bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of 2,3‐dihydropyrido‐ and 2,3‐dihydropyrimido‐[1,4]diazepines from triaminopyridine and triaminopyrimidine
Authors: Insuasty Braulio , Perez Alfredo , Valencia John , Quiroga Jairo
Published: April 2009

The reaction of 2,3,6‐triaminopyridine 1 and 4,5,6‐triaminopyrimidine 2 with one equivalent of the chal‐cones 3, in acetic acid, leads to the formation of the 8‐amino‐2,3‐dihydro‐1H‐pyrido[2,3‐b][1,4]diazepine and 6‐amino‐2,3‐dihydro‐1H‐pyrimido[4,5‐b][1,4]diazepine derivatives 4 and 5. The products were characterized by NMR techniques such as 13C, 1H, and DEPT including selective 13C{1H} decoupling experiments.
Synthesis of optically active β‐lactams by the reaction of 2‐acyl‐3‐phenyl‐l‐menthopyrazoles with CN compounds
Authors: Kashima Choji , Fukusaka Kiyoshi , Takahashi Katsumi
Published: April 2009

The reaction of 1‐acyl‐3,5‐dimethylpyrazoles 1 with CN compounds was kinetically controlled with syn stereoselectivity through a lithium enolate intermediate using lithium diisopropylamide. In contrast, the anti stereoselective reaction of 1 was caused by the action of diisopropylethylamine in the presence of magnesium bromide under the thermodynamic control. Reaction of 2‐acyl‐3‐phenyl‐l‐menthopyrazoles 12 with CN compounds was observed in higher chemical and optical yields with the predominant 2′S configuration. An especially diastereomerically pure product was isolated in the reaction of 2‐propanoyl‐3‐phenyl‐l‐menthopyrazole (12a) with N‐benzylidene‐4‐toluenesulfonamide (2). The products from N‐acyl‐pyrazoles and CN compounds were further cyclized into β‐lactams directly or with short conversion steps.
Chemistry of functionalized benzazepines. 5. Synthesis and chemical transformation of the 1,2,4,5‐tetrahydrospiro‐[3H‐2‐benzazepine‐3,1′‐cycloalkanes]
Authors: Kouznetsov Vladimir , Alirio Palma R. , Salas Sandra , Vargas Leonor Y. , Martinez Jairo René , Zubkov Fedor , Varlamov Alexei
Published: April 2009

The synthesis of new spiro derivatives of tetrahydro‐2‐benzazepine was accomplished and their nitration, bromination, allylation, acetylation, formylation and oxidation reactions were studied. Nitration and bromi‐nation of 5‐methyl(1,5‐dimethyl)‐1,2,4,5‐tetrahydrospiro[3H‐2‐benzazepine‐3,1‐cycloalkane] took place regioselectively on position C‐8 of the phenyl ring. A nitrone was obtained for the first time in the title series. The structures of the compounds were established by ir and nmr spcctroscopy.
Synthesis of 3,5‐disubstituted 1‐amino‐1,3,5‐triazine‐2,4,6‐triones (or 1‐aminocyanurates) by cyclic transformation of 1,3,4‐oxadiazol‐2(3H)‐one derivatives
Authors: Chau François , Malanda Jean‐Claude , Milcent René
Published: April 2009

The 5‐aryl(or methyl)‐3‐phenylcarbamoyl‐1,3,4‐oxadiazol‐2(3H)‐ones 2, in the presence of sodium hydride in anhydrous dimethylformamide, were transformed into 1‐benzamido(or acetamido)‐3,5‐diphenyl‐1,3,5‐triazine‐2,4,6‐trione derivatives 7 in poor yields. However, compounds 7 were obtained in better yields when the sodium salts of 5‐aryl(or methyl)‐1,3,4‐oxadiazol‐2(3H)‐ones 1 were treated with two equivalents of aryl(or ethyl)isocyanates. Acidic hydrolysis of 1‐acetamido‐3,5‐diphenyl‐1,3,5‐triazine‐2,4,6‐trione (7i) provided the corresponding free N‐amino derivative 9. Nitrous deamination of 9 gave the known 3,5‐diphenyl‐1,3,5‐triazine‐2,4,6‐trione (11). This cyclic transformation is the first one to be reported providing 1,3,5‐triazine‐2,4,6‐trione derivatives.
Studies on isoxazole and pyrazole formation by the reaction of trifluoromethyl‐substituted anilines with oxime and hydrazone dianions
Authors: Strekowski Lucjan , Lin Shou‐Yuan
Published: April 2009

5‐(2‐Aminophenyl)isoxazoles are obtained in good yields by the reaction of 2‐(trifluoromethyl)aniline with dilithio derivatives of oximes of acetone, 3‐pentanone, propiophenone, and cyclohexanone. An analogous synthesis of a substituted isoxazole from 4‐(trifluoromethyl)aniline and 3‐pentanone oxime and the synthesis of a substituted pyrazole from 2‐(trifluoromethyl)aniline and 3‐pentanone hydrazone are less efficient.
Synthesis of potential metabolites of the brain imaging agents methyl (1R,2S,3S,5S)‐3‐(4‐Iodophenyl)‐8‐alkyl‐8‐azabicyclo[3.2.1]octane‐2‐carboxylate
Authors: Andersen Annette , Wang Shaoyin , Thompson Robert D. , Neumeyer John L.
Published: April 2009

The synthesis of potential hydroxy metabolites of the brain imaging agents methyl (1R,2S,3S,5S)‐3‐(4‐iodophenyl)‐8‐methyl‐8‐azabicyclo[3.2.1]octane‐2‐carboxylate and methyl (1R,2S,3S,5S)‐3‐(4‐iodophenyl)‐8‐(3‐fluoropropyl)‐8‐azabicyclo[3.2.1]octane‐2‐carboxylate are reported. The nitration of iodophenyltropanes 1 or 2 with nitronium tetrafluoroborate afforded the nitro compounds 3 or 4 which were reduced with iron powder to the corresponding amino compounds 5 and 6. The final hydroxylated products 7 and 8 were obtained via a modified Sandmeyer reaction.
Reactions of O‐methyl o‐quinone monoximes with methyl‐, methylene‐ and methine‐ substituted aromatic compounds. Synthesis of benzo[d]oxazole and 1,4‐benzoxazine derivatives
Authors: Nicolaides Demetrios N. , Awad R. Wajih , Papageorgiou Georgios K. , Kojanni Efthalia , Tsoleridis Constantinos A.
Published: April 2009

O‐Methyl o‐quinone monoxime 1 reacts thermally with compounds 2a‐d or 6a,b or 7a,b to give mainly the corresponding 2‐substituted phenanthroxazoles 3a‐c and 8. The reaction of 1 with aromatic methylene compounds lOa‐c affords the ketones 13a‐c in moderate to high yields. Similar products are also obtained from the reaction of monoximes 15a,b with some of the above reactants. The unexpected products 5 and 20 are obtained from the reaction of 1 with 2‐methylimidazole (2d) and with phenyloxirane (19) respectively, while the 4H‐1,4‐oxazine derivative 23 is obtained from the reaction of 1 with indene (21).
A new approach for the synthesis of some 1,4‐benzoxathiin 4,4‐dioxide derivatives
Authors: Fan Ai‐Long , Cao Song , Zhang Zheng
Published: April 2009

A series of 1,4‐benzoxathiin 4,4‐dioxide derivatives have been prepared by a new synthetic route. The reactions of 2‐chloro‐4‐nitrobenzenethiol 1 with l‐aryl‐2‐chloroethanones 2 in the presence of sodium hydroxide give l‐aryl‐2‐(2‐chloro‐4‐nitrophenylthio)ethanones 3 which on oxidation with 30% aqueous hydrogen peroxide afford l‐aryl‐2‐(2‐chloro‐4‐nitrophenylsulfonyl)ethanones 4. By the reactions of compounds 4 with 2‐[3 or 4‐(bromomethyl)phenyl]benzoxazole in the potassium carbonate, triethylbenzyl‐ammonium chloride and dimethylformamide system, 2‐aryl‐3‐arylmethyl‐7‐nitro‐1,4‐benzoxathiin 4,4‐dioxides 5 or 6 are obtained via a tandem alkylation‐cyclization process.
Nonclassical 5‐substituted tetrahydroquinazolines as potential inhibitors of thymidylate synthase
Authors: Gangjee Aleem , Vasudevant Anil , Kisliuk Roy L.
Published: April 2009

Classical inhibitors of thymidylate synthase such as Nl0‐propargyl‐5,8‐dideazafolic acid (1), N‐(5‐[N‐(3,4‐dihydro‐2‐methyl‐4‐oxoquinazolin‐6‐ylmethyl)‐N‐methylamino]‐2‐thenoyl)‐L‐glutamic acid (ZD1694, 2) and N‐[2‐amino‐4‐oxo‐3,4‐dihydro(pyrrolo[2,3‐d]pyrintidin‐5‐yl)ethylbenzoyl]‐L‐glutamic acid (LY231514, 3) while potent, suffer from a number of potential disadvantages, such as impaired uptake due to an alteration of the active transport system required for their cellular uptake, as well as formation of long acting, non‐effluxing polyglutamates via the action of folylpolyglutamate synthetase, which are responsible for toxicity. To overcome some of the disadvantages of classical inhibitors, there has been considerable interest in the synthesis and evaluation of nonclassical thymidylate synthase inhibitors, which could enter cells via passive diffusion. In an attempt to elucidate the role of saturation of the B‐ring of non‐classical, quinazoline antifolate inhibitors of thymidylate synthase, analogues 7‐17 were designed. Analogues 13‐17 which contain a methyl group at the 7‐position, were synthesized in an attempt to align the methyl group in an orientation which allows interaction with tryptophan‐80 in the active site of thymidylate synthase. The synthesis of these analogues was achieved via the reaction of guanidine with the appropriately substituted cyclohexanone‐ketoester. These ketoesters were in turn synthesized via a Michael addition of the appropriate thiophenol with 2‐carbethoxycyclohexen‐1‐one or 5‐methyl‐2‐carbethoxycyclo‐hexen‐1‐one to afford a mixture of diastereomers. The most inhibitory compound was the 3,4‐dichloro, 7‐methyl derivative 17 which inhibited the Escherichia coli and Pneumocystis carinii thymidylate syntheses 50% at 5 × 105 M. Our results confirm the importance of the 7‐CH3 group and electron withdrawing groups on the aromatic side chain for thymidylate synthase inhibition.
A convenient preparation of 4,8‐dimethoxy‐3‐substituted‐2(1H)‐quinolones by an electrophilic reaction through base‐induced deprotonation and its synthetic application for the synthesis of new alkaloids, 3,4,8‐trimethoxy‐2(1H)‐quinolone and 3‐formyl‐4,7,8‐trimethoxy‐2(1H)‐quinolone(glycocitridine)
Authors: Tagawa Yoshinobu , Kawaoka Takamitsu , Goto Yoshinobu
Published: April 2009

Some 4,8‐dimethoxy‐3‐substituted‐2(1H)‐quinolones were prepared by electrophilic reaction of 4,8‐dimethoxy‐2(1H)‐quinolone with electrophiles in the presence of n‐butyllithium‐N,N,N',N'‐tetramethylethyl‐enediamine in fairly good yields. This present method was successfully applied for the synthesis of two new alkaloids bearing the 4,8‐dimethoxy‐2(1H)‐quinolone skeleton.
Studies in anthraquinone: Preparation of 2‐substituted pyrimidoanthraquinones and related fused 1,2,4‐triazolo, tetrazolo and pyrazolino derivatives
Authors: Kangani C. O. , Master H. E.
Published: April 2009

This paper describes the synthesis of 2‐substituted‐4(3H)‐oxopyrimido[4,5‐a]anthraquinone, 2‐substi‐tuted‐4‐hydrazinopyrimido[4,5‐a]anthraquinones, several 2‐substituted‐1,2,4‐triazolo[4,3‐c]pyrimido[4,5‐a]‐anthraquinones tetrazolo[4,5‐c]pyrimido[4,5‐a]anthraquinones and pyrazolinopyrimidoanthraquinone derivatives.
Nitrosation of methyl 2‐cinnamoylamino‐3‐dimethylaminopropenoates. Alkyl N‐cinnamoyloxalic acid hydroxyimidic amides, intermediates in the synthesis of alkyl 5‐styryl‐1,2,4‐oxadiazole‐3‐carboxylates
Authors: Kmetič Matej , Stanovnik Branko
Published: April 2009

Alkyl 2‐(substituted cinnamoylamino)‐3‐dimethylaminopropenoates 5, prepared either from glycine (1) and substituted cinnamoyl chlorides 2 via oxazol‐5(4H)‐ones 4, or from cinnamoylglycinate with t‐butoxy‐bisdimethylaminomethane, were transformed by nitrosation into 5‐substituted‐1,2,4‐oxadiazole‐3‐carboxylates 8. The formation of alkyl N‐cinnamoyloxalic acid hydroxyimidic amides 7, which were isolated as intermediates, represent a novel synthesis of N‐acyl substituted hydroxyimidic amides.
Synthesis of benzothiophene analogues of ketoconazole and itraconazole
Authors: Bolós Jordi , Gilbert Santiago , Anglada Lluis , Sacristan Aurelio , Ortiz José A.
Published: April 2009

The synthesis of the benzothiophene analogues of the orally active antifungal agents ketoconazole and itraconazole 3a and 3b is reported. The key heterocyclic system 3‐(1‐piperazinyl)benzo[b]thiophene is prepared by formation of the enamine between a benzothienone and ethyl 1‐piperazinecarboxylate. After elaboration of the respective N‐substituents, the methoxy group is cleaved with boron tribromide, and O‐alky‐1ated with the corresponding mesylates.
UV and MO study on the deprotonation of some 2‐aryl‐Δ2‐1,3,4‐oxadiazoline‐5‐thiones
Authors: Tsoleridis C. A. , Charistos D. A. , Vagenas G. V.
Published: April 2009

Substituent effects on the deprotonation processes of a series of 2‐aryl‐Δ2‐1,3,4‐oxadiazoline‐5‐thione (1) derivatives have been studied experimentally as well as theoretically. The acid dissociation constants pKa have been determined spectrophotometrically in ethanol‐water solutions (7.5‐92.5%) and vary between 3.76 and 5.80. Semiempirical molecular orbital (MO) calculations (AM1 and PM3) were used for the investigation of the existence of possible tautomeric thione and thiol forms of the studied compounds. Strong correlation between the pKa values and the deprotonation enthalpies were evaluated.
Synthesis and reduction ability of borane complexes of 2‐aminopyridine derivative having a chiral center at the amino nitrogen
Authors: Yamaguchi Yoshimi , Okamoto Yoshihisa , Takada Atsushi
Published: April 2009

A novel method for synthesis of a chiral amine borane is described and selective reductions of carbonyl compounds with the amine borane are investigated.
Oxidation of 1‐[(aryl)(phenylseleno)methyl]‐, 1‐[(aryl)(arylthio)‐(phenylseleno)methyl]‐, and l‐[(aryl)(diphenylseleno)methyl]benzotriazoles with m‐chloroperbenzoic acid
Authors: Kang Yoon Ho , Kim Kyongtae
Published: April 2009

During the last decade, benzotriazole (1) has received much attention as an excellent synthetic auxiliary [1]. Recently Katritzky, et al. [2] studied the oxidation of 1‐(phenylthiomethyl)benzotriazole (2a) and 1‐(2‐phenyl‐1‐phenylthioethyl)benzotriazole (2b) and obtained their sulfones and sulfoxides by treatment with wj‐chloroperbenzoic acid (m‐CPBA) and sodium periodate, respectively. No compounds derived from a heterolytic cleavage between the α‐carbon and the N‐1 atoms of the foregoing compounds were isolated.
Synthesis of 2‐phenylimidazo[2,1‐b]benzothiazole derivatives as modulators of multidrug resistance for tumor cells
Authors: Tasaka Shigeyuki , Tanabe Hirokazu , Sasaki Yoshiyuki , Machida Toshiki , Iino Mayumi , Kiue Akira , Naito Seiji , Kuwano Michihiko
Published: April 2009

We have investigated 3‐substituted‐2‐phenylimidazo[2,1‐b]benzothiazole derivatives and herein we have discussed their pharmaceutical activities. We found that some 2‐phenyl‐5,6,7,8‐tetrahydroimidazo[2,1‐b]‐benzothiazoles could overcome multidrug resistance for tumor cells. Among them, 2‐phenyl‐3‐(N‐methyl‐3‐piperidyl)carbonylammomiinomemyl‐5,6,7,8‐tetrahydVoimidazo[2,1‐b]benzothiazole [N276‐12] demonstrated the most potent activity for overcoming multidrug resistance.
Pyridinium betaines derived from thiazolo and imidazoacridinones
Authors: Galy Jean‐Pierre , Hanoun Jean‐Pierre , Pique Valerie , Jagerovic Nadine , Elguero JosÉ
Published: April 2009

Four betaines derived from imidazo[4,5‐a], imidazo[5,4‐a] and thiazolo[5,4‐a]acridine have been prepared in a six step procedure starting from 2‐chlorobenzimidazoles and benzothiazoles. The 1H and 13C nmr has been used to characterize the compounds, particularly the orientation of the step leading to the formation of the acridinone ring. The uv‐visible spectra of one betaine (wave numbers v in cm−1) shows a linear dependence with Reichardt's ET parameter and a high sensitivity to solvent effects.
An alternative synthesis of 10H‐indolo[3,2‐b]quinoline and its selective N‐alkylation
Authors: Fan Pingchen , Ablordeppey Seth Y.
Published: April 2009

A new and a more efficient synthesis of 10H‐Indolo[3,2‐b]quinoline (quindoline) is reported. The synthesis involved N‐arylation of 3‐aminoquinoline with triphenylbismuth diacetate followed by oxidative cyclization using paOadium(II) acetate. A selective N‐alkylation methodology for quindoline was also developed. Alkylation on N‐5 was obtained in sulpholane, while alkylation on N‐10 was achieved in acetone in the presence of potassium hydroxide. A sequential N‐5‐ and N‐10 double alkylation procedure was also formulated.
Synthesis of pyrazolo‐fused heterocycles by a tandem appel's dehydration/electrocyclization methodology
Authors: Lee Kee‐Jung , Kwon Heung‐Taeck , Kim Boo‐Geun
Published: April 2009

The hydrazones of benzophenone, benzil, and acetophenone were allowed to react with acetoacetanilide to give azinoamides 18, and the reaction of 18 with Appel's dehydrathon contiditons (triphenylphosphine/carbon tetra‐chloride/triethylatnine) led to the corresponding azinoketimines 19, which underwent elctrocyclic ring closure under the reaction conditions to give pyrazolo‐fused heterocycles. Azinoamide 18a gave a 4,9‐dihydropyazolo‐[5,1‐b]quinazoine 21, while 18b yielded 2,3‐dihydro‐1H‐imidazo[1,2‐b]pyrazol‐2‐one 26 and 1H‐imidazo[1,2‐b]‐pyrazole 29. Compound 18c gave a monocyclic N‐α‐styryl‐5‐(phenylamino)pyrazole 32.
Diethyl ethoxymethylenemalonate in triheterocycles: A new synthesis of pyrido[3,2‐e]pyrimido[1,2‐c]pyrimidines
Authors: Dave Chaitanya G. , Shukla Manish C.
Published: April 2009

Diethyl ethoxymethylenemalonate was used for the novel synthesis of the triheterocyclic 3‐carbethoxy‐9,ll‐disubstituted‐4‐oxo‐4H‐pyrido[3,2‐e]pyrimido[1,2‐c]pyrimidines from 4‐aminopyrido[2,3‐d]pyrim‐idines via thermal cyclization of the intermediate ethyl 2‐carbethoxy‐3‐[5,7‐disubstituted‐4‐amino‐pyrido[2,3‐d]pyrimidin‐4‐yl]acrylates. The alkaline hydrolysis of 3‐carbethoxy‐4‐oxo‐4H‐pyrido[3,2‐e]‐pyrimido[1,2‐c]pyrimidines was performed to give corresponding acid derivatives.
Reaction of 1,2‐diamines with 4‐hydroxycoumarin. Synthesis of 1,4‐diazepin‐5‐ones
Authors: Hamdi MaÂMar , Cottet Sophie , Tedeschi Christine , Spéziale Vincent
Published: April 2009

1,4‐diazepin‐5‐ones were obtained from 4‐hydroxycoumarin and substituted 1,2‐diamines by heating in 2‐methyl‐1‐propanol.
An unusual substituent effect in a cycloaddition of an azolium ylide 1,3‐dipole: An inverted V‐shaped hammett plot
Authors: Butler Richard N. , Grogan Denise C. , Burke Luke A.
Published: April 2009

An unusual inverted V‐shaped Hammett plot has been observed for substituent effects at the N‐terminus of 1,2,3‐triazolium‐1‐imide 1,3‐dipoles in cycloaddition reactions. Theoretical studies (3‐21G and 6‐31G) suggest strong resonance interactions separately stabilizing both ends of the dipole.
The synthesis of novel polycyclic heterocyclic ring systems. 3. Synthesis and NMR spectroscopy of 15‐chloro[1]benzo‐thieno[2″,3″:3′,4′]naphtho[1′,2′:4,5]thieno[2,3‐c]quinoline
Authors: Sasaki Kenji , Tokuda Osamu , Hirota Takashi , Luo Jiann‐Kuan , Federspiel Ronald F. , Castle Raymond N.
Published: April 2009

The polycyclic heterocyclic compound with a novel ring system, 15‐chloro[1]benzothieno[2″,3″:3′,4′]‐naphtho[1′,2′:4,5]thieno[2,3‐c]quinoline was synthesized via photocyclization of 3‐chloro‐N‐phenyl[1]‐benzothieno[2′,3′:3,4]naphtho[2,1‐b]fhiophene‐2‐carboxamide followed by chlorination with phosphorus oxychloride. The assignment of its 1H and 13C nmr spectra was accomplished by utilizing two‐dimensional nmr methods.
Photocyclization reactions. Part 7. Solvent and substituent effects in the synthesis of dihydrobenzofuranols using photocyclization of α‐(2‐acylphenoxy)toluenes and ethyl 2‐acylphenoxyacetates
Authors: Sharshira Essam Mohamed , Horaguchi Takaaki
Published: April 2009

Photocyclization reactions were carried out on α‐(2‐acylphenoxy)toluenes 1a‐e and 2‐acylphenoxy‐acetates 2a‐e in three solvents of different polarity (benzene, acetonitrile and methanol) to examine solvent and substituent effects on the cyclization of 1,5‐biradical intermediates to dihydrobenzofuranols. Irradiation of 1a‐e in benzene gave cis‐dihydrobenzofuranols cis‐4b‐e selectively in 14‐84% yields along with rearranged products, 2‐acylbenzophenones 5b‐d (23‐39% yields). Photocyclization of la‐e in acetonitrile or methanol gave a mixture of eis‐ and trans ‐dihydrobenzofuranols 4a‐e in 28‐81% yields and small amount of 2‐acylbenzophenones 5b‐c in 6‐12% yields. In polar acetonitrile or methanol, the cis and trans stereoselectivity of dihydrobenzofuranols decreased. The decrease in stereoselectivity was attributed to intermolecular hydrogen bonding between the hydroxyl group of 1,5‐biradicals and solvents. On the other hand, irradiation of esters 2a‐e in benzene afforded cis‐dihydrobenzofuranols cis‐13a‐e selectively in 48‐74% yields. Similarly, photocyclization of 2a‐e in acetonitrile or methanol produced dihydrobenzofuranols 13a‐e in a fair to good yields. In the photocyclization of 2b‐d, not only in nonpolar benzene but also in polar acetonitrile or methanol, increasing the size of alkyl group from methyl (R = Me) to ethyl or iso‐propyl group (R = Et or i‐Pr) gave cis‐dihydrobenzofuranols cis‐13b‐d predominantly. Conformational, solvent and substituent effects on the cyclization of 1,5‐biradicals and reaction pathways are discussed.
Direct conversion of hydroxy aromatic compounds to heteroarylamines via a one‐pot smiles rearrangement procedure
Authors: Weidner John J. , Peet Norton P.
Published: April 2009

8‐Hydroxyquinoline (9) was converted to 8‐aminequinoline (10) in a one‐pot procedure involving alleviation with 2‐bromo‐2‐methylpropionamide (2) followed by Smiles rearrangement and hydrolysis, in 41% yield. The scope and limitations of this new procedure were explored with additional hydroxyquinolines.
Clay catalized rearrangement of phenyloxiranes
Authors: Martínez Roberto , Velasco Micaela , Martínez Ignacio , Menconi Italo , Ramfrez Alberto , Angeles Enrique , Regla Ignacio , López Rafael
Published: April 2009

The reaction of phenyloxiranes with a clay produces aldehydes, ketones and cyclic ethers. This method has the advantage that experimental conditions are simple and the reagents used are cheaper.
Dynamical versus statistical downscaling methods for ocean wave heights
Authors: Wang Xiaolan L. , Swail Val R. , Cox Andrew
Published: April 2009

In this study, dynamical and statistical downscaling methods for estimating seasonal statistics of significant wave heights (SWH) were intercompared, with the downscaling results being evaluated against the ERA40 wave data in terms of climatological characteristics and interannual variability. It was also shown that biases in climate‐model‐simulated climate and variability of the atmospheric circulation (or predictors in general) can result in large biases in the estimated climate and variability of SWH (or the predictand in general), and that such biases can be effectively diminished by using standardized predictor quantities in statistical downscaling models. In dynamical downscaling, however, model variability biases remain to be dealt with, whereas the effects of model climate biases can be reduced to some extent by replacing the climate‐model‐simulated wind climate with the observed one. Therefore, the dynamical approach was found to be not as good as the statistical methods in terms of reproducing the observed climate and interannual variability of the predictand, although it bears substantial similarity to the statistical methods in terms of projected possible future changes. Also, it was shown that the observed interannual variability of seasonal statistics (including extremes) can be better reproduced by using 12‐hourly, rather than seasonal, data in statistical downscaling. This stresses the importance of availability of higher‐resolution data from climate model outputs. Nevertheless, a non‐stationary extreme value model with covariates was found to be the best in reproducing the observed climate of extremes. All the statistical downscaling methods and the intercomparison results are applicable to other climate variables (not limited to ocean wave heights). Copyright © 2009 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.
Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons
Authors: Schnabel Lauren V. , Lynch Maureen E. , van der Meulen Marjolein C.H. , Yeager Amy E. , Kornatowski Matthew A. , Nixon Alan J.
Published: April 2009

Tendinitis remains a catastrophic injury among athletes. Mesenchymal stem cells (MSCs) have recently been investigated for use in the treatment of tendinitis. Previous work has demonstrated the value of insulin‐like growth factor‐I (IGF‐I) to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendinitis. This study examined the effects of MSCs, as well as IGF‐I gene‐enhanced MSCs (AdIGF‐MSCs) on tendon healing in vivo. Collagenase‐induced bilateral tendinitis lesions were created in equine flexor digitorum superficialis tendons (SDFT). Tendons were treated with 10 × 106MSCs or 10 × 106AdIGF‐MSCs. Control limbs were injected with 1 mL of phosphate‐buffered saline (PBS). Ultrasound examinations were performed att = 0, 2, 4, 6, and 8 weeks. Horses were euthanized at 8 weeks and SDFTs were mechanically tested to failure and evaluated for biochemical composition and histologic characteristics. Expression of collagen types I and III, IGF‐I, cartilage oligomeric matrix protein (COMP), matrix metalloproteinase‐3 (MMP‐3), matrix metalloproteinase‐13 (MMP‐13), and aggrecanase‐1 (ADAMTS‐4) were similar in MSC and control tendons. Both MSC and AdIGF‐MSC injection resulted in significantly improved tendon histological scores. These findings indicate a benefit to the use of MSCs and AdIGF‐MSCs for the treatment of tendinitis. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1392–1398, 2009
Sustained and localized in vitro release of BMP‐2/7, RANKL, and tetracycline from Flexbone, an elastomeric osteoconductive bone substitute
Authors: Xu Jianwen , Li Xinning , Lian Jane B. , Ayers David C. , Song Jie
Published: April 2009

We tested the hypothesis that synthetic composites containing a high percentage of osteoconductive biominerals well‐integrated with a hydrophilic polymer matrix can be engineered to provide both the structural and biochemical framework of a viable synthetic bone substitute. FlexBone, an elastic hydrogel‐mineral composite exhibiting excellent structural integration was prepared by crosslinking poly(2‐hydroxyethyl methacrylate) hydrogel in the presence of 25 wt% nanocrystalline hydroxyapatite and 25 wt% tricalcium phosphate. Biologically active factors tetracycline, BMP‐2/7, and RANKL that stimulate bone formation and remodeling were encapsulated into FlexBone during polymerization or via postpolymerization adsorption. SEM and dynamic mechanical analyses showed that the encapsulation of tetracycline (5.0 wt%) did not compromise the structural integrity and compressive behavior of FlexBone, which could withstand repetitive megapascal‐compressive loadings and be securely press‐fitted into critical femoral defects. Dose‐dependent, sustained in vitro release of tetracycline was characterized by spectroscopy and bacterial inhibition. A single dose of 40 ng BMP‐2/7 or 10 ng RANKL pre‐encapsulated with 50 mg FlexBone, released over 1 week, was able to induce local osteogenic differentiation of myoblast C2C12 cells and osteoclastogenesis of macrophage RAW264.7 cells, respectively. With a bonelike structural composition, useful surgical handling characteristics, and tunable biochemical microenvironment, FlexBone provides an exciting opportunity for the treatment of hard‐to‐heal skeletal defects with minimal systemic side effects. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1306–1311, 2009
Cultivar and growing area effects on minor compounds of olive oil from autochthonous and European introduced cultivars in Tunisia
Authors: Dabbou Samia , Issaoui Manel , Esposto Sonia , Sifi Samira , Taticchi Agnese , Servili Maurizio , Montedoro Gian Francesco , Hammami Mohamed
Published: April 2009

BACKGROUND: Antioxidant profile and volatile compounds were characterized in three virgin olive oils from European countries introduced and cultivated under the same orchard conditions in comparison to some autochthonous cultivars planted in different areas of Tunisia.

RESULTS: Significant differences were observed between the oils. α‐Tocopherol content is more important in autochthonous Tunisian cultivars (cvs), higher (400 mg kg−1) than in European cvs. Total phenols showed that Chétoui cv. (grown in Zaghouan) had the highest level (446 mg kg−1), followed by Koroneiki (403 mg kg−1) and Chétoui cvs (grown in Béja) (398 mg kg−1). Koroneiki oils had the highest content of (3,4‐dihydroxyphenyl)ethanol and (p‐hydroxyphenyl)ethanol (20.5 and 43.5 mg kg−1, respectively), whereas (3,4‐dihydroxyphenyl)ethanol was not detected in Arbequina, Arbosana or Chemlali cvs (grown in Sahel). Chétoui cv. presented the highest content of dialdehydic form of decarboxymethyl elenolic acid linked to (3,4‐dihydroxyphenyl)ethanol (171 mg kg−1), whereas Chemlali (Sahel) cv. had the lowest content (29.6 mg kg−1). The volatile compounds showed an increase in C6 compounds and decrease in pentene isomers in olive oils from varieties cultivated in other growing areas.

CONCLUSION: Virgin olive oils studied demonstrate that the differences in phenols, tocopherol levels and volatile profiles may be explained by genetic factors and geographic areas, particularly altitude. Copyright © 2009 Society of Chemical Industry
The outcome of sentinel node biopsy in breast cancer patients with preoperative surgical biopsy
Authors: Leidenius Marjut H.K. , Vironen Jaana H. , von Smitten Karl A.J. , Heikkilä Päivi S. , Joensuu Heikki
Published: April 2009

Background

The aim of the study was to evaluate the outcome of sentinel node biopsy (SNB), especially the medium term axillary recurrence rate after negative SNB in patients with preoperative surgical biopsy (SB).

Patients and Methods

The study included 1,641 patients with a histological stage T1 tumours and SNB. In 77 patients, the diagnosis was obtained with SB, while 1,564 patients had underwent needle biopsy (NB) only. Axillary clearance was omitted in 56 SB patients and 921 NB patients after negative SNB. The median duration of follow‐up in these patients was 54 months.

Results

None of the SB patients had axillary recurrences during the follow‐up. Six NB patients had isolated axillary recurrences while three patients had concomitant local and axillary recurrences. There were no differences in local or distant recurrences or breast cancer deaths between the SB and the NB patients.

Conclusions

SNB seems a feasible axillary staging method in patients with histological stage T1 tumour also after preoperative SB. The risk of axillary recurrence after negative SNB is negligible in these patients. J. Surg. Oncol. 2009;99:420–423. © 2009 Wiley‐Liss, Inc.
Asymmetric flow field‐flow fractionation of liposomes: optimization of fractionation variables
Authors: Hupfeld Stefan , Ausbacher Dominik , Brandl Martin
Published: April 2009

The purpose of this study was to investigate the influence of ionic strength of the carrier liquid, cross flow rate, focus flow rate, and sample load on the retention behavior of liposomes in asymmetric flow field‐flow fractionation (AF4). Two differently prepared samples of large unilamellar vesicles (LUV) were used. Experiments were performed varying the factors systematically and evaluating their effect on both retention behavior of the liposomes and on particle size as obtained from online coupled multi‐angle light scattering (MALS) analysis. The results showed that the focus flow rate had the least influence on the elution of liposomes. Elution of LUV is mainly governed by the chosen cross flow condition and ionic strength of the carrier liquid as well as its sample load. Optimal fractionation and size analysis were achieved using a sample load of about 10 μg, a cross flow gradient from 1.0 to 0.1 mL/min over 35 min and a carrier solution of NaNO3 with a concentration of 10 mM.
Application of 10‐ethyl‐acridine‐3‐sulfonyl chloride for HPLC determination of aliphatic amines in environmental water using fluorescence and APCI‐MS
Authors: You Jinmao , Zhao Huaixin , Sun Zhiwei , Xia Lian , Yan Tao , Suo Yourui , Li Yulin
Published: April 2009

A simple, sensitive method for the determination of aliphatic amines based on a sulfonylation reaction using 10‐ethyl‐acridine‐3‐sulfonyl chloride (EASC) as pre‐column labeling reagent with fluorescence detection and APCI‐MS identification has been developed. The labeled derivatives exhibited high stability and were enough to be efficiently analyzed by HPLC with an excitation maximum at λex 270 nm and an emission maximum at λem 430 nm. Identification of derivatives was carried out by online post‐column MS in positive‐ion mode. Comparing with the widely used 5‐dimethylaminonaphthalene‐1‐sulfonylchloride (Dansyl‐Cl), EASC‐amine derivatives not only exhibited high fluorescence but also exhibited excellent MS ionizable potential. Detection limits obtained from 0.10 pmol injection, at a S/N of 3, were 4.0–12.7 fmol. The mean intra‐ and inter‐assay precision for all aliphatic amine levels were <3.84 and 3.21%, respectively. Excellent linear responses were observed with coefficients of >0.9995.
Characterization of poly(ethylene glycol)‐b‐ poly(ε‐caprolactone) by two‐dimensional liquid chromatography
Authors: Ahmed Hasnat , Trathnigg Bernd
Published: April 2009

Block copolymers of ethylene oxide and ε‐caprolactone were synthesized by microwave‐assisted polymerization of ε‐caprolactone with polyethylene glycol monomethyl ethers as initiator. The samples thus obtained were characterized by two‐dimensional liquid chromatography with liquid chromatography at critical conditions as the first and liquid exclusion adsorption chromatography as the second dimension. A full baseline separation of all oligomers could be achieved in both dimensions.
Direct estimation of an element of order matrix from 1H NMR spectra of strongly dipolar coupled spins
Authors: Manjunatha Reddy G. N. , Suryaprakash N.
Published: April 2009

NMR spectra of molecules oriented in thermotropic liquid crystalline media provide information on the molecular structure and order. The spins are generally strongly dipolar coupled and the spectral analyses require the tedious and time consuming numerical iterative calculations. The present study demonstrates the application of multiple quantum spin state selective detection of single quantum transitions for mimicking the homonuclear decoupling and the direct estimation of an element of ordering matrix. This information is utilized to estimate the nearly accurate starting dipolar couplings for iterative calculations. The studies on the spectra of strongly dipolar coupled five and six interacting spin systems are reported. Copyright © 2009 John Wiley & Sons, Ltd.
Solving the advection–diffusion equation on unstructured meshes with discontinuous/mixed finite elements and a local time stepping procedure
Authors: El Soueidy Ch. P. , Younes A. , Ackerer P.
Published: April 2009

Explicit schemes are known to provide less numerical diffusion in solving the advection–diffusion equation, especially for advection‐dominated problems. Traditional explicit schemes use fixed time steps restricted by the global CFL condition in order to guarantee stability. This is known to slow down the computation especially for heterogeneous domains and/or unstructured meshes. To avoid this problem, local time stepping procedures where the time step is allowed to vary spatially in order to satisfy a local CFL condition have been developed.

In this paper, a local time stepping approach is used with a numerical model based on discontinuous Galerkin/mixed finite element methods to solve the advection–diffusion equation. The developments are detailed for general unstructured triangular meshes.

Numerical experiments are performed to show the efficiency of the numerical model for the simulation of (i) the transport of a solute on highly unstructured meshes and (ii) density‐driven flow, where the velocity field changes at each time step.

The model gives stable results with significant reduction of the computational cost especially for the non‐linear problem. Moreover, numerical diffusion is also reduced for highly advective problems. Copyright © 2009 John Wiley & Sons, Ltd.
“I'm a mother first”: The influence of mothering in the decision‐making processes of battered immigrant Latino women
Authors: Kelly Ursula A.
Published: April 2009

Healthcare providers (HCPs) may be perplexed by the decision‐making processes of battered Latino women in situations involving intimate partner violence (IPV). In particular, decisions may appear contradictory and hazardous to the women's children. The findings of this interpretive descriptive study reveal that the mothering role was central to battered Latina mothers' decisions. The mothers strove to prioritize, protect, and provide for their children in every way, including managing the abuse and avoiding IPV disclosure to HCPs. Disparate understandings of the women's decisions and mothering create a Catch‐22 between battered Latina mothers and their HCPs. A trusting mother‐HCP relationship is necessary for effective screening and intervention for IPV. This requires HCPs' understanding of these mothers' decisions and changes in clinical practice. © 2009 Wiley Periodicals, Inc. Res Nurs Health 32:286–297, 2009
Strategic stakeholder orientations and performance consequences—a case of private nonprofit performing arts in the US
Authors: Hsieh Jasper
Published: April 2009

This paper borrows a market orientation perspective in considering how organizations behave toward stakeholders and the implications on performance in the institutional performing arts environment. To investigate the relationship between stakeholder orientations and organizational performance, both interviews and a survey instrument were used. Using nonprofit performing arts organizations in three metropolitan areas of Northwestern US as a sample frame, primary data was collected from leading directors of these organizations. The results generally indicate a positive relationship between stakeholder orientation and organizational performance. Complex relationships between dimensions of stakeholder orientation and performance consequences were also observed.

Copyright © 2009 John Wiley & Sons, Ltd.
Thermally denatured state determines refolding in lipase: Mutational analysis
Authors: Ahmad Shoeb , Rao Nalam Madhusudhana
Published: April 2009

Irreversibility of thermally denatured proteins due to aggregation limits thermodynamic characterization of proteins and also confounds the identification of thermostable mutants in protein populations. Identification of mutations that prevent the aggregation of unfolded proteins provides insights into folding pathways. In a lipase from Bacillus subtilis, evolved by directed evolution procedures, the irreversibility due to temperature‐mediated aggregation was completely prevented by a single mutation, M137P. Though the parent and the mutants unfold completely on heating, mutants having substitutions M137P, along with M134E and S163P, completely or partially prevent the formation of aggregation‐prone intermediate(s) at 75°C. The three mutants show only a marginal increase in free energy of unfolding (ΔG), however, the profiles of the residual activity with temperature shows remarkable shift to higher temperature compared to parent. The intermediate(s) were characterized by enhanced binding of bis‐ANS, a probe to titrate surface hydrophobicity, aggregation profiles and by estimation of soluble protein. Inclusion of salt in the refolding conditions prevents the reversibility of mutant having charge substitution, while the reversibility of mutant with the introduction of proline was unaffected, indicating the role of charge mediated interaction in M134E in preventing aggregation. Partial prevention of thermal aggregation in wild‐type lipase with single substitution, M137P, incorporated by site‐directed mutagenesis, suggests that the affect of M137P is independent of the intrinsic thermostability of lipase. Various effects of the mutations suggest their role is in prevention of the formation of aggregation prone intermediate(s). These mutations, describe yet another strategy to enhance the thermotolerance of proteins, where their influence is observed only on the denatured ensemble.
Black holes, first‐order flow equations and geodesics on symmetric spaces
Authors: Perz J. , Smyth P. , Van Riet T. , Vercnocke B.
Published: April 2009

For both extremal and non‐extremal spherically symmetric black holes in theories with massless scalars and vectors coupled to gravity, we derive a general form of first‐order gradient flow equations, equivalent to the equations of motion. For theories that have a symmetric moduli space after a dimensional reduction over the timelike direction, we discuss the condition for such a gradient flow to exist.
Confinement and non‐perturbative tachyons in brane‐antibrane systems
Authors: Gutiérrez N. , Lozano Y.
Published: April 2009

We present a worldvolume effective action suitable for the study of the confined phase of a

system at weak coupling, and we identify the mechanism by which the fundamental string arises from this action when the Dp and the

annihilate. We construct an explicit dual action, appropriate for the strong coupling regime, which realizes a generalized Higgs‐Stückelberg phase for the (relative) (p‐2)‐form dual to the (overall) BI vector, the mechanism put forward by Yi and collaborators for realizing non‐perturbatively the breaking of the overall U(1) gauge group. Our results provide an explicit realization of the perturbative breaking of the overall U(1) in a way that is consistent with the duality symmetries of String Theory.
Mechanical models for higher spin gauge fields
Authors: Bengtsson A.K.H.
Published: April 2009

Returning to an old idea of a certain two‐particle relativistic system as an underlying mechanical model for higher spin gauge fields, a space‐time picture is discussed for the interactions. This results in a general algorithm for the vertices.
Particle astrophysics of nonlinear supersymmetric general relativity
Authors: Shima K. , Tsuda M.
Published: April 2009

An explanation of relations between the large scale structure of the universe and the tiny scale structure of the particle physics, e.g. the observed mysterious relation between the (dark) energy density and the dark matter of the universe and the neutrino mass and the SUSY breaking mass scale of the particle physics may be given by the nonlinear supersymmetric general relativity (NLSUSY GR). NLSUSY GR shows that considering the physics before/of the big bang (BB) of the universe may be significant and may give new insight to unsolved problems of the low energy particle physics, cosmology and their relations.
Tachyon condensation as a cosmological model
Authors: Koshelev A.
Published: April 2009

In this note cosmological applications of the rolling tachyon coupled with the dilaton especially to the Dark Energy problem are considered.
Native state dynamics and mechanical properties of human topoisomerase I within a structure‐based coarse‐grained model
Authors: Szklarczyk Oliwia , Staroń Krzysztof , Cieplak Marek
Published: April 2009

A coarse grained molecular dynamics model with an implicit solvent is used to elucidate properties of the human topoisomerase I. The model is defined through the native structure and it allows covering significantly longer time scales than in all atom simulations. Single residue and double residue motional characteristics are studied. The results are consistent with all atom simulations reported in the literature indicating usefulness of the model in further studies of this protein. Novel findings include broadening of the description of the dynamic behavior of the lip and hinge regions and a characterization of the motional properties of the RRM binding site of the enzyme. We also consider mechanical stretching of the protein and identify sources of the force peaks. The elastic properties of topoisomerase I are predicted to be average in comparison to other proteins, yielding a maximum force of resistance to pulling which should be of order 120 pN. The contact unraveling pattern is consistent with the understanding of the structure and function of the protein. We find supporting evidence for the hypothesis that the C‐terminal domain acquires an ordered structure upon binding with the core enzyme even though it forms a molten globule when in isolation. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Control of Fusarium verticillioides, cause of ear rot of maize, by Pseudomonas fluorescens
Authors: Chandra Nayaka Siddaiah , Udaya Shankar Arakere C , Reddy Munagala S , Niranjana Siddapura R , Prakash Harishchandra S , Shetty Hunthrike S , Mortensen Carmen N
Published: April 2009

BACKGROUND: Maize is one of the staple food crops grown in India. Fusarium verticillioides (Sacc.) Nirenberg is the most important fungal pathogen of maize, associated with diseases such as ear rot and kernel rot. Apart from the disease, it is capable of producing fumonisins, which have elicited considerable attention over the past decade owing to their association with animal disease syndromes. Hence, the present study was conducted to evaluate ecofriendly approaches by using a maize rhizosphere isolate of Pseudomonas fluorescens (Trev.) Mig. and its formulation to control ear rot disease and fumonisin accumulation, and also to study the capacity to promote growth and yield of maize. In vitro assays were conducted to test the efficacy of P. fluorescens as a seed treatment on seed germination, seedling vigour and also the incidence of F. verticillioides in different maize cultivars. The field trials included both seed treatment and foliar spray. For all the experiments, P. fluorescens was formulated using corn starch, wheat bran and talc powder. In each case there were three different treatments of P. fluorescens, a non‐treated control and chemical control.

RESULTS: Pure culture and the formulations, in comparison with the control, increased plant growth and vigour as measured by seed germination, seedling vigour, plant height, 1000 seed weight and yield. P. fluorescens pure culture used as seed treatment and as spray treatment enhanced the growth parameters and reduced the incidence of F. verticillioides and the level of fumonisins to a maximum extent compared with the other treatments.

CONCLUSION: The study demonstrates the potential role of P. fluorescens and its formulations in ear rot disease management. The biocontrol potential of this isolate is more suited for fumonisin reduction in maize kernels intended for human and animal feed. Copyright © 2009 Society of Chemical Industry
Endogenous high‐performance liquid chromatography/tandem mass spectrometry interferences and the case of perfluorohexane sulfonate (PFHxS) in human serum; are we overestimating exposure?
Authors: Chan Emily , Sandhu Mandeep , Benskin Jonathan P. , Ralitsch Milan , Thibault Nicole , Birkholz Detlef , Martin Jonathan W.
Published: April 2009

Perfluorinated acids have received increasing scientific attention due to their widespread global distribution, environmental persistence and bioaccumulation in wildlife and humans. For perfluorohexane sulfonate (PFHxS, C6F13SO, m/z 399), all existing human data have been generated using high‐performance liquid chromatography (HPLC) and its most sensitive tandem mass spectrometric (MS/MS) transitions (m/z 399/80 [SO3]− or m/z 399/99 [SO3F]−), but this may be problematic because of co‐eluting endogenous steroid sulfates that share common fragmentation pathways. We examined the magnitude of over‐reporting for PFHxS in pregnant women (n = 29), and in pooled serum of males, non‐pregnant and pregnant females (n = 3, 100 samples per pool), by comparing m/z 399/80 and 399/99 data with an interference‐free transition, m/z 399/119. PFHxS concentrations in pregnant women determined using m/z 399/80 and 399/99 (p < 0.05), but not m/z 399/119, were positively correlated to the response of the steroid sulfates. This led to an average overestimation of PFHxS by 1.5‐ and 4.7‐fold, using m/z 399/80 and 399/99, respectively, and validated the use of m/z 399/119 for the first time. The interferences were a problem in all human serum samples, and analysis of pooled serum revealed statistically significant over‐reporting by m/z 399/80 and 399/99 for pregnant women > non‐pregnant women > men. The magnitude of over‐reporting here represents a worst‐case scenario, but the extent to which the published literature values are biased is unknown due to limited details of methods in existing reports. Instead of using the less sensitive m/z 399/119 transition, we showed that an alternative selection of column and mobile phase can allow for sufficient chromatographic separation of the interferences. In conclusion, it was shown that routine analytical methods are prone to systematically overestimating PFHxS concentrations in serum of men or women, but that this can be avoided by alternative chromatographic steps or MS/MS transitions. Copyright © 2009 John Wiley & Sons, Ltd.