Discovery of new class of methoxy carrying isoxazole derivatives as COX-II inhibitors: Investigation of a detailed molecular dynamics study

NASA Astrophysics Data System (ADS)

Joy, Monu; Elrashedy, Ahmed A.; Mathew, Bijo; Pillay, Ashona Singh; Mathews, Annie; Dev, Sanal; Soliman, Mahmoud E. S.; Sudarsanakumar, C.

2018-04-01

Two novel isoxazole derivatives were synthesized and characterized by NMR and single crystal X-ray crystallography techniques. The methoxy and dimethoxy functionalized variants of isoxazole were screened for its anti-inflammatory profile using cyclooxygenase fluorescent inhibitor screening assay methods along with standard drugs, Celecoxib and Diclofenac. The potent and selective nature of the two isoxazole derivatives on COX-II isoenzyme with a greater magnitude of inhibitory concentration, as compared to the standard drugs and further exploited through molecular dynamics (MD) simulation. Classical, accelerated and multiple MD simulations were performed to investigate the actual binding mode of the two non-steroidal anti-inflammatory drug candidates and addressed their functional selectivity towards COX-II enzyme inhibitory nature.

A simple method for the small scale synthesis and solid-phase extraction purification of steroid sulfates.

PubMed

Waller, Christopher C; McLeod, Malcolm D

2014-12-01

Steroid sulfates are a major class of steroid metabolite that are of growing importance in fields such as anti-doping analysis, the detection of residues in agricultural produce or medicine. Despite this, many steroid sulfate reference materials may have limited or no availability hampering the development of analytical methods. We report simple protocols for the rapid synthesis and purification of steroid sulfates that are suitable for adoption by analytical laboratories. Central to this approach is the use of solid-phase extraction (SPE) for purification, a technique routinely used for sample preparation in analytical laboratories around the world. The sulfate conjugates of sixteen steroid compounds encompassing a wide range of steroid substitution patterns and configurations are prepared, including the previously unreported sulfate conjugates of the designer steroids furazadrol (17β-hydroxyandrostan[2,3-d]isoxazole), isofurazadrol (17β-hydroxyandrostan[3,2-c]isoxazole) and trenazone (17β-hydroxyestra-4,9-dien-3-one). Structural characterization data, together with NMR and mass spectra are reported for all steroid sulfates, often for the first time. The scope of this approach for small scale synthesis is highlighted by the sulfation of 1μg of testosterone (17β-hydroxyandrost-4-en-3-one) as monitored by liquid chromatography-mass spectrometry (LCMS). Copyright © 2014 Elsevier Inc. All rights reserved.

Curcumin-derived pyrazoles and isoxazoles: Swiss army knives or blunt tools for Alzheimer's disease?

PubMed

Narlawar, Rajeshwar; Pickhardt, Marcus; Leuchtenberger, Stefanie; Baumann, Karlheinz; Krause, Sabine; Dyrks, Thomas; Weggen, Sascha; Mandelkow, Eckhard; Schmidt, Boris

2008-01-01

Curcumin binds to the amyloid beta peptide (Abeta) and inhibits or modulates amyloid precursor protein (APP) metabolism. Therefore, curcumin-derived isoxazoles and pyrazoles were synthesized to minimize the metal chelation properties of curcumin. The decreased rotational freedom and absence of stereoisomers was predicted to enhance affinity toward Abeta(42) aggregates. Accordingly, replacement of the 1,3-dicarbonyl moiety with isosteric heterocycles turned curcumin analogue isoxazoles and pyrazoles into potent ligands of fibrillar Abeta(42) aggregates. Additionally, several compounds are potent inhibitors of tau protein aggregation and depolymerized tau protein aggregates at low micromolar concentrations.

UV-laser photochemistry of isoxazole isolated in a low-temperature matrix.

PubMed

Nunes, Cláudio M; Reva, Igor; Pinho e Melo, Teresa M V D; Fausto, Rui

2012-10-05

The photochemistry of matrix-isolated isoxazole, induced by narrowband tunable UV-light, was investigated by infrared spectroscopy, with the aid of MP2/6-311++G(d,p) calculations. The isoxazole photoreaction starts to occur upon irradiation at λ = 240 nm, with the dominant pathway involving decomposition to ketene and hydrogen cyanide. However, upon irradiation at λ = 221 nm, in addition to this decomposition, isoxazole was also found to isomerize into several products: 2-formyl-2H-azirine, 3-formylketenimine, 3-hydroxypropenenitrile, imidoylketene, and 3-oxopropanenitrile. The structural and spectroscopic assignment of the different photoisomerization products was achieved by additional irradiation of the λ = 221 nm photolyzed matrix, using UV-light with λ ≥ 240 nm: (i) irradiation in the 330 ≤ λ ≤ 340 nm range induced direct transformation of 2-formyl-2H-azirine into 3-formylketenimine; (ii) irradiation with 310 ≤ λ ≤ 318 nm light induced the hitherto unobserved transformation of 3-formylketenimine into 3-hydroxypropenenitrile and imidoylketene; (iii) irradiation with λ = 280 nm light permits direct identification of 3-oxopropanenitrile; (iv) under λ = 240 nm irradiation, tautomerization of 3-hydroxypropenenitrile to 3-oxopropanenitrile is observed. On the basis of these findings, a detailed mechanistic proposal for isoxazole photochemistry is presented.

A complex study of 5-amino-3-methyl-4-[2-(5-amino-1,3,4-oxadiazolo)]-isoxazole monohydrate: A new low-molecular-weight immune response modifier

NASA Astrophysics Data System (ADS)

Ryng, Stanisław; Zimecki, Michał; Jezierska-Mazzarello, Aneta; Panek, Jarosław J.; Mączyński, Marcin; Głowiak, Tadeusz; Sawka-Dobrowolska, Wanda; Koll, Aleksander

2011-07-01

A new potential lead structure with immunological activity, 5-amino-3-methyl-4-[2-(5-amino-1,3,4-oxadiazolo)]-isoxazole monohydrate, was synthesized. A detailed description of synthesis is presented together with X-ray structural analysis. In vitro assays showed that the compound had a potent immunosuppressive activity. Next, Density Functional Theory (DFT) was employed to shed a light on molecular properties of the investigated isoxazole derivative. The molecular modeling part included geometric as well as electronic structure descriptions: (i) the conformational analysis was performed to localize the most appropriate conformation; (ii) the coordination energy and Basis Set Superposition Error (BSSE) were estimated for the complex of the isoxazole derivative interacting with water molecule; (iii) the potential energy distribution was used to assign molecular vibrations, and NBO population analysis served to describe the electronic structure; (iv) the electrostatic potential map was generated to provide the graphical presentation of regions exposed for intermolecular interactions. The contacts between the water molecule and the nitrogen atom of the isoxazole ring edge were present in the solid phase. On the other hand, the theoretical DFT prediction was that the oxygen atom of the edge should form a more stable complex with the water molecule.

Neurite outgrowth of murine cerebellar granule cells can be enhanced by aniracetam with or without alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA).

PubMed

Fushiki, S; Matsumoto, K; Nagata, A

1995-10-27

To assess the neurotrophic effects of a nootropic drug, aniracetam, we studied neurite extension of mouse cerebellar granule cells in culture with low or with high K+ under different combinations of drugs and then immunohistochemically stained the cells with an antibody against L1, a neural cell adhesion molecule on cerebellar granule cells. Quantitative analyses using parameters of the total neurite length, maximal neurite length and number of branches disclosed that aniracetam, in the presence of high K+ and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), significantly enhanced neurite extension of cultured granule neurons. Aniracetam alone also stimulated neurite extension of cerebellar granule cells at a longer period of culture with low K+ showing a bell-shaped dose response curve with maximal effects at 10 microM. Aniracetam may influence remodeling of the neural network after injury.

Transition Metal Free Multicomponent approach to Stereo-enriched Cyclopentyl-isoxazoles via C-C Bond Cleavage.

PubMed

Kaliappan, Krishna Pillai; Subramanian, Parthasarathi

2018-06-19

An efficient multicomponent reaction leading to the synthesis of stereo-enriched cyclopentyl-isoxazoles from camphor derived α-oxime, alkynes and MeOH is reported. Our method involves a series of cascade transformations such as in situ generation of catalyst I(III) which catalyzes the addition MeOH into a sterically hindered ketone, oxime oxidation and α-hydroxyiminium ion rearrangement to generate in situ nitrile oxide which upon [3+2]-cycloaddition reaction with alkynes delivers regioselective products. The reaction is very selective to syn-oxime. This multicomponent approach has also been extended for the synthesis of a novel glycoconjugate, camphoric ester-isoxazole C-galactoside. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Isoxazole moiety in the linker region of HDAC inhibitors adjacent to the Zn-chelating group: effects on HDAC biology and antiproliferative activity.

PubMed

Tapadar, Subhasish; He, Rong; Luchini, Doris N; Billadeau, Daniel D; Kozikowski, Alan P

2009-06-01

A series of hydroxamic acid based histone deacetylase inhibitors 6-15, containing an isoxazole moiety adjacent to the Zn-chelating hydroxamic acid, is reported herein. Some of these compounds showed nanomolar activity in the HDAC isoform inhibitory assay and exhibited micro molar inhibitory activity against five pancreatic cancer cell lines.

Methyl 6-eth-oxy-3-phenyl-3a,4-dihydro-3H-chromeno[4,3-c]isoxazole-3a-car-boxylate.

PubMed

Suresh, G; Srinivasan, J; Bakthadoss, M; Aravindhan, S

2013-02-01

In the title compound, C(20)H(19)NO(5), the dihedral angle between the mean plane of the pyran ring (which has a half-chair conformation) and the benzene ring of the chromeno ring system is 7.21 (7)°. The dihedral angle between the mean plane of the chromeno ring system and the isoxazole ring is 21.78 (6)°, while the isoxazole ring forms a dihedral angle of 72.60 (8)° with the attached phenyl ring. In the crystal, mol-ecules are linked via pairs of C-H⋯O hydrogen bonds, forming inversion dimers with an R(2) (2)(10) ring motif. These dimers are linked via C-H⋯N hydrogen bonds, forming chains along [001].

Chameleonic reactivity of vicinal diazonium salt of acetylenyl-9,10-anthraquinones: synthetic application toward two heterocyclic targets.

PubMed

Stepanov, A A; Gornostaev, L M; Vasilevsky, S F; Arnold, E V; Mamatyuk, V I; Fadeev, D S; Gold, B; Alabugin, I V

2011-11-04

The nature of products in the diazotization of 1-amino-2-acetylenyl-9,10-anthraquinones strongly depends on the nature of substituents at both the alkyne and at the anthraquinone core. Donor substitution (NHAr, OH) at the fourth position stabilizes the diazonium salt at C1, decelerating electrophilic cyclization at the arylethynyl substituent at C2. This effect allows the replacement of the diazonium with azide group and subsequent closure into isoxazole ring with preservation of the alkyne. In contrast, electrophilic 5-exo-dig cyclizations to condensed pyrazoles is observed for the combination of donor substituents at the aryl alkyne moiety and an OAc substituent at C4. The latter process provides a new synthetic route to 3-ethynyl-[1,9-cd]isoxazol-6-ones that are difficult to access otherwise. DFT calculations suggest that donor substituents have only a minor effect on alkyne and diazonium polarization in the reactant but provide specific transition state stabilization by stabilizing the incipient vinyl cation. This analysis provides the first computational data on electrophilic 5-exo-dig cyclization in its parent form and the nucleophile-promoted version. This cyclization is a relatively fast but endothermic process that is rendered thermodynamically feasible by the enol-keto tautomerization with concomitant aromatization in the five-membered heteroaromatic ring. Computations suggest that the importance of nucleophilic assistance in the transition state for a relatively weak nucleophile such as water is minor because the energy gain due to the Lewis base coordination to the carbocationic center is more than compensated for by the unfavorable entropic term for the bimolecular proces.

Photoinduced reactions of both 2-formyl-2H-azirine and isoxazole: A theoretical study based on electronic structure calculations and nonadiabatic dynamics simulations.

PubMed

Cao, Jun

2015-06-28

In the present work, the combined electronic structure calculations and dynamics simulations have been performed to explore photocleavages of 2-formyl-2H-azirine and isoxazole in the gas phase and the subsequent rearrangement reactions. The carbonyl n → π(*) transition induces a cleavage of the C-N single bond of 2-formyl-2H-azirine to yield β-formylvinylnitrene in open-shell singlet state. However, the n → π(*) excitation of the imine chromophore results in a cleavage of the C-C single bond, producing a nitrile ylide intermediate through an internal conversion to the ground state. β-formylvinylnitrene and nitrile ylide with the carbonyl group are easily transformed into 2-formyl-2H-azirine and oxazole, respectively. The N-O bond cleavages on both S1((1)ππ(*)) and S2((1)nNπ(*)) of isoxazole are ultrafast processes, and they give products of 2-formyl-2H-azirine, 3-formylketenimine, HCN + CHCHO, and HCO + CHCHN. Both 2H-azirines and ketenimines were suggested to be formed from the triplet vinylnitrenes by intersystem crossing in the previous studies. However, our calculations show that the singlet β-formylvinylnitrene is responsible for the formation of 2-formyl-2H-azirine and 3-formylketenimine, and the singlet vinylnitrenes can play a key role in the photoinduced reactions of both 2H-azirines and isoxazoles.

Photoinduced reactions of both 2-formyl-2H-azirine and isoxazole: A theoretical study based on electronic structure calculations and nonadiabatic dynamics simulations

NASA Astrophysics Data System (ADS)

Cao, Jun

2015-06-01

In the present work, the combined electronic structure calculations and dynamics simulations have been performed to explore photocleavages of 2-formyl-2H-azirine and isoxazole in the gas phase and the subsequent rearrangement reactions. The carbonyl n → π* transition induces a cleavage of the C—N single bond of 2-formyl-2H-azirine to yield β-formylvinylnitrene in open-shell singlet state. However, the n → π* excitation of the imine chromophore results in a cleavage of the C—C single bond, producing a nitrile ylide intermediate through an internal conversion to the ground state. β-formylvinylnitrene and nitrile ylide with the carbonyl group are easily transformed into 2-formyl-2H-azirine and oxazole, respectively. The N—O bond cleavages on both S1(1ππ*) and S2(1nNπ*) of isoxazole are ultrafast processes, and they give products of 2-formyl-2H-azirine, 3-formylketenimine, HCN + CHCHO, and HCO + CHCHN. Both 2H-azirines and ketenimines were suggested to be formed from the triplet vinylnitrenes by intersystem crossing in the previous studies. However, our calculations show that the singlet β-formylvinylnitrene is responsible for the formation of 2-formyl-2H-azirine and 3-formylketenimine, and the singlet vinylnitrenes can play a key role in the photoinduced reactions of both 2H-azirines and isoxazoles.

Photoinduced reactions of both 2-formyl-2H-azirine and isoxazole: A theoretical study based on electronic structure calculations and nonadiabatic dynamics simulations

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

Cao, Jun, E-mail: caojunbnu@mail.bnu.edu.cn

2015-06-28

In the present work, the combined electronic structure calculations and dynamics simulations have been performed to explore photocleavages of 2-formyl-2H-azirine and isoxazole in the gas phase and the subsequent rearrangement reactions. The carbonyl n → π{sup *} transition induces a cleavage of the C—N single bond of 2-formyl-2H-azirine to yield β-formylvinylnitrene in open-shell singlet state. However, the n → π{sup *} excitation of the imine chromophore results in a cleavage of the C—C single bond, producing a nitrile ylide intermediate through an internal conversion to the ground state. β-formylvinylnitrene and nitrile ylide with the carbonyl group are easily transformed intomore » 2-formyl-2H-azirine and oxazole, respectively. The N—O bond cleavages on both S{sub 1}({sup 1}ππ{sup *}) and S{sub 2}({sup 1}n{sub N}π{sup *}) of isoxazole are ultrafast processes, and they give products of 2-formyl-2H-azirine, 3-formylketenimine, HCN + CHCHO, and HCO + CHCHN. Both 2H-azirines and ketenimines were suggested to be formed from the triplet vinylnitrenes by intersystem crossing in the previous studies. However, our calculations show that the singlet β-formylvinylnitrene is responsible for the formation of 2-formyl-2H-azirine and 3-formylketenimine, and the singlet vinylnitrenes can play a key role in the photoinduced reactions of both 2H-azirines and isoxazoles.« less

An improved procedure to prepare 3-methyl-4-nitroalkylenethylisoxazoles and their reaction under catalytic enantioselective Michael addition with nitromethane.

PubMed

Moccia, Maria; Wells, Robert J; Adamo, Mauro F A

2015-02-21

Herein, we describe a short synthesis of 3-methyl-4-nitro-5-alkylethenyl isoxazoles and their reactivity as Michael acceptors. The title compounds reacted with nitromethane under phase-transfer catalysis to provide highly enantioenriched adducts (up to 93% ee) which were then converted to the corresponding γ-nitroacids.

Synthesis, crystal structure, photophysical properties and theoretical studies of a novel bis(phenylisoxazolyl) benzene derivative

NASA Astrophysics Data System (ADS)

de Brito, A. C. F.; Correa, R. S.; Pinto, A. A.; Matos, M. J. S.; Tenorio, J. C.; Taylor, J. G.; Cazati, T.

2018-07-01

Isoxazoles have well established biological activities but, have been underexplored as synthetic intermediates for applications in materials science. The aims of this work are to synthesis a novel isoxazole and analyze its structural and photophysical properties for application in electronic organic materials. The novel bis (phenylisoxazolyl) benzene compound was synthesized in four steps and characterized by NMR, high resolution mass spectrometry, differential thermal analysis, infrared spectroscopy, cyclic voltammetry, ultraviolet-visible spectroscopy, fluorescence spectroscopy, DFT and TDDFT calculations. The molecule presented optical absorption in the ultraviolet region (from 290 nm to 330 nm), with maximum absorption length centered at 306 nm. The molar extinction coefficients (ε), fluorescence emission spectra and quantum efficiencies in chloroform and dimethylformamide solution were determined. Cyclic voltammetry analysis was carried out for estimating the HOMO energy level and these properties make it desirable material for photovoltaic device applications. Finally, the excited-state properties of present compound were calculated by time-dependent density functional theory (TDDFT).

Microbial transformation of danazol with Cunninghamella blakesleeana and anti-cancer activity of danazol and its transformed products.

PubMed

Baydoun, Elias; Atia-tul-Wahab; Mehmood, Hina; Ahmad, Malik Shoaib; Malik, Rizwana; Smith, Colin; Choudhary, M Iqbal

2016-01-01

Biotransformation of danazol (1) (17β-hydroxy-17α-pregna-2,4-dien-20-yno-[2,3-d]-isoxazole) with Cunninghamella blakesleeana yielded three new metabolites 2-4 and a known metabolite 5. These metabolites were identified as 14β,17β-dihydroxy-2-(hydroxymethyl)-17α-pregn-4-en-20-yn-3-one (2), 1α,17β-dihydroxy-17α-pregna-2,4-dien-20-yno-[2,3-d]-isoxazole (3), 6β,17β-dihydroxy-17α-pregna-2,4-dien-20-yno-[2,3-d]-isoxazole (4), and 17β-hydroxy-2-(hydroxymethyl)-17α-pregn-1,4-dien-20-yn-3-one (5). Danazol (1) and its derivatives were evaluated against cervical cancer cell line (HeLa). Compound 1 showed a potent cytotoxicity with IC50=0.283±0.013 μM, as compared to doxorubicin (IC50=0.506±0.015 μM), where compound 3 was also found to be significantly active with IC50=13.427±0.819 μM. Copyright © 2015 Elsevier Inc. All rights reserved.

Activation of MRTF-A–dependent gene expression with a small molecule promotes myofibroblast differentiation and wound healing

PubMed Central

Velasquez, Lissette S.; Sutherland, Lillian B.; Liu, Zhenan; Grinnell, Frederick; Kamm, Kristine E.; Schneider, Jay W.; Olson, Eric N.; Small, Eric M.

2013-01-01

Myocardin-related transcription factors (MRTFs) regulate cellular contractility and motility by associating with serum response factor (SRF) and activating genes involved in cytoskeletal dynamics. We reported previously that MRTF-A contributes to pathological cardiac remodeling by promoting differentiation of fibroblasts to myofibroblasts following myocardial infarction. Here, we show that forced expression of MRTF-A in dermal fibroblasts stimulates contraction of a collagen matrix, whereas contractility of MRTF-A null fibroblasts is impaired under basal conditions and in response to TGF–β1 stimulation. We also identify an isoxazole ring-containing small molecule, previously shown to induce smooth muscle α-actin gene expression in cardiac progenitor cells, as an agonist of myofibroblast differentiation. Isoxazole stimulates myofibroblast differentiation via induction of MRTF-A–dependent gene expression. The MRTF-SRF signaling axis is activated in response to skin injury, and treatment of dermal wounds with isoxazole accelerates wound closure and suppresses the inflammatory response. These results reveal an important role for MRTF-SRF signaling in dermal myofibroblast differentiation and wound healing and suggest that targeting MRTFs pharmacologically may prove useful in treating diseases associated with inappropriate myofibroblast activity. PMID:24082095

Experimental and theoretical studies of the crystal structures of bis-isoxazole-bis-methylene dinitrate (BIDN) and bis-isoxazole tetramethylene tetranitrate (BITN) by x-ray crystallography and density functional theory

NASA Astrophysics Data System (ADS)

Taylor, Decarlos E.; Sausa, Rosario C.

2018-06-01

The determination of crystal structures plays an important role for model testing and validation, and understanding intra and intermolecular interactions that influence crystal packing. Here, we report the molecular structure of two recently synthesized energetic molecules, 3,3-bis-isoxazole-5,5‧-bis-methylene dinitrate (C8H6N4O8, BIDN) and bis-isoxazole tetramethylene tetranitrate (C10H8N6O14, BITN) determined by single crystal x-ray diffraction and solid state density functional theory (DFT). BIDN is composed of two planar alkyl nitrate groups (r.m.s deviation = 0.0004 (1) Å) bonded to two planar azole rings (r.m.s deviation = 0.001 (1) Å, whereas BITN is composed of four planar alkyl nitrate groups (average r.m.s deviation = 0.002 (1) Å) bonded to two planar azole rings (average r.m.s deviation = 0.002 (1) Å). The theoretical calculations predict very well the planarity of both the alkyl nitrate groups and rings for both compounds. Furthermore, they predict well the bond lengths and angles of both molecules with mean deviation values of 0.018 Å (BIDN) and 0.017 Å (BITN) and 0.481° (BIDN) and 0.747° (BITN). Overall, the DFT determined torsion angles agree well with those determined experimentally for both BIDN (average deviation = 1.139°) and BITN (average deviation = 0.604°). The theoretical cell constant values are in excellent agreement with those determined experimentally for both molecules, with the BIDN a cell value and β angle showing the largest deviation, 2.1% and -1.3%, respectively. Contacts between the atoms N and H dominate the intermolecular interactions of BIDN, whereas contacts involving the atoms O and H dominate the BITN intermolecular interactions. Electrostatic potential calculations at the B3LYP/6-31G* level reveal BIDN exhibits a lower sensitivity to impact compared to BITN.

40 CFR 180.537 - Isoxaflutole; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances... combined residues of isoxaflutole 5-cyclopropyl-4-(2-methylsulfonyl-4-trifluoromethylbenzoyl) isoxazole and...

40 CFR 180.537 - Isoxaflutole; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances... combined residues of isoxaflutole 5-cyclopropyl-4-(2-methylsulfonyl-4-trifluoromethylbenzoyl) isoxazole and...

Isolation and characterization of efficient isoxaben-transforming Microbacterium sp strains from four European soils.

PubMed

Arrault, Sandra; Desaint, Stephane; Catroux, Colette; Sémon, Etienne; Mougin, Christian; Fournier, Jean Claude

2002-12-01

Nutrient-agar plates containing isoxaben (500 mg litre(-1)) were used to isolate isoxaben-metabolising bacteria from four European soils incubated with the herbicide under laboratory conditions. In flask experiments, inoculation of a basal salts medium containing nitrogen and [phenyl-U-14C]isoxaben with an isolate (B2b) resulted in 33% recovery of the initial radioactivity as [14C]carbon dioxide after 2 weeks. A major metabolite identified by GC-MS and NMR analysis as 3-(1-ethyl-1-methylpropyl)isoxazol-5-ylamine accumulated both in basal salts and nutrient broth media. 2,6-Dimethoxybenzoic acid, a suspected metabolite of isoxaben, was not detected in either liquid media. However, the capability of the B2b isolate to use 2,6-dimethoxybenzoic acid as a source of carbon was demonstrated. Soil inoculation with the B2b strain resulted in an increase in the recovery of [14C] carbon dioxide from both [phenyl-U-14C] and [isoxazole-5-14C]isoxaben. The metabolite identified as 3-(1-ethyl-1-methylpropyl)isoxazole-5-ylamine only accumulated if the soil was autoclaved before inoculation. This metabolite was rapidly mineralized by the microflora of a natural soil without history of isoxaben treatment. Homology patterns of sequenced 16S rDNA between isoxaben-transforming isolates and reference strains showed that the four isolates identified belonged to the genus Microbacterium.

Co-ingestion of amatoxins and isoxazoles-containing mushrooms and successful treatment: A case report.

PubMed

Garcia, Juliana; Costa, Vera M; Costa, Ana Elisa; Andrade, Sérgio; Carneiro, Ana Cristina; Conceição, Filipe; Paiva, José Artur; de Pinho, Paula Guedes; Baptista, Paula; de Lourdes Bastos, Maria; Carvalho, Félix

2015-09-01

Mushroom poisonings occur when ingestion of wild mushrooms containing toxins takes place, placing the consumers at life-threatening risk. In the present case report, an unusual multiple poisoning with isoxazoles- and amatoxins-containing mushrooms in a context of altered mental state and poorly controlled hypertension is presented. A 68-year-old female was presented to São João hospital (Portugal) with complaints of extreme dizziness, hallucinations, vertigo and imbalance, 3 h after consuming a stew of wild mushrooms. The first observations revealed altered mental state and elevated blood pressure. The examination of cooked mushroom fragments allowed a preliminary identification of Amanita pantherina. Gas chromatography-mass spectrometry (GC-MS) showed the presence of muscimol in urine. Moreover, through high-performance liquid chromatography-ultraviolet detection (HPLC-UV) analysis of the gastric juice, the presence of α-amanitin was found, showing that amatoxins-containing mushrooms were also included in the stew. After 4 days of supportive treatment, activated charcoal, silybin and N-acetylcysteine, the patient recovered being discharged 10 days post-ingestion with no organ complications. The prompt and appropriate therapy protocol for life-threatening amatoxins toxicity probably saved the patient's life as oral absorption was decreased and also supportive care was immediately started. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of novel flavone/triazole/benzimidazole hybrids and flavone/isoxazole-annulated heterocycles as antiproliferative and antimycobacterial agents.

PubMed

Rao, Yerrabelly Jayaprakash; Sowjanya, Thummala; Thirupathi, Gogula; Murthy, Nandula Yadagiri Sreenivasa; Kotapalli, Sudha Sravanti

2018-06-04

A series of new flavone/isoxazole fused heterocycles 5a-f and flavone/1,2,3-triazole/benzimidazole hybrid heterocycles compounds 7a-t were synthesized via an intramolecular cyclization and Cu(I)-catalyzed click 1,3-dipolar cycloaddition. The products were evaluated for their antiproliferative activity against human breast cancer cell line (MCF-7) using sulforhodamine B assay (SRB) and antimycobacterial activity using turbidometric assay. The majority of the tested compounds exhibited antiproliferative activity and antimycobacterial activity. Compounds 7l, 7q and 7r showed moderate antiproliferative activity with IC50 values 17.9, 14.2, 19.1 [Formula: see text], respectively, and compound 5a showed moderate antimycobacterial activity with 41.7% of inhibition at 30 [Formula: see text] concentration.

Discovery and SAR study of c-Met kinase inhibitors bearing an 3-amino-benzo[d]isoxazole or 3-aminoindazole scaffold.

PubMed

Jiang, Xiaolong; Liu, Hongyan; Song, Zilan; Peng, Xia; Ji, Yinchun; Yao, Qizheng; Geng, Meiyu; Ai, Jing; Zhang, Ao

2015-02-01

A series of 3-amino-benzo[d]isoxazole-/3-aminoindazole-based compounds were designed, synthesized and pharmacologically evaluated as tyrosine kinase c-Met inhibitors. The SAR study was conducted leading to identification of nine compounds (8d, 8e, 12, 28a-d, 28h and 28i) with IC50s less than 10nM against c-Met. Compound 28a stood out as the most potent c-Met inhibitor displaying potent inhibitory effects both at enzymatic (IC50=1.8 nM) and cellular (IC50=0.18 μM on EBC-1 cells) levels. In addition, 28a had a relatively good selectivity compared to a panel of our in-house 14 RTKs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Validation of tautomeric and protomeric binding modes by free energy calculations. A case study for the structure based optimization of D-amino acid oxidase inhibitors.

PubMed

Orgován, Zoltán; Ferenczy, György G; Steinbrecher, Thomas; Szilágyi, Bence; Bajusz, Dávid; Keserű, György M

2018-02-01

Optimization of fragment size D-amino acid oxidase (DAAO) inhibitors was investigated using a combination of computational and experimental methods. Retrospective free energy perturbation (FEP) calculations were performed for benzo[d]isoxazole derivatives, a series of known inhibitors with two potential binding modes derived from X-ray structures of other DAAO inhibitors. The good agreement between experimental and computed binding free energies in only one of the hypothesized binding modes strongly support this bioactive conformation. Then, a series of 1-H-indazol-3-ol derivatives formerly not described as DAAO inhibitors was investigated. Binding geometries could be reliably identified by structural similarity to benzo[d]isoxazole and other well characterized series and FEP calculations were performed for several tautomers of the deprotonated and protonated compounds since all these forms are potentially present owing to the experimental pKa values of representative compounds in the series. Deprotonated compounds are proposed to be the most important bound species owing to the significantly better agreement between their calculated and measured affinities compared to the protonated forms. FEP calculations were also used for the prediction of the affinities of compounds not previously tested as DAAO inhibitors and for a comparative structure-activity relationship study of the benzo[d]isoxazole and indazole series. Selected indazole derivatives were synthesized and their measured binding affinity towards DAAO was in good agreement with FEP predictions.

Validation of tautomeric and protomeric binding modes by free energy calculations. A case study for the structure based optimization of d-amino acid oxidase inhibitors

NASA Astrophysics Data System (ADS)

Orgován, Zoltán; Ferenczy, György G.; Steinbrecher, Thomas; Szilágyi, Bence; Bajusz, Dávid; Keserű, György M.

2018-02-01

Optimization of fragment size d-amino acid oxidase (DAAO) inhibitors was investigated using a combination of computational and experimental methods. Retrospective free energy perturbation (FEP) calculations were performed for benzo[d]isoxazole derivatives, a series of known inhibitors with two potential binding modes derived from X-ray structures of other DAAO inhibitors. The good agreement between experimental and computed binding free energies in only one of the hypothesized binding modes strongly support this bioactive conformation. Then, a series of 1-H-indazol-3-ol derivatives formerly not described as DAAO inhibitors was investigated. Binding geometries could be reliably identified by structural similarity to benzo[d]isoxazole and other well characterized series and FEP calculations were performed for several tautomers of the deprotonated and protonated compounds since all these forms are potentially present owing to the experimental pKa values of representative compounds in the series. Deprotonated compounds are proposed to be the most important bound species owing to the significantly better agreement between their calculated and measured affinities compared to the protonated forms. FEP calculations were also used for the prediction of the affinities of compounds not previously tested as DAAO inhibitors and for a comparative structure-activity relationship study of the benzo[d]isoxazole and indazole series. Selected indazole derivatives were synthesized and their measured binding affinity towards DAAO was in good agreement with FEP predictions.

Inhibition of Androgen Receptor Function and Level in Castration-Resistant Prostate Cancer Cells by 2-[(isoxazol-4-ylmethyl)thio]-1-(4-phenylpiperazin-1-yl)ethanone.

PubMed

Masoodi, Khalid Z; Eisermann, Kurtis; Yang, Zhenyu; Dar, Javid A; Pascal, Laura E; Nguyen, Minh; O'Malley, Katherine; Parrinello, Erica; Feturi, Firuz G; Kenefake, Alex N; Nelson, Joel B; Johnston, Paul A; Wipf, Peter; Wang, Zhou

2017-10-01

The androgen receptor (AR) plays a critical role in the development of castration-resistant prostate cancer (CRPC) as well as in the resistance to the second-generation AR antagonist enzalutamide and the selective inhibitor of cytochrome P450 17A1 (CYP17A1) abiraterone. Novel agents targeting AR may inhibit the growth of prostate cancer cells resistant to enzalutamide and/or abiraterone. Through a high-throughput/high-content screening of a 220,000-member small molecule library, we have previously identified 2-[(isoxazol-4-ylmethyl)thio]-1-(4-phenylpiperazin-1-yl)ethanone (IMTPPE) (SID 3712502) as a novel small molecule capable of inhibiting AR transcriptional activity and protein level in C4-2 prostate cancer cells. In this study, we show that IMTPPE inhibits AR-target gene expression using real-time polymerase chain reaction, Western blot, and luciferase assays. IMTPPE inhibited proliferation of AR-positive, but not AR-negative, prostate cancer cells in culture. IMTPPE inhibited the transcriptional activity of a mutant AR lacking the ligand-binding domain (LBD), indicating that IMTPPE inhibition of AR is independent of the LBD. Furthermore, animal studies showed that IMTPPE inhibited the growth of 22Rv1 xenograft tumor, a model for enzalutamide-resistant prostate cancer. These findings suggest that IMTPPE is a potential lead compound for developing clinical candidates for the treatment of CRPC, including those resistant to enzalutamide. Copyright © 2017 Endocrine Society.

Synthesis and biological evaluation of aryl isoxazole derivatives as metabotropic glutamate receptor 1 antagonists: a potential treatment for neuropathic pain.

PubMed

Cho, Gyeong Hi; Kim, TaeHun; Son, Woo Seung; Seo, Seon Hee; Min, Sun-Joon; Cho, Yong Seo; Keum, Gyochang; Jeong, Kyu-Sung; Koh, Hun Yeong; Lee, Jiyoun; Pae, Ae Nim

2015-03-15

Glutamate is the major excitatory neurotransmitter and known to activate the metabotropic and ionotropic glutamate receptors in the brain. Among these glutamate receptors, metabotropic glutamate receptor 1 (mGluR1) has been implicated in various brain disorders including anxiety, schizophrenia and chronic pain. Several studies demonstrated that the blockade of mGluR1 signaling reduced pain responses in animal models, suggesting that mGluR1 is a promising target for the treatment of neuropathic pain. In this study, we have developed mGluR1 antagonists with an aryl isoxazole scaffold, and identify several compounds that are orally active in vivo. We believe that these compounds can serve as a useful tool for the investigation of the role of mGluR1 and a promising lead for the potential treatment of neuropathic pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Design, synthesis and biological screening of some pyridinylpyrazole and pyridinylisoxazole derivatives as potential anti-inflammatory, analgesic, antipyretic and antimicrobial agents.

PubMed

El-Hawash, Soad A M; Soliman, Raafat; Youssef, Amal M; Ragab, Hanan M A; Elzahhar, Perihan A S; El-Ashmawey, Ibrahim M; Abdel Wahab, Abeer E; Shaat, Iman A

2014-05-01

A series of substituted pyridinylpyrazole (or isoxazole) derivatives were synthesized and evaluated for their anti-inflammatory (AI) activity using formalin-induced paw edema bioassays. Their inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) were also determined. The analgesic activity of the same compounds was evaluated using rat-tail withdrawal technique. Their antipyretic activity was also evaluated. The results revealed that compounds 4a,b, 6a, 8a, 14c and 15a exhibited significant AI and analgesic activities. Compounds 5a, 6a and 8a displayed good antipyretic activity. Compounds 14c and 15a showed good COX-2 inhibitory activity and weak inhibition of COX-1. Additionally, the most active compounds were shown to have a large safety margin (ALD50 >300-400 mg / Kg) and minimal ulcerogenic potentialities when administered orally at a dose of 300 mg/Kg. Docking studies for 14c and 15a with COX-2 showed good binding profile. Antimicrobial evaluation proved that most of the compounds exhibited distinctive activity against the gram negative bacteria, P. aeruginosa and E coli.

Isoxazole-type derivatives related to combretastatin A-4, synthesis and biological evaluation.

PubMed

Kaffy, Julia; Pontikis, Renée; Carrez, Danièle; Croisy, Alain; Monneret, Claude; Florent, Jean-Claude

2006-06-15

Novel combretastatin analogues bearing various five-membered heterocycles with consecutive oxygen and nitrogen atoms, in place of the olefinic bridge of CA4, have been synthesized (isoxazole, isoxazoline, oxadiazole, etc). These compounds have been evaluated for cytotoxicity and their ability to inhibit the tubulin assembly. On the basis of the relative position of the aromatic A- and B-rings on the heterocyclic moiety, they could be split in two classes, the alpha,gamma- or alpha,beta-diaryl heterocyclic derivatives. In the first series, the 3,5-diaryloxadiazole 9a displayed comparable antitubulin activity to that of CA4, but was devoid of cytotoxic effects. Among the alpha,beta-diaryl heterocyclic derivatives, the 4,5-diarylisoxazole 35 exhibited greater antitubulin activity than that of CA4 (0.75 vs 1.2 microM), but modest antiproliferative activity. These data showed that minor alteration in the chemical structure of the heterocyclic ring and its relative orientation with regard to the two phenyl rings of CA4 could dramatically influence the tubulin binding properties.

Synthesis of novel forskolin isoxazole derivatives with potent anti-cancer activity against breast cancer cell lines.

PubMed

Burra, Srinivas; Voora, Vani; Rao, Ch Prasad; Vijay Kumar, P; Kancha, Rama Krishna; David Krupadanam, G L

2017-09-15

Forskolin C 1 -isoxazole derivatives (3,5-regioisomers) (11a-e, 14, 15a-h and 15, 16a-g) were synthesized regioselectively by adopting 1,3-dipolar cycloadditions. These derivatives were tested using estrogen receptor positive breast cancer cell lines MCF-7 and BT-474. Majority of the compounds exhibited activity against the p53-positive MCF-7 breast cancer cells but not against the p53-negative BT-474 breast cancer cells. Among forskolin derivatives, compounds 11a, 11c, 14a, 14f, 14g, 14h, 15b, 16g and 17b exhibited higher anti-cancer activity against MCF-7 cell line with an IC 50 ≤1µM. The derivative 14f exhibited highest activity in both p53-positive (MCF-7) and p53-negative (BT-474) breast cancer cell lines with an IC 50 of 0.5µM. Copyright © 2017. Published by Elsevier Ltd.

Synthesis and biological evaluation of novel 5-hydroxylaminoisoxazole derivatives as lipoxygenase inhibitors and metabolism enhancing agents.

PubMed

Averina, Elena B; Vasilenko, Dmitry A; Gracheva, Yulia A; Grishin, Yuri K; Radchenko, Eugene V; Burmistrov, Vladimir V; Butov, Gennady M; Neganova, Margarita E; Serkova, Tatyana P; Redkozubova, Olga M; Shevtsova, Elena F; Milaeva, Elena R; Kuznetsova, Tamara S; Zefirov, Nikolay S

2016-02-15

A versatile synthesis of novel 5-hydroxylaminoisoxazoles bearing adamantane moieties has been accomplished using the heterocyclization reactions of readily available unsaturated esters by the treatment with tetranitromethane in the presence of triethylamine and subsequent reduction of resulting 5-nitroisoxazoles by SnCl2 with the participation of THF. A number of obtained isoxazole derivatives were evaluated for their antioxidative activity, inhibition of lipoxygenases and impact on the rat liver mitochondria. The majority of tested compounds demonstrated moderate antiradical activity in DPPH test (up to EC50 16μM). The same compounds strongly inhibited soybean lipoxygenase (up to IC50 0.4μM) and Fe(2+)- and Fe(3+)-induced lipid peroxidation (LP) of rat brain cortex homogenate (up to IC50 0.3μM). All tested isoxazole derivatives promoted the phosphorylating respiratory activity simultaneously with maximal stimulated respiratory activity of mitochondria and do not reveal any toxicity towards the primary culture of rat cortex neurons. Copyright © 2015 Elsevier Ltd. All rights reserved.

EGAR, A Food Protein-Derived Tetrapeptide, Reduces Seizure Activity in Pentylenetetrazole-Induced Epilepsy Models Through α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionate Receptors.

PubMed

Cai, Song; Ling, Chuwen; Lu, Jun; Duan, Songwei; Wang, Yingzhao; Zhu, Huining; Lin, Ruibang; Chen, Liang; Pan, Xingchang; Cai, Muyi; Gu, Huaiyu

2017-01-01

A primary pathogeny of epilepsy is excessive activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs). To find potential molecules to inhibit AMPARs, high-throughput screening was performed in a library of tetrapeptides in silico. Computational results suggest that some tetrapeptides bind stably to the AMPAR. We aligned these sequences of tetrapeptide candidates with those from in vitro digestion of the trout skin protein. Among salmon-derived products, Glu-Gly-Ala-Arg (EGAR) showed a high biological affinity toward AMPAR when tested in silico. Accordingly, natural EGAR was hypothesized to have anticonvulsant activity, and in vitro experiments showed that EGAR selectively inhibited AMPAR-mediated synaptic transmission without affecting the electrophysiological properties of hippocampal pyramidal neurons. In addition, EGAR reduced neuronal spiking in an in vitro seizure model. Moreover, the ability of EGAR to reduce seizures was evaluated in a rodent epilepsy model. Briefer and less severe seizures versus controls were shown after mice were treated with EGAR. In conclusion, the promising experimental results suggest that EGAR inhibitor against AMPARs may be a target for antiepilepsy pharmaceuticals. Epilepsy is a common brain disorder characterized by the occurrence of recurring, unprovoked seizures. Twenty to 30 % of persons with epilepsy do not achieve adequate seizure control with any drug. Here we provide a possibility in which a natural and edible tetrapeptide, EGAR, can act as an antiepileptic agent. We have combined computation with in vitro experiments to show how EGAR modulates epilepsy. We also used an animal model of epilepsy to prove that EGAR can inhibit seizures in vivo. This study suggests EGAR as a potential pharmaceutical for the treatment of epilepsy.

The Nuclear Transcription Factor RAR Associates with Neuronal RNA Granules and Suppresses Translation

USDA-ARS?s Scientific Manuscript database

All-trans-retinoic acid stimulates dendritic growth in hippocampal neurons within minutes by activating mitogen-activated protein kinase and mTOR and increasing dendritic translation of calcium calmodulin-dependent protein kinase II alpha and the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionat...

Localized Disruption of Narp in Medial Prefrontal Cortex Blocks Reinforcer Devaluation Performance

ERIC Educational Resources Information Center

Johnson, Alexander W.; Han, Sungho; Blouin, Ashley M.; Saini, Jasjit; Worley, Paul F.; During, Matthew J.; Holland, Peter C.; Baraban, Jay M.; Reti, Irving M.

2010-01-01

Neuronal activity regulated pentraxin (Narp) is a secreted protein that regulates [alpha]-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPAR) aggregation and synaptogenesis. Mapping of Narp-positive neurons in brain has revealed it is prominently expressed in several limbic system projection pathways. Consistent with this…

1-(4-(6-Fluorobenzo [d] isoxazol-3-yl) piperidin-1-yl)-2-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl) ethanone: Synthesis, spectroscopic characterization, Hirshfeld surface analysis, cytotoxic studies and docking studies

NASA Astrophysics Data System (ADS)

Govindhan, M.; Viswanathan, V.; Karthikeyan, S.; Subramanian, K.; Velmurugan, D.

2017-08-01

Compound 1-(4-(6-fluorobenzo[d] isoxazol-3-yl) piperidin-1-yl)-2-(4-(hydroxymethyl)-1H-1, 2,3-triazol-1-yl) ethanone was synthesized in good yield by using click chemistry approach with 2-azido-1-(4-(6-flurobenzo[d]isooxazol-3-yl)piperidin-1-yl)ethanone as a starting material. The synthesized compound was characterized using IR, NMR and MS studies. Thermal stability of the compound was analyzed by using TGA and DSC technique. The single crystal XRD analysis was taken part, to confirm the structure of the compound. The intercontacts in the crystal structure are analyzed using Hirshfeld surfaces computational method. Cytotoxicity of the synthesized compound was evaluated and the results were reported. The binding analysis carried out between the newly synthesized molecule with human serum albumin using fluorescence spectroscopy technique to understand the pharmacokinetics nature of the compound for further biological application. The molecular docking studies were evaluated for the compound to elucidate insights of new molecules in carrier protein.

Coantagonism of Glutamate Receptors and Nicotinic Acetylcholinergic Receptors Disrupts Fear Conditioning and Latent Inhibition of Fear Conditioning

ERIC Educational Resources Information Center

Gould, Thomas J.; Lewis, Michael C.

2005-01-01

The present study investigated the hypothesis that both nicotinic acetylcholinergic receptors (nAChRs) and glutamate receptors ([alpha]-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) and N-methyl-D-aspartate glutamate receptors (NMDARs)) are involved in fear conditioning, and may modulate similar processes. The effects of the…

Synthesis and biological evaluation of a series of aminoalkyl-tetralones and tetralols as dual dopamine/serotonin ligands.

PubMed

Carro, Laura; Torrado, María; Raviña, Enrique; Masaguer, Christian F; Lage, Sonia; Brea, José; Loza, María I

2014-01-01

A series of novel α-tetralone and α-tetralol derivatives was synthesized, and their binding affinities for 5-HT(2A) and D₂ receptors, the most important targets implicated in the anti-schizophrenia drug action, were evaluated to elucidate how substitutions in the aromatic ring of the pharmacophore affect to the affinity or selectivity for these receptors. The replacement of the H-7 in the tetrahydronaphthalene system by an amino group resulted in privileged 5-HT(2A) affinity of the 6-fluorobenzo[d]isoxazol derivative 36 and the alcohol 25 both showing a pK(i) value for 5-HT(2A) higher than 8.3 and good binding affinities for D₂ receptor leading to a Meltzer's ratio characteristic of an atypical antipsychotic profile. Additionally, a small collection of 3-aminomethyltetralone derivatives was prepared and examined here for their affinities and selectivities as 5-HT(2A)/D₂ dual ligands. Compound 11 shows the best profile with good pKi values for 5-HT(2A) and D₂ receptors leading to a Meltzer's ratio characteristic of a typical antipsychotic behaviour. These three compounds behaved as competitive antagonists of both 5-HT(2A) and D₂ receptors, and might be promising pharmacological tools for the investigation of the dual function of the 5HT(2A)-D₂ ligands. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Microwave-Assisted Synthesis of some Novel Azoles and Azolopyrimidines as Antimicrobial Agents.

PubMed

Gomha, Sobhi M; Farghaly, Thoraya A; Mabkhot, Yahia Nasser; Zayed, Mohie E M; Mohamed, Amany M G

2017-02-23

In this study, new derivatives of pyrazole, isoxazole, pyrazolylthiazole, and azolopyrimidine having a thiophene ring were synthesized under microwave irradiation. Their pharmacological activity toward bacteria and fungi inhibition was screened and compared to the references Chloramphenicol and Trimethoprim / sulphamethoxazole . The antimicrobial results of the investigated compounds revealed promising results and some derivatives have activities similar to the references used.

Base induced chemical conversion of 3-carbamoyl-2-isoxazolines.

PubMed

Nishiwaki, Nagatoshi; Maki, Asaka; Ariga, Masahiro

2009-01-01

3-Carbamoyl-2-isoxazolines, prepared by cycloaddition of functionalized nitrile oxide, serve as masked 3-unsubstituted isoxazolines to afford 2-isoxazoline-3-carboxylic acid, beta-cyanoalcohol, alpha,beta-unsaturated nitrile, and alpha,beta-unsaturated amide upon heating in the alkaline solution. The present reaction is also applicable to synthesis of 3,4-difunctionalized isoxazoles and beta-hydroxy-gamma-lactone.

Design, synthesis and biological evaluation of diaziridinyl quinone isoxazole hybrids.

PubMed

Swapnaja, K Jones M; Yennam, Satyanarayana; Chavali, Murthy; Poornachandra, Y; Kumar, C Ganesh; Muthusamy, Krubakaran; Jayaraman, Venkatesh Babu; Arumugam, Premkumar; Balasubramanian, Sridhar; Sriram, Kiran Kumar

2016-07-19

A series of novel diaziridinyl quinone isoxazole hybrids (9a-9j) were synthesized starting from 2, 5-dimethoxy acetophenone 1 via Claisen reaction, cyclisation, alkoxy carbonylation, hydrolysis, oxidation and aziridine insertion. All the compounds were screened for antimicrobial, anti-biofilm and cytotoxic activities. Among the screened compounds, the compound 9h showed good antibacterial and anti-biofilm activities with MIC value of 3.9, 3.9, 3.9 and 7.8 μg/mL, respectively, and IC50 values of 1.9, 2.5, 2.8 and 5.1 μM, respectively, against Staphylococcus aureus MTCC 96, S. aureus MLS-16 MTCC 2940, Bacillus subtilis MTCC 121 and Klebsiella planticola MTCC 530, and also exhibited potent antifungal activity against Candida albicans MTCC 227, C. albicans MTCC 854 and Candida krusei MTCC 3020 equipotent to standard miconazole (MIC value 7.8 μg/mL). All the synthesized compounds exhibited promising cytotoxicity against A549 and PC3 cell lines (IC50 values between 1 and 4 μM). Compounds 9b and 9j exhibited IC50 value of 0.5 μM which was similar to that of Mitomycin C against PC3 cell line. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Design and synthesis of a new series of 3,5-disubstituted isoxazoles active against Trypanosoma cruzi and Leishmania amazonensis.

PubMed

da Rosa, Rafael; de Moraes, Milene Höehr; Zimmermann, Lara Almida; Schenkel, Eloir Paulo; Steindel, Mario; Bernardes, Lílian Sibelle Campos

2017-03-10

Chagas disease and leishmaniasis are neglected tropical diseases (NTDs) endemic in developing countries. Although there are drugs available for their treatment, efforts on finding new efficacious therapies are continuous. The natural lignans grandisin (1) and veraguensin (2) show activity against trypomastigote T. cruzi and their scaffold has been used as inspiration to design new derivatives with improved potency and chemical properties. We describe here the planning and microwave-irradiated synthesis of 26 isoxazole derivatives based on the structure of the lignans 1 and 2. In addition, the in vitro evaluation against culture trypomastigotes and intracellular amastigotes of T. cruzi and intracellular amastigotes of L. amazonensis and L. infantum is reported. Among the synthesized derivatives, compounds 17 (IC 50  = 5.26 μM for T. cruzi), 29 (IC 50  = 1.74 μM for T. cruzi) and 31 (IC 50  = 1.13 μM for T. cruzi and IC 50  = 5.08 μM for L. amazonensis) were the most active and were also evaluated against recombinant trypanothione reductase of T. cruzi in a preliminary study of their mechanism of action. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Solution-phase parallel synthesis of aryloxyimino amides via a novel multicomponent reaction among aromatic (Z)-chlorooximes, isocyanides, and electron-deficient phenols.

PubMed

Mercalli, Valentina; Giustiniano, Mariateresa; Del Grosso, Erika; Varese, Monica; Cassese, Hilde; Massarotti, Alberto; Novellino, Ettore; Tron, Gian Cesare

2014-11-10

A library of 41 aryloxyimino amides was prepared via solution phase parallel synthesis by extending the multicomponent reaction of (Z)-chlorooximes and isocyanides to the use of electron-deficient phenols. The resulting aryloxyiminoamide derivatives can be used as intermediates for the synthesis of benzo[d]isoxazole-3-carboxamides, dramatically reducing the number of synthetic steps required by other methods reported in literature.

3-(4-Chloro­phen­yl)-7-methyl-4-(4-methyl­phen­yl)-1-oxa-2,7-diaza­spiro­[4.5]dec-2-en-10-one

PubMed Central

Gayathri, D.; Velmurugan, D.; Ranjith Kumar, R.; Perumal, S.; Ravikumar, K.

2008-01-01

In the title compound, C21H21ClN2O2, the dihydro­isoxazole ring adopts an envelope conformation and the piperidinone ring is in a chair conformation. The dihedral angle between the two benzene rings is 84.2 (1)°. The crystal used was an inversion twin. PMID:21201426

Crystal structure of (2R*,3aR*)-2-phenyl-sulfonyl-2,3,3a,4,5,6-hexa-hydro-pyrrolo-[1,2-b]isoxazole.

PubMed

Hernández, Yaiza; Marcos, Isidro; Garrido, Narciso M; Sanz, Francisca; Diez, David

2017-01-01

The title compound, C 12 H 15 NO 3 S, was prepared by 1,3-dipolar cyclo-addition of 3,4-di-hydro-2 H -pyrrole 1-oxide and phenyl vinyl sulfone. In the mol-ecule, both fused five-membered rings display a twisted conformation. In the crystal, C-H⋯O hydrogen bonds link neighbouring mol-ecules, forming chains running parallel to the b axis.

Small scale separation of isoxazole structurally related analogues by chiral supercritical fluid chromatography.

PubMed

Zehani, Yasmine; Lemaire, Lucas; Millet, Regis; Lipka, Emmanuelle

2017-07-07

Chromatographic preparative enantioseparation is now the preferred method to obtain milligram amounts of pure enantiomers in the first step of the development of a therapeutic molecule. Supercritical fluid chromatography has many advantages over liquid chromatography and was therefore chosen for the small scale enantioseparation of four original 3-carboxamido-5-aryl isoxazole molecules, ligands of the CB2 cannabinoid receptors. The preparation of about 10mg of each of the eight enantiomers was achieved successfully on a Chiralpak ® AD-H (tris-3,5-dimethylphenylcarbamate of amylose) polysaccharide based stationary phase with various percentages of ethanol as a co-solvent, through mixed-stream injections and touching-band approach. For the all compounds, no peak distortion is observed during the volume overloading, in spite of the injection mode. Production rate (mgmin -1 ), productivity (kilogram of racemate separated per kilogram of CSP per day (kkd)) and solvent usage were found higher and environmental factors (E Factor) were found lower for compounds 1 and 3. The yields of each purified enantiomer were comprised between 60 and 94%. In order to improve the limit of detection calculated with the diode array detector, the hyphenation with an evaporating light scattering detector was explored and a factor of ten was won. Lastely, the enantiomeric excess and achiral purity of each of the eight individual enantiomer generated was determined and found higher than 98%. Copyright © 2017 Elsevier B.V. All rights reserved.

Pyrazolo[3,4-c]isothiazole and isothiazolo[4,3-d]isoxazole derivatives as antifungal agents.

PubMed

Vicentini, Chiara Beatrice; Romagnoli, Carlo; Manfredini, Stefano; Rossi, Damiano; Mares, Donatella

2011-05-01

The diseases of plants and humans due to pathogenic fungi are increasing. Among the substances used to combat fungi, the azoles are of primary interest, both in agricultural field both in health. To avoid fungal resistance phenomena, the synthesis and tests of new derivatives are necessary. This article discusses the synthesis and the antifungal activity of pyrazolo[3,4-c]isothiazole and isothiazolo[4,3-d]isoxazole derivatives against three fungi that are pathogenic only for plants and two fungi that are opportunistic in humans and plants. The compounds were prepared starting from 2-cyano-3-ethoxy-2-butenethioamide. The antifungal activity of the compounds was determined by measuring the inhibition of growth of the fungi tested at 20, 50, and 100 µg/mL in comparison with the controls. Results demonstrated that several compounds were able to control the mycelial growth of the tested fungi, even if they showed different sensitivity to the different azole-derivatives. In general Magnaporthe grisea (T.T. Hebert) Yaegashi & Udagawa was the most sensitive fungus, being blocked almost entirely by 4-chloro derivative even at 20 µg/mL, a concentration at which the reference commercial compound tricyclazole was nearly ineffective. These findings demonstrate that the pyrazolo[3,4-c]isothiazole derivatives have a wide spectrum of activity on phytopathogenic and opportunistic fungi. In particular the 4-chloro derivative seems to have a great potential as new product to combat M. grisea in the agricultural field.

A novel difunctional acylhydrazone with isoxazole and furan heterocycles: Syntheses, structure, spectroscopic properties, antibacterial activities and theoretical studies of (E)-N‧-(furan-2-ylmethylene)-5-methylisoxazole-4-carbohydrazide

NASA Astrophysics Data System (ADS)

Jin, Yan-Xian; Zhong, Ai-Guo; Ge, Chang-Hua; Pan, Fu-You; Yang, Jian-Guo; Wu, Ying; Xie, Min; Feng, Hai-Wan

2012-02-01

In order to explore new functional materials, a novel acylhydrazone with isoxazole and furan heterocycles was synthesized and thoroughly investigated by X-ray crystallography, UV and fluorescence spectroscopy, cyclic voltammetry, thermoanalysis, density functional theory (DFT) and time-dependent density functional theory (TDDFT). The molecule has been demonstrated to crystallize in the monoclinic space group P21/c, with the unit cell parameters of (a = 11.3522(19) Å, b = 8.0700(14) Å, c = 12.872(2) Å; α = 90°, β = 106.969(12)°, γ = 90°). In addition, this compound shows characteristic UV absorption peaks at 205, 222 and 308 nm, and fluorescence emission peak at 486.1 nm, which according to our theoretic calculation can all be attributed to (p, π) → π∗ and π → π∗ intraligand charge-transfer transition (ILCT) respectively. According to our cyclic voltammetry result, an oxidation peak of the compound can be observed with onset oxidation potential (Eox) of 0.44 V. Furthermore, the results of antibacterial activities indicate the compound has broad-spectrum against Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus, which can be supported by the molecular electrostatic potential (MEP). Therefore, this compound exhibits both antibacterial activity and photoluminescent property, namely difunctionality, suggesting that it has potential applications in many fields such as material science and photodynamic therapy.

Knocking on FXR's door: the "hammerhead"-structure series of FXR agonists - amphiphilic isoxazoles with potent in vitro and in vivo activities.

PubMed

Gege, Christian; Kinzel, Olaf; Steeneck, Christoph; Schulz, Andreas; Kremoser, Claus

2014-01-01

The Farnesoid X Receptor (FXR) was recently validated in clinical studies using the bile acid analogue Obeticholic Acid (OCA) as an attractive drug target for liver diseases such as Primary Biliary Cirrhosis (PBC) or Non-alcoholic Steatohepatitis (NASH). OCA, however, turned out to induce cholesterol- related side effects upon prolonged treatment and it shows bile acid like pharmacokinetics. The quest for synthetic non-steroidal FXR agonists with general drug likeliness and improved pharmacokinetic and - dynamic properties has started more than a decade ago: The first non-steroidal and selective FXR agonist with decent submicromolar potency, GW4064, was patented in 1998 and published in 2000. Since then, many pharmaceutical companies have taken GW4064 as a structural template for their efforts in identifying novel patentable FXR agonists with the GW-derived trisubstituted isoxazole general structure. However, so far only one compound out of these different series has made it into the early stages of clinical development: The Px-102/Px-104 from Phenex is currently tested in a phase IIa study in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). In this review we try to summarize from the patent and scientific literature the attempts to improve the GW4064 structure into different directions. Furthermore, we suggest directions for further improvements of this special class of synthetic FXR agonists which all display the typical "hammerhead"-conformation in the FXR ligand binding pocket that provides the basis for their impressive in vitro and in vivo potencies.

Free radical reactions of isoxazole and pyrazole derivatives of hispolon: kinetics correlated with molecular descriptors.

PubMed

Shaikh, Shaukat Ali M; Barik, Atanu; Singh, Beena G; Modukuri, Ramani V; Balaji, Neduri V; Subbaraju, Gottumukkala V; Naik, Devidas B; Priyadarsini, K Indira

2016-12-01

Hispolon (HS), a natural polyphenol found in medicinal mushrooms, and its isoxazole (HI) and pyrazole (HP) derivatives have been examined for free radical reactions and in vitro antioxidant activity. Reaction of these compounds with one-electron oxidant, azide radicals ([Formula: see text]) and trichloromethyl peroxyl radicals ([Formula: see text]), model peroxyl radicals, studied by nanosecond pulse radiolysis technique, indicated formation of phenoxyl radicals absorbing at 420 nm with half life of few hundred microseconds (μs). The formation of phenoxyl radicals confirmed that the phenolic OH is the active centre for free radical reactions. Rate constant for the reaction of these radicals with these compounds were in the order k HI ≅ k HP  >   k HS . Further the compounds were examined for their ability to inhibit lipid peroxidation in model membranes and also for the scavenging of 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical and superoxide ([Formula: see text]) radicals. The results suggested that HP and HI are less efficient than HS towards these radical reactions. Quantum chemical calculations were performed on these compounds to understand the mechanism of reaction with different radicals. Lower values of adiabatic ionization potential (AIP) and elevated highest occupied molecular orbital (HOMO) for HI and HP compared with HS controlled their activity towards [Formula: see text] and [Formula: see text] radicals, whereas the contribution of overall anion concentration was responsible for higher activity of HS for DPPH, [Formula: see text], and lipid peroxyl radical. The results confirm the role of different structural moieties on the antioxidant activity of hispolon derivatives.

Novel [(biphenyloxy)propyl]isoxazole derivatives for inhibition of human rhinovirus 2 and coxsackievirus B3 replication.

PubMed

Makarov, Vadim A; Riabova, Olga B; Granik, Vladimir G; Wutzler, Peter; Schmidtke, Michaela

2005-04-01

During this study, novel biphenyl derivatives were synthesized and tested for antiviral activity. A new method based on the Suzuki coupling reaction has been established for the synthesis of these polysubstituted chain systems. In parallel with cytotoxicity, the antiviral activity of biphenyl derivatives has been determined in cytopathic effect (CPE)-inhibitory assays with the pleconaril-resistant coxsackievirus B3 (CVB3) strain Nancy, human rhinovirus 2 (HRV-2) and 14 (HRV-14) and in plaque reduction assays with the pleconaril-sensitive human isolate CVB3 97-927 in HeLa cells. Based on the results from these investigations the selectivity index (SI) was determined as the ratio of the 50% cytotoxic concentration to the 50% inhibitory concentration. The new method based on the Suzuki coupling reaction includes the condensation of 2,6-dimethyl-4-bromophenol with pentyne chloride by means of potassium carbonate and potassium iodide in N-methylpyrrolidone-2 and yields 5-bromo-1,3-dimethyl-2-(4-pentynyloxy)benzene. Its condensation with methylacetaldoxime results in 3-methylisoxazole derivatives. The following reaction with different benzeneboronic acids by means of tetrakis(triphenylphosphine)-palladium(0) finally yields the corresponding derivatives. Several of the novel synthesized derivatives demonstrated a good antiviral activity on CVB3 (SI > 2 to > 37.5) and a strong anti-HRV-2 activity (SI > 50 to > 200). In contrast, none of the compounds inhibited the HRV-14-induced CPE. These results indicate that [(biphenyloxy)propyl]isoxazole derivatives are potential inhibitors of HRV-2 and CVB3 replication, and make them promising agents for the specific treatment of these virus infections.

Isobaric metabolite interferences and the requirement for close examination of raw data in addition to stringent chromatographic separations in liquid chromatography/tandem mass spectrometric analysis of drugs in biological matrix.

PubMed

Yan, Zhengyin; Maher, Noureddine; Torres, Rhoda; Cotto, Carlos; Hastings, Becki; Dasgupta, Malini; Hyman, Rolanda; Huebert, Norman; Caldwell, Gary W

2008-07-01

In addition to matrix effects, common interferences observed in liquid chromatography/tandem mass spectrometry (LC/MS/MS) analyses can be caused by the response of drug-related metabolites to the multiple reaction monitoring (MRM) channel of a given drug, as a result of in-source reactions or decomposition of either phase I or II metabolites. However, it has been largely ignored that, for some drugs, metabolism can lead to the formation of isobaric or isomeric metabolites that exhibit the same MRM transitions as parent drugs. The present study describes two examples demonstrating that interference caused by isobaric or isomeric metabolites is a practical issue in analyzing biological samples by LC/MS/MS. In the first case, two sequential metabolic reactions, demethylation followed by oxidation of a primary alcohol moiety to a carboxylic acid, produced an isobaric metabolite that exhibits a MRM transition identical to the parent drug. Because the drug compound was rapidly metabolized in rats and completely disappeared in plasma samples, the isobaric metabolite appeared as a single peak in the total ion current (TIC) trace and could easily be quantified as the drug since it was eluted at a retention time very close to that of the drug in a 12-min LC run. In the second example, metabolism via the ring-opening of a substituted isoxazole moiety led to the formation of an isomeric product that showed an almost identical collision-induced dissociation (CID) MS spectrum as the original drug. Because two components were co-eluted, the isomeric product could be mistakenly quantified and reported by data processing software as the parent drug if the TIC trace was not carefully inspected. Nowadays, all LC/MS data are processed by computer software in a highly automated fashion, and some analysts may spend much less time to visually examine raw TIC traces than they used to do. Two examples described in this article remind us that quality data require both adequate chromatographic separations and close examination of raw data in LC/MS/MS analyses of drugs in biological matrix.

Topiramate in opiate withdrawal.

PubMed

Zullino, Daniele F; Cottier, Anne-Claude; Besson, Jacques

2002-10-01

The alpha2-adrenergic agonist clonidine is the mainly used drug for the opiate withdrawal. Its efficacy and tolerance in treating withdrawal symptoms is, however, suboptimal. The pharmacological profile of topiramate suggests it could be rather valuable for opiate withdrawal, as there is some evidence that topiramate acts, among others, through inhibition of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, which play an important role in the withdrawal-induced activation of the locus coeruleus (LC) by glutamate. Three patients undergoing an inpatient opiate detoxification program were treated with topiramate, which achieved a nearly complete control of withdrawal symptoms.

Identification of matrix metalloproteinase inhibitors by chemical arrays.

PubMed

Kawatani, Makoto; Fukushima, Yukako; Kondoh, Yasumitsu; Honda, Kaori; Sekine, Tomomi; Yamaguchi, Yoshiki; Taniguchi, Naoyuki; Osada, Hiroyuki

2015-01-01

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade many extracellular matrix components and that have been implicated in the pathogenesis of various human diseases including cancer metastasis. Here, we screened MMP-9 inhibitors using photo-cross-linked chemical arrays, which can detect small-molecule ligand-protein interactions on a chip in a high-throughput manner. The array slides were probed sequentially with His-MMP-9, anti-His antibody, and a Cy5-labeled secondary antibody and then scanned with a microarray scanner. We obtained 27 hits among 24,275 compounds from the NPDepo library; 2 of the identified compounds (isoxazole compound 1 and naphthofluorescein) inhibited MMP-9 enzyme activity in vitro. We further explored 17 analogs of 1 and found that compound 18 had the strongest inhibitory activity. Compound 18 also inhibited other MMPs, including MMP-2, MMP-12, and MMP-13 and significantly inhibited cell migration in human fibrosarcoma HT1080 cells. These results suggest that 18 is a broad-spectrum MMP inhibitor.

alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionate attenuates glutamate-induced caspase-3 cleavage via regulation of glycogen synthase kinase 3beta.

PubMed

Nishimoto, Takaaki; Kihara, Takeshi; Akaike, Akinori; Niidome, Tetsuhiro; Sugimoto, Hachiro

2008-04-01

Preconditioning of sublethal ischemia exhibits neuroprotection against subsequent ischemia-induced neuronal death. It has been indicated that glutamate, an excitatory amino acid, is involved in the pathogenesis of ischemia-induced neuronal death or neurodegeneration. To elucidate whether prestimulation of glutamate receptor could counter ischemia-induced neuronal death or neurodegeneration, we examined the effect of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), an ionotropic subtype of glutamate receptor, on excess glutamate-induced excitotoxicity using primary cortical neuronal cultures. We found that AMPA exerted a neuroprotective effect in a time- and concentration-dependent manner. A blocker of phosphatidylinositol-3 kinase (PI3K), LY294002 (10 microM), significantly attenuated AMPA-induced protection. In addition, Ser473 of Akt/PKB, a downstream target of PI3K, was phosphorylated by AMPA administration (10 microM). Glycogen synthase kinase 3beta (GSK3beta), which has been reported to be inactivated by Akt, was phosphorylated at Ser9 by AMPA. Ser9-phosphorylated GSK3beta or inactivated form would be a key molecule for neuroprotection, insofar as lithium chloride (100 microM) and SB216763 (10 microM), inhibitors of GSK3beta, also induced phosphorylation of GSK3beta at Ser9 and exerted neuroprotection, respectively. Glutamate (100 microM) increased cleaved caspase-3, an apoptosis-related cysteine protease, and caspase-3 inhibitor (Ac-DEVD-CHO; 1 microM) blocked glutamate-induced excitotoxicity in our culture. AMPA (10 microM, 24 hr) and SB216763 (10 microM) prominently decreased glutamate-induced caspase-3 cleavage. These findings suggest that AMPA activates PI3K-Akt and subsequently inhibits GSK3beta and that inactivated GSK3beta attenuates glutamate-induced caspase-3 cleavage and neurotoxicity.

Roles of Fragile X Mental Retardation Protein in Dopaminergic Stimulation-induced Synapse-associated Protein Synthesis and Subsequent α-Amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) Receptor Internalization*

PubMed Central

Wang, Hansen; Kim, Susan S.; Zhuo, Min

2010-01-01

Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of α-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome. PMID:20457613

Roles of fragile X mental retardation protein in dopaminergic stimulation-induced synapse-associated protein synthesis and subsequent alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) receptor internalization.

PubMed

Wang, Hansen; Kim, Susan S; Zhuo, Min

2010-07-09

Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome.

Second harmonic generation and photochromic grating in polyurethane films containing diazo isoxazole chromophore

NASA Astrophysics Data System (ADS)

Marański, Krzysztof; Kucharski, Stanisław; Ortyl, Ewelina; Nunzi, Jean-Michel; Ahmadi-Kandjani, Sohrab; Dabos-Seignon, Sylvie; Chan, Siu-Wai; Barille, Regis

2008-08-01

The chromophoric intermediate: 2,2'-({4-[( E)-(5-methylisoxazol-3-yl)diazenyl]phenyl}-imino)diethanol was used in polyaddition reaction with di-isocyanate to obtain a new polyurethane polymeric material showing nonlinear optical and photochromic properties. The maximum absorption band of the polymer film was at 418 nm. The illumination of the film with crossed beams of the 488 nm Ar + laser yielded surface relief grating of regular structure. Measurement of the frequency doubling signal with 1064 nm laser indicated the polymer as interesting material for photooptical applications. The measured nonlinear optical coefficient, d33, reached 90.2 pm/V.

Increased accuracy of ligand sensing by receptor diffusion on cell surface

NASA Astrophysics Data System (ADS)

Aquino, Gerardo; Endres, Robert G.

2010-10-01

The physical limit with which a cell senses external ligand concentration corresponds to the perfect absorber, where all ligand particles are absorbed and overcounting of same ligand particles does not occur. Here, we analyze how the lateral diffusion of receptors on the cell membrane affects the accuracy of sensing ligand concentration. Specifically, we connect our modeling to neurotransmission in neural synapses where the diffusion of glutamate receptors is already known to refresh synaptic connections. We find that receptor diffusion indeed increases the accuracy of sensing for both the glutamate α -Amino-3-hydroxy-5-Methyl-4-isoxazolePropionic Acid (AMPA) and N -Methyl-D-aspartic Acid (NMDA) receptor, although the NMDA receptor is overall much noisier. We propose that the difference in accuracy of sensing of the two receptors can be linked to their different roles in neurotransmission. Specifically, the high accuracy in sensing glutamate is essential for the AMPA receptor to start membrane depolarization, while the NMDA receptor is believed to work in a second stage as a coincidence detector, involved in long-term potentiation and memory.

40 CFR Appendix B to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

Code of Federal Regulations, 2010 CFR

2010-07-01

... Use Conditions Substitutes Application Substitute Decision Conditions Comments Electronics Cleaning w.... Electronics cleaning w/CFC-113 Dibromomethane Unacceptable High ODP; other alternatives exist. Electronics...

Synthesis and antifungal activity of the derivatives of novel pyrazole carboxamide and isoxazolol pyrazole carboxylate.

PubMed

Sun, Jialong; Zhou, Yuanming

2015-03-09

A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives were designed and synthesized in this study. The structures of the compounds were elucidated based on spectral data (infrared, proton nuclear magnetic resonance and mass spectroscopy). Then, all of the compounds were bioassayed in vitro against four types of phytopathogenic fungi (Alternaria porri, Marssonina coronaria, Cercospora petroselini and Rhizoctonia solani) using the mycelium growth inhibition method. The results showed that some of the synthesized pyrazole carboxamides displayed notable antifungal activity. The isoxazole pyrazole carboxylate 7ai exhibited significant antifungal activity against R. solani, with an EC50 value of 0.37 μg/mL. Nonetheless, this value was lower than that of the commercial fungicide, carbendazol.

Amino acid substitutions in random mutagenesis libraries: lessons from analyzing 3000 mutations.

PubMed

Zhao, Jing; Frauenkron-Machedjou, Victorine Josiane; Kardashliev, Tsvetan; Ruff, Anna Joëlle; Zhu, Leilei; Bocola, Marco; Schwaneberg, Ulrich

2017-04-01

The quality of amino acid substitution patterns in random mutagenesis libraries is decisive for the success in directed evolution campaigns. In this manuscript, we provide a detailed analysis of the amino acid substitutions by analyzing 3000 mutations of three random mutagenesis libraries (1000 mutations each; epPCR with a low-mutation and a high-mutation frequency and SeSaM-Tv P/P) employing lipase A from Bacillus subtilis (bsla). A comparison of the obtained numbers of beneficial variants in the mentioned three random mutagenesis libraries with a site saturation mutagenesis (SSM) (covering the natural diversity at each amino acid position of BSLA) concludes the diversity analysis. Seventy-six percent of the SeSaM-Tv P/P-generated substitutions yield chemically different amino acid substitutions compared to 64% (epPCR-low) and 69% (epPCR-high). Unique substitutions from one amino acid to others are termed distinct amino acid substitutions. In the SeSaM-Tv P/P library, 35% of all theoretical distinct amino acid substitutions were found in the 1000 mutation library compared to 25% (epPCR-low) and 26% (epPCR-high). Thirty-six percent of distinct amino acid substitutions found in SeSaM-Tv P/P were unobtainable by epPCR-low. Comparison with the SSM library showed that epPCR-low covers 15%, epPCR-high 18%, and SeSaM-Tv P/P 21% of obtainable beneficial amino acid positions. In essence, this study provides first insights on the quality of epPCR and SeSaM-Tv P/P libraries in terms of amino acid substitutions, their chemical differences, and the number of obtainable beneficial amino acid positions.

Kinetic modeling of the monoamine oxidase B radioligand [¹¹C]SL25.1188 in human brain with high-resolution positron emission tomography.

PubMed

Rusjan, Pablo M; Wilson, Alan A; Miler, Laura; Fan, Ian; Mizrahi, Romina; Houle, Sylvain; Vasdev, Neil; Meyer, Jeffrey H

2014-05-01

This article describes the kinetic modeling of [(11)C]SL25.1188 ([(S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)-benzo[d]isoxazol-3-yl]-oxazolidin-2-[(11)C]one]) binding to monoamine oxidase B (MAO-B) in the human brain using high-resolution positron emission tomography (PET). Seven healthy subjects underwent two separate 90- minute PET scans after an intravenous injection of [(11)C]SL25.1188. Complementary arterial blood sampling was acquired. Radioactivity was quickly eliminated from plasma with 80% of parent compound remaining at 90 minutes. Metabolites were more polar than the parent compound. Time-activity curves showed high brain uptake, early peak and washout rate consistent with known regional MAO-B concentration. A two-tissue compartment model (2-TCM) provided better fits to the data than a 1-TCM. Measurement of total distribution volume (VT) showed very good identifiability (based on coefficient of variation (COV)) for all regions of interest (ROIs) (COV(VT)<8%), low between-subject variability (∼20%), and quick temporal convergence (within 5% of final value at 45 minutes). Logan graphical method produces very good estimation of VT. Regional VT highly correlated with previous postmortem report of MAO-B level (r(2)= ≥ 0.9). Specific binding would account from 70% to 90% of VT. Hence, VT measurement of [(11)C]SL25.1(1)88 PET is an excellent estimation of MAO-B concentration.

A Strategic Decision Matrix for Analyzing Food Service Operations at Air Force Bases

DTIC Science & Technology

2006-12-01

substitute product can replace your product, for example high - fructose corn syrup can substitute for sugar. Substitutes may negatively affect...dining facility closed and receive BAS. Customers can be happy with customer service and the quality of the food (a high customer satisfaction level...Services squadron may achieve significant cost savings by pursuing the NAF MOA but must also weigh the dollar savings against the threat of high

Statistical Physics of Complex Substitutive Systems

NASA Astrophysics Data System (ADS)

Jin, Qing

Diffusion processes are central to human interactions. Despite extensive studies that span multiple disciplines, our knowledge is limited to spreading processes in non-substitutive systems. Yet, a considerable number of ideas, products, and behaviors spread by substitution; to adopt a new one, agents must give up an existing one. This captures the spread of scientific constructs--forcing scientists to choose, for example, a deterministic or probabilistic worldview, as well as the adoption of durable items, such as mobile phones, cars, or homes. In this dissertation, I develop a statistical physics framework to describe, quantify, and understand substitutive systems. By empirically exploring three collected high-resolution datasets pertaining to such systems, I build a mechanistic model describing substitutions, which not only analytically predicts the universal macroscopic phenomenon discovered in the collected datasets, but also accurately captures the trajectories of individual items in a complex substitutive system, demonstrating a high degree of regularity and universality in substitutive systems. I also discuss the origins and insights of the parameters in the substitution model and possible generalization form of the mathematical framework. The systematical study of substitutive systems presented in this dissertation could potentially guide the understanding and prediction of all spreading phenomena driven by substitutions, from electric cars to scientific paradigms, and from renewable energy to new healthy habits.

Substituting freshwater: Can ocean desalination and water recycling capacities substitute for groundwater depletion in California?

PubMed

Badiuzzaman, Pierre; McLaughlin, Eoin; McCauley, Darren

2017-12-01

While the sustainability of resource depletion is a longstanding environmental concern, wider attention has recently been given to growing water scarcity and groundwater depletion. This study seeks to test the substitutability assumption embedded in weak sustainability indicators using a case study of Californian water supply. The volume of groundwater depletion is used as a proxy for unsustainable water consumption, and defined by synthesising existing research estimates into low, medium and high depletion baselines. These are compared against projected water supply increases from ocean desalination and water recycling by 2035, to determine whether new, drought-proof water sources can substitute for currently unsustainable groundwater consumption. Results show that the maximum projected supply of new water, 2.47 million acre-feet per year (MAF/yr), is sufficient to meet low depletion estimates of 2.02 MAF/yr, but fails to come near the high depletion estimate of 3.44 MAF/yr. This does not necessarily indicate physical limitations of substitutability, but more so socio-economic limitations influenced by high comparative costs. By including capacities in demand-substitutability via urban water conservation, maximum predicted capacities reach 5.57 MAF/yr, indicating wide room for substitution. Based on these results, investment in social and institutional capital is an important factor to enhance demand-side substitutability of water and other natural resources, which has been somewhat neglected by the literature on the substitutability of natural resources. Copyright © 2017 Elsevier Ltd. All rights reserved.

Promotion and prelacteal feeding of breastmilk substitutes among mothers in Kathmandu Valley, Nepal.

PubMed

Pries, Alissa M; Huffman, Sandra L; Adhikary, Indu; Upreti, Senendra Raj; Dhungel, Shrid; Champeny, Mary; Zehner, Elizabeth

2016-04-01

In 1992, Nepal passed the Mother's Milk Substitutes (Control of Sale and Distribution) Act in order to regulate the sale, distribution and promotion of substitutes for breastmilk within Nepal, in an effort to protect and promote breastfeeding. Helen Keller International, in collaboration with Nepal's Ministry of Health and Population's Child Health Division, implemented a study to assess mothers' exposure to promotions for and utilization of breastmilk substitutes in Kathmandu Valley, Nepal. A health facility-based, cross-sectional survey was conducted among 304 mothers being discharged after delivery. Prelacteal feeding of breastmilk substitutes is prevalent (55.9% of mothers, n = 170). Reported recommendations during antenatal checks and after delivery from health professionals to use breastmilk substitutes were prevalent, occurring among 47.4% (n = 144) of mothers; rates of these recommendations were significantly higher for mothers that delivered in private health facilities, as compared with public (67.7% vs. 38.0%, P < 0.001). Mothers that received a recommendation to use a breastmilk substitute from a health worker were 16.7 times more likely to provide a prelacteal feed of a breastmilk substitute, as compared with mothers that did not receive a recommendation (P < 0.001). Few mothers reported observation of commercial advertisements for breastmilk substitutes inside a health facility (reported by 3.6% of mothers). No mothers reported receiving a sample of a breastmilk substitute, bottle or teat from a health professional. More information is needed to determine why there is such a high rate of health worker recommendations for breastmilk substitute use in the first few days after delivery. While utilization of breastmilk substitutes is low among mothers of young children in Nepal, prelacteal feeding of breastmilk substitutes is highly prevalent in Kathmandu Valley. Reported recommendations from health professionals to use breastmilk substitutes are common (over 40%) and are associated with prelacteal feeding among Nepal mothers included in this study. Provision of lactation management training to health workers and monitoring their practices regularly could strengthen breastfeeding counselling, aid in reducing high rates of prelacteal feeding and contribute to improved infant feeding practices. © 2016 The Authors. Maternal & Child Nutrition published byJohn Wiley & Sons Ltd.

Improved methodologies for the preparation of highly substituted pyridines.

PubMed

Fernández Sainz, Yolanda; Raw, Steven A; Taylor, Richard J K

2005-11-25

[reaction: see text] Two separate strategies have been developed for the preparation of highly substituted pyridines from 1,2,4-triazines via the inverse-electron-demand Diels-Alder reaction: a microwave-promoted, solvent-free procedure and a tethered imine-enamine (TIE) approach. Both routes avoid the need for a discrete aromatization step and offer significant advantages over the classical methods, giving a wide variety of tri-, tetra-, and penta-substituted pyridines in high, optimized yields.

High-Temperature Thermoelectric and Microstructural Characteristics of Cobalt-Based Oxides with Ga Substituted on the Co-Site

NASA Astrophysics Data System (ADS)

Nong, N. V.; Yanagiya, S.; Monica, S.; Pryds, N.; Ohtaki, M.

2011-05-01

The effects of Ga substitution on the Co-site on the high-temperature thermoelectric properties and microstructure are investigated for the misfitlayered Ca3Co4O9 and the complex perovskite-related Sr3RECo4O10.5 (RE = rare earth) cobalt-based oxides. For both systems, substitution of Ga for Co results in a simultaneous increase in the Seebeck coefficient ( S) and the electrical conductivity ( σ), and the influence is more significant in the high temperature region. The power factor ( S 2 σ) is thereby remarkably improved by Ga substitution, particularly at high temperatures. Texture factor calculations using x-ray diffraction pattern data for pressed and powder samples reveal that the Ga-doped samples are highly textured. Microstructure observed by scanning electron microscopy shows very well-crystallized grains for the samples with Ga substitution for Co. Among the Ga-doped samples, Ca3Co3.95Ga0.05O9 shows the best ZT value of 0.45 at 1200 K, which is about 87.5% higher than the nondoped one, a considerable improvement.

Tunable ferromagnetic resonance in La-Co substituted barium hexaferrites at millimeter wave frequencies

NASA Astrophysics Data System (ADS)

Korolev, Konstantin A.; Wu, Chuanjian; Yu, Zhong; Sun, Ke; Afsar, Mohammed N.; Harris, Vincent G.

2018-05-01

Transmittance measurements have been performed on La-Co substituted barium hexaferrites in millimeter waves. Broadband millimeter-wave measurements have been carried out using the free space quasi-optical spectrometer, equipped with a set of high power backward wave oscillators covering the frequency range of 30 - 120 GHz. Strong absorption zones have been observed in the millimeter-wave transmittance spectra of all La-Co substituted barium hexaferrites due to the ferromagnetic resonance. Linear shift of ferromagnetic resonance frequency as functions of La-Co substitutions have been found. Real and imaginary parts of dielectric permittivity of La-Co substituted barium hexaferrites have been calculated using the analysis of recorded high precision transmittance spectra. Frequency dependences of magnetic permeability of La-Co substituted barium hexaferrites, as well as saturation magnetization and anisotropy field have been determined based on Schlömann's theory for partially magnetized ferrites. La-Co substituted barium hexaferrites have been further investigated by DC magnetization to assess magnetic behavior and compare with millimeter wave data. Consistency of saturation magnetization determined independently by both millimeter wave absorption and DC magnetization have been found for all La-Co substituted barium hexaferrites. These materials seem to be quite promising as tunable millimeter wave absorbers, filters, circulators, based on the adjusting of their substitution parameters.

Clinical review: impact of statin substitution policies on patient outcomes.

PubMed

Atar, Dan; Carmena, Rafael; Clemmensen, Peter; K-Laflamme, Annik; Wassmann, Sven; Lansberg, Peter; Hobbs, Richard

2009-01-01

The increasing awareness of cost issues in health care has led to the increasing use of policy-driven substitution of branded for generic medications, particularly relative to statin treatment for cardiovascular diseases. While there are potential short-term health care savings, the consequences for primary care are under-researched. Our objective was to review data on intensive statin therapy and generic substitution in patients at high cardiovascular risk. Current treatment guidelines for the prevention of cardiovascular disease are consistent in their recommendations regarding statin therapy and treatment targets. Clinical trials demonstrate that to reduce cardiovascular events, a statin is more effective than placebo, intensive statin therapy is more effective than moderate statin therapy in patients with established coronary disease, and in patients receiving intensive statin therapy the lowest risk is associated with the lowest low-density lipoprotein levels. However, in clinical practice, patients at high cardiovascular risk are prone to be undertreated. Observational studies suggest that mandatory statin substitution may increase the gap between achieved and recommended therapeutic targets. Substitution of generic statins may be cost-saving, particularly at the primary prevention level. However, statin substitution policies have not been adequately studied on a population level. Data raise concern that mandated statin substitution may lead to unfavourable treatment choices at the level of the individual high-risk patient.

Effects of disordered Ru substitution in BaFe2As2: possible realization of superdiffusion in real materials.

PubMed

Wang, Limin; Berlijn, Tom; Wang, Yan; Lin, Chia-Hui; Hirschfeld, P J; Ku, Wei

2013-01-18

An unexpected insensitivity of the Fermi surface to impurity scattering is found in Ru substituted BaFe(2)As(2) from first-principles theory, offering a natural explanation of the unusual resilience of transport and superconductivity to a high level of disordered substitution in this material. This robustness is shown to originate from a coherent interference of correlated on-site and intersite impurity scattering, similar in spirit to the microscopic mechanism of superdiffusion in one dimension. Our result also demonstrates a strong substitution dependence of the Fermi surface and carrier concentration and provides a resolution to current discrepancies in recent photoelectron spectroscopy. These effects offer a natural explanation of the diminishing long-range magnetic, orbital, and superconducting orders with high substitution.

Degradation of sulfamethoxazole by UV, UV/H2O2 and UV/persulfate (PDS): Formation of oxidation products and effect of bicarbonate.

PubMed

Yang, Yi; Lu, Xinglin; Jiang, Jin; Ma, Jun; Liu, Guanqi; Cao, Ying; Liu, Weili; Li, Juan; Pang, Suyan; Kong, Xiujuan; Luo, Congwei

2017-07-01

The frequent detection of sulfamethoxazole (SMX) in wastewater and surface waters gives rise of concerns about their ecotoxicological effects and potential risks to induce antibacterial resistant genes. UV/hydrogen peroxide (UV/H 2 O 2 ) and UV/persulfate (UV/PDS) advanced oxidation processes have been demonstrated to be effective for the elimination of SMX, but there is still a need for a deeper understanding of product formations. In this study, we identified and compared the transformation products of SMX in UV, UV/H 2 O 2 and UV/PDS processes. Because of the electrophilic nature of SO 4 - , the second-order rate constant for the reaction of sulfate radical (SO 4 - ) with the anionic form of SMX was higher than that with the neutral form, while hydroxyl radical (OH) exhibited comparable reactivity to both forms. The direct photolysis of SMX predominately occurred through cleavage of the NS bond, rearrangement of the isoxazole ring, and hydroxylation mechanisms. Hydroxylation was the dominant pathway for the reaction of OH with SMX. SO 4 - favored attack on NH 2 group of SMX to generate a nitro derivative and dimeric products. The presence of bicarbonate in UV/H 2 O 2 inhibited the formation of hydroxylated products, but promoted the formation of the nitro derivative and the dimeric products. In UV/PDS, bicarbonate increased the formation of the nitro derivative and the dimeric products, but decreased the formation of the hydroxylated dimeric products. The different effect of bicarbonate on transformation products in UV/H 2 O 2 vs. UV/PDS suggested that carbonate radical (CO 3 - ) oxidized SMX through the electron transfer mechanism similar to SO 4 - but with less oxidation capacity. Additionally, SO 4 - and CO 3 - exhibited higher reactivity to the oxazole ring than the isoxazole ring of SMX. Ecotoxicity of transformation products was estimated by ECOSAR program based on the quantitative structure-activity relationship analysis as well as by experiments using Vibrio fischeri, and these results indicated that the oxidation of SO 4 - or CO 3 - with SMX generated more toxic products than those of OH. Copyright © 2017 Elsevier Ltd. All rights reserved.

Eight Ways to Make Sure Substitute Teachers Aren't Baby-Sitters.

ERIC Educational Resources Information Center

Drury, William R.

1988-01-01

Substitutes might never be as good as regular teachers, but they still can provide high-quality instruction. Suggestions include meeting with them as a group twice a year, principal and peer support, and development workshops specifically for substitutes. (TE)

Pervasive promotion of breastmilk substitutes in Phnom Penh, Cambodia, and high usage by mothers for infant and young child feeding

PubMed Central

Huffman, Sandra L.; Mengkheang, Khin; Kroeun, Hou; Champeny, Mary; Roberts, Margarette; Zehner, Elizabeth

2016-01-01

Abstract In 2005, Cambodia passed the Sub‐Decree on Marketing of Products for Infant and Young Child Feeding (no. 133) to regulate promotion of commercial infant and young child food products, including breastmilk substitutes. Helen Keller International assessed mothers' exposure to commercial promotions for breastmilk substitutes and use of these products through a cross‐sectional survey among 294 mothers of children less than 24 months of age. Eighty‐six per cent of mothers reported observing commercial promotions for breastmilk substitutes, 19.0% reported observing infant and young child food product brands/logos on health facility equipment and 18.4% reported receiving a recommendation from a health professional to use a breastmilk substitute. Consumption of breastmilk substitutes was high, occurring among 43.1% of children 0–5 months and 29.3% of children 6–23 months of age. Findings also indicated a need to improve breastfeeding practices among Phnom Penh mothers. Only 36.1% of infants 0–5 months of age were exclusively breastfed, and 12.5% of children 20–23 months of age were still breastfed. Children that received a breastmilk substitute as a prelacteal feed were 3.9 times more likely to be currently consuming a breastmilk substitute than those who did not. Despite restriction of commercial promotions for breastmilk substitutes without government approval, occurrence of promotions is high and use is common among Phnom Penh mothers. In a country with high rates of child malnutrition and pervasive promotions in spite of restrictive national law, full implementation of Cambodia's Sub‐Decree 133 is necessary, as are policies and interventions to support exclusive and continued breastfeeding. Key messages Despite prohibition without specific approval by the national government, companies are pervasively promoting breast‐milk substitutes in Phnom Penh, particularly on television and at points of sale.Strengthened implementation and enforcement of Cambodia's subdecree 133 are needed to better regulate promotion in order to protect breastfeeding for the nutrition and health of infants and young children in Cambodia.Mothers who used a breast‐milk substitute as a prelacteal feed were 3.9 times more likely to currently feed this same child a breast‐milk substitute, as compared with mothers who did not provide breast‐milk substitute as a prelacteal feed. Supporting breastfeeding among mothers after delivery is critical to establish and sustain optimal breastfeeding practices.Use of breast‐milk substitutes is also very common among mothers of children under 2 years of age in Phnom Penh. We recommend promoting exclusive and continued breastfeeding as beneficial to children's health and development, and supporting policy and workplace environments that enable breastfeeding up to and beyond 24 months of age. PMID:27061955

Pervasive promotion of breastmilk substitutes in Phnom Penh, Cambodia, and high usage by mothers for infant and young child feeding.

PubMed

Pries, Alissa M; Huffman, Sandra L; Mengkheang, Khin; Kroeun, Hou; Champeny, Mary; Roberts, Margarette; Zehner, Elizabeth

2016-04-01

In 2005, Cambodia passed the Sub-Decree on Marketing of Products for Infant and Young Child Feeding (no. 133) to regulate promotion of commercial infant and young child food products, including breastmilk substitutes. Helen Keller International assessed mothers' exposure to commercial promotions for breastmilk substitutes and use of these products through a cross-sectional survey among 294 mothers of children less than 24 months of age. Eighty-six per cent of mothers reported observing commercial promotions for breastmilk substitutes, 19.0% reported observing infant and young child food product brands/logos on health facility equipment and 18.4% reported receiving a recommendation from a health professional to use a breastmilk substitute. Consumption of breastmilk substitutes was high, occurring among 43.1% of children 0-5 months and 29.3% of children 6-23 months of age. Findings also indicated a need to improve breastfeeding practices among Phnom Penh mothers. Only 36.1% of infants 0-5 months of age were exclusively breastfed, and 12.5% of children 20-23 months of age were still breastfed. Children that received a breastmilk substitute as a prelacteal feed were 3.9 times more likely to be currently consuming a breastmilk substitute than those who did not. Despite restriction of commercial promotions for breastmilk substitutes without government approval, occurrence of promotions is high and use is common among Phnom Penh mothers. In a country with high rates of child malnutrition and pervasive promotions in spite of restrictive national law, full implementation of Cambodia's Sub-Decree 133 is necessary, as are policies and interventions to support exclusive and continued breastfeeding. Despite prohibition without specific approval by the national government, companies are pervasively promoting breast-milk substitutes in Phnom Penh, particularly on television and at points of sale. Strengthened implementation and enforcement of Cambodia's subdecree 133 are needed to better regulate promotion in order to protect breastfeeding for the nutrition and health of infants and young children in Cambodia. Mothers who used a breast-milk substitute as a prelacteal feed were 3.9 times more likely to currently feed this same child a breast-milk substitute, as compared with mothers who did not provide breast-milk substitute as a prelacteal feed. Supporting breastfeeding among mothers after delivery is critical to establish and sustain optimal breastfeeding practices. Use of breast-milk substitutes is also very common among mothers of children under 2 years of age in Phnom Penh. We recommend promoting exclusive and continued breastfeeding as beneficial to children's health and development, and supporting policy and workplace environments that enable breastfeeding up to and beyond 24 months of age. © 2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons, Ltd.

An enantioselective route to alpha-methyl carboxylic acids via metal and enzyme catalysis.

PubMed

Norinder, Jakob; Bogár, Krisztián; Kanupp, Lisa; Bäckvall, Jan-E

2007-11-22

Dynamic kinetic resolution of allylic alcohols to allylic acetates followed by copper-catalyzed allylic substitution gave alkenes in high yields and high optical purity. Subsequent oxidative C-C double bond cleavage afforded pharmaceutically important alpha-methyl substituted carboxylic acids in high ee.

Perampanel as adjunctive therapy in highly refractory epilepsies: Real-world data from an Italian tertiary care epilepsy centre.

PubMed

Morano, Alessandra; Fattouch, Jinane; Albini, Mariarita; Casciato, Sara; Fanella, Martina; Basili, Luca Manfredi; Viganò, Alessandro; Manfredi, Mario; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

2018-07-15

Perampanel (PER) is a selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist, licensed as adjunctive therapy in focal epilepsy and primary generalized tonic-clonic seizures (pGTCSs). We performed a retrospective study on highly refractory adult patients taking PER, with 1-year follow-up. Retention rate represented the primary outcome of our work; seizure frequency reduction (≥50%), "switch rate" and proportion of adverse events (AEs) were evaluated as secondary endpoints. Eighty-nine subjects (47 females, age range: 19-78 years) were included. Seventy-three had focal epilepsy (FE), 9 generalized epilepsy and 7 epileptic encephalopathy. All patients were highly drug-resistant (medication failures: 5-17). Retention rate was 87.6%, 63% and 51.7% at 3, 6 and 12 months. Responders were 27/89 (30.3%), with 8/27 seizure-free. The number of previous treatment failures and the concomitant use of enzyme inducers negatively influenced clinical response, whereas no correlation was documented between PER dose and outcome. Responder proportion was more satisfying in structural FE than in FE of unknown etiology (33% versus 20%), and in secondarily GTCSs than focal seizures (54% vs 28%), whereas pGTCSs showed a lower reponse rate (25%). Mild-to-moderate AEs (mainly dizziness, gait disturbances and psychiatric effects) were reported by 40% of patients; serious psychiatric AEs usually occurred in subjects with psychiatric comorbidities. Our study confirms the tolerability and effectiveness of PER in highly drug-resistant patients with different epilepsy syndromes and aetiologies. Copyright © 2018 Elsevier B.V. All rights reserved.

A Bilayer Engineered Skin Substitute for Wound Repair in an Irradiation-Impeded Healing Model on Rat

PubMed Central

Mohd Hilmi, A.B.; Hassan, Asma; Halim, Ahmad Sukari

2015-01-01

Objective: An engineered skin substitute is produced to accelerate wound healing by increasing the mechanical strength of the skin wound via high production of collagen bundles. During the remodeling stage of wound healing, collagen deposition is the most important event. The collagen deposition process may be altered by nutritional deficiency, diabetes mellitus, microbial infection, or radiation exposure, leading to impaired healing. This study describes the fabrication of an engineered bilayer skin substitute and evaluates its effectiveness for the production of collagen bundles in an impaired healing model. Approach: Rats were exposed to 10 Gy of radiation. Two months postirradiation, the wounds were excised and treated with one of three skin replacement products: bilayer engineered skin substitutes, chitosan skin templates, or duoderm©. The collagen deposition was analyzed by hematoxylin and eosin staining. Results: On day 21 postwound, the irradiated wounds displayed increased collagen bundle deposition after treatment using bilayer engineered skin substitutes (3.4±0.25) and chitosan skin templates (3.2±0.58) compared with duoderm (2.0±0.63). Innovation: We provide the first report on the fabrication of bilayer engineered skin substitutes using high density human dermal fibroblasts cocultured with HFSCs on chitosan skin templates. Conclusion: The high density of fibroblasts significantly increases the penetration of cells into chitosan skin templates, contributing to the fabrication of bilayer engineered skin substitute. PMID:26005597

Synthesis of enyne and aryl vinyl sulfoxides: functionalization via Pummerer rearrangement.

PubMed

Souza, Frederico B; Shamim, Anwar; Argomedo, Luiz M Z; Pimenta, Daniel C; Stefani, Hélio A

2015-11-01

An efficient methodology for the synthesis of aryl-substituted vinyl sulfoxides through direct substitution of aryl-substituted alkynyl grignard reagents on menthyl-p-toluenesulfinate followed by Suzuki-Miyaura cross-coupling reaction has been developed. It has also been described that the reaction of alkyl-substituted and cycloalkyl-substituted alkynyl grignard reagents with menthyl-p-toluenesulfinate led to two products, i.e., alkynyl sulfoxide derivatives, as a result of substitution, and enyne sulfoxide derivatives, which resulted from substitution followed by Michael type addition. It was possible to selectively synthesize the enyne sulfoxide derivatives by changing the concentration of the grignard reagent. These alkenyl sulfoxides were transformed into the corresponding [Formula: see text]-thio aldehydes in high yields via additive Pummerer rearrangement.

Zn-site Substitution Effect in YbCo2Zn20

NASA Astrophysics Data System (ADS)

Kobayashi, Riki; Takamura, Haruki; Higa, Yasuyuki; Ikeda, Yoichi; Matsubayashi, Kazuyuki; Uwatoko, Yoshiya; Yoshizawa, Hideki; Aso, Naofumi

2017-04-01

We have investigated the substitution effect of YbCo2(Zn1-xTx)20 (T = Cu, Ga, and Cd) systems by using the experiments of X-ray powder diffraction (XRPD), specific heat, magnetic susceptibility, magnetization, and electrical resistivity in order to find out a material that approaches a quantum critical point by chemical pressure. The XRPD and electrical resistivity measurements clarify that the Cu-substitution makes the lattice constants shrink and keeps the magnetic electrical resistivity high, while the Ga- and the Cd-substitution show opposite relation of the Cu-substitution. However, we could not detect clear substitution effect in the specific heat, magnetic susceptibility, and magnetization measurements of Cu-substitution system within our experiments. It is necessary that to study the Cu-substitution samples that have higher x value at lower temperature.

Stereoselective synthesis of novel highly substituted isochromanone and isoquinolinone-containing exocyclic tetrasubstituted alkenes.

PubMed

Arthuis, Martin; Pontikis, Renée; Florent, Jean-Claude

2009-03-06

An efficient synthetic route toward the synthesis of highly substituted arylethylidene-isoquinolinones/isochromanones is reported. The tandem carbopalladation/Suzuki-Miyaura coupling sequence stereoselectively provided various functionalized polycyclic compounds in moderate to excellent yields.

catena-Poly[bis-(sulfamethoxazolium) [[trichloridocadmate(II)]-μ-chlorido] monohydrate].

PubMed

Subashini, Annamalai; Muthiah, Packianathan Thomas; Bocelli, Gabriele; Cantoni, Andrea

2007-12-21

In the title compound, {(C(10)H(12)N(3)O(3)S)(2)[CdCl(4)]·H(2)O}(n), the Cd(II) atom is five-coordinate with a distorted trigonal-bipyramidal geometry formed by chloride ions. The Cd atom and two of the Cl atoms lie on a mirror plane. The cation is protonated on the amino group N atom; it is not coordinated to cadmium, but is hydrogen bonded to the chlorido ligands. Each water mol-ecule bridges two chlorido ligands, generating ring motifs along the -Cd-Cl-Cd- chains. The isoxazole unit and the amide groups are linked through a pair of N-H⋯N hydrogen bonds. The crystal structure is stabilized by N-H⋯O, O-H⋯Cl, C-H⋯N, N-H⋯Cl and C-H⋯O hydrogen bonds.

catena-Poly[bis­(sulfamethoxazolium) [[trichloridocadmate(II)]-μ-chlorido] monohydrate

PubMed Central

Subashini, Annamalai; Muthiah, Packianathan Thomas; Bocelli, Gabriele; Cantoni, Andrea

2008-01-01

In the title compound, {(C10H12N3O3S)2[CdCl4]·H2O}n, the CdII atom is five-coordinate with a distorted trigonal–bipyramidal geometry formed by chloride ions. The Cd atom and two of the Cl atoms lie on a mirror plane. The cation is protonated on the amino group N atom; it is not coordinated to cadmium, but is hydrogen bonded to the chlorido ligands. Each water mol­ecule bridges two chlorido ligands, generating ring motifs along the –Cd—Cl—Cd– chains. The isoxazole unit and the amide groups are linked through a pair of N—H⋯N hydrogen bonds. The crystal structure is stabilized by N—H⋯O, O—H⋯Cl, C—H⋯N, N—H⋯Cl and C—H⋯O hydrogen bonds. PMID:21200590

Substitution of the nitro group with Grignard reagents: facile arylation and alkenylation of pyridine N-oxides.

PubMed

Zhang, Fang; Zhang, Song; Duan, Xin-Fang

2012-11-02

The unprecedented substitution of a nitro group with aryl or alkenyl groups of Grignard reagents affords 2-aryl or alkenylpyridine N-oxides in modest to high yields with high chemoselectivity. This protocol allows a simple and clean synthesis of various 2-substituted pyridine N-oxides and the corresponding pyridine derivatives. Furthermore, straightforward one-pot iterative functionality of pyridine N-oxides could also be achieved simply by successive applications of two Grignard reagents.

Effect of Substitution (Ta, Al, Ga) on the Conductivity of Li7La3Zr2O12

DTIC Science & Technology

2012-01-30

xTax012). Conductivity data was not included in their report. Similarly to Ta, Nb substitution for Zr should also lower the Li content of the LLZO and a...high Li ion conductivity (0.8 mS cm−1 at 298 K) cubic garnet sample has been reported with Nb substitution for Zr by Ohta et al. [15]. However, Ta is...substitution for Zr follows this approach and it is desirable for a couple rea- sons. First, Ta is stable relative to Li [13]. Second, Ta substitution

Nucleophilic substitution reaction for post-functionalization of polyoxometalates

DOE PAGES

Yin, Panchao; Li, Qiang; Zhang, Jin; ...

2015-07-06

In this study, a hexamolybdate-based organic inorganic hybrid molecule containing a chloralkane fragment is synthesized and its Cl atom can be substituted by iodine and nitrate through nucleophilic substitution reactions in high yields, which provide a post-functionalization protocol to bring in various additional functional groups into polyoxometalate-based hybrid materials under mild conditions.

Adaptive Molecular Evolution for 13,000 Phage Generations

PubMed Central

Wichman, Holly A.; Millstein, Jack; Bull, J. J.

2005-01-01

Bacteriophage φX174 was evolved on a continuous supply of sensitive hosts for 180 days (∼13,000 phage generations). The average rate of nucleotide substitution was nearly 0.2% (11 substitutions)/20 days, and, surprisingly, substitutions accumulated in a clock-like manner throughout the study, except for a low rate during the first 20 days. Rates of silent and missense substitutions varied over time and among genes. Approximately 40% of the 71 missense changes and 25% of the 58 silent changes have been observed in previous adaptations; the rate of parallel substitution was highest in the early phase of the evolution, but 7% of the later changes had evolved in previous studies of much shorter duration. Several lines of evidence suggest that most of the changes were adaptive, even many of the silent substitutions. The sustained, high rate of adaptive evolution for 180 days defies a model of adaptation to a constant environment. We instead suggest that continuing molecular evolution reflects a potentially indefinite arms race, stemming from high levels of co-infection and the resulting conflict among genomes competing within the same cell. PMID:15687276

Charge Transfer Directed Radical Substitution Enables para-Selective C–H Functionalization

PubMed Central

Boursalian, Gregory B.; Ham, Won Seok; Mazzotti, Anthony R.; Ritter, Tobias

2016-01-01

Efficient C–H functionalization requires selectivity for specific C–H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho- and meta- selectivity, but a general strategy for para-selective C–H functionalization has remained elusive. Herein, we introduce a previously unappreciated concept which enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit areneto-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate that the selectivity is predictable by a simple theoretical tool and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of charge transfer directed radical substitution could serve as the basis for the development of new, highly selective C–H functionalization reactions. PMID:27442288

Charge-transfer-directed radical substitution enables para-selective C-H functionalization

NASA Astrophysics Data System (ADS)

Boursalian, Gregory B.; Ham, Won Seok; Mazzotti, Anthony R.; Ritter, Tobias

2016-08-01

Efficient C-H functionalization requires selectivity for specific C-H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho and meta selectivity, but a general strategy for para-selective C-H functionalization has remained elusive. Herein we introduce a previously unappreciated concept that enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit arene-to-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate with a simple theoretical tool that the selectivity is predictable and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of radical substitution directed by charge transfer could serve as the basis for the development of new, highly selective C-H functionalization reactions.

Organocatalyzed Domino [3+2] Cycloaddition/Payne-Type Rearrangement using Carbon Dioxide and Epoxy Alcohols.

PubMed

Kleij, Arjan Willem; Sopeña, Sergio; Cozzolino, Mariachiara; Escudero-Adán, Eduardo C; Martínez Belmonte, Marta; Maquilón, Cristina

2018-05-09

An unprecedented organocatalytic approach towards highly substituted cyclic carbonates from tri- and tetra-substituted oxiranes and carbon dioxide has been developed. The protocol involves the use of a simple and cheap superbase under mild, additive- and metal-free conditions towards the initial formation of a less substituted carbonate product that equilibrates to a tri- or even tetra-substituted cyclic carbonate under thermodynamic control. The latter are conveniently trapped in situ providing overall a new domino process for synthetically elusive heterocyclic scaffolds. Control experiments provide a rationale for the observed cascade reactions, which demonstrate high similarity with the well-known Payne rearrangement of epoxy alcohols. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Amino Acid Substitutions in PB1 of Avian Influenza Viruses Influence Pathogenicity and Transmissibility in Chickens

PubMed Central

Suzuki, Yasushi; Uchida, Yuko; Tanikawa, Taichiro; Maeda, Naohiro; Takemae, Nobuhiro

2014-01-01

ABSTRACT Amino acid substitutions were introduced into avian influenza virus PB1 in order to characterize the interaction between polymerase activity and pathogenicity. Previously, we used recombinant viruses containing the hemagglutinin (HA) and neuraminidase (NA) genes from the highly pathogenic avian influenza virus (HPAIV) H5N1 strain and other internal genes from two low-pathogenicity avian influenza viruses isolated from chicken and wild-bird hosts (LP and WB, respectively) to demonstrate that the pathogenicity of highly pathogenic avian influenza viruses (HPAIVs) of subtype H5N1 in chickens is regulated by the PB1 gene (Y. Uchida et al., J. Virol. 86:2686–2695, 2012, doi:http://dx.doi.org/10.1128/JVI.06374-11). In the present study, we introduced a C38Y substitution into WB PB1 and demonstrated that this substitution increased both polymerase activity in DF-1 cells in vitro and the pathogenicity of the recombinant viruses in chickens. The V14A substitution in LP PB1 reduced polymerase activity but did not affect pathogenicity in chickens. Interestingly, the V14A substitution reduced viral shedding and transmissibility. These studies demonstrate that increased polymerase activity correlates directly with enhanced pathogenicity, while decreased polymerase activity does not always correlate with pathogenicity and requires further analysis. IMPORTANCE We identified 2 novel amino acid substitutions in the avian influenza virus PB1 gene that affect the characteristics of highly pathogenic avian influenza viruses (HPAIVs) of the H5N1 subtype, such as viral replication and polymerase activity in vitro and pathogenicity and transmissibly in chickens. An amino acid substitution at residue 38 in PB1 directly affected pathogenicity in chickens and was associated with changes in polymerase activity in vitro. A substitution at residue 14 reduced polymerase activity in vitro, while its effects on pathogenicity and transmissibility depended on the constellation of internal genes. PMID:25031333

Review: Potential Strength of Fly Ash-Based Geopolymer Paste with Substitution of Local Waste Materials with High-Temperature Effect

NASA Astrophysics Data System (ADS)

Subekti, S.; Bayuaji, R.; Darmawan, M. S.; Husin, N. A.; Wibowo, B.; Anugraha, B.; Irawan, S.; Dibiantara, D.

2017-11-01

This research provided an overview of the potential fly ash based geopolymer paste for application in building construction. Geopolymer paste with various variations of fly ash substitution with local waste material and high-temperature influence exploited with the fresh and hardened condition. The local waste material which utilized for this study were sandblasting waste, carbide waste, shell powder, bagasse ash, rice husk and bottom ash. The findings of this study indicated that fly-based geopolymer paste with local waste material substitution which had high-temperature influence ash showed a similar nature of OPC binders potentially used in civil engineering applications.

Novel high contrast electrochromic polymer materials based on 3,4-propylenedioxythiophene

NASA Astrophysics Data System (ADS)

Sahoo, Rabindra; Mishra, Sarada P.; Kumar, Anil; Sindhu, S.; Narasimha Rao, K.; Gopal, E. S. R.

2007-09-01

Mono and di allyl and napthyl substituted 3,4-propylenedioxythiophenes were synthesized and polymerized electrochemically. All the monomers were characterized for their molecular structures, and the polymers were characterized for their electrochemical properties. The disubstituted derivatives showed higher contrast than the corresponding mono substituted derivatives. The allyl substituted polymers showed higher contrast and faster switching time than corresponding napthyl substituted derivatives. The presence of the allyl group as the pendant can be used for further functionalization of the polymer.

Propargylic activation across a heterobimetallic ir-sn catalyst: nucleophilic substitution and indene formation with propargylic alcohols.

PubMed

Chatterjee, Paresh Nath; Roy, Sujit

2010-07-02

A nucleophilic substitution of propargylic alcohols with carbon (arene, heteroarene, and allyltrimethylsilane), sulfur (thiol), oxygen (alcohol), and nitrogen (sulfonamide) nucleophiles has been demonstrated using a high-valent [Ir(COD)(SnCl(3))Cl(mu-Cl)](2) catalyst in 1,2-dichloroethane to afford the corresponding propargylic products in moderate to excellent yields. Alkyl or aryl substituted tertiary propargylic alcohols produce substituted indenes with bulky arenes via allenylic intermediate. An electrophilic mechanism is proposed from Hammett correlation.

A DFT+U study of A-site and B-site substitution in BaFeO3-δ.

PubMed

Baiyee, Zarah Medina; Chen, Chi; Ciucci, Francesco

2015-09-28

BaFeO3-δ (BFO)-based perovskites have emerged as cheap and effective oxygen electrocatalysts for oxygen reduction reaction at high temperatures. The BFO cubic phase facilitates a high oxygen deficiency and is commonly stabilised by partial substitution. Understanding the electronic mechanisms of substitution and oxygen deficiency is key to rational material design, and can be realised through DFT analysis. In this work an in-depth first principle DFT+U study is undertaken to determine site distinctive characteristics for 12.5%, Y, La and Ce substitutions in BFO. In particular, it is shown that B-site doped structures exhibit a lower energy cost for oxygen vacancy formation relative to A site doping and pristine BFO. This is attributed to the stabilisation of holes in the oxygen sub-lattice and increased covalency of the Fe-O bonds of the FeO6 octahedra in B-site-substituted BFO. Charge analysis shows that A-site substitution amounts to donor doping and consequently impedes the accommodation of other donors (i.e. oxygen vacancies). However, A-site substitution may also exhibit a higher electronic conductivity due to less lattice distortion for oxygen deficiency compared to B-site doped structures. Furthermore, analysis of the local structural effects provides physical insight into stoichiometric expansions observed for this material.

pKa prediction from an ab initio bond length: part 3--benzoic acids and anilines.

PubMed

Harding, A P; Popelier, P L A

2011-06-21

The prediction of pK(a) from a single ab initio bond length has been extended to provide equations for benzoic acids and anilines. The HF/6-31G(d) level of theory is used for all geometry optimisations. Similarly to phenols (Part 2 of this series of publications), the meta-/para-substituted benzoic acids can be predicted from a single model constructed from one bond length. This model had an impressive RMSEP of 0.13 pK(a) units. The prediction of ortho-substituted benzoic acids required the identification of high-correlation subsets, where the compounds in the same subset have at least one of the same (e.g. halogens, hydroxy) ortho substituent. Two pK(a) equations are provided for o-halogen benzoic acids and o-hydroxybenzoic acids, where the RMSEP values are 0.19 and 0.15 pK(a) units, respectively. Interestingly, the bond length that provided the best model differed between these two high-correlation subsets. This demonstrates the importance of investigating the most predictive bond length, which is not necessarily the bond involving the acid hydrogen. Three high-correlation subsets were identified for the ortho-substituted anilines. These were o-halogen, o-nitro and o-alkyl-substituted aniline high-correlation subsets, where the RMSEP ranged from 0.23 to 0.44 pK(a) units. The RMSEP for the meta-/para-substituted aniline model was 0.54 pK(a) units. This value exceeded our threshold of 0.50 pK(a) units and was higher than both the m-/p-benzoic acids in this work and the m-/p-phenols (RMSEP = 0.43) of Part 2. Constructing two separate models for the meta- and para- substituted anilines, where RMSEP values of 0.63 and 0.33 pK(a) units were obtained respectively, revealed it was the meta-substituted anilines that caused the large RMSEP value. For unknown reasons the RMSEP value increased with the addition of a further twenty meta-substituted anilines to this model. The C-N bond always produced the best correlations with pK(a) for all the high-correlation subsets. A higher level of theory and an ammonia probe improved the statistics only marginally for the hydroxybenzoic acid high-correlation subsets.

Determination of isoxaflutole (balance) and its metabolites in water using solid phase extraction followed by high-performance liquid chromatography with ultraviolet or mass spectrometry

USGS Publications Warehouse

Lin, Chung-Ho; Lerch, Robert N.; Thurman, E. Michael; Garrett , Harold E.; George, Milon F.

2002-01-01

Balance (isoxaflutole, IXF) belongs to a new family of herbicides referred to as isoxazoles. IXF has a very short soil half-life (<24 h), degrading to a biologically active diketonitrile (DKN) metabolite that is more polar and considerably more stable. Further degradation of the DKN metabolite produces a nonbiologically active benzoic acid (BA) metabolite. Analytical methods using solid phase extraction followed by high-performance liquid chromatography−UV (HPLC-UV) or high-performance liquid chromatography−mass spectrometry (HPLC-MS) were developed for the analysis of IXF and its metabolites in distilled deionized water and ground water samples. To successfully detect and quantify the BA metabolite by HPLC-UV from ground water samples, a sequential elution scheme was necessary. Using HPLC-UV, the mean recoveries from sequential elution of the parent and its two metabolites from fortified ground water samples ranged from 68.6 to 101.4%. For HPLC-MS, solid phase extraction of ground water samples was performed using a polystyrene divinylbenzene polymer resin. The mean HPLC-MS recoveries of the three compounds from ground water samples spiked at 0.05−2 μg/L ranged from 100.9 to 110.3%. The limits of quantitation for HPLC-UV are approximately 150 ng/L for IXF, 100 ng/L for DKN, and 250 ng/L for BA. The limit of quantitation by HPLC-MS is 50 ng/L for each compound. The methods developed in this work can be applied to determine the transport and fate of Balance in the environment.

Identification of Small Molecule Inhibitors of Clostridium perfringens ε-Toxin Cytotoxicity Using a Cell-Based High-Throughput Screen.

PubMed

Lewis, Michelle; Weaver, Charles David; McClain, Mark S

2010-07-01

The Clostridium perfringens epsilon toxin, a select agent, is responsible for a severe, often fatal enterotoxemia characterized by edema in the heart, lungs, kidney, and brain. The toxin is believed to be an oligomeric pore-forming toxin. Currently, there is no effective therapy for countering the cytotoxic activity of the toxin in exposed individuals. Using a robust cell-based high-throughput screening (HTS) assay, we screened a 151,616-compound library for the ability to inhibit ε-toxin-induced cytotoxicity. Survival of MDCK cells exposed to the toxin was assessed by addition of resazurin to detect metabolic activity in surviving cells. The hit rate for this screen was 0.6%. Following a secondary screen of each hit in triplicate and assays to eliminate false positives, we focused on three structurally-distinct compounds: an N-cycloalkylbenzamide, a furo[2,3-b]quinoline, and a 6H-anthra[1,9-cd]isoxazol. None of the three compounds appeared to inhibit toxin binding to cells or the ability of the toxin to form oligomeric complexes. Additional assays demonstrated that two of the inhibitory compounds inhibited ε-toxin-induced permeabilization of MDCK cells to propidium iodide. Furthermore, the two compounds exhibited inhibitory effects on cells pre-treated with toxin. Structural analogs of one of the inhibitors identified through the high-throughput screen were analyzed and provided initial structure-activity data. These compounds should serve as the basis for further structure-activity refinement that may lead to the development of effective anti-ε-toxin therapeutics.

Identification of Small Molecule Inhibitors of Clostridium perfringens ε-Toxin Cytotoxicity Using a Cell-Based High-Throughput Screen

PubMed Central

Lewis, Michelle; Weaver, Charles David; McClain, Mark S.

2010-01-01

The Clostridium perfringens epsilon toxin, a select agent, is responsible for a severe, often fatal enterotoxemia characterized by edema in the heart, lungs, kidney, and brain. The toxin is believed to be an oligomeric pore-forming toxin. Currently, there is no effective therapy for countering the cytotoxic activity of the toxin in exposed individuals. Using a robust cell-based high-throughput screening (HTS) assay, we screened a 151,616-compound library for the ability to inhibit ε-toxin-induced cytotoxicity. Survival of MDCK cells exposed to the toxin was assessed by addition of resazurin to detect metabolic activity in surviving cells. The hit rate for this screen was 0.6%. Following a secondary screen of each hit in triplicate and assays to eliminate false positives, we focused on three structurally-distinct compounds: an N-cycloalkylbenzamide, a furo[2,3-b]quinoline, and a 6H-anthra[1,9-cd]isoxazol. None of the three compounds appeared to inhibit toxin binding to cells or the ability of the toxin to form oligomeric complexes. Additional assays demonstrated that two of the inhibitory compounds inhibited ε-toxin-induced permeabilization of MDCK cells to propidium iodide. Furthermore, the two compounds exhibited inhibitory effects on cells pre-treated with toxin. Structural analogs of one of the inhibitors identified through the high-throughput screen were analyzed and provided initial structure-activity data. These compounds should serve as the basis for further structure-activity refinement that may lead to the development of effective anti-ε-toxin therapeutics. PMID:20721308

Determination of isoxaflutole (balance) and its metabolites in water using solid phase extraction followed by high-performance liquid chromatography with ultraviolet or mass spectrometry.

PubMed

Lin, Chung-Ho; Lerch, Robert N; Thurman, E Michael; Garrett, Harold E; George, Milon F

2002-10-09

Balance (isoxaflutole, IXF) belongs to a new family of herbicides referred to as isoxazoles. IXF has a very short soil half-life (<24 h), degrading to a biologically active diketonitrile (DKN) metabolite that is more polar and considerably more stable. Further degradation of the DKN metabolite produces a nonbiologically active benzoic acid (BA) metabolite. Analytical methods using solid phase extraction followed by high-performance liquid chromatography-UV (HPLC-UV) or high-performance liquid chromatography-mass spectrometry (HPLC-MS) were developed for the analysis of IXF and its metabolites in distilled deionized water and ground water samples. To successfully detect and quantify the BA metabolite by HPLC-UV from ground water samples, a sequential elution scheme was necessary. Using HPLC-UV, the mean recoveries from sequential elution of the parent and its two metabolites from fortified ground water samples ranged from 68.6 to 101.4%. For HPLC-MS, solid phase extraction of ground water samples was performed using a polystyrene divinylbenzene polymer resin. The mean HPLC-MS recoveries of the three compounds from ground water samples spiked at 0.05-2 microg/L ranged from 100.9 to 110.3%. The limits of quantitation for HPLC-UV are approximately 150 ng/L for IXF, 100 ng/L for DKN, and 250 ng/L for BA. The limit of quantitation by HPLC-MS is 50 ng/L for each compound. The methods developed in this work can be applied to determine the transport and fate of Balance in the environment.

Straightforward Entry toward Highly Substituted 2,3-Dihydrobenz[ b]oxepines by Ring Expansion of Benzopyryliums with Donor-Acceptor Diazo Compounds.

PubMed

Courant, Thibaut; Pasco, Morgane; Lecourt, Thomas

2018-05-04

Ylide-type reactivity of diazo compounds is exploited in a new way to prepare benzo[ b]oxepines thanks to the formation of three chemical bonds and two contiguous and highly substituted stereocenters in a single pot. This cationic reaction cascade first involves addition of a donor-acceptor-substituted diazo compound to a benzopyrylium. Selective 1,2 migration of the endocyclic C-C bond then results in a ring-expansion and generates a second oxocarbenium that is trapped by a nucleophile added sequentially.

The Impact of Professional Development on Performance and Evaluation of Substitute Teachers in a Public School System

ERIC Educational Resources Information Center

Brown, Rhonda

2012-01-01

Research suggests that many substitute teachers do not have the educational pedagogy or teacher certification necessary to be considered highly qualified by the No Child Left Behind Act of 2001. To address that concern, professional development training for substitute teachers who lack proper certification and educational pedagogy has become an…

The Development of Substitute Object Pretense: The Differential Importance of Form and Function

ERIC Educational Resources Information Center

Hopkins, Emily J.; Smith, Eric D.; Weisberg, Deena Skolnick; Lillard, Angeline S.

2016-01-01

Substitute object pretense is one of the earliest-developing forms of pretense, and yet it changes considerably across the preschool years. By 3.5 years of age, children can pretend with substitutes that are highly dissimilar from their intended referents (Elder & Pederson, 1978), but even older children have difficulty understanding such…

Poly(arylene ether)s containing pendent ethynyl groups

NASA Technical Reports Server (NTRS)

Hergenrother, Paul M. (Inventor); Jensen, Brian J. (Inventor)

1996-01-01

Poly(arylene ether)s containing pendent ethynyl and substituted ethynyl groups and poly(arylene ether) copolymers containing pendent ethynyl and substituted ethynyl groups are readily prepared from bisphenols containing ethynyl and substituted ethynyl groups. The resulting polymers are cured up to 350.degree. C. to provide crosslinked poly(arylene ether)s with good solvent resistance, high strength and modulus.

Poly(arylene ether)s containing pendent ethynyl groups

NASA Technical Reports Server (NTRS)

Hergenrother, Paul M. (Inventor); Jensen, Brian J. (Inventor)

1994-01-01

Poly(arylene ether)s containing pendent ethynyl and substituted ethynyl groups and poly(arylene ether) copolymers containing pendent ethynyl and substituted ethynyl groups are readily prepared from bisphenols containing ethynyl and substituted ethynyl groups. The resulting polymers are cured up to 350 C to provide crosslinked poly(arylene ether)s with good solvent resistance, high strength and modulus.

Transglycosylation of stevioside to improve the edulcorant quality by lower substitution using cornstarch hydrolyzate and CGTase.

PubMed

Li, Sha; Li, Wei; Xiao, Qiu-yan; Xia, Yongmei

2013-06-01

Stevioside is an abundant sweetener extracted from Stevia rebaudiana leaf with a bitter aftertaste. Enzymatic transglycosylation of stevioside is a solution to improve the edulcorant quality of stevioside, but highly derivatised stevioside coming with high conversion of stevioside is undesired. In this experiment, the transglycosylation of stevioside was investigated by using a commercial cyclodextrin glucanotransferase and cornstarch hydrolyzate. With controlled parameters, the product was mainly composed of mono- and di-glucosylated stevioside while the highest stevioside conversion reached 77.11%. Neither kinetic nor thermodynamic factor stimulated the formation of high substituted steviosides. The simultaneous hydrolysis in the reaction might inhibit the yield of highly substituted steviosides. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lectins and substitution for helper function in anti-hapten responses in Xenopus laevis.

PubMed

Clothier, R H; James, H S; Ruben, L N; Balls, M

1984-08-01

Substitution by lectins for the carrier-priming requirement in thymus-dependent, antigen-binding responses in Xenopus laevis has been examined. Concanavalin A (Con A) was found to substitute for carrier priming in control, early-thymectomized and adult-thymectomized animals, but not in animals given a single, high dose of N-methyl-N-nitrosourea, which has a permanent effect on certain thymus-dependent functions in this species. Lipopolysaccharide and other lectins, such as peanut agglutinin and wheat germ agglutinin, were unable to substitute for carrier priming. These effects of Con A are discussed in terms of substitution via amplifier T cells or a helper T cell subset.

Tryptophan Scanning Reveals Dense Packing of Connexin Transmembrane Domains in Gap Junction Channels Composed of Connexin32.

PubMed

Brennan, Matthew J; Karcz, Jennifer; Vaughn, Nicholas R; Woolwine-Cunningham, Yvonne; DePriest, Adam D; Escalona, Yerko; Perez-Acle, Tomas; Skerrett, I Martha

2015-07-10

Tryptophan was substituted for residues in all four transmembrane domains of connexin32. Function was assayed using dual cell two-electrode voltage clamp after expression in Xenopus oocytes. Tryptophan substitution was poorly tolerated in all domains, with the greatest impact in TM1 and TM4. For instance, in TM1, 15 substitutions were made, six abolished coupling and five others significantly reduced function. Only TM2 and TM3 included a distinct helical face that lacked sensitivity to tryptophan substitution. Results were visualized on a comparative model of Cx32 hemichannel. In this model, a region midway through the membrane appears highly sensitive to tryptophan substitution and includes residues Arg-32, Ile-33, Met-34, and Val-35. In the modeled channel, pore-facing regions of TM1 and TM2 were highly sensitive to tryptophan substitution, whereas the lipid-facing regions of TM3 and TM4 were variably tolerant. Residues facing a putative intracellular water pocket (the IC pocket) were also highly sensitive to tryptophan substitution. Although future studies will be required to separate trafficking-defective mutants from those that alter channel function, a subset of interactions important for voltage gating was identified. Interactions important for voltage gating occurred mainly in the mid-region of the channel and focused on TM1. To determine whether results could be extrapolated to other connexins, TM1 of Cx43 was scanned revealing similar but not identical sensitivity to TM1 of Cx32. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Three dimensional quantitative structure-toxicity relationship modeling and prediction of acute toxicity for organic contaminants to algae.

PubMed

Jin, Xiangqin; Jin, Minghao; Sheng, Lianxi

2014-08-01

Although numerous chemicals have been identified to have significant toxicological effect on aquatic organisms, there is still lack of a reliable, high-throughput approach to evaluate, screen and monitor the presence of organic contaminants in aquatic system. In the current study, we proposed a synthetic pipeline to automatically model and predict the acute toxicity of chemicals to algae. In the procedure, a new alignment-free three dimensional (3D) structure characterization method was described and, with this method, several 3D-quantitative structure-toxicity relationship (3D-QSTR) models were developed, from which two were found to exhibit strong internal fitting ability and high external predictive power. The best model was established by Gaussian process (GP), which was further employed to perform extrapolation on a random compound library consisting of 1014 virtually generated substituted benzenes. It was found that (i) substitution number can only exert slight influence on chemical׳s toxicity, but low-substituted benzenes seem to have higher toxicity than those of high-substituted entities, and (ii) benzenes substituted by nitro group and halogens exhibit high acute toxicity as compared to other substituents such as methyl and carboxyl groups. Subsequently, several promising candidates suggested by computational prediction were assayed by using a standard algal growth inhibition test. Consequently, four substituted benzenes, namely 2,3-dinitrophenol, 2-chloro-4-nitroaniline, 1,2,3-trinitrobenzene and 3-bromophenol, were determined to have high acute toxicity to Scenedesmus obliquus, with their EC50 values of 2.5±0.8, 10.5±2.1, 1.4±0.2 and 42.7±5.4μmol/L, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of chalcone derivatives (mini review).

PubMed

Bukhari, Syed Nasir Abbas; Jasamai, Malina; Jantan, Ibrahim

2012-11-01

Chalcones are the principal precursors for the biosynthesis of flavonoids and isoflavonoids. A three carbon α, β-unsaturated carbonyl system constitutes chalcones. Chalcones are the condensation products of aromatic aldehyde with acetophenones in attendance of catalyst. They go through an assortment of chemical reactions and are found advantageous in synthesis of pyrazoline, isoxazole and a variety of heterocyclic compounds. In synthesizing a range of therapeutic compounds, chalcones impart key role. They have showed worth mentioning therapeutic efficacy for the treatment of various diseases. Chalcone based derivatives have gained heed since they own simple structures, and diverse pharmacological actions. A lot of methods and schemes have been reported for the synthesis of these compounds. Amongst all, Aldol condensation and Claisen-Schmidt condensation still grasp high up position. Other distinguished techniques include Suzuki reaction, Witting reaction, Friedel-Crafts acylation with cinnamoyl chloride, Photo-Fries rearrangement of phenyl cinnamates etc. These inventive techniques utilize various catalysts and reagents including SOCl(2) natural phosphate, lithium nitrate, amino grafted zeolites, zinc oxide, water, Na(2)CO(3), PEG400, silicasulfuric acid, ZrCl(4) and ionic liquid etc. The development of better techniques for the synthesis of α, β- unsaturated carbonyl compounds is still in high demand. In brief, we have explained the methods and catalysts used in the synthesis of chalcones along with their biological activities in a review form to provide information for the development of new-fangled processes targeting better yield, less reaction time and least side effects with utmost pharmacological properties.

Isovalent substitutes play in different ways: Effects of isovalent substitution on the thermoelectric properties of CoSi0.98B0.02

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

Sun, Hui; Lu, Xu; Morelli, Donald T.

Boron-added CoSi, CoSi 0.98B 0.02, possesses a very high thermoelectric power factor of 60 μW cm -1 K -2 at room temperature, which is among the highest power factors that have ever been reported for near-room-temperature thermoelectric applications. Since the electrical properties of this material have been tuned properly, isovalent substitution for its host atoms are intentionally employed to reduce the lattice thermal conductivity while maintaining the electronic properties unchanged. In our previous work, the effect of Rh substitution for Co atoms on the thermoelectric properties of CoSi 0.98B 0.02 has been studied. Here we present a study of themore » substitution of Ge for Si atoms in this compound. Even though Ge and Rh are isovalent with their corresponding host atoms, they play different roles in determining the electrical and thermal transport properties. Through the evaluation of the lattice thermal conductivity by the Debye approximation and the comparison between the high-temperature Seebeck coefficients, we propose that Rh substitution leads to a further overlapping of the conduction and the valence bands while Ge substitution only shifts the Fermi level upward into the conduction band. Lastly, our results show that the influence of isovalent substitution on the electronic structure cannot be ignored when the alloying method is used to improve thermoelectric properties.« less

Isovalent substitutes play in different ways: Effects of isovalent substitution on the thermoelectric properties of CoSi0.98B0.02

DOE PAGES

Sun, Hui; Lu, Xu; Morelli, Donald T.

2016-07-21

Boron-added CoSi, CoSi 0.98B 0.02, possesses a very high thermoelectric power factor of 60 μW cm -1 K -2 at room temperature, which is among the highest power factors that have ever been reported for near-room-temperature thermoelectric applications. Since the electrical properties of this material have been tuned properly, isovalent substitution for its host atoms are intentionally employed to reduce the lattice thermal conductivity while maintaining the electronic properties unchanged. In our previous work, the effect of Rh substitution for Co atoms on the thermoelectric properties of CoSi 0.98B 0.02 has been studied. Here we present a study of themore » substitution of Ge for Si atoms in this compound. Even though Ge and Rh are isovalent with their corresponding host atoms, they play different roles in determining the electrical and thermal transport properties. Through the evaluation of the lattice thermal conductivity by the Debye approximation and the comparison between the high-temperature Seebeck coefficients, we propose that Rh substitution leads to a further overlapping of the conduction and the valence bands while Ge substitution only shifts the Fermi level upward into the conduction band. Lastly, our results show that the influence of isovalent substitution on the electronic structure cannot be ignored when the alloying method is used to improve thermoelectric properties.« less

Hypothesis: is infantile autism a hypoglutamatergic disorder? Relevance of glutamate - serotonin interactions for pharmacotherapy.

PubMed

Carlsson, M L

1998-01-01

Based on 1) neuroanatomical and neuroimaging studies indicating aberrations in brain regions that are rich in glutamate neurons and 2) similarities between symptoms produced by N-methyl-D-aspartate (NMDA) antagonists in healthy subjects and those seen in autism, it is proposed in the present paper that infantile autism is a hypoglutamatergic disorder. Possible future pharmacological interventions in autism are discussed in the light of the intimate interplay between central glutamate and serotonin, notably the serotonin (5-HT) 2A receptor. The possible benefit of treatment with glutamate agonists [e.g. agents acting on the modulatory glycine site of the NMDA receptor, or so-called ampakines acting on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor] is discussed, as well as the potential usefulness of a selective 5-HT2A receptor antagonist.

FUNCTIONAL ANALYSIS OF A NOVEL POSITIVE ALLOSTERIC MODULATOR OF AMPA RECEPTORS DERIVED FROM A STRUCTURE-BASED DRUG DESIGN STRATEGY

PubMed Central

Harms, Jonathan E.; Benveniste, Morris; Maclean, John K. F.; Partin, Kathryn M.; Jamieson, Craig

2012-01-01

Positive allosteric modulators of α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors facilitate synaptic plasticity and can improve various forms of learning and memory. These modulators show promise as therapeutic agents for the treatment of neurological disorders such as schizophrenia, ADHD, and mental depression. Three classes of positive modulator, the benzamides, the thiadiazides, and the biarylsulfonamides differentially occupy a solvent accessible binding pocket at the interface between the two subunits that form the AMPA receptor ligand-binding pocket. Here, we describe the electrophysiological properties of a new chemotype derived from a structure-based drug design strategy (SBDD), which makes similar receptor interactions compared to previously reported classes of modulator. This pyrazole amide derivative, JAMI1001A, with a promising developability profile, efficaciously modulates AMPA receptor deactivation and desensitization of both flip and flop receptor isoforms. PMID:22735771

Biological Characterization of Novel Inhibitors of the Gram-Positive DNA Polymerase IIIC Enzyme

PubMed Central

Kuhl, Alexander; Svenstrup, Niels; Ladel, Christoph; Otteneder, Michael; Binas, Annegret; Schiffer, Guido; Brands, Michael; Lampe, Thomas; Ziegelbauer, Karl; Rübsamen-Waigmann, Helga; Haebich, Dieter; Ehlert, Kerstin

2005-01-01

Novel N-3-alkylated 6-anilinouracils have been identified as potent and selective inhibitors of bacterial DNA polymerase IIIC, the enzyme essential for the replication of chromosomal DNA in gram-positive bacteria. A nonradioactive assay measuring the enzymatic activity of the DNA polymerase IIIC in gram-positive bacteria has been assembled. The 6-anilinouracils described inhibited the polymerase IIIC enzyme at concentrations in the nanomolar range in this assay and displayed good in vitro activity (according to their MICs) against staphylococci, streptococci, and enterococci. The MICs of the most potent derivatives were about 4 μg/ml for this panel of bacteria. The 50% effective dose of the best compound (6-[(3-ethyl-4-methylphenyl)amino]-3-{[1-(isoxazol-5-ylcarbonyl)piperidin-4-yl]methyl}uracil) was 10 mg/kg of body weight after intravenous application in a staphylococcal sepsis model in mice, from which in vivo pharmacokinetic data were also acquired. PMID:15728893

Crystal structure of (1S,2S,2′R,3a′S,5R)-2′-[(5-bromo-1H-indol-3-yl)meth­yl]-2-isopropyl-5,5′-dimethyl­dihydro-2′H-spiro­[cyclo­hexane-1,6′-imidazo[1,5-b]isoxazol]-4′(5′H)-one

PubMed Central

Ghannay, Siwar; Brahmi, Jihed; Nasri, Soumaya; Aouadi, Kaïss; Jeanneau, Erwann; Msaddek, Moncef

2016-01-01

In the title compound, C24H32BrN3O2, the six-membered cyclo­hexane ring adopts a chair conformation and the isoxasolidine ring adopts a twisted conformation. The mol­ecule has five chiral centres and the absolute configuration has been determined in this analysis. The mol­ecular structure is stabilized by weak intra­molecular C—H⋯O and C—H⋯N contacts. In the crystal, mol­ecules are linked by N—H⋯N and C—H⋯O hydrogen bonds, forming undulating sheets parallel to the bc plane. PMID:27536387

Mountain substitutability and peak load pricing of high alpine peaks as a management tool to reduce environmental damage: a contingent valuation study.

PubMed

Loomis, John B; Keske, Catherine M

2009-04-01

High alpine peaks throughout the world are under increasing environmental pressure from hikers, trekkers, and climbers. Colorado's "Fourteeners", peaks with summits above 14,000 feet are no exception. Most of these peaks have no entrance fees, and reach ecological and social carrying capacity on weekends. This paper illustrates how a series of dichotomous choice contingent valuation questions can be used to evaluate substitutability between different alpine peaks and quantify the price responsiveness to an entrance fee. Using this approach, we find that peak load pricing would decrease use of popular Fourteeners in Colorado by 22%. This reduction is due almost entirely to substitution, rather than income effects. There is also price inelastic demand, as 60% of the hikers find no substitution for their specific Fourteener at the varying cost increases posed in the survey. The no substitute group has a mean net benefit of $294 per hiker, per trip, considerably higher than visitor net benefits in most recreational use studies.

Substitution of ceramics for high temperature alloys. [advantages of using silicon carbides and silicon nitrides in gas turbine engines

NASA Technical Reports Server (NTRS)

Probst, H. B.

1978-01-01

The high temperature capability of ceramics such as silicon nitride and silicon carbide can result in turbine engines of improved efficiency. Other advantages when compared to the nickel and cobalt alloys in current use are raw material availability, lower weight, erosion/corrosion resistance, and potentially lower cost. The use of ceramics in three different sizes of gas turbine is considered; these are the large utility turbines, advanced aircraft turbines, and small automotive turbines. Special consideration, unique to each of these applications, arise when one considers substituting ceramics for high temperature alloys. The effects of material substitutions are reviewed in terms of engine performance, operating economy, and secondary effects.

A test of the substitution-habitat hypothesis in amphibians.

PubMed

Martínez-Abraín, Alejandro; Galán, Pedro

2018-06-01

Most examples that support the substitution-habitat hypothesis (human-made habitats act as substitutes of original habitat) deal with birds and mammals. We tested this hypothesis in 14 amphibians by using percentage occupancy as a proxy of habitat quality (i.e., higher occupancy percentages indicate higher quality). We classified water body types as original habitat (no or little human influence) depending on anatomical, behavioral, or physiological adaptations of each amphibian species. Ten species had relatively high probabilities (0.16-0.28) of occurrence in original habitat, moderate probability of occurrence in substitution habitats (0.11-0.14), and low probability of occurrence in refuge habitats (0.05-0.08). Thus, the substitution-habitat hypothesis only partially applies to amphibians because the low occupancy of refuges could be due to the negligible human persecution of this group (indicating good conservation status). However, low occupancy of refuges could also be due to low tolerance of refuge conditions, which could have led to selective extinction or colonization problems due to poor dispersal capabilities. That original habitats had the highest probabilities of occupancy suggests amphibians have a good conservation status in the region. They also appeared highly adaptable to anthropogenic substitution habitats. © 2017 Society for Conservation Biology.

40 CFR Appendix A to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

Code of Federal Regulations, 2011 CFR

2011-07-01

... characteristic of concern for PFCs is that they have long atmospheric lifetimes and high global warming potentials. Although actual contributions to global warming depend upon the quantities of PFCs emitted, the... characteristic of concern for PFCs is that they have long atmospheric lifetimes and high global warming...

40 CFR Appendix A to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

Code of Federal Regulations, 2014 CFR

2014-07-01

... characteristic of concern for PFCs is that they have long atmospheric lifetimes and high global warming potentials. Although actual contributions to global warming depend upon the quantities of PFCs emitted, the... for PFCs is that they have long atmospheric lifetimes and high global warming potentials. Although...

40 CFR Appendix A to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

Code of Federal Regulations, 2012 CFR

2012-07-01

... characteristic of concern for PFCs is that they have long atmospheric lifetimes and high global warming potentials. Although actual contributions to global warming depend upon the quantities of PFCs emitted, the... characteristic of concern for PFCs is that they have long atmospheric lifetimes and high global warming...

40 CFR Appendix A to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes

Code of Federal Regulations, 2013 CFR

2013-07-01

... characteristic of concern for PFCs is that they have long atmospheric lifetimes and high global warming potentials. Although actual contributions to global warming depend upon the quantities of PFCs emitted, the... characteristic of concern for PFCs is that they have long atmospheric lifetimes and high global warming...

Unrealistic phylogenetic trees may improve phylogenetic footprinting.

PubMed

Nettling, Martin; Treutler, Hendrik; Cerquides, Jesus; Grosse, Ivo

2017-06-01

The computational investigation of DNA binding motifs from binding sites is one of the classic tasks in bioinformatics and a prerequisite for understanding gene regulation as a whole. Due to the development of sequencing technologies and the increasing number of available genomes, approaches based on phylogenetic footprinting become increasingly attractive. Phylogenetic footprinting requires phylogenetic trees with attached substitution probabilities for quantifying the evolution of binding sites, but these trees and substitution probabilities are typically not known and cannot be estimated easily. Here, we investigate the influence of phylogenetic trees with different substitution probabilities on the classification performance of phylogenetic footprinting using synthetic and real data. For synthetic data we find that the classification performance is highest when the substitution probability used for phylogenetic footprinting is similar to that used for data generation. For real data, however, we typically find that the classification performance of phylogenetic footprinting surprisingly increases with increasing substitution probabilities and is often highest for unrealistically high substitution probabilities close to one. This finding suggests that choosing realistic model assumptions might not always yield optimal predictions in general and that choosing unrealistically high substitution probabilities close to one might actually improve the classification performance of phylogenetic footprinting. The proposed PF is implemented in JAVA and can be downloaded from https://github.com/mgledi/PhyFoo. : martin.nettling@informatik.uni-halle.de. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press.

Enhancement of redox- and phase-stability of thermoelectric CaMnO3-δ by substitution

NASA Astrophysics Data System (ADS)

Thiel, Philipp; Populoh, Sascha; Yoon, Songhak; Weidenkaff, Anke

2015-09-01

Redox Reactivity and structural phase transitions have a major impact on transport and me-chemical properties of thermoelectric CaMnO3-δ. In this study series of Ca1-xAxMn1-yByO3-δ (0≤x,y≤0.8) compounds, each with A-site (Dy3+, Yb3+) or B-site (Nb5+, Ta5+ and Mo6+, W6+) substitution, were synthesized and crystallographically analyzed. It was found that the high-temperature oxygen content is widely independent from the substituent. Subsequently, with increasing temperature the differences in the Seebeck coefficient vanish above 1200 K. With increasing substitution the orthorhombic distortion of the perovskite-like phase increases. The orthorhombic distortion and the upper temperature limit of the stability of the orthorhombic crystal structure show an almost linear dependency. Accordingly, the mechanical stability of all-oxides thermoelectric converters at temperatures exceeding 1000 K will be increased employing materials with high substitution level and substituents inducing a high orthorhombic distortion.

No variation and low synonymous substitution rates in coral mtDNA despite high nuclear variation

PubMed Central

Hellberg, Michael E

2006-01-01

Background The mitochondrial DNA (mtDNA) of most animals evolves more rapidly than nuclear DNA, and often shows higher levels of intraspecific polymorphism and population subdivision. The mtDNA of anthozoans (corals, sea fans, and their kin), by contrast, appears to evolve slowly. Slow mtDNA evolution has been reported for several anthozoans, however this slow pace has been difficult to put in phylogenetic context without parallel surveys of nuclear variation or calibrated rates of synonymous substitution that could permit quantitative rate comparisons across taxa. Here, I survey variation in the coding region of a mitochondrial gene from a coral species (Balanophyllia elegans) known to possess high levels of nuclear gene variation, and estimate synonymous rates of mtDNA substitution by comparison to another coral (Tubastrea coccinea). Results The mtDNA surveyed (630 bp of cytochrome oxidase subunit I) was invariant among individuals sampled from 18 populations spanning 3000 km of the range of B. elegans, despite high levels of variation and population subdivision for allozymes over these same populations. The synonymous substitution rate between B. elegans and T. coccinea (0.05%/site/106 years) is similar to that in most plants, but 50–100 times lower than rates typical for most animals. In addition, while substitutions to mtDNA in most animals exhibit a strong bias toward transitions, mtDNA from these corals does not. Conclusion Slow rates of mitochondrial nucleotide substitution result in low levels of intraspecific mtDNA variation in corals, even when nuclear loci vary. Slow mtDNA evolution appears to be the basal condition among eukaryotes. mtDNA substitution rates switch from slow to fast abruptly and unidirectionally. This switch may stem from the loss of just one or a few mitochondrion-specific DNA repair or replication genes. PMID:16542456

Gold-catalyzed and N-iodosuccinimide-mediated cyclization of gamma-substituted allenamides.

PubMed

Hyland, Christopher J T; Hegedus, Louis S

2006-10-27

Chiral gamma-substituted allenamides have been shown to undergo efficient gold-catalyzed and N-iodosuccinimide-mediated cyclization to highly functionalized dihydrofurans. These reactions proceed rapidly and without loss of stereochemistry.

11.4% Efficiency non-fullerene polymer solar cells with trialkylsilyl substituted 2D-conjugated polymer as donor

PubMed Central

Bin, Haijun; Gao, Liang; Zhang, Zhi-Guo; Yang, Yankang; Zhang, Yindong; Zhang, Chunfeng; Chen, Shanshan; Xue, Lingwei; Yang, Changduk; Xiao, Min; Li, Yongfang

2016-01-01

Simutaneously high open circuit voltage and high short circuit current density is a big challenge for achieving high efficiency polymer solar cells due to the excitonic nature of organic semdonductors. Herein, we developed a trialkylsilyl substituted 2D-conjugated polymer with the highest occupied molecular orbital level down-shifted by Si–C bond interaction. The polymer solar cells obtained by pairing this polymer with a non-fullerene acceptor demonstrated a high power conversion efficiency of 11.41% with both high open circuit voltage of 0.94 V and high short circuit current density of 17.32 mA cm−2 benefitted from the complementary absorption of the donor and acceptor, and the high hole transfer efficiency from acceptor to donor although the highest occupied molecular orbital level difference between the donor and acceptor is only 0.11 eV. The results indicate that the alkylsilyl substitution is an effective way in designing high performance conjugated polymer photovoltaic materials. PMID:27905397

11.4% Efficiency non-fullerene polymer solar cells with trialkylsilyl substituted 2D-conjugated polymer as donor.

PubMed

Bin, Haijun; Gao, Liang; Zhang, Zhi-Guo; Yang, Yankang; Zhang, Yindong; Zhang, Chunfeng; Chen, Shanshan; Xue, Lingwei; Yang, Changduk; Xiao, Min; Li, Yongfang

2016-12-01

Simutaneously high open circuit voltage and high short circuit current density is a big challenge for achieving high efficiency polymer solar cells due to the excitonic nature of organic semdonductors. Herein, we developed a trialkylsilyl substituted 2D-conjugated polymer with the highest occupied molecular orbital level down-shifted by Si-C bond interaction. The polymer solar cells obtained by pairing this polymer with a non-fullerene acceptor demonstrated a high power conversion efficiency of 11.41% with both high open circuit voltage of 0.94 V and high short circuit current density of 17.32 mA cm -2 benefitted from the complementary absorption of the donor and acceptor, and the high hole transfer efficiency from acceptor to donor although the highest occupied molecular orbital level difference between the donor and acceptor is only 0.11 eV. The results indicate that the alkylsilyl substitution is an effective way in designing high performance conjugated polymer photovoltaic materials.

Accelerated hydrolysis of substituted cellulose for potential biofuel production: kinetic study and modeling.

PubMed

Mu, Bingnan; Xu, Helan; Yang, Yiqi

2015-11-01

In this work, kinetics of substitution accelerated cellulose hydrolysis with multiple reaction stages was investigated to lay foundation for mechanism study and molecular design of substituting compounds. High-efficiency hydrolysis of cellulose is critical for cellulose-based bioethanol production. It is known that, substitution could substantially decrease activation energy and increase reaction rate of acidic hydrolysis of glycosidic bonds in cellulose. However, reaction kinetics and mechanism of the accelerated hydrolysis were not fully revealed. In this research, it was proved that substitution therefore accelerated hydrolysis only occurred in amorphous regions of cellulose fibers, and was a process with multiple reaction stages. With molar ratio of substitution less than 1%, the overall hydrolysis rate could be increased for around 10 times. We also quantified the relationship between the hydrolysis rate of individual reaction stage and its major influences, including molar ratio of substitution, activation energy of acidic hydrolysis, pH and temperature. Copyright © 2015 Elsevier Ltd. All rights reserved.

An anion substitution route to low loss colossal dielectric CaCu{sub 3}Ti{sub 4}O{sub 12}

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

Smith, Andrew E.; Calvarese, T.G.; Sleight, A.W.

2009-02-15

An anion substitution route was utilized for lowering the dielectric loss in CaCu{sub 3}Ti{sub 4}O{sub 12} (CCTO) by partial replacement of oxygen by fluorine. This substitution reduced the dielectric loss, and retained a high dielectric constant that was essentially temperature independent from 25 to 200 deg. C. In particular, CaCu{sub 3}Ti{sub 4}O{sub 11.7}F{sub 0.3} exhibited a giant dielectric constant over 6000 and low dielectric loss below 0.075 at 100 kHz within a temperature range of 25-200 deg. C. Fluorine analysis confirmed the presence of fluorine in all samples measured. - Grapical Abstract: An anion substitution route was utilized for loweringmore » the dielectric loss in CaCu{sub 3}Ti{sub 4}O{sub 12} (CCTO) by partial replacement of oxygen by fluorine. This substitution, confirmed by fluorine analysis, reduced tan {delta}, and retained a high dielectric constant that was essentially temperature independent from 25 to 200 deg. C at 100 kHz.« less

Tandem SN2' nucleophilic substitution/oxidative radical cyclization of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds.

PubMed

Zhang, Zhen; Li, Cheng; Wang, Shao-Hua; Zhang, Fu-Min; Han, Xue; Tu, Yong-Qiang; Zhang, Xiao-Ming

2017-04-11

A novel and efficient tandem S N 2' nucleophilic substitution/oxidative radical cyclization reaction of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds has been developed by using Mn(OAc) 3 as an oxidant, which enables the expeditious synthesis of polysubstituted dihydrofuran (DHF) derivatives in moderate to high yields. The use of weakly acidic hexafluoroisopropanol (HFIP) as the solvent rather than AcOH has successfully improved the yields and expanded the substrate scope of this type of radical cyclization reactions. Mechanistic studies confirmed the cascade reaction process involving a final radical cyclization.

Structure-Activity Relationships of Truncated C2- or C8-Substituted Adenosine Derivatives as Dual Acting A2A and A3 Adenosine Receptor Ligands

PubMed Central

Hou, Xiyan; Majik, Mahesh S.; Kim, Kyunglim; Pyee, Yuna; Lee, Yoonji; Alexander, Varughese; Chung, Hwa-Jin; Lee, Hyuk Woo; Chandra, Girish; Lee, Jin Hee; Park, Seul-gi; Choi, Won Jun; Kim, Hea Ok; Phan, Khai; Gao, Zhan-Guo; Jacobson, Kenneth A.; Choi, Sun; Lee, Sang Kook; Jeong, Lak Shin

2011-01-01

Truncated N6-substituted-4′-oxo- and 4′-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A2A and A3 adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA2AAR, but hydrophobic C8 substitution abolished binding at the hA2AAR. However, most of synthesized compounds displayed medium to high binding affinity at the hA3AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA2AAR agonists. C2 substitution probed geometrically through hA2AAR-docking, was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA2AAR agonist and hA3AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases. PMID:22142423

Structure-activity relationships of truncated C2- or C8-substituted adenosine derivatives as dual acting A₂A and A₃ adenosine receptor ligands.

PubMed

Hou, Xiyan; Majik, Mahesh S; Kim, Kyunglim; Pyee, Yuna; Lee, Yoonji; Alexander, Varughese; Chung, Hwa-Jin; Lee, Hyuk Woo; Chandra, Girish; Lee, Jin Hee; Park, Seul-Gi; Choi, Won Jun; Kim, Hea Ok; Phan, Khai; Gao, Zhan-Guo; Jacobson, Kenneth A; Choi, Sun; Lee, Sang Kook; Jeong, Lak Shin

2012-01-12

Truncated N(6)-substituted-4'-oxo- and 4'-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A(2A) and A(3) adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross-coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA(2A)AR, but hydrophobic C8 substitution abolished binding at the hA(2A)AR. However, most of synthesized compounds displayed medium to high binding affinity at the hA(3)AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA(2A)AR agonists. C2 substitution probed geometrically through hA(2A)AR docking was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA(2A)AR agonist and hA(3)AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases.

The role of skin substitutes in the treatment of burn injuries.

PubMed

Shakespeare, Peter G

2005-01-01

Extensive burn wounds are difficult to manage and repair. Several engineered skin substitutes have been developed to aid in this process. These substitutes are designed with particular objectives in mind which dictate the circumstances under which they can, and should, be employed to promote healing or prepare the burn wound for final closure with autograft. This article discusses some of the rationale behind the use of skin substitutes and reviews some of the substitutes in use at the present time. Current perspectives suggest that skin substitute use is still in its infancy and that there is some way to go before their role in clinical practice becomes clear. Nevertheless the prospect of being able to supply new wound repair components and to influence the healing process to modify outcome and improve the quality of the healed burn wound will ensure a continuing high degree of interest in these potentially useful and beneficial medical devices.

Iridium-Catalyzed Kinetic Asymmetric Transformations of Racemic Allylic Benzoates

PubMed Central

Stanley, Levi M.; Bai, Chen; Ueda, Mitsuhiro; Hartwig, John F.

2010-01-01

Versatile methods for iridium-catalyzed, kinetic asymmetric substitution of racemic, branched allylic esters are reported. These reactions occur with a variety of aliphatic, aryl, and heteroaryl allylic benzoates to form the corresponding allylic substitution products in high yields (74–96%) with good to excellent enantioselectivity (84–98% ee) with a scope that encompasses a range of anionic carbon and heteroatom nucleophiles. These kinetic asymmetric processes occur with distinct stereochemical courses for racemic aliphatic and aromatic allylic benzoates, and the high reactivity of branched allylic benzoates enables enantioselective allylic substitutions that are slow or poorly selective with linear allylic electrophiles. PMID:20552969

Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry.

PubMed

Blincoe, William D; Rodriguez-Granillo, Agustina; Saurí, Josep; Pierson, Nicholas A; Joyce, Leo A; Mangion, Ian; Sheng, Huaming

2018-04-01

Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighboring group participation (NGP) effect to differentiate ortho-substituted benzoic acid/ester derivatives with high resolution mass spectrometry (HRMS 1 ). Significant water/alcohol loss (>30% abundance in MS 1 spectra) was observed for ortho-substituted nucleophilic groups; these fragment peaks are not observable for the corresponding para and meta-substituted analogs. Experiments were also extended to the analysis of two intermediates in the synthesis of suvorexant (Belsomra) with additional analysis conducted with nuclear magnetic resonance (NMR), density functional theory (DFT), and ion mobility spectrometry-mass spectrometry (IMS-MS) studies. Significant water/alcohol loss was also observed for 1-substituted 1, 2, 3-triazoles but not for the isomeric 2-substituted 1, 2, 3-triazole analogs. IMS-MS, NMR, and DFT studies were conducted to show that the preferred orientation of the 2-substituted triazole rotamer was away from the electrophilic center of the reaction, whereas the 1-subtituted triazole was oriented in close proximity to the center. Abundance of NGP product was determined to be a product of three factors: (1) proton affinity of the nucleophilic group; (2) steric impact of the nucleophile; and (3) proximity of the nucleophile to carboxylic acid/ester functional groups. Graphical Abstract ᅟ.

Isovalent substitutes play in different ways: Effects of isovalent substitution on the thermoelectric properties of CoSi{sub 0.98}B{sub 0.02}

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

Sun, Hui, E-mail: huisun3@iflytek.com; Lu, Xu; Morelli, Donald T.

Boron-added CoSi, CoSi{sub 0.98}B{sub 0.02}, possesses a very high thermoelectric power factor of 60 μW cm{sup −1} K{sup −2} at room temperature, which is among the highest power factors that have ever been reported for near-room-temperature thermoelectric applications. Since the electrical properties of this material have been tuned properly, isovalent substitution for its host atoms is intentionally employed to reduce the lattice thermal conductivity while maintaining the electronic properties unchanged. In our previous work, the effect of Rh substitution for Co atoms on the thermoelectric properties of CoSi{sub 0.98}B{sub 0.02} has been studied. Here, we present a study of the substitutionmore » of Ge for Si atoms in this compound. Even though Ge and Rh are isovalent with their corresponding host atoms, they play different roles in determining the electrical and thermal transport properties. Through the evaluation of the lattice thermal conductivity by the Debye approximation and the comparison between the high-temperature Seebeck coefficients, we propose that Rh substitution leads to a further overlapping of the conduction and the valence bands, while Ge substitution only shifts the Fermi level upward into the conduction band. Our results show that the influence of isovalent substitution on the electronic structure cannot be ignored when the alloying method is used to improve thermoelectric properties.« less

Identification of ortho-Substituted Benzoic Acid/Ester Derivatives via the Gas-Phase Neighboring Group Participation Effect in (+)-ESI High Resolution Mass Spectrometry

NASA Astrophysics Data System (ADS)

Blincoe, William D.; Rodriguez-Granillo, Agustina; Saurí, Josep; Pierson, Nicholas A.; Joyce, Leo A.; Mangion, Ian; Sheng, Huaming

2018-02-01

Benzoic acid/ester/amide derivatives are common moieties in pharmaceutical compounds and present a challenge in positional isomer identification by traditional tandem mass spectrometric analysis. A method is presented for exploiting the gas-phase neighboring group participation (NGP) effect to differentiate ortho-substituted benzoic acid/ester derivatives with high resolution mass spectrometry (HRMS1). Significant water/alcohol loss (>30% abundance in MS1 spectra) was observed for ortho-substituted nucleophilic groups; these fragment peaks are not observable for the corresponding para and meta-substituted analogs. Experiments were also extended to the analysis of two intermediates in the synthesis of suvorexant (Belsomra) with additional analysis conducted with nuclear magnetic resonance (NMR), density functional theory (DFT), and ion mobility spectrometry-mass spectrometry (IMS-MS) studies. Significant water/alcohol loss was also observed for 1-substituted 1, 2, 3-triazoles but not for the isomeric 2-substituted 1, 2, 3-triazole analogs. IMS-MS, NMR, and DFT studies were conducted to show that the preferred orientation of the 2-substituted triazole rotamer was away from the electrophilic center of the reaction, whereas the 1-subtituted triazole was oriented in close proximity to the center. Abundance of NGP product was determined to be a product of three factors: (1) proton affinity of the nucleophilic group; (2) steric impact of the nucleophile; and (3) proximity of the nucleophile to carboxylic acid/ester functional groups. [Figure not available: see fulltext.

Surfactant-assisted liquefaction of particulate carbonaceous substances

NASA Technical Reports Server (NTRS)

Hsu, G. C. (Inventor)

1978-01-01

A slurry of carbonaceous particles such as coal containing an oil soluble polar substituted oleophilic surfactant, suitably an amine substituted long chain hydrocarbon, is liquefied at high temperature and high hydrogen presence. The pressure of surfactant results in an increase in yield and the conversion product contains a higher proportion of light and heavy oils and less asphaltene than products from other liquefaction processes.

γ-Alumina Nanoparticle Catalyzed Efficient Synthesis of Highly Substituted Imidazoles.

PubMed

Reddy, Bandapalli Palakshi; Vijayakumar, Vijayaparthasarathi; Arasu, Mariadhas Valan; Al-Dhabi, Naif Abdullah

2015-10-21

γ-Alumina nano particle catalyzed multi component reaction of benzil, arylaldehyde and aryl amines afforded the highly substituted 1,2,4,5-tetraaryl imidazoles with good to excellent yield in less reaction time under the sonication as well as the conventional methods. Convenient operational simplicity, mild conditions and the reusability of catalyst were the other advantages of this developed protocol.

Toxicity and biodegradability of selected N-substituted phenols under anaerobic conditions

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

Donlon, B.; Razo-Flores, E.; Hwu, C.S.

1995-12-31

The anaerobic toxicity and biodegradability of N-substituted aromatics were evaluated in order to obtain information on their ultimate biotreatment. The toxicity of selected N-substituted aromatic compounds toward acetoclastic methanogens in granular sludge was measured in batch assays. This toxicity was highly correlated with compound hydrophobicity, indicating that partitioning into the bacterial membranes was an important factor in the toxicity. However, other factors, such as chemical interactions with key cell components, were suggested to be playing an important role. Nitroaromatic compounds were, on the average, over 300-fold more toxic than their amino-substituted counterparts. This finding suggests that the facile reduction ofmore » nitro-groups known to occur in anaerobic environments would result in a high level of detoxification. To test this hypothesis, continuous lab-scale upward-flow anaerobic sludge bed reactors treating 2-nitrophenol and 4-nitrophenol were established. The 4-nitrophenol was readily converted to the corresponding 4-aminophenol, whereas complete mineralization of 2-nitrophenol via intermediate formation of 2-aminophenol was obtained. These conversions led to a dramatic detoxification of the nitrophenols, because it was feasible to treat the highly toxic nitrophenolics at high organic loading rates.« less

Assessing the greenhouse impact of natural gas

NASA Astrophysics Data System (ADS)

Cathles, L. M.

2012-06-01

The global warming impact of substituting natural gas for coal and oil is currently in debate. We address this question here by comparing the reduction of greenhouse warming that would result from substituting gas for coal and some oil to the reduction which could be achieved by instead substituting zero carbon energy sources. We show that substitution of natural gas reduces global warming by 40% of that which could be attained by the substitution of zero carbon energy sources. At methane leakage rates that are ˜1% of production, which is similar to today's probable leakage rate of ˜1.5% of production, the 40% benefit is realized as gas substitution occurs. For short transitions the leakage rate must be more than 10 to 15% of production for gas substitution not to reduce warming, and for longer transitions the leakage must be much greater. But even if the leakage was so high that the substitution was not of immediate benefit, the 40%-of-zero-carbon benefit would be realized shortly after methane emissions ceased because methane is removed quickly from the atmosphere whereas CO2 is not. The benefits of substitution are unaffected by heat exchange to the ocean. CO2 emissions are the key to anthropogenic climate change, and substituting gas reduces them by 40% of that possible by conversion to zero carbon energy sources. Gas substitution also reduces the rate at which zero carbon energy sources must eventually be introduced.

Replacement of meat by meat substitutes. A survey on person- and product-related factors in consumer acceptance.

PubMed

Hoek, Annet C; Luning, Pieternel A; Weijzen, Pascalle; Engels, Wim; Kok, Frans J; de Graaf, Cees

2011-06-01

What does it take to increase the consumption of meat substitutes and attract new consumers? We identified main barriers and drivers by a consumer survey (n=553) in the U.K. and the Netherlands. Person-related factors (food neophobia and food choice motives) and product-related attitudes and beliefs towards meat and meat substitutes were compared between non-users (n=324), light/medium-users (n=133) and heavy-users of meat substitutes (n=96). Consumer acceptance was largely determined by the attitudes and beliefs towards meat substitutes and food neophobia. Key barriers for non-users and light/medium-users were the unfamiliarity with meat substitutes and the lower sensory attractiveness compared to meat. In addition, non-users had a higher tendency to avoid new foods. Hence, the less consumers were using meat substitutes, the more they wanted these products to be similar to meat. Although non-users and light/medium-users did recognize the ethical and weight-control aspects of meat substitutes, this was obviously less relevant to them. Actually, only heavy-users had high motivations to choose ethical foods, which explains their choice for meat substitutes. In order to make meat substitutes more attractive to meat consumers, we would not recommend to focus on communication of ethical arguments, but to significantly improve the sensory quality and resemblance to meat. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle

PubMed Central

Serre, Stéphanie B. N.; Jensen, Sanne B.; Ghanem, Lubna; Humes, Daryl G.; Ramirez, Santseharay; Li, Yi-Ping; Krarup, Henrik; Bukh, Jens

2016-01-01

Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified protease positions 54, 155, and 156 as hot spots for the selection of resistance substitutions under treatment with the first licensed PIs, telaprevir and boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir, faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged for three newer PIs. Substitution selection also depended on the specific recombinant. The substitutions identified conferred cross-resistance to several PIs; however, most substitutions selected under telaprevir or boceprevir treatment conferred less resistance to certain newer PIs. In a single-cycle production assay, across genotypes, PI treatment primarily decreased viral replication, which was rescued by PI resistance substitutions. The substitutions identified resulted in differential effects on viral fitness, depending on the original recombinant and the substitution. Across genotypes, fitness impairment induced by resistance substitutions was due primarily to decreased replication. Most combinations of substitutions that were identified increased resistance or fitness. Combinations of resistance substitutions with fitness-compensating substitutions either rescued replication or compensated for decreased replication by increasing assembly. This comprehensive study provides insight into the selection patterns and effects of PI resistance substitutions for HCV genotypes 1 to 6 in the context of the infectious viral life cycle, which is of interest for clinical and virological HCV research. PMID:27021330

Impacts of Vehicle Weight Reduction via Material Substitution on Life-Cycle Greenhouse Gas Emissions.

PubMed

Kelly, Jarod C; Sullivan, John L; Burnham, Andrew; Elgowainy, Amgad

2015-10-20

This study examines the vehicle-cycle and vehicle total life-cycle impacts of substituting lightweight materials into vehicles. We determine part-based greenhouse gas (GHG) emission ratios by collecting material substitution data and evaluating that alongside known mass-based GHG ratios (using and updating Argonne National Laboratory's GREET model) associated with material pair substitutions. Several vehicle parts are lightweighted via material substitution, using substitution ratios from a U.S. Department of Energy report, to determine GHG emissions. We then examine fuel-cycle GHG reductions from lightweighting. The fuel reduction value methodology is applied using FRV estimates of 0.15-0.25, and 0.25-0.5 L/(100km·100 kg), with and without powertrain adjustments, respectively. GHG breakeven values are derived for both driving distance and material substitution ratio. While material substitution can reduce vehicle weight, it often increases vehicle-cycle GHGs. It is likely that replacing steel (the dominant vehicle material) with wrought aluminum, carbon fiber reinforced plastic (CRFP), or magnesium will increase vehicle-cycle GHGs. However, lifetime fuel economy benefits often outweigh the vehicle-cycle, resulting in a net total life-cycle GHG benefit. This is the case for steel replaced by wrought aluminum in all assumed cases, and for CFRP and magnesium except for high substitution ratio and low FRV.

Tuna Species Substitution in the Spanish Commercial Chain: A Knock-On Effect.

PubMed

Gordoa, Ana; Carreras, Gustavo; Sanz, Nuria; Viñas, Jordi

2017-01-01

Intentional mislabelling of seafood is a widespread problem, particularly with high-value species like tuna. In this study we examine tuna mislabelling, deliberate species substitution, types of substitution and its impact on prices. The survey covered the commercial chain, from Merca-Barna to fishmongers and restaurants in the Spanish Autonomous Community of Catalonia. To understand the geographic extent of the problem we also sampled Merca-Madrid, Europe's biggest fish market, and Merca-Málaga for its proximity to the bluefin tuna migratory route and trap fishery. Monthly surveys were carried out over one year. The results showed a high deficiency in labelling: 75% of points of sale and 83% of restaurants did not specify the species, and in those cases the name of the species had to be asked. A total of 375 samples were analysed genetically, the largest dataset gathered in Europe so far. The identified species were Thunnus albacares, Thunnus thynnus and Thunnus obesus. Species substitution began at suppliers, with 40% of observed cases, increasing to 58% at fishmongers and 62% at restaurants. The substitution was mainly on bluefin tuna (T. thynnus), 73% of cases. At restaurants, only during the bluefin fishing season, we observed a decrease of Bluefin tuna substitution and an increase of reverse substitution revealing some illegal fishing. The effect of species substitution on species prices was relevant: T. obesus increased its price by around €12 kg-1 when it was sold as bluefin. In view of the deficiency of labelling, the abuse of generic names and the lack of the bluefin catch document, we conclude that the Spanish regulations are ineffective, highlighting the need for policy execution, and the urgent need for information campaigns to Spanish consumers.

A visible light photocatalyst: effects of vanadium substitution on ETS-10.

PubMed

Marie Shough, Anne; Lobo, Raul F; Doren, Douglas J

2007-10-07

Hybrid density functional theory/molecular mechanics (DFT/MM) methods have been used to investigate the effects of vanadium substitution in ETS-10. Models have been developed to contain varying concentrations of V(IV) and V(V) within the O-M-O (M = Ti, V) chain. Most of the V-substituted models have a localized mid-gap state. The occupation of this localized state depends upon the dopant oxidation state, leading to the addition of multiple low energy transitions. A linear correlation has been identified between band gap energies estimated using ground state orbital energies and those calculated using the more accurate and computationally demanding time-dependent DFT (TDDFT) method for a variety of transition metal substituted models of ETS-10. Consistent with experimental data for V substitution, our models predict a decrease in the optical band gap with increasing [V], due to a lowering of the delocalized d-orbital states at the bottom of the conduction band with increasing V d-orbital character. This effect is more pronounced in the case of V(V) substitution than V(IV). Excitation energies for the V-doped models, calculated with TDDFT methods correlate well with experimental data, allowing for the assignment of specific optical transitions to experimental UV-Vis spectra. The electronic structure of V-substituted ETS-10 at high V concentration demonstrates band gap energies within the visible range of the spectrum. Additionally, at high [V] the band gap energy and presence of low energy electron traps can be controlled by the relative concentration of V(IV) and V(V) along the O-M-O chain, establishing V-substituted ETS-10 as a promising visible light photocatalyst.

Tuna Species Substitution in the Spanish Commercial Chain: A Knock-On Effect

PubMed Central

Gordoa, Ana; Carreras, Gustavo; Sanz, Nuria; Viñas, Jordi

2017-01-01

Intentional mislabelling of seafood is a widespread problem, particularly with high-value species like tuna. In this study we examine tuna mislabelling, deliberate species substitution, types of substitution and its impact on prices. The survey covered the commercial chain, from Merca-Barna to fishmongers and restaurants in the Spanish Autonomous Community of Catalonia. To understand the geographic extent of the problem we also sampled Merca-Madrid, Europe’s biggest fish market, and Merca-Málaga for its proximity to the bluefin tuna migratory route and trap fishery. Monthly surveys were carried out over one year. The results showed a high deficiency in labelling: 75% of points of sale and 83% of restaurants did not specify the species, and in those cases the name of the species had to be asked. A total of 375 samples were analysed genetically, the largest dataset gathered in Europe so far. The identified species were Thunnus albacares, Thunnus thynnus and Thunnus obesus. Species substitution began at suppliers, with 40% of observed cases, increasing to 58% at fishmongers and 62% at restaurants. The substitution was mainly on bluefin tuna (T. thynnus), 73% of cases. At restaurants, only during the bluefin fishing season, we observed a decrease of Bluefin tuna substitution and an increase of reverse substitution revealing some illegal fishing. The effect of species substitution on species prices was relevant: T. obesus increased its price by around €12 kg-1 when it was sold as bluefin. In view of the deficiency of labelling, the abuse of generic names and the lack of the bluefin catch document, we conclude that the Spanish regulations are ineffective, highlighting the need for policy execution, and the urgent need for information campaigns to Spanish consumers. PMID:28125686

Charge-coupled substituted garnets (Y 3–x Ca 0.5x M 0.5x )Fe₅O₁₂ (M = Ce, Th): Structure and stability as crystalline nuclear waste forms

DOE PAGES

Guo, Xiaofeng; Kukkadapu, Ravi K.; Lanzirotti, Antonio; ...

2015-04-20

The garnet structure has been proposed as a potential crystalline nuclear waste form for accommodation of actinide elements, especially uranium (U). In this study, yttrium iron garnet (YIG) as a model garnet host was studied for the incorporation of U analogs, cerium (Ce) and thorium (Th), incorporated by a charge-coupled substitution with calcium (Ca) for yttrium (Y) in YIG, namely, 2Y³⁺ = Ca²⁺ + M⁴⁺, where M⁴⁺ = Ce⁴⁺ or Th⁴⁺. Single-phase garnets Y 3–xCa 0.5xM 0.5xFe₅O₁₂ (x = 0.1–0.7) were synthesized by the citrate–nitrate combustion method. Ce was confirmed to be tetravalent by X-ray absorption spectroscopy and X-ray photoelectronmore » spectroscopy. X-ray diffraction and ⁵⁷Fe–Mössbauer spectroscopy indicated that M⁴⁺ and Ca²⁺ cations are restricted to the c site, and the local environments of both the tetrahedral and the octahedral Fe³⁺ are systematically affected by the extent of substitution. The charge-coupled substitution has advantages in incorporating Ce/Th and in stabilizing the substituted phases compared to a single substitution strategy. Enthalpies of formation of garnets were obtained by high-temperature oxide melt solution calorimetry, and the enthalpies of substitution of Ce and Th were determined. The thermodynamic analysis demonstrates that the substituted garnets are entropically rather than energetically stabilized. This suggests that such garnets may form and persist in repositories at high temperature but might decompose near room temperature.« less

Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): implications for alcohol-induced behavioral plasticity.

PubMed

Ary, Alexis W; Cozzoli, Debra K; Finn, Deborah A; Crabbe, John C; Dehoff, Marlin H; Worley, Paul F; Szumlinski, Karen K

2012-06-01

Neuronal activity dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol. Published by Elsevier Inc.

Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): implications for alcohol-induced behavioral plasticity

PubMed Central

Ary, Alexis W.; Cozzoli, Debra K.; Finn, Deborah A.; Crabbe, John C.; Dehoff, Marlin H.; Worley, Paul F.; Szumlinski, Karen K.

2012-01-01

Neuronal activity-dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol. PMID:22444953

TiO2 supported on reed straw biochar as an adsorptive and photocatalytic composite for the efficient degradation of sulfamethoxazole in aqueous matrices.

PubMed

Zhang, Hanyu; Wang, Zhaowei; Li, Ruining; Guo, Jialei; Li, Yan; Zhu, Junmin; Xie, Xiaoyun

2017-10-01

Heterogeneous photocatalysis namely titanium dioxide supported on reed straw biochar (acid pre-treated) (TiO 2 /pBC) was synthesized by sol-gel method. The morphology, surface area and structure of TiO 2 /pBC were characterized by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), and X-ray diffraction (XRD). Low calcination condition maintained the structure of biochar completely and prevented the agglomeration of TiO 2 particles. Due to the combination of adsorption and photocatalysis, TiO 2 /pBC performed higher removal efficiency of sulfamethoxazole (SMX) than pure TiO 2 powder under UV light irradiation. The photocatalytic degradation (PCD) of SMX was also studied with the water collected from the Yellow River. Three high concentration inorganic anions (Cl - , NO 3 - , SO 4 2- ) of the river exerted certain degree of detrimental effects on the contaminant degradation. TiO 2 /pBC showed stable photocatalytic activity after five sequential PCD cycles. The biochar was able to promote further PCD on TiO 2 by adsorbing SMX and intermediates thereby prolonging the separation lifetime of electrons (e - ) and valence band hole (h + ). The transformation intermediates of SMX were identified and three possible degradation reactions of hydroxylation, opening of isoxazole ring and cleavage of SN bond might occur during the PCD of SMX. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dopaminergic Modulation of Excitatory Transmission in the Anterior Cingulate Cortex of Adult Mice

PubMed Central

Darvish-Ghane, Soroush; Yamanaka, Manabu

2016-01-01

Dopamine (DA) possesses potent neuromodulatory properties in the central nervous system. In the anterior cingulate cortex, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) are key ion channels in mediating nerve injury induced long-term potentiation (LTP) and chronic pain phenotype. In the present study, we reported the effects of DA on glutamate mediated excitatory post-synaptic currents (EPSCs) in pyramidal neurons of layer II/III of the ACC in adult mice. Bath application of DA (50 μM) caused a significant, rapid and reversible inhibition of evoked EPSCs (eEPSC). This inhibitory effect is dose-related and was absent in lower concentration of DA (5 μM). Furthermore, selective postsynaptic application of GDP-β-S (1.6 mM) in the internal solution completely abolished the inhibitory effects of DA (50 μM). We also investigated modulation of spontaneous EPSCs (sEPSCs) and TTX sensitive, miniature EPSCs (mEPSCs) by DA. Our results indicated mixed effects of potentiation and inhibition of frequency and amplitude for sEPSCs and mEPSCs. Furthermore, high doses of SCH23390 (100 μM) and sulpiride (100 μM) revealed that, inhibition of eEPSCs is mediated by postsynaptic D2-receptors (D2R). Our finding posits a pre- and postsynaptic mode of pyramidal neuron EPSC modulation in mice ACC by DA. PMID:27317578

Unraveling Complexity in the Solid Form Screening of a Pharmaceutical Salt: Why so Many Forms? Why so Few?

PubMed Central

2017-01-01

The solid form landscape of 5-HT2a antagonist 3-(4-(benzo[d]isoxazole-3-yl)piperazin-1-yl)-2,2-dimethylpropanoic acid hydrochloride (B5HCl) proved difficult to establish. Many crystalline materials were produced by solid form screening, but few forms readily grew high quality crystals to afford a clear picture or understanding of the solid form landscape. Careful control of crystallization conditions, a range of experimental methods, computational modeling of solvate structures, and crystal structure prediction were required to see potential arrangements of the salt in its crystal forms. Structural diversity in the solid form landscape of B5HCl was apparent in the layer structures for the anhydrate polymorphs (Forms I and II), dihydrate and a family of solvates with alcohols. The alcohol solvates, which provided a distinct packing from the neat forms and the dihydrate, form layers with conserved hydrogen bonding between B5HCl and the solvent, as well as stacking of the aromatic rings. The ability of the alcohol hydrocarbon moieties to efficiently pack between the layers accounted for the difficulty in growing some solvate crystals and the inability of other solvates to crystallize altogether. Through a combination of experiment and computation, the crystallization problems, form stability, and desolvation pathways of B5HCl have been rationalized at a molecular level. PMID:29018305

The Introduction of substitutional and non-substitutional dopants into MgB2 in high pressure/Temperature or non-equilibrium regimes

NASA Astrophysics Data System (ADS)

Sumption, Mike

2013-03-01

In an attempt to study the effect of doping of MgB2 under conditions leading to efficient doping, we used both an high temperature/high pressure induction furnace to dope into MgB2 bulks at temperatures up to 1600 C and 1500 Psi, and thin film, PLD multilayer and mixed layer film fabrication. The high temperature/high pressure formation was used to explore the solubility at high temperatures of various dopants, and the thin film formation was an attempt to use non-equilibrium conditions to inject dopants more effectively. The dopants used were C, Ti, and Zr. C was seen to reach a maximal level at 4 at% C site substituted into MgB2, as evidenced by EPMA and XRD results. Zr, of interest as a possible Mg site substitution in MgB2 was not seen to enter into the MgB2 phase (instead segregating) in the bulk high temperature/high pressure experiments, but was seen to enter in during PLD, as evidenced by STEM and XRD results. Ti additions were attempted in the high pressures and temperature rig, with some evidence for dopant introduction. Critical field measurements on the Zr doped samples where seen to suppress Bc2 for all except very low levels of Ti addition, presumably associated with the much greater doping efficiency. This work was supported by the U.S. Department of Energy, High Energy Physics university Grant No. DE-FG02-95ER40900

Enantioselective synthesis of allylic esters via asymmetric allylic substitution with metal carboxylates using planar-chiral cyclopentadienyl ruthenium catalysts.

PubMed

Kanbayashi, Naoya; Onitsuka, Kiyotaka

2010-02-03

An asymmetric allylic substitution with sodium carboxylate using a planar-chiral cyclopentadienyl ruthenium complex has been developed. Optically active allylic esters were prepared in good yields with high regio- and enantioselectivities.

Bioengineering a Human Plasma-Based Epidermal Substitute With Efficient Grafting Capacity and High Content in Clonogenic Cells

PubMed Central

Alexaline, Maia M.; Trouillas, Marina; Nivet, Muriel; Bourreau, Emilie; Leclerc, Thomas; Duhamel, Patrick; Martin, Michele T.; Doucet, Christelle; Fortunel, Nicolas O.

2015-01-01

Cultured epithelial autografts (CEAs) produced from a small, healthy skin biopsy represent a lifesaving surgical technique in cases of full-thickness skin burn covering >50% of total body surface area. CEAs also present numerous drawbacks, among them the use of animal proteins and cells, the high fragility of keratinocyte sheets, and the immaturity of the dermal-epidermal junction, leading to heavy cosmetic and functional sequelae. To overcome these weaknesses, we developed a human plasma-based epidermal substitute (hPBES) for epidermal coverage in cases of massive burn, as an alternative to traditional CEA, and set up critical quality controls for preclinical and clinical studies. In this study, phenotypical analyses in conjunction with functional assays (clonal analysis, long-term culture, or in vivo graft) showed that our new substitute fulfills the biological requirements for epidermal regeneration. hPBES keratinocytes showed high potential for cell proliferation and subsequent differentiation similar to healthy skin compared with a well-known reference material, as ascertained by a combination of quality controls. This work highlights the importance of integrating relevant multiparameter quality controls into the bioengineering of new skin substitutes before they reach clinical development. Significance This work involves the development of a new bioengineered epidermal substitute with pertinent functional quality controls. The novelty of this work is based on this quality approach. PMID:25848122

Bioengineering a human plasma-based epidermal substitute with efficient grafting capacity and high content in clonogenic cells.

PubMed

Alexaline, Maia M; Trouillas, Marina; Nivet, Muriel; Bourreau, Emilie; Leclerc, Thomas; Duhamel, Patrick; Martin, Michele T; Doucet, Christelle; Fortunel, Nicolas O; Lataillade, Jean-Jacques

2015-06-01

Cultured epithelial autografts (CEAs) produced from a small, healthy skin biopsy represent a lifesaving surgical technique in cases of full-thickness skin burn covering >50% of total body surface area. CEAs also present numerous drawbacks, among them the use of animal proteins and cells, the high fragility of keratinocyte sheets, and the immaturity of the dermal-epidermal junction, leading to heavy cosmetic and functional sequelae. To overcome these weaknesses, we developed a human plasma-based epidermal substitute (hPBES) for epidermal coverage in cases of massive burn, as an alternative to traditional CEA, and set up critical quality controls for preclinical and clinical studies. In this study, phenotypical analyses in conjunction with functional assays (clonal analysis, long-term culture, or in vivo graft) showed that our new substitute fulfills the biological requirements for epidermal regeneration. hPBES keratinocytes showed high potential for cell proliferation and subsequent differentiation similar to healthy skin compared with a well-known reference material, as ascertained by a combination of quality controls. This work highlights the importance of integrating relevant multiparameter quality controls into the bioengineering of new skin substitutes before they reach clinical development. This work involves the development of a new bioengineered epidermal substitute with pertinent functional quality controls. The novelty of this work is based on this quality approach. ©AlphaMed Press.

Reproducible Crystallite Size of Mono-Dispersed and Scalable Biologically Produced Metal-Substituted Nanometer-Sized Magnetites

NASA Astrophysics Data System (ADS)

Moon, J.; Rawn, C.; Rondinone, A.; Love, L.; Roh, Y.; Lauf, R.; Phelps, T.

2008-12-01

Our previous research demonstrated that biosynthesized magnetite (biomagnetite) exhibited similar properties as chemically synthesized magnetite. To complement uses of the traditional chemically synthesized magnetite (chem-magnetite) biomagnetite must be exhibit highly reproducible sizes and be available in scalable qualities. Here we emphasize potentially advantageous properties of biomagnetite regarding size, reproducibility and scaling availability. Average crystallite size (ACS) of biomagnetites ranging from 10-100 nm was determined after varied 1) incubation times, 2) substitution of metal and lanthanide species, 3) degrees of congruent incorporation or retardation of substitution elements, 4) bacterial species with their varied ability to substitute elemental species, and 6) incubation temperature that can influence coalescence. The microbial production of biomagnetite has demonstrated capacity to make highly crystalline nanoscale particles of metal-substituted ferrites including compounds of Co, Ni, Cr, Mn, Zn and the rare earths in large quantity. Selected Zn-substituted magnetite (nominal composition of Zn0.6Fe2.4O4) has been recovered at over 1 kg (wet weight) in batches from 30 L fermentations. The massively produced extracellular magnetites were confirmed to exhibit good mono- dispersity via transmission electron microscopy (TEM). TEM also validated highly reproducible ACS of 13.1±0.8 nm size as determined through X-ray diffraction (N=7) at a 99 % confidence level. Based on the scale-up experiments performed using the 35 L reactor, the reduction in ACS variability and shorted incubation times of several days may be attributed to increases of electron donor input, and availability of divalent ions of the substitution metal with less ferrous ions in the case of doped magnetite, or a combination of the above. While costs of commercial nanometer sized magnetite (25-50 nm) may vary from 500/kg to > 1,000/kg, microbial mass production is likely capable of producing 13-90 nm magnetite or doped magnetites at a fraction of the cost of traditional chemical synthesis. While there are numerous approaches for the synthesis of nanoparticles, bacterial fermentation of magnetite or metal-substituted magnetite may represent a disruptive manufacturing technology with respect to yield, reproducibility and scalability.

Regioselective palladium-catalyzed ring-opening reactions of C1-substituted oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylates

PubMed Central

Edmunds, Michael; Raheem, Mohammed Abdul; Boutin, Rebecca; Tait, Katrina

2016-01-01

Summary Palladium-catalyzed ring-opening reactions of C1 substituted 7-oxanorbornadiene derivatives with aryl iodides were investigated. The optimal conditions for this reaction were found to be PdCl2(PPh3)2, ZnCl2, Et3N and Zn in THF. Both steric and electronic factors played a role in the outcome of the reaction as increasing the steric bulk on the bridgehead carbon decreased the yield. These reactions were found to be highly regioselective, giving only one of the two possible regioisomers in all cases. A diverse collection of novel, highly substituted biphenyl derivatives were obtained. PMID:26977182

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

PubMed Central

Westphal, Julia C

2014-01-01

Summary A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification overcoming separation difficulties usually associated to triphenylphosphine oxide. PMID:24605158

Micropore-free surface-activated carbon for the analysis of polychlorinated dibenzo-p-dioxins-dibenzofurans and non-ortho-substituted polychlorinated biphenyls in environmental samples.

PubMed

Kemmochi, Yukio; Tsutsumi, Kaori; Arikawa, Akihiro; Nakazawa, Hiroyuki

2002-11-22

2,3,7,8-Substituted polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs) and non-ortho-substituted polychlorinated biphenyls (PCBs) account for almost all of the total toxic equivalents (TEQ) in environmental samples. Activated carbon columns are used to fractionate the samples for GC-MS analysis or bioassay. Micropore-free surface-activated carbon is highly selective for PCDD/Fs and non-ortho-PCBs and can improve the conventional activated carbon column clean-up. Along with sulfuric acid-coated diatomaceous earth columns, micropore-free surface-activated carbon provides a rapid, robust, and high-throughput sample preparation method for PCDD/Fs and non-ortho-PCBs analysis.

Meat analogues: Health promising sustainable meat substitutes.

PubMed

Kumar, Pavan; Chatli, M K; Mehta, Nitin; Singh, Parminder; Malav, O P; Verma, Akhilesh K

2017-03-24

There is a scarcity of protein of high biological value due to rapid increase in the world population and limited natural resources. Meat is a good source of protein of high biological value but converting the vegetable protein into animal protein is not economical. There is a trend of production of healthy and delicious meat free food for satisfaction of vegetarian and personal well beings. This resulted in increasing use of low cost vegetable protein such as textured soy protein, mushroom, wheat gluten, pulses etc as a substitute for animal-protein. These simulated meat-like products, with similar texture, flavor, color, and nutritive value can be substituted directly for meat to all sections of the society.

Regio- and Stereospecific Formation of Protected Allylic Alcohols via Zirconium-Mediated SN2' Substitution of Allylic Chlorides

PubMed Central

Fox, Richard J.; Lalic, Gojko; Bergman, Robert G.

2008-01-01

A new, highly regio- and stereospecific SN2' substitution reaction between a zirconium oxo complex and allylic chloride has been achieved. The resulting allylic alcohol or TBS-protected allylic ether products were isolated in good to excellent yields with a wide range of E-allylic chlorides. A mechanism for the SN2' allylic substitution consistent with kinetic, stereochemical and secondary isotope effect studies was proposed. PMID:17973391

Contribution of Golden Apple Snail Flour to Enhance Omega- 3 and Omega-6 Fatty Acids Contents in Weaning Food

NASA Astrophysics Data System (ADS)

Marsyha, D. D.; Wijayanti, H. S.; Nuryanto; Anjani, G.

2018-02-01

The case of undernourished children in Grobogan District (15.3%) is caused by children nutrients intake less than the Recommendation Dietary Allowance (RDA). To enhance children nutrients intake, be required formulation of weaning food using high-nutrient local food such as golden apple snail (Pomacea canaliculata). Golden apple snail flour contains high contents of zinc, iron, omega-3 and omega-6 fatty acids. This study aims to analyze the effect of golden apple snail flour substitution on nutrients content and organoleptic properties of weaning food (baby porridge). This is an experimental research by substitution of golden apple snail flour in the making of weaning food with four treatments of substitution (0%, 5%, 10%, 15%). Substitution of golden apple snails flour could affect the nutrient content levels of fat, zinc, iron (p=0.0001), carbohydrate (p=0.011), water (p=0.003), ash (p=0.001), omega-3 and omega-6 fatty acids. Whereas, it could not affect the content of energy (p=0.678), protein (p=0.129) and fiber (p=0.482). Furthermore, the substitution could affect the organoleptic properties include color, texture and taste (p=0.0001) while not for the aroma (p=0.798). Based on nutrient content analysis, substitution of golden apple snail flour could enhance the zinc, iron, omega-3 and omega-6 fatty acids contents of weaning food.

Fast synthesis of La-substituted apatite by the dry mechanochemical method and analysis of its structure

NASA Astrophysics Data System (ADS)

Bulina, Natalia V.; Chaikina, Marina V.; Prosanov, Igor Yu.; Dudina, Dina V.; Solovyov, Leonid A.

2017-08-01

Compared to pure apatite, La-substituted apatites have improved thermal, mechanical and biological characteristics. In this article, a fast synthesis of La-substituted apatites by a dry mechanochemical method is presented. Structural studies by X-ray diffraction and Fourier transform infrared spectroscopy indicated the formation of a single-phase nanosized product after 30 min of high-energy ball milling of the reaction mixtures. The dry mechanochemical method is technologically attractive for the preparation of La-substituted apatites, as it allows reducing the processing time down to half an hour and does not require prolonged high-temperature annealing normally used in the synthesis practice of the substituted apatite. As the mechanochemically synthesized samples are nanosized, it is difficult to determine the details of their crystal structure by the Rietveld refinement method. Therefore, a series of the mechanochemically synthesized samples with different concentrations of lanthanum were annealed at 1000°C for 5 h. It was found that the annealed powders are microcrystalline La-substituted apatites Ca10-xLax(PO4)6Ox(OH)2-x, where 0 ≤ x ≤2. In their structure, the Ca2+ ions are replaced by the La3+ ions localized near the Ca2 sites, and the OH- groups are replaced by the O2- ions in the hexagonal channels.

Gene-Specific Substitution Profiles Describe the Types and Frequencies of Amino Acid Changes during Antibody Somatic Hypermutation.

PubMed

Sheng, Zizhang; Schramm, Chaim A; Kong, Rui; Mullikin, James C; Mascola, John R; Kwong, Peter D; Shapiro, Lawrence

2017-01-01

Somatic hypermutation (SHM) plays a critical role in the maturation of antibodies, optimizing recognition initiated by recombination of V(D)J genes. Previous studies have shown that the propensity to mutate is modulated by the context of surrounding nucleotides and that SHM machinery generates biased substitutions. To investigate the intrinsic mutation frequency and substitution bias of SHMs at the amino acid level, we analyzed functional human antibody repertoires and developed mGSSP (method for gene-specific substitution profile), a method to construct amino acid substitution profiles from next-generation sequencing-determined B cell transcripts. We demonstrated that these gene-specific substitution profiles (GSSPs) are unique to each V gene and highly consistent between donors. We also showed that the GSSPs constructed from functional antibody repertoires are highly similar to those constructed from antibody sequences amplified from non-productively rearranged passenger alleles, which do not undergo functional selection. This suggests the types and frequencies, or mutational space, of a majority of amino acid changes sampled by the SHM machinery to be well captured by GSSPs. We further observed the rates of mutational exchange between some amino acids to be both asymmetric and context dependent and to correlate weakly with their biochemical properties. GSSPs provide an improved, position-dependent alternative to standard substitution matrices, and can be utilized to developing software for accurately modeling the SHM process. GSSPs can also be used for predicting the amino acid mutational space available for antigen-driven selection and for understanding factors modulating the maturation pathways of antibody lineages in a gene-specific context. The mGSSP method can be used to build, compare, and plot GSSPs; we report the GSSPs constructed for 69 common human V genes (DOI: 10.6084/m9.figshare.3511083) and provide high-resolution logo plots for each (DOI: 10.6084/m9.figshare.3511085).

Enhanced magnetism of perovskite oxides, Sr(Sn,Fe)O3- δ , by substitution of nonmagnetic Ca and Ti ions

NASA Astrophysics Data System (ADS)

Nomura, Kiyoshi; Suzuki, Shigeyo; Mizunuma, Tomoya; Koike, Yuya; Okazawa, Atsushi

2017-11-01

Magnetic properties of perovskite oxides, SrSn1- x Fe x O3- δ ( x ≤ 0.15), substituted with nonmagnetic Ca and Ti ions were studied. XRD patterns showed the orthorhombic structure (close to tetragonal) of (Sr1- y Ca y )(Sn1- x Fe x )O3- δ and Sr(Sn1- x- y Fe x Ti y )O3- δ . The cell volumes decreased with the increase of Ca and Ti doping rates. Although Ti-substituted Sr(Sn, Fe)O3- δ showed small saturation magnetizations as compared with non-Ti substituted one, the magnetization increased a little with Ti doping rates up to 15%. On the other hand, all Ca-substituted Sr(Sn, Fe)O3- δ showed larger saturation magnetization than non-Ca substituted one. Two doublets of Fe3+ and a doublet of Fe4+ were observed in Mössbauer spectra of Ca-substituted Sr(Sn, Fe)O3- δ with weak ferromagnetism, and two sextets of high spin Fe3+ were additionally observed in Mössbauer spectra of Ca-doped Sr(Sn, Fe)O3- δ with relatively strong ferromagnetism. When Sr(Sn, Fe)O3- δ were further codoped with Ca and Ti ions, they showed the stable and enhanced ferromagnetic properties. It is considered that magnetic polarons among high spin Fe3+ species are overlapped by shrinking or deforming the crystal structure of perovskite oxides. That is the magnetism induced by a chemical pressure of perovskite oxides.

Development of mono- and di-AcO substituted BODIPYs on the boron center.

PubMed

Jiang, Xin-Dong; Zhang, Jian; Furuyama, Taniyuki; Zhao, Weili

2012-01-06

Mono- and di-AcO substituted BODIPYs (1 and 2) were synthesized from TM-BDP. The structures of 1 and 2 were supported by single crystal X-ray analysis. Both 1 and 2 possess a large absorption coefficient, high fluorescence quantum yield, and high light stability. Compound 2 has much improved water solubility which is highly desirable for biological applications. Theoretical calculation supports our observations in X-ray analysis, absorption, and cyclic voltammetry. © 2011 American Chemical Society

Saccharide substituted zinc phthalocyanines: optical properties, interaction with bovine serum albumin and near infrared fluorescence imaging for sentinel lymph nodes.

PubMed

Lu, Li; Lv, Feng; Cao, Bo; He, Xujun; Liu, Tianjun

2014-01-03

Saccharide-substituted zinc phthalocyanines, [2,9(10),16(17),23(24)-tetrakis((1-(β-D-glucose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato]zinc(II) and [2,9(10), 16(17),23(24)-tetrakis((1-(β-D-lactose-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)phthalocyaninato] zinc(II), were evaluated as novel near infrared fluorescence agents. Their interaction with bovine serum albumin was investigated by fluorescence and circular dichroism spectroscopy and isothermal titration calorimetry. Near infrared imaging for sentinel lymph nodes in vivo was performed using nude mice as models. Results show that saccharide- substituted zinc phthalocyanines have favourable water solubility, good optical stability and high emission ability in the near infrared region. The interaction of lactose-substituted phthalocyanine with bovine serum albumin displays obvious differences to that of glucose- substituted phthalocyanine. Moreover, lactose-substituted phthalocyanine possesses obvious imaging effects for sentinel lymph nodes in vivo.

Possible High Thermoelectric Power in Semiconducting Carbon Nanotubes ˜A Case Study of Doped One-Dimensional Semiconductors˜

NASA Astrophysics Data System (ADS)

Yamamoto, Takahiro; Fukuyama, Hidetoshi

2018-02-01

We have theoretically investigated the thermoelectric properties of impurity-doped one-dimensional semiconductors, focusing on nitrogen-substituted (N-substituted) carbon nanotubes (CNTs), using the Kubo formula combined with a self-consistent t-matrix approximation. N-substituted CNTs exhibit extremely high thermoelectric power factor (PF) values originating from a characteristic of one-dimensional materials where decrease in the carrier density increase both the electrical conductivity and the Seebeck coefficient in the low-N regime. The chemical potential dependence of the PF values of semiconducting CNTs has also been studied as a field-effect transistor and it turns out that the PF values show a noticeable maximum in the vicinity of the band edges. This result demonstrates that "band-edge engineering" will be crucial for solid development of high-performance thermoelectric materials.

Effect of Element Substitution at V site on Thermoelectric Properties of Aurivillius Phase Bi2VO5.5

NASA Astrophysics Data System (ADS)

Kohri, Hitoshi; Yagasaki, Takayoshi

2016-10-01

Thermoelectric oxides are suitable at the high temperature range because of chemical stability. Aurivillius compounds are bismuth layered oxides, and known as oxygen ion conductors. The Aurivillius compounds consist of Perovskite layers and Bi-O layers. It is expected that nano-layered structure shows high Seebeck coefficients due to the quantum confinement of carriers in Perovskite layers. It was reported that the Seebeck coefficient of hot pressed specimens for Aurivillius phase Bi2VO5.5 was a high value of -28.3 mVK-1 at 1010 K, and the electrical resistivity of one was also a high value of 0.033 Ωm at 1010 K. In this paper, the effect of element substitution at the V site on thermoelectric properties of Aurivillius phase Bi2VO5.5 was investigated. Bi2V1- x M x O5.5 (M = Cr, Mo, W x = 0, 0.05, 0.1, 0.2) were prepared by solid-state reaction. The electrical resistivity of Cr-substituted specimens were indicated at larger values than the ones for unsubstituted specimens over the measurement temperature range. The resistivity above 800 K was reduced by substitution of W or Mo. W as a substituted element was effective for reducing the thermal conductivity of Bi2VO5.5. The maximum value of the dimensionless figure of merit ZT was 0.05 at 799 K for Bi2V0.8Mo0.2O5.5 and at 902 K for Bi2V0.8W0.1O5.5. The maximum ZT of an unsubstituted sample was 0.02 at 993 K. From these results, it was found that tungsten or molybdenum substitution was effective to improve ZT for Aurivillius phase Bi2VO5.5.

Processing waste fats into a fuel oil substitute

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

Pudel, F.; Lengenfeld, P.

1993-12-31

Waste fats have a high energy potential. They also contain impurities. For example, fats used for deep-frying contain high contents of solids, water, and chlorides. The process described in this paper removes the impurities by simple processing such as screening, washing, separating, drying, and filtering. The final quality of processed fat allows its use as a fuel oil substitute, and also as a raw material for chemical production.

Palladium-Catalyzed Asymmetric Allylic Alkylation of 4-Substituted Isoxazolidin-5-ones: Straightforward Access to β2,2 -Amino Acids.

PubMed

Nascimento de Oliveira, Marllon; Arseniyadis, Stellios; Cossy, Janine

2018-04-03

We report here an unprecedented and highly enantioselective palladium-catalyzed allylic alkylation applied to 4-substituted isoxazolidin-5-ones. Ultimately, the process provides a straightforward access to β 2,2 -amino acids bearing an all-carbon quaternary stereogenic center in great yields and a high degree of enantioselectivity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of Xylan Side-Chain Substitutions on Xylan-Cellulose Interactions and Implications for Thermal Pretreatment of Cellulosic Biomass.

PubMed

Pereira, Caroline S; Silveira, Rodrigo L; Dupree, Paul; Skaf, Munir S

2017-04-10

Lignocellulosic biomass is mainly constituted by cellulose, hemicellulose, and lignin and represents an important resource for the sustainable production of biofuels and green chemistry materials. Xylans, a common hemicellulose, interact with cellulose and often exhibit various side chain substitutions including acetate, (4-O-methyl) glucuronic acid, and arabinose. Recent studies have shown that the distribution of xylan substitutions is not random, but follows patterns that are dependent on the plant taxonomic family and cell wall type. Here, we use molecular dynamics simulations to investigate the role of substitutions on xylan interactions with the hydrophilic cellulose face, using the recently discovered xylan decoration pattern of the conifer gymnosperms as a model. The results show that α-1,2-linked substitutions stabilize the binding of single xylan chains independently of the nature of the substitution and that Ca 2+ ions can mediate cross-links between glucuronic acid substitutions of two neighboring xylan chains, thus stabilizing binding. At high temperature, xylans move from the hydrophilic to the hydrophobic cellulose surface and are also stabilized by Ca 2+ cross-links. Our results help to explain the role of substitutions on xylan-cellulose interactions, and improve our understanding of the plant cell wall architecture and the fundamentals of biomass pretreatments.

Picolinoxy group, a new leaving group for anti SN2' selective allylic substitution with aryl anions based on Grignard reagents.

PubMed

Kiyotsuka, Yohei; Acharya, Hukum P; Katayama, Yuji; Hyodo, Tomonori; Kobayashi, Yuichi

2008-05-01

The picolinoxy group was found to be an extremely powerful leaving group for allylic substitution with aryl nucleophiles derived from ArMgBr and CuBr*Me2S. The substitution proceeds with anti SN2' pathway and with high chirality transfer. The electron-withdrawing effect of the pyridyl group and chelation to MgBr2 are likely the origin of success. Results suggesting these effects were obtained.

Rh(III)-Catalyzed C-H Activation of Benzoylacetonitriles and Tandem Cyclization with Diazo Compounds to Substituted Benzo[ de]chromenes.

PubMed

Fang, Feifei; Zhang, Chunmei; Zhou, Chaofan; Li, Yazhou; Zhou, Yu; Liu, Hong

2018-04-06

Rh (III)-catalyzed C-H activation of benzoylacetonitriles in coupling with diazo compounds was developed to synthesize diversified substituted benzo[ de]chromenes via a formal (4 + 2) cycloaddition with a diazo compound and subsequent tandem (4 + 2) cycloaddition with another diazo compound. Intriguingly, synthesis of substituted benzo[ de]chromenes and their decarboxylation products could be realized by controlling the reaction conditions. These reactions have a broad range of substrates, moderate to good yields, and high regioselectivity.

High-resolution characterization of a hepatocellular carcinoma genome.

PubMed

Totoki, Yasushi; Tatsuno, Kenji; Yamamoto, Shogo; Arai, Yasuhito; Hosoda, Fumie; Ishikawa, Shumpei; Tsutsumi, Shuichi; Sonoda, Kohtaro; Totsuka, Hirohiko; Shirakihara, Takuya; Sakamoto, Hiromi; Wang, Linghua; Ojima, Hidenori; Shimada, Kazuaki; Kosuge, Tomoo; Okusaka, Takuji; Kato, Kazuto; Kusuda, Jun; Yoshida, Teruhiko; Aburatani, Hiroyuki; Shibata, Tatsuhiro

2011-05-01

Hepatocellular carcinoma, one of the most common virus-associated cancers, is the third most frequent cause of cancer-related death worldwide. By massively parallel sequencing of a primary hepatitis C virus-positive hepatocellular carcinoma (36× coverage) and matched lymphocytes (>28× coverage) from the same individual, we identified more than 11,000 somatic substitutions of the tumor genome that showed predominance of T>C/A>G transition and a decrease of the T>C substitution on the transcribed strand, suggesting preferential DNA repair. Gene annotation enrichment analysis of 63 validated non-synonymous substitutions revealed enrichment of phosphoproteins. We further validated 22 chromosomal rearrangements, generating four fusion transcripts that had altered transcriptional regulation (BCORL1-ELF4) or promoter activity. Whole-exome sequencing at a higher sequence depth (>76× coverage) revealed a TSC1 nonsense substitution in a subpopulation of the tumor cells. This first high-resolution characterization of a virus-associated cancer genome identified previously uncharacterized mutation patterns, intra-chromosomal rearrangements and fusion genes, as well as genetic heterogeneity within the tumor.

Substituent effect on photophysical properties of bi-1,3,4-oxadiazole derivatives in solution

NASA Astrophysics Data System (ADS)

Chen, Fangyi; Tian, Taiji; Zhao, Chengxiao; Bai, Binglian; Li, Min; Wang, Haitao

2016-04-01

A series of phenyl substituted bi-1,3,4-oxadiazole derivatives were designed and synthesized; the effect of substituent on the photophysical properties and molecular electronic structures was fully studied by the combination of experimental techniques and theoretical calculations. Compared to parent compound without any substituent (BOXD), fluoro-substituent shows little effect on the absorption and emission spectra, whilst a little larger spectral red-shift could be observed for methoxy-, nitro-substituted derivatives and thienyl-substituted bi-1,3,4-oxadiazole (TBOXD). These spectral changes can be well explained by theoretically calculated HOMO and LUMO energy level changes. All these molecules show high fluorescence quantum yield except for nitro-substituted derivative in dilute solutions. The quantum yield of BOXD changes with the concentration and exhibits a high value at the concentrated solution. This work revealed the influence of substituent on the photophysical properties of bi-1,3,4-oxadizaole derivatives in dilute solutions and provided guidance for designing molecules with potential application.

Development of amino acid substituted gemini surfactant-based mucoadhesive gene delivery systems for potential use as noninvasive vaginal genetic vaccination.

PubMed

Singh, Jagbir; Michel, Deborah; Getson, Heather M; Chitanda, Jackson M; Verrall, Ronald E; Badea, Ildiko

2015-02-01

Recently, we synthesized amino acid- and peptide-substituted gemini surfactants, 'biolipids' that exhibited high transfection efficiency in vitro. In this study, we developed these plasmid DNA and gemini surfactant lipid particles for noninvasive administration in vaginal cavity. Novel formulations of these gene delivery systems were prepared with poloxamer 407 to induce in situ gelling of the formulation and diethylene glycol monoethyl ether to improve their penetration across mucosal tissue. Poloxamer at 16% w/v concentration in diethylene glycol monoethyl ether aqueous solution produced dispersions that gelled near body temperature and had a high yield value, preventing leakage of the formulation from the vaginal cavity. Intravaginal administration in rabbits showed that the glycyl-lysine-substituted gemini surfactant led to a higher gene expression compared with the parent unsubstituted gemini surfactant. This provides a proof-of-concept that amino acid substituted gemini surfactants can be used as noninvasive mucosal (vaginal) gene delivery systems to treat diseases associated with mucosal epithelia.

Effect of B-ring substitution pattern on binding mode of propionamide selective androgen receptor modulators.

PubMed

Bohl, Casey E; Wu, Zengru; Chen, Jiyun; Mohler, Michael L; Yang, Jun; Hwang, Dong Jin; Mustafa, Suni; Miller, Duane D; Bell, Charles E; Dalton, James T

2008-10-15

Selective androgen receptor modulators (SARMs) are essentially prostate sparing androgens, which provide therapeutic potential in osteoporosis, male hormone replacement, and muscle wasting. Herein we report crystal structures of the androgen receptor (AR) ligand-binding domain (LBD) complexed to a series of potent synthetic nonsteroidal SARMs with a substituted pendant arene referred to as the B-ring. We found that hydrophilic B-ring para-substituted analogs exhibit an additional region of hydrogen bonding not seen with steroidal compounds and that multiple halogen substitutions affect the B-ring conformation and aromatic interactions with Trp741. This information elucidates interactions important for high AR binding affinity and provides new insight for structure-based drug design.

Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle.

PubMed

Serre, Stéphanie B N; Jensen, Sanne B; Ghanem, Lubna; Humes, Daryl G; Ramirez, Santseharay; Li, Yi-Ping; Krarup, Henrik; Bukh, Jens; Gottwein, Judith M

2016-06-01

Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified protease positions 54, 155, and 156 as hot spots for the selection of resistance substitutions under treatment with the first licensed PIs, telaprevir and boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir, faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged for three newer PIs. Substitution selection also depended on the specific recombinant. The substitutions identified conferred cross-resistance to several PIs; however, most substitutions selected under telaprevir or boceprevir treatment conferred less resistance to certain newer PIs. In a single-cycle production assay, across genotypes, PI treatment primarily decreased viral replication, which was rescued by PI resistance substitutions. The substitutions identified resulted in differential effects on viral fitness, depending on the original recombinant and the substitution. Across genotypes, fitness impairment induced by resistance substitutions was due primarily to decreased replication. Most combinations of substitutions that were identified increased resistance or fitness. Combinations of resistance substitutions with fitness-compensating substitutions either rescued replication or compensated for decreased replication by increasing assembly. This comprehensive study provides insight into the selection patterns and effects of PI resistance substitutions for HCV genotypes 1 to 6 in the context of the infectious viral life cycle, which is of interest for clinical and virological HCV research. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Localized disruption of Narp in medial prefrontal cortex blocks reinforcer devaluation performance

PubMed Central

Johnson, Alexander W.; Han, Sungho; Blouin, Ashley M.; Saini, Jasjit; Worley, Paul F.; During, Matthew J.; Holland, Peter C.; Baraban, Jay M.; Reti, Irving M.

2010-01-01

Neuronal activity regulated pentraxin (Narp) is a secreted protein that regulates α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPAR) aggregation and synaptogenesis. Mapping of Narp-positive neurons in brain has revealed it is prominently expressed in several limbic system projection pathways. Consistent with this localization pattern, Narp knockout mice show deficits in using the current value of a reinforcer to guide behavior, a critical function of the limbic system. To help assess whether this behavioral deficit is due to impairment of synaptogenesis during development or in modulating synaptic signaling in the mature brain, we have used a dominant negative Narp viral construct which blocks trafficking of endogenous Narp to axons. Focal injection of this viral construct into the medial prefrontal cortex (mPFC) of adult mice, a region containing Narp-positive projection neurons, blocked reinforcer devaluation. Thus, these results indicate that Narp released from mPFC neurons plays a key role in mediating synaptic changes underlying instrumental reinforcer devaluation. PMID:21127001

Spectroscopic, and thermal studies of some new binuclear transition metal(II) complexes with hydrazone ligands containing acetoacetanilide and isoxazole.

PubMed

Chen, Zhimin; Wu, Yiqun; Gu, Donghong; Gan, Fuxi

2007-11-01

A new chelating ligand, 2-(2-(5-tert-butylisoxazol-3-yl)hydrazono)-N-(2,4-dimethylphenyl)-3-oxobutanamide (HL), and its four binuclear transition metal complexes, M(2)(L)(2) (micro-OCH(3))(2) [M=Ni(II), Co(II), Cu(II), Zn(II)], were synthesized using the procedure of diazotization, coupling and metallization. Their structures were postulated based on elemental analysis, (1)H NMR, MALDI-MS, FT-IR spectra and UV-vis electronic absorption spectra. Smooth films of these complexes on K9 glass substrates were prepared using the spin-coating method and their absorption properties were evaluated. The thermal properties of the metal(II) complexes were investigated by thermogravimetry (TG) and differential scanning calorimetry (DSC). Different thermodynamic and kinetic parameters namely activation energy (E*), enthalpy of activation (DeltaH*), entropy of activation (DeltaS*) and free energy change of activation (DeltaG*) are calculated using Coats-Redfern (CR) equation.

A redox-mediated Kemp eliminase

NASA Astrophysics Data System (ADS)

Li, Aitao; Wang, Binju; Ilie, Adriana; Dubey, Kshatresh D.; Bange, Gert; Korendovych, Ivan V.; Shaik, Sason; Reetz, Manfred T.

2017-03-01

The acid/base-catalysed Kemp elimination of 5-nitro-benzisoxazole forming 2-cyano-4-nitrophenol has long served as a design platform of enzymes with non-natural reactions, providing new mechanistic insights in protein science. Here we describe an alternative concept based on redox catalysis by P450-BM3, leading to the same Kemp product via a fundamentally different mechanism. QM/MM computations show that it involves coordination of the substrate's N-atom to haem-Fe(II) with electron transfer and concomitant N-O heterolysis liberating an intermediate having a nitrogen radical moiety Fe(III)-N. and a phenoxyl anion. Product formation occurs by bond rotation and H-transfer. Two rationally chosen point mutations cause a notable increase in activity. The results shed light on the prevailing mechanistic uncertainties in human P450-catalysed metabolism of the immunomodulatory drug leflunomide, which likewise undergoes redox-mediated Kemp elimination by P450-BM3. Other isoxazole-based pharmaceuticals are probably also metabolized by a redox mechanism. Our work provides a basis for designing future artificial enzymes.

A review on cholinesterase inhibitors for Alzheimer's disease.

PubMed

Anand, Preet; Singh, Baldev

2013-04-01

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is characterized by the deficits in the cholinergic system and deposition of beta amyloid (Aβ) in the form of neurofibrillary tangles and amyloid plaques. Since the cholinergic system plays an important role in the regulation of learning and memory processes, it has been targetted for the design of anti-Alzheimer's drugs. Cholinesterase inhibitors enhance cholinergic transmission directly by inhibiting the enzyme acetylcholinesterase (AChE) which hydrolyses acetylcholine. Furthermore, it has been also demonstrated that both acetylcholinesterase and butrylcholinesterase (BuChE) play an important role in Aβ-aggregation during the early stages of senile plaque formation. Therefore, AChE and BuChE inhibition have been documented as critical targets for the effective management of AD by an increase in the availability of acetylcholine in the brain regions and decrease in the Aβ deposition. This review discusses the different classes of cholinesterase inhibitors including tacrine, donepezil, rivastigmine, galantamine, xanthostigmine, para-aminobenzoic acid, coumarin, flavonoid, and pyrrolo-isoxazole analogues developed for the treatment of AD.

Clinical Experience With Perampanel for Refractory Pediatric Epilepsy in One Canadian Center.

PubMed

Datta, Anita N; Xu, Qi; Sachedina, Shafina; Boelman, Cyrus; Huh, Linda; Connolly, Mary B

2017-08-01

Perampanel (PER) is a new antiseizure medication that inhibits the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) class of glutamate receptors. It is important for physicians to be aware of the efficacy and tolerability of new drugs in the postmarketing phase. We performed a retrospective review of our experience with perampanel at BC Children's Hospital. Twenty-four pediatric patients prescribed perampanel from 2014 to 2016 were identified. Fifteen (63%) discontinued perampanel, and 10 (42%) had greater than 50% reduction in seizures. Twelve (50%) had behavioral and 8 (33%) had nonbehavioral adverse events. One-third experienced serious adverse events. One patient experienced oculogyric crisis, which is not previously reported with perampanel. Adverse events were not dose related and were reversible. Possible risk factors for behavioral adverse events include a history of behavioral problems with other antiseizure medications and preexisting behavioral comorbidities. It is important to counsel patients about the potential for serious adverse events, particularly behavioral, when prescribing perampanel.

Developmental alterations in Huntington’s disease neural cells and pharmacological rescue in cells and mice

PubMed Central

2017-01-01

Neural cultures derived from Huntington’s disease (HD) patient-derived induced pluripotent stem cells were used for ‘omics’ analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation. We observed a strong correlation between HD-related histone marks, gene expression and unique peak profiles associated with dysregulated genes, suggesting a coordinated epigenetic program. Treatment with isoxazole-9, which targets key dysregulated pathways, led to amelioration of expanded polyglutamine repeat-associated phenotypes in neural cells and of cognitive impairment and synaptic pathology in HD model R6/2 mice. These data suggest that mutant huntingtin impairs neurodevelopmental pathways that could disrupt synaptic homeostasis and increase vulnerability to the pathologic consequence of expanded polyglutamine repeats over time. PMID:28319609

Strengthening of bridges by post-tensioning using monostrands in substituted cable ducts

NASA Astrophysics Data System (ADS)

Klusáček, Ladislav; Svoboda, Adam

2017-09-01

Post-tensioning is suitable, reliable and durable method of strengthening existing engineering structures, especially bridges. The high efficiency of post-tensioning can be seen in many applications throughout the world. In this paper the method is extended by a structural system of substituted cable ducts, which allows for significantly widening application of prestressing so it’s convenient mostly for application on beam bridges or slab bridges (built in years 1920 - 1960). The method of substituted cable ducts is based on theoretical knowledge and technical procedures, which were made possible through the development in prestressing systems, particularly the development of prestressing tendons (monostrands) and encased anchorages, as well as progress in drilling technology. This technique is highly recommended due to minimization of interventions into the constructions, unseen method of cable arrangement and hence the absence of impact on appearance, which is appreciated not only in case of valuable historical structures but also in general. It is possible to summarise that posttensioning by monostrands in substituted cable ducts is a highly effective method of strengthening existing bridges in order to increase their load capacities in terms of current traffic load and to extend their service life.

Feeding high-risk infants with family history of allergy.

PubMed

Cantani, A

1999-01-01

Since the turn of the century, CM (cow's milk) formulas have become progressively more common as breast milk substitutes when mother's milk is unavailable, and CM allergy (CMA) has thus gradually become a more common disorder. Therefore the management of CMA infants confronts pediatricians and allergists with one of the most demanding challenges. In the first year of life of many children, CM provides almost the entire dietary supply of proteins, carbohydrates, and fat; its high nutritional value and low cost should be noted. However, children with CMA can avoid CM without nutritional loss if nutrients are provided by other foods such as meat, fish, vegetables and fruit. Thus the choice of an adequate CM substitute for high-risk infants with family history of allergy is mandatory. The ideal CM substitute should be hypoallergenic; have an adequate nutritional value according to the infant's age; be easily available and inexpensive; and be palatable in order to obtain a good compliance. CM substitutes now available are soy protein formulas (SPF) and hydrolysate formulas (HF). Consequently pediatricians are now over-whelmed with a variety of information on new formulas called hypoallergenic and are faced with a difficult choice among them.

Association between salt substitutes/enhancers and changes in sodium levels in fast-food restaurants: a cross-sectional analysis.

PubMed

Scourboutakos, Mary J; Murphy, Sarah A; L'Abbé, Mary R

2018-03-07

Restaurant foods have high sodium levels, and efforts have been made to promote reductions. The objective of this study was to understand if salt substitutes and enhancers are associated with changes in sodium levels in fast-food restaurants. A longitudinal database (MENU-FLIP) containing nutrition information for Canadian chain restaurants with 20 or more locations nationally was created in 2010 and updated in 2013 and 2016. In 2016, when available, ingredient lists were collected from restaurant websites and searched for the presence of salt substitutes/enhancers. Changes in sodium levels (per serving) and the prevalence of salt substitutes/enhancers in 222 foods from 12 of the leading fast-food restaurant chains were compared across 3 time points. Sixty-nine percent of foods contained a salt substitute/enhancer. Substitutes/enhancers were found in every restaurant chain ( n = 12) for which ingredient data were available. The most common substitutes/enhancers were yeast extracts (in 30% of foods), calcium chloride (28%), monosodium glutamate (14%) and potassium chloride (12%). Sodium levels in foods that contained substitutes/enhancers decreased significantly more (190 ± 42 mg/serving) over the study period than those in foods that did not contain a substitute/enhancer (40 ± 17 mg/serving, p < 0.001). Salt substitutes and enhancers are prevalent in restaurant foods and are one means by which restaurants may be lowering sodium levels in their foods. At this time, the potential consequences of these findings, if any, are uncertain. Copyright 2018, Joule Inc. or its licensors.

Protein substitute dosage in PKU: how much do young patients need?

PubMed

MacDonald, A; Chakrapani, A; Hendriksz, C; Daly, A; Davies, P; Asplin, D; Hall, K; Booth, I W

2006-07-01

The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.(1) In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2-10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8-14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5-3.1 g/kg/day). When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 mumol/l (95% CI 215 to 386) and in the evening by 337 micromol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/- fat) content of the protein substitute.

Optimal Substitution of Cotton Burr and Linters in Thermoplastic Composites

USDA-ARS?s Scientific Manuscript database

A study was conducted to evaluate various substitutions of cotton burr and linters fractions of cotton gin waste (CGW) as a natural fiber source in ligno-cellulosic polymer composites (LCPC.) Samples were fabricated with approximately 50% natural fiber, 40% of high-density polyethylene (HDPE) powder...

Economic substitutability of electrical brain stimulation, food, and water.

PubMed Central

Green, L; Rachlin, H

1991-01-01

Concurrent variable-ratio schedules of electrical brain stimulation, food, and water were paired in various combinations as reinforcement of rats' lever presses. Relative prices of the concurrent reinforcers were varied by changing the ratio of the response requirements on the two levers. Economic substitutability, measured by the sensitivity of response ratio to changes in relative price, was highest with brain stimulation reinforcement of presses on both levers and lowest with food reinforcement of presses on one lever and water reinforcement of presses on the other. Substitutability with brain stimulation reinforcement of presses on one lever and either food or water reinforcement for presses on the other was about as high as with brain stimulation for presses on both levers. Electrical brain stimulation for rats may thus serve as an economic substitute for two reinforcers, neither of which is substitutable for the other. PMID:2037823

DETERMINATION OF 2,3,7,8 CHLORINE-SUBSTITUTED DIBENZO-P-DIOXINS AND FURANS AT THE PART PER TRILLION LEVEL IN UNITED STATES BEEF FAT USING HIGH-RESOLUTION GAS CHROMATOGRAPHY/HIGH-RESOLUTION MASS SPECTROMETRY

EPA Science Inventory

As part of the U.S. EPA Dioxin Reassessment Program, the 2,3,7,8-chlorine-substituted dibenzo-p-dioxins and furans were measured at part per trillion (ppt) levels in beef fat collected from slaughter facilities in the United States. This is the first statistically designed natio...

[Pd(μ-Cl)Cl(IPr*)]2: a highly hindered pre-catalyst for the synthesis of tetra-ortho-substituted biaryls via Grignard reagent cross-coupling.

PubMed

Lesieur, Mathieu; Slawin, Alexandra M Z; Cazin, Catherine S J

2014-08-14

The new well-defined catalyst [Pd(μ-Cl)Cl(IPr*)]2 enables the efficient Grignard reagent cross-coupling for the synthesis of tetra-ortho-substituted biaryls. The high reactivity of the complex is associated with the important bulkiness of the IPr* ligand. The dimer represents the most efficient catalyst reported to date for this challenging transformation.

Tandem High-pressure Freezing and Quick Freeze Substitution of Plant Tissues for Transmission Electron Microscopy

PubMed Central

Bobik, Krzysztof; Dunlap, John R.; Burch-Smith, Tessa M.

2014-01-01

Since the 1940s transmission electron microscopy (TEM) has been providing biologists with ultra-high resolution images of biological materials. Yet, because of laborious and time-consuming protocols that also demand experience in preparation of artifact-free samples, TEM is not considered a user-friendly technique. Traditional sample preparation for TEM used chemical fixatives to preserve cellular structures. High-pressure freezing is the cryofixation of biological samples under high pressures to produce very fast cooling rates, thereby restricting ice formation, which is detrimental to the integrity of cellular ultrastructure. High-pressure freezing and freeze substitution are currently the methods of choice for producing the highest quality morphology in resin sections for TEM. These methods minimize the artifacts normally associated with conventional processing for TEM of thin sections. After cryofixation the frozen water in the sample is replaced with liquid organic solvent at low temperatures, a process called freeze substitution. Freeze substitution is typically carried out over several days in dedicated, costly equipment. A recent innovation allows the process to be completed in three hours, instead of the usual two days. This is typically followed by several more days of sample preparation that includes infiltration and embedding in epoxy resins before sectioning. Here we present a protocol combining high-pressure freezing and quick freeze substitution that enables plant sample fixation to be accomplished within hours. The protocol can readily be adapted for working with other tissues or organisms. Plant tissues are of special concern because of the presence of aerated spaces and water-filled vacuoles that impede ice-free freezing of water. In addition, the process of chemical fixation is especially long in plants due to cell walls impeding the penetration of the chemicals to deep within the tissues. Plant tissues are therefore particularly challenging, but this protocol is reliable and produces samples of the highest quality. PMID:25350384

Do police arrestees substitute legal highs for other drugs?

PubMed

Wilkins, Chris; Parker, Karl; Prasad, Jitesh; Jawalkar, Sonie

2016-05-01

Some commentators have suggested legal highs (LH) might reduce existing illegal drug use and contribute to lower drug-related harm. However, no studies have specifically investigated substitution between LH and other drugs. To explore the extent to which police detainees substitute LH for illegal drugs. A total of 848 detainees at four central police stations were interviewed about their drug and LH use. Detainees were asked what impact their LH use had on their other drug use (i.e., 'no change', 'more', 'less' or 'stopped'). The detainees were placed into four groups: (i) no LH use; (ii) LH use and 'no change' in drug use; (iii) LH use and 'more' drug use; (iv) LH use and 'less' or 'stopped' drug use. Demographics and levels of drug use in the past month were compared between groups. Ninety-six percent of the LH using detainees had used synthetic cannabinoids (SC), and, of those who reported substituting a drug, 94% had substituted (natural) cannabis. Overall, 54% of the detainee sample had not used SC, 34% had used SC but not changed their cannabis use, 9% had used SC and used 'less' or 'stopped' cannabis use, and 3% had used SC and used 'more' cannabis. The SC users were more likely to have recently been in drug treatment. All those who used SC had higher cannabis consumption regardless of substitution behaviour. The SC users who used 'more' cannabis also used more methamphetamine and ecstasy. Twenty percent of those who used SC and cannabis reported reducing or stopping their cannabis use while 6% increased their cannabis use, suggesting a modest overall reduction in cannabis use. Further research is required to quantify the magnitude of substitution changes, the impact on drug-related harm, and extent to which substitution occurs for other LH and other populations. Copyright © 2016 Elsevier B.V. All rights reserved.

Charge-coupled Substituted Garnets (Y3-xCa0.5xM0.5x)Fe5O12 (M = Ce, Th): Structure and Stability as Crystalline Nuclear Waste Forms

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

Guo, Xiaofeng; Kukkadapu, Ravi K.; Lanzirotti, Anthony

2015-04-20

The garnet structure has been proposed as a potential crystalline nuclear waste form for accommodation of actinide elements, especially uranium (U). In this study, yttrium iron garnet (YIG) as a model garnet host was studied for the incorporation of U analogs, cerium (Ce), and thorium (Th), incorporated by a charge-coupled substitution with calci-um (Ca) for yttrium (Y) in YIG, namely 2Y3+ = Ca2+ + M4+, where M4+ = Ce4+ or Th4+. Single phase garnets Y3-xCa0.5xM0.5xFe5O12, synthesized by the citrate-nitrate combustion method, were obtained up to x = 0.7. Ce was confirmed to be tetravalent by X-ray absorption spectroscopy and X-raymore » photoelectron spectroscopy. X-ray diffraction and 57Fe-Mössbauer spectroscopy indicated that the samples are single phase, M4+ and Ca2+ cations are restricted to the c-site, the nature of M4+ has only a minor effect on the structure, and the local environments of both the tetrahedral and octahedral Fe3+ are systematically affected by the extent of substitution, especially on the tetrahedral sublattice. The charge coupled substitution has advantages in incorporating Ce/Th and in stabilizing the substituted phases, compared to a single substitution strategy. Enthalpies of formation of garnets were obtained by high temperature oxide melt solution calorimetry, and the enthalpies of substitution of Ce and Th were determined. The thermodynamic analysis demonstrates that the substituted garnets are entropically rather than energetically stabilized. This suggests that such garnets may form and persist in repositories at high temperature but might decompose near room temperature. These structural and thermodynamic findings shed light on possible incorporation of U in this garnet system.« less

An Escherichia coli Expression Assay and Screen for Human Immunodeficiency Virus Protease Variants with Decreased Susceptibility to Indinavir

PubMed Central

Melnick, Laurence; Yang, Shiow-Shong; Rossi, Rick; Zepp, Charlie; Heefner, Donald

1998-01-01

We have developed a recombinant Escherichia coli screening system for the rapid detection and identification of amino acid substitutions in the human immunodeficiency virus (HIV) protease associated with decreased susceptibility to the protease inhibitor indinavir (MK-639; Merck & Co.). The assay depends upon the correct processing of a segment of the HIV-1 HXB2 gag-pol polyprotein followed by detection of HIV reverse transcriptase activity by a highly sensitive, colorimetric enzyme-linked immunosorbent assay. The highly sensitive system detects the contributions of single substitutions such as I84V, L90M, and L63P. The combination of single substitutions further decreases the sensitivity to indinavir. We constructed a library of HIV protease variant genes containing dispersed mutations and, using the E. coli recombinant system, screened for mutants with decreased indinavir sensitivity. The discovered HIV protease variants contain amino acid substitutions commonly associated with indinavir resistance in clinical isolates, including the substitutions L90M, L63P, I64V, V82A, L24I, and I54T. One substitution, W6R, is also frequently found by the screen and has not been reported elsewhere. Of a total of 12,000 isolates that were screened, 12 protease variants with decreased sensitivity to indinavir were found. The L63P substitution, which is also associated with indinavir resistance, increases the stability of the isolated protease relative to that of the native HXB2 protease. The rapidity, sensitivity, and accuracy of this screen also make it useful for screening for novel inhibitors. We have found the approach described here to be useful for the detection of amino acid substitutions in HIV protease that have been associated with drug resistance as well as for the screening of novel compounds for inhibitory activity. PMID:9835523

Persistent Enhancement of Ethanol Drinking Following a Monosodium Glutamate-Substitution Procedure in C57BL6/J and DBA/2J Mice

PubMed Central

McCool, Brian A.; Chappell, Ann M.

2014-01-01

Inbred mouse strains such as C57BL/6J (B6) and DBA/2J (D2) and related strains have been used extensively to help identify genetic controls for a number of ethanol-related behaviors, including acute intoxication and sensitivity to repeated exposures. The disparate ethanol drinking behaviors of B6 mice expressing high-drinking/preference and D2 mice expressing low-drinking/preference have yielded considerable insight into the heritable control of alcohol drinking. However, the B6-high and D2-low drinking phenotypes are contrasted with ethanol-conditioned reward-like behaviors, which are robustly expressed by D2 mice and considerably less expressed by B6 mice. This suggests that peripheral factors, chiefly ethanol taste, may help drive ethanol drinking by these and related strains, which complicates mouse genetic studies designed to understand the relationships between reward-related behaviors and ethanol drinking. Traditional approaches such as the sucrose/saccharin-substitution procedure that normally accentuate ethanol drinking in rodents have had limited success in low drinking/preferring mice such as the D2 line. This may be due to allelic variations of the sweet taste receptor subunit, expressed by many ethanol low-drinking/preferring strains, which would limit the utility of these types of substitution approaches. We have recently shown (McCool & Chappell, 2012) that monosodium glutamate (MSG), the primary component of umami taste, can be used in a substitution procedure to initiate ethanol drinking in both B6 and D2 mice that greatly surpasses that initiated by a more traditional sucrose-substitution procedure. In this study, we show that ethanol drinking initiated by MSG substitution in D2 mice, but not sucrose substitution, can persist for several weeks following removal of the flavor. These findings further illustrate the utility of MSG substitution to initiate ethanol drinking in distinct mouse strains. PMID:24355071

Synthesis of Quaternary Carbon Stereogenic Centers through Enantioselective Cu-Catalyzed Allylic Substitutions with Vinylaluminum Reagents

PubMed Central

Gao, Fang; McGrath, Kevin P.; Lee, Yunmi; Hoveyda, Amir H.

2010-01-01

Catalytic enantioselective allylic substitution (EAS) reactions, which involve the use of alkyl- or aryl-substituted vinylaluminum reagents and afford 1,4-dienes containing a quaternary carbon stereogenic center at their C-3 site, are disclosed. The C–C bond forming transformations are promoted by 0.5–2.5 mol % of sulfonate bearing chiral bidentate N-heterocyclic carbene (NHC) complexes, furnishing the desired products efficiently (66–97% yield of isolated products) and in high site- (>98% SN2′) and enantioselectivity [up to 99:1 enantiomer ratio (er)]. To the best of our knowledge, the present report puts forward the first cases of allylic substitution reactions that result in the generation of all-carbon quaternary stereogenic centers through the addition of a vinyl unit. The aryl- and vinyl-substituted vinylaluminum reagents, which cannot be prepared in high efficiency through direct reaction with diisobutylaluminum hydride, are accessed through a recently introduced Ni-catalyzed reaction of the corresponding terminal alkynes with the same inexpensive metal-hydride agent. Sequential Ni-catalyzed hydrometallations and Cu-catalyzed C–C bond forming reactions allow for efficient and selective synthesis of a range of enantiomerically enriched EAS products, which cannot cannot be accessed by previously disclosed strategies (due to inefficient vinylmetal synthesis or low reactivity and/or selectivity with Si-substituted derivatives). The utility of the protocols developed is demonstrated through a concise enantioselective synthesis of natural product bakuchiol. PMID:20860365

The effect of inulin as a fat substitute on the physicochemical and sensory properties of chicken sausages.

PubMed

Alaei, Fereshteh; Hojjatoleslamy, Mohammad; Hashemi Dehkordi, Seyyed Majid

2018-03-01

Due to its high thermal resistance and compatibility with the sausage emulsion system, the long-chain inulin can be used as a fat substitute in the formulation of this product. This study was conducted to investigate the effect of inulin on the physicochemical, textural, and sensory properties of chicken sausages. The study included treatments of 25%, 50%, 75%, and 100% substitution. After preparing the samples, their physicochemical, textural, calorimetric, and sensory properties were evaluated. The treatment of 100% substitution of inulin had the maximum amount of sugar (29.90%), moisture (72.63%), protein (51.34), ash (6.95%), and salt (4.02%) (dry basis). The fat content was decreased with the increased levels of inulin substitution (p < .05). The increased amount of inulin reduced hardness, cohesiveness, gumminess, and stringiness, but increased springiness and chewiness up to the 25% substitution of inulin. The highest color difference and hue angle were related to 100% substitution treatment. The sensory evaluation of the samples showed that with the increase in the amount of inulin, the mean scores of the factors including color, appearance, and texture were increased, but the mean scores of smell and mouthfeel were decreased. Overall, the substitution of the entire fat existing in the formulation of the sausage with inulin led to the best physicochemical, textural, colorimetric, and sensory results. The use of inulin could be recommended as a fat substitute in the formulation of chicken sausages.

Mutations in the carboxyl terminal region of E2 glycoprotein of classical swine fever virus are responsible for viral attenuation in swine.

PubMed

Risatti, G R; Holinka, L G; Fernandez Sainz, I; Carrillo, C; Kutish, G F; Lu, Z; Zhu, J; Rock, D L; Borca, M V

2007-08-01

We have previously reported [Risatti, G.R., Borca, M.V., Kutish, G.F., Lu, Z., Holinka, L.G., French, R.A., Tulman, E.R., Rock, D.L. 2005a. The E2 glycoprotein of classical swine fever virus is a virulence determinant in swine. J. Virol. 79, 3787-3796] that chimeric virus 319.1v containing the E2 glycoprotein gene from Classical Swine Fever Virus (CSFV) vaccine strain CS with the genetic background of highly virulent CSFV strain Brescia (BICv) was markedly attenuated in pigs. To identify the amino acids mediating 319.1v attenuation a series of chimeric viruses containing CS E2 residues in the context of the Brescia strain were constructed. Chimera 357v, containing CS E2 residues 691 to 881 of CSFV polyprotein was virulent, while chimera 358v, containing CS E2 residues 882 to 1064, differing in thirteen amino acids from BICv, was attenuated in swine. Single or double substitutions of those amino acids in BICv E2 to CS E2 residues did not affect virulence. Groups of amino acids were then substituted in BICv E2 to CS E2 residues. Mutant 32v, with six substitutions between residues 975 and 1059, and mutant 33v, with six substitutions between 955 and 994, induced disease indistinguishable from BICv. Mutant 31v, with seven substitutions between residues 882 and 958, induced a delayed onset of lethal disease. Amino acids abrogating BICv virulence were then determined by progressively introducing six CS residues into 31v. Mutant 39v, containing nine residue substitutions, was virulent. Mutant 40v, containing ten residue substitutions, induced mild disease. Mutant 42v, containing twelve substitutions, and mutant 43v, with an amino acid composition identical to 358v, were attenuated in swine indicating that all substitutions were necessary for attenuation of the highly virulent strain Brescia. Importantly, 358v protected swine from challenge with virulent BICv at 3 and 28 days post-infection.

The potential of avocado paste (Persea americana) as fat substitute in non-dairy ice cream

NASA Astrophysics Data System (ADS)

Ervina; Surjawan, I.; Abdillah, E.

2018-01-01

Consumer preferences towards plant-based food have shifted significantly due to sustainable and healthy reasons. Dairy products consist of high Saturated Fatty Acid (SFA) and overconsumption of SFA could lead to cardiovascular diseases. Avocado contains high levels of fat dominated by Monounsaturated Fatty Acid (MUFA) and phytosterol that have the potential as a plant-based fat source to substitute dairy-fat in ice cream. The objective of this study was to analyze the physicochemical, rheological and sensorial properties of ice cream substituted with different concentrations of avocado paste ranging from 0%, 25%, 50%, 75% and 100% respectively against dairy fat to produce non-dairy fat ice cream. The psychochemical properties and total fat were determined. Sensorial quality and hedonic attributes of ice cream were investigated using 60 semi-trained panelists. There were significant differences (p<0.05) for overrun, melting rate, and viscosity of the ice cream substituted with avocado paste. The addition of avocado paste lead to the increase in viscosity and hardness of the ice cream significantly (p<0.05) while the sensorial properties for airiness and creaminess were perceived the same (p>0.05). The addition of 50% avocado paste was the most preferred among the panelists. Avocado could provide a potential substitution for dairy-fat in ice cream.

The S230R Integrase Substitution Associated with Viral Rebound during DTG Monotherapy Confers Low Levels INSTI Drug Resistance.

PubMed

Pham, Hanh T; Labrie, Lydia; Wijting, Ingeborg E A; Hassounah, Said; Lok, Ka Yee; Portna, Inna; Goring, Mark; Han, Yingshan; Lungu, Cynthia; van der Ende, Marchina E; Brenner, Bluma G; Boucher, Charles A; Rijnders, Bart J A; van Kampen, Jeroen J A; Mesplède, Thibault; Wainberg, Mark A

2018-03-29

Dolutegravir (DTG) is an integrase strand-transfer inhibitor (INSTI) used for treatment of HIV-infected individuals. Due to its high genetic barrier to resistance, DTG has been clinically investigated as maintenance monotherapy to maintain viral suppression and to reduce complication and healthcare costs. Our study aims to explain the underlying mechanism related to the emergence of a S230R substitution in patients who experienced virological failure while using DTG monotherapy. We evaluated the effect of S230R substitution in regard to IN enzyme activity, viral infectivity, replicative capacity and susceptibility to different INSTIs by biochemical and cell-based assays. S230R substitution conferred 63% reduction in enzyme efficiency. The S230R virus was 1.29-fold less infectious than wildtype (WT), but could replicate in PM1 cells without significant delay. Resistance levels against DTG, CAB, RAL and EVG in tissue culture were 3.85-, 3.72-, 1.52-, and 1.21-fold, respectively. Our data indicate that the S230R substitution is comparable to the previously reported R263K in some respects. Virological failure under DTG monotherapy can occur through the development of such S230R or R263K mutations without the need for high levels DTG resistance.

Effect of Fe and Co substitution on the martensitic stability and the elastic, electronic, and magnetic properties of Mn2NiGa : Insights from ab initio calculations

NASA Astrophysics Data System (ADS)

Kundu, Ashis; Ghosh, Sheuly; Ghosh, Subhradip

2017-11-01

We investigate the effects of Fe and Co substitutions on the phase stability of the martensitic phase and mechanical, electronic, and magnetic properties of the magnetic shape memory system Mn2NiGa by first-principles density functional theory calculations. The evolution of these aspects upon substitution of Fe and Co at different crystallographic sites is investigated by computing the electronic structure, mechanical properties (tetragonal shear constant, Pugh ratio, and Cauchy pressure), and magnetic exchange parameters. We find that the austenite phase of Mn2NiGa gradually stabilizes with increase in concentration of Fe/Co due to the weakening of the minority spin hybridization of Ni and Mn atoms occupying crystallographically equivalent sites. The interplay between relative structural stability and the compositional changes is understood from the variations in the elastic moduli and electronic structures. We find that like in the Ni2MnGa -based systems, the elastic shear modulus C' can be considered as a predictor of composition dependence of martensitic transformation temperature Tm in substituted Mn2NiGa , thus singling it out as the universally acceptable predictor for martensitic transformation in Ni-Mn-Ga compounds over a wide composition range. The magnetic properties of Mn2NiGa are found to be greatly improved by the substitutions due to stronger ferromagnetic interactions in the compounds. The gradually weaker (stronger) Jahn-Teller distortion (covalent bonding) in the minority spin densities of states due to substitutions leads to a half-metallic-like gap in these compounds resulting in materials with high spin polarization when the substitutions are complete. The substitutions at the Ga site result in the two compounds Mn2NiFe and Mn2NiCo with very high magnetic moments and Curie temperatures. Thus, our work indicates that although the substitutions destroy the martensitic transformation and thus the possibility of realization of shape memory properties in Mn2NiGa , magnetic materials with very good magnetic parameters that are potentially useful for novel magnetic applications can be obtained. This can trigger interest in the experimental community in further research on substituted Mn2NiGa .

The substitutability of reinforcers.

PubMed

Green, Leonard; Freed, Debra E

1993-07-01

Substitutability is a construct borrowed from microeconomics that describes a continuum of possible interactions among the reinforcers in a given situation. Highly substitutable reinforcers, which occupy one end of the continuum, are readily traded for each other due to their functional similarity. Complementary reinforcers, at the other end of the continuum, tend to be consumed jointly in fairly rigid proportion, and therefore cannot be traded for one another except to achieve that proportion. At the center of the continuum are reinforcers that are independent with respect to each other; consumption of one has no influence on consumption of another. Psychological research and analyses in terms of substitutability employ standard operant conditioning paradigms in which humans and nonhumans choose between alternative reinforcers. The range of reinforcer interactions found in these studies is more readily accommodated and predicted when behavior-analytic models of choice consider issues of substitutability. New insights are gained into such areas as eating and drinking, electrical brain stimulation, temporal separation of choice alternatives, behavior therapy, drug use, and addictions. Moreover, the generalized matching law (Baum, 1974) gains greater explanatory power and comprehensiveness when measures of substitutability are included.

Tuning the Curie temperature of L1{sub 0} ordered FePt thin films through site-specific substitution of Rh

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

Xu, Dongbin, E-mail: dongbin.xu@seagate.com; Department of Materials Science and Engineering, National University of Singapore, Singapore 117576; Sun, Cheng-Jun, E-mail: cjsun@aps.anl.gov, E-mail: msecgm@nus.edu.sg

2014-10-14

In structurally ordered magnetic thin films, the Curie temperature (T{sub C}) of ferromagnetic films depends on the exchange integral of the short range ordered neighboring atoms. The exchange integral may be adjusted by controlling the elemental substitutional concentration at the lattice site of interest. We show how to control the T{sub C} in high anisotropy L1{sub 0} Fe{sub 50}Pt{sub 50} magnetic thin films by substituting Rh into the Pt site. Rh substitution in L1{sub 0} FePt modified the local atomic environment and the corresponding electronic properties, while retaining the ordered L1{sub 0} phase. The analysis of extended x-ray Absorption Finemore » Structure spectra shows that Rh uniformly substitutes for Pt in L1{sub 0} FePt. A model of antiferromagnetic defects caused by controlled Rh substitution of the Pt site, reducing the T{sub C,} is proposed to interpret this phenomenon and its validity is further examined by ab initio density functional calculations.« less

The substitutability of reinforcers

PubMed Central

Green, Leonard; Freed, Debra E.

1993-01-01

Substitutability is a construct borrowed from microeconomics that describes a continuum of possible interactions among the reinforcers in a given situation. Highly substitutable reinforcers, which occupy one end of the continuum, are readily traded for each other due to their functional similarity. Complementary reinforcers, at the other end of the continuum, tend to be consumed jointly in fairly rigid proportion, and therefore cannot be traded for one another except to achieve that proportion. At the center of the continuum are reinforcers that are independent with respect to each other; consumption of one has no influence on consumption of another. Psychological research and analyses in terms of substitutability employ standard operant conditioning paradigms in which humans and nonhumans choose between alternative reinforcers. The range of reinforcer interactions found in these studies is more readily accommodated and predicted when behavior-analytic models of choice consider issues of substitutability. New insights are gained into such areas as eating and drinking, electrical brain stimulation, temporal separation of choice alternatives, behavior therapy, drug use, and addictions. Moreover, the generalized matching law (Baum, 1974) gains greater explanatory power and comprehensiveness when measures of substitutability are included. PMID:16812696

Dielectric and AC conductivity studies of Nd substituted 0.8BaTiO{sub 3}-0.2(Bi{sub 0.5(1-x)}Nd{sub 0.5x}K{sub 0.5})TiO{sub 3} lead free ceramics

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

Ramesh, M. N. V.; Ramesh, K. V., E-mail: kv-ramesh5@yahoo.co.in

2016-05-23

0.8BaTiO{sub 3} – 0.2(Bi{sub 0.5(1-x)}Nd{sub 0.5x}K{sub 0.5})TiO{sub 3} (0.01 ≤ x ≤ 0.06) lead free ceramic materials have been prepared by solid state reaction method and followed by high energy ball milling process. X-ray diffraction studies confirm the tetragonal structure of the materials at room temperature. Lattice parameters and density are decreasing with increase of Nd substitution. Microstructure studies were done by using Scanning electron microscope and it found that grain size is decreasing with increase of Nd substitution. Temperature and frequency dependent dielectric studies reveal relaxor behaviour of the materials. Dielectric constant, dielectric loss and Curie temperature are decreasingmore » with Nd substitution. Maximum Curie temperature of 195°C was observed at 1 MHz for x=0.01 Nd substituted sample. Degree of diffuseness was calculated from the modified Curie-Weiss law and it is increasing with Nd substitution. AC conductivity is increasing with increase of Nd substitution and observed maximum activation energy of 0.52 eV for x=0.02 Nd substituted sample.« less

Synthesis and antileishmanial activity of 6-mono-substituted and 3,6-di-substituted acridines obtained by acylation of proflavine.

PubMed

Di Giorgio, Carole; Shimi, Kamal; Boyer, Gérard; Delmas, Florence; Galy, Jean-Pierre

2007-10-01

Two new series of diaminoacridinic derivatives obtained from proflavine and N-(6-amino-3-acridinyl)acetamide were synthesised and assessed for their cytotoxic and antileishmanial activities. Two compounds, N-[6-(acetylamino)-3-acridinyl]acetamide and N-[6-(benzoylamino)-3-acridinyl]benzamide demonstrated highly specific antileishmanial properties against the intracellular amastigote form of the parasite. Structure-activity relationships established that the antiproliferative activity against human cells was greatly enhanced by the presence of a benzoylamino group in 6-mono-substituted acridines, while the presence of two acetylamino or benzoylamino groups in 3,6-di-substituted acridines strongly increased the specificity of the molecules for Leishmania parasite, suggesting that symmetric conformations could preferentially interfere with Leishmania metabolism.

Tuning of superconductivity by Ni substitution into noncentrosymmetric ThC o1 -xN ixC2

NASA Astrophysics Data System (ADS)

Grant, T. W.; Cigarroa, O. V.; Rosa, P. F. S.; Machado, A. J. S.; Fisk, Z.

2017-07-01

The recently discovered noncentrosymmetric superconductor ThCoC2 was observed to show unusual superconducting behavior with a critical temperature of Tc=2.65 K . Here we investigate the effect of nickel substitution on the superconducting state in ThC o1 -xN ixC2 . Magnetization, resistivity, and heat capacity measurements demonstrate Ni substitution has a dramatic effect with critical temperature increased up to Tc=12.1 K for x =0.4 Ni concentration, which is a rather high transition temperature for a noncentrosymmetric superconductor. In addition, the unusual superconducting characteristics observed in pure ThCoC2 appear to be suppressed or tuned with Ni substitution towards a more conventional fully gapped superconductor.

Effects of Mn Substitution on the Thermoelectric Properties and Thermal Excitations of the Electron-doped Perovskite Sr1-xLaxTiO3

NASA Astrophysics Data System (ADS)

Okuda, Tetsuji; Hata, Hiroto; Eto, Takahiro; Sobaru, Shogo; Oda, Ryosuke; Kaji, Hiroki; Nishina, Kousuke; Kuwahara, Hideki; Nakamura, Mitsutaka; Kajimoto, Ryoichi

2016-09-01

We studied how Mn substitution affects the thermoelectric properties and thermal excitations of the electron-doped perovskite Sr1-xLaxTiO3 by measuring its electrical and thermal transport properties, magnetization, specific heat, and inelastic neutron scattering. Slight Mn substitution with the lattice defects enhanced the Seebeck coefficient, perhaps because of coupling between itinerant electrons and localized spins or between itinerant electrons and local lattice distortion around Mn3+ ions, while it enhanced anharmonic lattice vibrations, which effectively suppressed thermal conductivity in a state of high electrical conductivity. Consequently, slight Mn substitution increased the dimensionless thermoelectric figure of merit for Sr1-xLaxTiO3 near room temperature.

Synthesis of the active form of loxoprofen by using allylic substitutions in two steps.

PubMed

Hyodo, Tomonori; Kiyotsuka, Yohei; Kobayashi, Yuichi

2009-03-05

High regioselectivity for allylic substitution of the cyclopentenyl picolinate 5 with benzylcopper reagent was attained with ZnBr(2), and the finding was applied to the p-BrC(6)H(4)CH(2) reagent. The cyclopentene moiety in the product was reduced to the cyclopentane, and the p-BrC(6)H(4) was converted to the "Cu"C(6)H(4) for the second allylic substitution with picolinate 8 to furnish the title compound after oxidative cleavage of the resulting olefin moiety.

High-energy lithium-ion battery using substituted LiCoPO4: From coin type to 1 Ah cell

NASA Astrophysics Data System (ADS)

Liu, D.; Zhu, W.; Kim, C.; Cho, M.; Guerfi, A.; Delp, S. A.; Allen, J. L.; Jow, T. R.; Zaghib, K.

2018-06-01

Cr, Fe and Si were added to improve the performance of olivine LiCoPO4 in cathodes for lithium-ion batteries. A substituted-LiCoPO4 in a half cell delivered a reversible capacity of 125 mAh/g at C/3 rate, with no capacity loss after over 100 cycles at 25 °C. The well-known capacity fade of LiCoPO4-based cathodes was almost completely eliminated by substituting Cr, Fe and Si.

The manufacture of synthetic non-sintered and degradable bone grafting substitutes.

PubMed

Gerike, W; Bienengräber, V; Henkel, K-O; Bayerlein, T; Proff, P; Gedrange, T; Gerber, Th

2006-02-01

A new synthetic bone grafting substitute (NanoBone, ARTOSS GmbH, Germany) is presented. This is produced by a new technique, the sol-gel-method. This bone grafting substitute consists of nanocrystalline hydroxyapatite (HA) and nanostructured silica (SiO2). By achieving a highly porous structure good osteoconductivity can be seen. In addition, the material will be completely biodegraded and new own bone is formed. It has been demonstrated that NanoBone is biodegraded by osteoclasts in a manner comparable to the natural bone remodelling process.

Improvement in low-temperature and instantaneous high-rate output performance of Al-free AB5-type hydrogen storage alloy for negative electrode in Ni/MH battery: Effect of thermodynamic and kinetic regulation via partial Mn substituting

NASA Astrophysics Data System (ADS)

Zhou, Wanhai; Zhu, Ding; Tang, Zhengyao; Wu, Chaoling; Huang, Liwu; Ma, Zhewen; Chen, Yungui

2017-03-01

A series of Al-free Mn-modified AB5-type hydrogen storage alloys have been designed and the effects of thermodynamic stability and electrochemical kinetics on electrochemical performance via Mn substituting have been investigated. Compared with high-Al alloys, the Al-free alloys in this study have better low-temperature performance and instantaneous high-rate output because of the higher surface catalytic ability. After partial substitution of Ni by Mn, both the hydrogen desorption capacity and plateau pressure decrease, and correspondingly results in an improved thermodynamic stability which is adverse to low-temperature delivery. Additionally, with the improvement of charge acceptance ability and anti-corrosion property via Mn substitution, the room-temperature discharge capacity and cycling stability increase slightly. However, Mn adversely affects the electrochemical kinetics and deteriorates both the surface catalytic ability and the bulk hydrogen diffusion ability, leading to the drop of low-temperature dischargeability, high-rate dischargeability and peak power (Ppeak). Based on the thermodynamic and kinetic regulation and overall electrochemical properties, the optimal composition is obtained when x = 0.2, the discharge capacity is 243.6 mAh g-1 at -40 °C with 60 mA g-1, and the Ppeak attains to 969.6 W kg-1 at -40 °C.

Analysis of Impingement between Patella Bone and Bearing Post in Cruciate-Substituting High-Flexion Total Knee Arthroplasty

PubMed Central

Chon, Jegyun; Shin, Sangyeop; Jang, Gunil; Jeon, Taehyeon

2016-01-01

Background We investigated the causes of impingement between the patella bone and the bearing post during high flexion in cruciate-substituting total knee arthroplasty and proposed a treatment strategy. Methods This prospective cohort study included 218 cases that had undergone cruciate-substituting total knee arthroplasty from February 2014 to January 2015; a single surgeon performed the operation using the same method without patellar resurfacing in all patients. Results In these patients, the occurrence of impingement was determined by performing more than 120° high knee flexion after inserting a bearing perioperatively. The incidence of impingement was significantly associated with bearing design, femoral implant size, patella bone length, and patella inferior pole angle (p < 0.05). The impingement was resolved by resection of the lower articular side of the patella bone. Conclusions In the cruciate-substituting high-flexion total knee arthroplasty, impingement between the patella bone and bearing post was more common in patients with mobile bearing, small-size femoral component, and a long patella or a large inferior pole angle. In cases of intraoperative impingement between the patella bone and the bearing post, resection in the lower portion of the patella prevented impingement of the bearing with soft tissue or the patella by widening the space between the patella and the bearing post, which in turn prevented postoperative reduction in range of motion. PMID:27247740

Analysis of Impingement between Patella Bone and Bearing Post in Cruciate-Substituting High-Flexion Total Knee Arthroplasty.

PubMed

Chon, Jegyun; Lee, Bongju; Shin, Sangyeop; Jang, Gunil; Jeon, Taehyeon

2016-06-01

We investigated the causes of impingement between the patella bone and the bearing post during high flexion in cruciate-substituting total knee arthroplasty and proposed a treatment strategy. This prospective cohort study included 218 cases that had undergone cruciate-substituting total knee arthroplasty from February 2014 to January 2015; a single surgeon performed the operation using the same method without patellar resurfacing in all patients. In these patients, the occurrence of impingement was determined by performing more than 120° high knee flexion after inserting a bearing perioperatively. The incidence of impingement was significantly associated with bearing design, femoral implant size, patella bone length, and patella inferior pole angle (p < 0.05). The impingement was resolved by resection of the lower articular side of the patella bone. In the cruciate-substituting high-flexion total knee arthroplasty, impingement between the patella bone and bearing post was more common in patients with mobile bearing, small-size femoral component, and a long patella or a large inferior pole angle. In cases of intraoperative impingement between the patella bone and the bearing post, resection in the lower portion of the patella prevented impingement of the bearing with soft tissue or the patella by widening the space between the patella and the bearing post, which in turn prevented postoperative reduction in range of motion.

Analysis of Running and Technical Performance in Substitute Players in International Male Rugby Union Competition.

PubMed

Lacome, Mathieu; Piscione, Julien; Hager, Jean-Philippe; Carling, Christopher

2016-09-01

To investigate the patterns and performance of substitutions in 18 international 15-a-side men's rugby union matches. A semiautomatic computerized time-motion system compiled 750 performance observations for 375 players (422 forwards, 328 backs). Running and technical-performance measures included total distance run, high-intensity running (>18.0 km/h), number of individual ball possessions and passes, percentage of passes completed, and number of attempted and percentage of successful tackles. A total of 184 substitutions (85.2%) were attributed to tactical and 32 (14.8%) to injury purposes respectively. The mean period for non-injury-purpose substitutions in backs (17.7%) occurred between 70 and 75 min, while forward substitutions peaked equally between 50-55 and 60-65 min (16.4%). Substitutes generally demonstrated improved running performance compared with both starter players who completed games and players whom they replaced (small differences, ES -0.2 to 0.5) in both forwards and backs over their entire time played. There was also a trend for better running performance in forward and back substitutes over their first 10 min of play compared with the final 10 min for replaced players (small to moderate differences, ES 0.3-0.6). Finally, running performance in both forward and back substitutes was generally lower (ES -0.1 to 0.3, unclear or small differences) over their entire 2nd-half time played compared with their first 10 min of play. The impact of substitutes on technical performance was generally considered unclear. This information provides practitioners with practical data relating to the physical and technical contributions of substitutions that subsequently could enable optimization of their impact on match play.

Generic medicines and generic substitution: contrasting perspectives of stakeholders in Ireland.

PubMed

O'Leary, A; Usher, C; Lynch, M; Hall, M; Hemeryk, L; Spillane, S; Gallagher, P; Barry, M

2015-12-15

The Health (Pricing and Supply of Medical Goods) Act 2013 passed into law in July 2013 and legislated for generic substitution in Ireland. The aim of the study was to ascertain the knowledge and perceptions of stakeholders i.e. patients, pharmacists and prescribers, of generic medicines and to generic substitution with the passing of legislation. Three stakeholder specific questionnaires were developed to assess knowledge of and perceptions to generic medicines and generic substitution. Purposive samples of patients, prescribers and pharmacists were analysed. Descriptive quantitative and qualitative analyses were undertaken. A total of 762 healthcare professionals and 353 patients were recruited. The study highlighted that over 84% of patients were familiar with generic medicines and are supportive of the concept of generic substitution. Approximately 74% of prescribers and 84% of pharmacists were supportive of generic substitution in most cases. The main areas of concern highlighted by the healthcare professionals that might impact on the successful implementation of the policy, were the issue of bioequivalence with generic medicines, the computer software systems used at present in general practitioner (GP) surgeries and the availability of branded generics. The findings from this study identify a high baseline rate of acceptance to generic medicines and generic substitution among patients, prescribers and pharmacists in the Irish setting. The concerns of the main stakeholders provide a valuable insight into the potential difficulties that may arise in its implementation, and the need for on-going reassurance and proactive dissemination of the impact of the generic substitution policy. The existing positive attitude to generic medicines and generic substitution among key stakeholders in Ireland to generic substitution, combined with appropriate support and collaboration should result in the desired increase in rates of prescribing, dispensing and use of generic medicines.

Pressure and phase dependence of the stereochemical course in hot tritium for hydrogen and chlorine-38 for chlorine substitution in meso- and rac-1,2-dichloro-1,2-difluoroethane

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

Machulla, H J; Stocklin, G

1974-03-28

The pressure dependence of the stereochemical course in hot homolytic T- for-H and /sup 38/ Cl-for-Cl substitution in mesoand rac-1,2-dichloro-l,2- difluoroethane has been studied from 10 to 10/sup 4/ Torr. Distinct differences are observed between the yield vs. density dependence of the retained and the inverted product. For both recoil tritium and chlorine, substitution with inversion of configuration is almost negligible in the gas phase and its yields remained constant over the entire pressure range studied. Typical pressure effects are observed, however, for substitution with retention of configuration, particularly for recoil chlorine. While the change from the high-pressure gas phasemore » to the liquid leaves T-for-H substitution almost unaffected, /sup 38/Cl-for- Cl substitution exhibits a strong phase effect. The absolute yields of the retained product increase by a factor of 2.5, that of the invented product by about 20, almost identical in both diastereomeric substrates. The density dependence of the HCl and HF elimination products is also different for recoil tritium and chlorine; in the latter case the yields follow the increasing trend observed for substitution. While for recoil tritium the predominant substitution channel seems to be a direct replacement with retention of configuration, even in the liquid phase, /sup 38/Cl-for-Cl substitution at higher densities cannot be satisfactorily explained on the basis of the impact model nor by caged radical combination. Alternatively, substitution via a caged complex is discussed. (auth)« less

Protein substitute dosage in PKU: how much do young patients need?

PubMed Central

MacDonald, A; Chakrapani, A; Hendriksz, C; Daly, A; Davies, P; Asplin, D; Hall, K; Booth, I W

2006-01-01

Background The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). Aim To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.1 Methods In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2–10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre‐breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8–14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5–3.1 g/kg/day). Results When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre‐breakfast by 301 μmol/l (95% CI 215 to 386) and in the evening by 337 μmol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. Conclusions A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/− fat) content of the protein substitute. PMID:16547085

Lives in Motion: A Review of Former Foster Youth in the Context of their Experiences in the Child Welfare System

PubMed Central

Havlicek, Judy

2011-01-01

In light of the poor prospects facing many former foster youth during the transition to adulthood, it is surprising that so little attention has been given to substitute care contexts during child welfare system involvement. A review of child welfare research finds that many former foster youth go through an alarming number of placement changes and report a high rate of placement into congregate care settings and other unplanned events. Future research should take explicit account of substitute care contexts in designing and carrying out studies examining the adult outcomes of aging out foster care populations. Interventions intended to circumvent high rates of movement in foster care should also be broadened to target multiple aspects of substitute care contexts. PMID:21643470

Adaptation of tick-borne encephalitis virus from human brain to different cell cultures induces multiple genomic substitutions.

PubMed

Ponomareva, Eugenia P; Ternovoi, Vladimir A; Mikryukova, Tamara P; Protopopova, Elena V; Gladysheva, Anastasia V; Shvalov, Alexander N; Konovalova, Svetlana N; Chausov, Eugene V; Loktev, Valery B

2017-10-01

The C11-13 strain from the Siberian subtype of tick-borne encephalitis virus (TBEV) was isolated from human brain using pig embryo kidney (PEK), 293, and Neuro-2a cells. Analysis of the complete viral genome of the C11-13 variants during six passages in these cells revealed that the cell-adapted C11-13 variants had multiple amino acid substitutions as compared to TBEV from human brain. Seven out of eight amino acids substitutions in the high-replicating C11-13(PEK) variant mapped to non-structural proteins; 13 out of 14 substitutions in the well-replicating C11-13(293) variant, and all four substitutions in the low-replicating C11-13(Neuro-2a) variant were also localized in non-structural proteins, predominantly in the NS2a (2), NS3 (6) and NS5 (3) proteins. The substitutions NS2a 1067 (Asn → Asp), NS2a 1168 (Leu → Val) in the N-terminus of NS2a and NS3 1745 (His → Gln) in the helicase domain of NS3 were found in all selected variants. We postulate that multiple substitutions in the NS2a, NS3 and NS5 genes play a key role in adaptation of TBEV to different cells.

Tuning the Curie temperature of L 1 0 ordered FePt thin films through site-specific substitution of Rh

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

Xu, Dongbin; Sun, Cheng-Jun; Chen, Jing-Sheng

2014-10-14

In structurally ordered magnetic thin films, the Curie temperature (TC) of ferromagnetic films depends on the exchange integral of the short range ordered neighboring atoms. The exchange integral may be adjusted by controlling elemental substitutional concentration at the lattice site of interest. We show how to control the TC in high anisotropy L10 Fe50Pt50 magnetic thin films by substituting Rh into the Pt site. Rh substitution in L10 FePt modified the local atomic environment and corresponding electronic properties while retaining the ordered L10 phase. The analysis of extended x-ray Absorption Fine Structure (EXAFS) spectra shows that Rh uniformly substitutes formore » Pt in L10 FePt. With 15 at. % of Rh substitution, temperature-dependent magnetic measurements show that the saturation magnetization (Ms) decreases from 1152 emu/cc to 670 emu/cc, the magnetocrystalline anisotropy (Ku) drops from 5×107 erg/cc to 2×107 erg/cc, and TC decreased from 750 to 500 K. A model of antiferromagnetic (AFM) defects caused by controlled Rh substitution of the Pt site, reducing the TC, is proposed to interpret this phenomenon and the validity is further examined by ab initio density functional calculations.« less

Diels-Alder Cycloadditions of Masked o-Benzoquinones with Alkenes.

PubMed

Georgopanou, Effie; Martini, Katerina-Irene; Pantazis, Panagiotis; Pelagias, Paulos; Voulgari, Penelope; Hadjiarapoglou, Lazaros P

2015-10-02

Diels-Alder cycloadditions of 3-oxobut-1-enyl substituted orthoquinone monoketals with olefinic dienophiles furnished functionalized ortho-endo bicyclo[2.2.2]octenone derivatives with high regio- and stereoselectivities. The competition between self-dimerization and Diels-Alder cycloaddition with an external dienophile usually exists, except in the case of 5-substituted orthoquinone monoketal.

Substitution and addition reactions of •OH with p-substituted-phenols

NASA Astrophysics Data System (ADS)

Albarrán, Guadalupe; Galicia-Jiménez, Eduardo; Mendoza, Edith; Schuler, Robert H.

2017-04-01

The directing effect of a hydroxyl group on the substitution and addition reactions of •OH to the substituted and free positions in aromatic rings of p-substituted-phenols were studied in aqueous solutions containing either K3Fe(CN)6 as an oxidant of the substituted hydroxycyclohexadienyl radical initially formed or using ascorbic acid. The results showed that the attack of the •OH to the substituted position (ipso position) was followed by elimination of the substituent producing hydroquinone. The addition reaction of the •OH to the free position on the ring produced 4-substituent-catechol and 4-substituent-resorcinol derivatives. Identification and quantification of the radiolytic products were carried out using high performance liquid chromatography. The results of the yields are given for the p-halogen-phenols (p-X-Ph) p-F-Ph, p-Cl-Ph, p-Br-Ph and p-I-Ph. Other compounds, p-nitro-Ph, p-OH-benzoic acid, p-OH-benzonitrile, p-OH-benzaldehyde, p-OH-anisole and p-OH-benzyl alcohol (represented as p-Z-Ph), were only studied using K3Fe(CN)6 as the oxidant. The results show that the p-X-Ph are attacked by the •OH at the ipso position to the halogen in the proportion 1:0.53:0.46:0.11 for F>Cl>Br>I. The •OH attacked at the ipso position to the p-Z-Phs through a substitution reaction, which depended on the substituent group. Thus, the strongly deactivating groups produced less hydroquinone, indicating less substitution reaction than the strongly activating groups.

Thin Bioactive Zn Substituted Hydroxyapatite Coating Deposited on Ultrafine Grained Titanium Substrate: Structure Analysis

NASA Astrophysics Data System (ADS)

Prosolov, Konstantin A.; Belyavskaya, Olga A.; Muehle, Uwe; Sharkeev, Yurii P.

2018-02-01

Nanocrystalline Zn substituted hydroxyapatite coatings were deposited by radiofrequency magnetron sputtering on the surface of ultrafine-grained titanium substrates. Cross section transmission electron microscopy provided information about the morphology and texture of the thin film while in-column energy dispersive X-ray analysis confirmed the presence of Zn in the coating. The Zn substituted hydroxyapatite coating was formed by an equiaxed polycrystalline grain structure. Effect of substrate crystallinity on the structure of deposited coating is discussed. An amorphous TiO2 sublayer of 8 nm thickness was detected in the interface between the polycrystalline coating and the Ti substrate. Its appearance in the amorphous state is attributed to prior to deposition etching of the substrate and subsequent condensation of oxygen-containing species sputtered from the target. This layer contributes to the high coating-to-substrate adhesion. The major P-O vibrational modes of high intensity were detected by Raman spectroscopy. The Zn substituted hydroxyapatite could be a material of choice when antibacterial osteoconductive coating with a possibility of withstanding mechanical stress during implantation and service is needed.

Dialkylthio Substitution: An Effective Method to Modulate the Molecular Energy Levels of 2D-BDT Photovoltaic Polymers.

PubMed

Yao, Huifeng; Zhang, Hao; Ye, Long; Zhao, Wenchao; Zhang, Shaoqing; Hou, Jianhui

2016-02-17

Dialkylthio-substituted thienyl-benzodithiophene (BDT-DST) was designed and synthesized as a building block to modulate the molecular levels of the conjugated polymers, and three copolymers named PDST-BDD, PDST-TT and PDST-DPP were prepared and applied in polymer solar cells (PSCs). Theoretical calculations and electrochemical cyclic voltammetry (CV) measurement suggested that the dialkylthio group could decrease the molecular energy levels of the resulting polymers distinctly. The open-circuit voltage (VOC) of PSC devices based on PDST-BDD, PDST-TT, and PDST-DPP are as high as 1.0, 0.98, and 0.88 V, respectively, which are ∼0.15 V higher than those of the corresponding alky-substituted analogues. Moreover, the influence of the dialkylthio group on the absorption spectra, crystalline properties, hole mobilities, and blend morphologies of the polymers was also investigated. The results indicate that the dialkythio substitution is an effective method to modulate the molecular energy levels and that the BDT-DST unit has potential for constructing high-efficiency photovoltaic polymers.

Structural studies of human alkaline phosphatase in complex with strontium: Implication for its secondary effect in bones

PubMed Central

Llinas, Paola; Masella, Michel; Stigbrand, Torgny; Ménez, André; Stura, Enrico A.; Le Du, Marie Hélène

2006-01-01

Strontium is used in the treatment of osteoporosis as a ranelate compound, and in the treatment of painful scattered bone metastases as isotope. At very high doses and in certain conditions, it can lead to osteomalacia characterized by impairment of bone mineralization. The osteomalacia symptoms resemble those of hypophosphatasia, a rare inherited disorder associated with mutations in the gene encoding for tissue-nonspecific alkaline phosphatase (TNAP). Human alkaline phosphatases have four metal binding sites—two for zinc, one for magnesium, and one for calcium ion—that can be substituted by strontium. Here we present the crystal structure of strontium-substituted human placental alkaline phosphatase (PLAP), a related isozyme of TNAP, in which such replacement can have important physiological implications. The structure shows that strontium substitutes the calcium ion with concomitant modification of the metal coordination. The use of the flexible and polarizable force-field TCPEp (topological and classical polarization effects for proteins) predicts that calcium or strontium has similar interaction energies at the calcium-binding site of PLAP. Since calcium helps stabilize a large area that includes loops 210–228 and 250–297, its substitution by strontium could affect the stability of this region. Energy calculations suggest that only at high doses of strontium, comparable to those found for calcium, can strontium substitute for calcium. Since osteomalacia is observed after ingestion of high doses of strontium, alkaline phosphatase is likely to be one of the targets of strontium, and thus this enzyme might be involved in this disease. PMID:16815919

Detecting Adaptation in Protein-Coding Genes Using a Bayesian Site-Heterogeneous Mutation-Selection Codon Substitution Model.

PubMed

Rodrigue, Nicolas; Lartillot, Nicolas

2017-01-01

Codon substitution models have traditionally attempted to uncover signatures of adaptation within protein-coding genes by contrasting the rates of synonymous and non-synonymous substitutions. Another modeling approach, known as the mutation-selection framework, attempts to explicitly account for selective patterns at the amino acid level, with some approaches allowing for heterogeneity in these patterns across codon sites. Under such a model, substitutions at a given position occur at the neutral or nearly neutral rate when they are synonymous, or when they correspond to replacements between amino acids of similar fitness; substitutions from high to low (low to high) fitness amino acids have comparatively low (high) rates. Here, we study the use of such a mutation-selection framework as a null model for the detection of adaptation. Following previous works in this direction, we include a deviation parameter that has the effect of capturing the surplus, or deficit, in non-synonymous rates, relative to what would be expected under a mutation-selection modeling framework that includes a Dirichlet process approach to account for across-codon-site variation in amino acid fitness profiles. We use simulations, along with a few real data sets, to study the behavior of the approach, and find it to have good power with a low false-positive rate. Altogether, we emphasize the potential of recent mutation-selection models in the detection of adaptation, calling for further model refinements as well as large-scale applications. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Biosynthesis of Novel Pyoverdines by Domain Substitution in a Nonribosomal Peptide Synthetase of Pseudomonas aeruginosa

PubMed Central

Calcott, Mark J.; Owen, Jeremy G.; Lamont, Iain L.

2014-01-01

Pyoverdine is a fluorescent nonribosomal peptide siderophore made by fluorescent pseudomonads. The Pseudomonas aeruginosa nonribosomal peptide synthetase (NRPS) PvdD contains two modules that each incorporate an l-threonine residue at the C-terminal end of pyoverdine. In an attempt to generate modified pyoverdine peptides, we substituted alternative-substrate-specifying adenylation (A) and peptide bond-catalyzing condensation (C) domains into the second module of PvdD. When just the A domain was substituted, the resulting strains produced only wild-type pyoverdine—at high levels if the introduced A domain specified threonine or at trace levels otherwise. The high levels of pyoverdine synthesis observed whenever the introduced A domain specified threonine indicated that these nonnative A domains were able to communicate effectively with the PvdD C domain. Moreover, the unexpected observation that non-threonine-specifying A domains nevertheless incorporated threonine into pyoverdine suggests that the native PvdD C domain exhibited stronger selectivity than these A domains for the incorporated amino acid substrate (i.e., misactivation of a threonine residue by the introduced A domains was more frequent than misincorporation of a nonthreonine residue by the PvdD C domain). In contrast, substitution of both the C and A domains of PvdD generated high yields of rationally modified pyoverdines in two instances, these pyoverdines having either a lysine or a serine residue in place of the terminal threonine. However, C-A domain substitution more commonly yielded a truncated peptide product, likely due to stalling of synthesis on a nonfunctional recombinant NRPS template. PMID:25015884

Phosphorus doped graphene by inductively coupled plasma and triphenylphosphine treatments

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

Shin, Dong-Wook, E-mail: shindong37@skku.edu; Kim, Tae Sung; Yoo, Ji-Beom, E-mail: jbyoo@skku.edu

Highlights: • Substitution doping is a promising method for opening the energy band gap of graphene. • Substitution doping with phosphorus in the graphene lattice has numerous advantage such as high band gap, low formation energy, and high net charge density compared to nitrogen. • V{sub dirac} of Inductively coupled plasma (ICP) and triphenylphosphine (TPP) treated graphene was −57 V, which provided clear evidence of n-type doping. • Substitutional doping of graphene with phosphorus is verified by the XPS spectra of P 2p core level and EELS mapping of phosphorus. • The chemical bonding between P and graphene is verymore » stable for a long time in air (2 months). - Abstract: Graphene is considered a host material for various applications in next-generation electronic devices. However, despite its excellent properties, one of the most important issues to be solved as an electronic material is the creation of an energy band gap. Substitution doping is a promising method for opening the energy band gap of graphene. Herein, we demonstrate the substitutional doping of graphene with phosphorus using inductively coupled plasma (ICP) and triphenylphosphine (TPP) treatments. The electrical transfer characteristics of the phosphorus doped graphene field effect transistor (GFET) have a V{sub dirac} of ∼ − 54 V. The chemical bonding between P and C was clearly observed in XPS spectra, and uniform distribution of phosphorus within graphene domains was confirmed by EELS mapping. The capability for substitutional doping of graphene with phosphorus can significantly promote the development of graphene based electronic devices.« less

High isolation rate and multidrug resistance tendency of penicillin-susceptible group B Streptococcus with reduced ceftibuten susceptibility in Japan.

PubMed

Banno, Hirotsugu; Kimura, Kouji; Seki, Tomomi; Jin, Wanchun; Wachino, Jun-Ichi; Yamada, Keiko; Nagano, Noriyuki; Arakawa, Yoshichika

2018-05-17

Group B Streptococcus (GBS) clinical isolates with reduced penicillin susceptibility (PRGBS) have emerged through acquisition of amino acid substitutions in penicillin-binding protein 2X (PBP2X). Moreover, we also reported the emergence of penicillin-susceptible GBS clinical isolates with reduced ceftibuten susceptibility (CTB r PSGBS) due to amino acid substitutions in PBPs. However, whether or not these amino acid substitutions are responsible for the reduced ceftibuten susceptibility (RCTBS) profile remains unclear. Furthermore, the rate of CTB r PSGBS isolation and their multidrug resistance tendency remain uncertain. Therefore, we collected 377 clinical GBS isolates from multiple regions in Japan between August 2013 and August 2015. These isolates were characterized by determining MICs and sequencing the pbp2x gene. The isolation rate of CTB r PSGBS was 7.2% (27/377). CTB r PSGBS isolate harbor two types of amino acid substitutions in PBP2X [(T394A type) and (I377V, G398A, Q412L, and H438H type)]. The relevance of the amino acid substitutions found to the RCTBS was confirmed with allelic exchange techniques. Allelic exchange recombinant clones acquired two types of amino acid substitutions in PBP2X showed RCTBS. Furthermore, total ratio of resistance and non-susceptibility to both macrolides and fluoroquinolones in CTB r PSGBS was 51.9% (14/27). The isolation rate of CTB r PSGBS is non-negligibly high and the CTB r PSGBS tends to exhibit resistance and non-susceptible profile to both macrolides and fluoroquinolones.

Diaminoethane adsorption and water substitution on hydrated TiO2: a thermochemical study based on first-principles calculations.

PubMed

Hémeryck, Anne; Motta, Alessandro; Swiatowska, Jolanta; Pereira-Nabais, Catarina; Marcus, Philippe; Costa, Dominique

2013-07-14

Epoxy-amines are used as structural adhesives deposited on Ti. The amine adhesion to a Ti surface depends highly on the surface state (oxidation, hydroxylation). Amines may adsorb above preadsorbed water molecules or substitute them to bind directly to surface Ti(4+) Lewis acid sites. The adsorption of a model amine molecule, diaminoethane (DAE), on a model surface, hydrated TiO2-anatase (101) surface, is investigated using Density Functional Theory including Dispersive forces (DFT-D) calculations. DAE adsorption and water substitution by DAE are exothermic processes and turn nearly isoenergetic at high coverage with adsorption-substitution energies around -0.3 eV (including dispersion forces and ZPE). Complementary ab initio molecular dynamics studies also suggest that the formation of an amine-water interaction induces water desorption from the surface at room temperature, a preliminary step towards the amine-Ti bond formation. An atomistic thermodynamic approach is developed to evaluate the interfacial free energy balance of both processes (adsorption and substitution). The main contributions to the energetic balance are dispersive interactions between molecules and the surface on the exergonic side, translational and rotational entropic contributions on the endergonic one. The substitution process is stabilized by 0.55 eV versus the adsorption one when free solvation, rotational and vibrational energies are considered. The main contribution to this free energy gain is due to water solvation. The calculations suggest that in toluene solvent with a water concentration of 10(-4) M or less, a full DAE layer replaces a preadsorbed water layer for a threshold concentration of DAE ≥ 0.1 M.

[Creation of artificial cartilage by nanotechnology].

PubMed

Murosaki, Takayuki; Gong, Jian Ping; Osada, Yoshihito

2006-02-01

Artificial joints are made from hard and dry materials like metal or ceramics, although these artificial joints have several problems such as bacterial infection, high surface friction and wear, lack in shock-absorption. From this viewpoint, hydrogels have a high potential as substitutes for articular cartilage, although most of them suffer from lack of mechanical strength. In our recent study, we have found hydrogels, that exhibit high fracture strength as several tens of megapascals, extremely low coefficient of friction as 10(-4), high wear resistance, and with biocompatibility. These gels might open new era of soft and wet materials as substitutes for articular cartilage and other tissues.

Fabrication of Material and Devices for Very High Density Information Storage.

DTIC Science & Technology

1986-11-24

IKawanishi, "Miagnetic anid opticeal propert I e of Co. I It substituted garnet films p~rep~ared by the lPE niethod and its ipplication to hlermtmt"Ile( i...medium. Highly Bi-substituted garnet films on glass and G( substrates were successfully RF sputtered and characterized by the group of M. Goni.1 The filns...writing due to the temperature dependence of the coercive force 11. Preparation of bismuth iron garnet films by ion bean sputtering onto GGG

Self-assembled pentamers and hexamers linked through quadruple-hydrogen-bonded 2-ureido-4[1H]-pyrimidinones.

PubMed

Keizer, Henk M; González, Juan J; Segura, Margarita; Prados, Pilar; Sijbesma, Rint P; Meijer, E W; de Mendoza, Javier

2005-08-05

The preorganization of bifunctional 2-ureido-4-pyrimidinones mediated by either 1,3-substituted adamantane or meta-substituted phenylene ring linkers leads to the preferred formation of stable pentameric (1)(5) and hexameric (2)(6) assemblies, respectively. Despite the high binding constant of the 2-ureido-4-pyrimidinone dimers and the highly preorganized structure of the monomer, the predominant formation of cycles (1)(5) and (2)(6) in solution occurs only within a specific concentration range.

A core-substituted naphthalene diimide fluoride sensor.

PubMed

Bhosale, Sheshanath V; Bhosale, Sidhanath V; Kalyankar, Mohan B; Langford, Steven J

2009-12-03

The synthesis and characterization of a highly fluorescent core-substituted naphthalene diimide sensor (varphi = 0.34) bearing a bis-sulfonamide group is described. The compound shows a unique selectivity and reactivity for the fluoride ion over other anions in CHCl(3) by a two-stage deprotonation process leading to a colorimetric response. In DMSO solution, the sensor is shown to be highly selective for fluoride (K(a) approximately 10(6) M(-1)) over other anions with more pronounced changes in absorption characteristics.

Kinetic Resolution of α-Hydroxy-Substituted Oxime Ethers by Enantioselective Cu-H-Catalyzed Si-O Coupling.

PubMed

Dong, Xichang; Kita, Yuji; Oestreich, Martin

2018-04-12

A catalyst-controlled enantioselective alcohol silylation by Cu-H-catalyzed dehydrogenative Si-O coupling of hydroxy groups α to an oxime ether and simple hydrosilanes is reported. The selectivity factors reached in this kinetic resolution are generally high (s≈50), and these reactions thereby provide reliable access to highly enantioenriched α-hydroxy-substituted oxime ethers. The synthetic usefulness of these compounds is also demonstrated. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of stereoelectronic effects on the non-opioid analgesics gaboxadol and gaboxadol hydrochloride: Spectral and DFT study

NASA Astrophysics Data System (ADS)

Leenaraj, D. R.; Joe, I. Hubert

2018-05-01

The stereoelectronic properties of the molecular structure of most stable conformers of gaboxadol and gaboxadol hydrochloride have been studied using DFT/B3P86-LANL2DZ methodology. The energies of stable conformers of gaboxadol and gaboxadol hydrochloride are -494.2689 and -510.0117 hartrees, respectively. The stability of the molecules arising from stereoelectronic interactions, leading to its bioactivity, has been confirmed using natural bond orbital analysis. The natural bond orbital analysis of donor-acceptor (σ→σ* and n→σ*) interactions showed that the stereoelectronic hyperconjugative and anomeric interactions are exhibited in gaboxadol hydrochloride and gaboxadol, respectively. Lengthening of the axial and equatorial C-H bond lengths and natural population analysis support these results. Spectral features of gaboxadol hydrochloride have been explored by the Fourier transform infrared, Raman and Nuclear magnetic resonance spectroscopic techniques combined with density functional theory computations. NH+ … Cl- hydrogen bonding has been noticeable as a broad and strong absorption in the 2800-2400 cm-1 region. Broad peaks obtained by proton NMR are a result of the quadrupole effect of the N+ atom. Docking studies using representative GABA receptor crystal structures revealed that molecules containing azinane and isoxazole cores fit within the ligand binding domains, and the gaboxadol hydrochloride molecule shows the best binding energy with the 3D32 GABA receptor. Also, gaboxadol hydrochloride has obtained a high value of HOMO energy and a narrow HOMO- LUMO energy gap, which enhances reactivity.

Fabrication, characterization, and in vitro study of zinc substituted hydroxyapatite/silk fibroin composite coatings on titanium for biomedical applications.

PubMed

Zhong, Zhenyu; Ma, Jun

2017-09-01

Zinc substituted hydroxyapatite/silk fibroin composite coatings were deposited on titanium substrates at room temperature by electrophoretic deposition. Microscopic characterization of the synthesized composite nanoparticles revealed that the particle size ranged 50-200 nm, which increased a little after zinc substitution. The obtained coatings maintained the phase of hydroxyapatite and they could induce fast apatite formation in simulated body fluid, indicating high bone activity. The cell culturing results showed that the biomimetic hydroxyapatite coatings could regulate adhesion, spreading, and proliferation of osteoblastic cells. Furthermore, the biological behavior of the zinc substituted hydroxyapatite coatings was found to be better than the bare titanium without coatings and hydroxyapatite coatings without zinc, increasing MC3T1-E1 cell differentiation in alkaline phosphatase expression.

The shadow price of substitutable sulfur in the US electric power plant: a distance function approach.

PubMed

Lee, Myunghun

2005-10-01

Given restrictions on sulfur dioxide emissions, a feasible long-run response could involve either an investment in improving boiler fuel-efficiency or a shift to a production process that is effective in removing sulfur dioxide. To allow for the possibility of substitution between sulfur and productive capital, we measure the shadow price of sulfur dioxide as the opportunity cost of lowering sulfur emissions in terms of forgone capital. The input distance function is estimated with data from 51 coal-fired US power units operating between 1977 and 1986. The indirect Morishima elasticities of substitution indicate that the substitutability of capital for sulfur is relatively high. The overall weighted average estimate of the shadow price of sulfur is -0.076 dollars per pound in constant 1976 dollars.

Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: selective inhibitors of Aurora B kinase with potent anti-tumor activity.

PubMed

Foote, Kevin M; Mortlock, Andrew A; Heron, Nicola M; Jung, Frédéric H; Hill, George B; Pasquet, Georges; Brady, Madeleine C; Green, Stephen; Heaton, Simon P; Kearney, Sarah; Keen, Nicholas J; Odedra, Rajesh; Wedge, Stephen R; Wilkinson, Robert W

2008-03-15

A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume.

Modulating the selectivity of affinity absorbents to multi-phosphopeptides by a competitive substitution strategy.

PubMed

Liu, Zheyi; Wang, Fangjun; Chen, Jin; Zhou, Ye; Zou, Hanfa

2016-08-26

Although many affinity adsorbents have been developed for phosphopeptides enrichment, high-specifically capturing the multi-phosphopeptides is still a big challenge. Here, we investigated the mechanism of phosphate ion coordination and substitution on affinity adsorbents surfaces and modulated the selectivity of affinity adsorbents to multi-phosphopeptides based on the different capability of mono- and multi-phosphopeptides in competitively substituting the pre-coordinated phosphate ions at strong acidic condition. We demonstrated both the species of pre-coordinated phosphate ions and the substituting conditions played crucial roles in modulating the enrichment selectivity to multi-phosphopeptides, and the pre-coordinated affinity materials with relative more surfaces positive charges exhibited better enrichment efficiency due to the cooperative effect of electrostatic interaction and competitive substitution. Finally, an enrichment selectivity of 85% to multi-phosphopeptides was feasibly achieved with 66% improvement in identification numbers for complex protein sample extracted from HepG2 cells. Data are available via ProteomeXchange with identifier PXD004252. Copyright © 2016 Elsevier B.V. All rights reserved.

Space-for-Time Substitution Works in Everglades Ecological Forecasting Models

PubMed Central

Banet, Amanda I.; Trexler, Joel C.

2013-01-01

Space-for-time substitution is often used in predictive models because long-term time-series data are not available. Critics of this method suggest factors other than the target driver may affect ecosystem response and could vary spatially, producing misleading results. Monitoring data from the Florida Everglades were used to test whether spatial data can be substituted for temporal data in forecasting models. Spatial models that predicted bluefin killifish (Lucania goodei) population response to a drying event performed comparably and sometimes better than temporal models. Models worked best when results were not extrapolated beyond the range of variation encompassed by the original dataset. These results were compared to other studies to determine whether ecosystem features influence whether space-for-time substitution is feasible. Taken in the context of other studies, these results suggest space-for-time substitution may work best in ecosystems with low beta-diversity, high connectivity between sites, and small lag in organismal response to the driver variable. PMID:24278368

Pinpointing proline substitution to be responsible for the loss of amyloidogenesis in IAPP.

PubMed

Chakraborty, Sandipan; Mukherjee, Barnali; Basu, Soumalee

2013-10-01

Human islet amyloid polypeptide (hIAPP) is highly amyloidogenic, whereas its homologs in rodents are non-amyloidogenic. This observed non-amyloidogenecity of rodent IAPP has been attributed to substitutions by proline in a region of IAPP that forms the core of the fibril. By employing molecular dynamics simulation, we have analyzed effects of position-specific proline substitution on amyloidogenesis of the core region of the hIAPP fibril (22-28). We depict that substitution to proline at the 25th position is primarily responsible for the loss of amyloidogenecity of the peptide. In addition, 25th and 26th double mutation to proline and valine has been observed to show significant fibril destabilizing ability. On the contrary, substitution at 28th position to proline has the least ability to destabilize the amyloid fibril. Results obtained from this study are particularly important to design variants of the existing antihyperglycemic drug with minimalistic mutation approach for use in patients with diabetes. © 2013 John Wiley & Sons A/S.

Defect engineering of the electronic transport through cuprous oxide interlayers

NASA Astrophysics Data System (ADS)

Fadlallah, Mohamed M.; Eckern, Ulrich; Schwingenschlögl, Udo

2016-06-01

The electronic transport through Au-(Cu2O)n-Au junctions is investigated using first-principles calculations and the nonequilibrium Green’s function method. The effect of varying the thickness (i.e., n) is studied as well as that of point defects and anion substitution. For all Cu2O thicknesses the conductance is more enhanced by bulk-like (in contrast to near-interface) defects, with the exception of O vacancies and Cl substitutional defects. A similar transmission behavior results from Cu deficiency and N substitution, as well as from Cl substitution and N interstitials for thick Cu2O junctions. In agreement with recent experimental observations, it is found that N and Cl doping enhances the conductance. A Frenkel defect, i.e., a superposition of an O interstitial and O substitutional defect, leads to a remarkably high conductance. From the analysis of the defect formation energies, Cu vacancies are found to be particularly stable, in agreement with earlier experimental and theoretical work.

Application of the Chinese steamed bun starter dough (CSB-SD) in breadmaking.

PubMed

Keeratipibul, Suwimon; Luangsakul, Naphatrapi; Otsuka, Shinya; Sakai, Shigeru; Hatano, Yasushi; Tanasupawat, Somboon

2010-01-01

The application of Chinese steamed bun starter dough (CSB-SD) in breadmaking was investigated. The activation of CSB-SD to activate the growth of lactic acid bacteria (LAB) and to increase the number of yeast, prior to making bread, was conducted by mixing CSB-SD with wheat flour and water and then incubating for 24 h. Wheat flour was then substituted by this activated CSB-SD (aCSB-SD) at 10%, 30%, and 50% (w/w) to make bread. Dough and bread properties were studied comparing to the control (without aCSB-SD). From the farinograph results, a high aCSB-SD substitution level resulted in a less stability in dough with a higher degree of softening. Extensigraph results suggested that after aging, all the substituted dough yielded a greater resistance to extension with lower extensibility values than the control. Substitutions with 30% and 50% (w/w) aCSB-SD significantly increased the total CO(2) gas generation. Scanning electron microscopy SEM images of the 30% and 50% (w/w) substituted dough showed a well-developed gluten matrix. The 50% (w/w) substituted breads obtained a greater risen volume, finer crumb grain, and retained more softness after 5-d storage than the control. In addition, both the 30% and 50% (w/w) substituted breads showed a slightly increased mold stability, as compared to the 0% and 10% (w/w) substituted breads. © 2010 Institute of Food Technologists®

Phonon structures of GaN-based random semiconductor alloys

NASA Astrophysics Data System (ADS)

Zhou, Mei; Chen, Xiaobin; Li, Gang; Zheng, Fawei; Zhang, Ping

2017-12-01

Accurate modeling of thermal properties is strikingly important for developing next-generation electronics with high performance. Many thermal properties are closely related to phonon dispersions, such as sound velocity. However, random substituted semiconductor alloys AxB1-x usually lack translational symmetry, and simulation with periodic boundary conditions often requires large supercells, which makes phonon dispersion highly folded and hardly comparable with experimental results. Here, we adopt a large supercell with randomly distributed A and B atoms to investigate substitution effect on the phonon dispersions of semiconductor alloys systematically by using phonon unfolding method [F. Zheng, P. Zhang, Comput. Mater. Sci. 125, 218 (2016)]. The results reveal the extent to which phonon band characteristics in (In,Ga)N and Ga(N,P) are preserved or lost at different compositions and q points. Generally, most characteristics of phonon dispersions can be preserved with indium substitution of gallium in GaN, while substitution of nitrogen with phosphorus strongly perturbs the phonon dispersion of GaN, showing a rapid disintegration of the Bloch characteristics of optical modes and introducing localized impurity modes. In addition, the sound velocities of both (In,Ga)N and Ga(N,P) display a nearly linear behavior as a function of substitution compositions. Supplementary material in the form of one pdf file available from the Journal web page at http://https://doi.org/10.1140/epjb/e2017-80481-0.

Factors associated with the acceptance of sugar and sugar substitutes by the public.

PubMed

Mackay, D A

1985-09-01

Acceptance is described in both market and sensory research terminology and recent developments in the fields of applied psychology and physiology are examined for their pertinence to public acceptance of sucrose and its substitutes. Information on the function of sucrose in foods other than beverages is presented with emphasis on salivation as an acceptance factor and attention is drawn to its possible dental significance. Distinctions are made between the sweetening and bulking properties of sucrose and sugar substitutes. Factors having a bearing on the acceptance of sweet foods and the determination of their optimal sugar content are described in detail. While major decreases in sucrose intake in the US resulted from high-fructose corn-sweetener usage in soft drinks, no evidence is yet available to suggest that the use of sugar substitutes of the intense artificial sweetener type has caused any decrease in ordinary sugar consumption. Neither is the consumption of polyols (sorbitol, mannitol, xylitol) high enough in confectionery categories to cause any discernible decrease in sugar usage. The evidence suggests not so much that sugar substitutes may have stopped the growth in sucrose usage, but that new product categories such as diet foods and "sugarless' confections may have been created. These categories were never available to fermentable carbohydrate sweeteners and equivalence in acceptance to sucrose-sweetened products was not an important factor in their growth.(ABSTRACT TRUNCATED AT 250 WORDS)

High-pressure electronic phase diagrams in FeSe1-xSx superconductors

NASA Astrophysics Data System (ADS)

Matsuura, Kohei; Arai, Yuki; Hosoi, Suguru; Ishida, Kousuke; Mizukami, Yuta; Watashige, Tatsuya; Kasahara, Shigeru; Matsuda, Yuji; Maejima, Naoyuki; Machida, Akihiko; Watanuki, Tetsu; Fukuda, Tatsuo; Uwatoko, Yoshiya; Shibauchi, Takasada

The spin fluctuations are believed to be related to the mechanism of the unconventional superconductors. On the other hand, many recent studies suggest that the nematic order that spontaneously breaks rotational symmetry of the system exists in the Fe-based superconductors and its quantum fluctuations may play an essential role for the superconductivity. However, this remains unclear because the nematic order usually coexists with the magnetic order. To solve this issue, FeSe exhibiting a nonmagnetic nematic order is a key system. Under pressure, this order is suppressed and concurrently magnetic order appears, which competes with high-Tc superconducting phase. In isovalent substitution system FeSe1-xSx, we found a nonmagnetic nematic quantum critical point. Here we report our recent high-pressure studies in high-quality single-crystalline FeSe1-xSx up to 8 GPa. We find a systematic change of the pressure phase diagram in FeSe by the S-substitution. Our results imply that the respective role of nematic and magnetic fluctuations can be elucidated from the precise control of pressure and substitution in this system.

Reduction in fluoride-induced genotoxicity in mouse bone marrow cells after substituting high fluoride-containing water with safe drinking water.

PubMed

Podder, Santosh; Chattopadhyay, Ansuman; Bhattacharya, Shelley

2011-10-01

Treatment of mice with 15 mg l(-1) sodium fluoride (NaF) for 30 days increased the number of cell death, chromosomal aberrations (CAs) and 'cells with chromatid breaks' (aberrant cells) compared with control. The present study was intended to determine whether the fluoride (F)-induced genotoxicity could be reduced by substituting high F-containing water after 30 days with safe drinking water, containing 0.1 mg F ions l(-1). A significant fall in percentage of CAs and aberrant cells after withdrawal of F-treatment following 30 days of safe water treatment in mice was observed which was highest after 90 days, although their levels still remained significantly high compared with the control group. This observation suggests that F-induced genotoxicity could be reduced by substituting high F-containing water with safe drinking water. Further study is warranted with different doses and extended treatment of safe water to determine whether the induced damages could be completely reduced or not. Copyright © 2011 John Wiley & Sons, Ltd.

Effect of Fe-site Substitution on Pressure-induced Spin Transition in SrFeO2

NASA Astrophysics Data System (ADS)

Kawakami, Takateru; Yamamoto, Takafumi; Yata, Kanami; Ishii, Minoru; Watanabe, Yoshitaka; Mizumaki, Masaichiro; Kawamura, Naomi; Ishimatsu, Naoki; Takahashi, Hiroki; Okada, Taku; Yagi, Takehiko; Kageyama, Hiroshi

2017-12-01

The effect of Fe-site substitution on structural and physical properties of the infinite layer iron oxide SrFeO2 was investigated under high pressure by 57Fe Mössbauer spectroscopy, X-ray diffraction, X-ray absorption spectroscopy, X-ray magnetic circular dichroism, and electrical resistance measurements using a diamond-anvil cell. Both 20% Mn- and Co-substituted samples exhibit spin transitions from a high-spin (S = 2) to an intermediate-spin (S = 1) state at Pc ˜ 32 GPa, which is much the same pressure 33 GPa observed in SrFeO2. This result indicates that the spin transition pressure is insensitive to the d-orbital electron counts [Mn2+ (d5), Fe2+ (d6), Co2+ (d7)], but is governed by the local structure around the Fe site.

Diels–Alder Exo-Selectivity in Terminal-Substituted Dienes and Dienophiles: Experimental Discoveries and Computational Explanations

PubMed Central

Lam, Yu-hong; Cheong, Paul Ha-Yeon; Mata, José M. Blasco; Stanway, Steven J.; Gouverneur, Véronique; Houk, K. N.

2009-01-01

The Diels–Alder reactions of a series of silyloxydienes and silylated dienes with acyclic α,β-unsaturated ketones and N-acyloxazolidinones have been investigated. The endo/exo stereochemical outcome is strongly influenced by the substitution pattern of the reactants. High exo selectivity was observed when the termini of the diene and the dienophile involved in the shorter forming bond are both substituted, while the normal endo preference was found otherwise. The exo-selective asymmetric Diels–Alder reactions using Evans’ oxazolidinone chiral auxiliary furnished a high level of π-facial selectivity in the same sense as their well-documented endo-selective counterparts. Computational results of these Diels–Alder reactions were consistent with the experimental endo/exo selectivity in most cases. A twist-asynchronous model accounts for the geometries and energies of the computed transition structures. PMID:19154113

Structural analysis of aluminium substituted nickel ferrite nanoparticles

NASA Astrophysics Data System (ADS)

Singh, H. S.; Sangwa, Neha

2018-05-01

Aluminium substituted nickel ferrite nanoparticles were synthesized by High Energy Ball milling (HEBM) of the mixture of α-NiO, α-Al2O3 and α-Fe2O3 followed by annealing at 1000˚C. X-ray diffraction (XRD) and Energy dispersive spectroscopy analysis (EDS) characterization was done for Aluminium substituted nickel ferrite. The structural analysis reveals the formation of the single phase compound. The average grain size was estimated by X-ray diffraction technique ranges from 30 to 10 nm with the increasing concentration of Aluminium. EDS spectra conforms the homogeneous mixing and purity of ferrite.

Amphoteric Be in GaN: Experimental Evidence for Switching between Substitutional and Interstitial Lattice Sites

NASA Astrophysics Data System (ADS)

Tuomisto, Filip; Prozheeva, Vera; Makkonen, Ilja; Myers, Thomas H.; Bockowski, Michal; Teisseyre, Henryk

2017-11-01

We show that Be exhibits amphoteric behavior in GaN, involving switching between substitutional and interstitial positions in the lattice. This behavior is observed through the dominance of BeGa in the positron annihilation signals in Be-doped GaN, while the emergence of VGa at high temperatures is a consequence of the Be impurities being driven to interstitial positions. The similarity of this behavior to that found for Na and Li in ZnO suggests that this could be a universal property of light dopants substituting for heavy cations in compound semiconductors.

Amphoteric Be in GaN: Experimental Evidence for Switching between Substitutional and Interstitial Lattice Sites.

PubMed

Tuomisto, Filip; Prozheeva, Vera; Makkonen, Ilja; Myers, Thomas H; Bockowski, Michal; Teisseyre, Henryk

2017-11-10

We show that Be exhibits amphoteric behavior in GaN, involving switching between substitutional and interstitial positions in the lattice. This behavior is observed through the dominance of Be_{Ga} in the positron annihilation signals in Be-doped GaN, while the emergence of V_{Ga} at high temperatures is a consequence of the Be impurities being driven to interstitial positions. The similarity of this behavior to that found for Na and Li in ZnO suggests that this could be a universal property of light dopants substituting for heavy cations in compound semiconductors.

High Definition Confocal Imaging Modalities for the Characterization of Tissue-Engineered Substitutes.

PubMed

Mayrand, Dominique; Fradette, Julie

2018-01-01

Optimal imaging methods are necessary in order to perform a detailed characterization of thick tissue samples from either native or engineered tissues. Tissue-engineered substitutes are featuring increasing complexity including multiple cell types and capillary-like networks. Therefore, technical approaches allowing the visualization of the inner structural organization and cellular composition of tissues are needed. This chapter describes an optical clearing technique which facilitates the detailed characterization of whole-mount samples from skin and adipose tissues (ex vivo tissues and in vitro tissue-engineered substitutes) when combined with spectral confocal microscopy and quantitative analysis on image renderings.

Facile synthesis of highly substituted 3-aminofurans from thiazolium salts, aldehydes, and dimethyl acetylenedicarboxylate.

PubMed

Ma, Cheng; Ding, Hanfeng; Wu, Guangming; Yang, Yewei

2005-10-28

[reaction: see text] A facile preparation of 3-aminofuran derivatives via multicomponent reactions of thiazole carbenes, aldehydes, and dimethyl acetylenedicarboxylate (DMAD) is reported. In this process, the thiazole carbenes, generated in situ from thiazolium salts, reacted with aldehydes and DMAD at -78 to 0 degree C in CH(2)Cl(2) to afford the substituted furans in moderate to good yields. Eight substituted thiazolium salts were employed as carbene precursors in the reaction. Besides aryl aldehydes, alpha,beta-unsaturated aldehydes, aliphatic aldehydes, and arenedial were also investigated and found to be applicable to this reaction.

Copper(II)-catalyzed enantioselective hydrosilylation of halo-substituted alkyl aryl and heteroaryl ketones: asymmetric synthesis of (R)-fluoxetine and (S)-duloxetine.

PubMed

Zhou, Ji-Ning; Fang, Qiang; Hu, Yi-Hu; Yang, Li-Yao; Wu, Fei-Fei; Xie, Lin-Jie; Wu, Jing; Li, Shijun

2014-02-14

A set of reaction conditions has been established to facilitate the non-precious copper-catalyzed enantioselective hydrosilylation of a number of structurally diverse β-, γ- or ε-halo-substituted alkyl aryl ketones and α-, β- or γ-halo-substituted alkyl heteroaryl ketones under air to afford a broad spectrum of halo alcohols in high yields and good to excellent enantioselectivities (up to 99% ee). The developed procedure has been successfully applied to the asymmetric synthesis of antidepressant drugs (R)-fluoxetine and (S)-duloxetine, which highlighted its synthetic utility.

High-pressure studies on electronic and mechanical properties of FeBO3 (B = Ti, Mn, Cr) ceramics - a first-principles study

NASA Astrophysics Data System (ADS)

Kishore, N.; Nagarajan, V.; Chandiramouli, R.

2018-04-01

Using the density functional theory (DFT) method, the electronic and mechanical properties of perovskites FeBO3 (B = Ti, Mn, Cr) nanostructures were studied in the pressure range of 0-100 GPa. The band structure studies show the change in the band structure upon substitution of different B cation in FeBO3 perovskite structure. The density of states spectrum gives the perception of change in the electronic properties of FeBO3 with the substitution of B cation. The bulk, shear and Young's moduli were calculated and an increase in the moduli is noticed. Moreover, the hardness increases under high pressure. The high-pressure studies of FeBO3 perovskite nanostructures are explored at atomistic level. The findings show that ductility and hardness of FeBO3 get increased upon an increase in the applied pressure. The substitution of Ti, Mn and Cr on FeBO3 shows a significant change in the electronic and mechanical properties.

Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase.

PubMed

Kim, In-Hae; Park, Yong-Kyu; Nishiwaki, Hisashi; Hammock, Bruce D; Nishi, Kosuke

2015-11-15

Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase (sEH) were investigated. First, a series of alkyl or aryl groups were substituted on the carbon alpha to the phosphonate function in amide compounds to see whether substituted phosphonates can act as a secondary pharmacophore. A tert-butyl group (16) on the alpha carbon was found to yield most potent inhibition on the target enzyme. A 4-50-fold drop in inhibition was induced by other substituents such as aryls, substituted aryls, cycloalkyls, and alkyls. Then, the modification of the O-substituents on the phosphonate function revealed that diethyl groups (16 and 23) were preferable for inhibition to other longer alkyls or substituted alkyls. In amide compounds with the optimized diethylphosphonate moiety and an alkyl substitution such as adamantane (16), tetrahydronaphthalene (31), or adamantanemethane (36), highly potent inhibitions were gained. In addition, the resulting potent amide-phosphonate compounds had reasonable water solubility, suggesting that substituted phosphonates in amide inhibitors are effective for both inhibition potency on the human sEH and water solubility as a secondary pharmacophore. Copyright © 2015 Elsevier Ltd. All rights reserved.

Carbon substitution for oxygen in silicates in planetary interiors

PubMed Central

Sen, Sabyasachi; Widgeon, Scarlett J.; Navrotsky, Alexandra; Mera, Gabriela; Tavakoli, Amir; Ionescu, Emanuel; Riedel, Ralf

2013-01-01

Amorphous silicon oxycarbide polymer-derived ceramics (PDCs), synthesized from organometallic precursors, contain carbon- and silica-rich nanodomains, the latter with extensive substitution of carbon for oxygen, linking Si-centered SiOxC4-x tetrahedra. Calorimetric studies demonstrated these PDCs to be thermodynamically more stable than a mixture of SiO2, C, and silicon carbide. Here, we show by multinuclear NMR spectroscopy that substitution of C for O is also attained in PDCs with depolymerized silica-rich domains containing lithium, associated with SiOxC4-x tetrahedra with nonbridging oxygen. We suggest that significant (several percent) substitution of C for O could occur in more complex geological silicate melts/glasses in contact with graphite at moderate pressure and high temperature and may be thermodynamically far more accessible than C for Si substitution. Carbon incorporation will change the local structure and may affect physical properties, such as viscosity. Analogous carbon substitution at grain boundaries, at defect sites, or as equilibrium states in nominally acarbonaceous crystalline silicates, even if present at levels at 10–100 ppm, might form an extensive and hitherto hidden reservoir of carbon in the lower crust and mantle. PMID:24043830

Carbon substitution for oxygen in silicates in planetary interiors.

PubMed

Sen, Sabyasachi; Widgeon, Scarlett J; Navrotsky, Alexandra; Mera, Gabriela; Tavakoli, Amir; Ionescu, Emanuel; Riedel, Ralf

2013-10-01

Amorphous silicon oxycarbide polymer-derived ceramics (PDCs), synthesized from organometallic precursors, contain carbon- and silica-rich nanodomains, the latter with extensive substitution of carbon for oxygen, linking Si-centered SiO(x)C(4-x) tetrahedra. Calorimetric studies demonstrated these PDCs to be thermodynamically more stable than a mixture of SiO2, C, and silicon carbide. Here, we show by multinuclear NMR spectroscopy that substitution of C for O is also attained in PDCs with depolymerized silica-rich domains containing lithium, associated with SiO(x)C(4-x) tetrahedra with nonbridging oxygen. We suggest that significant (several percent) substitution of C for O could occur in more complex geological silicate melts/glasses in contact with graphite at moderate pressure and high temperature and may be thermodynamically far more accessible than C for Si substitution. Carbon incorporation will change the local structure and may affect physical properties, such as viscosity. Analogous carbon substitution at grain boundaries, at defect sites, or as equilibrium states in nominally acarbonaceous crystalline silicates, even if present at levels at 10-100 ppm, might form an extensive and hitherto hidden reservoir of carbon in the lower crust and mantle.

Classification of group B streptococci with reduced β-lactam susceptibility (GBS-RBS) based on the amino acid substitutions in PBPs.

PubMed

Kimura, Kouji; Nagano, Noriyuki; Arakawa, Yoshichika

2015-01-01

All clinical isolates of group B Streptococcus (GBS; Streptococcus agalactiae) are considered uniformly susceptible to β-lactams, including penicillins. However, GBS with reduced penicillin susceptibility (PRGBS) were first identified by our group in Japan and have also been reported from North America. PRGBS are non-susceptible to penicillin because of acquisition of amino acid substitutions near the conserved active-site motifs in PBP2X. In particular, V405A and Q557E are considered the key amino acid substitutions responsible for penicillin non-susceptibility. We revealed that in addition to the substitutions in PBP2X, an amino acid substitution in PBP1A confers high-level cephalosporin resistance in GBS. As the number of publications on GBS with reduced β-lactam susceptibility (GBS-RBS), especially PRGBS, and concomitantly the need for a systematic classification of GBS-RBS is increasing, we propose here a classification of GBS-RBS based on the amino acid substitutions in their PBPs. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Density impact on performance of composite Si/graphite electrodes

DOE PAGES

Dufek, Eric J.; Picker, Michael; Petkovic, Lucia M.

2016-01-27

The ability of alkali-substituted binders for composite Si and graphite negative electrodes to minimize capacity fade for lithium ion batteries is investigated. Polymer films and electrodes are described and characterized by FTIR following immersion in electrolyte (1:2 EC:DMC) for 24 h. FTIR analysis following electrode formation displayed similar alkali-ion dependent shifts in peak location suggesting that changes in the vibrational structure of the binder are maintained after electrode formation. The Si and graphite composite electrodes prepared using the alkali-substituted polyacrylates were also exposed to electrochemical cycling and it has been found that the performance of the Na-substituted binder is superiormore » to a comparable density K-substituted system. However, in comparing performance across many different electrode densities attention needs to be placed on making comparisons at similar densities, as low density electrodes tend to exhibit lower capacity fade over cycling. This is highlighted by a 6% difference between a low density K-substituted electrode and a high density Na-substituted sample. As a result, this low variance between the two systems makes it difficult to quickly make a direct evaluation of binder performance unless electrode density is tightly controlled.« less

Cr-substituted LiCoPO4 core with a conductive carbon layer towards high-voltage lithium-ion batteries

NASA Astrophysics Data System (ADS)

Wang, Yue; Chen, Junhong; Qiu, Jingyi; Yu, Zhongbao; Ming, Hai; Li, Meng; Zhang, Songtong; Yang, Yusheng

2018-02-01

Electrical and ionic conductivity are two major limiting factors for LiCoPO4 cathode material. To overcome these shortcomings, a Cr-substituted LiCoPO4 core with a conductive carbon layer cathode material is synthesized using the sol-gel method. The physical chemistry properties of these materials are systematically investigated by using various characterization methods. For instance, the XRD and Rietveld refinement results reveal that Cr successfully substitutes the Co within the LiCoPO4 core to form LiCo1-1.5xCrxPO4/C (x = 0, 0.02, 0.04, 0.06) without changing the olivine structure but exhibits a decrease in the unit cell volume with increasing Cr substitution. SEM and TEM images indicate that Cr substitution does not lead to changes in the basic morphology of LiCo1-1.5xCrxPO4/C (x = 0, 0.02, 0.04, 0.06) material, which is composed of agglomerated nanoparticles with an 8 nm carbon layer on the surface. The EDS and XPS results confirm that Cr is uniformly distributed on the surface and that the oxidation state of Cr is +3. FTIR spectra indicate that the antisite defect concentration decreases with increasing Cr substitution. Furthermore, Cr substitution significantly improves the electrochemical performances of LiCo1-1.5xCrxPO4/C (x = 0.02, 0.04, 0.06) cathode. Notably, the LiCo0.94Cr0.04PO4/C delivers an initial discharge capacity of 144 mA h g-1 at 0.1 C and shows a capacity retention of 71% after 100 cycles between 3.0 and 5.0 V. The CV and EIS results indicate that the polarization is reduced and that the electronic and ionic conductivities are improved by Cr substitution. The good electrochemical performances for Cr-substituted LiCoPO4/C electrodes are attributed to the lower antisite defect concentration, as the reduction of polarization, the improvement of electronic and ion conductivity and the uniform carbon layer. These features will accelerate the commercial application of LiCoPO4 towards the start-art of the high voltage lithium-ion batteries.

Understanding high diastereomeric discrimination in formation of oligoribonucleotide phosphorothioate linkages: the first study of pKa-dependent activation in solid-supported coupling of 2'-O-substituted ribonucleoside phosphoramidites.

PubMed

Ravikumar, Vasulinga T; Cole, Douglas L

2003-01-01

Activation of 2'-O-substituted ribonucleoside phosphoramidites with various activators during solid-supported synthesis of phosphorothioate oligonucleotides was studied. The Rp:Sp diastereomeric composition of resulting phosphorothioate linkage dependent on pKa of activator utilized for coupling.

Lexical Competition is Enhanced in the Left Hemisphere: Evidence from Different Types of Orthographic Neighbors

ERIC Educational Resources Information Center

Perea, Manuel; Acha, Joana; Fraga, Isabel

2008-01-01

Two divided visual field lexical decision experiments were conducted to examine the role of the cerebral hemispheres in orthographic neighborhood effects. In Experiment 1, we employed two types of words: words with many substitution neighbors (high-"N") and words with few substitution neighbors (low-"N"). Results showed a facilitative effect of…

Comparisons of pollen substitute diets for honey bees: consumption rates by colonies and effects on brood and adult populations.

USDA-ARS?s Scientific Manuscript database

Commercially available pollen substitute diets for honey bees (Apis mellifera L.) were evaluated for consumption and colony growth (brood and adult populations) and compared with pollen cake and high fructose corn syrup (HFCS). Two trials were conducted; the first for 3 months during the fall and w...

EPA publishes notice to extend comment period to close 6/16/16 on proposal to list new substitutes and prohibit certain high-GWP HFCs as alternatives under SNAP

EPA Pesticide Factsheets

Proposed New Listings of Substitutes; Changes of Listing Status; and Reinterpretation of Unacceptability for Closed Cell Foam Products Under the Significant New Alternatives Policy Program; and Revision of Clean Air Act Section 608 Venting Prohibition for

Copper-Catalyzed Heteroarylboration of 1,3-Dienes with 3-Bromopyridines: A cine Substitution.

PubMed

Smith, Kevin B; Huang, Yuan; Brown, M Kevin

2018-04-26

A method for the heteroarylboration of 1,3-dienes is presented. The process involves an unusual cine substitution of 3-bromopyridine derivatives to deliver highly functionalized heterocyclic products. Mechanistic studies are included that clarify the details of this unusual process. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Initial glenoid fixation using two different reverse shoulder designs with an equivalent center of rotation in a low-density and high-density bone substitute.

PubMed

Stroud, Nicholas J; DiPaola, Matthew J; Martin, Brian L; Steiler, Cindy A; Flurin, Pierre-Henri; Wright, Thomas W; Zuckerman, Joseph D; Roche, Christopher P

2013-11-01

Numerous glenoid implant designs have been introduced into the global marketplace in recent years; however, little comparative biomechanical data exist to substantiate one design consideration over another. This study dynamically evaluated reverse shoulder glenoid baseplate fixation and compared the initial fixation associated with 2 reverse shoulder designs having an equivalent center of rotation in low-density and high-density bone substitute substrates. Significant differences in fixation were observed between implant designs, where the circular-porous reverse shoulder was associated with approximately twice the micromotion per equivalent test than the oblong-grit-blasted design. Additionally, 6 of the 7 circular-porous reverse shoulders failed catastrophically in the low-density bone model at an average of 2603 ± 981 cycles. None of the oblong-grit-blasted designs failed in the low-or high-density bone models and none of the circular-porous designs failed in the high-density bone models after 10,000 cycles of loading. These results demonstrate that significant differences in initial fixation exist between reverse shoulder implants having an equivalent center of rotation and suggest that design parameters, other than the position of the center of rotation, significantly affect fixation in low-density and high-density polyurethane bone substitutes. Subtle changes in glenoid baseplate design can dramatically affect fixation, particularly in low-density bone substitutes that are intended to simulate the bone quality of the recipient population for reverse shoulders. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

SINEs, evolution and genome structure in the opossum.

PubMed

Gu, Wanjun; Ray, David A; Walker, Jerilyn A; Barnes, Erin W; Gentles, Andrew J; Samollow, Paul B; Jurka, Jerzy; Batzer, Mark A; Pollock, David D

2007-07-01

Short INterspersed Elements (SINEs) are non-autonomous retrotransposons, usually between 100 and 500 base pairs (bp) in length, which are ubiquitous components of eukaryotic genomes. Their activity, distribution, and evolution can be highly informative on genomic structure and evolutionary processes. To determine recent activity, we amplified more than one hundred SINE1 loci in a panel of 43 M. domestica individuals derived from five diverse geographic locations. The SINE1 family has expanded recently enough that many loci were polymorphic, and the SINE1 insertion-based genetic distances among populations reflected geographic distance. Genome-wide comparisons of SINE1 densities and GC content revealed that high SINE1 density is associated with high GC content in a few long and many short spans. Young SINE1s, whether fixed or polymorphic, showed an unbiased GC content preference for insertion, indicating that the GC preference accumulates over long time periods, possibly in periodic bursts. SINE1 evolution is thus broadly similar to human Alu evolution, although it has an independent origin. High GC content adjacent to SINE1s is strongly correlated with bias towards higher AT to GC substitutions and lower GC to AT substitutions. This is consistent with biased gene conversion, and also indicates that like chickens, but unlike eutherian mammals, GC content heterogeneity (isochore structure) is reinforced by substitution processes in the M. domestica genome. Nevertheless, both high and low GC content regions are apparently headed towards lower GC content equilibria, possibly due to a relative shift to lower recombination rates in the recent Monodelphis ancestral lineage. Like eutherians, metatherian (marsupial) mammals have evolved high CpG substitution rates, but this is apparently a convergence in process rather than a shared ancestral state.

The potential of silk sericin protein as a serum substitute or an additive in cell culture and cryopreservation.

PubMed

Cao, Ting-Ting; Zhang, Yu-Qing

2017-06-01

Cell culture and cryopreservation are necessary for clinical therapy and cells storage. The addition of 10% (v/v) foetal bovine serum (FBS) to basal culture media has been common practice and is one of the most widely used methods. FBS media added with 10% DMSO (dimethyl sulfoxide) have also been used for cryopreservation cells. Ideally, FBS should be avoided because of high cost and bio-safety. Silk sericin has been used as a serum substitute and an additive due to its good hydrophilicity and biological safety. This article summarizes a few details about the processing of sericin and its application as a serum substitute or an additive for cell culture and cryopreservation media. Sericin can be a potential novel serum substitute or an additive for cell culture and cryopreservation media.

Tunable magnetic and magnetocaloric properties in heavy rare-earth based metallic glasses through the substitution of similar elements

NASA Astrophysics Data System (ADS)

Zhang, Huiyan; Li, Ran; Zhang, Leilei; Zhang, Tao

2014-04-01

The influence of interchangeable substitution of similar heavy rare-earth-elements (HRE), i.e., Gd-Ho, Gd-Er, and Ho-Er, on the magnetic and magnetocaloric properties of HRE55Al27.5Co17.5 metallic glasses was evaluated. The magnetic transition temperature (TC) can be tuned in a wide temperature range from 8 K to 93 K by adjusting the substitutional concentration in the resulting metallic glasses. A roughly linear correlation between peak value of magnetic entropy change (|ΔSMpk|) and TC-2/3 was obtained in the three systems. This kind of substitutional adjustment provides a useful method for designing desirable candidates in metallic glasses with high magnetic entropy change, large magnetic cooling efficiency, and tunable TC for magnetic refrigerant in nitrogen and hydrogen liquefaction temperature ranges.

Nucleophilic fluorination of aromatic compounds

DOEpatents

Satyamurthy, Nagichettiar; Barrio, Jorge R

2014-03-18

Iodylbenzene derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are used as precursors in aromatic nucleophilic substitution reactions. The iodyl group (IO.sub.2) is regiospecifically substituted by nucleophilic fluoride to provide the corresponding fluoroaryl derivatives. No-carrier-added [F-18]fluoride ion derived from anhydrous [F-18](F/Kryptofix, [F-18]CsF or a quaternary ammonium fluoride (e.g., Me.sub.4NF, Et.sub.4NF, n-Bu.sub.4NF, (PhCH.sub.2).sub.4NF) exclusively substitutes the iodyl moiety in these derivatives and provides high specific activity F-18 labeled fluoroaryl analogs. Iodyl derivatives of a benzothiazole analog and 6-iodyl-L-dopa derivatives have been synthesized as precursors and have been used in the preparation of no-carrier-added [F-18]fluorobenzothiazole as well as 6-[F-18]fluoro-L-dopa.

ArrayPitope: Automated Analysis of Amino Acid Substitutions for Peptide Microarray-Based Antibody Epitope Mapping.

PubMed

Hansen, Christian Skjødt; Østerbye, Thomas; Marcatili, Paolo; Lund, Ole; Buus, Søren; Nielsen, Morten

2017-01-01

Identification of epitopes targeted by antibodies (B cell epitopes) is of critical importance for the development of many diagnostic and therapeutic tools. For clinical usage, such epitopes must be extensively characterized in order to validate specificity and to document potential cross-reactivity. B cell epitopes are typically classified as either linear epitopes, i.e. short consecutive segments from the protein sequence or conformational epitopes adapted through native protein folding. Recent advances in high-density peptide microarrays enable high-throughput, high-resolution identification and characterization of linear B cell epitopes. Using exhaustive amino acid substitution analysis of peptides originating from target antigens, these microarrays can be used to address the specificity of polyclonal antibodies raised against such antigens containing hundreds of epitopes. However, the interpretation of the data provided in such large-scale screenings is far from trivial and in most cases it requires advanced computational and statistical skills. Here, we present an online application for automated identification of linear B cell epitopes, allowing the non-expert user to analyse peptide microarray data. The application takes as input quantitative peptide data of fully or partially substituted overlapping peptides from a given antigen sequence and identifies epitope residues (residues that are significantly affected by substitutions) and visualize the selectivity towards each residue by sequence logo plots. Demonstrating utility, the application was used to identify and address the antibody specificity of 18 linear epitope regions in Human Serum Albumin (HSA), using peptide microarray data consisting of fully substituted peptides spanning the entire sequence of HSA and incubated with polyclonal rabbit anti-HSA (and mouse anti-rabbit-Cy3). The application is made available at: www.cbs.dtu.dk/services/ArrayPitope.

Tuning the Magnetic Properties and Structural Stabilities of the 2-17-3 Magnets Sm2Fe17X3 (X =C , N) by Substituting La or Ce for Sm

NASA Astrophysics Data System (ADS)

Pandey, Tribhuwan; Du, Mao-Hua; Parker, David S.

2018-03-01

Designing a permanent magnet with reduced critical rare-earth content is of paramount importance in the development of cost-effective modern technologies. By performing comprehensive first-principles calculations, we investigate the potential avenues for reducing the critical rare-earth content in Sm2Fe17N3 and Sm2Fe17C3 by making a La or Ce substitution for Sm. The calculated magnetic properties of base compounds are in good agreement with the previous low-temperature (4.2-K) experimental measurements, and they show a large axial anisotropy. Although La or Ce substitution results in a slight reduction of magnetic anisotropy, the magnetic moments of Fe atoms mostly remain unchanged. Specifically, large axial anisotropies of 7.2 and 4.1 MJ /m3 are obtained for SmCeFe17 N3 and SmLaFe17 N3 , respectively. These values of anisotropies are comparable to the state-of-the-art permanent magnet Nd2 Fe14 B . The foremost limitation of Sm2 Fe17X3 magnets for practical application is the formation nitrogen or carbon vacancies at high temperatures. By calculating the N- (C)- vacancy formation energy, we show that La or Ce substitution enhances the vacancy formation energy. This enhanced vacancy formation energy will likely improve the thermodynamic stability of these alloys at high temperatures. Therefore, La- or Ce-substituted Sm2Fe17C3 and Sm2Fe17N3 compounds are promising candidates for high-performance permanent magnets with substantially reduced rare-earth content.

Data-driven discovery of energy materials: efficient BaM2Si3O10 : Eu2+ (M = Sc, Lu) phosphors for application in solid state white lighting.

PubMed

Brgoch, Jakoah; Hasz, Kathryn; Denault, Kristin A; Borg, Christopher K H; Mikhailovsky, Alexander A; Seshadri, Ram

2014-01-01

In developing phosphors for application in solid state lighting, it is advantageous to target structures from databases with highly condensed polyhedral networks that produce rigid host compounds. Rigidity limits channels for non-radiative decay that will decrease the luminescence quantum yield. BaM(2)Si(3)O(10) (M = Sc, Lu) follows this design criterion and is studied here as an efficient Eu(2+)-based phosphor. M = Sc(3+) and Lu(3+) compounds with Eu(2+) substitution were prepared and characterized using synchrotron X-ray powder diffraction and photoluminescence spectroscopy. Substitution with Eu(2+) according to Ba(1-x)Eu(x)Sc(2)Si(3)O(10) and Ba(1-x)Eu(x)Lu(2)Si(3)O(10) results in UV-to-blue and UV-to-blue-green phosphors, respectively. Interestingly, substitution with Eu(2+) in the Lu(3+) containing material produces two emission peaks at low temperature and with 365 nm excitation, as allowed by the two substitution sites. The photoluminescence of the Sc(3+) compound is robust at high temperature, decreasing by only 25% of its room temperature intensity at 503 K, while the Lu-analogue suffers a large drop (75%) from its room temperature intensity. The decrease in emission intensity is explained as stemming from charge transfer quenching due to the short distances separating the luminescent centers on the Lu(3+) substitution site. The correlation between structure and optical response in these two compounds indicates that even though the structures are three-dimensionally connected, high symmetry is required to prevent structural distortions that could impact photoluminescence.

Tuning the Magnetic Properties and Structural Stabilities of the 2-17-3 Magnets Sm 2Fe 17X 3 (X=C, N) by Substituting La or Ce for Sm

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

Pandey, Tribhuwan; Du, Mao-Hua; Parker, David S.

Designing a permanent magnet with reduced critical rare-earth content is of paramount importance in the development of cost-effective modern technologies. By performing comprehensive first-principles calculations, we investigate the potential avenues for reducing the critical rare-earth content in Sm 2Fe 17N 3 and Sm 2Fe 17C 3 by making a La or Ce substitution for Sm. The calculated magnetic properties of base compounds are in good agreement with the previous low-temperature (4.2-K) experimental measurements, and they show a large axial anisotropy. Although La or Ce substitution results in a slight reduction of magnetic anisotropy, the magnetic moments of Fe atoms mostlymore » remain unchanged. Specifically, large axial anisotropies of 7.2 and 4.1 MJ/m 3 are obtained for SmCeFe 17N 3 and SmLaFe 17N 3, respectively. These values of anisotropies are comparable to the state-of-the-art permanent magnet Nd 2Fe 14B. The foremost limitation of Sm 2Fe 17X 3 magnets for practical application is the formation nitrogen or carbon vacancies at high temperatures. By calculating the N- (C)- vacancy formation energy, we show that La or Ce substitution enhances the vacancy formation energy. Here, this enhanced vacancy formation energy will likely improve the thermodynamic stability of these alloys at high temperatures. Therefore, La- or Ce-substituted Sm 2Fe 17C 3 and Sm 2Fe 17N 3 compounds are promising candidates for high-performance permanent magnets with substantially reduced rare-earth content.« less

Tuning the Magnetic Properties and Structural Stabilities of the 2-17-3 Magnets Sm 2Fe 17X 3 (X=C, N) by Substituting La or Ce for Sm

DOE PAGES

Pandey, Tribhuwan; Du, Mao-Hua; Parker, David S.

2018-03-05

Designing a permanent magnet with reduced critical rare-earth content is of paramount importance in the development of cost-effective modern technologies. By performing comprehensive first-principles calculations, we investigate the potential avenues for reducing the critical rare-earth content in Sm 2Fe 17N 3 and Sm 2Fe 17C 3 by making a La or Ce substitution for Sm. The calculated magnetic properties of base compounds are in good agreement with the previous low-temperature (4.2-K) experimental measurements, and they show a large axial anisotropy. Although La or Ce substitution results in a slight reduction of magnetic anisotropy, the magnetic moments of Fe atoms mostlymore » remain unchanged. Specifically, large axial anisotropies of 7.2 and 4.1 MJ/m 3 are obtained for SmCeFe 17N 3 and SmLaFe 17N 3, respectively. These values of anisotropies are comparable to the state-of-the-art permanent magnet Nd 2Fe 14B. The foremost limitation of Sm 2Fe 17X 3 magnets for practical application is the formation nitrogen or carbon vacancies at high temperatures. By calculating the N- (C)- vacancy formation energy, we show that La or Ce substitution enhances the vacancy formation energy. Here, this enhanced vacancy formation energy will likely improve the thermodynamic stability of these alloys at high temperatures. Therefore, La- or Ce-substituted Sm 2Fe 17C 3 and Sm 2Fe 17N 3 compounds are promising candidates for high-performance permanent magnets with substantially reduced rare-earth content.« less

ArrayPitope: Automated Analysis of Amino Acid Substitutions for Peptide Microarray-Based Antibody Epitope Mapping

PubMed Central

Hansen, Christian Skjødt; Østerbye, Thomas; Marcatili, Paolo; Lund, Ole; Buus, Søren

2017-01-01

Identification of epitopes targeted by antibodies (B cell epitopes) is of critical importance for the development of many diagnostic and therapeutic tools. For clinical usage, such epitopes must be extensively characterized in order to validate specificity and to document potential cross-reactivity. B cell epitopes are typically classified as either linear epitopes, i.e. short consecutive segments from the protein sequence or conformational epitopes adapted through native protein folding. Recent advances in high-density peptide microarrays enable high-throughput, high-resolution identification and characterization of linear B cell epitopes. Using exhaustive amino acid substitution analysis of peptides originating from target antigens, these microarrays can be used to address the specificity of polyclonal antibodies raised against such antigens containing hundreds of epitopes. However, the interpretation of the data provided in such large-scale screenings is far from trivial and in most cases it requires advanced computational and statistical skills. Here, we present an online application for automated identification of linear B cell epitopes, allowing the non-expert user to analyse peptide microarray data. The application takes as input quantitative peptide data of fully or partially substituted overlapping peptides from a given antigen sequence and identifies epitope residues (residues that are significantly affected by substitutions) and visualize the selectivity towards each residue by sequence logo plots. Demonstrating utility, the application was used to identify and address the antibody specificity of 18 linear epitope regions in Human Serum Albumin (HSA), using peptide microarray data consisting of fully substituted peptides spanning the entire sequence of HSA and incubated with polyclonal rabbit anti-HSA (and mouse anti-rabbit-Cy3). The application is made available at: www.cbs.dtu.dk/services/ArrayPitope. PMID:28095436

Effect of Ni and Ti substitutions on Li1.05Mn2O4-δ electrical conductivities at high temperature

NASA Astrophysics Data System (ADS)

Abe, Satoko; Iwasaki, Shoko; Shimonishi, Yuta; Komine, Shigeki; Munakata, Fumio

2016-10-01

Samples of Li1.05Mn2O4-δ, Li1.05Mn1.5Ni0.5O4-δ, and Li1.05Mn1.0Ni0.5Ti0.5O4-δ were prepared by a solid-state reaction technique and ultimately refined to a space group Fd-3m of spinel structure by the Rietveld method using synchrotron powder X-ray diffraction data. Comparison of lattice constants suggested that Ni-substitution increased the covalency in the bonding of MO6 (M: metal ion at 16d site) octahedrals, but Ni/Ti co-substitution decreased the covalency of M-O bonds and introduced structural distortion. Electrical conductivity measurements by a four-probe method resulted in the determination that electrical conduction (within all samples) exhibits a nonadiabatic hopping process at high temperatures. The activation energies of Li1.05Mn2O4-δ and Li1.05Mn1.5Ni0.5O4-δ were found to be of similar values. The Ni/Ti co-substituted sample of Li1.05Mn1.0Ni0.5Ti0.5O4-δ, on the other hand, showed the highest activation energy among all the measured samples. Substitution reduced the electrical conductivity relative to Li1.05Mn2O4-δ; furthermore, both the substituted samples (Li1.05Mn1.5Ni0.5O4-δ and Li1.05Mn1.0Ni0.5Ti0.5O4-δ) were found to exhibit functional independence from oxygen partial pressure (PO2).

Can sterile and pyrogen-free on-line substitution fluid be routinely delivered? A multicentric study on the microbiological safety of on-line haemodiafiltration.

PubMed

Vaslaki, L; Karátson, A; Vörös, P; Major, L; Pethö, F; Ladányi, E; Weber, C; Mitteregger, R; Falkenhagen, D

2000-01-01

Microbial contamination is characterized not only by the presence of bacteria, but also by high concentrations of biologically active by-products. They are potentially able to cross ultrafiltration and dialysis membranes and stimulate immunocompetent blood cells to synthesize cytokines. In turn, cytokine induction causes acute symptoms and has been incriminated in the long-term complications of haemodialysis patients. Infusion of large volumes of substitution fluids following ultrafiltration of microbially contaminated dialysis fluids may place patients on on-line therapies at particular risk. In this study we evaluated 30 machines with a two-stage ultrafiltration system in routine clinical haemodiafiltration settings in six centres for 6 months. Microbiological safety was assessed monthly and at the last use of the filters by determining microbial counts, endotoxin concentration and cytokine-inducing activity. No pyrogenic episodes were observed during the study period. Double-filtration of standard dialysis fluid (range, <1-895 cfu/ml, 0.0028-4.6822 IU/ml) resulted in sterile substitution fluids with endotoxin concentrations well below the Ph.Eur. standard for haemofiltration solutions (range, 0.0014-0.0281 vs 0.25 IU/ml). Moreover, they did not differ from commercial haemofiltration solutions and depyrogenated saline. Likewise, there was no difference in the cytokine-inducing activity between the solutions tested. The high microbiological quality of the ultrafiltered dialysis fluid, which was in the same range as substitution fluid, translates into both the absence of cytokine induction by dialyser back-transport and a redundant safety mode of the on-line system by a second filtration step. On-line HDF treatment can routinely be provided with ultra-pure dialysis fluids and sterile substitution fluids at pyrogen-free levels. The online preparation of substitution fluids thus can be considered microbiologically safe.

Substituting values for censored data from Texas, USA, reservoirs inflated and obscured trends in analyses commonly used for water quality target development.

PubMed

Grantz, Erin; Haggard, Brian; Scott, J Thad

2018-06-12

We calculated four median datasets (chlorophyll a, Chl a; total phosphorus, TP; and transparency) using multiple approaches to handling censored observations, including substituting fractions of the quantification limit (QL; dataset 1 = 1QL, dataset 2 = 0.5QL) and statistical methods for censored datasets (datasets 3-4) for approximately 100 Texas, USA reservoirs. Trend analyses of differences between dataset 1 and 3 medians indicated percent difference increased linearly above thresholds in percent censored data (%Cen). This relationship was extrapolated to estimate medians for site-parameter combinations with %Cen > 80%, which were combined with dataset 3 as dataset 4. Changepoint analysis of Chl a- and transparency-TP relationships indicated threshold differences up to 50% between datasets. Recursive analysis identified secondary thresholds in dataset 4. Threshold differences show that information introduced via substitution or missing due to limitations of statistical methods biased values, underestimated error, and inflated the strength of TP thresholds identified in datasets 1-3. Analysis of covariance identified differences in linear regression models relating transparency-TP between datasets 1, 2, and the more statistically robust datasets 3-4. Study findings identify high-risk scenarios for biased analytical outcomes when using substitution. These include high probability of median overestimation when %Cen > 50-60% for a single QL, or when %Cen is as low 16% for multiple QL's. Changepoint analysis was uniquely vulnerable to substitution effects when using medians from sites with %Cen > 50%. Linear regression analysis was less sensitive to substitution and missing data effects, but differences in model parameters for transparency cannot be discounted and could be magnified by log-transformation of the variables.

Spherical Al-substituted ɑ-nickel hydroxide with high tapping density applied in Ni-MH battery

NASA Astrophysics Data System (ADS)

Wu, Xing-Hua; Feng, Qing-Ping; Wang, Man; Huang, Gui-Wen

2016-10-01

Spherical Al-substituted ɑ-Ni(OH)2 with high tapping density are prepared with controlled crystallization method, where the synthesis parameters are previously calculated out according to theoretical analysis. The formation mechanism of Ni(OH)2 particles is analyzed based on theoretical calculation, the optimal conditions for the formation of spherical Al-substituted ɑ-Ni(OH)2 with high tapping density are figured out and a formula indicates the restrictions among main synthesis parameters is derived, which is reference meaningful for the synthesis of commercialized electrode powders. Synthesized by using the calculated parameters, the obtained ɑ-Ni(OH)2 shows uniform spherical morphology, high crystal phase purity and reasonable high tapping density of 1.37 g cm-3, which demonstrates the feasibility of the derived formula. Since the electrical conductivity of the pure Ni(OH)2 is quite low, 5 wt% of CoOOH are coated on the ɑ-Ni(OH)2 surface to improve their electrochemical performances. The synthesized CoOOH coated ɑ-Ni(OH)2 shows relative high specific capacity of 327 mAh g-1 at 0.1 C and acceptable high-rate dischargeability. The simultaneously achieving of high tapping density and high specific capacity in ɑ-Ni(OH)2 makes it own the great potential to be applied in new generation of Ni-MH batteries.

Antiviral Activity of 3(2H)- and 6-Chloro-3(2H)-Isoflavenes against Highly Diverged, Neurovirulent Vaccine-Derived, Type2 Poliovirus Sewage Isolates

PubMed Central

Shulman, Lester M.; Sofer, Danit; Manor, Yossi; Mendelson, Ella; Balanant, Jean; Salvati, Anna Laura; Delpeyroux, Francis; Fiore, Lucia

2011-01-01

Background Substituted flavanoids interfere with uncoating of Enteroviruses including Sabin-2 polio vaccine strains. However flavanoid resistant and dependent, type-2 polio vaccine strains (minimally-diverged), emerged during in vitro infections. Between 1998–2009, highly-diverged (8 to >15%) type-2, aVDPV2s, from two unrelated persistent infections were periodically isolated from Israeli sewage. Aim To determine whether highly evolved aVDPV2s derived from persistent infections retained sensitivity to isoflavenes. Methods Sabin-2 and ten aVDPV2 isolates from two independent Israeli sources were titered on HEp2C cells in the presence and absence of 3(2H)- Isoflavene and 6-chloro-3(2H)-Isoflavene. Neurovirulence of nine aVDPV2s was measured in PVR-Tg-21 transgenic mice. Differences were related to unique amino acid substitutions within capsid proteins. Principal Findings The presence of either flavanoid inhibited viral titers of Sabin-2 and nine of ten aVDPV2s by one to two log10. The tenth aVDPV2, which had unique amino acid substitution distant from the isoflavene-binding pocket but clustered at the three- and five-fold axies of symmetry between capsomeres, was unaffected by both flavanoids. Genotypic neurovirulence attenuation sites in the 5′UTR and VP1 reverted in all aVDPV2s and all reacquired a full neurovirulent phenotype except one with amino acid substitutions flanking the VP1 site. Conclusion Both isoflavenes worked equally well against Sabin 2 and most of the highly-diverged, Israeli, aVDPV2s isolates. Thus, functionality of the hydrophobic pocket may be unaffected by selective pressures exerted during persistent poliovirus infections. Amino acid substitutions at sites remote from the drug-binding pocket and adjacent to a neurovirulence attenuation site may influence flavanoid antiviral activity, and neurovirulence, respectively. PMID:21904594

Vanadium-substituted heteropolyacids immobilized on amine- functionalized mesoporous MCM-41: A recyclable catalyst for selective oxidation of alcohols with H{sub 2}O{sub 2}

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

Dong, Xinbo; Wang, Danjun; College of Chemistry Chemical Engineering, Yanan University, Shaanxi Key Laboratory of Chemical Reaction Engineering, Yan'an 716000

2014-09-15

Graphical abstract: Vanadium-substituted phosphotungstic acids are immobilized on amine- functionalized mesoporous MCM-41 and the hybrid catalyst is proved to be a highly efficient solid catalyst for the oxidation of aromatic alcohols to the corresponding carbonyl compounds with H{sub 2}O{sub 2}, featured by the high conversion and selectivity, easy recovery, and quite steady reuse. - Highlights: • Vanadium-substituted phosphotungstic acid immobilized on amine-functionalized mesoporous MCM-41 are prepared. • HPAs were fixed on the inner surface of mesoporous MCM-41 by chemical bonding to aminosilane groups. • The hybrid catalyst showed much higher catalytic activity than the pure HPAs. • The hybrid catalystmore » is a highly efficient recyclable solid catalyst for the selective oxidation of aromatic alcohols. - Abstract: New hybrid materials of vanadium-substituted phosphotungstic acids (VHPW) immobilized on amine-functionalized mesoporous MCM-41 (VHPW/MCM-41/NH{sub 2}) are prepared and characterized by FT-IR, XRD, N{sub 2} adsorption, elemental analysis, SEM and TEM for their structural integrity and physicochemical properties. It is found that the structure of the heteropolyacids is retained upon immobilization over mesoporous materials. The catalytic activities of these hybrid materials are tested in the selective oxidation of alcohols to the carbonyl products with 30% aqueous H{sub 2}O{sub 2} as oxidant in toluene. The catalytic activities of different number of vanadium-substituted phosphotungstic acid are investigated, and among the catalysts, H{sub 5}[PV{sub 2}W{sub 10}O{sub 40}] immobilized on amine-functionalized MCM-41 exhibits the highest activity with 97% conversion and 99% selectivity in the oxidation of benzyl alcohol to benzaldehyde. The hybrid catalyst is proved to be a highly efficient recyclable solid catalyst for the selective oxidation of aromatic alcohols to the corresponding aldehydes with H{sub 2}O{sub 2}.« less

Evaluation of cultured human dermal- and dermo-epidermal substitutes focusing on extracellular matrix components: Comparison of protein and RNA analysis.

PubMed

Oostendorp, Corien; Meyer, Sarah; Sobrio, Monia; van Arendonk, Joyce; Reichmann, Ernst; Daamen, Willeke F; van Kuppevelt, Toin H

2017-05-01

Treatment of full-thickness skin defects with split-thickness skin grafts is generally associated with contraction and scar formation and cellular skin substitutes have been developed to improve skin regeneration. The evaluation of cultured skin substitutes is generally based on qualitative parameters focusing on histology. In this study we focused on quantitative evaluation to provide a template for comparison of human bio-engineered skin substitutes between clinical and/or research centers, and to supplement histological data. We focused on extracellular matrix proteins since these components play an important role in skin regeneration. As a model we analyzed the human dermal substitute denovoDerm and the dermo-epidermal skin substitute denovoSkin. The quantification of the extracellular matrix proteins type III collagen and laminin 5 in tissue homogenates using western blotting analysis and ELISA was not successful. The same was true for assaying lysyl oxidase, an enzyme involved in crosslinking of matrix molecules. As an alternative, gene expression levels were measured using qPCR. Various RNA isolation procedures were probed. The gene expression profile for specific dermal and epidermal genes could be measured reliably and reproducibly. Differences caused by changes in the cell culture conditions could easily be detected. The number of cells in the skin substitutes was measured using the PicoGreen dsDNA assay, which was found highly quantitative and reproducible. The (dis) advantages of assays used for quantitative evaluation of skin substitutes are discussed. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Lattice parameters guide superconductivity in iron-arsenides

DOE PAGES

Konzen, Lance M. N.; Sefat, Athena S.

2017-01-12

The discovery of superconducting materials has led to their use in modern technological marvels, such as magnetic field sensors in MRI machines, powerful research magnets, and high-speed trains. Despite such applications, the uses of superconductors are not widespread due to high cooling costs. Since the discovery of Cu- and Fe-based high-temperature superconductors (HTS), numerous studies have tried to explain and understand the superconducting phenomenon. While no exact explanations are given, several trends are reported in relation to the materials basis in magnetism and spin excitations. In fact, most HTS have antiferromagnetic undoped ‘parent’ materials that undergo a superconducting transition uponmore » small chemical substitutions in them. As it is currently unclear which ‘dopants’ can favor of superconductivity, this manuscript investigates crystal structure changes upon chemical substitutions, to find clues in lattice parameters for the superconducting occurrence. We review the chemical substitution effects on the crystal lattice of iron-based materials (2008 to present). We note that (a) HTS compounds have nearly tetragonal structures with a-lattice parameter close to 4 Å, and (b) superconductivity can depend strongly on the c-lattice parameter changes with chemical substitution. For example, a decrease in c-lattice parameter is required to induce ‘in-plane’ superconductivity. The review of lattice parameter trends in iron-based superconductors presented here, should guide synthesis of new materials and give clues for superconductivity.« less

Preparation and Physical Properties of Starch Stearates of Low to High Degree of Substitution

USDA-ARS?s Scientific Manuscript database

Starch stearates of degree of substitution (DS) 0.07-2.40 were prepared by heating dry starch and vinyl stearate in the ionic liquid BMIM dca at 75 Degrees C. Starch stearate of low DS (0.07) was insoluble in water but formed a gel and absorbed over seven times its weight of water. Starch stearate...

A Diastereoselective Multicomponent Reaction for Construction of Alkynylamide-Substituted α,β-Diamino Acid Derivatives To Hunt Hits.

PubMed

Lei, Ruirui; Wu, Yong; Dong, Suzhen; Jia, Kaili; Liu, Shunying; Hu, Wenhao

2017-03-17

A highly diasetereoselective Mannich-type multicomponent reaction was developed to rapidly construct alkynylamide-substituted α,β-diamino acid derivatives from simple starting materials under mild conditions in moderate to good yields for hit hunting. Most of the resulting products 4 exhibited good anticancer activity in HCT116, BEL7402, and SMMC7721 cells.

Nucleophilic addition of Grignard reagents to 3-acylindoles: stereoselective synthesis of highly substituted indoline scaffolds.

PubMed

Wang, Lu; Shao, Yushang; Liu, Yuanhong

2012-08-03

3-Acylindoles undergo nucleophilic-type reactions with Grignard reagents to efficiently afford either cis- or trans-substituted indolines, depending on the different quenching procedures. The enolate intermediate could be trapped by aryl acyl chlorides to provide indolines bearing a quaternary carbon center with high stereoselectivity. In contrast, the use of benzyl bromide as an electrophile results in the fragmentation of the indole ring. The indoline products could be easily transformed into indoles through oxidation with DDQ in a one-pot manner.

Deep Sequencing of Random Mutant Libraries Reveals the Active Site of the Narrow Specificity CphA Metallo-β-Lactamase is Fragile to Mutations.

PubMed

Sun, Zhizeng; Mehta, Shrenik C; Adamski, Carolyn J; Gibbs, Richard A; Palzkill, Timothy

2016-09-12

CphA is a Zn(2+)-dependent metallo-β-lactamase that efficiently hydrolyzes only carbapenem antibiotics. To understand the sequence requirements for CphA function, single codon random mutant libraries were constructed for residues in and near the active site and mutants were selected for E. coli growth on increasing concentrations of imipenem, a carbapenem antibiotic. At high concentrations of imipenem that select for phenotypically wild-type mutants, the active-site residues exhibit stringent sequence requirements in that nearly all residues in positions that contact zinc, the substrate, or the catalytic water do not tolerate amino acid substitutions. In addition, at high imipenem concentrations a number of residues that do not directly contact zinc or substrate are also essential and do not tolerate substitutions. Biochemical analysis confirmed that amino acid substitutions at essential positions decreased the stability or catalytic activity of the CphA enzyme. Therefore, the CphA active - site is fragile to substitutions, suggesting active-site residues are optimized for imipenem hydrolysis. These results also suggest that resistance to inhibitors targeted to the CphA active site would be slow to develop because of the strong sequence constraints on function.

Near-Infrared Phosphorus-Substituted Rhodamine with Emission Wavelength above 700 nm for Bioimaging.

PubMed

Chai, Xiaoyun; Cui, Xiaoyan; Wang, Baogang; Yang, Fan; Cai, Yi; Wu, Qiuye; Wang, Ting

2015-11-16

Phosphorus has been successfully fused into a classic rhodamine framework, in which it replaces the bridging oxygen atom to give a series of phosphorus-substituted rhodamines (PRs). Because of the electron-accepting properties of the phosphorus moiety, which is due to effective σ*-π* interactions and strengthened by the inductivity of phosphine oxide, PR exhibits extraordinary long-wavelength fluorescence emission, elongating to the region above 700 nm, with bathochromic shifts of 140 and 40 nm relative to rhodamine and silicon-substituted rhodamine, respectively. Other advantageous properties of the rhodamine family, including high molar extinction coefficient, considerable quantum efficiency, high water solubility, pH-independent emission, great tolerance to photobleaching, and low cytotoxicity, stay intact in PR. Given these excellent properties, PR is desirable for NIR-fluorescence imaging in vivo. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of rare-earth substitution at La-site on structural, electrical and thermoelectric properties of La0.7-xRExSr0.3MnO3 compounds (x = 0, 0.2, 0.3; RE = Eu, Gd, Y)

NASA Astrophysics Data System (ADS)

Choudhary, Y. R. S.; Mangavati, Suraj; Patil, Siddanagouda; Rao, Ashok; Nagaraja, B. S.; Thomas, Riya; Okram, G. S.; Kini, Savitha G.

2018-04-01

In the present communication, we present results on the effect of rare-earth (RE) substitution at La-site on the structural, electrical and thermoelectric properties of La0.7-xRExSr0.3MnO3 compounds. The lattice parameters are observed to decrease with RE-doping which is attributed to the fact that the substituted RE ions (RE = Eu, Gd and Y) are smaller than that of La ion. In high temperature semiconducting regime, small polaron hopping (SPH) model is valid, whereas, variable hopping model is valid in low temperature metallic region. The resistivity in the entire temperature range follows percolation model. All the samples exhibit sign reversal in thermopower, S. From temperature dependent S data, it is seen that SPH model is applicable in high temperature regime.

Co2+Ti4+ substituted Z-type barium ferrite with enhanced imaginary permeability and resonance frequency

NASA Astrophysics Data System (ADS)

Li, Z. W.; Guoqing, Lin; Chen, Linfeng; Yuping, Wu; Ong, C. K.

2006-03-01

Co2+Ti4+ substitution for Fe3+ in Co2Z (Ba3Co2Fe24O41) has been prepared. The crystal structure and static and high-frequency magnetic properties have been studied for Ba3Co2+xTixFe24-2xO41 and the corresponding ferrite/polymer composites. As compared to the general Co2Z ferrite/polymer composite, the CoTi substituted ferrite/polymer composite with x=1.0 has a high natural resonance frequency (4.5 GHz), due to its large out-of-plane anisotropy fields Hθ. Furthermore, the maximum imaginary permeability μmax'' is increased by about 50%. The increase is attributed to a decreased damping coefficient, based on the curve-fitted results to the complex permeability spectra. The composites are good electromagnetic attenuation materials with low reflectivity and broad bandwidth at microwave frequencies.

Substitutional alloy of Ce and Al

PubMed Central

Zeng, Qiao-Shi; Ding, Yang; Mao, Wendy L.; Luo, Wei; Blomqvist, Andreas; Ahuja, Rajeev; Yang, Wenge; Shu, Jinfu; Sinogeikin, Stas V.; Meng, Yue; Brewe, Dale L.; Jiang, Jian-Zhong; Mao, Ho-kwang

2009-01-01

The formation of substitutional alloys has been restricted to elements with similar atomic radii and electronegativity. Using high-pressure at 298 K, we synthesized a face-centered cubic disordered alloy of highly dissimilar elements (large Ce and small Al atoms) by compressing the Ce3Al intermetallic compound >15 GPa or the Ce3Al metallic glass >25 GPa. Synchrotron X-ray diffraction, Ce L3-edge absorption spectroscopy, and ab initio calculations revealed that the pressure-induced Kondo volume collapse and 4f electron delocalization of Ce reduced the differences between Ce and Al and brought them within the Hume-Rothery (HR) limit for substitutional alloying. The alloy remained after complete release of pressure, which was also accompanied by the transformation of Ce back to its ambient 4f electron localized state and reversal of the Kondo volume collapse, resulting in a non-HR alloy at ambient conditions. PMID:19188608

Exploring the potential of high resolution mass spectrometry for the investigation of lignin-derived phenol substitutes in phenolic resin syntheses.

PubMed

Dier, Tobias K F; Fleckenstein, Marco; Militz, Holger; Volmer, Dietrich A

2017-05-01

Chemical degradation is an efficient method to obtain bio-oils and other compounds from lignin. Lignin bio-oils are potential substitutes for the phenol component of phenol formaldehyde (PF) resins. Here, we developed an analytical method based on high resolution mass spectrometry that provided structural information for the synthesized lignin-derived resins and supported the prediction of their properties. Different model resins based on typical lignin degradation products were analyzed by electrospray ionization in negative ionization mode. Utilizing enhanced mass defect filter techniques provided detailed structural information of the lignin-based model resins and readily complemented the analytical data from differential scanning calorimetry and thermogravimetric analysis. Relative reactivity and chemical diversity of the phenol substitutes were significant determinants of the outcome of the PF resin synthesis and thus controlled the areas of application of the resulting polymers. Graphical abstract ᅟ.

Hydroacylation of 2-vinyl benzaldehyde systems: an efficient method for the synthesis of chiral 3-substituted indanones.

PubMed

Kundu, Kousik; McCullagh, James V; Morehead, Andrew T

2005-11-23

Asymmetric rhodium-catalyzed hydroacylation has been utilized in the synthesis of 3-substituted indanones with high conversions and enantioselectivity. The hydroacylation reaction of 2-vinyl benzaldehyde had been previously reported to give a low yield of indanone and an unidentified product. We have identified this compound as a dimer of the starting material. Substitution at the alpha-position of the 2-vinyl benzaldehyde substrates blocks the competitive dimerization reaction and allows the reaction to proceed with yields generally greater than 90%. Utilization of BINAP as a chiral ligand results in good chemical yields and enantioselectivity greater than 95% in most cases.

Effect of size and site preference of trivalent non-magnetic metal ions (Al3+, Ga3+, In3+) substituted for Fe3+ on the magnetostrictive properties of sintered CoFe2O4

NASA Astrophysics Data System (ADS)

Anantharamaiah, P. N.; Joy, P. A.

2017-11-01

The influence of size and crystallographic site preference of three non-magnetic isovalent metal ions of larger (In3+), comparable (Ga3+) and smaller (Al3+) sizes, substituted for Fe3+ in the spinel lattice of CoFe2O4 on its magnetostrictive properties is compared. For the different compositions in CoFe2-x M x O4 (M  =  In3+, Ga3+, Al3+ and 0  ⩽  x  ⩽  0.3), significant changes in the structural and magnetic parameters are observed with the degree of substitution, due to the size and site preferences. Magnetic and Raman spectral studies revealed that Al3+ is substituted for Fe3+ at both octahedral and tetrahedral sites for all compositions, whereas In3+ and Ga3+ are substituted for Fe3+ at the tetrahedral site only for x  ⩽  0.2 and partly at the octahedral site for x  >  0.2. Regardless of the differences in the ionic size, site preference and the magnetic properties, compositions in all three series with x  =  0.1 showed almost equal magnitude of maximum magnetostriction (λ max  =  ~230 ppm), marginally higher than that of x  =  0 (217 ppm). However, at higher substituted compositions, λ max is decreased with x, but the decrease is much faster for the Al-substituted compositions. The maximum strain sensitivity, [dλ/dH]max, is also found to be comparable for all three compositions. The comparable magnetostriction characteristics and high strain at low magnetic fields for different substituted compositions at low levels of substitution are attributed to the local structural distortions associated with the inhomogeneous distribution of the substituted ions in the spinel ferrite lattice. The studies suggest ways to optimise the magnetostriction properties of properly substituted sintered cobalt ferrite for applications in sensors and actuators.

High coercivity Gd-substituted Ba hexaferrites, prepared by chemical coprecipitation

NASA Astrophysics Data System (ADS)

Litsardakis, G.; Manolakis, I.; Serletis, C.; Efthimiadis, K. G.

2008-04-01

A series of Gd-substituted Ba hexaferrites with nominal formula (Ba1-xGdx)Oṡ5.25 Fe2O3 (x=0-0.30) were prepared by the chemical coprecipitation method from nitrate precursors and heating at T =800-1200°C for 2h. The samples have been examined by x-ray diffraction, vibrating-sample magnetometer, and scanning electron microscopy methods. Gd substituted samples form single phase materials with the M-type hexaferrite structure at all heating temperatures, in the range of x ⩽0.10-0.20. The saturation magnetization (at 1.8T) varies slightly with x in most cases and, for x =0.05-0.10, it increases up to 66.7Am2/kg, exceeding the value of the unsubstituted hexaferrite. A strong enhancement of the coercivity is observed for all substituted samples, with maximum values Hc=457kA/m for the single-phase x =0.10 sample annealed at 1000°C and Hc=477kA/m for the x =0.25 sample annealed at 1100°C which contains Fe2O3 and GdFeO3 impurities. As the variation of coercivity with either substitution rate (x ) or annealing temperature is not monotonic, three different factors may account for the high coercivities that are obtained: (a) an inhibition of grain growth due to the presence of Gd, (b) a possible inherent effect on magnetocrystalline anisotropy, especially for single phase samples, and (c) a microstructural effect of secondary phases.

Generic Substitution of Orphan Drugs for the Treatment of Rare Diseases: Exploring the Potential Challenges.

PubMed

Di Paolo, Antonello; Arrigoni, Elena

2018-03-01

Generic drugs are important components of measures introduced by healthcare regulatory authorities to reduce treatment costs. In most patients and conditions the switch from a branded drug to its generic counterpart is performed with no major complications. However, evidence from complex diseases suggests that generic substitution requires careful evaluation in some settings and that current bioequivalence criteria may not always be adequate for establishing the interchangeability of branded and generic products. Rare diseases, also called orphan diseases, are a group of heterogeneous diseases that share important characteristics: in addition to their scarcity, most are severe, chronic, highly debilitating, and often present in early childhood. Finding a treatment for a rare disease is challenging. Thanks to incentives that encourage research and development programs in rare diseases, several orphan drugs are currently available. The elevated cost of orphan drugs is a highly debated issue and a cause of limited access to treatment for many patients. As patent protection and the exclusivity period of several orphan drugs will expire soon, generic versions of orphan drugs should reach the market shortly, with great expectations about their impact on the economic burden of rare diseases. However, consistent with other complex diseases, generic substitution may require thoughtful considerations and may be even contraindicated in some rare conditions. This article provides an overview of rare disease characteristics, reviews reports of problematic generic substitution, and discusses why generic substitution of orphan drugs may be challenging and should be undertaken carefully in rare disease patients.

Partial substitution of Zn Effects on the Structural and Electrical Properties of High Temperature Hg0.95Ag0.05Ba2Ca2Cu3O8+δ Superconductors

NASA Astrophysics Data System (ADS)

Abed, Noor S.; Fathi, Sabah J.; Jassim, Kareem A.; Mahdi, Shatha H.

2018-05-01

The effect of the Ag partial substitution at Hg site in HgOδ layer and Zn partial substitution at Ca site in CaO layer on the structure,Tc,electrical properties, and oxygen content for Hg-1223 have been studied. Bulk polycrystalline Hg1-xAgxBa2Ca2-yZnyCu3O8+δ compound samples with x=0.05 and y=0.0, 0.05, 0.1, 0.15, 0.2, 0.25, and 0.3, are synthesized by a solid state reaction process. Structural properties are studied by using X-ray powder pattern, the high temperature phase superconductor (Hg-1223) of the tetragonal structure didn't change with the partial substitution of Zn and Ag ions, lattice parameters c,c/a are established to vary with Ag and Zn- substitution. The surface morphology has been studied by using atomic force microscopes (AFM), showed that all specimens have good crystalline and homogeneous surface. Also give a best nano size value is 75.72 nm at x=0.05 and y=0.3. Four probe technique is used to measure Tc. The Tc were found to be increases from 129 K to 147 K and oxygen content were found to be increases with increasing Zn. In addition, dielectric properties (dielectric constant, dielectric loss factor, and the alternating electrical conductivity) are characterized directly by relating with Ag and Zn concentration.

Interspecific diversity reduces and functionally substitutes for intraspecific variation in biofilm communities

PubMed Central

Kelvin Lee, Kai Wei; Hoong Yam, Joey Kuok; Mukherjee, Manisha; Periasamy, Saravanan; Steinberg, Peter D; Kjelleberg, Staffan; Rice, Scott A

2016-01-01

Diversity has a key role in the dynamics and resilience of communities and both interspecific (species) and intraspecific (genotypic) diversity can have important effects on community structure and function. However, a critical and unresolved question for understanding the ecology of a community is to what extent these two levels of diversity are functionally substitutable? Here we show, for a mixed-species biofilm community composed of Pseudomonas aeruginosa, P. protegens and Klebsiella pneumoniae, that increased interspecific diversity reduces and functionally substitutes for intraspecific diversity in mediating tolerance to stress. Biofilm populations generated high percentages of genotypic variants, which were largely absent in biofilm communities. Biofilms with either high intra- or interspecific diversity were more tolerant to SDS stress than biofilms with no or low diversity. Unexpectedly, genotypic variants decreased the tolerance of biofilm communities when experimentally introduced into the communities. For example, substituting P. protegens wild type with its genotypic variant within biofilm communities decreased SDS tolerance by twofold, apparently due to perturbation of interspecific interactions. A decrease in variant frequency was also observed when biofilm populations were exposed to cell-free effluents from another species, suggesting that extracellular factors have a role in selection against the appearance of intraspecific variants. This work demonstrates the functional substitution of inter- and intraspecific diversity for an emergent property of biofilms. It also provides a potential explanation for a long-standing paradox in microbiology, in which morphotypic variants are common in laboratory grown biofilm populations, but are rare in diverse, environmental biofilm communities. PMID:26405829

Aerobic biodegradation of the sulfonamide antibiotic sulfamethoxazole by activated sludge applied as co-substrate and sole carbon and nitrogen source.

PubMed

Müller, Elisabeth; Schüssler, Walter; Horn, Harald; Lemmer, Hilde

2013-08-01

Potential aerobic biodegradation mechanisms of the widely used polar, low-adsorptive sulfonamide antibiotic sulfamethoxazole (SMX) were investigated in activated sludge at bench scale. The study focused on (i) SMX co-metabolism with acetate and ammonium nitrate and (ii) SMX utilization when present as the sole carbon and nitrogen source. With SMX adsorption being negligible, elimination was primarily based on biodegradation. Activated sludge was able to utilize SMX both as a carbon and/or nitrogen source. SMX biodegradation was enhanced when a readily degradable energy supply (acetate) was provided which fostered metabolic activity. Moreover, it was raised under nitrogen deficiency conditions. The mass balance for dissolved organic carbon showed an incomplete SMX mineralization with two scenarios: (i) with SMX as a co-substrate, 3-amino-5-methyl-isoxazole represented the main stable metabolite and (ii) SMX as sole carbon and nitrogen source possibly yielded hydroxyl-N-(5-methyl-1,2-oxazole-3-yl)benzene-1-sulfonamide as a further metabolite. Copyright © 2013 Elsevier Ltd. All rights reserved.

Thermodynamics and Mechanism of the Interaction of Willardiine Partial Agonists with a Glutamate Receptor: Implications for Drug Development

PubMed Central

2015-01-01

Understanding the thermodynamics of binding of a lead compound to a receptor can provide valuable information for drug design. The binding of compounds, particularly partial agonists, to subtypes of the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor is, in some cases, driven by increases in entropy. Using a series of partial agonists based on the structure of the natural product, willardiine, we show that the charged state of the ligand determines the enthalpic contribution to binding. Willardiines have uracil rings with pKa values ranging from 5.5 to 10. The binding of the charged form is largely driven by enthalpy, while that of the uncharged form is largely driven by entropy. This is due at least in part to changes in the hydrogen bonding network within the binding site involving one water molecule. This work illustrates the importance of charge to the thermodynamics of binding of agonists and antagonists to AMPA receptors and provides clues for further drug discovery. PMID:24850223

Alkaloids as important scaffolds in therapeutic drugs for the treatments of cancer, tuberculosis, and smoking cessation.

PubMed

Kittakoop, Prasat; Mahidol, Chulabhorn; Ruchirawat, Somsak

2014-01-01

Alkaloid molecules can act, depending on a type of amine functionality present in alkalods, as either hydrogenacceptor or hydrogen-donor for hydrogen bonding that is critically important for the interaction (binding) between targets (enzymes, proteins and receptors) and drugs (ligands). Because of this unique property, alkaloid scaffolds are therefore present in several drugs and lead compounds. This review highlights alkaloid scaffolds in drugs, particularly those recently approved in 2012; it also covers the scaffolds in leads and drug candidates which are in clinical trials and preclinical pipeline. The review focuses on three therapeutic areas including treatments of cancer, tuberculosis, and tobacco cessation. Alkaloid scaffolds in drugs and leads are inspired by those of naturally occurring alkaloids, and these scaffolds include pyridine, piperidine, quinoline, quinolinone, quinazoline, isoquinoline, indole, indolinone, isoindole, isoxazole, imidazole, indazole, thiazole, pyrazole, oxazolidinone, oxadiazole, and benzazepine. In addition to medicinal chemistry aspects, natural products possessing an individual alkaloid scaffold, as well as the mechanism of action of drugs and leads, are also discussed in this review.

Food toxins, ampa receptors, and motor neuron diseases.

PubMed

Spencer, P S

1999-08-01

Environmental chemicals involved in the etiology of human neurodegenerative disorders are challenging to identify. Described here is research designed to determine the etiology and molecular pathogenesis of nerve cell degeneration in two little known corticomotoneuronal diseases with established environmental triggers. Both conditions are toxic-nutritional disorders dominated by persistent spastic weakness of the legs and degeneration of corresponding corticospinal pathways. Lathyrism, a disease caused by dietary dependence on grass pea (Lathyrus sativus), is mediated by a stereospecific plant amino acid (beta-N-oxalylamino-L-alanine) that serves as a potent agonist at the (RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) subclass of neuronal glutamate receptors. A neurologically similar disorder, konzo ("tied legs"), is found among protein-poor African communities that rely for food on cyanogen-containing cassava roots. Thiocyanate, the principal metabolite of cyanide, is an attractive etiologic candidate for konzo because it selectively promotes the action of glutamate at AMPA receptors. Studies are urgently needed to assess the health effects of cassava and other cyanogenic plants, components of which are widely used as food.

Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis.

PubMed

Dong, Zhifang; Han, Huili; Li, Hongjie; Bai, Yanrui; Wang, Wei; Tu, Man; Peng, Yan; Zhou, Limin; He, Wenting; Wu, Xiaobin; Tan, Tao; Liu, Mingjing; Wu, Xiaoyan; Zhou, Weihui; Jin, Wuyang; Zhang, Shu; Sacktor, Todd Charlton; Li, Tingyu; Song, Weihong; Wang, Yu Tian

2015-01-01

Long-term potentiation (LTP) of synaptic strength between hippocampal neurons is associated with learning and memory, and LTP dysfunction is thought to underlie memory loss. LTP can be temporally and mechanistically classified into decaying (early-phase) LTP and nondecaying (late-phase) LTP. While the nondecaying nature of LTP is thought to depend on protein synthesis and contribute to memory maintenance, little is known about the mechanisms and roles of decaying LTP. Here, we demonstrated that inhibiting endocytosis of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) prevents LTP decay, thereby converting it into nondecaying LTP. Conversely, restoration of AMPAR endocytosis by inhibiting protein kinase Mζ (PKMζ) converted nondecaying LTP into decaying LTP. Similarly, inhibition of AMPAR endocytosis prolonged memory retention in normal animals and reduced memory loss in a murine model of Alzheimer's disease. These results strongly suggest that an active process that involves AMPAR endocytosis mediates the decay of LTP and that inhibition of this process can prolong the longevity of LTP as well as memory under both physiological and pathological conditions.

Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.

PubMed

Han, Jing; Kesner, Philip; Metna-Laurent, Mathilde; Duan, Tingting; Xu, Lin; Georges, Francois; Koehl, Muriel; Abrous, Djoher Nora; Mendizabal-Zubiaga, Juan; Grandes, Pedro; Liu, Qingsong; Bai, Guang; Wang, Wei; Xiong, Lize; Ren, Wei; Marsicano, Giovanni; Zhang, Xia

2012-03-02

Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

Coordination ability determined transition metal ions substitution of Tb in Tb-Asp fluorescent nanocrystals and a facile ions-detection approach.

PubMed

Duan, Jiazhi; Ma, Baojin; Liu, Feng; Zhang, Shan; Wang, Shicai; Kong, Ying; Du, Min; Han, Lin; Wang, Jianjun; Sang, Yuanhua; Liu, Hong

2018-04-26

Although the synthesis and fluorescent properties of lanthanide-amino acid complex nanostructures have been investigated extensively, limited studies have been reported on metal ions' substitution ability for the lanthanide ions in the complex and their effect on the fluorescent property. In this study, taking biocompatible Tb-aspartic acid (Tb-Asp) complex nanocrystals as a model, the substitution mechanism of metal ions, particularly transition metals, for Tb ions in Tb-Asp nanocrystals and the change in the fluorescent property of the Tb-Asp nanocrystals after substitution were systematically investigated. The experimental results illustrated that metal ions with higher electronegativity, higher valence, and smaller radius possess stronger ability for Tb ions' substitution in Tb-Asp nanocrystals. Based on the effect of substituting ions' concentration on the fluorescent property of Tb-Asp, a facile method for copper ions detection with high sensitivity was proposed by measuring the fluorescent intensity of Tb-Asp nanocrystals' suspensions containing different concentrations of copper ions. The good biocompatibility, great convenience of synthesis and sensitive detection ability make Tb-Asp nanocrystals a very low cost and effective material for metal ions detection, which also opens a new door for practical applications of metal-Asp coordinated nanocrystals.

Reduced thermal conductivity by nanoscale intergrowths in perovskite like layered structure La{sub 2}Ti{sub 2}O{sub 7}

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

Khaliq, Jibran; Chen, Kan; Li, Chunchun

2015-02-21

The effect of substitution and oxidation-reduction on the thermal conductivity of perovskite-like layered structure (PLS) ceramics was investigated in relation to mass contrast and non-stoichiometry. Sr (acceptor) was substituted on the A site, while Ta (donor) was substituted on the B site of La{sub 2}Ti{sub 2}O{sub 7}. Substitution in PLS materials creates atomic scale disorders to accommodate the non-stoichiometry. High resolution transmission electron microscopy and X ray diffraction revealed that acceptor substitution in La{sub 2}Ti{sub 2}O{sub 7} produced nanoscale intergrowths of n = 5 layered phase, while donor substitution produced nanoscale intergrowths of n = 3 layered phase. As a result of these nanoscalemore » intergrowths, the thermal conductivity value reduced by as much as ∼20%. Pure La{sub 2}Ti{sub 2}O{sub 7} has a thermal conductivity value of ∼1.3 W/m K which dropped to a value of ∼1.12 W/m K for Sr doped La{sub 2}Ti{sub 2}O{sub 7} and ∼0.93 W/m K for Ta doped La{sub 2}Ti{sub 2}O{sub 7} at 573 K.« less

Photocatalytic CO2 reduction by Cr-substituted Ba2(In2-xCrx)O5·(H2O)δ (0.04 ≤ x ≤ 0.60)

NASA Astrophysics Data System (ADS)

Yoon, Songhak; Gaul, Michael; Sharma, Sitansh; Son, Kwanghyo; Hagemann, Hans; Ziegenbalg, Dirk; Schwingenschlogl, Udo; Widenmeyer, Marc; Weidenkaff, Anke

2018-04-01

Cr-substituted polycrystalline Ba2(In2-xCrx)O5·(H2O)δ powders (0.04 ≤ x ≤ 0.60) were synthesized by solid state reaction to investigate the relation of crystal structure, thermochemical, magnetic, and optical properties. The Cr-substitution results in an unit cell expansion and formation of the higher-symmetric tetragonal phase together with increased oxygen and hydrogen contents. Magnetic property measurements reveal that the diamagnetic pristine Ba2In2O5·(H2O)δ becomes magnetically ordered upon Cr-substitution. By UV-vis spectroscopy a gradual shift of the absorption-edge energy to lower values was observed. Numerical calculations showed that the observed bandgap narrowing was ascribed to the Cr induced states near the Fermi level. The correlation between the changes of crystal chemistry, magnetic, and optical properties of Cr-substituted Ba2(In2-xCrx)O5·(H2O)δ can be explained by the replacement of In by Cr. Consequently, an enhanced photocatalytic CO2 reduction activity was observed with increasing Cr substitution, compatible with the state-of-the-art high surface area TiO2 photocatalyst (P-25).

Enhanced red fluorescence in Sr2Si1-xGexO4:Eu3+ phosphors by the substitution of Si by Ge for white light emitting diodes

NASA Astrophysics Data System (ADS)

Huang, Lihui; Xu, Shiqing; Guo, Meiquan; Wang, Chenyue; Hua, Youjie; Zhao, Shilong; Deng, Degang; Wang, Huanping; Jia, Guohua

2012-07-01

Eu3+-doped Sr2Si1-xGexO4 (x=0-1) phosphors have been prepared by the high temperature solid-state reaction method. The luminescent properties of these phosphors were investigated. Red fluorescence of Eu3+ is enhanced gradually in the samples with increasing substitution of Si by Ge upon the excitation of 393 nm light. The intensity is increased by 50% with full substitution of Si by Ge. These results are originated from the structural changes and the phonon energy reduction in the samples due to the substitution of Si by Ge. The CIE chromaticity coordinates of the phosphors vary slightly around (0.62, 0.37) and all are in the red color region. The results indicate that these phosphors could be promising red phosphors for white light emitting diodes.

Analysis on Potential of Electric Energy Market based on Large Industrial Consumer

NASA Astrophysics Data System (ADS)

Lin, Jingyi; Zhu, Xinzhi; Yang, Shuo; Xia, Huaijian; Yang, Di; Li, Hao; Lin, Haiying

2018-01-01

The implementation of electric energy substitution by enterprises plays an important role in promoting the development of energy conservation and emission reduction in china. In order to explore alternative energy potential of industrial enterprises, to simulate and analyze the process of industrial enterprises, identify high energy consumption process and equipment, give priority to alternative energy technologies, and determine the enterprise electric energy substitution potential predictive value, this paper constructs the evaluation model of the influence factors of the electric energy substitution potential of industrial enterprises, and uses the combined weight method to determine the weight value of the evaluation factors to calculate the target value of the electric energy substitution potential. Taking the iron and steel industry as an example, this method is used to excavate the potential. The results show that the method can effectively tap the potential of the electric power industry

Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses

PubMed Central

Harvey, William T.; Benton, Donald J.; Gregory, Victoria; Hall, James P. J.; Daniels, Rodney S.; Bedford, Trevor; Haydon, Daniel T.; Hay, Alan J.; McCauley, John W.; Reeve, Richard

2016-01-01

Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity. Here, sequence and 3-D structural information of hemagglutinin (HA) glycoproteins were analyzed together with corresponding HI assay data for former seasonal influenza A(H1N1) virus isolates (1997–2009) and reference viruses. The models developed identify and quantify the impact of eighteen amino acid substitutions on the antigenicity of HA, two of which were responsible for major transitions in antigenic phenotype. We used reverse genetics to demonstrate the causal effect on antigenicity for a subset of these substitutions. Information on the impact of substitutions allowed us to predict antigenic phenotypes of emerging viruses directly from HA gene sequence data and accuracy was doubled by including all substitutions causing antigenic changes over a model incorporating only the substitutions with the largest impact. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine emerging techniques that predict the evolution of virus populations from one year to the next, leading to stronger theoretical foundations for selection of candidate vaccine viruses. These techniques have great potential to be extended to other antigenically variable pathogens. PMID:27057693

Toxicity of N-substituted aromatics to acetoclastic methanogenic activity in granular sludge

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

Donlon, B.A.; Razo-Flores, E.; Field, J.A.

1995-11-01

N-substituted aromatics are important priority pollutants entering the environment primarily through anthropogenic activities associated associated with the industrial production of dyes, explosives, pestides, and pharmaceuticals. Anaerobic treatment of wastewaters discharged by these industries could potentially be problematical as a result of the high toxicity of N-substituted aromatics. The objective of this study was to examine the structure-toxicity relationship of N-substituted aromatic compounds to acetoclastic methanogenic bacteria. The toxicity was assayed to serum flasks by measuring methane production in granular sludge. Unacclimated cultures were used to minimize the biotransformation of the toxic organic chemicals during the test. The nature and themore » degree of the aromatic substitution were observed to have a profound effect on the toxicity of the test compound. Nitroaromatic compounds were, on the average, over 500-fold more toxic than their corresponding aromatic amines. Considering the facile reduction of nitro groups by anerobic microorganisms, a dramatic detoxification of nitroaromatics towards methanogens can be expected to occur during anaerobic wastewater treatment. While the toxicity exerted by the N-substituted aromatic compounds was closely correlated with compound apolarity (log P), it was observed that at any given log P, N-substituted phenols had a toxicity that was 2 orders of magnitude higher than that of chlorophenols and alkylphenols. This indicates that toxicity due to the chemical reactivity of nitroaromatics is much more important than partitioning effects in bacterial membranes. 41 refs., 3 figs., 1 tab.« less

Whole-Gene Positive Selection, Elevated Synonymous Substitution Rates, Duplication, and Indel Evolution of the Chloroplast clpP1 Gene

PubMed Central

Erixon, Per; Oxelman, Bengt

2008-01-01

Background Synonymous DNA substitution rates in the plant chloroplast genome are generally relatively slow and lineage dependent. Non-synonymous rates are usually even slower due to purifying selection acting on the genes. Positive selection is expected to speed up non-synonymous substitution rates, whereas synonymous rates are expected to be unaffected. Until recently, positive selection has seldom been observed in chloroplast genes, and large-scale structural rearrangements leading to gene duplications are hitherto supposed to be rare. Methodology/Principle Findings We found high substitution rates in the exons of the plastid clpP1 gene in Oenothera (the Evening Primrose family) and three separate lineages in the tribe Sileneae (Caryophyllaceae, the Carnation family). Introns have been lost in some of the lineages, but where present, the intron sequences have substitution rates similar to those found in other introns of their genomes. The elevated substitution rates of clpP1 are associated with statistically significant whole-gene positive selection in three branches of the phylogeny. In two of the lineages we found multiple copies of the gene. Neighboring genes present in the duplicated fragments do not show signs of elevated substitution rates or positive selection. Although non-synonymous substitutions account for most of the increase in substitution rates, synonymous rates are also markedly elevated in some lineages. Whereas plant clpP1 genes experiencing negative (purifying) selection are characterized by having very conserved lengths, genes under positive selection often have large insertions of more or less repetitive amino acid sequence motifs. Conclusions/Significance We found positive selection of the clpP1 gene in various plant lineages to correlated with repeated duplication of the clpP1 gene and surrounding regions, repetitive amino acid sequences, and increase in synonymous substitution rates. The present study sheds light on the controversial issue of whether negative or positive selection is to be expected after gene duplications by providing evidence for the latter alternative. The observed increase in synonymous substitution rates in some of the lineages indicates that the detection of positive selection may be obscured under such circumstances. Future studies are required to explore the functional significance of the large inserted repeated amino acid motifs, as well as the possibility that synonymous substitution rates may be affected by positive selection. PMID:18167545

Relationship between Al content and substitution mechanism of Al-bearing anhydrous bridgmanites

NASA Astrophysics Data System (ADS)

Noda, M.; Inoue, T.; Kakizawa, S.

2017-12-01

It is considered that two substitution mechanisms, Tschermak substitution and oxygen vacancy substitution, exist in MgSiO3 bridgmanite for the incorporation of Al in anhydrous condition. Kubo and Akaogi (2000) has conducted the phase equilibrium experiment in the system MgSiO3-Al2O3, and established the phase diagram up to 28 GPa. However the careful observation in the bridgmanite shows that the chemical compositions are slightly deviated from Tschermak substitution join. The same tendency can be also observed in the run products by Irifune et al. (1996). This result indicates that pure Tschermak substitution bridgmanite cannot be stable even in the MgSiO3-Al2O3 join experiment. However, the previous studies used powder samples as the starting materials, so the absorbed water may affect the results. Therefore, we tried to conduct the experiment in the join MgSiO3-Al2O3 in extremely anhydrous condition to clarify whether the pure Tschermak substitution bridgmanite can be stable or not. In addition, we also examined the stability of oxygen vacancy bridgmanite in the extremely anhydrous condition for the comparison. The high pressure synthesis experiments were conducted at 28 GPa and 1600-1700° for 1hour using a Kawai-type multi-anvil apparatus. Four different Al content samples were prepared as the starting materials along the ideal substitution line of Tschermak (Al=0.025, 0.05, 0.1, 0.15 mol) and oxygen-vacancy (Al=0.025, 0.05, 0.075, 0.1 mol) substitutions, respectively (when total cation of 2). The glass rods were used as the starting materials to eliminate the absorbed water on the sample surface. The chemical compositions of the synthesized bridgmanite could not be measured by EPMA because of small grain size less than submicron. Therefore the chemical compositions were estimated from the result of the XRD pattern by subtracting the amount of the other phases. The estimated chemical compositions of Tschermak substitution bridgmanites were consistent with the ideal compositions. On the other hand, oxygen-vacancy substitution bridgmanite was possible to be existed less than Al=0.25 mol on the basis of total cation of 2. These results show that both Tschermak and oxygen-vacancy substitution bridgmanites can exist in low Al content in anhydrous condition.

Ionic Liquid Epoxy Resin Monomers

NASA Technical Reports Server (NTRS)

Paley, Mark S. (Inventor)

2013-01-01

Ionic liquid epoxide monomers capable of reacting with cross-linking agents to form polymers with high tensile and adhesive strengths. Ionic liquid epoxide monomers comprising at least one bis(glycidyl) N-substituted nitrogen heterocyclic cation are made from nitrogen heterocycles corresponding to the bis(glycidyl) N-substituted nitrogen heterocyclic cations by a method involving a non-nucleophilic anion, an alkali metal cation, epichlorohydrin, and a strong base.

Biological Synthesis of Substituted o-Aminophenols

DTIC Science & Technology

1991-02-01

AMINOPHENOLS FINAL REPORT (November 1, 1987- December 31,1990) Work Performed Under Contract F49620-88-C-0016 Prepared for: I AIR FORCE OFFICE OF...Security Classification) Biological Synthesis of Substituted o- Aminophenols 12. PERSONAL AUTHOR(S) Dr. Terry K. Leib 13 . YP OF REPORT 3. TIME COVERED...0601 0706 high-temperature polymers, o- aminophenols , polvbenzoxazoles. 19. ABSTRACT (Continue on reverse if ne(essary and identify by block number

Rhodium-catalyzed asymmetric construction of quaternary carbon stereocenters: ligand-dependent regiocontrol in the 1,4-addition to substituted maleimides.

PubMed

Shintani, Ryo; Duan, Wei-Liang; Hayashi, Tamio

2006-05-03

A rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to substituted maleimides has been described. The regioselectivity in this reaction is controlled by the choice of ligand (dienes or bisphosphines), and 1,4-adducts with a quaternary stereocenter can be obtained with high regio- and enantioselectivity by the use of (R)-H8-binap.

High-Level Fosfomycin Resistance in Vancomycin-Resistant Enterococcus faecium

PubMed Central

Guo, Yan; Tomich, Adam D.; McElheny, Christi L.; Cooper, Vaughn S.; Tait-Kamradt, Amelia; Wang, Minggui; Hu, Fupin; Rice, Louis B.; Sluis-Cremer, Nicolas

2017-01-01

Of 890 vancomycin-resistant Enterococcus faecium isolates obtained by rectal screening from patients in Pittsburgh, Pennsylvania, USA, 4 had MICs >1,024 μg/mL for fosfomycin. These isolates had a Cys119Asp substitution in the active site of UDP-N-acetylglucosamine enolpyruvyl transferase. This substitution increased the fosfomycin MIC >4-fold and rendered this drug inactive in biochemical assays. PMID:29048285

Asymmetric vinylogous Mukaiyama aldol reaction of isatins under bifunctional organocatalysis: enantioselective synthesis of substituted 3-hydroxy-2-oxindoles.

PubMed

Laina-Martín, Víctor; Humbrías-Martín, Jorge; Fernández-Salas, José A; Alemán, José

2018-03-13

A highly enantioselective organocatalytic vinylogous Mukaiyama aldol reaction of silyloxy dienes and isatins under bifunctional organocatalysis is presented. Substituted 3-hydroxy-2-oxindoles are synthesised in good yields and enantioselectivities. These synthetic intermediates are used for the construction of more complex molecules with biological properties such as the formal synthesis of a CB2 agonist presented.

Raman Spectroscopy of Water-rich Stishovite and Dense High-Pressure Silica up to 55 GPa

NASA Astrophysics Data System (ADS)

Nisr, C.; Shim, S. H.; Leinenweber, K. D.; Chizmeshya, A. V.

2017-12-01

Recent studies have shown that mineral phases such as δ-AlOOH, (Mg,Si)OOH, (Mg,Si,Al)OOH, (Al,Si)O2 and SiO2 with rutile-type or modified rutile-type crystal structures can store large amounts of water and be stable at high pressure and high temperature relevant to the Earth's lower mantle. The Al-H charge coupled substitution has been proposed to explain the large storage capacity of these phases. However, the substitution cannot explain the large water storage found in pure stishovite (Spektor et al., 2011). Instead, an octahedral version of hydrogarnet-like substitution has been proposed for the incorporation of hydrogen in pure stishovite. We have performed Raman spectroscopy measurements on pure hydrous stishovite with 3.2 wt% water up to 55 GPa. At ambient pressure, we found that the OH stretching mode frequencies range between those of low-water aluminous stishovite and δ-AlOOH, suggesting an intermediate strength of hydrogen bonding between these two phases. In the lattice mode range, we observe modes similar to the IR-active modes of anhydrous stishovite after decompression to 1 bar, suggesting Si defects in the crystal structure that activate the inactive modes. Our data show a series of changes at pressures between 24 and 28 GPa, supporting our observation of a phase transition (likely to the CaCl2 type) in X-Ray diffraction measurements (Nisr et al., 2017, JGR). We found that the OH mode of hydrous stishovite has a positive frequency shift with an increase in pressure. The behavior is the opposite to that found in δ-AlOOH, indicating that the OH incorporation mechanism in hydrous silica is different from that of aluminous low-water stishovite and δ-AlOOH, likely through direct substitution (Si ⇄ 4H+). Because the mantle hydrous phases would have complex compositions, our study suggests that the direct substitution should also be considered together with the Al substitution for the deep mantle storage of water.

Self-Substitution and the Temperature Effects on the Electrochemical Performance in the High Voltage Cathode System LiMn 1.5+xNi 0.5-xO 4 (x = 0.1)

DOE PAGES

Xu, Yun; Zhao, Mingyang; Khalid, Syed; ...

2017-05-09

The high voltage cathode material, LiMn 1.6Ni 0.4O 4, was prepared by a polymer-assisted method. The novelty of this paper is the substitution of Ni with Mn, which already exists in the crystal structure instead of other isovalent metal ion dopants which would result in capacity loss. The electrochemical performance testing including stability and rate capability was evaluated. The temperature was found to impose a change on the valence and structure of the cathode materials. Specifically, manganese tends to be reduced at a high temperature of 800 °C and leads to structural changes. The manganese substituted LiMn 1.5Ni 0.5O 4more » (LMN) has proved to be a good candidate material for Li-ion battery cathodes displaying good rate capability and capacity retention. Finally, the cathode materials processed at 550 °C showed a stable performance with negligible capacity loss for 400 cycles.« less

Highly solid-state emissive pyridinium-substituted tetraphenylethylene salts: emission color-tuning with counter anions and application for optical waveguides.

PubMed

Hu, Fang; Zhang, Guanxin; Zhan, Chi; Zhang, Wei; Yan, Yongli; Zhao, Yongsheng; Fu, Hongbing; Zhang, Deqing

2015-03-18

In this paper seven salts of pyridinium-substituted tetraphenylethylene with different anions are reported. They show typical aggregation-induced emission. Crystal structures of three of the salts with (CF(3)SO(2))(2) N(-), CF(3) SO(3)(-), and SbF(6)(-) as the respective counter anions, are determined. The emission behavior of their amorphous and crystalline solids is investigated. Both amorphous and crystalline solids, except for the one with I(-), are highly emissive. Certain amorphous solids are red-emissive with almost the same quantum yields and fluorescence life-times. However, some crystalline solids are found to show different emission colors varying from green to yellow. Thus, their emission colors can be tuned by the counter anions. Furthermore, certain crystalline solids are highly emissive compared to the respective amorphous solids. Such solid-state emission behavior of these pyridinium-substituted tetraphenylethylene salts is interpreted on the basis of their crystal structures. In addition, optical waveguiding behavior of fabricated microrods is presented. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A comparative study of rhodopsin function in the great bowerbird (P tilonorhynchus nuchalis): Spectral tuning and light‐activated kinetics

PubMed Central

van Hazel, Ilke; Dungan, Sarah Z.; Hauser, Frances E.; Morrow, James M.; Endler, John A.

2016-01-01

Abstract Rhodopsin is the visual pigment responsible for initiating the phototransduction cascade in vertebrate rod photoreceptors. Although well‐characterized in a few model systems, comparative studies of rhodopsin function, particularly for nonmammalian vertebrates are comparatively lacking. Bowerbirds are rare among passerines in possessing a key substitution, D83N, at a site that is otherwise highly conserved among G protein‐coupled receptors. While this substitution is present in some dim‐light adapted vertebrates, often accompanying another unusual substitution, A292S, its functional relevance in birds is uncertain. To investigate functional effects associated with these two substitutions, we use the rhodopsin gene from the great bowerbird (Ptilonorhynchus nuchalis) as a background for site‐directed mutagenesis, in vitro expression and functional characterization. We also mutated these sites in two additional rhodopsins that do not naturally possess N83, chicken and bovine, for comparison. Both sites were found to contribute to spectral blue‐shifts, but had opposing effects on kinetic rates. Substitutions at site 83 were found to primarily affect the kinetics of light‐activated rhodopsin, while substitutions at site 292 had a larger impact on spectral tuning. The contribution of substitutions at site 83 to spectral tuning in particular depended on genetic background, but overall, the effects of substitutions were otherwise surprisingly additive, and the magnitudes of functional shifts were roughly similar across all three genetic backgrounds. By employing a comparative approach with multiple species, our study provides new insight into the joint impact of sites 83 and 292 on rhodopsin structure‐function as well as their evolutionary significance for dim‐light vision across vertebrates. PMID:26889650

Isomorphous Substitution of Rare-Earth Elements in Lacunary Apatite Pb8Na2(PO4)6.

PubMed

Get'man, Evgeni I; Loboda, Stanislav N; Ignatov, Alexey V; Prisedsky, Vadim V; Abdul Jabar, Mohammed A B; Ardanova, Lyudmyla I

2016-03-07

The substitution of rare-earth elements (REEs) for Pb in the lacunary apatite Pb8Na2(PO4)6 with void structural channels was studied by means of powder X-ray diffraction (including the Rietveld refinement), scanning electron microscopy, energy-dispersive X-ray microanalysis, and IR spectroscopy and also measurements of the electrical conductivity. The substitution limits (xmax in Pb8-xLnxNa2(PO4)6Ox/2) at 800 °C were found to decrease with the atomic number of the REE from 1.40 for La to 0.12 for Yb with a rapid drop from light to heavy lanthanides (between Gd and Tb). The REE atoms substitute for Pb predominantly at Pb2 sites of the apatite structure according to the scheme 2Pb(2+) + □ → 2Ln(3+) + O(2-), where □ is a vacancy in the structural channel. The substitution in lacunary apatite produces quite different changes in the structural parameters compared with broadly studied alkaline-earth hydroxyapatites. In spite of the much lower ionic radii of REE than that of Pb(2+), the mean distances ⟨Pb1-O⟩ somewhat increase, whereas the distances ⟨Pb2-Pb2⟩ and ⟨Pb2-O4⟩ do not change considerably with the degree of substitution. This implies control of the substitution by not only spatial and charge accommodation of REE ions but also the availability of a stereochemically active 6s(2) electron pair on Pb(2+). The high-temperature electrical conductivity shows dependence on the degree of substitution with a minimum at x = 0.2 indicative of a possible change of the type of conductivity.

A comparative study of rhodopsin function in the great bowerbird (Ptilonorhynchus nuchalis): Spectral tuning and light-activated kinetics.

PubMed

van Hazel, Ilke; Dungan, Sarah Z; Hauser, Frances E; Morrow, James M; Endler, John A; Chang, Belinda S W

2016-07-01

Rhodopsin is the visual pigment responsible for initiating the phototransduction cascade in vertebrate rod photoreceptors. Although well-characterized in a few model systems, comparative studies of rhodopsin function, particularly for nonmammalian vertebrates are comparatively lacking. Bowerbirds are rare among passerines in possessing a key substitution, D83N, at a site that is otherwise highly conserved among G protein-coupled receptors. While this substitution is present in some dim-light adapted vertebrates, often accompanying another unusual substitution, A292S, its functional relevance in birds is uncertain. To investigate functional effects associated with these two substitutions, we use the rhodopsin gene from the great bowerbird (Ptilonorhynchus nuchalis) as a background for site-directed mutagenesis, in vitro expression and functional characterization. We also mutated these sites in two additional rhodopsins that do not naturally possess N83, chicken and bovine, for comparison. Both sites were found to contribute to spectral blue-shifts, but had opposing effects on kinetic rates. Substitutions at site 83 were found to primarily affect the kinetics of light-activated rhodopsin, while substitutions at site 292 had a larger impact on spectral tuning. The contribution of substitutions at site 83 to spectral tuning in particular depended on genetic background, but overall, the effects of substitutions were otherwise surprisingly additive, and the magnitudes of functional shifts were roughly similar across all three genetic backgrounds. By employing a comparative approach with multiple species, our study provides new insight into the joint impact of sites 83 and 292 on rhodopsin structure-function as well as their evolutionary significance for dim-light vision across vertebrates. © 2016 The Protein Society.

High Yields of Hydrogen Production Induced by Meta-Substituted Dichlorophenols Biodegradation from the Green Alga Scenedesmus obliquus

PubMed Central

Papazi, Aikaterini; Andronis, Efthimios; Ioannidis, Nikolaos E.; Chaniotakis, Nikolaos; Kotzabasis, Kiriakos

2012-01-01

Hydrogen is a highly promising energy source with important social and economic implications. The ability of green algae to produce photosynthetic hydrogen under anaerobic conditions has been known for years. However, until today the yield of production has been very low, limiting an industrial scale use. In the present paper, 73 years after the first report on H2-production from green algae, we present a combinational biological system where the biodegradation procedure of one meta-substituted dichlorophenol (m-dcp) is the key element for maintaining continuous and high rate H2-production (>100 times higher than previously reported) in chloroplasts and mitochondria of the green alga Scenedesmus obliquus. In particular, we report that reduced m-dcps (biodegradation intermediates) mimic endogenous electron and proton carriers in chloroplasts and mitochondria, inhibit Photosystem II (PSII) activity (and therefore O2 production) and enhance Photosystem I (PSI) and hydrogenase activity. In addition, we show that there are some indications for hydrogen production from sources other than chloroplasts in Scenedesmus obliquus. The regulation of these multistage and highly evolved redox pathways leads to high yields of hydrogen production and paves the way for an efficient application to industrial scale use, utilizing simple energy sources and one meta-substituted dichlorophenol as regulating elements. PMID:23145057

Comparison of six bone-graft substitutes regarding to cell seeding efficiency, metabolism and growth behaviour of human mesenchymal stem cells (MSC) in vitro.

PubMed

Seebach, Caroline; Schultheiss, Judith; Wilhelm, Kerstin; Frank, Johannes; Henrich, Dirk

2010-07-01

Various synthetic bone-graft substitutes are used commercially as osteoconductive scaffolds in the treatment of bone defects and fractures. The role of bone-graft substitutes is changing from osteoconductive conduits for growth to an delivery system for biologic fracture treatments. Achieving optimal bone regeneration requires biologics (e.g. MSC) and using the correct scaffold incorporated into a local environment for bone regeneration. The need for an unlimited supply with high quality bone-graft substitutes continue to find alternatives for bone replacement surgery. This in vitro study investigates cell seeding efficiency, metabolism, gene expression and growth behaviour of MSC sown on six commercially clinical available bone-graft substitutes in order to define their biological properties: synthetic silicate-substituted porous hydroxyapatite (Actifuse ABX), synthetic alpha-TCP (Biobase), synthetic beta-TCP (Vitoss), synthetic beta-TCP (Chronos), processed human cancellous allograft (Tutoplast) and processed bovines hydroxyapatite ceramic (Cerabone). 250,000 MSC derived from human bone marrow (n=4) were seeded onto the scaffolds, respectively. On days 2, 6 and 10 the adherence of MSC (fluorescence microscopy) and cellular activity (MTT assay) were analysed. Osteogenic gene expression (cbfa-1) was analysed by RT-PCR and scanning electron microscopy was performed. The highest number of adhering cells was found on Tutoplast (e.g. day 6: 110.0+/-24.0 cells/microscopic field; p<0.05) followed by Chronos (47.5+/-19.5, p<0.05), Actifuse ABX (19.1+/-4.4), Biobase (15.7+/-9.9), Vitoss (8.8+/-8.7) and Cerabone (8.1+/-2.2). MSC seeded onto Tutoplast showed highest metabolic activity and gene expression of cbfa-1. These data are confirmed by scanning electron microscopy. The cell shapes varied from round-shaped cells to wide spread cells and cell clusters, depending on the bone-graft substitutes. Processed human cancellous allograft is a well-structured and biocompatible scaffold for ingrowing MSC in vitro. Of all other synthetical scaffolds, beta-tricalcium phosphate (Chronos) have shown the best growth behaviour for MSC. Our results indicate that various bone-graft substitutes influence cell seeding efficiency, metabolic activity and growth behaviour of MSC in different manners. We detected a high variety of cellular integration of MSC in vitro, which may be important for bony integration in the clinical setting. 2010 Elsevier Ltd. All rights reserved.

Scope and mechanism in palladium-catalyzed isomerizations of highly substituted allylic, homoallylic, and alkenyl alcohols.

PubMed

Larionov, Evgeny; Lin, Luqing; Guénée, Laure; Mazet, Clément

2014-12-03

Herein we report the palladium-catalyzed isomerization of highly substituted allylic alcohols and alkenyl alcohols by means of a single catalytic system. The operationally simple reaction protocol is applicable to a broad range of substrates and displays a wide functional group tolerance, and the products are usually isolated in high chemical yield. Experimental and computational mechanistic investigations provide complementary and converging evidence for a chain-walking process consisting of repeated migratory insertion/β-H elimination sequences. Interestingly, the catalyst does not dissociate from the substrate in the isomerization of allylic alcohols, whereas it disengages during the isomerization of alkenyl alcohols when additional substituents are present on the alkyl chain.

SubVis: an interactive R package for exploring the effects of multiple substitution matrices on pairwise sequence alignment

PubMed Central

Coan, Heather B.; Youker, Robert T.

2017-01-01

Understanding how proteins mutate is critical to solving a host of biological problems. Mutations occur when an amino acid is substituted for another in a protein sequence. The set of likelihoods for amino acid substitutions is stored in a matrix and input to alignment algorithms. The quality of the resulting alignment is used to assess the similarity of two or more sequences and can vary according to assumptions modeled by the substitution matrix. Substitution strategies with minor parameter variations are often grouped together in families. For example, the BLOSUM and PAM matrix families are commonly used because they provide a standard, predefined way of modeling substitutions. However, researchers often do not know if a given matrix family or any individual matrix within a family is the most suitable. Furthermore, predefined matrix families may inaccurately reflect a particular hypothesis that a researcher wishes to model or otherwise result in unsatisfactory alignments. In these cases, the ability to compare the effects of one or more custom matrices may be needed. This laborious process is often performed manually because the ability to simultaneously load multiple matrices and then compare their effects on alignments is not readily available in current software tools. This paper presents SubVis, an interactive R package for loading and applying multiple substitution matrices to pairwise alignments. Users can simultaneously explore alignments resulting from multiple predefined and custom substitution matrices. SubVis utilizes several of the alignment functions found in R, a common language among protein scientists. Functions are tied together with the Shiny platform which allows the modification of input parameters. Information regarding alignment quality and individual amino acid substitutions is displayed with the JavaScript language which provides interactive visualizations for revealing both high-level and low-level alignment information. PMID:28674656

A survey of nuclear ribosomal internal transcribed spacer substitution rates across angiosperms: an approximate molecular clock with life history effects

PubMed Central

Kay, Kathleen M; Whittall, Justen B; Hodges, Scott A

2006-01-01

Background A full understanding of the patterns and processes of biological diversification requires the dating of evolutionary events, yet the fossil record is inadequate for most lineages under study. Alternatively, a molecular clock approach, in which DNA or amino acid substitution rates are calibrated with fossils or geological/climatic events, can provide indirect estimates of clade ages and diversification rates. The utility of this approach depends on the rate constancy of molecular evolution at a genetic locus across time and across lineages. Although the nuclear ribosomal internal transcribed spacer region (nrITS) is increasingly being used to infer clade ages in plants, little is known about the sources or magnitude of variation in its substitution rate. Here, we systematically review the literature to assess substitution rate variation in nrITS among angiosperms, and we evaluate possible correlates of the variation. Results We summarize 28 independently calibrated nrITS substitution rates ranging from 0.38 × 10-9 to 8.34 × 10-9 substitutions/site/yr. We find that herbaceous lineages have substitution rates almost twice as high as woody plants, on average. We do not find any among-lineage phylogenetic constraint to the rates, or any effect of the type of calibration used. Within life history categories, both the magnitude of the rates and the variance among rates tend to decrease with calibration age. Conclusion Angiosperm nrITS substitution rates vary by approximately an order of magnitude, and some of this variation can be attributed to life history categories. We make cautious recommendations for the use of nrITS as an approximate plant molecular clock, including an outline of more appropriate phylogenetic methodology and caveats against over interpretation of results. We also suggest that for lineages with independent calibrations, much of the variation in nrITS substitution rates may come from uncertainty in calibration date estimates, highlighting the importance of accurate and/or multiple calibration dates. PMID:16638138

Determining the optimal model for role-substitution in NHS dental services in the United Kingdom.

PubMed

Brocklehurst, Paul; Birch, Stephen; McDonald, Ruth; Tickle, Martin

2013-09-24

Role-substitution describes a model of dental care where Dental Care Professionals (DCPs) provide some of the clinical activity previously undertaken by General Dental Practitioners. This has the potential to increase technical efficiency, the capacity to care and reduce costs. Technical efficiency is defined as the production of the maximum amount of output from a given amount of input so that the service operates at the production frontier i.e. optimal level of productivity. Academic research into technical efficiency is becoming increasingly utilised in health care, although no studies have investigated the efficiency of NHS dentistry or role-substitution in high-street dental practices. The aim of this study is to examine the barriers and enablers that exist for role-substitution in general dental practices in the NHS and to determine the most technically efficient model for role-substitution. A screening questionnaire will be sent to DCPs to determine the type and location of role-substitutive models employed in NHS dental practices in the United Kingdom (UK). Semi-structured interviews will then be conducted with practice owners, DCPs and patients at selected sites identified by the questionnaire. Detail will be recorded about the organisational structure of the dental team, the number of NHS hours worked and the clinical activity undertaken. The interviews will continue until saturation and will record the views and attitudes of the members of the dental team. Final numbers of interviews will be determined by saturation.The second work-stream will examine the technical efficiency of the selected practices using Data Envelopment Analysis and Stochastic Frontier Modeling. The former is a non-parametric technique and is considered to be a highly flexible approach for applied health applications. The latter is parametric and is based on frontier regression models that estimate a conventional cost function. Maximising health for a given level and mix of resources is an ethical imperative for health service planners. This study will determine the technical efficiency of role-substitution and so address one of the key recommendations of the Independent Review of NHS dentistry in England.

Determining the optimal model for role-substitution in NHS dental services in the United Kingdom

PubMed Central

2013-01-01

Background Role-substitution describes a model of dental care where Dental Care Professionals (DCPs) provide some of the clinical activity previously undertaken by General Dental Practitioners. This has the potential to increase technical efficiency, the capacity to care and reduce costs. Technical efficiency is defined as the production of the maximum amount of output from a given amount of input so that the service operates at the production frontier i.e. optimal level of productivity. Academic research into technical efficiency is becoming increasingly utilised in health care, although no studies have investigated the efficiency of NHS dentistry or role-substitution in high-street dental practices. The aim of this study is to examine the barriers and enablers that exist for role-substitution in general dental practices in the NHS and to determine the most technically efficient model for role-substitution. Methods/design A screening questionnaire will be sent to DCPs to determine the type and location of role-substitutive models employed in NHS dental practices in the United Kingdom (UK). Semi-structured interviews will then be conducted with practice owners, DCPs and patients at selected sites identified by the questionnaire. Detail will be recorded about the organisational structure of the dental team, the number of NHS hours worked and the clinical activity undertaken. The interviews will continue until saturation and will record the views and attitudes of the members of the dental team. Final numbers of interviews will be determined by saturation. The second work-stream will examine the technical efficiency of the selected practices using Data Envelopment Analysis and Stochastic Frontier Modeling. The former is a non-parametric technique and is considered to be a highly flexible approach for applied health applications. The latter is parametric and is based on frontier regression models that estimate a conventional cost function. Discussion Maximising health for a given level and mix of resources is an ethical imperative for health service planners. This study will determine the technical efficiency of role-substitution and so address one of the key recommendations of the Independent Review of NHS dentistry in England. PMID:24063247

The Electronic Structure and Formation Energies of Ni-doped CuAlO2 by Density Functional Theory Calculation

NASA Astrophysics Data System (ADS)

Xu, Ying; Li, Fei; Sheng, Wei; Nie, Guo-Zheng; Yuan, Ding-Wang

2014-03-01

The electronic structure and formation energies of Ni-doped CuAlO2 are calculated by first-principles calculations. Our results show that Ni is good for p-type doping in CuAlO2. When Ni is doped into CuAlO2, it prefers to substitute Al-site. NiAl is a shallow acceptor, while NiCu is a deep acceptor and its formation energy is high. Further electronic structure calculations show that strong hybridization happens between Ni-3d and O-2p states for Ni substituting Al-site, while localized Ni-3d states are found for Ni substituting Cu-site.

[Generic drug substitution].

PubMed

Tamir, Orly; Halkin, Hillel; Shemer, Joshua

2006-09-01

The rapidly rising health care expenditures, attributed mainly to the high cost of prescription drugs, have led governments around the world to look to generics as a means of containing costs in the pharmaceutical market. Generic drugs provide a less expensive alternative to brand name drugs due to the elimination of the need to perform lengthy and costly clinical trials, as required for innovative drugs. Essentially, generic substitution of drugs may be performed only after showing unequivocally that the generic formulation is identical in its active ingredients, strength, and route of administration as its innovative counterpart, and that they are bioequivalent to each other. Although the two are in essence the same, generic substitution is occasionally a controversial matter.

A Brillouin Light Scattering Study of Magnetic Excitations.

DTIC Science & Technology

1986-01-30

collaborative project with CNR-Rome, with materials emphasis on substi- tuted LPE garnet thin films . "Localized Canting Models for Substituted Magnetic Oxides...thermal magnons in FeBO 3, exchange in substituted ferrites, parametric spin-waves in epitaxial yttrium iron garnet (YIG. films , surface magnon angle...and surface magnons in thin films . Central to the research was the develooment of a hiqh contrast, high resolu- tion multipassltandem Fabry; Perot

Asymmetric conjugate addition of Grignard reagents to pyranones.

PubMed

Mao, Bin; Fañanás-Mastral, Martín; Feringa, Ben L

2013-01-18

An efficient enantioselective synthesis of lactones was developed based on the catalytic asymmetric conjugate addition (ACA) of alkyl Grignard reagents to pyranones. The use of 2H-pyran-2-one for the first time in the ACA with Grignard reagents allows for a variety of further transformations to access highly versatile building blocks such as β-alkyl substituted aldehydes or β-bromo-γ-alkyl substituted alcohols with excellent regio- and stereoselectivity.

Site Dependency of the High Conductivity of Ga 2 In 6 Sn 2 O 16 : The Role of the 7-Coordinate Site

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

Rickert, Karl; Huq, Ashfia; Lapidus, Saul H.

The 6-coordinated cation site is the fundamental building block of the most effective transparent conducting oxides. Ga2In6Sn2O16, however, maintains 4-, 6-, 7-, and 8-coordinated cation sites and still exhibits desirable transparency and high conductivity. To investigate the potential impact of these alternative sites, we partially replace the Sn in Ga2In6Sn2O16 with Ti, Zr, or Hf and use a combined approach of DFT-based calculations, X-ray diffraction, and neutron diffraction to establish that the substitution occurs preferentially on the 7-coordinate site. In contrast to Sn, the empty d orbitals of Ti, Zr, and Hf promote spd covalency with the surrounding oxygen whichmore » decreases the conductivity. Pairing the substitutional site preference with the magnitude of this decrease demonstrates that the 7-coordinate site is the major contributor to the conductivity. The optical band gaps, in contrast, are shown to be site independent and composition dependent. Continued replacement of Sn after all 7-coordinate Sn has been substituted results in the formation of a 7-coordinate In antisite or replacement of 6-coordinate Sn, depending on the identity of the d0 substitute.« less

Site Dependency of the High Conductivity of Ga 2 In 6 Sn 2 O 16 : The Role of the 7-Coordinate Site

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

Rickert, Karl; Huq, Ashfia; Lapidus, Saul H.

In 6-coordinated cation sites, we find that it is the fundamental building block of the most effective transparent conducting oxides. Ga 2In 6SnO 16, however, maintains 4-, 6-, 7-, and 8-coordinated cation sites and still exhibits desirable transparency and high conductivity. To investigate the potential impact of these alternative sites, we partially replace the Sn in Ga 2In 6Sn 2O 16 with Ti, Zr, or Hf and use a combined approach of density functional theory-based calculations, X-ray diffraction, and neutron diffraction to establish that the substitution occurs preferentially on the 7-coordinate site. Conversely to Sn, the empty d orbitals ofmore » Ti, Zr, and Hf promote spd covalency with the surrounding oxygen, which decreases the conductivity. Pairing the substitutional site preference with the magnitude of this decrease demonstrates that the 7-coordinate site is the V major contributor to conductivity. The optical band gaps, in contrast, are shown to be site-independent and composition-dependent. After all 7-coordinate Sn has been replaced, the continued substitution of Sn results in the formation of a 7-coordinate In antisite or replacement of 6-coordinate Sn, depending on the identity of the d(0) substitute.« less

Site Dependency of the High Conductivity of Ga 2 In 6 Sn 2 O 16 : The Role of the 7-Coordinate Site

DOE PAGES

Rickert, Karl; Huq, Ashfia; Lapidus, Saul H.; ...

2015-11-11

In 6-coordinated cation sites, we find that it is the fundamental building block of the most effective transparent conducting oxides. Ga 2In 6SnO 16, however, maintains 4-, 6-, 7-, and 8-coordinated cation sites and still exhibits desirable transparency and high conductivity. To investigate the potential impact of these alternative sites, we partially replace the Sn in Ga 2In 6Sn 2O 16 with Ti, Zr, or Hf and use a combined approach of density functional theory-based calculations, X-ray diffraction, and neutron diffraction to establish that the substitution occurs preferentially on the 7-coordinate site. Conversely to Sn, the empty d orbitals ofmore » Ti, Zr, and Hf promote spd covalency with the surrounding oxygen, which decreases the conductivity. Pairing the substitutional site preference with the magnitude of this decrease demonstrates that the 7-coordinate site is the V major contributor to conductivity. The optical band gaps, in contrast, are shown to be site-independent and composition-dependent. After all 7-coordinate Sn has been replaced, the continued substitution of Sn results in the formation of a 7-coordinate In antisite or replacement of 6-coordinate Sn, depending on the identity of the d(0) substitute.« less

The effect of spherical nanoparticles on rheological properties of bi-dispersed magnetorheological fluids

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

Kannappan, K. Thiruppathi, E-mail: thiruppathi.ka@gmail.com; Laherisheth, Zarana; Parekh, Kinnari

2015-06-24

In the present investigation, the rheological properties of bi-dispersed magnetorheological (MR) fluid based on Fe{sub 3}O{sub 4} nanosphere and microsphere of iron particles are experimentally investigated. The MR fluid is prepared by substituting nanosphere of 40nm Fe{sub 3}O{sub 4} particles in MR fluids having microsphere iron particles (7-8 μm). Three different weight fractions (0%, 1% and 3%) of nanosphere-microsphere MR fluids are synthesized. In the absence of the magnetic field, substitution of magnetic nanosphere decreases the viscosity lower than without substituted sample at high as well as low shear rate. Upon the application of the magnetic field, the particles alignmore » along the direction of the field, which promotes the yield stress. Here too the yield stress value decreases with magnetic nanosphere substitution. This behaviour is explain based on the inter-particle interaction as well as formation of nanosphere cloud around the magnetic microsphere, which effectively reduces the viscosity and works as weak point when chains are formed. Variation of dynamic yield stress with magnetic field is explained using microscopic model. In any event such fluid does not sediment and is not abrasive so it could be useful if not too high yield stress is needed.« less

A-Site (MCe) Substitution Effects on the Structures and Properties of CaBi4Ti4O15 Ceramics

NASA Astrophysics Data System (ADS)

Yan, Haixue; Li, Chengen; Zhou, Jiaguang; Zhu, Weimin; He, Lianxin; Song, Yuxin

2000-11-01

We investigated the effect of A-site compound substitution on the structures and properties of Ca0.8(MCe)0.1Bi4Ti4O15 (M denotes Li, Na and K) ceramics. The samples were prepared by the conventional ceramic technique. Sintering characteristics of Ca0.8(MCe)0.1Bi4Ti4O15 and CaBi4Ti4O15 ceramics were discussed. X-ray powder diffraction patterns of the three modified CBT-based compounds show a single phase of bismuth oxide layer type structure with m=4. The hysteresis loops of polarization versus electric field of the four compounds were also measured. A-site compound substitution improves the piezoelectric properties and the high-temperature resistivity of these materials. A-site (LiCe) and (KCe) substitution not only improves the Curie temperature but also decreases the temperature coefficient of dielectric constant (TK\\varepsilon). Among the three modified ceramics, only the Curie temperature of Ca0.8(NaCe)0.1Bi4Ti4O15 is lower than that of CaBi4Ti4O15; however, its TK\\varepsilon is the lowest. As a result, all the three modified CBT-based ceramics were found to be excellent high-temperature piezoelectric materials.

Aniracetam reversed learning and memory deficits following prenatal ethanol exposure by modulating functions of synaptic AMPA receptors.

PubMed

Vaglenova, Julia; Pandiella, Noemi; Wijayawardhane, Nayana; Vaithianathan, Tiru; Birru, Sandjay; Breese, Charles; Suppiramaniam, Vishnu; Randal, Clark

2008-04-01

Specific pharmacological treatments are currently not available to address problems resulting from fetal ethanol exposure, described as Fetal Alcohol Syndrome or Fetal Alcohol Spectrum Disorders (FASD). The present study evaluated the therapeutic effects of aniracetam against cognitive deficits in a well-characterized and sensitive FASD Sprague-Dawley rat model. Ethanol, administered orally at a moderate dose (4 g/kg/24 h; 38% v/v) during the entire course of pregnancy, caused severe cognitive deficits in offspring. Furthermore, both progeny genders were affected by a spectrum of behavioral abnormalities, such as a delay in the development of the righting reflex, poor novelty seeking behavior, and high anxiety levels in female rats. Cognitive disabilities, monitored in adult rats by a two-way active avoidance task, correlated well with a significant reduction of AMPA (alpha-amino-3 hydro-5 methyl-isoxazole propionic acid) receptor-mediated miniature excitatory postsynaptic responses (mEPSCs) in the hippocampus. Administration of aniracetam for 10 days (post-natal days (PND) 18-27), at a dose of 50 mg/kg reversed cognitive deficits in both rat genders, indicated by a significant increase in the number of avoidances and the number of 'good learners'. After the termination of the nootropic treatment, a significant increase in both amplitude and frequency of AMPA receptor-mediated mEPSCs in hippocampal CA-1 pyramidal cells was observed. Significant anxiolytic effects on PND 40 also preceded acquisition improvements in the avoidance task. This study provides evidence for the therapeutic potential of aniracetam in reversing cognitive deficits associated with FASD through positive post-natal modulation of AMPA receptors.

Different structural requirements for functional ion pore transplantation suggest different gating mechanisms of NMDA and kainate receptors.

PubMed

Villmann, Carmen; Hoffmann, Jutta; Werner, Markus; Kott, Sabine; Strutz-Seebohm, Nathalie; Nilsson, Tanja; Hollmann, Michael

2008-10-01

Although considerable progress has been made in characterizing the physiological function of the high-affinity kainate (KA) receptor subunits KA1 and KA2, no homomeric ion channel function has been shown. An ion channel transplantation approach was employed in this study to directly test if homomerically expressed KA1 and KA2 pore domains are capable of conducting currents. Transplantation of the ion pore of KA1 or KA2 into GluR6 generated perfectly functional ion channels that allowed characterization of those electrophysiological and pharmacological properties that are determined exclusively by the ion pore of KA1 or KA2. This demonstrates for the first time that KA1 and KA2 ion pore domains are intrinsically capable of conducting ions even in homomeric pore assemblies. NMDA receptors, similar to KA1- or KA2-containing receptors, function only as heteromeric complexes. They are composed of NR1 and NR2 subunits, which both are non-functional when expressed homomerically. In contrast to NR1, the homomeric NR2B ion pore failed to translate ligand binding into pore opening when transplanted into GluR6. Similarly, heteromeric coexpression of the ion channel domains of both NR1 and NR2 inserted into GluR6 failed to produce functional channels. Therefore, we conclude that the mechanism underlying the ion channel opening in the obligatorily heterotetrameric NMDA receptors differs significantly from that in the facultatively heterotetrameric alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and KA receptors.

Combustion synthesized copper-ion substituted FeAl2O4 (Cu0.1Fe0.9Al2O4): A superior catalyst for methanol steam reforming compared to its impregnated analogue

NASA Astrophysics Data System (ADS)

Maiti, Sayantani; Llorca, Jordi; Dominguez, Montserrat; Colussi, Sara; Trovarelli, Alessandro; Priolkar, Kaustubh R.; Aquilanti, Giuliana; Gayen, Arup

2016-02-01

A series of copper ion substituted MAl2O4 (M = Mg, Mn, Fe and Zn) spinels is prepared by a single step solution combustion synthesis (SCS) and tested for methanol steam reforming (MSR). The copper ion substituted Cu0.1Fe0.9Al2O4 appears to be the most active, showing ∼98% methanol conversion at 300 °C with ∼5% CO selectivity at GHSV = 30,000 h-1 and H2O:CH3OH = 1.1. The analogous impregnated catalyst, CuO (10 at%)/FeAl2O4, is found to be much less active. These materials are characterized by XRD, H2-TPR, BET, HRTEM, XPS and XANES analyses. Spinel phase formation is highly facilitated upon Cu-ion substitution and Cu loading beyond 10 at% leads to the formation of CuO as an additional phase. The ionic substitution of copper in FeAl2O4 leads to the highly crystalline SCS catalyst containing Cu2+ ion sites that are shown to be more active than the dispersed CuO nano-crystallites on the FeAl2O4 impregnated catalyst, despite its lower surface area. The as prepared SCS catalyst contains also a portion of copper as Cu1+ that increases when subjected to reforming atmosphere. The MSR activity of the SCS catalyst decreases with time-on-stream due to the sintering of catalyst crystallites as established from XPS and HRTEM analyses.

Modulation of selenium tissue distribution and selenoprotein expression in Atlantic salmon (Salmo salar L.) fed diets with graded levels of plant ingredients.

PubMed

Betancor, Monica B; Dam, Thi M C; Walton, James; Morken, Thea; Campbell, Patrick J; Tocher, Douglas R

2016-04-01

Increased substitution of marine ingredients by terrestrial plant products in aquafeeds has been proven to be suitable for Atlantic salmon farming. However, a reduction in n-3 long-chain PUFA is a consequence of this substitution. In contrast, relatively little attention has been paid to the effects of fishmeal and oil substitution on levels of micronutrients such as Se, considering fish are major sources of this mineral for human consumers. To evaluate the effects of dietary marine ingredient substitution on tissue Se distribution and the expression of Se metabolism and antioxidant enzyme genes, Atlantic salmons were fed three feeds based on commercial formulations with increasing levels of plant proteins (PP) and vegetable oil. Lipid content in flesh did not vary at any sampling point, but it was higher in the liver of 1 kg of fish fed higher PP. Fatty acid content reflected dietary input and was related to oxidation levels (thiobarbituric acid-reactive substances). Liver had the highest Se levels, followed by head kidney, whereas the lowest contents were found in brain and gill. The Se concentration of flesh decreased considerably with high levels of substitution, reducing the added value of fish consumption. Only the brain showed significant differences in glutathione peroxidase, transfer RNA selenocysteine 1-associated protein 1b and superoxide dismutase expression, whereas no significant regulation of Se-related genes was found in liver. Although Se levels in the diets satisfied the essential requirements of salmon, high PP levels led to a reduction in the supply of this essential micronutrient.

Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

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

Zhang, Xinsheng, E-mail: xzhang@iavi.org; Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY; Wallace, Olivia L.

Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions,more » which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance.« less

Influence of SrO substitution for CaO on the properties of bioactive glass S53P4.

PubMed

Massera, Jonathan; Hupa, Leena

2014-03-01

Commercial melt-quenched bioactive glasses consist of the oxides of silicon, phosphorus, calcium and sodium. Doping of the glasses with oxides of some other elements is known to affect their capability to support hydroxyapatite formation and thus bone tissue healing but also to modify their high temperature processing parameters. In the present study, the influence of gradual substitution of SrO for CaO on the properties of the bioactive glass S53P4 was studied. Thermal analysis and hot stage microscopy were utilized to measure the thermal properties of the glasses. The in vitro bioactivity and solubility was measured by immersing the glasses in simulated body fluid for 6 h to 1 week. The formation of silica rich and hydroxyapatite layers was assessed from FTIR spectra analysis and SEM images of the glass surface. Increasing substitution of SrO for CaO decreased all characteristic temperatures and led to a slightly stronger glass network. The initial glass dissolution rate increased with SrO content. Hydroxyapatite layer was formed on all glasses but on the SrO containing glasses the layer was thinner and contained also strontium. The results suggest that substituting SrO for CaO in S53P4 glass retards the bioactivity. However, substitution greater than 10 mol% allow for precipitation of a strontium substituted hydroxyapatite layer.

Discriminative stimulus effects of alpidem, a new imidazopyridine anxiolytic.

PubMed

Sanger, D J; Zivkovic, B

1994-01-01

Alpidem in an imidazopyridine derivative which binds selectively to the omega 1 (BZ1) receptor subtype. It is active in some, but not all, behavioural tests sensitive to benzodiazepine anxiolytics and has clinical anti-anxiety effects. However, in a previous study, it was shown that alpidem did not substitute for chlordiazepoxide in rats trained to discriminate this benzodiazepine. The present experiments were carried out to investigate the discriminative stimulus properties of alpidem in greater detail. In the first experiment rats learned to discriminate a dose of 10 mg/kg alpidem from saline. Acquisition of the discrimination was long and performance unstable. Chlordiazepoxide, clorazepate and zolpidem substituted only partially for alpidem but the effects of the training dose of alpidem were blocked by 10 mg/kg flumazenil. The second experiment established stimulus control more rapidly to a dose of 30 mg/kg alpidem. Alpidem induced dose-related stimulus control, and dose-related and complete substitution for alpidem was produced by zolpidem, abecarnil, CL 218,872, triazolam and suriclone. Partial substitution occurred with chlordiazepoxide, clorazepate and pentobarbital. In most cases, high levels of substitution were produced only by doses which greatly reduced response rates even though the training dose of alpidem produced only modest decreases in rates. Ethanol, buspirone and bretazenil produced very little substitution for alpidem and both flumazenil and bretazenil antagonised the effects of alpidem. In two further experiments alpidem was found to substitute for the stimulus produced by zolpidem (2 mg/kg) but not for that produced by ethanol (1.5 g/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Primary stability of different plate positions and the role of bone substitute in open wedge high tibial osteotomy.

PubMed

Takeuchi, Ryohei; Woon-Hwa, Jung; Ishikawa, Hiroyuki; Yamaguchi, Yuichiro; Osawa, Katsunari; Akamatsu, Yasushi; Kuroda, Koichi

2017-12-01

The purpose of this study was to compare the mechanical fixation strengths of anteromedial and medial plate positions in osteotomy, and clarify the effects of bone substitute placement into the osteotomy site. Twenty-eight sawbone tibia models were used. Four different models were prepared: Group A, the osteotomy site was open and the plate position was anteromedial; Group B, bone substitutes were inserted into the osteotomy site and the plate position was anteromedial; Group C, the osteotomy site was open and the plate position was medial; and Group D, bone substitutes were inserted into the osteotomy site and the plate position was medial. The loading condition ranged from 0 to 800N and one hertz cycles were applied. Changes of the tibial posterior slope angle (TPS), stress on the plate and lateral hinge were measured. The changes in the TPS and the stress on the plate were significantly larger in Group A than in Group C. These were significantly larger in Group A than in Group B, and in Group C than in Group D. There was no significant difference between Group B and Group D, and no significant difference between knee flexion angles of 0° and 10°. Stress on the lateral hinge was significantly smaller when bone substitute was used. A medial plate position was biomechanically superior to an anteromedial position if bone substitute was not used. Bone substitute distributed the stress concentration around the osteotomy gap and prevented an increase in TPS angle regardless of the plate position. Copyright © 2017. Published by Elsevier B.V.

Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis.

PubMed

Visan, Lucian; Sanchez, Violette; Kania, Margaux; de Montfort, Aymeric; de la Maza, Luis M; Ausar, Salvador Fernando

2016-09-01

Chlamydia trachomatis is one of the most common sexually transmitted pathogens and the development of an effective vaccine is highly desirable. The Major Outer Membrane Protein (MOMP) is one of the most abundant and immunogenic chlamydial proteins. Here we investigated the effects of phosphate substitution on the physicochemical and immunochemical properties of an experimental vaccine composed of serovar E recombinant MOMP (rMOMP) and a proprietary adjuvant system SPA08, consisting of aluminum oxyhydroxide (AlOOH) containing the TLR4 agonist E6020. An increase in phosphate substitution in the AlOOH component of the adjuvant markedly decreased the adsorptive coefficient and adsorptive capacity for both Ser E rMOMP and E6020. In vaccine formulations used for immunizations, phosphate substitution induced a decrease in the % adsorption of Ser E rMOMP without affecting the % adsorption of E6020. Immunogenicity studies in CD1 mice showed that an increase in phosphate substitution of the SPA08 adjuvant resulted in an increase in Ser E rMOMP-specific serum total IgG and IgG1 but not IgG2a titers. The degree of phosphate substitution in SPA08 also significantly increased in vitro neutralization concomitant with a decrease in proinflammatory cytokines secreted by Ser E rMOMP-restimulated splenocytes. Taken together, the results of these studies suggest that the degree of phosphate substitution in AlOOH greatly affects the adsorption of E6020 and Ser E rMOMP to AlOOH resulting in significant effects on vaccine-induced cellular and humoral responses.

Effects of salt substitute on home blood pressure differs according to age and degree of blood pressure in hypertensive patients and their families.

PubMed

Hu, Jihong; Zhao, Liancheng; Thompson, Brian; Zhang, Yawei; Wu, Yangfeng

2018-02-05

It is known that home blood pressure (HBP) is a more reliable assessment of hypertension treatments than clinical blood pressure (BP). Despite this, HBP response to a salt substitute has only been evaluated by one study which, did not look at the salt substitute's effect on family members and did not analyze by age, gender, or BP degree. The aim of this current study was to assess the effects of a low-sodium and high-potassium salt substitute on HBP among hypertensive patients and their family members. A total of 220 households (including 220 hypertensive patients and 380 their families) were randomly assigned to the regular salt or salt substitute groups. HBP was measured at the beginning, 3rd, 6th, and 12th months. Among the patients (n = 220), only home systolic blood pressure (HSBP) was significantly reduced, by an adjusted baseline BP of 4.2 mm Hg (95% CI: 1.3-7.0 mm Hg), in the salt substitute group compared with those in the regular salt group at each visit (all P < 0.05). There were no detectable differences between groups for home diastolic blood pressure (HDBP) at any visit. Among the family members, HSBP and HDBP were not significantly different between the groups. Furthermore, Individuals ≥60 years old, hypertensive patients with stage-2 hypertension, family members with hypertension, and women experienced greater HSBP reduction. Older subjects, those with higher blood pressure, and women experienced greater home blood pressure reduction from the salt substitute compared to regular salt.

Theoretical Effects of Substituting Butter with Margarine on Risk of Cardiovascular Disease.

PubMed

Liu, Qing; Rossouw, Jacques E; Roberts, Mary B; Liu, Simin; Johnson, Karen C; Shikany, James M; Manson, JoAnn E; Tinker, Lesley F; Eaton, Charles B

2017-01-01

Several recent articles have called into question the deleterious effects of high animal fat diets due to mixed results from epidemiologic studies and the lack of clinical trial evidence in meta-analyses of dietary intervention trials. We were interested in examining the theoretical effects of substituting plant-based fats from different types of margarine for animal-based fat from butter on the risk of atherosclerosis-related cardiovascular disease (CVD). We prospectively studied 71,410 women, aged 50-79 years, and evaluated their risk for clinical myocardial infarction (MI), total coronary heart disease (CHD), ischemic stroke, and atherosclerosis-related CVD with an average of 13.2 years of follow-up. Butter and margarine intakes were obtained at baseline and year 3 by means of a validated food frequency questionnaire. Cox proportional hazards regression using a cumulative average diet method was used to estimate the theoretical effect of substituting 1 teaspoon/day of three types of margarine for the same amount of butter. Substituting butter or stick margarine with tub margarine was associated with lower risk of MI (HRs = 0.95 and 0.91). Subgroup analyses, which evaluated these substitutions among participants with a single source of spreadable fat, showed stronger associations for MI (HRs = 0.92 and 0.87). Outcomes of total CHD, ischemic stroke, and atherosclerosis-related CVD showed wide confidence intervals but the same trends as the MI results. This theoretical dietary substitution analysis suggests that substituting butter and stick margarine with tub margarine when spreadable fats are eaten may be associated with reduced risk of myocardial infarction.

Theoretical effects of substituting butter with margarine on risk of cardiovascular disease

PubMed Central

Liu, Qing; Rossouw, Jacques E.; Roberts, Mary B.; Liu, Simin; Johnson, Karen C.; Shikany, James M.; Manson, JoAnn E.; Tinker, Lesley F.; Eaton, Charles B.

2017-01-01

Background Several recent papers have called into question the deleterious effects of high animal fat diets due to mixed results from epidemiologic studies and the lack of clinical trial evidence in meta-analyses of dietary intervention trials. We were interested in examining the theoretical effects of substituting plant-based fats from different types of margarine for animal based fat from butter on the risk of atherosclerosis-related cardiovascular disease (CVD). Methods We prospectively studied 71,410 women, aged 50–79 years, and evaluated their risk for clinical myocardial infarction (MI), total coronary heart disease (CHD), ischemic stroke and atherosclerosis-related CVD with an average of 13.2 years of follow-up. Butter and margarine intakes were obtained at baseline and Year 3 by means of a validated food frequency questionnaire. Cox proportional hazards regression using a cumulative average diet method was used to estimate the theoretical effect of substituting 1 teaspoon/day of three types of margarine for the same amount of butter. Results Substituting butter or stick margarine with tub margarine was associated with lower risk of MI (HRs=0.95 and 0.91). Subgroup analyses, which evaluated these substitutions among participants with a single source of spreadable fat, showed stronger associations for MI (HRs=0.92 and 0.87). Outcomes of total CHD, ischemic stroke, and atherosclerosis-related CVD showed wide confidence intervals but the same trends as the MI results. Conclusions This theoretical dietary substitution analysis suggests that substituting butter and stick margarine with tub margarine when spreadable fats are eaten may be associated with reduced risk of myocardial infarction. PMID:27648593

The Impact of Marketing of Breast-Milk Substitutes on WHO-Recommended Breastfeeding Practices.

PubMed

Piwoz, Ellen G; Huffman, Sandra L

2015-12-01

Suboptimal breastfeeding results in 800 000 child deaths annually. There are multiple causes of suboptimal breastfeeding, including marketing of breast-milk substitutes. To describe sales and marketing of breast-milk substitutes and their influence on World Health Organization-recommended breastfeeding behaviors, focusing on low- and middle-income countries. Literature review. Global sales of breast-milk substitutes reached US$40 billion in 2013. Growth in sales exceeds 10% annually in many low- and middle-income countries, while it is close to stagnant in high-income countries. Breast-milk substitutes are marketed directly to consumers via mass media and print advertisements and indirectly via incentives, free supplies, and promotions to and through health workers and facilities, retailers, and policy makers. Internet marketing via company web sites and social media is on the rise. Marketing influences social norms by making formula use seem to be extensive, modern, and comparable to or better than breast milk. Clear evidence of a negative impact is found when breast-milk substitutes are provided for free in maternity facilities and when they are promoted by health workers and in the media. Influences through other channels are plausible, but rigorous studies are lacking. It was not possible with the data available to quantify the impact of marketing relative to other factors on suboptimal breastfeeding behaviors. Marketing remains widespread even in countries that have adopted the International Code of Marketing of Breast-milk Substitutes to restrict such activities. Adoption of stricter regulatory frameworks coupled with independent, quantitative monitoring and compliance enforcement are needed to counter the impacts of formula marketing globally. © The Author(s) 2015.

Physical, chemical and sensory properties of brownies substituted with sweet potato flour (Ipomoea batatas L.) with addition of black cumin oil (Nigella sativa L.)

NASA Astrophysics Data System (ADS)

Ligarnasari, I. P.; Anam, C.; Sanjaya, A. P.

2018-01-01

Effect of addition black cumin oil on the physical (hardness) characteristics, chemical (water, ash, fat, protein, carbohydrate, antioxidant IC50, total phenol and active component) characteristics and sensory (flavor, taste, texture, overall) characteristics of brownies substituted sweet potato flour were investigated. Substituted brownies was added with 0.05%, 0.10%, 0.15%, 0.20% and 0.25% of nigella sativa oil. The result showed that water content, ash, protein, fat, total phenol were increased and carbohydrate, antioxidant IC50 was decreased by the addition of nigella sativa oil. Due to the sensory characteristics, panelist gave the high score for substituted brownies which was added 0.05% nigella sativa oil. The result showed that the best formula of substituted brownies which was added 0.05% of nigella sativa oil had 24.89% water content, 1.19% ash content, 7.54% protein content, 37.79% fat content, 53.06% carbohydrate contain, 1043.6 ppm IC50 antioxidant and 0.22% total phenol. The active component on the brownies using GCMS identification were palmitic acid, oleic acid, lauric acid, theobromine and vitamin E.

Chromatographic methods for determination of S-substituted cysteine derivatives--a comparative study.

PubMed

Kubec, Roman; Dadáková, Eva

2009-10-09

A novel HPLC method for determination of a wide variety of S-substituted cysteine derivatives in Allium species has been developed and validated. This method allows simultaneous separation and quantification of S-alk(en)ylcysteine S-oxides, gamma-glutamyl-S-alk(en)ylcysteines and gamma-glutamyl-S-alk(en)ylcysteine S-oxides in a single run. The procedure is based on extraction of these amino acids and dipeptides by methanol, their derivatization by dansyl chloride and subsequent separation by reversed phase HPLC. The main advantages of the new method are simplicity, excellent stability of derivatives, high sensitivity, specificity and the ability to simultaneously analyze the whole range of S-substituted cysteine derivatives. This method was critically compared with other chromatographic procedures used for quantification of S-substituted cysteine derivatives, namely with two other HPLC methods (derivatization by o-phthaldialdehyde/tert-butylthiol and fluorenylmethyl chloroformate), and with determination by gas chromatography or capillary electrophoresis. Major advantages and drawbacks of these analytical procedures are discussed. Employing these various chromatographic methods, the content and relative proportions of individual S-substituted cysteine derivatives were determined in four most frequently consumed alliaceous vegetables (garlic, onion, shallot, and leek).

Insights from the predicted structural analysis of carborane substituted withaferin A with Indoleamine - 2,3-dioxygenase as a potent inhibitor.

PubMed

Basha, Syed Hussain; Thakur, Abhishek; Samad, Firoz A

2016-01-01

Indoleamine-2,3-dioxygenase (IDO) an immunoregulatory enzyme and emerging as a new therapeutic drug target for the treatment of cancer. Carboranes, an icosahedral arrangement of eleven boron atoms plus one carbon atom with unique pharmacological properties such low toxicity, isosterism with phenyl ring and stability to hydrolysis. On the other hand, carboranes are known to increase the interaction of ligand with non-polar region of the protein provides an excellent platform to explore these carboranes towards designing and development of novel, potent and target specific drug candidates with further enhanced binding affinities. Despite of their many potential applications, molecular modeling studies of carborane-substituted ligands with macromolecules have been rarely reported. Previously, we have demonstrated the promising high binding affinity of Withaferin-A (WA) for IDO. In this present study, we investigated the effect of carborane substitutions on WA compound towards developing novel analogs for target specific IDO inhibition with better potency. Interesting docked poses and molecular interactions for the carborane substituted WA ligands were elucidated. Based on our In-silico studies, carborane substituted at various position of WA has shown enhanced binding affinity towards IDO, worth of considering for further studies.

Insights from the predicted structural analysis of carborane substituted withaferin A with Indoleamine - 2,3-dioxygenase as a potent inhibitor

PubMed Central

Samad, Firoz A

2016-01-01

Indoleamine-2,3-dioxygenase (IDO) an immunoregulatory enzyme and emerging as a new therapeutic drug target for the treatment of cancer. Carboranes, an icosahedral arrangement of eleven boron atoms plus one carbon atom with unique pharmacological properties such low toxicity, isosterism with phenyl ring and stability to hydrolysis. On the other hand, carboranes are known to increase the interaction of ligand with non-polar region of the protein provides an excellent platform to explore these carboranes towards designing and development of novel, potent and target specific drug candidates with further enhanced binding affinities. Despite of their many potential applications, molecular modeling studies of carborane-substituted ligands with macromolecules have been rarely reported. Previously, we have demonstrated the promising high binding affinity of Withaferin-A (WA) for IDO. In this present study, we investigated the effect of carborane substitutions on WA compound towards developing novel analogs for target specific IDO inhibition with better potency. Interesting docked poses and molecular interactions for the carborane substituted WA ligands were elucidated. Based on our In-silico studies, carborane substituted at various position of WA has shown enhanced binding affinity towards IDO, worth of considering for further studies. PMID:28250615

Decoding the Effect of Isobaric Substitutions on Identifying Missing Proteins and Variant Peptides in Human Proteome.

PubMed

Choong, Wai-Kok; Lih, Tung-Shing Mamie; Chen, Yu-Ju; Sung, Ting-Yi

2017-12-01

To confirm the existence of missing proteins, we need to identify at least two unique peptides with length of 9-40 amino acids of a missing protein in bottom-up mass-spectrometry-based proteomic experiments. However, an identified unique peptide of the missing protein, even identified with high level of confidence, could possibly coincide with a peptide of a commonly observed protein due to isobaric substitutions, mass modifications, alternative splice isoforms, or single amino acid variants (SAAVs). Besides unique peptides of missing proteins, identified variant peptides (SAAV-containing peptides) could also alternatively map to peptides of other proteins due to the aforementioned issues. Therefore, we conducted a thorough comparative analysis on data sets in PeptideAtlas Tiered Human Integrated Search Proteome (THISP, 2017-03 release), including neXtProt (2017-01 release), to systematically investigate the possibility of unique peptides in missing proteins (PE2-4), unique peptides in dubious proteins, and variant peptides affected by isobaric substitutions, causing doubtful identification results. In this study, we considered 11 isobaric substitutions. From our analysis, we found <5% of the unique peptides of missing proteins and >6% of variant peptides became shared with peptides of PE1 proteins after isobaric substitutions.

Hydroxycinnamic acid bound arabinoxylans from millet brans-structural features and antioxidant activity.

PubMed

Bijalwan, Vandana; Ali, Usman; Kesarwani, Atul Kumar; Yadav, Kamalendra; Mazumder, Koushik

2016-07-01

Hydroxycinnamic acid bound arabinoxylans (HCA-AXs) were extracted from brans of five Indian millet varieties and response surface methodology was used to optimize the extraction conditions. The optimal condition to obtain highest yield of millet HCA-AXs was determined as follows: time 61min, temperature 66°C, ratio of solvent to sample 12ml/g. Linkage analysis indicated that hydroxycinnamic acid bound arabinoxylan from kodo millet (KM-HCA-AX) contained comparatively low branched arabinoxylan consisting of 14.6% mono-substituted, 1.2% di-substituted and 41.2% un-substituted Xylp residues. The HPLC analysis of millet HCA-AXs showed significant variation in the content of three major bound hydroxycinnamic acids (caffeic, p-coumaric and ferulic acid). The antioxidant activity of millet HCA-AXs were evaluated using three in vitro assay methods (DPPH, FRAP and β-carotene linoleate emulsion assays) which suggested both phenolic acid composition and structural characteristics of arabinoxylans could be correlated to their antioxidant potential, the detailed structural analysis revealed that low substituted KM-HCA-AX exhibited relatively higher antioxidant activity compared to other medium and highly substituted HCA-AXs from finger (FM), proso (PM), barnyard (BM) and foxtail (FOXM) millet. Copyright © 2016. Published by Elsevier B.V.

Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) beta-carboline derivatives.

PubMed

Formagio, Anelise S Nazari; Tonin, Lilian T Düsman; Foglio, Mary Ann; Madjarof, Christiana; de Carvalho, João Ernesto; da Costa, Willian Ferreira; Cardoso, Flávia P; Sarragiotto, Maria Helena

2008-11-15

Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50)<100 microM) for all eight different types of human cancer cell lines tested. The beta-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI(50) values lying in the nanomolar concentration range (GI(50)=10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50)=0.06 microM), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents.

Structure of selenium incorporated in pyrite and mackinawite as determined by XAFS analyses

NASA Astrophysics Data System (ADS)

Diener, A.; Neumann, T.; Kramar, U.; Schild, D.

2012-05-01

Selenium has a toxic potential leading to diseases by ingestion and a radiotoxic potential as 79Se radionuclide if discharged from a high-level nuclear waste repository in deep geological formations into the biosphere. Selenium is often associated with sulfides, such as pyrite, the most important near-surface iron sulfide and constituent of host rocks and bentonite backfills considered for radioactive waste disposal. This study was aimed at investigating the incorporation of Se2- and Se4+ into pyrite and mackinawite to determine the relevance of iron sulfides to Se retention and the type of structural bonding. The syntheses of pyrite and mackinawite occurred via direct precipitation in batches and also produced coatings on natural pyrite in mixed-flow reactor experiments (MFR) under anoxic conditions at Se concentrations in the solutions of up to 10- 3 mol/L. Mineralogical analyses by SEM and XRD reveal the formation of pyrite and mackinawite phases. The average Se2- uptake in pyrite in batch experiments amounts to 98.6%. In MFR syntheses, it reaches 99.5%, both suggesting a high potential for retention. XAFS results indicate a substitution of sulfur by selenide during instantaneous precipitation in highly supersaturated solutions only. In selenide-doted mackinawite S2- was substituted by Se2-, resulting in a mackinawite-type compound. S- is substituted by Se- in selenide-doted pyrite, yielding a FeSSe compound as a slightly distorted pyrite structure. Under slighter supersaturated conditions, XAFS results indicate an incorporation of Se2- and Se4+ predominantly as Se0. This study shows that a substitution of S by Se in iron sulfides is probable only for highly supersaturated solutions under acidic and anoxic conditions. Under closer equilibrium conditions, Se0 is expected to be the most stable species.

Altered virulence of Highly Pathogenic Avian Influenza (HPAI) H5N8 reassortant viruses in mammalian models.

PubMed

Park, Su-Jin; Kim, Eun-Ha; Kwon, Hyeok-Il; Song, Min-Suk; Kim, Se Mi; Kim, Young-Il; Si, Young-Jae; Lee, In-Won; Nguyen, Hiep Dinh; Shin, Ok Sarah; Kim, Chul-Joong; Choi, Young Ki

2018-01-01

Recently identified highly pathogenic avian influenza (HPAI) H5N8 viruses (clade 2.3.4.4) are relatively low to moderately pathogenic in mammalian hosts compared with HPAI H5N1 viruses. In this study, we generated reassortant viruses comprised of A/MD/Korea/W452/2014(H5N8) with substitution of individual genes from A/EM/Korea/W149/2006(H5N1) to understand the contribution of each viral gene to virulence in mammals. Substituting the PB2 gene segment or the NA gene segment of the H5N8 virus by that from the H5N1 virus resulted in significantly enhanced pathogenicity compared with the parental H5N8 virus in mice. Of note, substitution of the PB2 gene segment of the H5N8 virus by that from the H5N1 virus resulted in a 1000-fold increase in virulence for mice compared with the parental virus (MLD 50 decreased from 10 5.8 to 10 2.5 EID 50 ). Further, the W452 W149PB2 virus also induced the highest virus titers in lungs at all time points and the highest levels of inflammatory cytokine responses among all viruses tested. This high virulence phenotype was also confirmed by high viral titers in the respiratory tracts of infected ferrets. Further, a mini-genome assay revealed that W452 W149PB2 has significantly increased polymerase activity (p < 0.001). Taken together, our study demonstrates that a single gene substitution from other avian influenza viruses can alter the pathogenicity of recent H5N8 viruses, and therefore emphasizes the need for intensive monitoring of reassortment events among co-circulating avian and mammalian viruses.

Altered virulence of Highly Pathogenic Avian Influenza (HPAI) H5N8 reassortant viruses in mammalian models

PubMed Central

Park, Su-Jin; Kim, Eun-Ha; Kwon, Hyeok-Il; Song, Min-Suk; Kim, Se Mi; Kim, Young-Il; Si, Young-Jae; Lee, In-Won; Nguyen, Hiep Dinh; Shin, Ok Sarah; Kim, Chul-Joong; Choi, Young Ki

2018-01-01

ABSTRACT Recently identified highly pathogenic avian influenza (HPAI) H5N8 viruses (clade 2.3.4.4) are relatively low to moderately pathogenic in mammalian hosts compared with HPAI H5N1 viruses. In this study, we generated reassortant viruses comprised of A/MD/Korea/W452/2014(H5N8) with substitution of individual genes from A/EM/Korea/W149/2006(H5N1) to understand the contribution of each viral gene to virulence in mammals. Substituting the PB2 gene segment or the NA gene segment of the H5N8 virus by that from the H5N1 virus resulted in significantly enhanced pathogenicity compared with the parental H5N8 virus in mice. Of note, substitution of the PB2 gene segment of the H5N8 virus by that from the H5N1 virus resulted in a 1000-fold increase in virulence for mice compared with the parental virus (MLD50 decreased from 105.8 to 102.5 EID50). Further, the W452W149PB2 virus also induced the highest virus titers in lungs at all time points and the highest levels of inflammatory cytokine responses among all viruses tested. This high virulence phenotype was also confirmed by high viral titers in the respiratory tracts of infected ferrets. Further, a mini-genome assay revealed that W452W149PB2 has significantly increased polymerase activity (p < 0.001). Taken together, our study demonstrates that a single gene substitution from other avian influenza viruses can alter the pathogenicity of recent H5N8 viruses, and therefore emphasizes the need for intensive monitoring of reassortment events among co-circulating avian and mammalian viruses. PMID:28873012

Mechanistically Driven Development of Iridium Catalysts for Asymmetric Allylic Substitution

PubMed Central

Hartwig, John F.; Stanley, Levi M.

2010-01-01

Conspectus Enantioselective allylic substitution reactions comprise some of the most versatile methods for preparing enantiomerically enriched materials. These reactions form products that contain multiple functionalities by creating carbon–nitrogen, carbon–oxygen, carbon–carbon, and carbon–sulfur bonds. For many years, the development of catalysts for allylic substitution focused on palladium complexes. However, studies of complexes of other metals have revealed selectivities that often complement those of palladium systems. Most striking is the observation that reactions with unsymmetrical allylic electrophiles that typically occur with palladium catalysts at the less hindered site of an allylic electrophile occur at the more hindered site with catalysts based on other metals. In this Account, we describe an iridium precursor and a phosphoramidite ligand that catalyze reactions with a particularly broad scope of nucleophiles. The active form of this iridium catalyst is not generated by the simple binding of the phosphoramidite ligand to the metal precursor. Instead, the initial phosphoramidite and iridium precursor react in the presence of base to form a metallacyclic species that is the active catalyst. This species is generated either in situ or separately in isolated form by reactions with added base. The identification of the structure of the active catalyst led to the development of simplified catalysts as well as the most active form of the catalyst now available, which is stabilized by a loosely bound ethylene. Most recently, this structure was used to prepare intermediates containing allyl ligands, the structures of which provide a model for the enantioselectivities discussed here. Initial studies from our laboratory on the scope of iridium-catalyzed allylic substitution showed that reactions of primary and secondary amines, including alkylamines, benzylamines, and allylamines, and reactions of phenoxides and alkoxides occurred in high yields, with high branched-to-linear ratios and high enantioselectivities. Parallel mechanistic studies had revealed the metallacyclic structure of the active catalyst, and subsequent experiments with the purposefully formed metallacycle increased the reaction scope dramatically. Aromatic amines, azoles, ammonia, and amides and carbamates as ammonia equivalents all reacted with high selectivities and yields. Moreover, weakly basic enolates (such as silyl enol ethers) and enolate equivalents (such as enamines) also reacted, and other research groups have used this catalyst to conduct reactions of stabilized carbon nucleophiles in the absence of additional base. One hallmark of the reactions catalyzed by this iridium system is the invariably high enantioselectivity, which reflects a high stereoselectivity for formation of the allyl intermediate. Enantioselectivity typically exceeds 95%, regioselectivity for formation of branched over linear products is usually near 20:1, and yields generally exceed 75% and are often greater than 90%. Thus, the development of iridium catalysts for enantioselective allylic substitution shows how studies of reaction mechanism can lead to a particularly active and a remarkably general system for an enantioselective process. In this case, a readily accessible catalyst effects allylic substitution, with high enantioselectivity and regioselectivity complementary to that of the venerable palladium systems. PMID:20873839

Pressure demagnetization of synthetic Al substituted hematite and its implications for planetary studies

NASA Astrophysics Data System (ADS)

Jiang, Zhaoxia; Rochette, Pierre; Liu, Qingsong; Gattacceca, Jérôme; Yu, Yongjae; Barrón, Vidal; Torrent, José

2013-11-01

Magnetic minerals can undergo high pressures during their formation and subsequent evolution, which can modify both their intrinsic magnetic properties and remanent magnetization. Aluminum-substituted hematite (Al-hematite) occurs in significant proportion in many soils and sediments, especially in temperate and warm areas. In this work we investigated the effect of high hydrostatic pressures on the magnetic remanence of two series of synthetic Al-hematites. A pressure of 1.44 GPa resulted in 50% reduction of the isothermal remanent magnetization (IRM), which was more effective than alternating field (AF) demagnetization with the largest peak field of 120 mT. In addition, repeated application of the same pressure leads to further demagnetization. Aluminum substitution may increase the resistance to the pressure effect by decreasing particle size and generating defects in magnetic lattices, which results in an increase in coercivity. Our study contributes to understanding the effects of pressure on rocks from the interior of Earth and other planets as well as shocked planetary surfaces, which is significant for future planetary studies.

High temperature dissolution of chromium substituted nickel ferrite in nitrilotriacetic acid medium

NASA Astrophysics Data System (ADS)

Sathyaseelan, V. S.; Chandramohan, P.; Velmurugan, S.

2016-12-01

High temperature (HT) dissolution of chromium substituted nickel ferrite was carried out with relevance to the decontamination of nuclear reactors by way of chemical dissolution of contaminated corrosion product oxides present on stainless steel coolant circuit surfaces. Chromium substituted nickel ferrites of composition, NiFe(2-x)CrxO4 (x ≤ 1), was synthetically prepared and characterized. HT dissolution of these oxides was carried out in nitrilotriacetic acid medium at 160 °C. Dissolution was remarkably increased at 160 °C when compared to at 85 °C in a reducing decontamination formulation. Complete dissolution could be achieved for the oxides with chromium content 0 and 0.2. Increasing the chromium content brought about a marked reduction in the dissolution rate. About 40 fold decrease in rate of dissolution was observed when chromium was increased from 0 to 1. The rate of dissolution was not very significantly reduced in the presence of N2H4. Dissolution of oxide was found to be stoichiometric.

Synthesis, characterization and investigation of the photophysical and photochemical properties of highly soluble novel metal-free, zinc(II), and indium(III) phthalocyanines substituted with 2,3,6-trimethylphenoxy moieties.

PubMed

Gürel, Ekrem; Pişkin, Mehmet; Altun, Selçuk; Odabaş, Zafer; Durmuş, Mahmut

2015-04-07

This work presents the synthesis and characterization of metal-free, zinc(II), and indium(III)acetate phthalocyanines substituted with 2,3,6-trimethylphenoxy groups at the peripheral and non-peripheral positions. The photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen generation and photodegradation under light irradiation) properties of these novel phthalocyanines and unsubstituted zinc(II) and indium(III)acetate phthalocyanines were investigated in dimethylformamide solution. The effects of the types of substituents and their positions and the variety of central metal ions on the phthalocyanine core on their spectroscopic, photophysical and photochemical properties were also determined. The studied 2,3,6-trimethylphenoxy substituted metal-free, zinc(II) and indium(III)acetate phthalocyanines especially indium(III)acetate derivatives exhibited appropriate photophysical and photochemical properties such as high singlet oxygen generation and these phthalocyanines can be potential Type II photosensitizers for photodynamic therapy in cancer applications.

Saturated fatty acids and risk of coronary heart disease: modulation by replacement nutrients.

PubMed

Siri-Tarino, Patty W; Sun, Qi; Hu, Frank B; Krauss, Ronald M

2010-11-01

Despite the well-established observation that substitution of saturated fats for carbohydrates or unsaturated fats increases low-density lipoprotein (LDL) cholesterol in humans and animal models, the relationship of saturated fat intake to risk for atherosclerotic cardiovascular disease in humans remains controversial. A critical question is what macronutrient should be used to replace saturated fat. Substituting polyunsaturated fat for saturated fat reduces LDL cholesterol and the total cholesterol to high-density lipoprotein cholesterol ratio. However, replacement of saturated fat by carbohydrates, particularly refined carbohydrates and added sugars, increases levels of triglyceride and small LDL particles and reduces high-density lipoprotein cholesterol, effects that are of particular concern in the context of the increased prevalence of obesity and insulin resistance. Epidemiologic studies and randomized clinical trials have provided consistent evidence that replacing saturated fat with polyunsaturated fat, but not carbohydrates, is beneficial for coronary heart disease. Therefore, dietary recommendations should emphasize substitution of polyunsaturated fat and minimally processed grains for saturated fat.

Synthesis and stereochemical analysis of β-nitromethane substituted γ-amino acids and peptides.

PubMed

Ganesh Kumar, Mothukuri; Mali, Sachitanand M; Gopi, Hosahudya N

2013-02-07

The high diastereoselectivity in the Michael addition of nitromethane to α,β-unsaturated γ-amino esters, crystal conformations of β-nitromethane substituted γ-amino acids and peptides are studied. Results suggest that the N-Boc protected amide NH, conformations of α,β-unsaturated γ-amino esters and alkyl side chains play a crucial role in dictating the high diastereoselectivity of nitromethane addition to E-vinylogous amino esters. Investigation of the crystal conformations of both α,β-unsaturated γ-amino esters and the Michael addition products suggests that an H-C(γ)-C(β)=C(α) eclipsed conformer of the unsaturated amino ester leads to the major (anti) product compared to that of an N-C(γ)-C(β)=C(α) eclipsed conformer. The major diastereomers were separated and subjected to the peptide synthesis. The single crystal analysis of the dipeptide containing β-nitromethane substituted γ-amino acids reveals a helical type of folded conformation with an isolated H-bond involving a nine-atom pseudocycle.

Fabrication and characterization of environmental-friendly Ni1-xRxTiO3 nanopigments with high NIR reflectance

NASA Astrophysics Data System (ADS)

Tong, Yu-Ping; Chen, Zheng; Wang, Hui-Xian; Zhang, Xu-Fang; Ma, Jun-Tao; Chen, Xi

2015-04-01

A series of novel high dispersed environmental-friendly nanopigments based on NiTiO3 doped with rare earth ion such as Y, La, Eu, Sm have been developed. The products were characterized by X-ray diffractometer (XRD), scanning electron microscopy (SEM), commission internationale de l'Eclairage (CIE) 1976 L*α*b* color scales and UV-Vis-near-infrared radiation (NIR) reflectance spectroscopy. The substitution of R3+ for Ni2+ in NiTiO3 can improve the yellowness of pigments, especially for Eu3+ substitution. The sample with the substitution of Eu3+ for Ni2+ processes the highest NIR reflectance and enhances the NIR reflectance to 89.0%. SEM results revealed that the obtained pigments were composed of well-dispersed spherical-like particles with the range of 40-60 nm. EDS results indicated that the distribution of Ni, Ti, R, O element was considerably uniform with no chemical segregation phenomenon.

NMR characterization of sulphur substitution effects in the K xFe 2-ySe 2-zS z high-T c superconductor

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

Torchetti, D. A.; Imai, T.; Lei, H. C.

2012-04-17

We present a⁷⁷ Se NMR study of the effect of S substitution in the high-T c superconductor K xFe 2-ySe 2-zS z in a temperature range up to 250 K. We examine two S concentrations, with z=0.8 (Tc~ 26 K) and z=1.6 (nonsuperconducting). The samples containing sulphur exhibit broader NMR line shapes than the K xFe₂Se₂ sample due to local disorder in the Se environment. Our Knight shift ⁷⁷K data indicate that in all samples, uniform spin susceptibility decreases with temperature, and that the magnitude of the Knight shift itself decreases with increased S concentration. In addition, S substitution progressivelymore » suppresses low-frequency spin fluctuations. None of the samples exhibit an enhancement of low-frequency antiferromagnetic spin fluctuations near T c in 1/T₁T, as seen in FeSe.« less

NMR characterization of sulphur substitution effects in the K xFe 2-ySe 2-xS z high-T c superconductor

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

Torchetti, D. A.; Imai, T.; Lei, H. C.

2012-04-17

We present a 77Se NMR study of the effect of S substitution in the high-T c superconductor K xFe 2-ySe 2-zS z in a temperature range up to 250 K. We examine two S concentrations, with z=0.8 (T c~ 26 K) and z=1.6 (nonsuperconducting). The samples containing sulphur exhibit broader NMR line shapes than the K xFe 2Se 2 sample due to local disorder in the Se environment. Our Knight shift 77K data indicate that in all samples, uniform spin susceptibility decreases with temperature, and that the magnitude of the Knight shift itself decreases with increased S concentration. In addition,more » S substitution progressively suppresses low-frequency spin fluctuations. None of the samples exhibit an enhancement of low-frequency antiferromagnetic spin fluctuations near T c in 1/T 1T, as seen in FeSe.« less

Compost Grown Agaricus bisporus Lacks the Ability to Degrade and Consume Highly Substituted Xylan Fragments

PubMed Central

de Vries, Ronald P.; Gruppen, Harry; Kabel, Mirjam A.

2015-01-01

The fungus Agaricus bisporus is commercially grown for the production of edible mushrooms. This cultivation occurs on compost, but not all of this substrate is consumed by the fungus. To determine why certain fractions remain unused, carbohydrate degrading enzymes, water-extracted from mushroom-grown compost at different stages of mycelium growth and fruiting body formation, were analyzed for their ability to degrade a range of polysaccharides. Mainly endo-xylanase, endo-glucanase, β-xylosidase and β-glucanase activities were determined in the compost extracts obtained during mushroom growth. Interestingly, arabinofuranosidase activity able to remove arabinosyl residues from doubly substituted xylose residues and α-glucuronidase activity were not detected in the compost enzyme extracts. This correlates with the observed accumulation of arabinosyl and glucuronic acid substituents on the xylan backbone in the compost towards the end of the cultivation. Hence, it was concluded that compost grown A. bisporus lacks the ability to degrade and consume highly substituted xylan fragments. PMID:26237450

Ultrastructure of sea urchin calcified tissues after high-pressure freezing and freeze substitution.

PubMed

Ameye, L; Hermann, R; Dubois, P

2000-08-01

The improvements brought by high-pressure freezing/freeze substitution fixation methods to the ultrastructural preservation of echinoderm mineralized tissues are investigated in developing pedicellariae and teeth of the echinoid Paracentrotus lividus. Three freeze substitution (FS) protocols were tested: one in the presence of osmium tetroxide, one in the presence of uranyl acetate, and the last in the presence of gallic acid. FS in the presence of osmium tetroxide significantly improved cell ultrastructure preservation and should especially be used for ultrastructural studies involving vesicles and the Golgi apparatus. With all protocols, multivesicular bodies, suggested to contain Ca(2+), were evident for the first time in skeleton-forming cells. FS in the presence of gallic acid allowed us to confirm the structured and insoluble character of a part of the organic matrix of mineralization in the calcification sites of the tooth, an observation which modifies the current understanding of biomineralization control in echinoderms. Copyright 2000 Academic Press.

Mutational analysis of the transcriptional activator VirG of Agrobacterium tumefaciens.

PubMed Central

Scheeren-Groot, E P; Rodenburg, K W; den Dulk-Ras, A; Turk, S C; Hooykaas, P J

1994-01-01

To find VirG proteins with altered properties, the virG gene was mutagenized. Random chemical mutagenesis of single-stranded DNA containing the Agrobacterium tumefaciens virG gene led with high frequency to the inactivation of the gene. Sequence analysis showed that 29% of the mutants contained a virG gene with one single-base-pair substitution somewhere in the open reading frame. Thirty-nine different mutations that rendered the VirG protein inactive were mapped. Besides these inactive mutants, two mutants in which the vir genes were active even in the absence of acetosyringone were found on indicator plates. A VirG protein with an N54D substitution turned out to be able to induce a virB-lacZ reporter gene to a high level even in the absence of the inducer acetosyringone. A VirG protein with an I77V substitution exhibited almost no induction in the absence of acetosyringone but showed a maximum induction level already at low concentrations of acetosyringone. Images PMID:7961391

Exploring High-Performance n-Type Thermoelectric Composites Using Amino-Substituted Rylene Dimides and Carbon Nanotubes.

PubMed

Wu, Guangbao; Zhang, Zhi-Guo; Li, Yongfang; Gao, Caiyan; Wang, Xin; Chen, Guangming

2017-06-27

Taking advantage of the high electrical conductivity of a single-walled carbon nanotube (SWCNT) and the large Seebeck coefficient of rylene diimide, a convenient strategy is proposed to achieve high-performance n-type thermoelectric (TE) composites containing a SWCNT and amino-substituted perylene diimide (PDINE) or naphthalene diimide (NDINE). The obtained n-type composites display greatly enhanced TE performance with maximum power factors of 112 ± 8 (PDINE/SWCNT) and 135 ± 14 (NDINE/SWCNT) μW m -1 K -2 . A short doping time of 0.5 h can ensure high TE performance. The corresponding TE module consisting of five p-n junctions reaches a large output power of 3.3 μW under a 50 °C temperature gradient. In addition, the n-type composites exhibit high air stability and excellent thermal stability. This design strategy benefits the future fabricating of high-performance n-type TE materials and devices.

Effect of Se substitution on the phase change properties of Ge2Sb2Te5

NASA Astrophysics Data System (ADS)

Shekhawat, Roopali; Rangappa, Ramanna; Gopal, E. S. R.; Ramesh, K.

2018-05-01

Ge2Sb2Te5 popularly known as GST is being explored for non-volatile phase change random access memory(PCRAM) applications. Under high electric field, thin films of amorphous GST undergo a phase change from amorphous to crystalline with a high contrast in electrical resistivity (about 103). The phase change is between amorphous and metastable NaCl structure occurs at about 150°C and not to the stable hexagonal phase which occurs at a high temperature (> 250 °C). In GST, about 50 % of Te substituted by Se (Ge2Sb2Te2.5Se2.5) is found to increase the contrast in electrical resistivity by 7 orders of magnitude (about 4 orders of magnitude higher than GST). The phase transition in Se added GST also found to be between amorphous and the stable hexagonal structure. The threshold voltage at which the Ge2Sb2Te2.5Se2.5 switches to the high conducting state increases to 9V as compared to 2V in GST. Interestingly, the threshold current decrease to 1mA as compared to 1.8mA in GST indicating the Se substitution reduces the power needed for switching between the low and high conducting states. The reduction in power needed for phase change, high contrast in electrical resistivity with high thermal stability makes Ge2Sb2Te2.5Se2.5 as a better candidate for PCRAM.

Nanorelief of the natural cleavage surface of triglycine sulphate crystals with substitutional and interstitial impurities

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

Belugina, N. V.; Gainutdinov, R. V.; Tolstikhina, A. L., E-mail: alla@ns.crys.ras.ru

2011-11-15

Ferroelectric triglycine sulphate crystals (TGS) with substitutional (LADTGS+ADP, DTGS) and interstitial (Cr) impurities have been studied by atomic-force microscopy, X-ray diffraction, and X-ray fluorescence. The nanorelief parameters of the mirror cleavage TGS(010) surface have been measured with a high accuracy. A correlation between the crystal defect density in the bulk and the cleavage surface nanorelief is revealed at the submicrometer level.

Carbamoyl anion-initiated cascade reaction for stereoselective synthesis of substituted α-hydroxy-β-amino amides.

PubMed

Lin, Chao-Yang; Ma, Peng-Ju; Sun, Zhao; Lu, Chong-Dao; Xu, Yan-Jun

2016-01-18

A carbamoyl anion-initiated cascade reaction with acylsilanes and imines has been used to rapidly construct substituted α-hydroxy-β-amino amides. The Brook rearrangement-mediated cascade allows the formation of two C-C bonds and one O-Si bond in a single pot. Using this approach, a range of α-aryl α-hydroxy-β-amino amides has been synthesized in high yields with excellent diastereoselectivities.

Spectrophotometric determination of copper in alkaline solutions and evaluation of some hydroxy-substituted 1,10-phenanthrolines as chromogenic reagents.

PubMed

Dunbar, W E; Schilt, A A

1972-09-01

Seven new hydroxy-substituted 1,10-phenanthroline derivatives have been evaluated as chromogenic reagents for the determination of copper in strongly alkaline solution. The most sensitive of these, 2,9-dimethyl-4,7-dihydroxy-1,10-phenanthroline, has proven to be highly effective in a simple, rapid procedure for determining trace amounts of copper in sodium hydroxide, potassium carbonate, sodium phosphate or ammonium hydroxide.

p-TSA/Base-Promoted Propargylation/Cyclization of β-Ketothioamides for the Regioselective Synthesis of Highly Substituted (Hydro)thiophenes.

PubMed

Nandi, Ganesh Chandra; Singh, Maya Shankar

2016-07-15

Metal-free, p-toluenesulfonic acid (p-TSA)-mediated, straightforward propargylation of β-ketothioamides with aryl propargyl alcohol has been achieved at room temperature. In addition, the reaction also provided thiazole rings as byproducts. Furthermore, the propargylated thioamides undergo intramolecular 1,5-cyclization to afford fully substituted (hydro)thiophenes in the presence of base. Notably, the approach is pot, atom, and step economical (PASE).

Lewis acid tuned facial stereodivergent HDA reactions using beta-substituted N-vinyloxazolidinones.

PubMed

Gohier, Frédéric; Bouhadjera, Keltoum; Faye, Djibril; Gaulon, Catherine; Maisonneuve, Vincent; Dujardin, Gilles; Dhal, Robert

2007-01-18

The [4 + 2] acido-catalyzed heterocycloaddition between new beta-substituted N-vinyl-1,3-oxazolidin-2-ones (with R' = Me, Ar, CH2 Ar) and beta,gamma-unsaturated alpha-ketoesters (R = Ar) afforded heteroadducts with high levels of endo and facial selectivities. A complete reversal of facial differentiation was achieved by varying the Lewis acid, leading to the stereoselective formation of either endo-alpha or endo-beta adducts. [reaction: see text].

Diastereoselective synthesis of enantiopure morpholines by electrophilic selenium-induced 6-exo cyclizations on chiral 3-allyl-2-hydroxymethylperhydro-1,3-benzoxazine derivatives.

PubMed

Pedrosa, Rafael; Andrés, Celia; Mendiguchía, Pilar; Nieto, Javier

2006-11-10

Enantiopure morpholine derivatives have been prepared by selenocyclofunctionalization of chiral 3-allyl-2-hydroxymethyl-substituted perhydro-1,3-benzoxazine derivatives. The cyclization occurs in high yields and diastereoselection, although the temperature of the reaction and the structure of the substituent at C-2 and the substitution pattern of the double bond can modify the regio- and stereochemistry of the final products.

Nano- and micro-scale Bi-substituted iron garnet films for photonics and magneto-optic eddy current defectoscopy

NASA Astrophysics Data System (ADS)

Berzhansky, V. N.; Karavainikov, A. V.; Mikhailova, T. V.; Prokopov, A. R.; Shaposhnikov, A. N.; Shumilov, A. G.; Lugovskoy, N. V.; Semuk, E. Yu.; Kharchenko, M. F.; Lukienko, I. M.; Kharchenko, Yu. M.; Belotelov, V. I.

2017-10-01

Synthesis technology of nano-scale Bi-substituted iron garnets films with high magneto-optic activity for photonics and plasmonics applications were proposed. The micro-scale single-crystal garnet films with different types of magnetic anisotropy as a magneto-optic sensors were synthesized. It was shown that easy-axis anisotropy films demonstrated the best results for visualization of redistribution eddy current magnetic field near defects.

Enhancement of polyisoprene latex production

NASA Technical Reports Server (NTRS)

Bauman, Albert J. (Inventor)

1979-01-01

Production of high molecular weight polyisoprene latex is enhanced by administering to plants, particularly Guayule Plants, an amine containing at least one two-carbon chain substituent and preferably substituted trialkylamine of the general structure: ##STR1## where R.sub.4, R.sub.5 and R.sub.6 are alkyl, preferably ethyl and at least one of R.sub.4, R.sub.5 and R.sub.6 is preferably an electron withdrawing group substituted aryloxy or arylthio ethyl group.

Tailoring the surface properties of LiNi 0.4Mn 0.4Co 0.2O₂ by titanium substitution for improved high voltage cycling performance

DOE PAGES

Wolff-Goodrich, Silas; Xin, Huolin L.; Lin, Feng; ...

2015-07-30

The present research aims to provide insights into the behavior of LiNi0.4Mn0.4Co0.2O2 (NMC442) and LiNi 0.4Mn 0.4Co 0.2O₂ (NMC442-Ti02) cathode materials under galvanostatic cycling to high potentials, in the context of previous work which predicted that Ti-substituted variants should deliver higher capacities and exhibit better cycling stability than the unsubstituted compounds. It is found that NMC cathodes containing Ti show equivalent capacity fading but greater specific capacity than those without Ti in the same potential range. When repeatedly charged to the same degree of delithiation, NMC cathodes containing Ti showed better capacity retention. Soft x-ray absorption spectroscopy (XAS) spectra formore » Mn and Co indicated increased reduction in these elements for NMC cathodes without Ti, indicating that the substitution of Ti for Co acts to suppress the formation of a high impedance rock salt phase at the surface of NMC cathode particles. The results of this study validate the adoption of a facile change to existing NMC chemistries to improve cathode capacity retention under high voltage cycling conditions.« less

A silicon sol-gel approach to the development of forensic blood substitutes: Design Considerations for Research and Training

NASA Astrophysics Data System (ADS)

Stotesbury, Theresa E.

The research and development of synthetic blood substitutes is a reported need within the forensic community. This work contributes to the growing body of knowledge in bloodstain pattern analysis by offering a materials science approach to designing, producing and testing synthetic forensic blood substitutes. A key deliverable from this research is the creation of a robust silicon-based material using the solution-gelation technique that has been validated for controlled passive drip and spatter simulation. The work investigates the physical properties (viscosity, surface tension and density) of forensic blood substitute formulations and describes the similarity in the spreading dynamics of the optimized material to whole human blood. It then explores how blood and other fluids behave in impact simulation using high-speed video analysis and supports the use of the optimized material for spatter simulation. Finally, the work highlights the practical value of the material as an educational tool for both basic and advanced bloodstain experimentation and training.

How to regulate energy levels and hole mobility of spiro-type hole transport materials in perovskite solar cells.

PubMed

Chi, Wei-Jie; Sun, Ping-Ping; Li, Ze-Sheng

2016-10-21

Methoxyaniline-based organic small molecules with three-dimensional structure have been proven as the most promising hole conductor for state-of-the-art perovskite devices. A fundamental understanding of the electronic properties and hole transport behavior of spiro-CPDT analogues, which is dependent on the number and position of the -OCH 3 groups, is significant for their potential applications as hole transport materials of perovskite solar cells. Our results from density functional theory calculations indicate that meta-substitution is more beneficial to reduce the highest occupied molecular orbital (HOMO) levels of molecules compared with ortho- and para-substitution. Furthermore, the hole mobility can be improved by ortho-substitution or mixed ortho- and para-substitution. Most interestingly, it is found that the improvement in hole mobility is at the expense of raising the HOMO level of spiro-CPDT analogues. These results can be useful in the process of designing and synthesizing excellent hole transport materials with suitable HOMO levels and high hole mobility.

Differences in the incorporation of bromodeoxyuridine by human lymphoblastoid cell lines

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

Henderson, E.E.; Strauss, B.

1975-08-01

Long term human lymphoblastoid lines differ in their ability to grow in medium containing bromodeoxyuridine (BrdU) and to incorporate analog into their DNA. Eight Burkitts' lymphoma cell lines divided at least twice in BrdU-containing medium and made DNA in which over 90 percent of the thymidine residues were substituted with analog in both strands. Three infectious mononucleosis-derived lines and 24 lines transformed in vitro were inhibited by BrdU after one cell division and made only hybrid DNA in which one strand was substituted with analog. One out of eight normal individuals from whom long term lines were prepared gave cellmore » lines which divided at least twice in BrdU and gave DNA in which both strands were substituted with analog. It would appear that intrinsic cellular factors regulate the response to BrdU and that Burkitt's tumor lines are characterized by their ability to make stable doubly substituted DNA containing a high proportion of halogenated analog.« less

First-principles study on stability of transition metal solutes in aluminum by analyzing the underlying forces

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

Liu, Wei; Xu, Yichun; Li, Xiangyan

2015-05-07

Although there have been some investigations on behaviors of solutes in metals under strain, the underlying mechanism of how strain changes the stability of a solute is still unknown. To gain such knowledge, first-principles calculations are performed on substitution energy of transition metal solutes in fcc Al host under rhombohedral strain (RS). Our results show that under RS, substitution energy decreases linearly with the increase of outermost d radius r{sub d} of the solute due to Pauli repulsion. The screened Coulomb interaction increases or decreases the substitution energy of a solute on condition that its Pauling electronegativity scale ϕ{sub P}more » is less or greater than that of Al under RS. This paper verifies a linear relation of substitution energy change versus r{sub d} and ϕ{sub P} under RS, which might be instructive for composition design of long life alloys serving in high stress condition.« less

The effect of fluorine substitutions on the refractive index properties for π-conjugated calamitic nematic materials

NASA Astrophysics Data System (ADS)

Arakawa, Yuki; Tsuji, Hideto

2017-06-01

In order to reveal the effect of fluorine substitutions on the refractive index properties for calamitic nematic materials, we carried out a comparative study with respect to non-fluorinated and two types of laterally fluorinated 1,4-bis[4-(hexyloxy)phenyl]ethynylbenzene molecules. Phase transition behaviours were investigated by differential scanning calorimetry and polarised optical microscopy. Additionally, extraordinary and ordinary refractive index and birefringence were evaluated from each single component system. All the analogues exhibited high birefringence values beyond 0.3 at 550 nm, of which an analogue with a fluorine substitution at the central benzene ring showed the highest Δn-value of 0.43. With respect to an analogue with the highest level of fluorination, Δn as well as ne and no values were declined due to decreased order parameter and diluted molecular density. Not only the mesomorphic behaviours but also optical properties strongly relied on the manner of fluorine substitution including the number and position.

Paracrystalline Disorder from Phosphate Ion Orientation and Substitution in Synthetic Bone Mineral.

PubMed

Marisa, Mary E; Zhou, Shiliang; Melot, Brent C; Peaslee, Graham F; Neilson, James R

2016-12-05

Hydroxyapatite is an inorganic mineral closely resembling the mineral phase in bone. However, as a biological mineral, it is highly disordered, and its composition and atomistic structure remain poorly understood. Here, synchrotron X-ray total scattering and pair distribution function analysis methods provide insight into the nature of atomistic disorder in a synthetic bone mineral analogue, chemically substituted hydroxyapatite. By varying the effective hydrolysis rate and/or carbonate concentration during growth of the mineral, compounds with varied degrees of paracrystallinity are prepared. From advanced simulations constrained by the experimental pair distribution function and density functional theory, the paracrystalline disorder prevalent in these materials appears to result from accommodation of carbonate in the lattice through random displacement of the phosphate groups. Though many substitution modalities are likely to occur in concert, the most predominant substitution places carbonate into the mirror plane of an ideal phosphate site. Understanding the mineralogical imperfections of a biologically analogous hydroxyapatite is important not only to potential bone grafting applications but also to biological mineralization processes themselves.

Structural, dielectric and magnetic properties of nickel substituted cobalt ferrite nanoparticles: Effect of nickel concentration

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

Velhal, Ninad B.; Patil, Narayan D.; Puri, Vijaya R., E-mail: vijayapuri1@gmail.com

2015-09-15

Nickel substituted cobalt ferrite nanoparticles with composition Co{sub 1−x}Ni{sub x}Fe{sub 2}O{sub 4} (0.0 ≤ x ≤ 1.0) was synthesized using simple, low temperature auto combustion method. The X-ray diffraction patterns reveal the formation of cubic phase spinel structure. The crystallite size varies from 30-44 nm with the nickel content. Porous and agglomerated morphology of the bulk sample was displayed in the scanning electron microscopy. Micro Raman spectroscopy reveals continuous shift of E{sub g} and E{sub g}(2) stokes line up to 0.8 Ni substitution. The dispersion behavior of the dielectric constant with frequency and the semicircle nature of the impedance spectramore » show the cobalt nickel ferrite to have high resistance. The ferromagnetic nature is observed in all the samples, however, the maximum saturation magnetization was achieved by the 0.4 Ni substituted cobalt ferrite, which is up to the 92.87 emu/gm at 30K.« less

Alkaline earth metallocenes coordinated with ester pendants: synthesis, structural characterization, and application in metathesis reactions.

PubMed

Li, Heng; Zhang, Wen-Xiong; Xi, Zhenfeng

2013-09-16

A variety of ester-substituted cyclopentadiene derivatives have been synthesized by one-pot reactions of 1,4-dilithio-1,3-butadienes, CO, and acid chlorides. Direct deprotonation of the ester-substituted cyclopentadienes with Ae[N(SiMe3 )2 ]2 (Ae=Ca, Sr, Ba) efficiently generated members of a new class of heavier alkaline earth (Ca, Sr, Ba) metallocenes in good to excellent yields. Single-crystal X-ray structural analysis demonstrated that these heavier alkaline earth metallocenes incorporated two intramolecularly coordinated ester pendants and multiply-substituted cyclopentadienyl ligands. The corresponding transition metal metallocenes, such as ferrocene derivatives and half-sandwich cyclopentadienyl tricarbonylrhenium complexes, could be generated highly efficiently by metathesis reactions. The multiply-substituted cyclopentadiene ligands bearing an ester pendant, and the corresponding heavier alkaline earth and transition-metal metallocenes, may have further applications in coordination chemistry, organometallic chemistry, and organic synthesis. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ionic Substitutions in Non-Apatitic Calcium Phosphates

PubMed Central

Laskus, Aleksandra; Kolmas, Joanna

2017-01-01

Calcium phosphate materials (CaPs) are similar to inorganic part of human mineralized tissues (i.e., bone, enamel, and dentin). Owing to their high biocompatibility, CaPs, mainly hydroxyapatite (HA), have been investigated for their use in various medical applications. One of the most widely used ways to improve the biological and physicochemical properties of HA is ionic substitution with trace ions. Recent developments in bioceramics have already demonstrated that introducing foreign ions is also possible in other CaPs, such as tricalcium phosphates (amorphous as well as α and β crystalline forms) and brushite. The purpose of this paper is to review recent achievements in the field of non-apatitic CaPs substituted with various ions. Particular attention will be focused on tricalcium phosphates (TCP) and “additives” such as magnesium, zinc, strontium, and silicate ions, all of which have been widely investigated thanks to their important biological role. This review also highlights some of the potential biomedical applications of non-apatitic substituted CaPs. PMID:29186932

Molecular interaction between lipoteichoic acids and Lactobacillus delbrueckii phages depends on D-alanyl and alpha-glucose substitution of poly(glycerophosphate) backbones.

PubMed

Räisänen, Liisa; Draing, Christian; Pfitzenmaier, Markus; Schubert, Karin; Jaakonsaari, Tiina; von Aulock, Sonja; Hartung, Thomas; Alatossava, Tapani

2007-06-01

Lipoteichoic acids (LTAs) have been shown to act as bacterial counterparts to the receptor binding proteins of LL-H, LL-H host range mutant LL-H-a21, and JCL1032. Here we have used LTAs purified by hydrophobic interaction chromatography from different phage-resistant and -sensitive strains of Lactobacillus delbrueckii subsp. lactis. Nuclear magnetic resonance analyses revealed variation in the degree of alpha-glucosyl and D-alanyl substitution of the 1,3-linked poly(glycerophosphate) LTAs between the phage-sensitive and phage-resistant strains. Inactivation of phages was less effective if there was a high level of D-alanine residues in the LTA backbones. Prior incubation of the LTAs with alpha-glucose-specific lectin inhibited the LL-H phage inactivation. The overall level of decoration or the specific spatial combination of alpha-glucosyl-substituted, D-alanyl-substituted, and nonsubstituted glycerol residues may also affect phage adsorption.

Molecular Interaction between Lipoteichoic Acids and Lactobacillus delbrueckii Phages Depends on d-Alanyl and α-Glucose Substitution of Poly(Glycerophosphate) Backbones▿

PubMed Central

Räisänen, Liisa; Draing, Christian; Pfitzenmaier, Markus; Schubert, Karin; Jaakonsaari, Tiina; von Aulock, Sonja; Hartung, Thomas; Alatossava, Tapani

2007-01-01

Lipoteichoic acids (LTAs) have been shown to act as bacterial counterparts to the receptor binding proteins of LL-H, LL-H host range mutant LL-H-a21, and JCL1032. Here we have used LTAs purified by hydrophobic interaction chromatography from different phage-resistant and -sensitive strains of Lactobacillus delbrueckii subsp. lactis. Nuclear magnetic resonance analyses revealed variation in the degree of α-glucosyl and d-alanyl substitution of the 1,3-linked poly(glycerophosphate) LTAs between the phage-sensitive and phage-resistant strains. Inactivation of phages was less effective if there was a high level of d-alanine residues in the LTA backbones. Prior incubation of the LTAs with α-glucose-specific lectin inhibited the LL-H phage inactivation. The overall level of decoration or the specific spatial combination of α-glucosyl-substituted, d-alanyl-substituted, and nonsubstituted glycerol residues may also affect phage adsorption. PMID:17416656

Opting Out and Buying Out: Wives’ Earnings and Housework Time

PubMed Central

Killewald, Alexandra

2011-01-01

It has been proposed that the negative association between wives’ earnings and their time in housework is due to greater outsourcing of household labor by households with high-earning wives, but this hypothesis has not been tested directly. In a sample of dual-earner married couples in the Consumption and Activities Mail Survey of the Health and Retirement Study (N = 796), use of market substitutes for women’s housework was found to be only weakly associated with wives’ time cooking and cleaning. Furthermore, expenditures on market substitutes explain less than 15% of the earnings–housework time relationship. This suggests that use of market substitutes plays a smaller role in explaining variation in wives’ time in household labor than has previously been hypothesized. PMID:22053115

The long-sought seventeen-electron radical [(C6Me6)Cr(CO)3](+): isolation, crystal structure and substitution reaction.

PubMed

Wang, Wenqing; Wang, Xingyong; Zhang, Zaichao; Yuan, Ningning; Wang, Xinping

2015-05-18

A highly air-sensitive seventeen-electron half-sandwich radical, [(C6Me6)Cr(CO)3](+), which has been long sought over 40 years, was isolated and structurally characterized. EPR spectroscopy and theoretical calculations indicate that the spin density mainly resides on the chromium atom. The radical can undergo a substitution reaction with PPh3 to form a more stable cation, [(C6Me6)Cr(CO)2(PPh3)](+). This work provides a direct observation of the radical process for CO-substitution reactions found in (arene)M(CO)3 (M = Cr, Mo, or W) systems, and suggests that other stable radicals of the type [(arene)M(CO)3](+) are accessible.

Synthesis and evaluation of novel N-H and N-substituted indole-2- and 3-carboxamide derivatives as antioxidants agents.

PubMed

Olgen, Süreyya; Kiliç, Zuhal; Ada, Ahmet O; Coban, Tulay

2007-08-01

We have previously reported on the synthesis of novel indole derivatives where some compounds showed significant antioxidant activity. Here, we report the synthesis of novel N-H and N-substituted indole-2- and 3-carboxamide derivatives and investigated their antioxidant role in order to identify structural characteristics responsible for activity. Although all compounds showed a strong inhibitory (95-100%) effect on superoxide anion (SOD) only compounds 4, 5 and 6 showed simliar potency for the inhibition of lipid peroxidation (81-94%) which revealed that compounds 4, 5 and 6 possessed highly potent antioxidant properties. Substitution in the 1-position of the indole ring caused the significant differences between the activity results regarding lipid peroxidation inhibition.

Quantum Chemical Design Guidelines for Absorption and Emission Color Tuning of fac-Ir(ppy)₃ Complexes.

PubMed

Natori, Yoshiki; Kitagawa, Yasutaka; Aoki, Shogo; Teramoto, Rena; Tada, Hayato; Era, Iori; Nakano, Masayoshi

2018-03-05

The fac -Ir(ppy)₃ complex, where ppy denotes 2-phenylpyridine, is one of the well-known luminescent metal complexes having a high quantum yield. However, there have been no specific molecular design guidelines for color tuning. For example, it is still unclear how its optical properties are changed when changing substitution groups of ligands. Therefore, in this study, differences in the electronic structures and optical properties among several substituted fac -Ir(ppy)₃ derivatives are examined in detail by density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. On the basis of those results, we present rational design guidelines for absorption and emission color tuning by modifying the species of substituents and their substitution positions.

A new synthetic route to the preparation of a series of strong photoreducing agents: fac Tris-ortho-metalated complexes of iridium(III) with substituted 2-phenylpyridines

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

Zhang, Y.; Baer, C.D.; Camaioni-Neto, C.

1991-04-17

A new procedure is reported for the high-yield synthesis of fac-tris-ortho-metalated complexes of Ir(III) with 2-phenylpyridine (Hppy) and with substituted 2-phenylpyridine (R-Hppy) ligands. The reported procedure uses the Ir(III) starting material Ir(acac){sub 3} (acac = 2,4-pentanedionate) and typically produces the fac-tris-ortho-metalated complexes in yields of 40-75%. Each of the complexes formed with substituted phenylpyridines exhibited a luminescence lifetime of approximately 2-5 microseconds in nitrogen-saturated acetonitrile at room temperature, and each complex is characterized by a reversible oxidative wave in cyclic voltammetry in acetonitrile. 42 refs., 1 fig., 1 tab.

Doping mechanism of antinomy in PbWO4

NASA Astrophysics Data System (ADS)

Li, Wensheng; Tang, Tong B.; Feng, Xiqi

2002-01-01

Sb doped PbWO4 (Sb:PWO) shows unique features in its dielectric and visible spectra. We propose that, in low concentration, the dopant enters the lattice as interstitial ions, and at high level it also substitute for W6+ sties. The existence of interstitial ions with relatively high mobility leads to non-negligible dc conductivity, whereas the substitutional impurity produces O23- color centers, which results in absorption at 420 nm, as well as holes hopping among oxygen ions in the Sb-O tetrahedra, that is the origin for the observed dielectric relaxation with an unusually low activation energy of 30±2 meV.

Substituted N-aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors

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

Devadas, Balekudru; Selness, Shaun R.; Xing, Li

2012-02-28

A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (>90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-{alpha} in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model.

Highly efficient water-mediated approach to access benzazoles: metal catalyst and base-free synthesis of 2-substituted benzimidazoles, benzoxazoles, and benzothiazoles.

PubMed

Bala, Manju; Verma, Praveen Kumar; Sharma, Deepika; Kumar, Neeraj; Singh, Bikram

2015-05-01

An efficient water-catalyzed method has been developed for the synthesis of 2-substituted benzimidazoles, benzoxazoles, and benzothiazoles in one step. The present method excludes the usage of toxic metal catalysts and bases to produce benzazoles in good to excellent yields. An efficient and versatile water-mediated method has been established for the synthesis of various 2-arylbenzazoles. The present protocol excludes the usage of any catalyst and additive provided excellent selectivities and yields with high functional group tolerance for the synthesis of 2-arylated benzimidazoles, benzoxazoles, and benzothiazoles. Benzazolones were also synthesized using similar reaction protocol.

Acquiring High-Performance Deep-Blue OLED Emitters through an Unexpected Blueshift Color-Tuning Effect Induced by Electron-Donating -OMe Substituents.

PubMed

Peng, Song; Zhao, Yihuan; Fu, Caixia; Pu, Xuemei; Zhou, Liang; Huang, Yan; Lu, Zhiyun

2018-06-07

A series of blue-emissive 7-(diphenylamino)-4-phenoxycoumarin derivatives bearing -CF 3 , -OMe, or -N(Me) 2 substituents on the phenoxy subunit were synthesized. Although both the -CF 3 and -N(Me) 2 modifications were found to trigger redshifted fluorescence, the -OMe substitution was demonstrated to exert an unexpected blueshift color-tuning effect toward the deep-blue region. The reason is that the moderate electron-donating -OMe group can endow coumarins with unaltered HOMO but elevated LUMO energy levels. Moreover, the -OMe substitution was found to be beneficial to the thermal stability of these coumarins. Therefore, the trimethoxy-substituted objective compound can act as a high-performance deep-blue organic light-emitting diode (OLED) emitter, and OLED based on it emits deep-blue light with CIE coordinates of (0.148, 0.084), maximum luminance of 7800 cd m -2 , and maximum external quantum efficiency of 5.1 %. These results not only shed light on the molecular design strategy for high-performance deep-blue OLED emitters through color-tuning, but also show the perspective of coumarin derivatives as deep-blue OLED emitters. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A High-Coverage Yersinia pestis Genome from a Sixth-Century Justinianic Plague Victim

PubMed Central

Feldman, Michal; Harbeck, Michaela; Keller, Marcel; Spyrou, Maria A.; Rott, Andreas; Trautmann, Bernd; Scholz, Holger C.; Päffgen, Bernd; Peters, Joris; McCormick, Michael; Bos, Kirsten; Herbig, Alexander; Krause, Johannes

2016-01-01

The Justinianic Plague, which started in the sixth century and lasted to the mid eighth century, is thought to be the first of three historically documented plague pandemics causing massive casualties. Historical accounts and molecular data suggest the bacterium Yersinia pestis as its etiological agent. Here we present a new high-coverage (17.9-fold) Y. pestis genome obtained from a sixth-century skeleton recovered from a southern German burial site close to Munich. The reconstructed genome enabled the detection of 30 unique substitutions as well as structural differences that have not been previously described. We report indels affecting a lacl family transcription regulator gene as well as nonsynonymous substitutions in the nrdE, fadJ, and pcp genes, that have been suggested as plague virulence determinants or have been shown to be upregulated in different models of plague infection. In addition, we identify 19 false positive substitutions in a previously published lower-coverage Y. pestis genome from another archaeological site of the same time period and geographical region that is otherwise genetically identical to the high-coverage genome sequence reported here, suggesting low-genetic diversity of the plague during the sixth century in rural southern Germany. PMID:27578768

Novel mutations and mutation combinations of ryanodine receptor in a chlorantraniliprole resistant population of Plutella xylostella (L.)

PubMed Central

Guo, Lei; Liang, Pei; Zhou, Xuguo; Gao, Xiwu

2014-01-01

A previous study documented a glycine to glutamic acid mutation (G4946E) in ryanodine receptor (RyR) was highly correlated to diamide insecticide resistance in field populations of Plutella xylostella (Lepidoptera: Plutellidae). In this study, a field population collected in Yunnan province, China, exhibited a 2128-fold resistance to chlorantraniliprole. Sequence comparison between resistant and susceptible P. xylostella revealed three novel mutations including a glutamic acid to valine substitution (E1338D), a glutamine to leucine substitution (Q4594L) and an isoleucine to methionine substitution (I4790M) in highly conserved regions of RyR. Frequency analysis of all four mutations in this field population showed that the three new mutations showed a high frequency of 100%, while the G4946E had a frequency of 20%. Furthermore, the florescent ligand binding assay revealed that the RyR containing multiple mutations displayed a significantly lower affinity to the chlorantraniliprole. The combined results suggested that the co-existence of different combinations of the four mutations was involved in the chlorantraniliprole resistance. An allele-specific PCR based method was developed for the diagnosis of the four mutations in the field populations of P. xylostella. PMID:25377064

Structure evolution upon chemical and physical pressure in (Sr{sub 1−x}Ba{sub x}){sub 2}FeSbO{sub 6}

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

Tiittanen, T.; Karppinen, M., E-mail: maarit.karppinen@aalto.fi

Here we demonstrate the gradual structural transformation from the monoclinic I2/m to tetragonal I4/m, cubic Fm-3m and hexagonal P6{sub 3}/mmc structure upon the isovalent larger-for-smaller A-site cation substitution in the B-site ordered double-perovskite system (Sr{sub 1−x}Ba{sub x}){sub 2}FeSbO{sub 6}. This is the same transformation sequence previously observed up to Fm-3m upon heating the parent Sr{sub 2}FeSbO{sub 6} phase to high temperatures. High-pressure treatment, on the other hand, transforms the hexagonal P6{sub 3}/mmc structure of the other end member Ba{sub 2}FeSbO{sub 6} back to the cubic Fm-3m structure. Hence we may conclude that chemical pressure, physical pressure and decreasing temperature allmore » work towards the same direction in the (Sr{sub 1−x}Ba{sub x}){sub 2}FeSbO{sub 6} system. Also shown is that with increasing Ba-for-Sr substitution level, i.e. with decreasing chemical pressure effect, the degree-of-order among the B-site cations, Fe and Sb, decreases. - Graphical abstract: In the (Sr{sub 1−x}Ba{sub x}){sub 2}FeSbO{sub 6} double-perovskite system the gradual structural transformation from the monoclinic I2/m to tetragonal I4/m, cubic Fm-3m and hexagonal P6{sub 3}/mmc structure is seen upon the isovalent larger-for-smaller A-site cation substitution. High-pressure treatment under 4 GPa extends stability of the cubic Fm-3m structure within a wider substitution range of x. - Highlights: • Gradual structural transitions upon A-cation substitution in (Sr{sub 1−x}Ba{sub x}){sub 2}FeSbO{sub 6.} • With increasing x structure changes from I2/m to I4/m, Fm-3m and P6{sub 3}/mmc. • Degree of B-site order decreases with increasing x and A-site cation radius. • High-pressure treatment extends cubic Fm-3m phase stability for wider x range. • High-pressure treatment affects bond lengths mostly around the A-cation.« less

In vitro genotoxicity of asbestos substitutes induced by coupled stimulation of dissolved high-valence ions and oxide radicals.

PubMed

Huo, Tingting; Dong, Faqin; Deng, Jianjun; Zhang, Qingbi; Ye, Wei; Zhang, Wei; Wang, Pingping; Sun, Dongping

2017-08-01

The wide use of asbestos and its substitutes has given rise to studies on their possible harmful effects on human health and environment. However, their toxic effects remain unclear. The present study was aimed to disclose the coupled effects of dissolved high-valence ions and oxide radicals using the in vitro cytotoxicity and genotoxicity of chrysotile (CA), nano-SiO 2 (NS), ceramic fiber (CF), glass fiber (GF), and rock wool (RW) on Chinese hamster lung cells V79. All samples induced cell mortality correlated well with the chemical SiO 2 content of asbestos substitutes and the amount of dissolved Si. Alkali or alkaline earth metal elements relieved mortality of V79 cells; Al 2 O 3 reinforced toxicity of materials. Asbestos substitutes generated lasting, increasing amount of acellular ·OH which formed at the fiber surface at sites with loose/unsaturated bonds, as well as by catalytic reaction through dissolved iron. Accumulated mechanical and radical stimulation induced the intracellular reactive oxygen species (ROS) elevation, morphology change, and deviating trans-membrane ion flux. The cellular ROS appeared as NS > GF > CF ≈ CA > RW, consistent with cell mortality rather than with acellular ·OH generation. Chromosomal and DNA lesions in V79 cells were not directly associated with the cellular ROS, while influenced by dissolved high-valence irons in the co-culture medium. In conclusion, ions from short-time dissolution of dust samples and the generation of extracellular ·OH presented combined effects in the elevation of intracellular ROS, which further synergistically induced cytotoxicity and genotoxicity.

Polymorphisms A387P in thrombospondin-4 and N700S in thrombospondin-1 perturb calcium binding sites.

PubMed

Stenina, Olga I; Ustinov, Valentin; Krukovets, Irene; Marinic, Tina; Topol, Eric J; Plow, Edward F

2005-11-01

Recent genetic studies have associated members of the thrombospondin (TSP) gene family with premature cardiovascular disease. The disease-associated polymorphisms lead to single amino acid changes in TSP-4 (A387P) and TSP-1 (N700S). These substitutions reside in adjacent domains of these highly homologous proteins. Secondary structural predictive programs and the homology of the domains harboring these amino acid substitutions to those in other proteins pointed to potential alterations of putative Ca2+ binding sites that reside in close proximity to the polymorphic amino acids. Since Ca2+ binding is critical for the structure and function of TSP family members, direct evidence for differences in Ca2+ binding by the polymorphic forms was sought. Using synthetic peptides and purified recombinant variant fragments bearing the amino acid substitutions, we measured differences in Tb3+ luminescence as an index of Ca2+ binding. The Tb3+ binding constants placed the TSP-1 region affected by N700S polymorphism among other high-affinity Ca2+ binding sites. The affinity of Ca2+ binding was lower for peptides (3.5-fold) and recombinant fragments (10-fold) containing the S700 vs. the N700 form. In TSP-4, the P387 form acquired an additional Ca2+ binding site absent in the A387 form. The results of our study suggest that both substitutions (A387P in TSP-4 and N700S in TSP-1) alter Ca2+ binding properties. Since these substitutions exert the opposite effects on Ca2+ binding, a decrease in TSP-1 and an increase in TSP-4, the two TSP variants are likely to influence cardiovascular functions in distinct but yet pathogenic ways.

The Influence of Fe Substitution in Lanthanum Calcium Cobalt Oxide on the Oxygen Evolution Reaction in Alkaline Media

DOE PAGES

Abreu-Sepulveda, Maria A.; Dhital, Chetan; Huq, Ashfia; ...

2016-07-30

The effect due to systematic substitution of cobalt by iron in La 0.6Ca 0.4Co 1-xFe xO 3 towards the oxygen evolution reaction(OER) in alkaline media has been investigated. We synthesized these compounds by a facile glycine-nitrate synthesis and the phase formation was confirmed by X-ray diffraction and Neutron Diffraction elemental analysis. The apparent OER activity was evaluated by quasi steady state current measurements in alkaline media using a traditional three-electrode cell. X-ray photoelectron spectroscopy shows iron substitution causes an increase in the surface concentration of various cobalt oxidation states. Tafel slope in the vicinity of 60 mV/decade and electrochemical reactionmore » order towards OH- near unity were achieved for the unsubstituted La 0.6Ca 0.4CoO 3. Moreover, a decrease in the Tafel slope to 49 mV/decade was observed when iron is substituted in high amounts in the perovskite structure. The area specific current density showed dependence on the Fe fraction, however the relationship of specific current density with Fe fraction is not linear. High Fe substitutions, La 0.6Ca 0.4Co 0.2Fe 0.8O 3 and La 0.6Ca 0.4Co 0.1Fe 0.9O 3 showed higher area specific activity towards OER than La 0.6Ca 0.4CoO 3 or La 0.6Ca 0.4FeO 3. Finally, we believe iron inclusion in the cobalt sites of the perovskite helps decrease the electron transfer barrier and facilitates the formation of cobalt-hydroxide at the surface. Possible OER mechanisms based on the observed kinetic parameters will be discussed.« less

Emergence of Avian Influenza Viruses with Enhanced Transcription Activity by a Single Amino Acid Substitution in the Nucleoprotein during Replication in Chicken Brains ▿

PubMed Central

Tada, Tatsuya; Suzuki, Koutaro; Sakurai, Yu; Kubo, Masanori; Okada, Hironao; Itoh, Toshihiro; Tsukamoto, Kenji

2011-01-01

To explore the genetic basis of the pathogenesis and adaptation of avian influenza viruses (AIVs) to chickens, the A/duck/Yokohama/aq10/2003 (H5N1) (DkYK10) virus was passaged five times in the brains of chickens. The brain-passaged DkYK10-B5 caused quick death of chickens through rapid and efficient replication in tissues, accompanied by severe apoptosis. Genome sequence comparison of two viruses identified a single amino acid substitution at position 109 in NP from isoleucine to threonine (NP I109T). By analyzing viruses constructed by the reverse-genetic method, we established that the NP I109T substitution also contributed to increased viral replication and polymerase activity in chicken embryo fibroblasts, but not in duck embryo fibroblasts. Real-time RT-PCR analysis demonstrated that the NP I109T substitution enhances mRNA synthesis quickly and then cRNA and viral RNA (vRNA) synthesis slowly. Next, to determine the mechanism underlying the appearance of the NP I109T substitution during passages, four H5N1 highly pathogenic AIVs (HPAIVs) were passaged in the lungs and brains of chicken embryos. Single-nucleotide polymorphism analysis, together with a database search, suggests that the NP I109T mutation would be induced frequently during replication of HPAIVs in brains, but not in lungs. These results demonstrate that the amino acid at position 109 in NP enhances viral RNA synthesis and the pathogenicity of highly pathogenic avian influenza viruses in chickens and that the NP mutation emerges quickly during replication of the viruses in chicken brains. PMID:21795332

Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients.

PubMed

Lucas, Philippe; Walsh, Zach

2017-04-01

In 2014 Health Canada replaced the Marihuana for Medical Access Regulations (MMAR) with the Marihuana for Medical Purposes Regulations (MMPR). One of the primary changes in the new program has been to move from a single Licensed Producer (LP) of cannabis to multiple Licensed Producers. This is the first comprehensive survey of patients enrolled in the MMPR. Patients registered to purchase cannabis from Tilray, a federally authorized Licenced Producer (LP) within the MMPR, were invited to complete an online survey consisting of 107 questions on demographics, patterns of use, and cannabis substitution effect. The survey was completed by 271 respondents. Cannabis is perceived to be an effective treatment for diverse conditions, with pain and mental health the most prominent. Findings include high self-reported use of cannabis as a substitute for prescription drugs (63%), particularly pharmaceutical opioids (30%), benzodiazepines (16%), and antidepressants (12%). Patients also reported substituting cannabis for alcohol (25%), cigarettes/tobacco (12%), and illicit drugs (3%). A significant percentage of patients (42%) reported accessing cannabis from illegal/unregulated sources in addition to access via LPs, and over half (55%) were charged to receive a medical recommendation to use cannabis, with nearly 25% paying $300 or more. The finding that patients report its use as a substitute for prescription drugs supports prior research on medical cannabis users; however, this study is the first to specify the classes of prescription drugs for which cannabis it is used as a substitute, and to match this substitution to specific diagnostic categories. The findings that some authorized patients purchase cannabis from unregulated sources and that a significant percentage of patients were charged for medical cannabis recommendations highlight ongoing policy challenges for this federal program. Copyright © 2017 Elsevier B.V. All rights reserved.

Fish mislabelling in France: substitution rates and retail types.

PubMed

Bénard-Capelle, Julien; Guillonneau, Victoire; Nouvian, Claire; Fournier, Nicolas; Le Loët, Karine; Dettai, Agnès

2015-01-01

Market policies have profound implications for consumers as well as for the management of resources. One of the major concerns in fish trading is species mislabelling: the commercial name used does not correspond to the product, most often because the product is in fact a cheaper or a more easily available species. Substitution rates depend heavily on species, some often being sold mislabelled while others rarely or never mislabelled. Rates also vary largely depending on countries. In this study, we analyse the first market-wide dataset collected for France, the largest sea food market in Europe, for fish species substitution. We sequenced and analysed 371 samples bearing 55 commercial species names, collected in fishmonger shops, supermarkets and restaurants; the largest dataset assembled to date in an European country. Sampling included fish fillets, both fresh and frozen, and prepared meals. We found a total of 14 cases of mislabelling in five species: bluefin tuna, cod, yellowfin tuna, sole and seabream, setting the overall substitution rate at 3.7% CI [2.2-6.4], one of the lowest observed for comparable surveys with large sampling. We detected no case of species mislabelling among the frozen fillets or in industrially prepared meals, and all the substitutions were observed in products sold in fishmongers shops or restaurants. The rate of mislabelling does not differ between species, except for bluefin tuna. Despite a very small sample size ( n = 6), the rate observed for this species (83.3% CI [36-99]) stands in sharp contrast with the low substitution rate observed for the other substituted species. In agreement with studies from other countries, this work shows that fish mislabelling can vary greatly within a country depending on the species. It further suggests that more efforts should be directed to the control of high value species like bluefin tuna.

Traumatic strictures of the posterior urethra in boys with special reference to recurrent strictures.

PubMed

Aggarwal, Satish Kumar; Sinha, Shandip K; Kumar, Arun; Pant, Nitin; Borkar, Nitin Kumar; Dhua, Anjan

2011-06-01

We report 18 years' experience of traumatic urethral strictures in boys with emphasis on recurrent strictures. Thirty-four boys with pelvic fracture urethral strictures underwent 35 repairs: 23 in the primary group (initial suprapubic cystostomy, but no urethral repair) and 12 in the re-do group (previously failed attempt(s) at urethroplasty elsewhere). The median age at operation and stricture length was 8.4 years and 3 cm in the primary and 9 years and 5.4 cm in the re-do group, respectively. Anastomotic urethroplasty was performed wherever possible, or failing this a substitution urethroplasty. Median follow up was 9 years for primary group and 8 years for re-do group. Primary group: urethroplasty was successful in 22/23, with 10 by perineal and 13 by additional transpubic approach. Two have stress incontinence. Erectile function is unchanged in all and upper tracts are maintained. One had recurrent stricture. Re-do group (12 including 1 recurrence from primary group): anastomotic urethroplasty was done in 5 and substitution urethroplasty in 7. Patients needing substitution had long stricture (>5 cm), stricture extending to distal bulb, or high riding bladder neck. All patients are voiding urethrally. Two patients with substitution required dilatation for early re-stenosis. One appendix substitution required delayed revision. Two have stress incontinence. Erectile function was unaffected. Upper tracts are maintained. Anastomotic urethroplasty was successful in over 95% of primary cases. In re-do cases it was viable in only 41% of cases; the rest required substitution urethroplasty. Urethral substitution also gave acceptable results. Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

A density functional theory study of the structure of pure-silica and aluminium-substituted MFI nanosheets

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

Hernandez-Tamargo, Carlos E.; Roldan, Alberto; School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT

The layered MFI zeolite allows a straightforward hierarchization of the pore system which accelerates mass transfer and increases its lifetime as a catalyst. Here, we present a theoretical study of the structural features of the pure-silica and aluminium-substituted MFI nanosheets. We have analysed the effects of aluminium substitution on the vibrational properties of silanols as well as the features of protons as counter-ions. The formation of the two-dimensional system did not lead to appreciable distortions within the framework. Moreover, the effects on the structure due to the aluminium dopants were the same in both the bulk and the slab. Themore » principal differences were related to the silanol groups that form hydrogen-bonds with neighbouring aluminium-substituted silanols, whereas intra-framework hydrogen-bonds increase the stability of aluminium-substituted silanols toward dehydration. Thus, we have complemented previous experimental and theoretical studies, showing the lamellar MFI zeolite to be a very stable material of high crystallinity regardless of its very thin structure. - Graphical abstract: The structure of MFI zeolite nanosheet was investigated using Density Functional Theory. The results showed no differences against the bulk-type material upon aluminium doping. The aluminium-substituted silanol dehydrates toward a more stable configuration composed by a water molecule adsorbed on a Lewis centre. - Highlights: • MFI nanosheets with variable thicknesses were characterised using DFT calculations. • The distortions in the nanosheets after Al substitution reproduced those of the bulk. • H-bonds were only observed between silanol groups when the Al substitution took place. • The kinetic of the Al-silanol dehydration is dependent on intra-framework H-bonds. • Lewis acids with adsorbed water are more stable than Al-silanols. • The proton accessibility was related to the framework O atom binding the proton.« less

Carbanion-Accelerated Claisen Rearrangements Asymmetric Induction with Chiral Phosphorus-Stabilized Anions‡

PubMed Central

Denmark, Scott E.; Marlin, John E.; Rajendra, G.

2012-01-01

The carbanion-accelerated Claisen rearrangement has been extended to include phosphorus carbanion-stabilizing groups. The appropriately substituted allyl vinyl ethers are synthesized by the nucleophilic addition of allyloxides to phosphorus-substituted allenes, which are obtained in one step from simple starting materials. The phosphorus-stabilized, carbanion-accelerated Claisen rearrangements proceed rapidly at room temperature in high yield, and the rearrangements are highly site and stereoselective. The first examples of asymmetric induction in the Claisen rearrangement with chiral, phosphorus, anion-stabilizing groups are described. The observed asymmetric induction is highly dependent on the structure of the auxiliary and the metal counterion involved. Both internal and relative diastereoselectivity are high. A model for the observed sense of internal diastereoselectivity is proposed that is founded in the current understanding of the structure of phosphorus-stabilized anions. PMID:23101563

Effect of conformational mobility and hydrogen-bonding interactions on the selectivity of some guanidinoaryl-substituted mechanism-based inhibitors of trypsin-like serine proteases.

PubMed

Rai, R; Katzenellenbogen, J A

1992-11-13

Previously, we have reported that some guanidino-substituted alpha- and beta-aryl enol lactones I and II behaved as selective, mechanism-based inhibitors of some trypsin-like proteases (Rai, R.; Katzenellenbogen, J.A. J. Med. Chem., submitted). In this study, we describe the synthesis and kinetic evaluation of some related, guanidino-substituted enol lactones having greater conformational mobility and affording additional hydrogen-bonding sites at the active site. The alpha-aryl-substituted lactones 1 and 2, which have greater conformational mobility in the guanidinoaryl linkage than I, selectively inhibited the trypsin-like enzymes, and they were relatively poor inactivators of alpha-chymotrypsin and human neutrophil elastase (HNE). The iodo enol lactone 2 permanently inactivated trypsin, urokinase, tissue plasminogen activator, and plasmin, showing exceptionally high specificity in its interaction with trypsin and urokinase. The selectivity pattern exhibited by the closely related, conformationally less mobile alpha-aryl-substituted iodo lactone Ib, which was previously shown to be a selective suicide substrate of urokinase and plasmin, provides an interesting comparison. The alpha-benzamido-substituted lactones 3 and 4, which afford an additional site for active-site hydrogen bonding, were found to be very potent alternate substrate inhibitors of trypsin and urokinase. In addition, the iodo lactone 4 permanently inactivated alpha-chymotrypsin. The importance of secondary interactions in increasing the specificities in the case of alpha-chymotrypsin is discussed.

Slow Strain Rate Testing for Hydrogen Embrittlement Susceptibility of Alloy 718 in Substitute Ocean Water

NASA Astrophysics Data System (ADS)

LaCoursiere, M. P.; Aidun, D. K.; Morrison, D. J.

2017-05-01

The hydrogen embrittlement susceptibility of near-peak-aged UNS N07718 (Alloy 718) was evaluated by performing slow strain rate tests at room temperature in air and substitute ocean water. Tests in substitute ocean water were accomplished in an environmental cell that enabled in situ cathodic charging under an applied potential of -1.1 V versus SCE. Some specimens were cathodically precharged for 4 or 16 weeks at the same potential in a 3.5 wt.% NaCl-distilled water solution at 50 °C. Unprecharged specimens tested in substitute ocean water exhibited only moderate embrittlement with plastic strain to failure decreasing by about 20% compared to unprecharged specimens tested in air. However, precharged specimens exhibited significant embrittlement with plastic strain to failure decreasing by about 70%. Test environment (air or substitute ocean water with in situ charging) and precharge time (4 or 16 weeks) had little effect on the results of the precharged specimens. Fracture surfaces of precharged specimens were typical of hydrogen embrittlement and consisted of an outer brittle ring related to the region in which hydrogen infused during precharging, a finely dimpled transition zone probably related to the region where hydrogen was drawn in by dislocation transport, and a central highly dimpled ductile region. Fracture surfaces of unprecharged specimens tested in substitute ocean water consisted of a finely dimpled outer ring and heavily dimpled central region typical of ductile fracture.

Isotemporal Substitution Analysis for Physical Activity, Television Watching, and Risk of Depression

PubMed Central

Mekary, Rania A.; Lucas, Michel; Pan, An; Okereke, Olivia I.; Willett, Walter C.; Hu, Frank B.; Ding, Eric L.

2013-01-01

The isotemporal substitution model (ISM) was previously developed as a methodology to study the time-substitution effects of 1 type of activity for another in a data setting with continuous outcomes. To demonstrate the application of ISM with a dichotomous outcome, we prospectively examined the associations of different activities with various activity displacements with depression risk among 32,900 US women from the Nurses' Health Study who were free from depressive symptoms at baseline (in 1996). During a 10-year follow-up, 5,730 incident depression cases were documented. Results from the ISMs indicated that for each physical activity, differences in magnitude of effects of each activity type were observed, dependent on the activity being displaced/substituted. Notably, an isotemporal substitution gradient was found for television watching, in which its association with depression risk varied by its substitution for slow-, average-, or brisk-paced walking in a gradient toward high depression risk when television watching replaced a faster walking pace (relative risk = 1.18, 95% confidence interval: 1.05, 1.31). Conversely, no association with depression was found for replacement of television watching with 60 minutes/day of slow walking, whereas a lower depression risk (relative risk = 0.85, 95% confidence interval: 0.76, 0.95) was found when 60 minutes/day of brisk walking replaced 60 minutes/day of television watching. Thus, the ISM could offer a more meaningful alternative to the standard nonsubstitution models to support public health recommendations. PMID:23785112

Effects of Vanadium Substitution on the Structure and Photocatalytic Behavior of ETS-10

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

Shough,A.; Doren, D.; Nash, M.

2007-01-01

A combination of experimental and computational methods has been used to investigate the effects of vanadium doping in ETS-10. Near edge X-ray absorption fine structure (NEXAFS) spectra reveal octahedrally coordinated V{sup IV} and V{sup V} species within V-doped ETS-10 materials, confirming substitution for Ti{sup IV} sites only. Computational models, using hybrid density functional theory/molecular mechanics (DFT/MM) methods, have been developed that contain varying concentrations of V{sup IV} and V{sup V} within the O-M-O (M = Ti, V) chain. Geometry optimizations indicate that V{sup V} substitution leads to larger changes in the local chain geometry than V{sup IV} substitution. Substitution energeticsmore » for V{sup IV} and V{sup V} in different sites have been calculated to determine preferred locations of the two species, suggesting that long chains of V{sup V} are not stable and demonstrating the need for both V{sup V} and V{sup IV} within V-substituted materials. Wavefunctions for systems with an electron added or removed are used to identify electron and hole trapping sites associated with the V{sup V} and V{sup IV} doping centers respectively. An increase in photocatalytic activity is predicted at low [V] due to improved charge separation. However photocatalytic activity is expected to decrease at high [V] due to increased carrier recombination. These results are consistent with recent experimental data.« less

An enantioselective approach to the preparation of chiral sulfones by Ir-catalyzed asymmetric hydrogenation.

PubMed

Peters, Byron K; Zhou, Taigang; Rujirawanich, Janjira; Cadu, Alban; Singh, Thishana; Rabten, Wangchuk; Kerdphon, Sutthichat; Andersson, Pher G

2014-11-26

Several chiral sulfonyl compounds were prepared using the iridium catalyzed asymmetric hydrogenation reaction. Vinylic, allylic and homoallylic sulfone substitutions were investigated, and high enantioselectivity is maintained regardless of the location of the olefin with respect to the sulfone. Impressive stereoselectivity was obtained for dialkyl substitutions, which typically are challenging substrates in the hydrogenation. As expected, the more bulky Z-substrates were hydrogenated slower than the corresponding E isomers, and in slightly lower enantioselectivity.

Trifluoromethyl-substituted polymers

NASA Technical Reports Server (NTRS)

1993-01-01

Current work sponsored by the grant at Southwest Texas State University is directed toward the synthesis and characterization of: (1) N-alkylated polyamides derived from o-fluorinated diacids; (2) highly fluorinated polyethers; (3) polyesters derived from 2-hydroxy-2-propyl substituted arenes and/or 2,5-difluoroterephthalic acid; and (4) silicon-containing fluoropolymers. Work during the period from 1 July to 31 Dec. 1993 focused primarily on items 3 and 4 and on the development of a phosphorus containing modification of '12F-PEK.'

7-endo selenocyclization reactions on chiral 3-prenyl and 3-cinnamyl-2-hydroxymethylperhydro-1,3-benzoxazine derivatives. A way to enantiopure 1,4-oxazepanes.

PubMed

Nieto, Javier; Andrés, Celia; Pérez-Encabo, Alfonso

2015-09-14

Enantiopure 1,4-oxazepane derivatives have been prepared by selenocyclofunctionalization of chiral 3-prenyl- and 3-cinnamyl-2-hydroxymethyl-substituted perhydro-1,3-benzoxazine derivatives. The 7-endo-cyclization occurs in high yields and diastereoselection. The regio- and stereochemistry of the cyclization products was dependent on the substitution pattern of the double bond, the nature of the hydroxyl group and the experimental conditions.

CCR5 receptor antagonists: discovery and SAR study of guanylhydrazone derivatives.

PubMed

Wei, Robert G; Arnaiz, Damian O; Chou, Yuo-Ling; Davey, Dave; Dunning, Laura; Lee, Wheeseong; Lu, Shou-Fu; Onuffer, James; Ye, Bin; Phillips, Gary

2007-01-01

High throughput screening (HTS) led to the identification of the guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde as a CCR5 receptor antagonist. Initial modifications of the guanylhydrazone series indicated that substitution of the benzyl group at the para-position was well tolerated. Substitution at the 5-position of the central phenyl ring was critical for potency. Replacement of the guanylhydrazone group led to the discovery of a novel series of CCR5 antagonists.

Lattice parameters guide superconductivity in iron-arsenides

NASA Astrophysics Data System (ADS)

Konzen, Lance M. N.; Sefat, Athena S.

2017-03-01

The discovery of superconducting materials has led to their use in technological marvels such as magnetic-field sensors in MRI machines, powerful research magnets, short transmission cables, and high-speed trains. Despite such applications, the uses of superconductors are not widespread because they function much below room-temperature, hence the costly cooling. Since the discovery of Cu- and Fe-based high-temperature superconductors (HTS), much intense effort has tried to explain and understand the superconducting phenomenon. While no exact explanations are given, several trends are reported in relation to the materials basis in magnetism and spin excitations. In fact, most HTS have antiferromagnetic undoped ‘parent’ materials that undergo a superconducting transition upon small chemical substitutions in them. As it is currently unclear which ‘dopants’ can favor superconductivity, this manuscript investigates crystal structure changes upon chemical substitutions, to find clues in lattice parameters for the superconducting occurrence. We review the chemical substitution effects on the crystal lattice of iron-arsenide-based crystals (2008 to present). We note that (a) HTS compounds have nearly tetragonal structures with a-lattice parameter close to 4 Å, and (b) superconductivity can depend strongly on the c-lattice parameter changes with chemical substitution. For example, a decrease in c-lattice parameter is required to induce ‘in-plane’ superconductivity. The review of lattice parameter trends in iron-arsenides presented here should guide synthesis of new materials and provoke theoretical input, giving clues for HTS.

One molecule of ionic liquid and tert-alcohol on a polystyrene-support as catalysts for efficient nucleophilic substitution including fluorination.

PubMed

Shinde, Sandip S; Patil, Sunil N

2014-12-07

The tert-alcohol and ionic liquid solvents in one molecule [mim-(t)OH][OMs] was immobilized on polystyrene and reported to be a highly efficient catalyst in aliphatic nucleophilic substitution using alkali metal salts. Herein, we investigated the catalytic activity of a new structurally modified polymer-supported tert-alcohol functionalized imidazolium salt catalyst in nucleophilic substitution of 2-(3-methanesulfonyloxypropyoxy)naphthalene as a model substrate with various metal nucleophiles. The tert-alcohol moiety of the ionic liquid with a hexyl chain distance from polystyrene had a better catalytic activity compared to the other resin which lacked an alkyl linker and tert-alcohol moiety. We found that the maximum [mim-(t)OH][OMs] loading had the best catalytic efficacy among the tested polystyrene-based ionic liquids (PSILs) in nucleophilic fluorination. The catalytic efficiency of the PS[him-(t)OH][OMs] as a phase transfer catalyst (PTC) was determined by carrying out various nucleophilic substitutions using the corresponding alkali metal salts from the third to sixth periodic in CH3CN or tert-BuOH media. The scope of this protocol with primary and secondary polar substrates containing many heteroatoms is also reported. This PS[him-(t)OH][OMs] catalyst not only enhances the reactivity of alkali metal salts and reduces the formation of by-products but also affords high yield with easy isolation.

Lattice parameters guide superconductivity in iron-arsenides.

PubMed

Konzen, Lance M N; Sefat, Athena S

2017-03-01

The discovery of superconducting materials has led to their use in technological marvels such as magnetic-field sensors in MRI machines, powerful research magnets, short transmission cables, and high-speed trains. Despite such applications, the uses of superconductors are not widespread because they function much below room-temperature, hence the costly cooling. Since the discovery of Cu- and Fe-based high-temperature superconductors (HTS), much intense effort has tried to explain and understand the superconducting phenomenon. While no exact explanations are given, several trends are reported in relation to the materials basis in magnetism and spin excitations. In fact, most HTS have antiferromagnetic undoped 'parent' materials that undergo a superconducting transition upon small chemical substitutions in them. As it is currently unclear which 'dopants' can favor superconductivity, this manuscript investigates crystal structure changes upon chemical substitutions, to find clues in lattice parameters for the superconducting occurrence. We review the chemical substitution effects on the crystal lattice of iron-arsenide-based crystals (2008 to present). We note that (a) HTS compounds have nearly tetragonal structures with a-lattice parameter close to 4 Å, and (b) superconductivity can depend strongly on the c-lattice parameter changes with chemical substitution. For example, a decrease in c-lattice parameter is required to induce 'in-plane' superconductivity. The review of lattice parameter trends in iron-arsenides presented here should guide synthesis of new materials and provoke theoretical input, giving clues for HTS.

Global carbon benefits of material substitution in passenger cars until 2050 and the impact on the steel and aluminum industries.

PubMed

Modaresi, Roja; Pauliuk, Stefan; Løvik, Amund N; Müller, Daniel B

2014-09-16

Light-weighting of passenger cars using high-strength steel or aluminum is a common emissions mitigation strategy. We provide a first estimate of the global impact of light-weighting by material substitution on GHG emissions from passenger cars and the steel and aluminum industries until 2050. We develop a dynamic stock model of the global car fleet and combine it with a dynamic MFA of the associated steel, aluminum, and energy supply industries. We propose four scenarios for substitution of conventional steel with high-strength steel and aluminum at different rates over the period 2010-2050. We show that light-weighting of passenger cars can become a "gigaton solution": Between 2010 and 2050, persistent light-weighting of passenger cars can, under optimal conditions, lead to cumulative GHG emissions savings of 9-18 gigatons CO2-eq compared to development business-as-usual. Annual savings can be up to 1 gigaton per year. After 2030, enhanced material recycling can lead to further reductions: closed-loop metal recycling in the automotive sector may reduce cumulative emissions by another 4-6 gigatons CO2-eq. The effectiveness of emissions mitigation by material substitution significantly depends on how the recycling system evolves. At present, policies focusing on tailpipe emissions and life cycle assessments of individual cars do not consider this important effect.

Structure–Activity Relationships for a Novel Series of Dopamine D2-like Receptor Ligands Based on N-Substituted 3-Aryl-8-azabicyclo[3.2.1]octan-3-ol

PubMed Central

Paul, Noel M.; Taylor, Michelle; Kumar, Rakesh; Deschamps, Jeffrey R.; Luedtke, Robert R.; Newman, Amy Hauck

2011-01-01

Discovering dopamine D2-like receptor subtype-selective ligands has been a focus of significant investigation. The D2R-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole (1, L741,626; Ki(D2R/D3R) = 11.2:163 nM) has previously provided a lead template for chemical modification. Herein, analogues have been synthesized where the piperidine was replaced by a tropane ring that reversed the selectivity seen in the parent compound, in human hD2LR- or hD3R-transfected HEK 293 cells (31, Ki(D2R/D3R) = 33.4: 15.5 nM). Further exploration of both N-substituted and aryl ring-substituted analogues resulted in the discovery of several high affinity D2R/D3R ligands with 3-benzofurylmethyl-substituents (e.g., 45, Ki(D2R/D3R) = 1.7:0.34 nM) that induced high affinity not achieved in similarly N-substituted piperidine analogues and significantly (470-fold) improved D3R binding affinity compared to the parent ligand 1. X-ray crystallographic data revealed a distinctive spatial arrangement of pharmacophoric elements in the piperidinol vs tropine analogues, providing clues for the diversity in SAR at the D2 and D3 receptor subtypes. PMID:18774793

Structural, magnetic, and Mössbauer spectroscopy of Cu substituted M-type hexaferrites

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

Awadallah, Ahmad, E-mail: ahmadmoh@yahoo.co; Mahmood, Sami H., E-mail: s.mahmood@ju.edu.jo; Maswadeh, Yazan, E-mail: nawabra251@gmail.com

2016-02-15

Highlights: • Single BaM hexaferrite structural phases with Cu substations were prepared. • The magnetocrystalline anisotropy decreased with Cu substitution. • The coercivity was significantly modified while the magnetization remained high. • Hexaferrites with 0.2–0.4 Cu possess properties suitable for magnetic recording. • Ionic distributions from structural refinement agreed with Mössbauer spectroscopy. - Abstract: BaFe{sub 12−x}Cu{sub x}O{sub 19} hexaferrites were prepared using ball milling and sintering at 1100 °C. Refinement of the X-ray diffraction patterns was carried out to determine the structural parameters and the ionic distribution over the crystallographic sites. The preferential site occupation and valence state of Cumore » was consistent with the results obtained from the analysis of Mössbauer spectra. Further, the magnetic parameters of the samples were discussed in light of the structural and Mössbauer analyses. The magnetic phase transition temperature was found to decrease with the level of Cu substitution, in accordance with the reduction of the superexchange interactions. Further, the magnetic softening of the hexaferrite and the significant reduction in magnetocrystalline anisotropy with Cu substitution was consistent with the ionic distribution in the lattice. This study clearly demonstrated the feasibility of using a simple method to fabricate hexaferrites with a modified coercivity, while maintain the saturation magnetization high enough for practical applications.« less

Superior stability for perovskite solar cells with 20% efficiency using vacuum co-evaporation.

PubMed

Zhu, Xuejie; Yang, Dong; Yang, Ruixia; Yang, Bin; Yang, Zhou; Ren, Xiaodong; Zhang, Jian; Niu, Jinzhi; Feng, Jiangshan; Liu, Shengzhong Frank

2017-08-31

Chemical composition and film quality are two key figures of merit for large-area high-efficiency perovskite solar cells. To date, all studies on mixed perovskites have used solution-processing, which results in imperfect surface coverage and pin-holes generated during solvent evaporation, execrably influencing the stability and efficiency of perovskite solar cells. Herein, we report our development using a vacuum co-evaporation deposition method to fabricate pin-hole-free cesium (Cs)-substituted perovskite films with complete surface coverage. Apart from the simplified procedure, the present method also promises tunable band gap, reduced trap-state density and longer carrier lifetime, leading to solar cell efficiency as high as 20.13%, which is among the highest reported for planar perovskite solar cells. The splendid performance is attributed to superior merits of the Cs-substituted perovskite film including tunable band gap, reduced trap-state density and longer carrier lifetime. Moreover, the Cs-substituted perovskite device without encapsulation exhibits significantly higher stability in ambient air compared with the single-component counterpart. When the Cs-substituted perovskite solar cells are stored in dark for one year, the PCE remains at 19.25%, degrading only 4.37% of the initial efficiency. The excellent stability originates from reduced lattice constant and relaxed strain in perovskite lattice by incorporating Cs cations into the crystal lattice, as demonstrated by the positive peak shifts and reduced peak width in X-ray diffraction analysis.

High-pressure freezing and freeze substitution of Arabidopsis for electron microscopy.

PubMed

Austin, Jotham R

2014-01-01

The objectives of electron microscopy ultrastructural studies are to examine cellular architecture and relate the cell's structural machinery to dynamic functional roles. This aspiration is difficult to achieve if specimens have not been adequately preserved in a "living state"; hence specimen preparation is of the utmost importance for the success of any electron micrographic study. High-pressure freezing (HPF)/freeze substitution (FS) has long been recognized as the primer technique for the preservation of ultrastructure in biological samples. In most cases a basic HPF/freeze substitution protocol is sufficient to obtain superior ultrastructural preservation and structural contrast, which allows one to use more advanced microscopy techniques such as 3D electron tomography. However, for plant tissues, which have a thick cell wall, large water-filled vacuoles, and air spaces (all of which are detrimental to cryopreservation), these basic HPF/FS protocols often yield undesirable results. In particular, ice crystal artifacts and the staining of membrane systems are often poorly or negatively stained, which make 3D segmentation of a tomogram difficult. To overcome these problems, various aspects of the HPF/FS protocol can be altered, including the cryo-filler(s) used, freeze substitution cocktail, and the resin infiltration process. This chapter will describe these modifications for the preparation of plant tissues for routine electron microscopic studies, immunocytochemistry, and 3D tomographic electron imaging.

40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

Code of Federal Regulations, 2010 CFR

2010-07-01

... substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo...

40 CFR 721.10126 - Alkyl amino substituted triazine amino substituted benezenesulfonic acid reaction product with...

Code of Federal Regulations, 2011 CFR

2011-07-01

... substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo substituted phenyl azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo... substituted triazine amino substituted benezenesulfonic acid reaction product with naphthalenesulfonato azo...

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2014 CFR

2014-07-01

... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject to...

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2013 CFR

2013-07-01

... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject to...

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2012 CFR

2012-07-01

... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject to...

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.

Code of Federal Regulations, 2011 CFR

2011-07-01

... naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721.981 Protection of Environment...-substituted naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance and significant new... naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is subject to...

Sequence-Based Analysis of Thermal Adaptation and Protein Energy Landscapes in an Invasive Blue Mussel (Mytilus galloprovincialis).

PubMed

Saarman, Norah P; Kober, Kord M; Simison, W Brian; Pogson, Grant H

2017-10-01

Adaptive responses to thermal stress in poikilotherms plays an important role in determining competitive ability and species distributions. Amino acid substitutions that affect protein stability and modify the thermal optima of orthologous proteins may be particularly important in this context. Here, we examine a set of 2,770 protein-coding genes to determine if proteins in a highly invasive heat tolerant blue mussel (Mytilus galloprovincialis) contain signals of adaptive increases in protein stability relative to orthologs in a more cold tolerant M. trossulus. Such thermal adaptations might help to explain, mechanistically, the success with which the invasive marine mussel M. galloprovincialis has displaced native species in contact zones in the eastern (California) and western (Japan) Pacific. We tested for stabilizing amino acid substitutions in warm tolerant M. galloprovincialis relative to cold tolerant M. trossulus with a generalized linear model that compares in silico estimates of recent changes in protein stability among closely related congeners. Fixed substitutions in M. galloprovincialis were 3,180.0 calories per mol per substitution more stabilizing at genes with both elevated dN/dS ratios and transcriptional responses to heat stress, and 705.8 calories per mol per substitution more stabilizing across all 2,770 loci investigated. Amino acid substitutions concentrated in a small number of genes were more stabilizing in M. galloprovincialis compared with cold tolerant M. trossulus. We also tested for, but did not find, enrichment of a priori GO terms in genes with elevated dN/dS ratios in M. galloprovincialis. This might indicate that selection for thermodynamic stability is generic across all lineages, and suggests that the high change in estimated protein stability that we observed in M. galloprovincialis is driven by selection for extra stabilizing substitutions, rather than by higher incidence of selection in a greater number of genes in this lineage. Nonetheless, our finding of more stabilizing amino acid changes in the warm adapted lineage is important because it suggests that adaption for thermal stability has contributed to M. galloprovincialis' superior tolerance to heat stress, and that pairing tests for positive selection and tests for transcriptional response to heat stress can identify candidates of protein stability adaptation. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Bioengineered vascular scaffolds: the state of the art.

PubMed

Palumbo, Vincenzo D; Bruno, Antonio; Tomasello, Giovanni; Damiano, Giuseppe; Lo Monte, Attilio I

2014-07-31

To date, there is increasing clinical need for vascular substitutes due to accidents, malformations, and ischemic diseases. Over the years, many approaches have been developed to solve this problem, starting from autologous native vessels to artificial vascular grafts; unfortunately, none of these have provided the perfect vascular substitute. All have been burdened by various complications, including infection, thrombogenicity, calcification, foreign body reaction, lack of growth potential, late stenosis and occlusion from intimal hyperplasia, and pseudoaneurysm formation. In the last few years, vascular tissue engineering has emerged as one of the most promising approaches for producing mechanically competent vascular substitutes. Nanotechnologies have contributed their part, allowing extraordinarily biostable and biocompatible materials to be developed. Specifically, the use of electrospinning to manufacture conduits able to guarantee a stable flow of biological fluids and guide the formation of a new vessel has revolutionized the concept of the vascular substitute. The electrospinning technique allows extracellular matrix (ECM) to be mimicked with high fidelity, reproducing its porosity and complexity, and providing an environment suitable for cell growth. In the future, a better knowledge of ECM and the manufacture of new materials will allow us to "create" functional biological vessels - the base required to develop organ substitutes and eventually solve the problem of organ failure.

Spin-state responses to light impurity substitution in low-spin perovskite LaCoO3

NASA Astrophysics Data System (ADS)

Tomiyasu, Keisuke; Kubota, Yuuki; Shimomura, Saya; Onodera, Mitsugi; Koyama, Syun-Ichi; Nojima, Tsutomu; Ishihara, Sumio; Nakao, Hironori; Murakami, Youichi

2013-06-01

We studied the spin-state responses to light impurity substitution in low-spin perovskite LaCoO3 (Co3+: d6) through magnetization, x-ray fluorescence, and electrical resistivity measurements of single-crystal LaCo0.99M0.01O3 (M = Cr, Mn, Fe, Ni). In the magnetization curves measured at 1.8 K, a change in the spin-state was not observed for Cr, Mn, or Fe substitution but was observed for Ni substitution. Strong magnetic anisotropy was also found in the Ni-substituted sample. The fluorescence measurements revealed that the valences were roughly estimated to be Cr3+, Mn(4-δ)+, Fe(3+δ')+, and Ni3+. From the observed chemical trends, we propose that the chemical potential is a key factor in inducing the change of the low-spin state. By expanding a model of the ferromagnetic spin-state heptamer generated by hole doping [Podlesnyak , Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.101.247603 101, 247603 (2008)], the emergence of highly anisotropic spin-state molecular ferromagnets induced by low-spin Ni3+ with Jahn-Teller activity is suggested. We also discuss applicability of the present results to other materials with Fe (d6).

Improved Methods to Produce Tissue-Engineered Skin Substitutes Suitable for the Permanent Closure of Full-Thickness Skin Injuries

PubMed Central

Larouche, Danielle; Cantin-Warren, Laurence; Desgagné, Maxime; Guignard, Rina; Martel, Israël; Ayoub, Akram; Lavoie, Amélie; Gauvin, Robert; Auger, François A.; Moulin, Véronique J.; Germain, Lucie

2016-01-01

Abstract There is a clinical need for skin substitutes to replace full-thickness skin loss. Our group has developed a bilayered skin substitute produced from the patient's own fibroblasts and keratinocytes referred to as Self-Assembled Skin Substitute (SASS). After cell isolation and expansion, the current time required to produce SASS is 45 days. We aimed to optimize the manufacturing process to standardize the production of SASS and to reduce production time. The new approach consisted in seeding keratinocytes on a fibroblast-derived tissue sheet before its detachment from the culture plate. Four days following keratinocyte seeding, the resulting tissue was stacked on two fibroblast-derived tissue sheets and cultured at the air–liquid interface for 10 days. The resulting total production time was 31 days. An alternative method adapted to more contractile fibroblasts was also developed. It consisted in adding a peripheral frame before seeding fibroblasts in the culture plate. SASSs produced by both new methods shared similar histology, contractile behavior in vitro and in vivo evolution after grafting onto mice when compared with SASSs produced by the 45-day standard method. In conclusion, the new approach for the production of high-quality human skin substitutes should allow an earlier autologous grafting for the treatment of severely burned patients. PMID:27872793

Cooking characterization of Coleus tuberosus noodle in various arenga starch substitution

NASA Astrophysics Data System (ADS)

Miftakhussolikhah, Ariani, Dini; Angwar, Mukhamad; Jeremia Kevin M., M.

2017-01-01

Coleus tuberosus is one of local commodities in Indonesia which contains high carbohydrate. However, its utilization isn't done maximally. Therefore, C. tuberosus made into flour by grater method, and then be used for noodle making with arenga strach as substituting material. The aim of this study was to determine the effect of C. tuberosus flour substitution in the noodle preparation from arenga starch on its cooking properties. In this study, noodle was made in some variations which were 100% arenga starch; 75% arenga starch:25% C. tuberosus flour; 50% arenga starch:50% C. tuberosus flour; 25% arenga starch:75% C. tuberosus flour and 100% C. tuberosus flour. Characterization of noodle were investigated including water content, cooking time, cooking loss, swelling index, and expansion ratio Noodle was compared with two commercial products. The result showed that arenga starch substitution in C. tuberosus noodle affect cooking properties of noodle. The higher concentration of C. tuberosus flour caused swelling index and expansion ratio getting low. The water content, cooking loss and cooking time were increased as the C. tuberosus flour substitution ratio increase. None of the noodle resulted from C. tuberosus flour and arenga starch mixture was exactly as same as maize and rice commercial noodles. However 25% of C.tuberosus noodle has better characteristics than other C.tuberosus noodles.

A Dicobalt Complex with an Unsymmetrical Quinonoid Bridge Isolated in Three Units of Charge: A Combined Structural, (Spectro)electrochemical, Magnetic and Spectroscopic Study.

PubMed

van der Meer, Margarethe; Rechkemmer, Yvonne; Frank, Uta; Breitgoff, Frauke D; Hohloch, Stephan; Su, Cheng-Yong; Neugebauer, Petr; Marx, Raphael; Dörfel, María; van Slageren, Joris; Sarkar, Biprajit

2016-09-19

Quinonoid ligands are excellent bridges for generating redox-rich dinuclear assemblies. A large majority of these bridges are symmetrically substituted, with examples of unsymmetrically substituted quinonoid bridges being extremely rare. We present here a dicobalt complex in its various redox states with an unsymmetrically substituted quinonoid bridging ligand. Two homovalent forms and one mixed-valent form have been isolated and characterized by single crystal X-ray diffraction. The complex displays a large comproportionation constant for the mixed-valent state which is three orders of magnitude higher than that observed for the analogous complex with a symmetrically substituted bridge. Results from electrochemistry, UV/Vis/NIR spectroelectrochemistry, SQUID magnetometry, multi-frequency EPR spectroscopy and FIR spectroscopy are used to probe the electronic structures of these complexes. FIR provides direct evidence of exchange coupling. The results presented here display the advantages of using an unsymmetrically substituted bridge: site specific redox chemistry, high thermodynamic stabilization of the mixed-valent form, isolation and crystallization of various redox forms of the complex. This work represents an important step on the way to generating heterodinuclear complexes for use in cooperative catalysis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrochemical properties of LaNi{sub 5{minus}x}Ge{sub x} alloys in Ni-MH batteries

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

Witham, C.; Hightower, A.; Fultz, B.

1997-11-01

Electrochemical studies were performed on LaNi{sub 5{minus}x}Ge{sub x} metal hydride alloys with 0 {le} x {le} 0.5. The authors carried out single-electrode studies to understand the effects of the Ge substituent on the hydrogen absorption characteristics, the electrochemical capacity, and the electrochemical kinetics of hydrogen absorption and desorption. The electrochemical characteristics of the Ge-substituted alloys are compared to those of the Sn-substituted alloys reported earlier. LaNi{sub 5{minus}x}Ge{sub x} alloys show compositional trends similar to LaNi{sub 5{minus}x}Sn{sub x} alloys, but unlike the Sn-substituted alloys, Ge-substituted alloys continue to exhibit facile kinetics for hydrogen absorption/desorption at high solute concentrations. Cycle lives ofmore » LaNi{sub 5{minus}x}Ge{sub x} electrodes were measured in 300 mAh laboratory test cells and were found to be superior to the Sn-substituted LaNi{sub 5} and comparable to a Mm(Ni, Co, Mn, Al){sub 5} alloy. The optimum Ge content for LaNi{sub 5{minus}x}Ge{sub x} metal hydride alloys in alkaline rechargeable cells is in the range 0.4 {le} x {le} 0.5.« less

Enhanced bioactivity, biocompatibility and mechanical behavior of strontium substituted bioactive glasses.

PubMed

Arepalli, Sampath Kumar; Tripathi, Himanshu; Hira, Sumit Kumar; Manna, Partha Pratim; Pyare, Ram; S P Singh

2016-12-01

Strontium contained biomaterials have been reported as a potential bioactive material for bone regeneration, as it reduces bone resorption and stimulates bone formation. In the present investigation, the bioactive glasses were designed to partially substitute SrO for SiO2 in Na2O-CaO-SrO-P2O5-SiO2 system. This work demonstrates that the substitution of SrO for SiO2 has got significant benefit than substitution for CaO in the bioactive glass. Bioactivity was assessed by the immersion of the samples in simulated body fluid for different intervals. The formation of hydroxy carbonate apatite layer was identified by X-ray diffractometry, scanning electron microscopy (SEM) and energy dispersive spectroscopy. The elastic modulus of the bioactive glasses was measured and found to increase with increasing SrO for SiO2. The blood compatibility of the samples was evaluated. In vitro cell culture studies of the samples were performed using human osteosarcoma U2-OS cell lines and found a significant improvement in cell viability and proliferation. The investigation showed enhancement in bioactivity, mechanical and biological properties of the strontia substituted for silica in glasses. Thus, these bioactive glasses would be highly potential for bone regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

Improved bioactivity of G-rich triplex-forming oligonucleotides containing modified guanine bases

PubMed Central

Rogers, Faye A; Lloyd, Janice A; Tiwari, Meetu Kaushik

2014-01-01

Triplex structures generated by sequence-specific triplex-forming oligonucleotides (TFOs) have proven to be promising tools for gene targeting strategies. In addition, triplex technology has been highly utilized to study the molecular mechanisms of DNA repair, recombination and mutagenesis. However, triplex formation utilizing guanine-rich oligonucleotides as third strands can be inhibited by potassium-induced self-association resulting in G-quadruplex formation. We report here that guanine-rich TFOs partially substituted with 8-aza-7-deaza-guanine (PPG) have improved target site binding in potassium compared with TFOs containing the natural guanine base. We designed PPG-substituted TFOs to bind to a polypurine sequence in the supFG1 reporter gene. The binding efficiency of PPG-substituted TFOs to the target sequence was analyzed using electrophoresis mobility gel shift assays. We have determined that in the presence of potassium, the non-substituted TFO, AG30 did not bind to its target sequence, however binding was observed with the PPG-substituted AG30 under conditions with up to 140 mM KCl. The PPG-TFOs were able to maintain their ability to induce genomic modifications as measured by an assay for gene-targeted mutagenesis. In addition, these compounds were capable of triplex-induced DNA double strand breaks, which resulted in activation of apoptosis. PMID:25483840

New Imidazole-based High Nitrogen Energetic Materials

NASA Astrophysics Data System (ADS)

Windler, G. Kenneth; Leonard, Philip; Schulze, Maxwell; Hartline, Ernest

2017-06-01

Energetic materials derive their power from energy release, usually in the form of gaseous products. The type and quantity of these products contribute to performance and detonation parameters. In particular, high-nitrogen materials produce large quantities of elemental nitrogen, and can be tuned via molecular structure for suitability as propellants (gas generators) or explosives. In this work, the five-membered nitrogen heterocycle imidazole is used as a substrate for a variety of high-nitrogen materials. Substitution of the imidazole ring directly with nitro-, azido-, diazo-, and tetrazole moieties allows for tunable properties of the resultant energetic material. Properties can be further tailored by salt formation at the acidic proton(s) on the molecules. The various combinations of these derivatives are presented, along with the substitution effects on physical, chemical, and explosive properties.

The review of various synthesis methods of barium titanate with the enhanced dielectric properties

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

More, S. P., E-mail: smitalomte@gmail.com; Topare, R. J., E-mail: r-topare@yahoo.com

2016-05-06

The Barium Titanate is a very well known dielectric ceramic belongs to perovskite structure. It has very wide applications in the field of electronic, electro ceramic, electromechanical and electro-optical applications. Barium Titanate has very high dielectric constant as well as low dielectric loss. Substituted dielectrics are one of the most important technological compounds in modern electro ceramics. Its electrical properties can be tuned flexibly by a simple substitution technique. This has encouraged researchers to select a typical cation to be substituted at cationic sites. In the present paper, the review of various synthesis methods of Barium Titanate compound with themore » effect of different dopants, the grain size on the dielectric properties at various temperatures is discussed.« less

Adlayer structure of octa-alkoxy-substituted copper(II) phthalocyanine on Au(111) by electrochemical scanning tunneling microscopy.

PubMed

Wang, Li; Ou-Yang, Liangyue; Yau, Shueh-Lin

2008-01-01

Electrochemical scanning tunneling microscopy (ECSTM) has been used to examine the adlayer of octa-alkoxy-substituted copper(II) phthalocyanines (CuPc(OC(8)H(17))(8)) on Au(111) in 0.1 M HClO(4), where the molecular adlayer was prepared by spontaneous adsorption from a benzene solution containing this molecule. Topography STM scans revealed long-range ordered, interweaved arrays of CuPc(OC(8)H(17))(8) with coexistent rectangular and hexagonal symmetries. High-quality STM molecular resolution yielded the internal molecular structure and the orientation of CuPc(OC(8)H(17))(8) admolecules. These STM results could shed insight into the method of generating ordered molecular assemblies of phthalocyanine molecules with long-chained substitutes on metal surface. 2007 Wiley-Liss, Inc

Evaluation of substitution monopole models for tire noise sound synthesis

NASA Astrophysics Data System (ADS)

Berckmans, D.; Kindt, P.; Sas, P.; Desmet, W.

2010-01-01

Due to the considerable efforts in engine noise reduction, tire noise has become one of the major sources of passenger car noise nowadays and the demand for accurate prediction models is high. A rolling tire is therefore experimentally characterized by means of the substitution monopole technique, suiting a general sound synthesis approach with a focus on perceived sound quality. The running tire is substituted by a monopole distribution covering the static tire. All monopoles have mutual phase relationships and a well-defined volume velocity distribution which is derived by means of the airborne source quantification technique; i.e. by combining static transfer function measurements with operating indicator pressure measurements close to the rolling tire. Models with varying numbers/locations of monopoles are discussed and the application of different regularization techniques is evaluated.

Ruthenium-Catalyzed Cycloaddition of 1-Haloalkynes with Nitrile Oxides and Organic Azides; Synthesis of 4-Halo Isoxazoles and 5-Halo Triazoles

PubMed Central

Oakdale, James S.; Sit, Rakesh K.

2015-01-01

(Cyclopentadienyl)(cyclooctadiene) ruthenium(II) chloride [CpRuCl(cod)] catalyzes the reaction between nitrile oxides and electronically deficient 1-choro-, 1-bromo- and 1-iodoalkynes leading to 4-haloisoxazoles. Organic azides are also suitable 1,3-dipoles, resulting in 5-halo-1,2,3-triazoles. These air tolerant reactions can be performed at room temperature with 1.25 equiv of the respective 1,3-dipole relative to the alkyne component. Reactive 1-haloalkynes include propiolic amides, esters, ketones and phosphonates. Post-functionalization of the halogenated azole products can be accomplished using palladium-catalyzed cross-coupling reactions as well as via manipulation of reactive amide groups. The lack of catalysis observed with Cp*RuCl(cod) is attributed to steric demands of the Cp* (η5-C5Me5) ligand in comparison to the parent Cp (η5-C5H5). This hypothesis is supported by the poor reactivity of (η5-C5Me4CF3)RuCl(cod), which serves as a an isosteric mimic of Cp* and as an isoelectronic analog of Cp. PMID:25059647

Non-fibrillar amyloid-{beta} peptide reduces NMDA-induced neurotoxicity, but not AMPA-induced neurotoxicity

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

Niidome, Tetsuhiro, E-mail: tniidome@pharm.kyoto-u.ac.jp; Goto, Yasuaki; Kato, Masaru

2009-09-04

Amyloid-{beta} peptide (A{beta}) is thought to be linked to the pathogenesis of Alzheimer's disease. Recent studies suggest that A{beta} has important physiological roles in addition to its pathological roles. We recently demonstrated that A{beta}42 protects hippocampal neurons from glutamate-induced neurotoxicity, but the relationship between A{beta}42 assemblies and their neuroprotective effects remains largely unknown. In this study, we prepared non-fibrillar and fibrillar A{beta}42 based on the results of the thioflavin T assay, Western blot analysis, and atomic force microscopy, and examined the effects of non-fibrillar and fibrillar A{beta}42 on glutamate-induced neurotoxicity. Non-fibrillar A{beta}42, but not fibrillar A{beta}42, protected hippocampal neurons frommore » glutamate-induced neurotoxicity. Furthermore, non-fibrillar A{beta}42 decreased both neurotoxicity and increases in the intracellular Ca{sup 2+} concentration induced by N-methyl-D-aspartate (NMDA), but not by {alpha}-amino-3-hydrozy-5-methyl-4-isoxazole propionic acid (AMPA). Our results suggest that non-fibrillar A{beta}42 protects hippocampal neurons from glutamate-induced neurotoxicity through regulation of the NMDA receptor.« less

Nootropic agents stimulate neurogenesis. Brain Cells, Inc.: WO2007104035.

PubMed

Taupin, Philippe

2009-05-01

The application is in the field of adult neurogenesis, neural stem cells and cellular therapy. It aims to characterize the activity of nootropic agents on adult neurogenesis in vitro. Nootropic agents are substances improving cognitive and mental abilities. AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) and nootropic agents were assessed for the potential to differentiate human neural progenitor and stem cells into neuronal cells in vitro. They were also tested for their behavioural activity on the novel object recognition task. AMPA, piracetam, FK-960 and SGS-111 induce and stimulate neuronal differentiation of human-derived neural progenitor and stem cells. SGS-111 increases the number of visits to the novel object. The neurogenic activity of piracetam and SGS-111 is mediated through AMPA receptor. The neurogenic activity of SGS-111 may contribute and play a role in its nootropic activity. These results suggest that nootropic agents may elicit some of their effects through their neurogenic activity. The application claims the use of nootropic agents for their neurogenic activity and for the treatment of neurological diseases, disorders and injuries, by stimulating or increasing the generation of neuronal cells in the adult brain.

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

PubMed Central

Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S.S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate, Carlos A.; Gould, Todd D.

2016-01-01

Major depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine’s unique antidepressant properties, which involves the required activity of a distinct metabolite and is independent of NMDAR inhibition. These findings have relevance for the development of next generation, rapid-acting antidepressants. PMID:27144355

Dopamine D1-like receptor in lateral habenula nucleus affects contextual fear memory and long-term potentiation in hippocampal CA1 in rats.

PubMed

Chan, Jiangping; Guan, Xin; Ni, Yiling; Luo, Lilu; Yang, Liqiang; Zhang, Pengyue; Zhang, Jichuan; Chen, Yanmei

2017-03-15

The Lateral Habenula (LHb) plays an important role in emotion and cognition. Recent experiments suggest that LHb has functional interaction with the hippocampus and plays an important role in spatial learning. LHb is reciprocally connected with midbrain monoaminergic brain areas such as the ventral tegmental area (VTA). However, the role of dopamine type 1 receptor (D1R) in LHb in learning and memory is not clear yet. In the present study, D1R agonist or antagonist were administered bilaterally into the LHb in rats. We found that both D1R agonist and antagonist impaired the acquisition of contextual fear memory in rats. D1R agonist or antagonist also impaired long term potentiation (LTP) in hippocampal CA3-CA1 synapses in freely moving rats and attenuated learning induced phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) at Ser831 and Ser845 in hippocampus. Taken together, our results suggested that dysfunction of D1R in LHb affected the function of hippocampus. Copyright © 2016 Elsevier B.V. All rights reserved.

Glutamatergic synapses in neurodevelopmental disorders.

PubMed

Moretto, Edoardo; Murru, Luca; Martano, Giuseppe; Sassone, Jenny; Passafaro, Maria

2018-06-08

Neurodevelopmental disorders (NDDs) are a group of diseases whose symptoms arise during childhood or adolescence and that impact several higher cognitive functions such as learning, sociability and mood. Accruing evidence suggests that a shared pathogenic mechanism underlying these diseases is the dysfunction of glutamatergic synapses. We summarize present knowledge on autism spectrum disorders (ASD), intellectual disability (ID), Down syndrome (DS), Rett syndrome (RS) and attention-deficit hyperactivity disorder (ADHD), highlighting the involvement of glutamatergic synapses and receptors in these disorders. The most commonly shared defects involve α-amino-3-hydroxy-5-methyl- 4-isoxazole propionic acid receptors (AMPARs), N-methyl-d-aspartate receptors (NMDARs) and metabotropic glutamate receptors (mGluRs), whose functions are strongly linked to synaptic plasticity, affecting both cell-autonomous features as well as circuit formation. Moreover, the major scaffolding proteins and, thus, the general structure of the synapse are often deregulated in neurodevelopmental disorders, which is not surprising considering their crucial role in the regulation of glutamate receptor positioning and functioning. This convergence of defects supports the definition of neurodevelopmental disorders as a continuum of pathological manifestations, suggesting that glutamatergic synapses could be a therapeutic target to ameliorate patient symptomatology. Copyright © 2017. Published by Elsevier Inc.

New derivatives of (E,E)-azomethines: Design, quantum chemical modeling, spectroscopic (FT-IR, UV/Vis, polarization) studies, synthesis and their applications: Experimental and theoretical investigations

NASA Astrophysics Data System (ADS)

Sheikhi, Masoome; Shahab, Siyamak; Filippovich, Liudmila; Yahyaei, Hooriye; Dikusar, Evgenij; Khaleghian, Mehrnoosh

2018-01-01

In present work, Polarization, Excited States, FT-IR, 1H, 13C NMR, Trans-Cis (E → Z) Isomerization Properties and Anisotropy of Thermal and Electrical Conductivity of the three new Azomethines dyes such as: 4-((E)-((4-((E)-phenyldiazenyl)phenyl)imino)methyl)benzoic acid (I), 5-phenyl-N-(pyrimidin-2-yl)isoxazole-3-carboxamide (II) and (Z)-1-(4-((E)-((4-phenylcyclopenta-1,4-dien-1-yl)methylene)amino)phenyl)ethanone oxime (III) in the presence of polyvinyl alcohol (PVA) matrix were studied. The absorption spectrum of the I, II and III in dimethylformamide (DMF) solution was calculated. The nature of absorption peaks of the dyes in the UV/Vis spectral regions was interpreted. The molecular HOMO-LUMO, excitation energies and oscillator strengths for E and Z isomers of the I, II and III have also been calculated and presented. Optical Properties of the PVA-films containing these new synthesized dyes have investigated. Polarizing Efficiency (PE) of obtained PVA-film is 97-98% at Stretching Degree (Rs) 3.5. Anisotropy of thermal and electrical conductivity of the PVA-films containing the title compounds was also measured and discussed.

Piracetam defines a new binding site for allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors.

PubMed

Ahmed, Ahmed H; Oswald, Robert E

2010-03-11

Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system and are important potential drug targets for cognitive enhancement and the treatment of schizophrenia. Allosteric modulators of AMPA receptors promote dimerization by binding to a dimer interface and reducing desensitization and deactivation. The pyrrolidine allosteric modulators, piracetam and aniracetam, were among the first of this class of drugs to be discovered. We have determined the structure of the ligand binding domain of the AMPA receptor subtypes GluA2 and GluA3 with piracetam and a corresponding structure of GluA3 with aniracetam. Both drugs bind to GluA2 and GluA3 in a very similar manner, suggesting little subunit specificity. However, the binding sites for piracetam and aniracetam differ considerably. Aniracetam binds to a symmetrical site at the center of the dimer interface. Piracetam binds to multiple sites along the dimer interface with low occupation, one of which is a unique binding site for potential allosteric modulators. This new site may be of importance in the design of new allosteric regulators.

Piracetam Defines a New Binding Site for Allosteric Modulators of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors§

PubMed Central

Ahmed, Ahmed H.; Oswald, Robert E.

2010-01-01

Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system and are important potential drug targets for cognitive enhancement and the treatment of schizophrenia. Allosteric modulators of AMPA receptors promote dimerization by binding to a dimer interface and reducing desensitization and deactivation. The pyrrolidine allosteric modulators, piracetam and aniracetam, were among the first of this class of drugs to be discovered. We have determined the structure of the ligand binding domain of the AMPA receptor subtypes GluA2 and GluA3 with piracetam and a corresponding structure of GluA3 with aniracetam. Both drugs bind to both GluA2 and GluA3 in a very similar manner, suggesting little subunit specificity. However, the binding sites for piracetam and aniracetam differ considerably. Aniracetam binds to a symmetrical site at the center of the dimer interface. Piracetam binds to multiple sites along the dimer interface with low occupation, one of which is a unique binding site for potential allosteric modulators. This new site may be of importance in the design of new allosteric regulators. PMID:20163115

Development of Pyrazolone and Isoxazol-5-one Cambinol Analogues as Sirtuin Inhibitors

PubMed Central

2015-01-01

Sirtuins are a family of NAD+-dependent protein deacetylases that play critical roles in epigenetic regulation, stress responses, and cellular aging in eukaryotic cells. In an effort to identify small molecule inhibitors of sirtuins for potential use as chemotherapeutics as well as tools to modulate sirtuin activity, we previously identified a nonselective sirtuin inhibitor called cambinol (IC50 ≈ 50 μM for SIRT1 and SIRT2) with in vitro and in vivo antilymphoma activity. In the current study, we used saturation transfer difference (STD) NMR experiments with recombinant SIRT1 and 20 to map parts of the inhibitor that interacted with the protein. Our ongoing efforts to optimize cambinol analogues for potency and selectivity have resulted in the identification of isoform selective analogues: 17 with >7.8-fold selectivity for SIRT1, 24 with >15.4-fold selectivity for SIRT2, and 8 with 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively. In vitro cytotoxicity studies with these compounds as well as EX527, a potent and selective SIRT1 inhibitor, suggest that antilymphoma activity of this compound class may be predominantly due to SIRT2 inhibition. PMID:24697269

Epilepsy

PubMed Central

Saipetch, Chutima; Sachs, Ezekiel

2016-01-01

Abstract Purpose of review: Technological advance has revolutionized epilepsy management recently. Herein, we review some recent developments. Recent findings: Responsive neurostimulation (Food and Drug Administration [FDA]-approved 2013) works by continuous analysis of brain rhythms and direct brain stimulation on detecting patterns thought to be epileptogenic, thereby aborting seizures. Cardio-responsive vagus nerve stimulation (FDA-approved 2015) is an improvement over traditional vagus nerve stimulation systems, taking advantage of the fact that 80% of seizures are associated with tachycardia. Automated tachycardia detection leads to vagus nerve stimulation to abort seizures. In MRI-guided stereotactic laser ablation (developed 2012), a directed laser emitting fiberoptic catheter is used to ablate epileptogenic lesions. The procedure can be completed in 3 to 4 hours, potentially under local anesthesia and with next-day discharge. Perampanel (FDA-approved 2012) is a promising new class of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-antagonist antiseizure therapy. Meanwhile, a millennia-old remedy for epilepsy, cannabis, is staging a comeback with recent legal and social permissiveness accelerating research into this use. Summary: The coming years will demonstrate how these recent advances in device and drug management will improve the care of epilepsy. PMID:29443283

Rh(III)-Catalyzed Decarboxylative Coupling of Acrylic Acids with Unsaturated Oxime Esters: Carboxylic Acids Serve as Traceless Activators

PubMed Central

2015-01-01

α,β-Unsaturated carboxylic acids undergo Rh(III)-catalyzed decarboxylative coupling with α,β-unsaturated O-pivaloyl oximes to provide substituted pyridines in good yield. The carboxylic acid, which is removed by decarboxylation, serves as a traceless activating group, giving 5-substituted pyridines with very high levels of regioselectivity. Mechanistic studies rule out a picolinic acid intermediate, and an isolable rhodium complex sheds further light on the reaction mechanism. PMID:24512241

Novel quinazoline ring synthesis by cycloaddition of N-arylketenimines with N,N-disubstituted cyanamides.

PubMed

Shimizu, Masao; Oishi, Akihiro; Taguchi, Yoichi; Gama, Yasuo; Shibuya, Isao

2002-03-01

The reaction of N-aryl-substituted ketenimines with N,N-disubstituted cyanamides or (MeS)2C=N-CN under high pressure afforded 4-(N,N-disubstituted amino) or 4-(MeS)2C=N-substituted quinazoline derivatives, respectively. These products were formed by [4+2] cycloaddition between the aza-diene moieties of the N-arylsubstituted ketenimines and cyano groups. A 4-(unsubstituted amino)quinazoline derivative was synthesized by hydrolysis of the latter product.