyloidophilic peptide p5 and its analogues impacts ligand binding - In vitro characterization

DOE PAGES

Wall, Jonathan S.; Williams, Angela; Wooliver, Craig; ...

2016-08-11

Here, polybasic helical peptides, such as peptide p5, bind human amyloid extracts and synthetic amyloid fibrils. When radio labeled, peptide p5 has been shown to specifically bind amyloid in vivo thereby allowing imaging of the disease. Structural requirements for heparin and amyloid binding have been studied using analogues of p5 that modify helicity and chirality.

Benzyloxynitrostyrene analogues - A novel class of selective and highly potent inhibitors of monoamine oxidase B.

PubMed

Van der Walt, Mietha M; Terre'Blanche, Gisella; Petzer, Jacobus P; Petzer, Anél

2017-01-05

This study examines a series of novel 3-benzyloxy-β-nitrostyrene analogues as a novel class of inhibitors of the monoamine oxidase (MAO) enzymes. MAO inhibitors are considered useful for the treatment of depression and Parkinson's disease, and have recently attracted attention as potential therapeutic agents for a range of disorders including Alzheimer's disease, prostate cancer and certain cardiomyopathies. This study shows that the 3-benzyloxy-β-nitrostyrene analogues are potent inhibitors of the MAO-B isoform with IC 50 values in the nanomolar range (39-565 nM). Significantly, effectiveness towards MAO-B inhibition seems to be governed by the introduction of a 4″-fluoro-substituent on the benzyloxy ring, with compound 2b exhibiting the highest degree of MAO-B inhibition potency (IC 50  = 0.039 μM) and selectivity (SI = 166) among the compounds investigated. Since some of the 3-benzyloxy-β-nitrostyrene analogues possess potencies that are comparable to that of the reversible inhibitor, safinamide (IC 50  = 0.080 μM), it may be concluded that this class may be promising leads for the development of reversible and selective MAO-B inhibitors, that may be useful for the management of Parkinson's disease. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Pooled analysis of two case-control studies on the use of cellular and cordless telephones and the risk of benign brain tumours diagnosed during 1997-2003.

PubMed

Hardell, Lennart; Carlberg, Michael; Hansson Mild, Kjell

2006-02-01

The use of cellular and cordless telephones and the risk of brain tumours is of concern since the brain is a high exposure area. We present the results of a pooled analysis of two case-control studies on benign brain tumours diagnosed during 1997-2003 including answers from 1,254 (88%) cases and 2,162 (89%) controls aged 20-80 years. For acoustic neuroma, the use of analogue cellular phones gave an odds ratio (OR) of 2.9 and a 95% confidence interval (CI) of 2.0-4.3; for digital cellular phones, OR=1.5; 95% CI=1.1-2.1; and for cordless telephones, OR=1.5, 95% CI=1.04-2.0. The highest OR was found for analogue phones with a latency period of >15 years; OR=3.8, 95% CI=1.4-10. Regarding meningioma, the results were as follows: for analogue phones, OR=1.3, 95% CI=0.99-1.7; for digital phones, OR=1.1, 95% CI=0.9-1.3; and for cordless phones, OR=1.1, 95% CI=0.9-1.4. In the multivariate analysis, a significantly increased risk of acoustic neuroma was found with the use of analogue phones.

Spectroscopic characterization of metal bound phytochelatin analogue (Glu-Cys)4-Gly.

PubMed

Cheng, Yongsheng; Yan, Yong-Bin; Liu, Jinyuan

2005-10-01

The metal ion binding properties of a phytochelatin (PC) analogue, (Glu-Cys)4-Gly (named as EC4), have been studied by a divalent metal ion binding assay monitored by UV-visible spectroscopy, circular dichroism and NMR spectroscopy. Spectro- photometric titration with different divalent metal ions have revealed that the stiochoimetry of metal-bound EC4 was 1:1, and its metal binding affinities with different divalent metal ions in the order of Cd(II)>Cu(II)>Zn(II)>Pb(II)>Ni(II)>Co(II). UV-visible spectroscopic analysis of metal complexes indicated that four sulfur atoms in cysteine residues are attributable to ligand-to-metal charge transfer (LMCT) between divalent metal ions and EC4, and further confirmed by 1D H1 NMR study and Circular Dichroism. In addition, Circular Dichroism spectra of both free and metal-bound forms of EC4 revealed that metal coordination drives the nonapeptide chain to fold into a turned conformation. The comprehensive analysis of spectroscopic properties of the nonapeptide complexed with metal ions not only provides a fundamental description of the metal ion binding properties of PC analogue, but also shows a correlation between metal binding affinity of PC analogue and the induction activity of metal ions.

Parturient perineal distensibility tolerance assessed by EPI-NO: an observational study

PubMed Central

Nakamura, Mary Uchiyama; Sass, Nelson; Elito, Julio; Petricelli, Carla Dellabarba; Alexandre, Sandra Maria; Araujo, Edward; Zanetti, Miriam Raquel Diniz

2014-01-01

ABSTRACT Objective: To determine how parturient women tolerate the use of a perineal distensibility assessment technique using the EPI-NO device. Methods: An observational study with a total of 227 full-term parturient women was performed. During the evaluation with EPI-NO, parturient patients were asked about their sensation of discomfort. The degree of discomfort was measured using the Visual Analogue Scale, with a score from zero to 10. The Mann-Whitney test was applied to assess perineal distensibility measured by EPI-NO and the degree of discomfort caused by the test according to parity. The relation between perineal distensibility and discomfort was analyzed by using the Spearman correlation test (r). Results: The test with EPI-NO caused only slight discomfort (mean Visual Analogue Scale of 3.8), and primiparous women reported significantly greater discomfort (mean Visual Analogue Scale of 4.5) than did multiparous (mean Visual Analogue Scale=3.1), with p<0.001 women. A negative correlation was observed, in other words, the greater the perineal distensibility on the EPI-NO, the lower the pain reported by the patients (r=-0.424; p<0.001). Conclusion: The assessment of perineal distensibility with EPI-NO was well tolerated by the parturient women. PMID:24728241

Theoretical study on the influence of different para-substituents on 13C NMR of the single carbonyl curcumin analogues

NASA Astrophysics Data System (ADS)

Jia, Fei-yun; Ran, Ming; Zhang, Bo

2015-12-01

The structure of eight kinds of different para-substituents curcumin analogues has been optimized at the level of B3LYP/6-31G( d, p), under which the stability has been verified by means of vibration analysis. Moreover, NMR spectra of curcumin analogues compounds have been studied at the level of B3LYP/6-311G( d, p) by GIAO method. The results show that the structure of eight compounds, a larger conjugated system, has good planarity. The effect of ortho-substituents on bond lengths and bond angles is greater than para and meta. Different substituents and different positions of substituents all have different influence on NMR of the single carbonyl curcumin analogues. In general, after the hydrogen atom on the benzene ring is substituted by other groups, the δ value of α-C changes significantly, the δ value of ortho-carbon atom may also have great change, but the δ value change of meta-carbon atoms is not too obvious. The effect of substituent electronegativity on α-C atoms presents obvious regularity, while the influence of conjugate effect on carbon atoms of benzene ring is more complex. Finally, the bigger substituted alkyl is, the more the δ value of α-C increases.

Comparison study on mechanical properties single step and three step artificial aging on duralium

NASA Astrophysics Data System (ADS)

Tsamroh, Dewi Izzatus; Puspitasari, Poppy; Andoko, Sasongko, M. Ilman N.; Yazirin, Cepi

2017-09-01

Duralium is kind of non-ferro alloy that used widely in industrial. That caused its properties such as mild, high ductility, and resistance from corrosion. This study aimed to know mechanical properties of duralium on single step and three step articial aging process. Mechanical properties that discussed in this study focused on toughness value, tensile strength, and microstructure of duralium. Toughness value of single step artificial aging was 0.082 joule/mm2, and toughness value of three step artificial aging was 0,0721 joule/mm2. Duralium tensile strength of single step artificial aging was 32.36 kgf/mm^2, and duralium tensile strength of three step artificial aging was 32,70 kgf/mm^2. Based on microstructure photo of duralium of single step artificial aging showed that precipitate (θ) was not spreading evenly indicated by black spot which increasing the toughness of material. While microstructure photo of duralium that treated by three step artificial aging showed that it had more precipitate (θ) spread evenly compared with duralium that treated by single step artificial aging.

Modeling and analysis of biomagnetic blood Carreau fluid flow through a stenosis artery with magnetic heat transfer: A transient study.

PubMed

Abdollahzadeh Jamalabadi, Mohammad Yaghoub; Daqiqshirazi, Mohammadreza; Nasiri, Hossein; Safaei, Mohammad Reza; Nguyen, Truong Khang

2018-01-01

We present a numerical investigation of tapered arteries that addresses the transient simulation of non-Newtonian bio-magnetic fluid dynamics (BFD) of blood through a stenosis artery in the presence of a transverse magnetic field. The current model is consistent with ferro-hydrodynamic (FHD) and magneto-hydrodynamic (MHD) principles. In the present work, blood in small arteries is analyzed using the Carreau-Yasuda model. The arterial wall is assumed to be fixed with cosine geometry for the stenosis. A parametric study was conducted to reveal the effects of the stenosis intensity and the Hartman number on a wide range of flow parameters, such as the flow velocity, temperature, and wall shear stress. Current findings are in a good agreement with recent findings in previous research studies. The results show that wall temperature control can keep the blood in its ideal blood temperature range (below 40°C) and that a severe pressure drop occurs for blockages of more than 60 percent. Additionally, with an increase in the Ha number, a velocity drop in the blood vessel is experienced.

Synthetic mixed-signal computation in living cells

PubMed Central

Rubens, Jacob R.; Selvaggio, Gianluca; Lu, Timothy K.

2016-01-01

Living cells implement complex computations on the continuous environmental signals that they encounter. These computations involve both analogue- and digital-like processing of signals to give rise to complex developmental programs, context-dependent behaviours and homeostatic activities. In contrast to natural biological systems, synthetic biological systems have largely focused on either digital or analogue computation separately. Here we integrate analogue and digital computation to implement complex hybrid synthetic genetic programs in living cells. We present a framework for building comparator gene circuits to digitize analogue inputs based on different thresholds. We then demonstrate that comparators can be predictably composed together to build band-pass filters, ternary logic systems and multi-level analogue-to-digital converters. In addition, we interface these analogue-to-digital circuits with other digital gene circuits to enable concentration-dependent logic. We expect that this hybrid computational paradigm will enable new industrial, diagnostic and therapeutic applications with engineered cells. PMID:27255669

Novel Analogues of (R)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (Sumanirole) Provide Clues to Dopamine D2/D3 Receptor Agonist Selectivity

PubMed Central

2016-01-01

Novel 1-, 5-, and 8-substituted analogues of sumanirole (1), a dopamine D2/D3 receptor (D2R/D3R) agonist, were synthesized. Binding affinities at both D2R and D3R were higher when determined in competition with the agonist radioligand [3H]7-hydroxy-N,N-dipropyl-2-aminotetralin (7-OH-DPAT) than with the antagonist radioligand [3H]N-methylspiperone. Although 1 was confirmed as a D2R-preferential agonist, its selectivity in binding and functional studies was lower than previously reported. All analogues were determined to be D2R/D3R agonists in both GoBRET and mitogenesis functional assays. Loss of efficacy was detected for the N-1-substituted analogues at D3R. In contrast, the N-5-alkyl-substituted analogues, and notably the n-butyl-arylamides (22b and 22c), all showed improved affinity at D2R over 1 with neither a loss of efficacy nor an increase in selectivity. Computational modeling provided a structural basis for the D2R selectivity of 1, illustrating how subtle differences in the highly homologous orthosteric binding site (OBS) differentially affect D2R/D3R affinity and functional efficacy. PMID:27035329

The power of clinicians' affective communication: how reassurance about non-abandonment can reduce patients' physiological arousal and increase information recall in bad news consultations. An experimental study using analogue patients.

PubMed

Sep, Milou S C; van Osch, Mara; van Vliet, Liesbeth M; Smets, Ellen M A; Bensing, Jozien M

2014-04-01

The diagnosis of incurable cancer may evoke physiological arousal in patients. Physiological arousal can negatively impact patients' recall of information provided in the medical consultation. We aim to investigate whether clinicians' affective communication during a bad news consultation will decrease patients' physiological arousal and will improve recall. Healthy women (N=50), acting as analogue patients, were randomly assigned to watch one out of the two versions of a scripted video-vignette of a bad news consultation in which clinician's communication differed: standard vs. affective communication. Participants' skin conductance levels were obtained during video-watching, and afterwards their recall was assessed. While the diagnosis increased skin conductance levels in all analogue patients, skin conductance levels during the remainder of the consultation decreased more in the affective communication condition than in the standard condition. Analogue patients' recall was significantly higher in the affective condition. Breaking bad news evokes physiological arousal. Affective communication can decrease this evoked physiological arousal and might be partly responsible for analogue patients' enhanced information recall. Although our findings need to be translated to clinical patients, they suggest that clinicians need to deal with patients' emotions before providing additional medical information. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Synthesis of cis- and trans-α-l-[4.3.0]bicyclo-DNA monomers for antisense technology: methods for the diastereoselective formation of bicyclic nucleosides.

PubMed

Hanessian, Stephen; Schroeder, Benjamin R; Merner, Bradley L; Chen, Bin; Swayze, Eric E; Seth, Punit P

2013-09-20

Two α-L-ribo-configured bicyclic nucleic acid modifications, represented by analogues 12 and 13, which are epimeric at C3' and C5' have been synthesized using a carbohydrate-based approach to build the bicyclic core structure. An intramolecular L-proline-mediated aldol reaction was employed to generate the cis-configured ring junction of analogue 12 and represents a rare application of this venerable organocatalytic reaction to a carbohydrate system. In the case of analogue 13, where a trans-ring junction was desired, an intermolecular diastereoselective Grignard reaction followed by ring-closing metathesis was used. In order to set the desired stereochemistry at the C5' positions of both nucleoside targets, a study of diastereoselective Lewis acid mediated allylation reactions on a common bicyclic aldehyde precursor was carried out. Analogue 12 was incorporated in oligonucleotide sequences, and thermal denaturation experiments indicate that it is destabilizing when paired with complementary DNA and RNA. However, this construct shows a significant improvement in nuclease stability relative to a DNA oligonucleotide.

Genotoxicity and Cytotoxicity Evaluation of the Neolignan Analogue 2-(4-Nitrophenoxy)-1Phenylethanone and its Protective Effect Against DNA Damage

PubMed Central

Hanusch, Alex Lucas; de Oliveira, Guilherme Roberto; de Sabóia-Morais, Simone Maria Teixeira; Machado, Rafael Cosme; dos Anjos, Murilo Machado; Chen Chen, Lee

2015-01-01

Neolignans are secondary metabolites found in various groups of Angiosperms. They belong to a class of natural compounds with great diversity of chemical structures and pharmacological activities. These compounds are formed by linking two phenylpropanoid units. Several compounds that have ability to prevent genetic damage have been isolated from plants, and can be used to prevent or delay the development of tumor cells. Genetic toxicology evaluation is widely used in risk assessment of new drugs in preclinical screening tests. In this study, we evaluated the genotoxicity and cytotoxicity of the neolignan analogue 2-(4-nitrophenoxy)-1-phenylethanone (4NF) and its protective effect against DNA damage using the mouse bone marrow micronucleus test and the comet assay in mouse peripheral blood. Our results showed that this neolignan analogue had no genotoxic activity and was able to reduce induced damage both in mouse bone marrow and peripheral blood. Although the neolignan analogue 4NF was cytotoxic, it reduced cyclophosphamide-induced cytotoxicity. In conclusion, it showed no genotoxic action, but exhibited cytotoxic, antigenotoxic, and anticytotoxic activities. PMID:26554835

Structure-activity relationship of S-trityl-L-cysteine analogues as inhibitors of the human mitotic kinesin Eg5.

PubMed

Debonis, Salvatore; Skoufias, Dimitrios A; Indorato, Rose-Laure; Liger, François; Marquet, Bernard; Laggner, Christian; Joseph, Benoît; Kozielski, Frank

2008-03-13

The human kinesin Eg5 is a potential drug target for cancer chemotherapy. Eg5 specific inhibitors cause cells to block in mitosis with a characteristic monoastral spindle phenotype. Prolonged metaphase block eventually leads to apoptotic cell death. S-trityl-L-cysteine (STLC) is a tight-binding inhibitor of Eg5 that prevents mitotic progression. It has proven antitumor activity as shown in the NCI 60 tumor cell line screen. It is of considerable interest to define the minimum chemical structure that is essential for Eg5 inhibition and to develop more potent STLC analogues. An initial structure-activity relationship study on a series of STLC analogues reveals the minimal skeleton necessary for Eg5 inhibition as well as indications of how to obtain more potent analogues. The most effective compounds investigated with substitutions at the para-position of one phenyl ring have an estimated K i (app) of 100 nM in vitro and induce mitotic arrest with an EC 50 of 200 nM.

Induction of human spermine oxidase SMO(PAOh1) is regulated at the levels of new mRNA synthesis, mRNA stabilization and newly synthesized protein

PubMed Central

2004-01-01

The oxidation of polyamines induced by antitumour polyamine analogues has been associated with tumour response to specific agents. The human spermine oxidase, SMO(PAOh1), is one enzyme that may play a direct role in the cellular response to the antitumour polyamine analogues. In the present study, the induction of SMO(PAOh1) enzyme activity by CPENSpm [N1-ethyl-N11-(cyclopropyl)methyl-4,8,diazaundecane] is demonstrated to be a result of newly synthesized mRNA and protein. Inhibition of new RNA synthesis by actinomycin D inhibits both the appearance of SMO(PAOh1) mRNA and enzyme activity. Similarly, inhibition of newly synthesized protein with cycloheximide prevents analogue-induced enzyme activity. Half-life determinations indicate that stabilization of SMO(PAOh1) protein does not play a significant role in analogue-induced activity. However, half-life experiments using actinomycin D indicate that CPENSpm treatment not only increases mRNA expression, but also leads to a significant increase in mRNA half-life (17.1 and 8.8 h for CPENSpm-treated cells and control respectively). Using reporter constructs encompassing the SMO(PAOh1) promoter region, a 30–90% increase in transcription is observed after exposure to CPENSpm. The present results are consistent with the hypothesis that analogue-induced expression of SMO(PAOh1) is a result of increased transcription and stabilization of SMO(PAOh1) mRNA, leading to increased protein production and enzyme activity. These data indicate that the major level of control of SMO(PAOh1) expression in response to polyamine analogues exposure is at the level of mRNA. PMID:15496143

Comparing effects of insulin analogues and human insulin on nocturnal glycaemia in hypoglycaemia-prone people with Type 1 diabetes.

PubMed

Kristensen, P L; Tarnow, L; Bay, C; Nørgaard, K; Jensen, T; Parving, H-H; Perrild, H; Beck-Nielsen, H; Christiansen, J S; Thorsteinsson, B; Pedersen-Bjergaard, U

2017-05-01

To assess the difference between analogue and human insulin with regard to nocturnal glucose profiles and risk of hypoglycaemia in people with recurrent severe hypoglycaemia. A total of 72 people [46 men, mean ± sd age 54 ± 12 years, mean ± sd HbA 1c 65 ± 12 mmol/mol (8.1 ± 1.1%), mean ± sd duration of diabetes 30 ± 14 years], who participated in a 2-year randomized, crossover trial of basal-bolus therapy with insulin detemir/insulin aspart or human NPH insulin/human regular insulin (the HypoAna trial) were studied for 2 nights during each treatment. Venous blood was drawn hourly during sleep. Primary endpoints were nocturnal glucose profiles and occurrence of hypoglycaemia (blood glucose ≤ 3.9 mmol/l). During insulin analogue treatment, the mean nocturnal plasma glucose level was significantly higher than during treatment with human insulin (10.6 vs 8.1 mmol/l). The fasting plasma glucose level was similar between the treatments. Nocturnal hypoglycaemia was registered during 41/101 nights (41%) in the human insulin arm and 19/117 nights (16%) in the insulin analogue arm, corresponding to a hazard ratio of 0.26 (95% CI 0.14 to 0.45; P < 0.0001) with insulin analogue. Treatment with insulin analogue reduces the occurrence of nocturnal hypoglycaemia assessed by nocturnal glucose profiles in people with Type 1 diabetes prone to severe hypoglycaemia. Nocturnal glucose profiles provide a more comprehensive assessment of clinical benefit of insulin regimens as compared to conventional recording of hypoglycaemia. © 2017 Diabetes UK.

Enhancing the anti-lymphoma potential of 3,4-methylenedioxymethamphetamine ('ecstasy') through iterative chemical redesign: mechanisms and pathways to cell death.

PubMed

Wasik, Agata M; Gandy, Michael N; McIldowie, Matthew; Holder, Michelle J; Chamba, Anita; Challa, Anita; Lewis, Katie D; Young, Stephen P; Scheel-Toellner, Dagmar; Dyer, Martin J; Barnes, Nicholas M; Piggott, Matthew J; Gordon, John

2012-08-01

While 3,4-methylenedioxymethamphetamine (MDMA/'ecstasy') is cytostatic towards lymphoma cells in vitro, the concentrations required militate against its translation directly to a therapeutic in vivo. The possibility of 'redesigning the designer drug', separating desired anti-lymphoma activity from unwanted psychoactivity and neurotoxicity, was therefore mooted. From an initial analysis of MDMA analogues synthesized with a modified α-substituent, it was found that incorporating a phenyl group increased potency against sensitive, Bcl-2-deplete, Burkitt's lymphoma (BL) cells 10-fold relative to MDMA. From this lead, related analogs were synthesized with the 'best' compounds (containing 1- and 2-naphthyl and para-biphenyl substituents) some 100-fold more potent than MDMA versus the BL target. When assessed against derived lines from a diversity of B-cell tumors MDMA analogues were seen to impact the broad spectrum of malignancy. Expressing a BCL2 transgene in BL cells afforded only scant protection against the analogues and across the malignancies no significant correlation between constitutive Bcl-2 levels and sensitivity to compounds was observed. Bcl-2-deplete cells displayed hallmarks of apoptotic death in response to the analogues while BCL2 overexpressing equivalents died in a caspase-3-independent manner. Despite lymphoma cells expressing monoamine transporters, their pharmacological blockade failed to reverse the anti-lymphoma actions of the analogues studied. Neither did reactive oxygen species account for ensuing cell death. Enhanced cytotoxic performance did however track with predicted lipophilicity amongst the designed compounds. In conclusion, MDMA analogues have been discovered with enhanced cytotoxic efficacy against lymphoma subtypes amongst which high-level Bcl-2--often a barrier to drug performance for this indication--fails to protect.

Evaluation of the quality of life of patients with diabetes mellitus treated with conventional or analogue insulins.

PubMed

Machado-Alba, Jorge Enrique; Medina-Morales, Diego Alejandro; Echeverri-Cataño, Luis Felipe

2016-06-01

The results of two scales that measure quality of life of patients with diabetes mellitus treated with conventional or analogue insulin were evaluated and compared. Descriptive, observational, cross-sectional study, conducted in the cities of Pereira and Manizales, Colombia, in a care facility between 1 August 2013 and 30 March 2014. A total of 238 patients diagnosed with diabetes mellitus type 1 or type 2 who had been undergoing treatment with conventional or analogue insulin for at least 6months. Comparison of the results of the Diabetes 39 (specific) and European Quality of Life-5 Dimensions (EQ-5D) (generic) tools it was performed. Comparisons between the results of the two instruments were performed. Tests for parametric and non-parametric distribution (Pearson's correlation coefficient, Mann-Whitney U test, Student's t-test and Wilcoxon test) were used. The mean age was 57.7±16.6years. Conventional insulin was prescribed to 69.6% of patients, and analogue insulin was prescribed to 30.4% of patients. Diabetes-39 (D-39) showed 24.7% of subjects with a high quality of life. No statistically significant differences were found when comparing patients prescribed conventional or analogue insulin (p=0.35; 95% confidence interval [CI]: 0.375-1.419). In the EQ-5D survey, 45.7% claimed to have a high quality of life, without statistically significant differences between groups (p=0.56; 95%CI: 0.676-2.047). No differences between patients receiving conventional insulin versus analogue insulin were detected in terms of quality of life. The group aged over 60years requires special attention to improve their quality of life, and programs should focus on those individuals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DOTA-derivatives of octreotide dicarba-analogues with high affinity for somatostatin sst2,5 receptors

NASA Astrophysics Data System (ADS)

Pratesi, Alessandro; Ginanneschi, Mauro; Lumini, Marco; Papini, Anna M.; Novellino, Ettore; Brancaccio, Diego; Carotenuto, Alfonso

2017-02-01

In vivo somatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumours and their metastases. In fact, peptide ligands of somatostatin receptors (sst’s) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogues, which show interesting binding profiles at sst’s. In this context, it was mandatory to explore the possibility that our analogues could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogues of octreotide. Interestingly, two conjugated analogues exhibited nanomolar affinities on sst2 and sst5 somatostatin receptor subtypes.

The 57Fe hyperfine interactions in human liver ferritin and its iron-polymaltose analogues: the heterogeneous iron core model

NASA Astrophysics Data System (ADS)

Oshtrakh, M. I.; Alenkina, I. V.; Semionkin, V. A.

2016-12-01

Human liver ferritin and its iron-polymaltose pharmaceutical analogues Ferrum Lek, Maltofer® and Ferrifol® were studied using Mössbauer spectroscopy at 295 and 90 K. The Mössbauer spectra were fitted on the basis of a new model of heterogeneous iron core structure using five quadrupole doublets. These components were related to the corresponding more or less close-packed iron core layers/regions demonstrating some variations in the 57Fe hyperfine parameters for the studied samples.

Pena blanca natural analogue project: summary of activities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levy, Schon S; Goldstein, Steven J; Abdel - Fattah, Amr I

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.

The project De Caldas International Project: An example of a large-scale radwaste isolation natural analogue study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shea, M.

1995-09-01

The proper isolation of radioactive waste is one of today`s most pressing environmental issues. Research is being carried out by many countries around the world in order to answer critical and perplexing questions regarding the safe disposal of radioactive waste. Natural analogue studies are an increasingly important facet of this international research effort. The Pocos de Caldas Project represents a major effort of the international technical and scientific community towards addressing one of modern civilization`s most critical environmental issues - radioactive waste isolation.

Structural Analogues of Selfotel.

PubMed

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

2016-06-17

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

Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.

PubMed

Maruyama, Mitsunori; Xiao, Jianmin; Zhou, Qiang; Vembaiyan, Kannan; Chua, Su-Kiat; Rubart-von der Lohe, Michael; Lin, Shien-Fong; Back, Thomas G; Chen, S R Wayne; Chen, Peng-Sheng

2013-01-01

Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2). To test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs). Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects. Spontaneous intracellular Ca(2+) elevations (SCaEs) during diastole were induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in which phase 2 and phase 3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied. A carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by the suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Biocatalysis of a Paclitaxel Analogue: Conversion of Baccatin III to N-Debenzoyl-N-(2-furoyl)paclitaxel and Characterization of an Amino Phenylpropanoyl CoA Transferase.

PubMed

Thornburg, Chelsea K; Walter, Tyler; Walker, Kevin D

2017-11-07

In this study, we demonstrate an enzyme cascade reaction using a benzoate CoA ligase (BadA), a modified nonribosomal peptide synthase (PheAT), a phenylpropanoyltransferase (BAPT), and a benzoyltransferase (NDTNBT) to produce an anticancer paclitaxel analogue and its precursor from the commercially available biosynthetic intermediate baccatin III. BAPT and NDTNBT are acyltransferases on the biosynthetic pathway to the antineoplastic drug paclitaxel in Taxus plants. For this study, we addressed the recalcitrant expression of BAPT by expressing it as a soluble maltose binding protein fusion (MBP-BAPT). Further, the preparative-scale in vitro biocatalysis of phenylisoserinyl CoA using PheAT enabled thorough kinetic analysis of MBP-BAPT, for the first time, with the cosubstrate baccatin III. The turnover rate of MBP-BAPT was calculated for the product N-debenzoylpaclitaxel, a key intermediate to various bioactive paclitaxel analogues. MBP-BAPT also converted, albeit more slowly, 10-deacetylbaccatin III to N-deacyldocetaxel, a precursor of the pharmaceutical docetaxel. With PheAT available to make phenylisoserinyl CoA and kinetic characterization of MBP-BAPT, we used Michaelis-Menten parameters of the four enzymes to adjust catalyst and substrate loads in a 200-μL one-pot reaction. This multienzyme network produced a paclitaxel analogue N-debenzoyl-N-(2-furoyl)paclitaxel (230 ng) that is more cytotoxic than paclitaxel against certain macrophage cell types. Also in this pilot reaction, the versatile N-debenzoylpaclitaxel intermediate was made at an amount 20-fold greater than the N-(2-furoyl) product. This reaction network has great potential for optimization to scale-up production and is attractive in its regioselective O- and N-acylation steps that remove protecting group manipulations used in paclitaxel analogue synthesis.

Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: impact of novel therapies.

PubMed

García-Suárez, Julio; de Miguel, Dunia; Krsnik, Isabel; Bañas, Helena; Arribas, Ignacio; Burgaleta, Carmen

2005-12-01

The aims of this study were to evaluate the clinical characteristics of HIV-negative patients affected by lymphoproliferative disorders (LPD) who developed progressive multifocal leukoencephalopathy (PML), to delineate the risk factors, and to analyze whether the new antineoplastic therapies are changing the natural history of this infectious disease. We retrospectively analyzed 46 cases with confirmed LPD-associated PML published from 1958 to 2004. Patients were stratified according to two different time periods: group A included patients diagnosed before 1989, and group B included patients diagnosed since 1990, after introduction of purine analogues. Group A patients (n = 22) had received alkylating agents and/or radiotherapy, and the majority (63.6%) had advanced Hodgkin disease. At univariate analysis, uncontrolled Hodgkin disease was the only risk factor for PML. In group B patients (n = 24), the most frequent treatments received were purine analogues (58.3%) and high-dose therapy with hematopoietic stem cell transplantation (33.3%; HDT/HSCT). B-cell chronic lymphocytic leukemia (45.8%) and aggressive non-Hodgkin lymphoma (24.9%) were the most frequent underlying LPDs. Patients treated with purine analogues were more likely to have active LPD, lower CD4 cell counts, and to be older and male than were HSCT recipients. The median interval from purine analogues or HDT/HSCT to PML was 11 months. In HDT/HSCT recipients, this interval was delayed for 10 months when peri-transplantation rituximab was used. Univariate analysis identified age >55 years, male sex, and CD4 cell counts

Corticosteroidogenesis in the toad Bufo arenarum H: evidence for a precursor role for an aldosterone 3 beta-hydroxy-5-ene analogue (3 beta, 11 beta, 21-trihydroxy-20-oxo-5-pregnen-18-al).

PubMed Central

Ceballos, N R; Shackleton, C H; Harnik, M; Cozza, E N; Gros, E G; Lantos, C P

1993-01-01

A material isolated following pregnenolone incubations with toad (Bufo arenarum) inter-renal tissue at 28 degrees C has been identified as a 3 beta-hydroxy-5-ene analogue of aldosterone (3 beta, 11 beta, 21-trihydroxy-20-oxo-5-pregnen-18-al). The initial identification was made by enzymic and m.s. methods, and structural confirmation was achieved through comparison with chemically synthesized authentic material. The relative efficacy of corticosterone, 18-hydroxycorticosterone and the 3 beta-hydroxy-5-ene aldosterone analogue as aldosterone precursors was evaluated. In the in vitro situation studied, the 3 beta-hydroxy-5-ene steroid was by far the best precursor. PMID:8503841

Corticosteroidogenesis in the toad Bufo arenarum H: evidence for a precursor role for an aldosterone 3 beta-hydroxy-5-ene analogue (3 beta, 11 beta, 21-trihydroxy-20-oxo-5-pregnen-18-al).

PubMed

Ceballos, N R; Shackleton, C H; Harnik, M; Cozza, E N; Gros, E G; Lantos, C P

1993-05-15

A material isolated following pregnenolone incubations with toad (Bufo arenarum) inter-renal tissue at 28 degrees C has been identified as a 3 beta-hydroxy-5-ene analogue of aldosterone (3 beta, 11 beta, 21-trihydroxy-20-oxo-5-pregnen-18-al). The initial identification was made by enzymic and m.s. methods, and structural confirmation was achieved through comparison with chemically synthesized authentic material. The relative efficacy of corticosterone, 18-hydroxycorticosterone and the 3 beta-hydroxy-5-ene aldosterone analogue as aldosterone precursors was evaluated. In the in vitro situation studied, the 3 beta-hydroxy-5-ene steroid was by far the best precursor.

[Somatostatin and the digestive system. Clinical experiences].

PubMed

Herszényi, László; Mihály, Emese; Tulassay, Zsolt

2013-09-29

The effect of somatostatin on the gastrointestinal tract is complex; it inhibits the release of gastrointestinal hormones, the exocrine function of the stomach, pancreas and bile, decreases motility and influences absorption as well. Based on these diverse effects there was an increased expectation towards the success of somatostatin therapy in various gastrointestinal disorders. The preconditions for somatostatin treatment was created by the development of long acting somatostatin analogues (octreotide, lanreotide). During the last twenty-five years large trials clarified the role of somatostatin analogues in the treatment of various gastrointestinal diseases. This study summarizes shortly these results. Somatostatin analogue treatment could be effective in various pathological conditions of the gastrointestinal tract, however, this therapeutic modality became a part of the clinical routine only in neuroendocrine tumours and adjuvant treatment of oesophageal variceal bleeding and pancreatic fistulas.

Pion and proton showers in the CALICE scintillator-steel analogue hadron calorimeter

NASA Astrophysics Data System (ADS)

Bilki, B.; Repond, J.; Xia, L.; Eigen, G.; Thomson, M. A.; Ward, D. R.; Benchekroun, D.; Hoummada, A.; Khoulaki, Y.; Chang, S.; Khan, A.; Kim, D. H.; Kong, D. J.; Oh, Y. D.; Blazey, G. C.; Dyshkant, A.; Francis, K.; Lima, J. G. R.; Salcido, R.; Zutshi, V.; Salvatore, F.; Kawagoe, K.; Miyazaki, Y.; Sudo, Y.; Suehara, T.; Tomita, T.; Ueno, H.; Yoshioka, T.; Apostolakis, J.; Dannheim, D.; Folger, G.; Ivantchenko, V.; Klempt, W.; Lucaci-Timoce, A.-I.; Ribon, A.; Schlatter, D.; Sicking, E.; Uzhinskiy, V.; Giraud, J.; Grondin, D.; Hostachy, J.-Y.; Morin, L.; Brianne, E.; Cornett, U.; David, D.; Ebrahimi, A.; Falley, G.; Gadow, K.; Göttlicher, P.; Günter, C.; Hartbrich, O.; Hermberg, B.; Karstensen, S.; Krivan, F.; Krüger, K.; Lu, S.; Lutz, B.; Morozov, S.; Morgunov, V.; Neubüser, C.; Reinecke, M.; Sefkow, F.; Smirnov, P.; Tran, H. L.; Buhmann, P.; Garutti, E.; Laurien, S.; Matysek, M.; Ramilli, M.; Briggl, K.; Eckert, P.; Harion, T.; Munwes, Y.; Schultz-Coulon, H.-Ch.; Shen, W.; Stamen, R.; Norbeck, E.; Northacker, D.; Onel, Y.; van Doren, B.; Wilson, G. W.; Wing, M.; Combaret, C.; Caponetto, L.; Eté, R.; Grenier, G.; Han, R.; Ianigro, J. C.; Kieffer, R.; Laktineh, I.; Lumb, N.; Mathez, H.; Mirabito, L.; Petrukhin, A.; Steen, A.; Berenguer Antequera, J.; Calvo Alamillo, E.; Fouz, M.-C.; Marin, J.; Puerta-Pelayo, J.; Verdugo, A.; Corriveau, F.; Bobchenko, B.; Chistov, R.; Chadeeva, M.; Danilov, M.; Drutskoy, A.; Epifantsev, A.; Markin, O.; Mironov, D.; Mizuk, R.; Novikov, E.; Rusinov, V.; Tarkovsky, E.; Besson, D.; Buzhan, P.; Ilyin, A.; Popova, E.; Gabriel, M.; Kiesling, C.; van der Kolk, N.; Simon, F.; Soldner, C.; Szalay, M.; Tesar, M.; Weuste, L.; Amjad, M. S.; Bonis, J.; Callier, S.; Conforti di Lorenzo, S.; Cornebise, P.; Dulucq, F.; Fleury, J.; Frisson, T.; Martin-Chassard, G.; Pöschl, R.; Raux, L.; Richard, F.; Rouëné, J.; Seguin-Moreau, N.; de la Taille, Ch.; Anduze, M.; Boudry, V.; Brient, J.-C.; Clerc, C.; Cornat, R.; Frotin, M.; Gastaldi, F.; Matthieu, A.; Mora de Freitas, P.; Musat, G.; Ruan, M.; Videau, H.; Zacek, J.; Cvach, J.; Gallus, P.; Havranek, M.; Janata, M.; Kvasnicka, J.; Lednicky, D.; Marcisovsky, M.; Polak, I.; Popule, J.; Tomasek, L.; Tomasek, M.; Sicho, P.; Smolik, J.; Vrba, V.; Zalesak, J.; Jeans, D.; Weber, S.

2015-04-01

Showers produced by positive hadrons in the highly granular CALICE scintillator-steel analogue hadron calorimeter were studied. The experimental data were collected at CERN and FNAL for single particles with initial momenta from 10 to 80 GeV/c. The calorimeter response and resolution and spatial characteristics of shower development for proton- and pion-induced showers for test beam data and simulations using GEANT4 version 9.6 are compared.

Synthesis and SAR studies of marine natural products ma'edamines A, B and their analogues.

PubMed

Saha, Sanjay; Reddy, Ch Venkata Ramana; Xu, Shili; Sankar, Saranya; Neamati, Nouri; Patro, Balaram

2013-09-15

The synthesis of several analogues of ma'edamines A and B are reported. The synthesized compounds were tested on hormone receptor positive and HER2 positive breast cancer cell lines, by MTT assay. MED-114, 115, 117, 119, 120, 124, 128 and 131 were found to be equally active as Lapatinib on HER2 +ve cell line SKBR3. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hyperspectral imaging polarimeter in the infrared

NASA Astrophysics Data System (ADS)

Jensen, Gary L.; Peterson, James Q.

1998-11-01

The Space Dynamics Laboratory at Utah State University is building an infrared Hyperspectral Imaging Polarimeter (HIP). Designed for high spatial and spectral resolution polarimetry of backscattered sunlight from cloud tops in the 2.7 micrometer water band, it will fly aboard the Flying Infrared Signatures Technology Aircraft (FISTA), an Air Force KC-135. It is a proof-of-concept sensor, combining hyperspectral pushbroom imaging with high speed, solid state polarimetry, using as many off-the-shelf components as possible, and utilizing an optical breadboard design for rapid prototyping. It is based around a 256 X 320 window selectable InSb camera, a solid-state Ferro-electric Liquid Crystal (FLC) polarimeter, and a transmissive diffraction grating.

Structure, strain, and control of ground state property in LaTiO3/LaAlO3 superlattice

NASA Astrophysics Data System (ADS)

Lee, Alex Taekyung; Han, Myung Joon

2014-03-01

We examined the ground state property of LaTiO3/LaAlO3 superlattice through density functional band calculations. Total energy calculations, including the structural distortions, U dependence, and the exchange correlation functional dependence, clearly showed that the spin and orbital ground state can be controlled systematically by the epitaxial strain. In the wide range of strain, the ferromagnetic-spin and antiferro-orbital order are stabilized, which is notably different from the previously reported ground state in the titanate systems. By applying +2.8% of tensile strains, we showed that the antiferromagnetic-spin and ferro-orbital ordered phase become stabilized.

[Cloning, expressing of exendin-4 analogue and bioactivity analysis in vivo].

PubMed

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).

Novel DOTA-based prochelator for divalent peptide vectorization: synthesis of dimeric bombesin analogues for multimodality tumor imaging and therapy.

PubMed

Abiraj, Keelara; Jaccard, Hugues; Kretzschmar, Martin; Helm, Lothar; Maecke, Helmut R

2008-07-28

Dimeric peptidic vectors, obtained by the divalent grafting of bombesin analogues on a newly synthesized DOTA-based prochelator, showed improved qualities as tumor targeted imaging probes in comparison to their monomeric analogues.

A review of synthetic phosphodiesterase type 5 inhibitors (PDE-5i) found as adulterants in dietary supplements.

PubMed

Kee, Chee-Leong; Ge, Xiaowei; Gilard, Véronique; Malet-Martino, Myriam; Low, Min-Yong

2018-01-05

To date, there are 80 synthetic PDE-5i found as adulterants in dietary supplements. Analogues of sildenafil remain as the top list with 50 (62%) and are followed by analogues of tadalafil, 21 (26%), analogues of vardenafil, 7 (9%) and others, 2 (3%). The sildenafil group can be sub-categorized into sulphonamide-bonded (24, 48%), acetyl-bonded (11, 22%), carbonyl or thiocarbonyl-bonded (8, 16%) and other types (7, 14%) based on the functional group linked to pyrazolopyrimidine-one moieties. Meanwhile, analogues of tadalafil have become popularly found as adulterants in dietary supplements like beverages and herbal extracts from 2015 to 2016. The uptrend has been observed with the increase in number and complexity with more trans-oriented and dimerized tadalafil analogues being reported. Interestingly, there is no much increase for analogues of vardenafil. About two thirds of analogues have been reported from the Asian countries (67%), followed by Europe (22%) and North America (11%). South Korea and Singapore have reported the most number of analogues with a total number of 40 (50%). One plausible contributing factor to this trend is the convenient purchase of sexual enhancement dietary supplements, especially the on-line purchase. In terms of analytical methodologies, high performance liquid chromatography (HPLC) hyphenated to ultra-violet (UV) and/or mass spectrometry (MS) detection have been preferred in the screening analysis, i.e. 70 out of 77 compounds have been analysed by HPLC-UV. In addition, the electrospray ionization multistage fragmentation experiments (ESI-MS n ) for acquiring low- and high-resolution mass spectra have been successfully applied to detect and quantify PDE-5i in adulterated products simultaneously. Nuclear magnetic resonance (NMR) is another important technique in the structural elucidation of novel analogues. Copyright © 2017 Elsevier B.V. All rights reserved.

Radioprotection of intestinal stem cells and whole body radiation lethality from photons and neutrons by prostaglandins along or in combination with WR-2721. Technical report 24 Feb 86-30 Sep 89

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanson, W.R.

1990-12-01

Prostaglandins (PGs) have been shown to protect the gastrointestinal and hematopoietic cell renewal systems from some degree of radiation damage. The mechanism(s) to account for these observations are unknown. Based on preliminary evidence that PGs varied in the degree to which they afforded protection of intestinal stem cells, we studied protection by several PGs and their analogues. The most protective PGs found to date were 16,16 dm PGE2, misoprostol, a PGE1 analogues, and iloprost, a PGI2 analogue. The relative degrees of protection were 400%, 700% and 800% above control values at a dose of 13.5 137 Cs gamma radiation. Thesemore » three PGs were used for subsequent studies. Iloprost is a stable PG at room temperature and was found to be protective given orally. In addition to radioprotection of the intestinal stem cells, these Pgs increased the LD50/6, LD50/30 and animal longevity through both the gastrointestinal and hematopoietic syndromes. Misoprostol protected the gut from JANUS neutrons and increased animal longevity following neutron irradiation. Although the mechanism for PG-induced radioprotection is unknown, it appears to be different compared to the widely studied amino thiol, WR-2721. Evidence to support this contention came from data showing that all these analogues were additive to the protective effect of Wr-2721.« less

Understanding Rubredoxin Redox Sites by Density Functional Theory Studies of Analogues

PubMed Central

Luo, Yan; Niu, Shuqiang; Ichiye, Toshiko

2012-01-01

Determining the redox energetics of redox site analogues of metalloproteins is essential in unraveling the various contributions to electron transfer properties of these proteins. Since studies of the [4Fe-4S] analogues show that the energies are dependent on the ligand dihedral angles, broken symmetry density functional theory (BS-DFT) with the B3LYP functional and double-ζ basis sets calculations of optimized geometries and electron detachment energies of [1Fe] rubredoxin analogues are compared to crystal structures and gas-phase photoelectron spectroscopy data, respectively, for [Fe(SCH3)4]0/1-/2-, [Fe(S2-o-xyl2)]0/1-/2-, and Na+[Fe(S2-o-xyl)2]1-/2- in different conformations. In particular, the study of Na+[Fe(S2-o-xyl)2]1-/2- is the only direct comparison of calculated and experimental gas phase detachment energies for the 1-/2- couple found in the rubredoxins. These results show that variations in the inner sphere energetics by up to ~0.4 eV can be caused by differences in the ligand dihedral angles in either or both redox states. Moreover, these results indicate that the protein stabilizes the conformation that favors reduction. In addition, the free energies and reorganization energies of oxidation and reduction as well as electrostatic potential charges are calculated, which can be used as estimates in continuum electrostatic calculations of electron transfer properties of [1Fe] proteins. PMID:22881577

Characterisation of Growth and Ultrastructural Effects of the Xanthoria elegans Photobiont After 1.5 Years of Space Exposure on the International Space Station

NASA Astrophysics Data System (ADS)

Brandt, Annette; Posthoff, Eva; de Vera, Jean-Pierre; Onofri, Silvano; Ott, Sieglinde

2016-06-01

The lichen Xanthoria elegans has been exposed to space and simulated Mars-analogue environment in the Lichen and Fungi Experiment (LIFE) on the EXPOSE-E facility at the International Space Station (ISS). This long-term exposure of 559 days tested the ability of various organisms to cope with either low earth orbit (LEO) or Mars-analogue conditions, such as vacuum, Mars-analogue atmosphere, rapid temperature cycling, cosmic radiation of up to 215 ± 16 mGy, and insolation of accumulated doses up to 4.87 GJm-2, including up to 0.314 GJm-2 of UV irradiation. In a previous study, X. elegans demonstrated considerable resistance towards these conditions by means of photosynthetic activity as well as by post-exposure metabolic activity of 50-80 % in the algal and 60-90 % in the fungal symbiont (Brandt et al. Int J Astrobiol 14(3):411-425, 2015). The two objectives of the present study were complementary: First, to verify the high post-exposure viability by using a qualitative cultivation assay. Second, to characterise the cellular damages by transmission electron microscopy (TEM) which were caused by the space and Mars-analogue exposure conditions of LIFE. Since the algal symbiont of lichens is considered as the more susceptible partner (de Vera and Ott 2010), the analyses focused on the photobiont. The study demonstrated growth and proliferation of the isolated photobiont after all exposure conditions of LIFE. The ultrastructural analysis of the algal cells provided an insight to cellular damages caused by long-term exposure and highlighted that desiccation-induced breakdown of cellular integrity is more pronounced under the more severe space vacuum than under Mars-analogue atmospheric conditions. In conclusion, desiccation-induced damages were identified as a major threat to the photobiont of X. elegans. Nonetheless, a fraction of the photobiont cells remained cultivable after all exposure conditions tested in LIFE.

Influence of Unweighting on Insulin Signal Transduction in Muscle

NASA Technical Reports Server (NTRS)

Tischler, Marc E.

2002-01-01

Unweighting of the juvenile soleus muscle is characterized by an increased binding capacity for insulin relative to muscle mass due to sparing of the receptors during atrophy. Although carbohydrate metabolism and protein degradation in the unweighted muscle develop increased sensitivity to insulin in vivo, protein synthesis in vivo and system A amino acid transport in vitro do not appear to develop such an enhanced response. The long-term goal is to identify the precise nature of this apparent resistance in the insulin signal transduction pathway and to consider how reduced weight-bearing may elicit this effect, by evaluating specific components of the insulin signalling pathway. Because the insulin-signalling pathway has components in common with the signal transduction pathway for insulin-like growth factor (IGF-1) and potentially other growth factors, the study could have important implications in the role of weight-bearing function on muscle growth and development. Since the insulin signalling pathway diverges following activation of insulin receptor tyrosine kinase, the immediate specific aims will be to study the receptor tyrosine kinase (IRTK) and those branches, which lead to phosphorylation of insulin receptor substrate-1 (IRS-1) and of Shc protein. To achieve these broader objectives, we will test in situ, by intramuscular injection, the responses of glucose transport, system A amino acid transport and protein synthesis to insulin analogues for which the receptor has either a weaker or much stronger binding affinity compared to insulin. Studies will include: (1) estimation of the ED(sub 50) for each analogue for these three processes; (2) the effect of duration (one to four days) of unweighting on the response of each process to all analogues tested; (3) the effect of unweighting and the analogues on IRTK activity; and (4) the comparative effects of unweighting and analogue binding on the tyrosine phosphorylation of IRTK, IRS-1, and Shc protein.

Characterisation of Growth and Ultrastructural Effects of the Xanthoria elegans Photobiont After 1.5 Years of Space Exposure on the International Space Station.

PubMed

Brandt, Annette; Posthoff, Eva; de Vera, Jean-Pierre; Onofri, Silvano; Ott, Sieglinde

2016-06-01

The lichen Xanthoria elegans has been exposed to space and simulated Mars-analogue environment in the Lichen and Fungi Experiment (LIFE) on the EXPOSE-E facility at the International Space Station (ISS). This long-term exposure of 559 days tested the ability of various organisms to cope with either low earth orbit (LEO) or Mars-analogue conditions, such as vacuum, Mars-analogue atmosphere, rapid temperature cycling, cosmic radiation of up to 215 ± 16 mGy, and insolation of accumulated doses up to 4.87 GJm(-2), including up to 0.314 GJm(-2) of UV irradiation. In a previous study, X. elegans demonstrated considerable resistance towards these conditions by means of photosynthetic activity as well as by post-exposure metabolic activity of 50-80% in the algal and 60-90% in the fungal symbiont (Brandt et al. Int J Astrobiol 14(3):411-425, 2015). The two objectives of the present study were complementary: First, to verify the high post-exposure viability by using a qualitative cultivation assay. Second, to characterise the cellular damages by transmission electron microscopy (TEM) which were caused by the space and Mars-analogue exposure conditions of LIFE. Since the algal symbiont of lichens is considered as the more susceptible partner (de Vera and Ott 2010), the analyses focused on the photobiont. The study demonstrated growth and proliferation of the isolated photobiont after all exposure conditions of LIFE. The ultrastructural analysis of the algal cells provided an insight to cellular damages caused by long-term exposure and highlighted that desiccation-induced breakdown of cellular integrity is more pronounced under the more severe space vacuum than under Mars-analogue atmospheric conditions. In conclusion, desiccation-induced damages were identified as a major threat to the photobiont of X. elegans. Nonetheless, a fraction of the photobiont cells remained cultivable after all exposure conditions tested in LIFE.

Legumes and meat analogues consumption are associated with hip fracture risk independently of meat intake among Caucasian men and women: the Adventist Health Study-2

PubMed Central

Lousuebsakul-Matthews, Vichuda; Thorpe, Donna L; Knutsen, Raymond; Beeson, W Larry; Fraser, Gary E; Knutsen, Synnove F

2014-01-01

Objective In contrast to non-vegetarians, vegetarians consume more legumes and meat analogues as sources of protein to substitute for meat intake. The present study aimed to assess the association between foods with high protein content (legumes, meat, meat analogues) by dietary pattern (vegetarians, non-vegetarians) and hip fracture incidence, adjusted for selected lifestyle factors. Design A prospective cohort of Adventist Health Study-2 (AHS-2) enrollees who completed a comprehensive lifestyle and dietary questionnaire between 2002 and 2007. Setting Every two years after enrolment, a short questionnaire on hospitalizations and selected disease outcomes including hip fractures was sent to these members. Subjects Respondents (n 33 208) to a baseline and a follow-up questionnaire. Results In a multivariable model, legumes intake of once daily or more reduced the risk of hip fracture by 64% (hazard ratio=0·36, 95% CI 0·21, 0·61) compared with those with legumes intake of less than once weekly. Similarly, meat intake of four or more times weekly was associated with a 40% reduced risk of hip fracture (hazard ratio=0·60, 95% CI 0·41, 0·87) compared with those whose meat intake was less than once weekly. Furthermore, consumption of meat analogues once daily or more was associated with a 49% reduced risk of hip fracture (hazard ratio=0·51, 95% CI 0·27, 0·98) compared with an intake of less than once weekly. Conclusions Hip fracture incidence was inversely associated with legumes intake and, to a lesser extent, meat intake, after accounting for other food groups and important covariates. Similarly, a high intake of meat analogues was associated with a significantly reduced risk of hip fracture. PMID:24103482

Successful desensitization to Gonadotropin-releasing hormone analogue Triptorelin Acetate using a sustained-release depot preparation.

PubMed

Chan Ng, Pauline; Huang, Chiung-Hui; Rajakulendran, Mohana; Tan, Michelle Meiling; Wang, Ping Ping; Tay, Lei Qiu; Goh, Siok Ying; Shek, Lynette Pei-Chi; Tham, Elizabeth Huiwen

2018-05-29

Gonadotropin-releasing hormone (GnRH) analogues are commonly used in pediatric patients in the treatment of central precocious puberty 1 . GnRH analogues suppress the secretion of gonadotropins and sex hormones, preventing progression to advanced puberty and reduced final adult height secondary to accelerated fusion of growth plates. GnRH analogues are also used in adults for treatment of endometriosis 2 and prostatic cancer 3 . Hypersensitivity reactions to GnRH analogues are exceedingly rare 4-6 and to date, we are unaware of any desensitization protocols for GnRH hypersensitivity in the literature or used in clinical practice. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Comparative study of the effect of BPA and its selected analogues on hemoglobin oxidation, morphological alterations and hemolytic changes in human erythrocytes.

PubMed

Maćczak, Aneta; Bukowska, Bożena; Michałowicz, Jaromir

2015-01-01

Bisphenol A (BPA) has been shown to provoke many deleterious impacts on human health, and thus it is now successively substituted by BPA analogues, whose effects have been poorly investigated. Up to now, only one study has been realized to assess the effect of BPA on human erythrocytes, which showed its significant hemolytic and oxidative potential. Moreover, no study has been conducted to evaluate the effect of BPA analogues on red blood cells. The purpose of the present study was to compare the impact of BPA and its selected analogues such as bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF) on hemolytic and morphological changes and hemoglobin oxidation (methemoglobin formation) of human erythrocytes. The erythrocytes were incubated with different bisphenols concentrations ranging from 0.5 to 500μg/ml for 1, 4 and 24h. The compounds examined caused hemolysis in human erythrocytes with BPAF exhibiting the strongest effect. All bisphenols examined caused methemoglobin formation with BPA inducing the strongest oxidative potential. Flow cytometry analysis showed that all bisphenols (excluding BPS) induced significant changes in erythrocytes size. Changes in red blood cells shape were conducted using phase contrast microscopy. It was noticed that BPA and BPAF induced echinocytosis, BPF caused stomatocytosis, while BPS did not provoke significant changes in shape of red blood cells. Generally, the results showed that BPS, which is the main substituent of bisphenol A in polymers and thermal paper production, exhibited significantly lower disturbance of erythrocyte functions than BPA. Copyright © 2015 Elsevier Inc. All rights reserved.

Medical judgement analogue studies with applications to spaceflight crew medical officer

PubMed Central

McCarroll, Michele L; Ahmed, Rami A; Schwartz, Alan; Gothard, Michael David; Atkinson, Steven Scott; Hughes, Patrick; Brito, Jose Cepeda; Assad, Lori; Myers, Jerry; George, Richard L

2017-01-01

Background The National Aeronautics and Space Administration (NASA) developed plans for potential emergency conditions from the Exploration Medical Conditions List. In an effort to mitigate conditions on the Exploration Medical Conditions List, NASA implemented a crew medical officer (CMO) designation for eligible astronauts. This pilot study aims to add knowledge that could be used in the Integrated Medical Model. Methods An analogue population was recruited for two categories: administrative physicians (AP) representing the physician CMOs and technical professionals (TP) representing the non-physician CMOs. Participants completed four medical simulations focused on abdominal pain: cholecystitis (CH) and renal colic (RC) and chest pain: cardiac ischaemia (STEMI; ST-segment elevation myocardial infarction) and pneumothorax (PX). The Medical Judgment Metric (MJM) was used to evaluate medical decision making. Results There were no significant differences between the AP and TP groups in age, gender, race, ethnicity, education and baseline heart rate. Significant differences were noted in MJM average rater scores in AP versus TP in CH: 13.0 (±2.25), 4.5 (±0.48), p=<0.001; RC: 12.3 (±2.66), 4.8 (±0.94); STEMI: 12.1 (±3.33), 4.9 (±0.56); and PX: 13.5 (±2.53), 5.3 (±1.01), respectively. Discussion There could be a positive effect on crew health risk by having a physician CMO. The MJM demonstrated the ability to quantify medical judgement between the two analogue groups of spaceflight CMOs. Future studies should incorporate the MJM in a larger analogue population study to assess the medical risk for spaceflight crewmembers. PMID:29354280

Medical judgement analogue studies with applications to spaceflight crew medical officer.

PubMed

McCarroll, Michele L; Ahmed, Rami A; Schwartz, Alan; Gothard, Michael David; Atkinson, Steven Scott; Hughes, Patrick; Brito, Jose Cepeda; Assad, Lori; Myers, Jerry; George, Richard L

2017-10-01

The National Aeronautics and Space Administration (NASA) developed plans for potential emergency conditions from the Exploration Medical Conditions List. In an effort to mitigate conditions on the Exploration Medical Conditions List, NASA implemented a crew medical officer (CMO) designation for eligible astronauts. This pilot study aims to add knowledge that could be used in the Integrated Medical Model. An analogue population was recruited for two categories: administrative physicians (AP) representing the physician CMOs and technical professionals (TP) representing the non-physician CMOs. Participants completed four medical simulations focused on abdominal pain: cholecystitis (CH) and renal colic (RC) and chest pain: cardiac ischaemia (STEMI; ST-segment elevation myocardial infarction) and pneumothorax (PX). The Medical Judgment Metric (MJM) was used to evaluate medical decision making. There were no significant differences between the AP and TP groups in age, gender, race, ethnicity, education and baseline heart rate. Significant differences were noted in MJM average rater scores in AP versus TP in CH: 13.0 (±2.25), 4.5 (±0.48), p=<0.001; RC: 12.3 (±2.66), 4.8 (±0.94); STEMI: 12.1 (±3.33), 4.9 (±0.56); and PX: 13.5 (±2.53), 5.3 (±1.01), respectively. There could be a positive effect on crew health risk by having a physician CMO. The MJM demonstrated the ability to quantify medical judgement between the two analogue groups of spaceflight CMOs. Future studies should incorporate the MJM in a larger analogue population study to assess the medical risk for spaceflight crewmembers.

20170913 - Systematic Approaches to Biological/Chemical Read-Across for Hazard Identification (EMGS)

EPA Science Inventory

Read-across is a well-established data gap filling technique used within chemical category and analogue approaches for regulatory purposes. The category/analogue workflow comprises a number of steps starting from decision context, data gap analysis through to analogue identificat...

Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

PubMed Central

Tutton, P. J.; Barkla, D. H.

1980-01-01

The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours. PMID:7362778

Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

PubMed

Tutton, P J; Barkla, D H

1980-01-01

The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours.

Effect of Nucleos(t)ide Analogue Therapy on Risk of Intrahepatic Cholangiocarcinoma in Patients With Chronic Hepatitis B.

PubMed

Lee, Teng-Yu; Hsu, Yao-Chun; Yu, Shi-Hang; Lin, Jaw-Town; Wu, Ming-Shiang; Wu, Chun-Ying

2018-06-01

Chronic infection with hepatitis B virus (HBV) increases risk of intrahepatic cholangiocarcinoma (ICC), but it is not clear whether antiviral therapy reduces risk. We investigated the association between nucleos(t)ide analogue therapy and ICC risk. We performed a nationwide long-term cohort study using Taiwan's National Health Insurance Research Database to obtain data on 185,843 patients with chronic HBV infection from October 1, 2003 through December 31, 2012. We excluded patients with confounding disorders such as infection with hepatitis C virus, HIV, or other hepatitis-associated viruses; liver flukes; biliary stone diseases; cholangitis; congenital biliary anomalies; biliary tract surgeries; or cancer. We identified 10,062 patients who received nucleos(t)ide analogue therapy (the treated group), and used propensity scores to match them (1:1) with patients who received hepatoprotectants (the untreated group). Cumulative incidences of and hazard ratios (HRs) for ICC development were analyzed. The cumulative incidence of ICC was significantly lower in the treated group after 3 years of therapy (1.28%; 95% CI, 0.56-2.01) than in the untreated group (3.14%; 95% CI, 2.02-4.27) and after 5 years of therapy (1.53%; 95% CI, 0.73-2.33 vs 4.32% in untreated group; 95% CI, 2.96-5.6869). In multivariable regression analysis, nucleos(t)ide analogue therapy was independently associated with a reduced risk of ICC (HR, 0.44; 95% CI, 0.25-0.78; P = .005). Older age (HR 1.05 per year; 95% CI, 1.03-1.07) and cirrhosis (HR, 2.80; 95% CI, 1.52-5.1415) were independently associated with an increased risk of ICC. Sensitivity analyses verified the association between nucleos(t)ide analogue therapy and a reduced ICC risk. A nationwide long-term cohort study in Taiwan showed that nucleos(t)ide analogue therapy for chronic HBV infection is significantly associated with a reduced ICC risk. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

A Computational Study of Structure and Reactivity of N-Substitued-4-Piperidones Curcumin Analogues and Their Radical Anions.

PubMed

Martínez-Cifuentes, Maximiliano; Weiss-López, Boris; Araya-Maturana, Ramiro

2016-12-02

In this work, a computational study of a series of N -substitued-4-piperidones curcumin analogues is presented. The molecular structure of the neutral molecules and their radical anions, as well as their reactivity, are investigated. N -substituents include methyl and benzyl groups, while substituents on the aromatic rings cover electron-donor and electron-acceptor groups. Substitutions at the nitrogen atom do not significantly affect the geometry and frontier molecular orbitals (FMO) energies of these molecules. On the other hand, substituents on the aromatic rings modify the distribution of FMO. In addition, they influence the capability of these molecules to attach an additional electron, which was studied through adiabatic (AEA) and vertical electron affinities (VEA), as well as vertical detachment energy (VDE). To study electrophilic properties of these structures, local reactivity indices, such as Fukui ( f ⁺) and Parr ( P ⁺) functions, were calculated, and show the influence of the aromatic rings substituents on the reactivity of α,β-unsaturated ketones towards nucleophilic attack. This study has potential implications for the design of curcumin analogues based on a 4-piperidone core with desired reactivity.

A Systematic Exploration of Macrocyclization in Apelin-13: Impact on Binding, Signaling, Stability, and Cardiovascular Effects.

PubMed

Trân, Kien; Murza, Alexandre; Sainsily, Xavier; Coquerel, David; Côté, Jérôme; Belleville, Karine; Haroune, Lounès; Longpré, Jean-Michel; Dumaine, Robert; Salvail, Dany; Lesur, Olivier; Auger-Messier, Mannix; Sarret, Philippe; Marsault, Éric

2018-03-22

The apelin receptor generates increasing interest as a potential target across several cardiovascular indications. However, the short half-life of its cognate ligands, the apelin peptides, is a limiting factor for pharmacological use. In this study, we systematically explored each position of apelin-13 to find the best position to cyclize the peptide, with the goal to improve its stability while optimizing its binding affinity and signaling profile. Macrocyclic analogues showed a remarkably higher stability in rat plasma (half-life >3 h versus 24 min for Pyr-apelin-13), accompanied by improved affinity (analogue 15, K i 0.15 nM and t 1/2 6.8 h). Several compounds displayed higher inotropic effects ex vivo in the Langendorff isolated heart model in rats (analogues 13 and 15, maximum response at 0.003 nM versus 0.03 nM of apelin-13). In conclusion, this study provides stable and active compounds to better characterize the pharmacology of the apelinergic system.

Engineered jadomycin analogues with altered sugar moieties revealing JadS as a substrate flexible O-glycosyltransferase.

PubMed

Li, Liyuan; Pan, Guohui; Zhu, Xifen; Fan, Keqiang; Gao, Wubin; Ai, Guomin; Ren, Jinwei; Shi, Mingxin; Olano, Carlos; Salas, José A; Yang, Keqian

2017-07-01

Glycosyltransferases (GTs)-mediated glycodiversification studies have drawn significant attention recently, with the goal of generating bioactive compounds with improved pharmacological properties by diversifying the appended sugars. The key to achieving glycodiversification is to identify natural and/or engineered flexible GTs capable of acting upon a broad range of substrates. Here, we report the use of a combinatorial biosynthetic approach to probe the substrate flexibility of JadS, the GT in jadomycin biosynthesis, towards different non-native NDP-sugar substrates, enabling us to identify six jadomycin B analogues with different sugar moieties. Further structural engineering by precursor-directed biosynthesis allowed us to obtain 11 new jadomycin analogues. Our results for the first time show that JadS is a flexible O-GT that can utilize both L- and D- sugars as donor substrates, and tolerate structural changes at the C2, C4 and C6 positions of the sugar moiety. JadS may be further exploited to generate novel glycosylated jadomycin molecules in future glycodiversification studies.

Eco-Friendly Insecticide Discovery via Peptidomimetics: Design, Synthesis, and Aphicidal Activity of Novel Insect Kinin Analogues.

PubMed

Zhang, Chuanliang; Qu, Yanyan; Wu, Xiaoqing; Song, Dunlun; Ling, Yun; Yang, Xinling

2015-05-13

Insect kinin neuropeptides are pleiotropic peptides that are involved in the regulation of hindgut contraction, diuresis, and digestive enzyme release. They share a common C-terminal pentapeptide sequence of Phe(1)-Xaa(2)-Yaa(3)-Trp(4)-Gly(5)-NH2 (where Xaa(2) = His, Asn, Phe, Ser, or Tyr; Yaa(3) = Pro, Ser, or Ala). Recently, the aphicidal activity of insect kinin analogues has attracted the attention of researchers. Our previous work demonstrated that the sequence-simplified insect kinin pentapeptide analogue Phe-Phe-[Aib]-Trp-Gly-NH2 could retain good aphicidal activity and be the lead compound for the further discovery of eco-friendly insecticides which encompassed a broad array of biochemicals derived from micro-organisms and other natural sources. Using the peptidomimetics strategy, we chose Phe-Phe-[Aib]-Trp-Gly-NH2 as the lead compound, and we designed and synthesized three series, including 31 novel insect kinin analogues. The aphicidal activity of the new analogues against soybean aphid was determined. The results showed that all of the analogues exhibited aphicidal activity. Of particular interest was the analogue II-1, which exhibited improved aphicidal activity with an LC50 of 0.019 mmol/L compared with the lead compound (LC50 = 0.045 mmol/L) or the commercial insecticide pymetrozine (LC50 = 0.034 mmol/L). This suggests that the analogue II-1 could be used as a new lead for the discovery of potential eco-friendly insecticides.

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing.

PubMed

Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Mårtensson, Martin; Strid, Mette Aagaard; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid Brück

2017-06-01

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin analogues. Human insulin (HI) is frequently used as a reference compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model.

Simulation of Martian surface conditions and dust transport

NASA Astrophysics Data System (ADS)

Nørnberg, P.; Merrison, J. P.; Finster, K.; Folkmann, F.; Gunnlaugsson, H. P.; Hansen, A.; Jensen, J.; Kinch, K.; Lomstein, B. Aa.; Mugford, R.

2002-11-01

The suspended atmospheric dust which is also found deposited over most of the Martian globe plays an important (possibly vital) role in shaping the surface environment. It affects the weather (solar flux), water transport and possibly also the electrical properties at the surface. The simulation facilities at Aarhus provide excellent tools for studying the properties of this Martian environment. Much can be learned from such simulations, supporting and often inspiring new investigations of the planet. Electrical charging of a Mars analogue dust is being studied within a wind tunnel simulation aerosol. Here electric fields are used to extract dust from suspension. Although preliminary the results indicate that a large fraction of the dust is charged to a high degree, sufficient to dominate adhesion/cohesion processes. A Mars analogue dust layer has been shown to be an excellent trap for moisture, causing increased humidity in the soil below. This allows the possibility for liquid water to be stable close to the surface (less than 10 cm). This is being investigated in an environment simulator where heat and moisture transport can be studied through layers of Mars analogue dust.

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

NASA Astrophysics Data System (ADS)

Mock, Cary Jeffrey

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

Nano-LC-MS/MS for Quantification of Lyso-Gb3 and Its Analogues Reveals a Useful Biomarker for Fabry Disease

PubMed Central

Sueoka, Hideaki; Ichihara, Junji; Tsukimura, Takahiro; Togawa, Tadayasu; Sakuraba, Hitoshi

2015-01-01

Biomarkers useful for diagnosis and evaluation of treatment for patients with Fabry disease are urgently needed. Recently, plasma globotriaosylsphingosine (lyso-Gb3) and lyso-Gb3-related analogues have attracted attention as promising biomarkers of Fabry disease. However, the plasma concentrations of lyso-Gb3 and its analogues are extremely low or below the detection limits in some Fabry patients as well as in healthy subjects. In this paper, we introduce the novel application of a nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) system to the measurement of lyso-Gb3 and its analogues in plasma. Nano-LC-MS/MS requires smaller amounts of samples and is more sensitive than conventional techniques. Using this method, we measured the plasma concentrations of lyso-Gb3 and its analogues in 40 healthy subjects, 5 functional variants (males with E66Q), and various Fabry patients (9 classic Fabry males/9 mutations; 7 later-onset Fabry males/5 mutations; and 10 Fabry females/9 mutations). The results revealed that the mean lyso-Gb3 and lyso-Gb3(-2) concentrations in all the Fabry patient subgroups were statistically higher, especially in the classic Fabry males, than those in the functional variants and healthy subjects. The plasma concentrations of lyso-Gb3 and its analogues in healthy subjects, functional variants, and some Fabry patients with specific mutations (R112H and M296I) that cannot be established by conventional techniques were successfully determined by means of nano-LC-MS/MS. The lyso-Gb3 and lyso-Gb3(-2) concentrations in male patients with these mutations were lower than those in most Fabry patients having other mutations, but higher than those in the functional variants and healthy subjects. This new method is expected to be useful for sensitive determination of the plasma concentrations of lyso-Gb3 and its analogues. This study also revealed that not only lyso-Gb3 but also lyso-Gb3(-2) in plasma is a useful biomarker for the diagnosis of Fabry disease. PMID:25965380

Synthesis and preliminary antileukemic studies of cyclic mitoguazone analogues.

PubMed

Krezel, I; Graczyk, J

1998-03-01

Analogues of mitoguazone bearing a terminal amidino group as a part of the seven-membered ring of 1,3-diazepine and six-membered ring of pyrimidine were prepared in order to evaluate in vivo antileukemic action towards L1210 leukemia in mice. Preliminary pharmacological screening showed that the investigated compounds increase the life span (T/C%) of the treated mice in comparison with the untreated animals. The strongest antineoplastic effect was exhibited by compound 8.

Comparison of the impact of human vs analogue insulins on glycosylated haemoglobin in a population with diabetes mellitus.

PubMed

Machado-Alba, Jorge Enrique; Medina-Morales, Diego Alejandro

2016-12-01

To compare the effect on metabolic control of treatment with conventional and analogue insulins for patients with diabetes mellitus. Retrospective cohort study held in cities of Colombia (Pereira and Manizales). People insured by the paid healthcare system, who were diagnosed with diabetes mellitus type 1 and 2, and treated with conventional and analogue insulin for at least 6 months prior to the start of the study were sampled and followed up for 18 months. Data were collected from clinical records for each patient. Treatment groups were compared according to the type of insulin received. A total of 313 patients were included; overall, 56.9% were women and the mean age was 57.3 years. No statistically significant difference was found in glycosylated haemoglobin reduction at 3, 6 and 18 months when comparing patients receiving glargine vs NPH insulin (P=.403) and NPH plus zinc crystalline insulin vs glargine plus glulisine (P=.514). The percentage of patients with metabolic control increased from 27.8% to 34.2% during follow-up with all types of insulin. Insulin analogues were not superior to human insulin for glycaemic control. A significant proportion of patients did not attain the treatment goals; therefore, it is necessary to implement measures to improve the monitoring and control of diabetes mellitus. © 2016 John Wiley & Sons Ltd.

Structure based comprehensive modelling, spatial fingerprints mapping and ADME screening of curcumin analogues as novel ALR2 inhibitors

PubMed Central

Verma, Sant Kumar

2017-01-01

Aldose reductase (ALR2) inhibition is the most legitimate approach for the management of diabetic complications. The limited triumph in the drug development against ALR2 is mainly because of its close structural similarity with the other members of aldo-keto reductase (AKR) superfamily viz. ALR1, AKR1B10; and lipophilicity problem i.e. poor diffusion of synthetic aldose reductase inhibitors (ARIs) to target tissues. The literature evidenced that naturally occurring curcumin demonstrates relatively specific and non-competitive inhibition towards human recombinant ALR2 over ALR1 and AKR1B10; however β-diketone moiety of curcumin is a specific substrate for liver AKRs and accountable for it’s rapid in vivo metabolism. In the present study, structure based comprehensive modelling studies were used to map the pharmacophoric features/spatial fingerprints of curcumin analogues responsible for their ALR2 specificity along with potency on a data set of synthetic curcumin analogues and naturally occurring curcuminoids. The data set molecules were also screened for drug-likeness or ADME parameters, and the screening data strongly support that curcumin analogues could be proposed as a good drug candidate for the development of ALR2 inhibitors with improved pharmacokinetic profile compared to curcuminoids due to the absence of β-diketone moiety in their structural framework. PMID:28399135

Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin.

PubMed

Deck, Lorraine M; Hunsaker, Lucy A; Vander Jagt, Thomas A; Whalen, Lisa J; Royer, Robert E; Vander Jagt, David L

2018-01-01

Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC 50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues. Copyright © 2017. Published by Elsevier Masson SAS.

A precision analogue integrator system for heavy current measurement in MFDC resistance spot welding

NASA Astrophysics Data System (ADS)

Xia, Yu-Jun; Zhang, Zhong-Dian; Xia, Zhen-Xin; Zhu, Shi-Liang; Zhang, Rui

2016-02-01

In order to control and monitor the quality of middle frequency direct current (MFDC) resistance spot welding (RSW), precision measurement of the welding current up to 100 kA is required, for which Rogowski coils are the only viable current transducers at present. Thus, a highly accurate analogue integrator is the key to restoring the converted signals collected from the Rogowski coils. Previous studies emphasised that the integration drift is a major factor that influences the performance of analogue integrators, but capacitive leakage error also has a significant impact on the result, especially in long-time pulse integration. In this article, new methods of measuring and compensating capacitive leakage error are proposed to fabricate a precision analogue integrator system for MFDC RSW. A voltage holding test is carried out to measure the integration error caused by capacitive leakage, and an original integrator with a feedback adder is designed to compensate capacitive leakage error in real time. The experimental results and statistical analysis show that the new analogue integrator system could constrain both drift and capacitive leakage error, of which the effect is robust to different voltage levels of output signals. The total integration error is limited within  ±0.09 mV s-1 0.005% s-1 or full scale at a 95% confidence level, which makes it possible to achieve the precision measurement of the welding current of MFDC RSW with Rogowski coils of 0.1% accuracy class.

The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs

PubMed Central

Sun, Yubo; Kiraly, Alex J.; Cox, Michael; Mauerhan, David R.; Hanley, Edward N.

2018-01-01

Phosphocitrate (PC) and its analogue, PC-β ethyl ester, inhibit articular cartilage degeneration in Hartley guinea pigs. However, the underlying molecular mechanisms remain unclear. The present study aimed to investigate the hypothesis that PC exerted its disease-modifying effect on osteoarthritis (OA), in part, by inhibiting a molecular program similar to that in the endochondral pathway of ossification. The results demonstrated that severe proteoglycan loss occurred in the superficial and middle zones, as well as in the calcified zone of articular cartilage in the Hartley guinea pigs. Subchondral bone advance was greater in the control Hartley guinea pigs compared with PC- or PC analogue-treated guinea pigs. Resorption of cartilage bars or islands and vascular invasion in the growth plate were also greater in the control guinea pigs compared with the PC- or PC analogue-treated guinea pigs. The levels of matrix metalloproteinase-13 and type X collagen within the articular cartilage and growth plate were significantly increased in the control guinea pigs compared with PC-treated guinea pigs (P<0.05). These results indicated that articular chondrocytes in Hartley guinea pigs exhibited a hypertrophic phenotype and recapitulated a developmental molecular program similar to the endochondral pathway of ossification. Activation of this molecular program resulted in resorption of calcified articular cartilage and subchondral bone advance. This suggests that PC and PC analogues exerted their OA disease-modifying activity, in part, by inhibiting this molecular program. PMID:29545850

Examining the base stacking interaction in a dinucleotide context via reversible cyclobutane dimer analogue formation under UV irradiation.

PubMed

Liu, Degang; Li, Lei

2013-11-14

Substituted tolyl groups are considered as close isosteres of the thymine (T) residue. They can be recognized by DNA polymerases as if they were thymine. Although these toluene derivatives are relatively inert toward radical additions, our recent finding suggests that the dinucleotide analogue TpTo (To = 2'-deoxy-1-(3-tolyl)-β-D-ribofuranose) supports an ortho photocycloaddition reaction upon UV irradiation, producing two cyclobutane pyrimidine dimer (CPD) analogues 2 and 3 . Our report here further shows that formation of these CPD species is reversible under UVC irradiation, resembling the photochemical property of the CPD species formed between two Ts. Analyzing the stability of these CPD analogues suggests that one ( 2 ) is more stable than the other ( 3 ). The TpTo conformer responsible for 2 formation is also more stable than that responsible for 3 formation, as indicated by the Gibbs free energy change calculated from the constructed Bordwell thermodynamic cycle. These different stabilities are not due to the varying photochemical properties, as proved by quantum yields determined from the corresponding photoreactions. Instead, they are ascribed to the different stacking interaction between the T and the To rings both in the TpTo dinucleotide as well as in the formed CPD analogues. Factors contributing to the ring stacking interactions are also discussed. Our proof-of-concept approach suggests that a carefully designed Bordwell cycle coupled with reversible CPD formations under UV irradiation can be very useful in studying DNA base interactions.

Examining the base stacking interaction in a dinucleotide context via reversible cyclobutane dimer analogue formation under UV irradiation

PubMed Central

Liu, Degang; Li, Lei

2013-01-01

Substituted tolyl groups are considered as close isosteres of the thymine (T) residue. They can be recognized by DNA polymerases as if they were thymine. Although these toluene derivatives are relatively inert toward radical additions, our recent finding suggests that the dinucleotide analogue TpTo (To = 2'-deoxy-1-(3-tolyl)-β-D-ribofuranose) supports an ortho photocycloaddition reaction upon UV irradiation, producing two cyclobutane pyrimidine dimer (CPD) analogues 2 and 3. Our report here further shows that formation of these CPD species is reversible under UVC irradiation, resembling the photochemical property of the CPD species formed between two Ts. Analyzing the stability of these CPD analogues suggests that one (2) is more stable than the other (3). The TpTo conformer responsible for 2 formation is also more stable than that responsible for 3 formation, as indicated by the Gibbs free energy change calculated from the constructed Bordwell thermodynamic cycle. These different stabilities are not due to the varying photochemical properties, as proved by quantum yields determined from the corresponding photoreactions. Instead, they are ascribed to the different stacking interaction between the T and the To rings both in the TpTo dinucleotide as well as in the formed CPD analogues. Factors contributing to the ring stacking interactions are also discussed. Our proof-of-concept approach suggests that a carefully designed Bordwell cycle coupled with reversible CPD formations under UV irradiation can be very useful in studying DNA base interactions. PMID:24223299

Synthesis and biological evaluation of febrifugine analogues.

PubMed

Mai, Huong Doan Thi; Thanh, Giang Vo; Tran, Van Hieu; Vu, Van Nam; Vu, Van Loi; Le, Cong Vinh; Nguyen, Thuy Linh; Phi, Thi Dao; Truong, Bich Ngan; Chau, Van Minh; Pham, Van Cuong

2014-12-01

A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.

Novel synthesis of cyclic amide-linked analogues of angiotensins II and III.

PubMed

Matsoukas, J M; Hondrelis, J; Agelis, G; Barlos, K; Gatos, D; Ganter, R; Moore, D; Moore, G J

1994-09-02

Cyclic amide-linked angiotension II (ANGII) analogues have been synthesized by novel strategies, in an attempt to test the ring clustering and the charge relay bioactive conformation recently suggested. These analogues were synthesized by connecting side chain amino and carboxyl groups at positions 1 and 8, 2 and 8, 3 and 8, and 3 and 5, N-terminal amino and C-terminal carboxyl groups at positions 1 and 8, 2 and 8, and 4 and 8, and side chain amino to C-terminal carboxyl group at positions 1 and 8. All these analogues were biologically inactive, except for cyclic [Sar1, Asp3, Lys5]ANGII (analogue 10) which had high contractile activity in the rat uterus assay (30% of ANGII) and [Lys1, Tyr(Me)4, Glu8]ANGII (analogue 7) which had weak antagonist activity (PA2 approximately 6). Precyclic linear peptides synthesized using 2-chlorotrityl chloride resin and N alpha-Fmoc-amino acids with suitable side chain protection were obtained in high yield and purity and were readily cyclized with benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate as coupling reagent. Molecular modeling suggests that the ring structure of the potent analogue can be accommodated in the charge relay conformation proposed for ANGII.

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

PubMed Central

Satishkumar, Sakilam; Vuram, Prasanna K.; Relangi, Siva Subrahmanyam; Gurram, Venkateshwarlu; Zhou, Hong; Kreitman, Robert J.; Montemayor, Michelle M. Martínez; Yang, Lijia; Kaliyaperumal, Muralidharan; Sharma, Somesh; Pottabathini, Narender; Lakshman, Mahesh K.

2016-01-01

Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest on the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL), and chronic lymphocytic leukemia (CLL) cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribo analogue of cladribine possessed activity, but was least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, only cladribine and its ribose analogue were most active. PMID:26556315

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

PubMed

Satishkumar, Sakilam; Vuram, Prasanna K; Relangi, Siva Subrahmanyam; Gurram, Venkateshwarlu; Zhou, Hong; Kreitman, Robert J; Montemayor, Michelle M Martínez; Yang, Lijia; Kaliyaperumal, Muralidharan; Sharma, Somesh; Pottabathini, Narender; Lakshman, Mahesh K

2015-10-09

Cladribine, 2-chloro-2'-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O⁶-(benzotriazol-1-yl)-2'-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic leukemia (CLL), cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribose analogue of cladribine showed activity, but was the least active among the C6-NH₂-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, cladribine and its ribose analogue were most active.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Apps, J.A.

1995-09-01

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

Chemical tailoring of teicoplanin with site-selective reactions.

PubMed

Pathak, Tejas P; Miller, Scott J

2013-06-05

Semisynthesis of natural product derivatives combines the power of fermentation with orthogonal chemical reactions. Yet, chemical modification of complex structures represents an unmet challenge, as poor selectivity often undermines efficiency. The complex antibiotic teicoplanin eradicates bacterial infections. However, as resistance emerges, the demand for improved analogues grows. We have discovered chemical reactions that achieve site-selective alteration of teicoplanin. Utilizing peptide-based additives that alter reaction selectivities, certain bromo-teicoplanins are accessible. These new compounds are also scaffolds for selective cross-coupling reactions, enabling further molecular diversification. These studies enable two-step access to glycopeptide analogues not available through either biosynthesis or rapid total chemical synthesis alone. The new compounds exhibit a spectrum of activities, revealing that selective chemical alteration of teicoplanin may lead to analogues with attenuated or enhanced antibacterial properties, in particular against vancomycin- and teicoplanin-resistant strains.

Visualizing ferromagnetic domains in undoped and Fe-doped Sr4Ru3O10

NASA Astrophysics Data System (ADS)

Sass, Paul; Wu, Weida; Mao, Zhiqiang; Li, Peigang

Transition-metal oxides have proven to be a great source of interesting phenomena and new quantum phases of matter with high potential for developing exciting technologies. A remarkable sub-class of these materials with layer dependent properties is the ruthenium perovskites of the Ruddlesden-Popper series, specifically Srn + 1RunO3 n + 1 , exhibiting a range of behavior from ferromagnetism and metamagnetic quantum criticality to p-wave superconductivity. The triple layered oxide Sr4Ru3O10 exhibits coexistence of ferro- (TC < 105 K) and meta- (TM < 50 K) magnetism with strong anisotropy. Despite many studies on bulk magnetic properties of this material, the microscopic nature of the magnetic phase is still unclear. What is lacking is the real space imaging of magnetic domains. To this end, we report our variable temperature magnetic force microscopy studies on floating-zone grown undoped and Fe-doped Sr4Ru3O10 single crystals. Various stripe and branch-like domain patterns were observed below This work is supported by DOE BES under award DE-SC0008147.

Pyroelectricity of silicon-doped hafnium oxide thin films

NASA Astrophysics Data System (ADS)

Jachalke, Sven; Schenk, Tony; Park, Min Hyuk; Schroeder, Uwe; Mikolajick, Thomas; Stöcker, Hartmut; Mehner, Erik; Meyer, Dirk C.

2018-04-01

Ferroelectricity in hafnium oxide thin films is known to be induced by various doping elements and in solid-solution with zirconia. While a wealth of studies is focused on their basic ferroelectric properties and memory applications, thorough studies of the related pyroelectric properties and their application potential are only rarely found. This work investigates the impact of Si doping on the phase composition and ferro- as well as pyroelectric properties of thin film capacitors. Dynamic hysteresis measurements and the field-free Sharp-Garn method were used to correlate the reported orthorhombic phase fractions with the remanent polarization and pyroelectric coefficient. Maximum values of 8.21 µC cm-2 and -46.2 µC K-1 m-2 for remanent polarization and pyroelectric coefficient were found for a Si content of 2.0 at%, respectively. Moreover, temperature-dependent measurements reveal nearly constant values for the pyroelectric coefficient and remanent polarization over the temperature range of 0 ° C to 170 ° C , which make the material a promising candidate for IR sensor and energy conversion applications beyond the commonly discussed use in memory applications.

Hybrid-exchange density-functional theory study of the electronic structure of MnV2O4 : Exotic orbital ordering in the cubic structure

NASA Astrophysics Data System (ADS)

Wu, Wei

2015-05-01

The electronic structures of cubic and tetragonal MnV2O4 have been studied using hybrid-exchange density-functional theory. The computed electronic structure of the tetragonal phase shows an antiferro-orbital ordering on V sites and a ferrimagnetic ground state (the spins on V and Mn are antialigned). These results are in good agreement with the previous theoretical result obtained from the local-density approximation + U methods [S. Sarkar et al., Phys. Rev. Lett. 102, 216405 (2009), 10.1103/PhysRevLett.102.216405]. Moreover, the electronic structure, especially the projected density of states of the cubic phase, has been predicted with good agreement with the recent soft x-ray spectroscopy experiment. Similar to the tetragonal phase, the spins on V and Mn in the cubic structure favor a ferrimagnetic configuration. Most interesting is that the computed charge densities of the spin-carrying orbitals on V in the cubic phase show an exotic orbital ordering, i.e., a ferro-orbital ordering along [110] but an antiferro-orbital ordering along [1 ¯10 ] .

Revisiting the Birth of 7YSZ Thermal Barrier Coatings: Steve Stecura

NASA Technical Reports Server (NTRS)

Smialek, James L.; Miller, Robert A.

2017-01-01

Thermal barrier coatings are widely used in all turbine engines, typically using a 7 wt% Y2O3-ZrO2 formulation. Extensive research and development over many decades have refined the processing and structure of these coatings for increased durability and reliability. New compositions demonstrate some unique advantages and are gaining in application. However, the "7YSZ" formulation predominates and is still in widespread use. This special composition has been universally found to produce nanoscale precipitates of metastable t' tetragonal phase, giving rise to a unique toughening mechanism via ferro-elastic switching under stress. This note recalls the original study that identified superior properties of 6 to 8 wt% YSZ plasma sprayed thermal barrier coatings, published in 1978. The impact of this discovery, arguably, continues in some form to this day. At one point, 7YSZ thermal barrier coatings were used in every new aircraft and ground power turbine engine produced worldwide. It is a tribute to its inventor, Dr. Stephan J. Stecura, NASA retiree.

Uniaxial strain control of spin-polarization in multicomponent nematic order of BaFe 2As 2

DOE PAGES

Kissikov, T.; Sarkar, R.; Lawson, M.; ...

2018-03-13

The iron-based high temperature superconductors exhibit a rich phase diagram reflecting a complex interplay between spin, lattice, and orbital degrees of freedom. The nematic state observed in these compounds epitomizes this complexity, by entangling a real-space anisotropy in the spin fluctuation spectrum with ferro-orbital order and an orthorhombic lattice distortion. A subtle and less-explored facet of the interplay between these degrees of freedom arises from the sizable spin-orbit coupling present in these systems, which translates anisotropies in real space into anisotropies in spin space. We present nuclear magnetic resonance studies, which reveal that the magnetic fluctuation spectrum in the paramagneticmore » phase of BaFe 2As 2 acquires an anisotropic response in spin-space upon application of a tetragonal symmetry-breaking strain field. Lastly, our results unveil an internal spin structure of the nematic order parameter, indicating that electronic nematic materials may offer a route to magneto-mechanical control.« less

Longitudinal magnetization dynamics in Heisenberg magnets: Spin Green functions approach (Review Article)

NASA Astrophysics Data System (ADS)

Krivoruchko, V. N.

2017-11-01

In spite of the fact that dynamical properties of magnets have been extensively studied over the past years, the longitudinal magnetization dynamics is still much less understood than transverse one even in the equilibrium state of a system. In this paper, we give a review of existing, based on quantum-mechanical approach, theoretical descriptions of the longitudinal magnetization dynamics for ferro-, ferri- and antiferromagnetic dielectrics. The aim is to reveal specific features of this type of magnetization vibrations under description a system within the framework of one of the basic model theory of magnetism—the Heisenberg model. Related experimental investigations as well as open questions are also briefly discussed. We hope that understanding of the longitudinal magnetization dynamics distinctive features in the equilibrium state have to be a reference point for a theory uncovering the physical mechanisms that govern ultrafast spin dynamics after femtosecond laser pulse demagnetization when a system is far beyond an equilibrium state.

Identification of methionine aminopeptidase 2 as a molecular target of the organoselenium drug ebselen and its derivatives/analogues: Synthesis, inhibitory activity and molecular modeling study.

PubMed

Węglarz-Tomczak, Ewelina; Burda-Grabowska, Małgorzata; Giurg, Mirosław; Mucha, Artur

2016-11-01

A collection of twenty-six organoselenium compounds, ebselen and its structural analogues, provided a novel approach for inhibiting the activity of human methionine aminopeptidase 2 (MetAP2). This metalloprotease, being responsible for the removal of the amino-terminal methionine from newly synthesized proteins, plays a key role in angiogenesis, which is essential for the progression of diseases, including solid tumor cancers. In this work, we discovered that ebselen, a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity, inhibits one of the main enzymes in the tumor progression pathway. Using three-step synthesis, we obtained twenty-five ebselen derivatives/analogues, ten of which are new, and tested their inhibitory activity toward three neutral aminopeptidases (MetAP2, alanine and leucine aminopeptidases). All of the tested compounds proved to be selective, slow-binding inhibitors of MetAP2. Similarly to ebselen, most of its analogues exhibited a moderate potency (IC 50 =1-12μM). Moreover, we identified three strong inhibitors that bind favorably to the enzyme with the half maximal inhibitory concentration in the submicromolar range. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biologically relevant conformational features of linear and cyclic proteolipid protein (PLP) peptide analogues obtained by high-resolution nuclear magnetic resonance and molecular dynamics

NASA Astrophysics Data System (ADS)

Kordopati, Golfo G.; Tzoupis, Haralambos; Troganis, Anastassios N.; Tsivgoulis, Gerasimos M.; Golic Grdadolnik, Simona; Simal, Carmen; Tselios, Theodore V.

2017-09-01

Proteolipid protein (PLP) is one of the main proteins of myelin sheath that are destroyed during the progress of multiple sclerosis (MS). The immunodominant PLP139-151 epitope is known to induce experimental autoimmune encephalomyelitis (EAE, animal model of MS), wherein residues 144 and 147 are recognized by T cell receptor (TCR) during the formation of trimolecular complex with peptide-antigen and major histocompability complex. The conformational behavior of linear and cyclic peptide analogues of PLP, namely PLP139-151 and cyclic (139-151) (L144, R147) PLP139-151, have been studied in solution by means of nuclear magnetic resonance (NMR) methods in combination with unrestrained molecular dynamics simulations. The results indicate that the side chains of mutated amino acids in the cyclic analogue have different spatial orientation compared with the corresponding side chains of the linear analogue, which can lead to reduced affinity to TCR. NMR experiments combined with theoretical calculations pave the way for the design and synthesis of potent restricted peptides of immunodominant PLP139-151 epitope as well as non peptide mimetics that rises as an ultimate goal.

Pro Free Will Priming Enhances “Risk-Taking” Behavior in the Iowa Gambling Task, but Not in the Balloon Analogue Risk Task: Two Independent Priming Studies

PubMed Central

Schrag, Yann; Tremea, Alessandro; Lagger, Cyril; Ohana, Noé; Mohr, Christine

2016-01-01

Studies indicated that people behave less responsibly after exposure to information containing deterministic statements as compared to free will statements or neutral statements. Thus, deterministic primes should lead to enhanced risk-taking behavior. We tested this prediction in two studies with healthy participants. In experiment 1, we tested 144 students (24 men) in the laboratory using the Iowa Gambling Task. In experiment 2, we tested 274 participants (104 men) online using the Balloon Analogue Risk Task. In the Iowa Gambling Task, the free will priming condition resulted in more risky decisions than both the deterministic and neutral priming conditions. We observed no priming effects on risk-taking behavior in the Balloon Analogue Risk Task. To explain these unpredicted findings, we consider the somatic marker hypothesis, a gain frequency approach as well as attention to gains and / or inattention to losses. In addition, we highlight the necessity to consider both pro free will and deterministic priming conditions in future studies. Importantly, our and previous results indicate that the effects of pro free will and deterministic priming do not oppose each other on a frequently assumed continuum. PMID:27018854

Pro Free Will Priming Enhances "Risk-Taking" Behavior in the Iowa Gambling Task, but Not in the Balloon Analogue Risk Task: Two Independent Priming Studies.

PubMed

Schrag, Yann; Tremea, Alessandro; Lagger, Cyril; Ohana, Noé; Mohr, Christine

2016-01-01

Studies indicated that people behave less responsibly after exposure to information containing deterministic statements as compared to free will statements or neutral statements. Thus, deterministic primes should lead to enhanced risk-taking behavior. We tested this prediction in two studies with healthy participants. In experiment 1, we tested 144 students (24 men) in the laboratory using the Iowa Gambling Task. In experiment 2, we tested 274 participants (104 men) online using the Balloon Analogue Risk Task. In the Iowa Gambling Task, the free will priming condition resulted in more risky decisions than both the deterministic and neutral priming conditions. We observed no priming effects on risk-taking behavior in the Balloon Analogue Risk Task. To explain these unpredicted findings, we consider the somatic marker hypothesis, a gain frequency approach as well as attention to gains and / or inattention to losses. In addition, we highlight the necessity to consider both pro free will and deterministic priming conditions in future studies. Importantly, our and previous results indicate that the effects of pro free will and deterministic priming do not oppose each other on a frequently assumed continuum.

Invariom based electron density studies on the C/Si analogues haloperidol/sila-haloperidol and venlafaxine/sila-venlafaxine.

PubMed

Luger, Peter; Dittrich, Birger; Tacke, Reinhold

2015-09-14

The subjects of this study are the structures and electron densities of the carbon/silicon analogues haloperidol/sila-haloperidol (1a/1b) and venlafaxine/sila-venlafaxine (2a/2b). The parent carbon compounds 1a (an antipsychotic agent) and 2a (an antidepressant) are both in clinical use. For haloperidol/sila-haloperidol, three published structures were studied in more detail: the structures of haloperidol hydrochloride (1a·HCl), haloperidol hydropicrate (1a·HPic) and sila-haloperidol hydrochloride (1b·HCl). For venlafaxine/sila-venlafaxine, the published structures of venlafaxine (2a), venlafaxine hydrochloride (2a·HCl; as orthorhombic (2a·HCl-ortho) and monoclinic polymorph (2a·HCl-mono)) and sila-venlafaxine hydrochloride (2b·HCl) were investigated. Based on these structures, the molecular electron densities were reconstructed by using the invariom formalism. They were further analysed in terms of Bader's quantum theory of atoms in molecules, electrostatic potentials mapped onto electron density isosurfaces and Hirshfeld surfaces. These studies were performed with a special emphasis on the comparison of the corresponding carbon/silicon analogues.

Synthesis, fungicidal activity, structure-activity relationships (SARs) and density functional theory (DFT) studies of novel strobilurin analogues containing arylpyrazole rings.

PubMed

Liu, Yuanyuan; Lv, Kunzhi; Li, Yi; Nan, Qiuli; Xu, Jinyuan

2018-05-18

A series of novel strobilurin analogues (1a-1f, 2a-2e, 3a-3e) containing arylpyrazole rings were synthesized and characterized by NMR spectroscopy. The structures of 1f, 2b and 3b were also determined by single crystal X-ray diffraction analysis. These analogues were collected together with other twenty-eight similar compounds 4a-4f, 5a-5h, 6a-6h and 7a-7f from our previous studies, for in vitro bioassays and thorough structure-activity relationships (SARs) studies. Most compounds exhibited excellent-to-good fungicidal activity against Rhizoctonia solani, especially 5c, 7a, 6c, and 3b with 98.94%, 83.40%, 71.40% and 65.87% inhibition rates at 0.1 μg mL -1 , respectively, better than commercial pyraclostrobin. Comparative molecular field analysis (CoMFA) was employed to study three-dimensional quantitative structure-activity relationships (3D-QSARs). Density functional theory (DFT) calculation was also carried out to provide more information regarding SARs. The present work provided some hints for developing novel strobilurin fungicides.

Synthesis and solution conformation studies of the modified nucleoside N(4),2'-O-dimethylcytidine (m(4)Cm) and its analogues.

PubMed

Mahto, Santosh K; Chow, Christine S

2008-10-01

The dimethylated ribosomal nucleoside m(4)Cm and its monomethylated analogues Cm and m(4)C were synthesized. The conformations (syn vs anti) of the three modified nucleosides and cytidine were determined by CD and 1D NOE difference spectroscopy. The ribose sugar puckers were determined by the use of proton coupling constants. The position of modification (e.g., O vs N methylation) was found to have an effect on the sugar pucker of cytidine.

Drug Evaluation in the Plasmodium falciparum - Aotus Model

DTIC Science & Technology

1984-09-01

consecutive days to Colombian Aotus. Six amodiaquin analogues were evaluated for their capacity to cure in- fections of chloroquine -sensitive and...AMODIAQUIN ANALOGUES AND AMODIAQUIN AGAINST INFECTIONS OF CHLOROQUINE -SENSITIVE AND CHLOROQUINE -RESISTANT STRAINS OF PLASMODIUM FALCIPARUM 14...AMODIAQUIN ANALOGUES AND AMOOIAQUIN AGAINST INFECTIONS OF CHLOROQUINE -SENSITIVE AND CHLOROQUINE - RESISTANT STRAINS OF PLASMODIUM FALCIPARUM Following

Ricin - inhibitor design. Annual report, 15 April 1994-14 April 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schramm, V.L.

1995-05-14

Substrates for ricin A-chain include short RNA stem-loop structures which have been synthesized with radioactive labels for ease of catalytic assay and for kinetic isotope effects. Ricin A-chain from several sources is incapable of completing multiple catalytic cycles using these substrates. A family of ricin substrate analogue molecules have been synthesized and tested which are specific for transition states with oxycarbonium character or for enzymatic mechanisms involving protonation of the adenine leaving group. Formycin analogues were incorporated into RNA oligomeric structures and tested for binding to ricin A-chain or as inhibitors of the ricin-inactivation of in vitro translation using rabbitmore » reticulocyte lysates. Ribo-oxycarbonium ion analogues containing iminoribitol analogues of ribose were synthetically incorporated into RNA oligomeric structures. Neither formycin nor ribo-oxycarbonium analogues, either singly or in RNA oligomers caused significant inhibition of ricin A-chain when assayed in reticulocyte lysate translation assays. The results indicate a novel transition state mechanism for ricin A-chain, or a requirement for additional features of 28s rRNA to bind transition state analogues.« less

The role of polyamine catabolism in anti-tumour drug response.

PubMed

Casero, R A; Wang, Y; Stewart, T M; Devereux, W; Hacker, A; Wang, Y; Smith, R; Woster, P M

2003-04-01

Interest in polyamine catabolism has increased since it has been directly associated with the cytotoxic response of multiple tumour types to exposure to specific anti-tumour polyamine analogues. Human polyamine catabolism was considered to be a two-step pathway regulated by the rate-limiting enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) that provides substrate for an acetylpolyamine oxidase (APAO). Further, the super-induction of SSAT by several anti-tumour polyamine analogues has been implicated in the cytotoxic response of specific solid-tumour phenotypes to these agents. This high induction of SSAT has been correlated with cellular response to the anti-tumour polyamine analogues in several systems and considerable progress has been made in understanding the molecular mechanisms that regulate the analogue-induced expression of SSAT. A polyamine response element has been identified and the transacting transcription factors that bind and stimulate transcription of SSAT have been cloned and characterized. The link between SSAT activity and cellular toxicity is thought to be based on the production of H(2)O(2) by the activity of the constitutive APAO that uses the SSAT-produced acetylated polyamines. The high induction of SSAT and the subsequent activity of APAO are linked to the cytotoxic response of some tumour cell types to specific polyamine analogues. However, we have recently cloned a variably spliced human polyamine oxidase (PAOh1) that is inducible by specific polyamine analogues, efficiently uses unacetylated spermine as a substrate, and also produces toxic H(2)O(2) as a product. The results of studies with PAOh1 suggest that it is an additional enzyme in polyamine catabolism that has the potential to significantly contribute to polyamine homoeostasis and drug response. Most importantly, PAOh1 is induced by specific polyamine analogues in a tumour-phenotype-specific manner in cell lines representative of the major forms of solid tumours, including lung, breast, colon and prostate. The sensitivity to these anti-tumour polyamine analogues can be significantly reduced if the tumour cells are co-treated with 250 microM of the polyamine oxidase inhibitor N (1), N (4)-bis(2,3-butadienyl)-1,4-butanediamine (MDL 72,527), suggesting that the H(2)O(2) produced by PAOh1 does in fact play a direct role in the observed cytotoxicity. These results strongly implicate PAOh1 as a new target that, in combination with SSAT, may be exploited for therapeutic advantage. The current understanding of the role and regulation of these two important polyamine catabolic enzymes are discussed.

Affinity alkylation of the active site of C/sub 21/ steroid side-chain cleavage cytochrome P-450 from neonatal porcine testis: a unique cysteine residue alkylated by 17-(bromoacetoxy)progesterone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onoda, M.; Haniu, M.; Yanagibashi, K.

1987-01-27

The affinity alkylating progesterone analogue 17-(bromoacetoxy)progesterone has been used to label the active site of a microsomal cytochrome P-450 enzyme from neonatal pig testis. The enzyme causes removal of the C/sub 20/ and C/sub 21/ side chains from the substrates progesterone and pregnenolone by catalyzing both 17-hydroxylase and C/sub 17,20/-lyase reactions, which produce the corresponding C/sub 1//sup 9/ steroidal precursors of testosterone. The progesterone analogue causes simultaneous inactivation of the two catalytic activities of the enzyme by a first-order kinetic process that obeys saturation kinetics. Progesterone and 17-hydroxyprogesterone each protect the enzyme against inactivation. The progesterone analogue is a competitivemore » inhibitor of the enzyme with K/sub i/ values of 8.4 ..mu..M and 7.8 ..mu..M for progesterone and 17-hydroxyprogesterone, respectively. The enzyme inactivation and kinetic data are consistent with a theory proposing that the analogue and the two substrates compete for the same active site. The radioactive analogue 17-((/sup 14/C)bromoacetoxy)progesterone causes inactivation of the enzyme with incorporation of 1.5-2.2 mol of the analogue per mole of inactivated enzyme. When this experiment is carried out in the presence of a substrate, then 0.9-1.2 mol of radioactive analogue is incorporated per mole of inactivated enzyme. The data suggest that the analogue can bind to two different sites, one of which is related to the catalytic site. Radiolabeled enzyme samples, from reactions of the /sup 14/C-labeled analogue with the enzyme alone or with enzyme in the presence of a substrate, were subjected to amino acid analysis and also in tryptic digestion and peptide mapping.« less

Assessment of periodontal bone level revisited: a controlled study on the diagnostic accuracy of clinical evaluation methods and intra-oral radiography.

PubMed

Christiaens, Véronique; De Bruyn, Hugo; Thevissen, Eric; Koole, Sebastiaan; Dierens, Melissa; Cosyn, Jan

2018-01-01

The accuracy of analogue and especially digital intra-oral radiography in assessing interdental bone level needs further documentation. The aim of this study was to compare clinical and radiographic bone level assessment to intra-surgical bone level registration (1) and to identify the clinical variables rendering interdental bone level assessment inaccurate (2). The study sample included 49 interdental sites in 17 periodontitis patients. Evaluation methods included vertical relative probing attachment level (RAL-V), analogue and digital intra-oral radiography and bone sounding without and with flap elevation. The latter was considered the true bone level. Five examiners evaluated all radiographs. Significant underestimation of the true bone level was observed for all evaluation methods pointing to 2.7 mm on average for analogue radiography, 2.5 mm for digital radiography, 1.8 mm for RAL-V and 0.6 mm for bone sounding without flap elevation (p < 0.001). Radiographic underestimation of the true bone level was higher in the (pre)molar region (p ≤ 0.047) and increased with defect depth (p < 0.001). Variation between clinicians was huge (range analogue radiography 2.2-3.2 mm; range digital radiography 2.1-3.0 mm). All evaluation methods significantly underestimated the true bone level. Bone sounding was most accurate, whereas intra-oral radiographs were least accurate. Deep periodontal defects in the (pre)molar region were most underrated by intra-oral radiography. Bone sounding had the highest accuracy in assessing interdental bone level.

Hierarchically Superstructured Prussian Blue Analogues: Spontaneous Assembly Synthesis and Applications as Pseudocapacitive Materials

DOE PAGES

Yue, Yanfeng; Zhang, Zhiyong; Binder, Andrew J.; ...

2014-11-10

Hierarchically superstructured Prussian blue analogues (hexa- conventional hybrid graphene/MnO 2 nanostructured textiles. cyanoferrate, M = Ni II, Co II and Cu II) are synthesized through Because sodium or potassium ions are involved in energy stor- a spontaneous assembly technique. In sharp contrast to mac- age processes, more environmentally neutral electrolytes can roporous-only Prussian blue analogues, the hierarchically su- be utilized, making the superstructured porous Prussian blue perstructured porous Prussian blue materials are demonstrated analogues a great contender for applications as high-per- to possess a high capacitance, which is similar to those of the formance pseudocapacitors.

GnRH Analogues in the Prevention of Ovarian Hyperstimulation Syndrome

PubMed Central

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

Divergent strategy for the synthesis of alpha-aryl-substituted fosmidomycin analogues.

PubMed

Devreux, Vincent; Wiesner, Jochen; Jomaa, Hassan; Rozenski, Jef; Van der Eycken, Johan; Van Calenbergh, Serge

2007-05-11

Fosmidomycin is the first representative of a new class of antimalarial drugs acting through inhibition of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway for the synthesis of isoprenoids. This work describes a divergent strategy for the synthesis of a series of alpha-aryl-substituted fosmidomycin analogues, featuring a palladium-catalyzed Stille coupling as the key step. An alpha-(4-cyanophenyl)fosmidomycin analogue emerged as the most potent analogue in the present series. Its antimalarial activity clearly surpasses that of the reference compound fosmidomycin.

The discovery of a novel antagonist - Manduca sexta allatotropin analogue - as an insect midgut active ion transport inhibitor.

PubMed

Deng, Xi-le; Kai, Zhen-Peng; Chamberlin, Mary E; Horodyski, Frank M; Yang, Xin-Ling

2016-11-01

The midgut is an important site for both nutrient absorption and ionic regulation in lepidopteran larvae, major pests in agriculture. The larval lepidopteran midgut has become a potent insecticide target over the past few decades. Recent studies have shown that an insect neuropeptide, Manduca sexta allatotropin (Manse-AT), exhibits inhibition of active ion transport (AIT) across the larval midgut epithelium. The full characteristic of the AIT inhibition capacity of Manse-AT is essential to assay. In this study, AIT inhibition across the M. sexta midgut by Manse-AT and its analogues in a range of concentrations was assayed. The structure-activity relationship of Manse-AT was also studied by truncated and alanine-replacement strategies. Our results identified three residues, Thr4, Arg6 and Phe8, as the most important components for activity on the midgut. Replacement of Glu1, Met2 and Met3 reduced the potency of the analogues. The conservative substitution of Gly7 with alanine had little effect on the potency of the analogues. We demonstrated for the first time that Manse-AT (10-13) behaves as a potent antagonist in vitro on active ion transport across the epithelium of the posterior midgut in M. sexta. Structure-activity studies of Manse-AT are useful in developing lead compounds for the design and testing of synthetic antagonists, ultimately to develop potent and specific pest control strategies. Manse-AT (10-13) has been discovered as the first Manse-AT antagonist, with a significant effect and a short sequence compared with other insect neuropeptides. It may be a new potential pest control agent in the future. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Manganese and lead levels in settled dust in elementary schools are correlated with biomarkers of exposure in school-aged children.

PubMed

Rodrigues, Juliana L G; Bandeira, Matheus J; Araújo, Cecília F S; Dos Santos, Nathália R; Anjos, Ana Laura S; Koin, Ng Lai; Pereira, Laiz C; Oliveira, Sérgio S P; Mergler, Donna; Menezes-Filho, José A

2018-05-01

Previously, we showed that manganese (Mn) levels in settled dust in elementary schools increased at a rate of 34.1% per km closer to a ferro-manganese alloy plant in the rainy season. In this study, we investigated how this environmental pollution indicator varied in the dry season and if there was an association with Mn biomarker levels in school-aged children. Dust samples were collected with passive samplers (disposable Petri dishes) placed in interior and exterior environments of 14 elementary schools. Occipital hair, toenails and blood samples were collected from 173 students aged 7-12 years from three of these schools, with varying distance from the industrial plant. Mn and lead (Pb) levels were measured by graphite furnace atomic absorption spectrometry. Mn concentration geometric means (GM) in dust fall accumulation in interior environments of schools located at 2, 4, 6 and > 6 km-radii from the plant were 2212, 584, 625 and 224 μg Mn/m 2 /30 days, respectively. The modelled rate of change of dust Mn levels decreases by 59.8% for each km further from the plant. Pb levels in settled dust varied between 18 and 81 μg/m 2 /30 days with no association with distance from the plant. Blood lead levels median (range) were 1.2 μg/dL (0.2-15.6), of which 97.8% were <5 μg/dL. Mn in hair and toenails were 0.66 μg/g (0.16-8.79) and 0.86 μg/g (0.15-13.30), respectively. Mn loading rates were positively associated with log MnH (β = 1.42 × 10 -5 , p < 0.001) after adjusting for children's age; and also with log MnTn (β = 2.31 × 10 -5 , p < 0.001) independent of age. Mn loading rates explained 18.5% and 28.5% of the variance in MnH and MnTn levels, respectively. School-aged children exposure to Mn, independently of age, increases significantly with school proximity to the ferro-manganese alloy plant. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interaction of staphylococcal delta-toxin and synthetic analogues with erythrocytes and phospholipid vesicles. Biological and physical properties of the amphipathic peptides.

PubMed

Alouf, J E; Dufourcq, J; Siffert, O; Thiaudiere, E; Geoffroy, C

1989-08-01

Staphylococcal delta-toxin, a 26-residue amphiphilic peptide is lytic for cells and phospholipid vesicles and is assumed to insert as an amphipathic helix and oligomerize in membranes. For the first time, the relationship between these properties and toxin structure is investigated by means of eight synthetic peptides, one identical in sequence to the natural toxin, five 26-residue analogues and two shorter peptides corresponding to residues 1-11 and 11-26. These peptides were designed by the Edmundson wheel axial projection in order to maintain: (a) the hydrophilic/hydrophobic balance while rationalizing the sequence, (b) the alpha-helical configuration and (c) the common epitopic structure. The fluorescence of the single Trp residue was used to monitor the behaviour of the natural toxin and analogues. All 26-residue analogues were hemolytically active although to a lesser extent than natural toxin. The peptide of residues 11-26 bound lipids weakly and was hemolytic at high concentration. The peptide of residues 1-11 did not bind lipids and was hemolytically inactive. All peptides except the latter cross-reacted in immunoprecipitation tests with the natural toxin. The study of a 26-residue analogue by circular dichroism revealed an alpha-helical configuration in both the free and lipid-bound state. Changes in the fluorescence of the peptides in the presence of lipid micelles and bilayers varied according to the position of the reporter group. When bound to lipids, Trp5, Trp16 and the Fmoc-1 positions of the analogues became buried while Trp15 of the natural toxin and its synthetic replicate remained more exposed. All changes are rationalized by the proposal of an amphipathic helix whose hydrophobic face is embedded within the apolar core of bilayers while the hydrophilic and charged face remains more exposed to solvent.

B-ring-aryl substituted luotonin A analogues with a new binding mode to the topoisomerase 1-DNA complex show enhanced cytotoxic activity.

PubMed

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

2014-01-01

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

Patients' preferences when comparing analogue implant impressions using a polyether impression material versus digital impressions (Intraoral Scan) of dental implants.

PubMed

Wismeijer, Daniel; Mans, Ronny; van Genuchten, Michiel; Reijers, Hajo A

2014-10-01

The primary objective of this clinical study was to assess the patients' perception of the difference between an analogue impression approach on the one hand and an intra-oral scan (IO scan) on the other when restoring implants in the non-aesthetic zone. A second objective was to analyse the difference in time needed to perform these two procedures. Thirty consecutive patients who had received 41 implants (Straumann tissue level) in the non-aesthetic zone in an implant-based referral practice setting in the Netherlands. As they were to receive crown and or bridge work on the implants, in one session, the final impressions were taken with both an analogue technique and with an intraoral scan. Patients were also asked if, directly after the treatment was carried out, they would be prepared to fill out a questionnaire on their perception of both techniques. The time involved following these two procedures was also recorded. The preparatory activities of the treatment, the taste of the impression material and the overall preference of the patients were significantly in favour of the IO scan. The bite registration, the scan head and gag reflex positively tended to the IO scan, but none of these effects were significant. The overall time involved with the IO scan was more negatively perceived than the analogue impression. Overall less time was involved when following the analogue impression technique than with the IO scan. The overall preference of the patients in our sample is significantly in favour of the approach using the IO scan. This preference relates mainly to the differences between the compared approaches with respect to taste effects and their preparatory activities. The patients did perceive the duration of IO scan more negatively than the analogue impression approach. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue.

PubMed

Fiebrich, H-B; Van Den Berg, G; Kema, I P; Links, T P; Kleibeuker, J H; Van Beek, A P; Walenkamp, A M E; Sluiter, W J; De Vries, E G E

2010-12-01

Somatostatin analogues are administered to control hormone hypersecretion in acromegaly and carcinoid patients. Somatostatin analogues can increase fat in the stools, which can lead to loss of fat-soluble vitamins. The effect of long-term somatostatin analogue use on vitamin levels remains unknown. To investigate the prevalence of fat-soluble vitamin deficiencies in long-term somatostatin analogue users. All acromegaly and carcinoid patients using somatostatin analogues for ≥ 18 months visiting the University Medical Center Groningen between December 2008 and April 2009 were eligible. Vitamin levels of fat-soluble vitamins in blood, clinical and vitamin-dependent laboratory parameters were collected. In all, 19 acromegaly and 35 carcinoid patients were included. Twelve patients experienced steatorrhoea; two carcinoid patients experienced night blindness. Forty-two (78%) were deficient for one or more vitamins, and 32% (n = 17) had multiple deficiencies. Deficiencies for vitamin A, D, E, K1 and E in erythrocytes occurred in 6%, 28%, 15%, 63% and 58% of the patients. Prevalence of vitamin D, E and K1 deficiencies was similar in both patient groups. Treatment duration did not influence vitamin levels. The length of intestinal resection and age correlated negatively with vitamin A levels. Fat-soluble vitamin deficiencies are frequent during long-term somatostatin analogue treatment. Therefore, fat-soluble vitamins should be monitored in these patients. © 2010 Blackwell Publishing Ltd.

Bioproduction of mushroom mycelium of Agaricus bisporus by commercial submerged fermentation for the production of meat analogue.

PubMed

Kim, Kyoungju; Choi, Byungsun; Lee, Inhee; Lee, Hyeyoung; Kwon, Soonhyang; Oh, Kyoungyoung; Kim, Augustine Yonghwi

2011-07-01

As worldwide interest in healthy and delicious meat analogues increases, the texture of these products has become an important indicator of quality. Mycoprotein as fungal mycelium could provide a distinctive chewing sensation; however, the unfavorable consumer perception of fungal mycelium demands the production of meat analogues with true mushroom mycelium. The industrial and economical bioprocess was developed using an inexpensive medium (30 g L(-1) sugar cane extract (SCE), 10 g L(-1) NaNO(3) and 5 g L(-1) yeast extract) and A. bisporus Suksung. The SCE was maintained at around 10 g L(-1) to minimize osmotic shock. The maximum mycelium production of 15.0 g L(-1) (dry weight) was reached within 4 days. Scanning electron microscopic analysis showed fibrous and directional structure rather than a more typical pellet structure. Meat analogues with mushroom mycelium had better textural properties, being higher in hardness, springiness, and chewiness and with preferable umami characteristics compared to meat analogues utilizing soy protein. The overall acceptance of meat analogues prepared with mycelium and soy protein, and a ground beef patty, were 5, 2 and 10, respectively. The development of an industrial bioprocess for A. bisporus mycelium allowed the production of a highly acceptable meat analogue having not only superior textural properties but also umami characteristics when compared to that of soy protein. Copyright © 2011 Society of Chemical Industry.

Chemical Preparation Laboratory for IND Candidate Compounds

DTIC Science & Technology

1990-08-10

Confirmation by 500 MHz Spectroscopy of an Analogue of the Amaryllidaceae Alkaloids, Narciclasine and Pancratistatin." Bjarne Gabrielsen, Department...subdivided into modified nucleosides, alkaloids with synthetically modified precursors and analogues , and miscellaneous heterocycles that possess...or antitumor compounds were modified synthet 4cally to possibly yield novel analogues that possess enhanced activities or show a specific mode of

Design and synthesis of paracaseolide A analogues as selective protein tyrosine phosphatase 1B inhibitors.

PubMed

Yin, Jian-Peng; Tang, Chun-Lan; Gao, Li-Xin; Ma, Wei-Ping; Li, Jing-Ya; Li, Ying; Li, Jia; Nan, Fa-Jun

2014-06-07

A series of structurally related analogues of the natural product paracaseolide A were synthesized and identified as potent PTP1B inhibitors. Among these analogues, compound 10 in particular showed improved PTP1B enzyme inhibitory activity, high selectivity for PTP1B over TC-PTP, and improved cellular effects.

Use of somatostatin analogues to treat chylothorax in a child with Generalised Lymphatic Dysplasia

PubMed Central

Brodlie, Malcolm; Abdelgalil, Sara; Mansour, Sahar; Spencer, David A.

2011-01-01

Generalised Lymphatic Dysplasia is a rare condition that may be associated with significant chylothoraces. The management of such effusions is often challenging. We present the case of a 15-year-old girl with bilateral chylothoraces and lymphoedema of her limbs. A clinical diagnosis of Generalised Lymphatic Dysplasia was made and long-term treatment with somatostatin analogues (somatostatin initially followed by monthly octreotide) was initiated. Over 12 months there was symptomatic benefit with some objective improvement in lung function and no adverse effects. After a year of treatment there was some reaccumulation of fluid, however this did not require any intervention. This is the first paediatric report of the use of somatostatin analogues to manage chylothorax in Generalised Lymphatic Dysplasia and we conclude that they represent a potentially useful treatment modality. Experience is only anecdotal however and further studies are required to establish an evidence base with regard to efficacy and safety. PMID:26056769

Optical analogue of relativistic Dirac solitons in binary waveguide arrays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tran, Truong X., E-mail: truong.tran@mpl.mpg.de; Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen; Longhi, Stefano

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 opticalmore » 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.« less

Heuristic for learning common emitter amplification with bipolar transistors

NASA Astrophysics Data System (ADS)

Staffas, Kjell

2017-11-01

Mathematics in engineering education causes many thresholds in the courses because of the demand of abstract conceptualisation. Electronics depend heavily on more or less complex mathematics. Therefore the concepts of analogue electronics are hard to learn since a great deal of students struggle with the calculations and procedures needed. A survey was done focusing on students' struggle to pass a course in analogue electronics by introducing a top-down perspective and the revised taxonomy of Bloom. From a top-down perspective you can create learning environments from any spot in the taxonomy using a step-by-step approach of the verbs understand and apply. Three textbooks with a top-down perspective on analogue electronics are analysed on the concept of amplifying with a transistor circuit. The study claims issues when losing the top-down perspective to present concepts and procedures of the content to be learned.